EFSA supporting publication 2014:EN-629 EXTERNAL SCIENTIFIC REPORT Comprehensive literature search and review of breast milk composition as preparatory work for the setting of dietary reference values for vitamins and minerals1 LASER Analytica ABSTRACT This work summarises the outcome of a comprehensive literature search on the breast milk concentrations of folate, zinc, vitamin B6, vitamin E, choline, phosphorus, potassium, vitamin A, vitamin B1, chloride, sodium, copper and magnesium in healthy women from Europe, North America and Australia published from January 2000 for folate, zinc, vitamin B6, vitamin E, choline, phosphorus, vitamin A, vitamin B1, chloride and sodium, from October 2010 for potassium and magnesium and from January 2011 for copper. The results present ranges of concentrations reported for the general population of healthy nursing women. Where appropriate, separate results are presented according to the stages of lactation, the gestational age at birth (i.e., milk from mothers of term vs. pre-term infants), and the use or not of a supplement containing the micronutrient of interest. When assessed, data on the relationships between dietary intake (including the effect of supplementation) or status of the micronutrient of interest and breast milk concentration are presented. © LASER Analytica, 2014 KEY WORDS breast milk, vitamins, minerals DISCLAIMER The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. 1 Question No EFSA-Q-2013-01027. Any enquiries related to this output should be addressed to [email protected] Suggested citation: LASER Analytica, 2014. Comprehensive literature search and review of breast milk composition as preparatory work for the setting of dietary reference values for vitamins and minerals. EFSA supporting publication 2014:EN-629, 154 pp. Available online: www.efsa.europa.eu/publications © European Food Safety Authority, 2014 Vitamin and mineral content of breast milk SUMMARY Several comprehensive literature searches have been performed to record all data available on breast milk concentrations of folate, zinc, vitamin B6, vitamin E, choline, phosphorus, potassium, vitamin A, vitamin B1, chloride, sodium, copper and magnesium in healthy women from Europe, North America and Australia according to specific time periods. Studies included in the review where those published from January 2000 for folate, zinc, vitamin B6, vitamin E, choline, phosphorus, vitamin A, vitamin B1, chloride and sodium, those published from October 2010 for potassium and magnesium and those published from January 2011 for copper. Besides the provision of major findings for each included study in tables, a qualitative critical appraisal was performed. Criteria considered were confounding factors associated with the characteristics of the study population (details on the supplementation or not, health status) and milk samples (stage of lactation, i.e., colostrum, transitional milk, mature milk). Reliability/usefulness of analytical methods applied was also assessed for each study individually according to the presence of quality controls (standard reference materials) and sufficient details on the validation of the analytical method applied (i.e., recovery, repeatability, limit of detection (LOD), limit of quantification (LOQ)). The results were pooled in order to present weighted means and 95 % confidence intervals (CIs) for the general population of healthy nursing women (i.e., all milk samples included) and specific subgroups (according to the stages of lactation for mothers of term infants, the gestational age at birth (i.e., milk from mothers of term vs. pre-term infants), and the use or not of a supplement containing the micronutrient of interest). When assessed, data on the relationships between dietary intake (including the effect of supplementation) or status of the micronutrient of interest and breast milk concentration are presented. The comprehensive literature searches on folate concentration in human breast milk retrieved 8 relevant studies. Two studies were free of confounders. When reported, the analytical method used for folate analysis was mainly high performance liquid chromatography–mass spectrometry (HPLCMS/MS, 4 studies). Microbiological assays were also used (3 studies). One study did not report the analytical method for folate. Forms of folate analysed were total folate (reduced forms of folic acid, including tetrahydrofolate (H4-folate) and 5-methyltetrahydrofolate (5-CH3-H4 folate), 7 studies), folic acid (2 studies), 5-CH3-H4 folate (2 studies), H4-folate (1 study), and the catabolites paminobenzoylglutamate and acetamide-p-aminobenzoylglutamate (1 study). The weighted mean (95% CI) folate concentration from all samples was 57.3 (52.6 – 62.0) µg/L. Three studies involved mothers of term infants, all of those were performed on mature milk samples (weighted mean (95% CI): 52.7 (45.0 – 63.0) µg/L). Regarding the relationship between folate intake/status and breast milk concentration, two studies found no association between folic acid supplementation and total folate concentration in breast milk. A third study found a relationship between folic acid concentration in breast milk and folate intake, but not between total folate concentration in breast milk and folate intake. Women supplemented with folic acid presented breast milk concentrations of total folate of (weighted mean (95% CI)) 60.4 (54.8 – 65.9) µg/L; those not supplemented presented breast milk concentrations of total folate of (weighted mean (95% CI)) 48.7 (39.6 – 57.8) µg/L. Forty-one studies, reported in 42 papers, reported zinc concentrations in breast milk. Six studies were free of confounders. For zinc determination, the analytical method used was mainly atomic absorption spectrometry (25 studies); ICP-MS was used in 6 studies; voltammetry was used in 1 study. Ten studies did not report the analytical method for zinc. The weighted mean (95% CI) zinc concentration from all samples was 2.06 (2.05 – 2.07) mg/L. Colostrum contained high zinc concentrations (weighted mean (95% CI): 8.60 (5.03 – 12.17) mg/L); zinc concentrations were lower for transitional milk (weighted mean (95% CI): 2.72 (2.33 – 3.11) mg/L) and mature milk (weighted mean (95% CI): 1.48 (1.46 – 1.51) mg/L). Milk samples were collected from mothers who gave birth to both term and pre-term infants. Mothers of term infants presented a 5-fold higher breast milk zinc concentration EFSA supporting publication 2014:EN-629 2 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (weighted mean (95% CI): 2.51 (2.32 – 2.71) mg/L) than mothers of preterm infants (weighted mean (95% CI): 0.47 (0.39 – 0.55) mg/L). Two studies showed no significant correlation between milk zinc concentration and maternal plasma zinc. Another study found no relationship between zinc dietary intake and breast milk concentration. Four studies reported concentration of total vitamin B6 (2 studies) or individual forms of vitamin B6 (pyridoxal, pyridoxine, pyridoxamine) (2 studies) in breast milk. Three studies were free of confounders. Total vitamin B6 was measured via microbiological assays (2 studies); pyridoxal (2 studies), pyridoxamine (1 study) and pyridoxine (1 study) were measured via HPLC-MS/MS. The 2 studies dealing with total vitamin B6 concentration involved supplemented mothers of term infants, all of those were performed on mature milk samples. The weighted mean (95% CI) for total vitamin B6 concentration for these two studies was 244 (232 – 256) µg/L. An additional study reported total vitamin B6 concentration as the sum of pyridoxal, pyridoxamine and pyridoxine. Women were mothers of term infants and were mostly supplemented with undefined nutrients. The weighted mean (95% CI) for total vitamin B6 concentration from all samples coming from these 3 studies was 233 (222 – 244) µg/L. There were no data on vitamin B6 concentration in breast milk of non-supplemented mothers. Three studies reported intake data; only 1 reported data on status (as plasma total vitamin B6 concentration). One study reported a significant positive correlation between vitamin B6 intake and breast milk pyridoxal concentration, while the relationship was not investigated in the 3 other studies. Vitamin E breast milk concentration was assessed in 24 publications (23 studies) via the quantification of alpha-tocopherol, beta-tocopherol, delta-tocopherol, gamma-tocopherol, or total vitamin E (defined in most of cases as alpha-tocopherol + 0.25 gamma-tocopherol). Five studies were free of confounders. The analytical method employed was HPLC-MS/MS (23 studies). Five studies reported total vitamin E expressed as tocopherol-equivalent (TE, TE (mg) = alpha-tocopherol (mg) + 0.25 gamma-tocopherol (mg)). The weighted mean (95% CI) for TE concentration from all samples was 3.87 (3.53 – 4.22) mg/L. Weighted means (95% CIs) for TE at different stages of lactation are as follows: transitional milk = 4.27 (0.01 – 8.54) mg/L; mature milk = 3.30 (1.09 – 5.51) mg/L. When specified, milk samples were collected from mothers who gave birth to term infants. Mothers of term infants presented TE concentration of 3.51 (1.54 – 5.47) mg/L. When women were supplemented with vitamin E, weighted mean (95% CI) for TE was 3.59 (2.73 – 4.45) mg/L. Nineteen studies reported alpha-tocopherol concentration in women milk. The weighted mean (95% CI) for alpha-tocopherol concentration from all samples was 3.74 (3.63 – 3.85) mg/L. Weighted means (95% CIs) at different stages of lactation were as follows: colostrum = 24.11 (13.17 – 35.05) mg/L; transitional milk = 11.86 (10.77 – 12.95) mg/L; mature milk = 3.30 (3.16 – 3.44) mg/L. Milk samples were collected from mothers who gave birth to both term or pre-term infants. Weighted mean (95% CI) was 6.84 (5.99 – 7.69) mg/L) for breast milk of mothers of preterm infants and 3.45 (3.31 – 3.59) mg/L for breast milk of mothers of term infants. The weighted means (95% CIs) were 8.28 (7.65 – 8.90) mg/L for milk from non-supplemented women vs. 3.46 (2.61 – 4.32) mg/L for milk from supplemented women. Seven studies reported intake data; 3 reported data on status (as plasmatic alpha-tocopherol concentration, sum of plasmatic alpha- and gamma-tocopherols, or “total vitamin E” concentration (with no precision on the tocopherol(s) considered)). Two studies showed a correlation between the concentration of vitamin E in the milk (alpha-TE as the sum of alpha- and gamma-tocopherols) and its intake (forms not specified, range 6 – 9 mg/day), whereas 3 other studies did not find a correlation between breast milk vitamin E concentration (alpha-TE as the sum of alpha- and gamma-tocopherols) and intake (forms not specified, 3.43 – 16.67 mg/day). One study failed to show a correlation between maternal plasma alpha-tocopherol and TE (alpha- + gamma-tocopherol) milk concentrations. Five studies dealt with choline breast milk concentration (free and/or total choline, phosphatidylcholine, phosphocholine, glycerophosphocholine, phospholipid-bound choline). Two studies were free of confounders. Free choline (5 studies), total choline (4 studies), phosphatidylcholine (1 study), phosphocholine (1 study), glycerophosphocholine (1 study) and phospholipid-bound choline (1 study) were measured via HPLC-MS/MS (2 studies), enzymatic EFSA supporting publication 2014:EN-629 3 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk method (2 studies) or proton nuclear magnetic resonance spectroscopy (1 study). One study did not report the analytical method for choline analysis. The weighted means (95% CIs) from all samples was 12.82 (12.21 – 13.44) mg/L for free choline and 105.71 (101.08 – 110.35) mg/L for total choline concentrations, respectively. Weighted means (95% CIs) at different stages of lactation were as follows (free choline/total choline): colostrum = 7.40 (0.59 – 14.21)/42.40 (23.58 – 61.22) mg/L; mature milk = 9.69 (5.07 – 14.31)/159.59 (109.52 – 209.66) mg/L. When specified, milk samples were collected from mothers who gave birth to term infants (weighted mean (95% CI) for free choline/total choline: 8.97 (5.14 – 12.79)/56.90 (39.29 – 74.51) mg/L). Free choline breast milk concentrations were (weighted means (95% CIs)): 11.63 (10.71 – 12.54) mg/L in women supplemented with choline and 10.01 (8.97 – 11.05) mg/L in women non-supplemented. Total choline concentration was only reported for non-supplemented women (weighted mean (95% CI)): 56.90 (39.29 – 74.51) mg/L. Two studies investigated choline status (defined by free choline plasma concentration) and found a correlation between choline status and breast milk free choline concentration. Breast milk concentrations of choline, phosphatidylcholine and phosphocholine were significantly correlated with total choline intake (mean 1088 mg/day) in one study. Five studies reported phosphorus breast milk concentration. One study was free of confounders. Phosphorus concentration was quantified via the ICP-MS analytical method (two studies). Three studies did not report the analytical method for phosphorus. The weighted mean (95% CI) phosphorus concentration from all samples was 132 (118 – 146) mg/L. Three studies were performed on mature milk samples and 2 other studies did not give information on the stage of lactation. The involvement of mothers of term or preterm infants was not specified. Phosphorus status (as defined by plasma phosphorus concentration) was reported in 1 study. There was no information from these studies on the relationship between phosphorus intake (including supplementation) or status and breast milk concentration. Three studies reported potassium breast milk concentration. No study was free of confounders. Potassium concentration was quantified via the ICP-MS analytical method (3 studies). The weighted mean (95% CI) potassium concentration from all samples was 561.10 (505.62 – 616.58) mg/L. Mothers of preterm infants presented potassium breast milk concentration of (weighted mean (95% CI)): 505.09 (411.82 – 598.35) mg/L; mothers of term infants presented potassium breast milk concentration of (weighted mean (95% CI)): 449.63 (304.02 – 595.24) mg/L. None of the studies reported intake and/or status data. There was no information from these studies on the relationship between potassium intake (including supplementation) or status and breast milk concentration. Vitamin A breast milk concentration was assessed in 19 publications (18 studies) via the quantification of alpha-carotene (4 studies), beta-carotene (6 studies) or all-trans-retinol (8 studies). One study also calculated total vitamin A concentration in retinol equivalents (RE), while 5 other studies reported “vitamin A” concentration without specifying the compounds that were considered. Nine studies were free of confounders. The analytical method employed was HPLC (17 studies). One study did not record the analytical method. The weighted mean (95% CI) for retinol concentration from all samples was 206.06 (195.14 – 216.97) µg/L. Weighted means (95% CIs) at different stages of lactation were the followings: colostrum = 1 353.03 (271.72 – 2434.34) µg/L; transitional milk = 2 380.97 (2 125.18 – 2 636.75) µg/L; mature milk = 228.55 (216.15 – 240.94) µg/L. Weighted mean (95% CI) was 233.74 (221.36 – 246.12) µg/L for milk of mothers of term infants. The weighted mean (95% CI) was 333.13 (317.12 – 349.15) µg/L for milk from non-supplemented women. There was no data on breast milk retinol concentration from supplemented women. Seven studies reported intake data; 6 studies reported data on status as alpha-carotene, beta-carotene or retinol plasma concentration. One study showed a positive correlation between the concentration of retinol in the milk and the intake of cod liver, 1 study showed a positive correlation between maternal vitamin A intakes (as measured by total “vitamin A + retinol” daily intakes) and milk retinol concentrations and between maternal plasma and milk beta-carotene concentrations in non-smoker mothers, but not in smoker ones. Another study did not find a correlation between breast milk vitamin A concentration (not specified) and intake of betaEFSA supporting publication 2014:EN-629 4 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk carotene. Two studies showed a positive correlation between maternal plasma retinol and milk retinol concentrations. Vitamin B1 breast milk concentration was assessed in 2 studies. One study was free of confounders. The analytical method employed was either HPLC (1 study) or fluorimetry (1 study). The weighted mean (95% CI) for vitamin B1 concentration from all samples was 44.7 (27.9 – 61.5) µg/L. Weighted means (95% CIs) at different stages of lactation are as follows: transitional milk = 234.8 (24.6 – 494.1); mature milk = 68.6 (32.6 – 104.5). Milks were collected from mothers who gave birth to term infants in one study, while in the other study the gestation stage was not specified. Weighted mean (95% CI) was 71.7 (36.1 – 107.3) µg/L for milk of mothers of term infants. The weighted means (95% CIs) were 67.1 (30.8 – 103.5) µg/L for milk from non-supplemented women vs. 185.3 (4.1 – 366.4) µg/L for milk from supplemented women with vitamin B1. One study reported intake and status data (vitamin B1 status assessed by erythrocyte transketolase activation assay). One study showed a correlation between the concentration of vitamin B1 in mature milk and its intake. Chloride breast milk concentration was assessed in 1 study. The analytical method employed was spectrometric absorption. The weighted mean (95% CI) for chloride concentration from all samples was 381.0 (328.4 – 433.7) mg/L. Milks were collected from mothers who gave birth to both term and pre-term infants. Weighted means (95% CIs) were 373.8 (293.3 – 454.3) mg/L for breast milk of mothers of preterm infants and 386.4 (317.0 – 455.9) mg/L for breast milk of mothers of term infants. Copper breast milk concentration was assessed in 3 studies. None of the studies was free of confounders. The analytical method employed was ICP-MS (2 studies) or FAAS (flame atomic absorption spectrometry, 1 study). The weighted mean (95% CI) for copper concentration from all samples was 264.05 (206.64 – 321.46) µg/L. Mature milks were collected from mothers who gave birth to both term and preterm infants in one study, while in the 2 other studies the gestation stage was not specified. None of the study reported maternal intake or status data allowing to assess the relation between intake/status and breast milk concentration. Magnesium breast milk concentration was assessed in 3 studies. None of the studies was free of confounders. The analytical method employed was absorption spectrometry (1 study), ICP-AES (1 study) and ICP-MS (1 study). The weighted mean (95% CI) for magnesium concentration from all samples was 34.83 (30.15 – 39.51) mg/L. Milks were collected from mothers who gave birth to both term and pre-term infants. Weighted means (95% CIs) was 39.60 (32.67 – 46.54) mg/L for breast milk of mothers of preterm infants and 31.60 (22.07 – 41.12) mg/L for breast milk of mothers of term infants. None of the studies reported maternal intake or status data allowing to assess the relation between intake/status and breast milk concentration. Sodium breast milk concentration was assessed in 12 publications. None of the studies was free of confounders. The analytical method employed was flame photometry (2 studies), absorption spectrometry (1 study), gasometry (1 study), ICP-MS (1 study) and ion selective method (1 study). Six studies did not report the analytical method used. The weighted mean (95% CI) for sodium concentration from all samples was 371.1 (353.3 – 388.9) mg/L. Weighted means (95% CIs) at different stages of lactation are as follows: colostrum = 538.2 (490.4 – 585.9) mg/L; transitional milk = 1642.6 (1583.4 – 1701.8) mg/L (data on mature milk not reported). Milk samples were collected from mothers who gave birth to both term and pre-term infants. Weighted means (95% CIs) were 183.6 (162.0 – 205.1) mg/L for breast milk of mothers of preterm infants and 850.4 (816.7 – 884.0) mg/L for breast milk of mothers of term infants. None of the studies reported mothers’ intake or status data allowing to assess the relation between intake/status and breast milk concentration. EFSA supporting publication 2014:EN-629 5 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk TABLE OF CONTENTS Abstract .................................................................................................................................................... 1 Summary .................................................................................................................................................. 2 Table of contents ...................................................................................................................................... 6 Background as provided by efsa .............................................................................................................. 7 Terms of reference as provided by efsa .................................................................................................... 7 Objectives ................................................................................................................................................. 8 Materials and Methods ............................................................................................................................. 8 1. Data collection ................................................................................................................................. 8 1.1. Literature searches .................................................................................................................. 8 1.1.1. Search strategies ................................................................................................................. 8 1.1.2. Sources of publications ....................................................................................................... 9 1.1.3. Study selection.................................................................................................................... 9 1.1.4. Study management ........................................................................................................... 10 1.2. Data extraction ...................................................................................................................... 11 1.2.1. Database ........................................................................................................................... 11 1.2.2. Quality assessment ........................................................................................................... 12 2. Data synthesis ................................................................................................................................ 13 2.1. Data management: scaling .................................................................................................... 13 2.2. Other processes ..................................................................................................................... 13 Results .................................................................................................................................................... 15 3. Literature searches and data collection .......................................................................................... 15 3.1. Folates ................................................................................................................................... 15 3.2. Zinc ....................................................................................................................................... 16 3.3. Vitamin B6, Vitamin E, choline, phosphorus, potassium ..................................................... 16 3.4. Vitamin A, Vitamin B1, chloride, sodium, copper and magnesium ..................................... 17 4. Description of results and analyses................................................................................................ 18 4.1. Folates ................................................................................................................................... 18 4.2. Zinc ....................................................................................................................................... 25 4.3. Vitamin B6, Vitamin E, choline, phosphorus, potassium ..................................................... 38 4.3.1. Vitamin B6 ....................................................................................................................... 38 4.3.2. Vitamin E.......................................................................................................................... 46 4.3.3. Choline ............................................................................................................................. 63 4.3.4. Phosphorus ....................................................................................................................... 71 4.3.5. Potassium.......................................................................................................................... 73 4.4. Vitamin A, Vitamin B1, chloride, copper, magnesium, sodium ........................................... 75 4.4.1. Vitamin A ......................................................................................................................... 75 4.4.2. Vitamin B1 ....................................................................................................................... 87 4.4.3. Chloride ............................................................................................................................ 89 4.4.4. Copper .............................................................................................................................. 91 4.4.5. Magnesium ....................................................................................................................... 92 4.4.6. Sodium.............................................................................................................................. 94 Conclusions ............................................................................................................................................ 99 References included ............................................................................................................................. 100 Appendices ........................................................................................................................................... 110 A. Search strategies for folates ......................................................................................................... 110 B. Search strategies for zinc ............................................................................................................. 116 C. Search strategies for Vitamin B6, Vitamin E, choline, phosphorus and potassium .................... 124 D. Search strategies for Vitamin A, Vitamin B1, chloride, copper, magnesium and sodium .......... 135 E. References for studies excluded on the basis of the country ....................................................... 145 F. References for studies excluded on the basis of the language ..................................................... 153 EFSA supporting publication 2014:EN-629 6 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk BACKGROUND AS PROVIDED BY EFSA In 2005, the European Food Safety Authority (EFSA) received a mandate from the European Commission to review the existing advice of the Scientific Committee for Food (SCF) published in 1993 (SCF 1993) on Dietary Reference Values (DRVs) for energy, macro- and micronutrients and other substances with a nutritional or physiological effect. While the setting of DRVs for macronutrients and energy has been finalised by the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), the work on micronutrients is ongoing. A comprehensive literature search and review of compositional data of human breast milk is requested in order to collect up-to-date information as preparatory work which will serve as a basis for the assessment of the Working Group on DRVs for Vitamins and Minerals of the EFSA NDA Panel, in relation to the establishment of DRVs for a selection of micronutrients. In 2003, the Scientific Committee on Food (SCF) revised the essential requirements of infant formulae and follow on formulae (SCF 2003), which included a review of compositional data of human milk available at that time. In addition, more recent compositional data have already been collected for some micronutrients in calls for tender CFT/EFSA/NUTRI/2011/01 (CFT/EFSA/NUTRI/2011/01 covered copper concentration of breast milk) and CFT/EFSA/NDA/03 (CFT/EFSA/NDA/03 covered magnesium, potassium and fluoride concentrations of breast milk) in the context of EFSA’s work to establish DRVs for micronutrients. The objective of the current project is to complement and update data available from these sources. TERMS OF REFERENCE AS PROVIDED BY EFSA Comprehensive literature search and review of breast milk composition as preparatory work for the setting of dietary reference values for vitamins and minerals. Call for tender RC/EFSA/NUTRI/2013/06 – OC/EFSA/SAS/2012/01. This contract was awarded by EFSA to: Contractor: LASER Analytica Europe Limited, 66 Chiltern Street, London, W1U 4JT Contract title: Comprehensive literature search and review of breast milk composition as preparatory work for the setting of dietary reference values for vitamins and minerals Contract number: RC/EFSA/NUTRI/2013/06 – OC/EFSA/SAS/2012/01 EFSA supporting publication 2014:EN-629 7 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk OBJECTIVES The overall aim of this project was to collect data from the scientific literature on breast milk concentrations for the following micronutrients: - Vitamins: vitamin A, vitamin E, choline, folate, vitamin B6, vitamin B1 - Minerals: phosphorus, zinc, chloride, sodium, copper, potassium and magnesium Information was collected following a systematic review process, involving literature searches and data extraction in a database. MATERIALS AND METHODS 1. Data collection 1.1. Literature searches 1.1.1. Search strategies Search strategies for the electronic databases consist of a logic combination (through Boolean operators) of free text/specific database terms, based on search terms identified during preliminary searches. Preliminary searches consisted in developing synonyms and other relevant keywords for the nutrients of interest and on identifying keywords relative to breast milk composition. Grey literature was searched by hand, by using some relevant keywords e.g., "breast/human milk composition", "breast/human milk, vitamin", "breast/human milk, minerals" on search engines of indicated websites/databases. Websites interface and structure were carefully screened for identifying any relevant information. The search strategy was conducted: - according to the search terms defined for each electronic database (see Section 1.1.2 and appendices A-D); - with broad terms like “breast milk composition", "breast milk, vitamins", "breast milk, minerals" for the grey literature searches; - in English language for the electronic databases; for the “grey literature” searches, English, Polish and French searches were done; - when available, reviews were hand-searched for other relevant references, as was the reference lists of included studies. In order to meet EFSA’s requirements in terms of timeframe, searches for data on folates and zinc were conducted separately while combined searches were carried out for data on vitamin B6, vitamin E, choline, phosphorus and potassium, and for data on vitamin A, vitamin B1, chloride, sodium, copper and magnesium, respectively. The search strategies for the electronic databases and grey literature are detailed in full as appendices A-D, together with the number of search results for each of the data sources. EFSA supporting publication 2014:EN-629 8 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 1.1.2. Sources of publications In order to identify all pertinent citations, a focused search of the published literature was conducted on the basis of the search strategies presented in the appendices. The following electronic databases were searched: - PubMed - Web of Science - Embase Additional searches under grey literature were also performed in parallel (national and international health agencies, Google, Google scholar, Google books, Codex, Scientific Web plus, clinicaltrials.gov, OAISTER, OpenGrey, other nursing databases, websites of organisations related to infant nutrition and health e.g., World Health Organization, European Society for Paediatric Gastroenterology, Hepatology and Nutrition or American Academy of Pediatrics and other relevant websites (see appendices)) to obtain relevant data. Reports, such as reports from national and international health agencies or reports from expert bodies, handbooks, and other non-peer reviewed studies were screened according to inclusion and exclusion criteria. Sources from the EFSA Inventory of information sources (http://www.metaxis.com/EFSAInventory/) have also been searched. 1.1.3. Study selection In compliance with the systematic review procedure recommended by EFSA2, study screening was undertaken in two steps: - Initial screen – Screening of the titles and abstracts of all studies retrieved from the searches. Studies included following this initial screening phase were processed for a more detailed examination. - Detailed screen – Full text versions of the studies included following the initial screening phase were then examined for inclusion in the review. An initial screening of titles and abstracts against the inclusion and exclusion criteria presented in Table 1 was conducted to identify potentially pertinent papers. All references sorted into the “include” category were obtained for retrieval. For all references sorted as “uncertain” (when a definite decision could not be made based on the title and/or abstract alone), the full paper was obtained for detailed assessment against the inclusion criteria, thus enhancing the sensitivity of the initial selection step. Two reviewers independently evaluated each potentially relevant reference (both on the basis of titles and abstracts and full-texts). If there were any differences between the two reviewers in the decision to include/exclude a study, a decision was taken by a third reviewer. Moreover, 10% of the excluded studies were double-checked by a senior team member. Information obtained from the grey literature in English, French and Polish languages was processed for a detailed screening. 2 EFSA (European Food Safety Authority), 2010. Application of systematic review methodology to food and feed safety assessments to support decision making. EFSA Journal 2010;8(6):1637, 90 pp. doi:10.2903/j.efsa.2010.1637 Available online : http://www.efsa.europa.eu/fr/efsajournal/pub/1637.htm EFSA supporting publication 2014:EN-629 9 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Table 1: Inclusion and exclusion criteria which applied for selecting studies according to the field considered Breast milk concentration Review question What is the concentration of folate, zinc, vitamin B6, vitamin E, choline, phosphorus, potassium, vitamin A, vitamin B1, chloride, sodium, copper and magnesium in breast milk? Inclusion and exclusion criteria Inclusion criteria: Population of interest Healthy, well-nourished lactating women from Europe (geographical Europe, excluding Russia), North America, Australia and New Zealand Meta-analysis or systematic review Inclusion criteria: Study design Intervention studies Observational studies Studies reporting on the composition of milk from milk banks Inclusion criteria: Outcome of interest Concentration of folate, zinc, vitamin B6, vitamin E, choline, phosphorus, potassium, vitamin A, vitamin B1, chloride, sodium, copper and magnesium in breast milk samples Articles published before January 2000 for folate, zinc, vitamin B6, vitamin E, choline, phosphorus, vitamin A, vitamin B1, chloride and sodium Articles published before October 2010 for potassium and magnesium Articles published before January 2011 for copper Exclusion criteria Irrelevant population (considered not to be healthy, well-nourished or from other countries) Studies which do not report information on breast milk concentration for the selected micronutrients Duplicates: in the case where data are used in more than one study (1 original plus 1 or more secondary publications), the study providing the most complete and detailed information was chosen 1.1.4. Study management The references were managed either directly with EndNoteTM software or with Reference Manager before a conversion into EndNoteTM libraries. Separate libraries were created for included and excluded studies, and based on the reason of exclusion. The main reasons of exclusion were defined during the screening process (e.g., irrelevant population (e.g., unhealthy women), absence of outcome of interest). EFSA supporting publication 2014:EN-629 10 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Lists for studies excluded based on the country and potential relevant studies in other EU languages are provided in Appendices E and F. 1.2. Data extraction 1.2.1. Database The Excel database template, developed to include relevant study specifications (study design, methods, population) and outcomes of interest as defined in the study protocol, served to collate information extracted from both published scientific literature and grey literature. Each study was described along with elements to support the critical appraisal of the strengths and limitations of the recorded information. Data on breast milk concentration of the selected micronutrients and their metabolites were extracted. The concentrations and structure of the extraction grid was tailored to the requirements of EFSA. Controlled terminology lists/picklists, based on the picklists used in the OECD templates, were used as much as possible. Data extraction was performed independently by two reviewers, with any discrepancies in extractions to be corrected by a third reviewer. Statistical descriptors of the primary endpoints and study design (e.g., sample size, geometric mean and standard deviation, median, range, CIs, percentiles) were reported. Micronutrient concentrations are expressed in µg/L or mg/L. When the reporting of nutrient concentrations was done according to several units in the same publication, only values in µg/L or mg/L were reported. If the study reports data in other units only, raw data were extracted in the database before being converted. Data extraction includes the following information, when available: - Reference: o reference type; o first author; o year; o title. - Study quality assessment: o consideration of confounders (yes/no/unclear); o description of confounders considered. - Study characteristics: o type of study; o number of subjects at start; o number of subjects excluded (reason for exclusion)/lost at follow-up; o final number of subjects per group (sample size); o main statistical descriptor for age; value (years); o statistical descriptor associated to age (variability); value (years); o main statistical descriptor for weight; value (kg); o statistical descriptor associated to weight (variability); value (kg); o BMI; o ethnicity (country of origin); EFSA supporting publication 2014:EN-629 11 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk o country; o smoking status; o supplementation (vitamins, minerals); o details on supplementation; o micronutrient intake (intake from dietary sources, oral supplements and/or fortified foods); o data on the methods used to collect intake data; o micronutrient status (whole-blood/serum or plasma/erythrocyte concentrations of the micronutrient of interest; urinary excretion of the micronutrients; other relevant biomarkers of status for the micronutrient of interest); o main statistical descriptor for micronutrient status; value; unit; o statistical descriptor associated to micronutrient status (variability); value; unit. o data on the methods used to estimate status; o vegan/vegetarian diet; o other individual specificities (alcohol consumption, delivery by vaginal route or caesarean section, primiparous/multiparous); o mothers of term/preterm infants; o stage of lactation (defined as follows: colostrum: 1-4 days post-partum; transitional milk: 5-15 days postpartum; mature milk: > 15 days postpartum); o number of days/months post-partum; o breast feeding; o type of milk sample; o type of extraction; o method for data collection (year/period/time of the day); o analytical method applied; o validation status for the analytical method (appropriate quality controls?); o Limit of detection (LOD)/Limit of Quantification (LOQ) of analytical method applied. - Micronutrient concentrations: o number of samples analysed o micronutrient of interest o micronutrient (parent compound, specific isomer, metabolite, as recorded in the publication) o type of reporting o main statistical descriptor for concentration; value; unit; o statistical descriptor associated (uncertainty, variability); value; unit. o other statistical descriptor for concentration; value; unit; o statistical descriptor associated (uncertainty, variability); value; unit; - Relationship between intake/status and milk concentration of micronutrient of interest When information was not available from the paper, “not reported” or “not recorded” or “-” was recorded in the corresponding field. The Excel extraction datasheet is provided to EFSA together with this report. 1.2.2. Quality assessment Besides the provision of study summary and major findings for each included study, a qualitative critical appraisal was performed for both peer-reviewed articles and grey literature. EFSA supporting publication 2014:EN-629 12 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Attention was paid to potential confounding factors associated with the characteristics of the study population (details on supplementation or not, health status) and milk samples (stage of lactation, i.e., colostrum, transitional milk, mature milk). Consideration of potential confounders was recorded in the Excel database as free text. However, as the confounding factors were mainly explained by the lack of information (e.g., when there was no detail on supplementation, breast milks samples may come from women supplemented, not supplemented, or from both women supplemented and those not supplemented), both studies free of confounders and those presenting confounders were used in the analyses, except if explicitly stated (when there were strong doubts according to study quality). Reliability/usefulness of analytical methods applied was also assessed for each study individually according to the presence of quality controls (standard reference materials) and sufficient details on the validation of the analytical method applied (i.e., recovery, repeatability, limit of detection (LOD), limit of quantification (LOQ)). For all studies, there was sufficient information on the method used to consider it as reliable. However, for some studies, there were strong doubts according to the units recorded. Results coming from these studies were reported in the database but not used in the analyses. 2. 2.1. Data synthesis Data management: scaling When the values for micronutrient concentrations were expressed in other units than µg/L or mg/L, a conversion was made in an additional column of the excel sheet. When the values were expressed in molar concentration, the molecular masses used were: 35.45 g/mol for chloride; 104.17 g/mol for choline (free and total); 441.39 g/mol for folate, 445.43 g/mol for tetrahydrofolate, 459.46 g/mol for 5-methyltetrahydrofolate; 24.30 g/mol for magnesium; 31 g/mol for phosphorus; 39.10 g/mol for potassium; 22.99 g/mol for sodium; 286.45 g/mol for retinol, 538.87 g/mol for alpha and beta-carotene; 265.3546 g/mol for vitamin B1; 430.70 g/mol for alpha-tocopherol, 402.65 g/mol for delta-tocopherol, 416.68 g/mol for gamma-tocopherol; 169.18 g/mol for vitamin B6, 167.16 for pyridoxal, 168.19 g/mol for pyridoxamine, 169.18 g/mol for pyridoxine; 65.39 g/mol for zinc. 2.2. Other processes A weighted mean analysis on micronutrient concentrations in milk was performed on all the data for the identified sub-groups: 1) all samples (i.e., samples from mothers of term or pre-term infants, supplemented or not, all stages of lactation). 2) mothers of pre-term infants (when explicitly stated); 3) mothers of term infants (when explicitly stated); 4) colostrum milk samples (1-4 days post-partum), from women of term infants (when no information was available on the length of gestation (term vs. preterm), values were excluded from the calculations); 5) transitional milk samples (5-15 days postpartum), from women of term infants; EFSA supporting publication 2014:EN-629 13 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 6) mature milk samples (> 15 days postpartum), from women of term infants; 7) milks from mothers supplemented with the micronutrient of interest (when explicitly stated than more than ¾ of the women took supplements containing the micronutrient of interest); 8) milks from mothers non-supplemented with the micronutrient of interest (when explicitly stated) Weighted means were weighted according to the inverse variance: (1) where are the individual inverse variances and the individual means or medians3. Standard error for each weighted mean was computed as below: (2) The lower limit of the 95% CI LCI was calculated as: (3) The upper limit of the 95% CI UCI was calculated as: (4) 3 Hozo, S. P., Djulbegovic, B. et al. (2005). “Estimating the mean and variance from the median, range, and the size of a sample.” BMC Medical Research Methodology 5(13). EFSA supporting publication 2014:EN-629 14 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk RESULTS 3. 3.1. Literature searches and data collection Folates The merging of records retrieved from the three databases provided a total of 968 abstracts, after elimination of duplicates. Screening of the reference lists of the included articles allowed the retrieval of one study. Searches on the grey literature, as detailed in Appendix A, did not recover relevant sources of information. The following Figure 1 presents the flowchart for the studies dealing with folate which have been identified, extracted and selected. Figure 1: Flowchart for studies on folates EFSA supporting publication 2014:EN-629 15 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 3.2. Zinc The merging of records retrieved from the three databases provided a total of 973 abstracts, after elimination of duplicates. No additional articles were retrieved from the screening of the reference lists of the included articles. Searches on the grey literature, as detailed in Appendix B, did not recover relevant sources of information. The following Figure 2 presents the flowchart for the studies dealing with zinc which have been identified, extracted and selected. Figure 2: Flowchart for studies on zinc 3.3. Vitamin B6, Vitamin E, choline, phosphorus, potassium The merging of records retrieved from the three databases provided a total of 1081 abstracts, after elimination of duplicates. No additional articles were retrieved from the screening of the reference lists of the included articles. Searches on the grey literature, as detailed in Appendix C, did not recover relevant sources of information. The following Figure 3 presents the flowchart for the studies dealing with vitamin B6, vitamin E, choline, phosphorus and potassium which have been identified, extracted and selected. EFSA supporting publication 2014:EN-629 16 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Figure 3: Flowchart for studies on vitamin B6, vitamin E, choline, phosphorus and potassium 3.4. Vitamin A, Vitamin B1, chloride, sodium, copper and magnesium The merging of records retrieved from the three databases provided a total of 3 227 abstracts, after elimination of duplicates. No additional articles were retrieved from the screening of the reference lists of the included articles. Searches on the grey literature, as detailed in Appendix D, did not recover relevant sources of information. The following Figure 4 presents the flowchart for the studies dealing with vitamin A, vitamin B1, chloride, copper, magnesium and sodium which have been identified, extracted and selected. EFSA supporting publication 2014:EN-629 17 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Figure 4: Flowchart for studies on vitamin A, vitamin B1, chloride, copper, magnesium and sodium A full list of included and excluded studies, further grouped according to the rationale for their exclusion, are provided under the form of EndNoteTM libraries. Full-texts of the included studies are also shared with EFSA. 4. 4.1. Description of results and analyses Folates As described in the study flow diagram, 8 publications were included from the comprehensive literature search on folate breast milk concentration (January 2000 – January 2014). Details on which are in the following Table 2. EFSA supporting publication 2014:EN-629 18 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Table 2: Publication (SanchezHidalgo, FloresHuerta et al. 2000) Summary of the included studies for folate Population main characteristics Supplementation? Maternal folate intake Stage of lactation Confounding factors? Analytical method “Folate” concentration in breast milk (a) Number of women (number of samples) Not reported Not reported Not reported Not reported Yes: no information on type of milk nor on women details; besides, there is a strong suspicion of a mistake in the article for the recording of the value (this measure has been excluded from the calculations) Not reported Total folate: Mean: 0.05 µg/L Not reported (Not reported) Total folate: Mean ± SD: 47.8 ± 31.9 µg/L 68 (68) (Villalpando, Latulippe et al. 2003) Hispanic population from a specific community of Mexico; mothers of term infants Not reported Median (1st, 3rd quartile): 86 (38, 137) µg Mature milk (22 ± 13 days postpartum) Yes: targeted population and “nutritional anemia” (as reported in the publication) for 62% of women (Kim, Yang et al. 2004) Canadian women mothers of term infants Yes: 9 of the 12 lactating mothers consumed vitamin supplements; all containing 4001000 µg of folic acid Not reported Mature milk (1-6 months postpartum) Yes: few information on population and lack of information on specific folate supplementation Microbiological assay Microbiological assay Total folate: All women (9 supplemented, 3 not supplemented): Mean ± SD: 51.6 ± 20.3 µg/L 12 (12) Median (1st-3rd quartiles): 53.4 EFSA supporting publication 2014:EN-629 19 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation? Maternal folate intake Stage of lactation Confounding factors? Analytical method “Folate” concentration in breast milk (a) Number of women (number of samples) µg/L (35.4 – 59.9) (Khambalia, Latulippe et al. 2006) (Houghton, Yang et al. 2009) Hispanic population from a specific community of Mexico; mothers of term infants (same population than the one investigated in the Villalpando 2003 study; here subgroups of population are investigated) Canadian women No Median (1st, 3rd quartile): 86 (38, 137) µg Mature milk (22 ± 13 days postpartum) Yes: multivitamin supplements comprising folic acid 400 µg and Fe 18 mg (length of supplementation before sampling not reported) Mature milk (82 ± 15 days postpartum) Yes: multivitamin supplements comprising folic acid 400 µg without Fe and with other vitamins (length of supplementation before sampling not reported) Mature milk (138 ± 18 days postpartum) Yes: [6S]-5methylTHF (416 µg/d) EFSA supporting publication 2014:EN-629 Yes: targeted population and “nutritional anemia” (as reported in the publication) for 62% of women Total folate: Median (1st-3rd quartiles): 45.2 µg/L (39.5 – 57.0) Microbiological assay Daily average dose (mean ± SD): 416 µg 5-Me-THF during lactation + 911 ± 251 µg folic acid during pregnancy Mature milk (4 weeks postpartum) Total folate: Median (1st-3rd quartiles): 68.4 µg/L (56.8 – 78.7) 68 (68) Total folate: Median (1st-3rd quartiles): 63.6 µg/L (53.9 – 79.1) No Liquid chromatography Total folate: Mean ± SD: 83.4 ± 23.0 µg/L 55 (55) (no detail on number by subgroup) 20 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation? Maternal folate intake Stage of lactation Confounding factors? Analytical method “Folate” concentration in breast milk (a) No during lactation Daily average dose (mean ± SD): 911 ± 251 µg folic acid during pregnancy Total folate: Mean ± SD: 77.2 ± 19.0 µg/L Yes: Folic acid, 400 µg/d Daily average dose (mean ± SD): 400 µg during lactation + 911 ± 251 µg folic acid during pregnancy Total folate: Mean ± SD: 80.3 ± 45.0 µg/L Yes: [6S]-5methylTHF (416 µg/d) Daily average dose (mean ± SD): 416 µg 5-Me-THF during lactation + 911 ± 251 µg folic acid during pregnancy No during lactation Daily average dose (mean ± SD): 911 ± 251 µg folic acid during pregnancy Total folate: Mean ± SD: 91.4 ± 33.5 µg/L Yes: Folic acid, 400 µg/d Daily average dose (mean ± SD): 400 µg during lactation + 911 ± 251 µg folic acid during pregnancy Total folate: Mean ± SD: 80.8 ± 25.2 µg/L Yes: [6S]-5methylTHF (416 Daily average dose (mean ± SD): 416 EFSA supporting publication 2014:EN-629 Mature milk (8 weeks postpartum) Mature milk (16 weeks Number of women (number of samples) Total folate: Mean ± SD: 85.2 ± 27.4 µg/L Total folate: Mean ± SD: 68.4 53 (53) (no detail on number by subgroup) 21 (21) 21 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Stage of lactation µg/d) µg 5-Me-THF during lactation + 911 ± 251 µg folic acid during pregnancy postpartum) No during lactation Daily average dose (mean ± SD): 911 ± 251 µg folic acid during pregnancy Total folate: Mean ± SD: 77.7 ± 35.3 µg/L 20 (20) Daily average dose (mean ± SD): 400 µg during lactation + 911 ± 251 µg folic acid during pregnancy Total folate: Mean ± SD: 70.2 ± 34.9 µg/L 16 (16) Folic acid: Mean ± SD: 18.4 ± 0.6 µg/L Not reported (5) Yes: Folic acid, 400 µg/d (Alvarez-Sanchez, Priego-Capote et al. 2010) Not reported (West, Yan et al. 2012) and (Yan, Jiang et al. 2012) for description American women Not reported Yes: 750 µg/d of folic acid EFSA supporting publication 2014:EN-629 Not reported Daily average dose from both food and supplementation (mean): 1150 µg Not reported Mature milk (5 weeks postpartum) Confounding factors? Analytical method “Folate” concentration in breast milk (a) Maternal folate intake Supplementation? Number of women (number of samples) ± 24.3 µg/L Yes: no information on type of milk nor on women characteristics Liquid chromatography No Liquid chromatography Total folate: Mean (95% CI): 56.2 (48.8 – 64.2) µg/L 28 (28) 5-CH3-H4-folate: Mean (95% CI): 14 (10.8 – 17.6) µg/L 22 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation? Maternal folate intake Stage of lactation Confounding factors? Analytical method “Folate” concentration in breast milk (a) Number of women (number of samples) Folic acid: Mean (95% CI): 16.2 (11.8 – 21.3) µg/L Mature milk (15 weeks postpartum) Total folate: Mean (95% CI): 61.8 (54.1 – 70.0) µg/L 5-CH3-H4-folate: Mean (95% CI): 16.3 (12.8 – 20.2) µg/L Folic acid: Mean (95% CI): 24.1 (18.7 – 30.3) µg/L (Buttner, Witthoft et al. 2013) Not reported, samples coming from Swedish milk banks Not reported, samples coming from Swedish milk banks Not reported Mature milk (until 3 months postpartum) Yes: information population no on Total folate: Mean ± SD: 66.2 ± 20.3 µg/L Liquid chromatography H4-folate: Mean ± SD: 14.70 ± 6.68 µg/L n.a. (38) 5-CH3-H4-folate: Mean ± SD: 53.76 ± 17.00 µg/L EFSA supporting publication 2014:EN-629 23 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation? Maternal folate intake Stage of lactation Confounding factors? Analytical method “Folate” concentration in breast milk (a) Number of women (number of samples) Weighted mean analysis for total folate concentration in women mature milk: Women supplemented with folic acid or [6S]-5-methylTHF (weighted mean ± SE (95% CI)): 60.4 ± 2.8 µg/L (54.8 – 65.9) (4 studies) Women not supplemented (weighted mean ± SE (95% CI)): 48.7 ± 4.7 µg/L (39.6 – 57.8) (3 studies) Women mothers of term infants, mature milk (weighted mean ± SE (95% CI)): 52.7 ± 3.9 µg/L (45.0 – 60.3) (3 studies) All samples (weighted mean ± SE (95% CI)): 57.3 ± 2.4 µg/L (52.6 – 62.0) (6 studies) (a) Total folate concentrations are reported. Folic acid, 5-CH3-H4 folate, H4 folate concentrations are also reported, when available. The comprehensive literature searches on folate concentration in human breast milk retrieved 8 relevant studies. Two studies were free of confounders (Houghton, Yang et al. 2009; West, Yan et al. 2012). When reported, the analytical method used for folate measurements is mainly high performance liquid chromatography– mass spectrometry (HPLC-MS/MS, 4 studies). Microbiological assays are also reported (3 studies). One study did not report the analytical method for folate. Forms of folate analysed are total folate (7 studies), folic acid (2 studies), 5-CH3-H4 folate (2 studies), H4 folate (1 study), and the catabolites p-aminobenzoylglutamate and acetamide-p-aminobenzoylglutamate (1 study). In 4 of the studies, mothers were taking folate supplement (folic acid ranging 400-1000 µg/d or [6S]-5methylTHF 416 µg/d) (Kim, Yang et al. 2004; Khambalia, Latulippe et al. 2006; Houghton, Yang et al. 2009; West, Yan et al. 2012). The weighted mean and 95% CI folate concentration from all samples was 57.3 (52.6 – 62.0) µg/L. Three studies involved mothers of term infants, all of those were performed on mature milk samples (weighted mean and 95% confidence interval (CI): 52.7 (45.0 – 60.3) µg/L). Relationship between intake/status and breast milk concentration of folate was assessed in 3 studies (Khambalia, Latulippe et al. 2006; Houghton, Yang et al. 2009; West, Yan et al. 2012). Two studies found no association between folic acid supplementation and total folate concentration in breast milk (Khambalia, Latulippe et al. 2006; Houghton, Yang et al. 2009). The third one (West, Yan et al. 2012) found a relationship between folic acid concentration in breast milk and intake of folates (i.e., natural folate + folic acid supplementation), but not between total folate concentration in breast milk and folate intake. Women supplemented with folic acid presented breast milk concentrations of total folate of (weighted mean and 95% CI) 60.4 (54.8 – 65.9) µg/L; those not supplemented presented breast milk concentrations of total folate of (weighted mean and 95% CI) 48.7 (39.6 – 57.8) µg/L. EFSA supporting publication 2014:EN-629 24 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.2. Zinc As described in the study flow diagram, 41 studies were included from the comprehensive literature search on zinc breast milk concentration (January 2000 – January 2014). Details on which are in the following Table 3. Table 3: Summary of the included studies for zinc Publication Population main characteristics (Silvestre, Lagarda et al. 2000) Study performed in Spain (Silvestre, Lagarda et al. 2000) Study performed in Spain Supplementation with the nutrient of interest? Not reported No Maternal zinc intake Not reported Not reported Stage of lactation Colostrum Study performed in Spain Not reported EFSA supporting publication 2014:EN-629 Not reported Yes: no information on supplementation Analytical method FAAS(a) microwave digestion with Zinc concentration in breast milk Mean ± SD: 8.60 ± 1.82 mg/L Transitional milk Mean ± SD: 3.45 ± 0.58 mg/L Mature milk (30 days postpartum) Mean ± SD: 1.97 ± 0.25 mg/L Mature milk (60 days postpartum) Mean ± SD: 1.24 ± 0.33 mg/L Mature milk (90 days postpartum) Mean ± SD: 0.89 ± 0.27 mg/L Colostrum (3 days postpartum) Transitional (15 postpartum) (Rodriguez Rodriguez, Sanz Alaejos et al. 2000) Confounding factors? No FAAS microwave digestion milk days Mature milk (2 weeks – 5 months postpartum) Yes: no information on supplementation AAS(a) with Number of women (number of samples) Not reported (10) Mean ± SD: 7.73 ± 0.86 mg/L 39 (unclear) Mean ± SD: 3.15 ± 0.86 mg/L 15 (unclear) Mean ± SD (range): 2.10 ± 1.10 (0.14 – 3.99) 11 (56) 25 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Zinc concentration in breast milk Number of women (number of samples) mg/L (Sanchez-Hidalgo, Flores-Huerta et al. 2000) Study performed in Mexico Not reported Not reported Milk for preterm newborn Yes: no information on type of milk nor on women details Not reported Individual 1.20 mg/L (Bocca, Alimonti et al. 2000) Study performed in Italy Not reported Not reported Not reported Yes: no information on supplementation liquid chromatography with ICP-AES Mean ± SD (median/range): 2.72 ± 0.07 (0.65/0.28-2.42) mg/L Not reported (60) (Bosscher, Van Caillie-Bertrand et al. 2001) Not reported Not reported Not reported Mature milk Yes: no information on supplementation FAAS Mean ± SD: 1.00 ± 0.1 mg/L 4 (4) (Gulson, Mizon et al. 2001) Study conducted in Australia on 6 Australians and 31 migrants (17 subjects remained included in the study) Not reported 5,33 mg/day for migrants, 6,76 mg/day for australians Not reported Yes: no information on supplementation Not reported Mean ± SD (Median): 2.08 ± 0.91 (1.89) mg/L 17 (78) (Hendricks, Guo et al. 2001) Not reported Not reported Not reported Mature milk months postpartum) (4 Yes: no information on supplementation AES Mean ± SD: 1.20 ± 0.01 mg/L 7 (7) (Kantola and Vartiainen 2001) Study performed in Finland with samples collected in 1987 Not reported Not reported Mature milk (4 weeks postpartum) Yes: no information on supplementation FAAS Mean ± SD: 3.00 ± 1.00 mg/L 175 (175) EFSA supporting publication 2014:EN-629 data: Not reported (Not reported) 26 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Study performed in Finland with samples collected in 1993-95 Zinc concentration in breast milk Number of women (number of samples) Mean ± SD: 1.40 ± 0.70 mg/L 81 (81) (Turan, Saygi et al. 2001) Study performed in Turkey No Not reported Colostrum (48 hours post-partum) No FAAS Mean ± SD (range): 12.9 ± 7.30 (4.5-27.1) mg/L 30 (30) (Silvestre, Martinez-Costa et al. 2001) Study performed in Spain, mothers of term infants Not reported Not reported Colostrum (day 2 and 4 postpartum) Yes: no information on supplementation FAAS Mean ± SD: 7.99 ± 3.23 mg/L 22 (110) (Wasowicz, Gromadzinska al. 2001) et Study performed in Poland, mothers of term infants Not reported Not reported Transitional milk (during the 2nd week) Mean ± SD: 3.31 ± 1.06 mg/L Mature milk (30 days postpartum) Mean ± SD: 2.41 ± 0.90 mg/L Mature milk (60 days postpartum) Mean ± SD: 1.40 ± 0.65 mg/L Mature milk (90 days postpartum) Mean ± SD: 1.05 ± 0.71 mg/L Colostrum (0-4 days postpartum) Transitional (5-9 postpartum) EFSA supporting publication 2014:EN-629 milk days Yes: no information on supplementation ICP-AES Mean ± SD: 8.2 ± 2.8 mg/L 43 (not recorded) Mean ± SD: 3.7 ± 1.8 mg/L 46 (not recorded) 27 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Mature milk (10-30 days postpartum) Zinc concentration in breast milk Number of women (number of samples) Mean ± SD: 1.4 ± 0.7 mg/L 41 (not recorded) (Guillot, Roth et al. 2003) Caucasian (France) mother of preterm infant Not reported Not reported Mixed ColostrumTransitionalmature milk (< 45 days postpartum) Yes: low representativity of the results (1 case) Not reported Individual 0.35 mg/L data: 1 (1) (Bosscher, Van et al. 2003) Not reported Not reported Not reported Mature milk Yes: no information on supplementation FAAS Mean ± SD: 3.00 ± 0.3 mg/L 4 (4) (Domellof, Hernell et al. 2004; Domellof, Lonnerdal et al. 2004) Data on women in Sweden Not reported Not reported Mature milk (6-9 months postpartum) Yes: no information on supplementation AAS Mean ± SD: 0.46 ± 0.86 mg/L 86 (Etcheverry, Wallingford et al. 2004) Mothers of term infants Not reported Not reported Not reported Yes: no information on supplementation ICP-ES Individual 0.30 mg/L Not reported (5) (Sievers and Schaub 2004) Study performed in Germany: woman 1 followed for her 1st baby Not reported Not reported Mature milk (5 weeks postpartum) Yes: low representativity of the results (case study with only 1 woman per group) AAS Median (range): 2.70 (1.00 – 4.40) mg/L 1 (54) Median (range): 2.90 (0.80 – 5.90) mg/L 1 (47) Median (range): 1.80 (0.80 – 2.50) mg/L 1 (24) Mature milk (8 weeks postpartum) Mature milk (12 weeks postpartum) EFSA supporting publication 2014:EN-629 As several samples analysed, results included in weighted milk were these were the mean data: 28 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Mature milk (16 weeks postpartum) Study performed in Germany: woman 1 followed for her 2nd baby Study performed in Germany: woman 2 followed for her n baby EFSA supporting publication 2014:EN-629 Confounding factors? analyses. Analytical method Zinc concentration in breast milk Number of women (number of samples) Median (range): 1.60 (0.60 – 4.00) mg/L 1 (29) Mature milk (5 weeks postpartum) Median (range): 2.50 (2.00 – 3.70) mg/L 1 (12) Mature milk (8 weeks postpartum) Median (range): 2.20 (1.40 – 3.10) mg/L 1 (19) Mature milk (12 weeks postpartum) Median (range): 1.70 (0.30 – 2.10) mg/L 1 (13) Mature milk (16 weeks postpartum) Median (range): 1.70 (1.20 – 2.40) mg/L 1 (20) Mature milk (5 weeks postpartum) Median (range): 3.60 (2.90 – 4.20) mg/L 1 (47) Mature milk (8 weeks postpartum) Median (range): 2.50 (1.20 – 3.30) mg/L 1 (52) Mature milk (12 weeks postpartum) Median (range): 2.30 (1.40 – 3.30) mg/L 1 (43) 29 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Study performed in Germany: woman 2 multiparous for her n+1 baby Stage of lactation Confounding factors? Analytical method Zinc concentration in breast milk Number of women (number of samples) Mature milk (16 weeks postpartum) Median (range): 1.90 (1.00 – 3.40) mg/L 1 (54) Mature milk (5 weeks postpartum) Median (range): 2.90 (1.80 – 4.30) mg/L 1 (14) Mature milk (8 weeks postpartum) Median (range): 2.90 (1.50 – 3.90) mg/L 1 (44) Mature milk (12 weeks postpartum) Median (range): 1.50 (0.60 – 2.90) mg/L 1 (43) Mature milk (16 weeks postpartum) Median (range): 2.00 (1.00 – 3.40) mg/L 1 (42) (Elmastas, Can et al. 2005) Study performed in Turkey Not reported Not reported Mature milk No FAAS Mean ± SD: 1.20 ± 0.01 mg/L 32 (32) (Spevackova, Rychlik et 2005) Study conducted in Czech Republic Not reported Not reported Not reported Yes: no information on supplementation FAAS Mean ± SD: 41.7 ± 2.1 µg/g (not taken into account in the weighted mean analysis because unit conversion was undoable) 207 (not reported) al. (Ustundag, Yilmaz Study performed in Not reported Not reported Colostrum Yes: no information FAAS Mean ± SD: 3.08 ± 20 (20) EFSA supporting publication 2014:EN-629 (0-7 30 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication et al. 2005) Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Turkey, mothers of term infants Stage of lactation days postpartum) Transitional (7-14 postpartum) Study performed in Turkey, mothers of preterm infants (Leotsinidis, Alexopoulos et al. 2005) Greek women No Not reported Analytical method on supplementation Zinc concentration in breast milk Mean ± SD: 2.72 ± 0.20 mg/L Mature milk (21 days postpartum) Mean ± SD: 2.65 ± 0.20 mg/L Mature milk (60 days postpartum) Mean ± SD: 2.81 ± 0.18 mg/L Colostrum (0-7 days postpartum) Mean ± SD: 2.41 ± 0.28 mg/L Transitional (7-14 postpartum) milk days Mean ± SD: 2.28 ± 0.19 mg/L Mature milk (21 days postpartum) Mean ± SD: 2.39 ± 0.20 mg/L Mature milk (60 days postpartum) Mean ± SD: 2.01 ± 0.18 mg/L Colostrum (3 days postpartum) milk days No Number of women (number of samples) 0.30 mg/L milk days Transitional (17 EFSA supporting publication 2014:EN-629 Confounding factors? FAAS Mean ± SD (median/range): 4.91 ± 1.73 (5.01/1.32-9.12) mg/L 180 (180) 95 (95) Mean ± SD (median/range): 31 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method postpartum) Zinc concentration in breast milk Number of women (number of samples) 2.99 ± 0.92 (2.97/0.86-6.55) mg/L (Leverkus, Kutt et al. 2006) Mothers of preterm infants Not reported Not reported Mature milk Yes: low representativity of the result (1 case) Not reported Individual 0.14 mg/L (Piotrowska-Dept, PiotrowskaJastrzebska et al. 2006) Study performed in Poland, white women Not reported Zinc: average intake of natural food 10.7 ± 3.3 mg/d (range: 5.718.2 mg/d) Mixed (< 30 days postpartum) Yes: no information on supplementation AAS Mean ± SD (range): 3.42 ± 1.62 (0.53 – 7.28) mg/L 27 (27) Mature milk (31-90 days postpartum) Mean ± SD (range): 1.50 ± 0.87 (0.12 – 3.58) mg/L 18 (18) Mature milk (90 days postpartum) Mean ± SD (range): 0.86 ± 0.57 (0.28 – 1.51) mg/L 8 (8) Individual 0.26 mg/L data: 1 (1) Individual 0.23 mg/L data: 1 (1) Individual 1.20 mg/L data: 1 (1) (Chowanadisai, Lonnerdal et al. 2006) (Coelho, Fernandes et al. 2006) Study performed in USA Mother of preterm infant Not reported Not reported EFSA supporting publication 2014:EN-629 Not reported Not reported Mature milk Not reported Yes: low reliability of the results (1 case) Yes: low representativity of the result (1 case) Not reported Not reported data: 1 (1) 32 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics (Kienast, Roth et al. 2007) Mother of preterm infant Supplementation with the nutrient of interest? Not reported Maternal zinc intake Not reported Stage of lactation Confounding factors? Mature milk (20 weeks postpartum) Yes: low representativity of the result (1 case) Analytical method Not reported Zinc concentration in breast milk Number of women (number of samples) Individual 0.27 mg/L value: 1 (1) Individual 0.33 mg/L value: 1 (1) Individual 0.16 mg/L value: 1 (1) (Stawarz, Formicki et al. 2007) Polish women Not reported Not reported Mature milk (12 weeks postpartum) Yes: no information on supplementation Voltametric method Mean ± SD (range): 17.94 ± 7.07 (4.42-38.61) mg/kg (not taken into account in the weighted mean analysis because conversion was undoable) 5 (210) (O'Brien, Krebs et al. 2007) 96% Caucasians Yes: 16 of the 26 women received 15 mg zinc supplement all the study long Dietary zinc intake (mean ± SD): 26.1 ± 1.0 mg/d for women supplemented, 12.8 ± 1.4 mg/d for nonsupplemented women Mature milk (0.5 month postpartum) No AAS Mean ± SD: 3.70 ± 1.00 mg/L 26 (26) EFSA supporting publication 2014:EN-629 Mature milk months postpartum) (3 Mean ± SD: 1.50 ± 0.80 mg/L Mature milk months postpartum) (5 Mean ± SD: 1.20 ± 0.70 mg/L Mature months (7 Mean ± SD: 0.80 ± 0.50 mg/L milk 33 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Zinc concentration in breast milk Number of women (number of samples) postpartum) (Almeida, Lopes et al. 2008) Study conducted in Portugal, mother of both term and preterm infants Not reported Not reported Colostrum (2 days postpartum) Yes: no information on supplementation (Mandato, Rubegni et al. 2009) Mother of preterm infant Not reported Not reported Not reported Yes: low representativity of the results (1 case) (Yalcn, Baykan et al. 2009) Study conducted in Turkey, mothers of term infants No Not reported Not reported (Hannan, Faraji et al. 2009) Mexican-American women No Not reported Mature milk (30-45 days postpartum) ICP-MS Mean ± SD: 12.14 ± 4.71 mg/L 34 (34) Mean ± SD: 2.79 ± 1.21 mg/L 19 (19) Not reported Individual 0.05 mg/L 1 (1) No AAS Mean ± SD (median): 4.78 ± 1.83 (4.5) mg/L 47 (47) No FAAS Mean ± SD: 2.1 ± 1.4 mg/L 31 (30) Mean ± SD: 2.0 ± 1.7 mg/L 17 (17) Mean ± SD: 4.01 ± 1.18 mg/kg ((not taken into account in the weighted mean analysis because conversion was undoable) 31 (155 - samples were collected 5 times from each subject: after 1, 4, 8, 12 and 16 weeks of giving birth) Mature milk (1 month postpartum) Mature milk (75-90 days postpartum) (Matos, Moutinho et al. 2009) Study performed in Portugal Not reported Not reported Transitional (7 postpartum) milk days Mature milk (4 weeks postpartum EFSA supporting publication 2014:EN-629 Yes: no information on supplementation ICP-MS data: Mean ± SD: 2.16 ± 0.59 mg/kg ((not taken into account 34 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Zinc concentration in breast milk Number of women (number of samples) in the weighted mean analysis because conversion was undoable) (Yalcin, Yurdakok et al. 2010) Study performed in Turkey, mothers of term infants Not reported EFSA supporting publication 2014:EN-629 Not reported Mature milk (8 weeks postpartum Mean ± SD: 1.49 ± 0.62 mg/kg ((not taken into account in the weighted mean analysis because conversion was undoable) Mature milk (12 weeks postpartum Mean ± SD: 1.08 ± 0.54 mg/kg ((not taken into account in the weighted mean analysis because conversion was undoable) Mature milk (16 weeks postpartum Mean ± SD: 1.01 ± 0.46 µg/kg ((not taken into account in the weighted mean analysis because conversion was undoable) Mixed (10-20 days postpartum) Yes: no information on supplementation AAS Mean ± SD (range): 4.78 ± 1.83 (1.5-9.0) mg/L 44 35 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Zinc concentration in breast milk (Gass, Hafiji et al. 2010) Not reported Not reported Not reported Not reported Yes: low representativity of the results (1 case) Not reported Individual 0.44 mg/L (Orun, Songul Yalcin et al. 2012) Study performed in Turkey, mothers of both term and preterm infants Not reported Not reported Mature milk (52-60 days postpartum) Yes: no information on supplementation ICP-MS Median (1st-3rd quartiles): 0.63 (0.48-0.89) mg/L 142 (not reported) (Bjorklund, Vahter et al. 2012) Study performed in Sweden Not reported Not reported Mature milk (14-21 days postpartum) Yes: no information on supplementation ICP-MS Mean ± SD (median / range): 3.47 ± 0.98 (3.52/1.24-5.71) mg/L 60 (60) (Milacic, Ajlec et al.) Not reported Not reported Not reported Mature milk (16 weeks postpartum) Yes: no information on supplementation FAAS, ICP-MS Mean ± SD: 3.93 ± 0.11 mg/L 1 (not reported) (Miletta, Bieri et al. 2013) Mother infant of term Not reported EFSA supporting publication 2014:EN-629 Not reported data: Number of women (number of samples) Mature milk (26 weeks postpartum) Mean ± SD: 3.06 ± 0.08 mg/L Mature milk (8 weeks postpartum) Mean ± SD: 1.82 ± 0.02 mg/L Mature milk (26 weeks postpartum) Mean ± SD: 1.12 ± 0.02 mg/L Not reported Yes: low representativity of the results (1 case) Not reported Individual data: 0.12 mg/kg (not taken into account in the weighted mean analysis because conversion 1 1 (1) 36 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation with the nutrient of interest? Maternal zinc intake Stage of lactation Confounding factors? Analytical method Zinc concentration in breast milk Number of women (number of samples) was undoable) (Bieri, Petkovic et al. 2013) Not reported Not reported Not reported Not reported Yes: low representativity of the result (1 case) Not reported Individual data: 0.12 mg/kg (not taken into account in the weighted mean analysis because conversion was undoable) 1 (WiniarskaMieczan, 2014) Study performed in Poland Not reported Not reported Mature milk (1-12 months) Yes: No information on supplementation FAAS Mean (range): 323 (323) ± SD Zinc: 1.62 ± 1.76 (0.043-8.16) mg/L Weighted mean analysis for zinc concentration in women milk: Mothers of preterm infants (weighted mean ± SE (95% CI)): 0.47 ± 0.04 mg/L (0.39 – 0.55) (6 studies) Mothers of term infants (weighted mean ± SE (95% CI)): 2.51 ± 0.10 mg/L (2.32 – 2.71) (3 studies) Colostrum (weighted mean ± SE (95% CI)): 8.60 ± 1.82 mg/L (5.03 – 12.17) (1 study) Transitional milk (weighted mean ± SE (95% CI)): 2.72 ± 0.20 mg/L (2.33 – 3.11) (1 study) Mature milk (weighted mean ± SE (95% CI)): 2.48 ± 0.01 mg/L (1.46 – 1.51) (1 study) All samples (weighted mean ± SE (95% CI)): 2.06 ± 0.01 mg/L (2.05 – 2.07) (36 studies) (a) AAS (Atomic Absorption Spectrometry) vs. FAAS (Flame Atomic Absorption Spectrometry). AAS is a more general term than FAAS. Among other methods of AAS methods stands out: ETAAS (Electrothermal Atomic Absorption Spectrometry) and CVAAS (Cold Vapor Atomic Absorption Spectrometry). EFSA supporting publication 2014:EN-629 37 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Forty-one studies, reported in 42 papers, reported zinc concentration in breast milk. Six studies were free of confounders (Silvestre, Lagarda et al. 2000; Turan, Saygi et al. 2001; Elmastas, Can et al. 2005; Leotsinidis, Alexopoulos et al. 2005; O'Brien, Krebs et al. 2007; Yalcn, Baykan et al. 2009; Hannan, Faraji et al. 2009). For zinc determination, the analytical method used is mainly atomic absorption spectrometry (25 studies); ICP-MS is used in 6 studies; voltammetry is used in 1 study. Ten studies did not report the analytical method for zinc dosage. Milks were collected from mothers who gave birth to term (3 studies) and preterm (6 studies) infants, while in the other studies the gestational age was mixed/unspecified (27 studies). Milk samples from women of term infants included colostrum (1 study), transitional milk (1 study), mature milk (1 study) or mixed/unspecified samples (2 studies). The intake of zinc supplements was not reported in any study. Zinc intake was assessed in 4 studies (Gulson, Mizon et al. 2001; Piotrowska-Dept, Piotrowska-Jastrzebska et al. 2006; O'Brien, Krebs et al. 2007; Hannan, Faraji et al. 2009). Zinc status (defined as plasma zinc concentration) was assessed in 8 studies (Wasowicz, Gromadzinska et al. 2001; Guillot, Roth et al. 2003; Domellof, Hernell et al. 2004; Almeida, Lopes et al. 2008; Mandato, Rubegni et al. 2009; Gass, Hafiji et al. 2010; Yalcin, Yurdakok et al. 2010; Bieri, Petkovic et al. 2013). The weighted mean and 95% CI zinc concentration from all samples was 2.06 (2.05 – 2.07) mg/L. The weighted mean analysis shows high levels of zinc in colostrum (weighted mean and 95% CI: 8.60 (5.03 – 12.17) mg/L), then these levels decrease for transitional milk (weighted mean and 95% CI: 2.72 (2.33 – 3.11) mg/L) and mature milk (weighted mean and 95% CI: 1.48 (1.46 – 1.51) mg/L). Mothers of term infants had a 5-fold higher breast milk zinc concentration (weighted mean and 95% CI: 2.51 (2.32 – 2.71) mg/L) than mothers of preterm infants (weighted mean and 95% CI: 0.47 (0.39 – 0.55) mg/L). Two studies showed no significant correlation between milk zinc concentration and maternal plasma zinc (Domellof, Hernell et al. 2004; Gass, Hafiji et al. 2010). Another study found no relationship between zinc dietary intake and breast milk concentration (Hannan, Faraji et al. 2009). The relationship between zinc intake/status and breast milk concentration was not investigated in the other studies. 4.3. Vitamin B6, Vitamin E, choline, phosphorus, potassium 4.3.1. Vitamin B6 As described in the study flow diagram, 4 publications, all from the USA, were included from the comprehensive literature search on vitamin B6, providing data on composition for “vitamin B6” (2 studies), pyridoxal (2 studies), pyridoxamine and pyridoxine (1 study) (January 2000 – January 2014). Details are reported in the following Table 4. EFSA supporting publication 2014:EN-629 38 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Table 4: Summary of the included studies for vitamin B6 Publication Population main characteristics (Lovelady, Williams et al. 2001) American women: Non-Hispanic White (n=8), Black (n=3) Mothers of term infants Supplementation Yes: All women were given a multivitamin supplement which contained 2.0 mg vitamin B6 (pyridoxine-HCl form) Maternal micronutrients intake Stage of lactation Confounding factors No Analytical method microbiologic al assay (using Saccharomyce s uvarum) “Vitamin B6” concentration in breast milk (a) Weight loss group: Dietary vitamin B6 intake: Mature milk: 2.7 ± 0.6 mg/day (baseline), 4-6 weeks (baseline), 146.85 ± 14.89 µg/L (baseline), 1.9 ± 0.2 mg/day (midpoint), 9-11 weeks (midpoint), 179.67 ± 19.46µg/L (midpoint), 1.8 ± 0.3 mg/day (end); 14-16 weeks (endpoint) 174.09 ± 18.95 µg/L (end) Weight loss group Vitamin B6 (mean ± SE): Number of women (number of samples) Weight loss group: 11 (11) Total vitamin B6 intake: 4.5 ± 0.6 mg/day (baseline), 3.8 ± 0.2 mg/day (midpoint), 3.8 ± 0.3 mg/day (end) Control group: Dietary vitamin B6 intake: 2.2 ± 0.1 mg/day (baseline), Control group: Vitamin B6 (mean ± SE): 1 Control group: 10 (10) 141.10 ± 12.86 µg/L (baseline), 161.23 ± 18.61 µg/L 1.9 ± 0.2 mg/day EFSA supporting publication 2014:EN-629 39 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin B6” concentration in breast milk (a) (midpoint), (midpoint), 1.8 ± 0.2 mg/day (end); 173.41 ± 19.46 µg/L (end) Number of women (number of samples) Total vitamin B6 intake: 4.0 ± 0.3 mg/day (baseline), 3.9 ± 0.2 mg/day (midpoint), 3.8 ± 0.2 mg/day (end) (Boylan, Hart et al. 2002) USA: White (16), African-American (2), Hispanic (6), other (1) All were mothers of term infants Yes, with undefined nutrients. Among the 25 subjects, 2: no any vitamin supplements, 5: vitamin supplements (prenatal vitamins or a multivitamin mineral supplement) every other day. All other subjects reported daily supplement use. Vitamin B6 intake (from food and supplements), mean ± SD (median; range): 3.47 ± 1.36 (2.90; 1.22 - 7.18) mg/day. Only 1 subject had an intake of vitamin B6 below the RDA for lactation of 2.0 mg/day. Transitional milk (8-11 days postpartum) No HPLC (highperformance liquid chromatograp hy) Mean ± SD (median; range): Pyridoxal: 25 (25) Pyridoxal: 70.21 ± 50.15 (55.16; 20.06 – 215.64) µg/L Pyridoxamine (when levels were detectable): 21 (21) Pyridoxamine: 10.09 ± 10.09 (8.41; 1.68 – 40.60) µg/L Pyridoxine: 10.15 ± 3.38 (10.15; 6.77 – 13.53) µg/L Pyridoxine (when levels were detectable): 3 (3) No phosphorylated forms of the B-6 vitamers were detected in any of the breast EFSA supporting publication 2014:EN-629 40 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin B6” concentration in breast milk (a) Number of women (number of samples) milk samples (Chang and Kirksey 2002) Study performed in USA with mothers of term infants Yes: vitamin B6 as PNxHCl 2.5 mg Total intake of vitamin B6: 4.1 ± 0.2 mg/d Yes: vitamin B6 as PNxHCl 4.0 mg Vitamin B6 (mean ± SE): 150.74 ± 5.06 µg/L 11 (11) Total intake of vitamin B6: 6.2 ± 0.2 mg/d Vitamin B6 (mean ± SE): 200.31 ± 8.59 µg/L 15 (15) Yes: vitamin B6 as PNxHCl 7.5 mg Total intake of vitamin B6: 9.1 ± 0.2 mg/d Vitamin B6 (mean ± SE): 296.42 ± 14.67 µg/L 10 (10) Yes: vitamin B6 as PNxHCl 10 mg Total intake of vitamin B6: 11.5 ± 0.4 mg/d Vitamin B6 (mean ± SE): 288.33 ± 6.58 µg/L 10 (10) Yes: vitamin B6 as PNxHCl 2.5 mg Total intake of vitamin B6: 3.9 ± 0.2 mg/d Vitamin B6 (mean ± SE): 200.31 ± 5.57 µg/L 9 (9) Yes: vitamin B6 as PNxHCl 4.0 mg Total intake of vitamin B6: 6.3 ± 0.3 mg/d Vitamin B6 (mean ± SE): 293.39 ± 10.62 µg/L 16 (16) Yes: vitamin B6 as PNxHCl 7.5 mg Total intake of vitamin B6: 8.7 ± 0.2 mg/d Vitamin B6 (mean ± SE): 336.89 ± 13.65 µg/L 10 (10) Yes: vitamin B6 as Total intake of vitamin Vitamin B6 (mean ± SE): 375.34 ± 16.70 11 (11) EFSA supporting publication 2014:EN-629 Mature milk (1 month) Mature milk (2 months) No microbiologic al assay (using Saccharomyce s uvarum) 41 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake PNxHCl 10 mg B6: 11.3 ± 0.2 mg/d Yes: vitamin B6 as PNxHCl 2.5 mg Total intake of vitamin B6: 4.4 ± 0.5 mg/d Yes: vitamin B6 as PNxHCl 4.0 mg Stage of lactation Confounding factors Analytical method “Vitamin B6” concentration in breast milk (a) Number of women (number of samples) µg/L Vitamin B6 (mean ± SE): 212.46 ± 9.61 µg/L 10 (10) Total intake of vitamin B6: 5.9 ± 0.1 mg/d Vitamin B6 (mean ± SE): 271.13 ± 9.10 µg/L 16 (16) Yes: vitamin B6 as PNxHCl 7.5 mg Total intake of vitamin B6: 8.9 ± 0.2 mg/d Vitamin B6 (mean ± SE): 357.12 ± 8.09 µg/L 10 (10) Yes: vitamin B6 as PNxHCl 10 mg Total intake of vitamin B6: 11.3 ± 0.2 mg/d Vitamin B6 (mean ± SE): 384.44 ± 20.23 µg/L 11(11) Yes: vitamin B6 as PNxHCl 2.5 mg Total intake of vitamin B6: 3.7 ± 0.1 mg/d Vitamin B6 (mean ± SE): 205.37 ± 8.09 µg/L 7 (7) Yes: vitamin B6 as PNxHCl 4.0 mg Total intake of vitamin B6: 5.9 ± 0.2 mg/d Vitamin B6 (mean ± SE): 321.71 ± 10.12 µg/L 16 (16) Yes: vitamin B6 as PNxHCl 7.5 mg Total intake of vitamin B6: 8.5 ± 0.1 mg/d Vitamin B6 (mean ± SE): 407.71 ± 15.68 µg/L 10 (10) Yes: vitamin B6 as Total intake of vitamin Vitamin B6 (mean ± SE): 487.64 ± 27.83 10 (10) EFSA supporting publication 2014:EN-629 Mature milk (3 months) Mature milk (4 months) 42 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake PNxHCl 10 mg B6: 11.2 ± 0.2 mg/d Yes: vitamin B6 as PNxHCl 2.5 mg Total intake of vitamin B6: 3.6 ± 0.2 mg/d Yes: vitamin B6 as PNxHCl 4.0 mg Stage of lactation Confounding factors Analytical method “Vitamin B6” concentration in breast milk (a) Number of women (number of samples) µg/L Vitamin B6 (mean ± SE): 201.32 ± 8.59 µg/L 5 (5) Total intake of vitamin B6: 5.9 ± 0.2 mg/d Vitamin B6 (mean ± SE): 330.83 ± 13.15 µg/L 13 (13) Yes: vitamin B6 as PNxHCl 7.5 mg Total intake of vitamin B6: 8.8 ± 0.2 mg/d Vitamin B6 (mean ± SE): 401.65 ± 15.18 µg/L 10 (10) Yes: vitamin B6 as PNxHCl 10 mg Total intake of vitamin B6: 11.2 ± 0.2 mg/d Vitamin B6 (mean ± SE): 465.38 ± 21.76 µg/L 8 (8) Yes: vitamin B6 as PNxHCl 2.5 mg Total intake of vitamin B6: 6.0 ± 0.2 mg/d Vitamin B6 (mean ± SE): 222.57 ± 12.65 µg/L 4 (4) Yes: vitamin B6 as PNxHCl 4.0 mg Total intake of vitamin B6: 9.0 ± 0.2 mg/d Vitamin B6 (mean ± SE): 328.80 ± 12.65 µg/L 12 (12) Yes: vitamin B6 as PNxHCl 7.5 mg Total intake of vitamin B6: 11.0 ± 0.1 mg/d Vitamin B6 (mean ± SE): 385.46 ± 14.67 µg/L 10 (10) Yes: vitamin B6 as Total intake of vitamin Vitamin B6 (mean ± SE): 395.56 ± 17.71 6 (6) EFSA supporting publication 2014:EN-629 Mature milk (5 months) Mature milk (6 months) 43 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics (Hampel, York et al. 2012) Caucasian women (from USA) Supplementation Maternal micronutrients intake PNxHCl 10 mg B6: 4.1 ± 0.2 mg/d Not reported Not reported Stage of lactation Confounding factors Analytical method “Vitamin B6” concentration in breast milk (a) Number of women (number of samples) µg/L Mature milk: 4-12 weeks Yes: Few information on population and lack of information on specific supplementation UPLCMS/MS) (ultraperformance liquid chromatograp hy tandem massspectrometry) pyridoxal (median (range)): 29 (6-82) µg/L 28 (28) Weighted mean analysis for total vitamin B6 concentration in women milk (3 studies): All samples dealing with total vitamin B6 concentration (mature milk from supplemented mothers of term infants) (weighted mean ± SE (95% CI)): 244.14 ± 5.96 µg/L (232.45 – 255.83) (2 studies) All samples dealing with both total vitamin B6 concentration and sum of pyridoxal, pyridoxamine and pyridoxine (mature and transitional milks from supplemented mothers of term infants) (weighted mean ± SE (95% CI)): 233.15 ± 5.75 µg/L (221.89 – 244.42) (3 studies) (a) Total vitamin B6 concentrations are reported. Concentrations in individual forms pyridoxal, pyridoxamine and pyridoxine are reported, when available. EFSA supporting publication 2014:EN-629 44 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Four studies reported concentration of total vitamin B6 (2 studies) or individual forms of vitamin B6 (pyridoxal, pyridoxine, pyridoxamine) (2 studies) in breast milk. Three studies were free of confounders (Lovelady, Williams et al. 2001; Boylan, Hart et al. 2002; Chang and Kirksey 2002). Total vitamin B6 was measured via microbiological assays (2 studies); pyridoxal (2 studies), pyridoxamine (1 study) and pyridoxine (1 study) were measured via HPLC-MS/MS. Milk samples included transitional milk (1 study) and mature milk (3 studies). Three studies involved mothers of term infants while the length of gestation was not specified in 1 other study. In two of the studies, mothers were taking vitamin B6 supplements (pyridoxine-HCl form, 2 – 10 mg) (Lovelady, Williams et al. 2001; Chang and Kirksey 2002); in one study mothers were taking multivitamins supplement of undefined concentration (Boylan, Hart et al. 2002) and in one study supplementation was not reported (Hampel, York et al. 2012). Three studies reported intake data (total vitamin B6 intake of 3.47 to 11.5 mg/day) (Lovelady, Williams et al. 2001; Boylan, Hart et al. 2002; Chang and Kirksey 2002); 1 reported data on mothers’ status (defined as plasma total vitamin B6 concentration) (Lovelady, Williams et al. 2001). From data on infant status, Chang and Kirksey 2002 showed that a maternal pyridoxine-HCl supplement of 2.5 mg/day provided an adequate amount of vitamin B6 in breast milk (0.15 mg/day) for the vitamin B6 status parameters and the growth of breast-fed infants. All analyses on total vitamin B6 concentration were performed on mature milk samples from women supplemented with vitamin B6 who gave birth to term infants (2 studies) (weighted mean and 95% CI: 244.14 (232.45 – 255.83) µg/L). An additional study reported total vitamin B6 concentration as the sum of pyridoxal, pyridoxamine and pyridoxine. Samples were transitional milk; women were mothers of term infants and were mostly supplemented with undefined nutrients. The weighted mean and 95% CI for total vitamin B6 concentration from all samples coming from these 3 studies was 233.15 (221.89 – 244.42) µg/L. One study reported that mothers with vitamin B6 intake greater than the median value had a significantly higher median pyridoxal level in their breast milk than did the mothers with intakes below the median value (Boylan, Hart et al. 2002), while the relationship was not investigated in the 3 other studies. EFSA supporting publication 2014:EN-629 45 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.3.2. Vitamin E As described in the study flow diagram, 24 publications (23 studies with the Gossage et al. study reported in 2 references) were included from the comprehensive literature search on “total vitamin E” or tocopherols (alpha-, beta-, delta-, gamma-, individually and/or sums of them) (January 2000 – January 2014). Twenty studies are from Europe, 3 studies are from North America. Details are reported in the following Table 5. Table 5: Publication (Gossage, Deyhim et al. 2000; Gossage, Deyhim et al. 2002) Summary of the included studies for vitamin E Population main characteristics Supplementation Maternal micronutrients intake European American (n=17), Hispanic (n=2), African American (n=2) Yes, but with other nutrient: Betacarotene group with 30 mg/day betacarotene Beta-carotene group: dietary intakes (mean ± SD) No: Placebo group Placebo group: dietary intakes (mean ± SD) Stage of lactation Colostrum: 4 days postpartum Vitamin E: 7.0 ± 4.5 mg Vitamin E: 7.0 ± 3.8 mg Confounding factors No Analytical method HPLC “Vitamin E” concentration in breast milk (a) Both supplemented and placebo groups (mean ± SD): alpha-tocopherol: 13.35 ± 1.98 mg/L Mature milk: 32 days postpartum Both supplemented and placebo groups (mean ± SD): Number of women (number of samples) Beta-carotene group: 10 (80 (8 samples per woman)) Placebo group: 9 (72 (8 samples per woman)) alpha-tocopherol: 4.05 ± 0.52 mg/L EFSA supporting publication 2014:EN-629 46 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (Olafsdottir, Wagner et al. 2001) Study performed in Iceland Yes: cod liver oil (no other supplements) No: no cod liver oil group Cod liver oil group Mature milk: 2-4 months postpartum Vitamin E daily intake: 9.0 ± 1.5 mg/day Yes: lack of information on supplementation of the nutrients of interest (in the article are described only data about cod liver oil supplementation) HPLC Both cod liver oil and no cod liver oil groups alpha-tocopherol (mean ± SE): 4.14 ± 0.20 mg/L gamma-tocopherol (mean ± SE): 1.03 ± 0.06 mg/L tocopherol equivalents TE (alpha-TE = alphatocopherol + 0.25 gamma-tocopherol) (mean ± SE): 4.40 ± 0.21 mg/L No cod liver oil group Vitamin E daily intake: 6.0 ± 0.5 mg/day (Thijssen, Drittij et al. 2002) Study performed in Netherlands, mothers of term infants Yes, with other nutrient than the one of interest (phylloquinone: 0; 0.8; 2.0 or 4.0 mg/day) Not reported Colostrum: 4 days Transitional milk: 8 days Mature milk: 16 days EFSA supporting publication 2014:EN-629 Yes: Few information on population As this calculation method for vitamin E as TE (sum of alpha- + gammatocopherols) is used only once, results were not included in the weighted mean Cod liver oil group: 18 (18) HPLC No cod liver oil group: 59 (59) Vitamin E as TE (alpha- + gammatocopherol) (mean ± SD): 11.41 ± 7.97 mg/L 31 (31) Vitamin E as TE (alpha- + gammatocopherols) (mean ± SD): 5.77 ± 5.38 mg/L 29 (29) Vitamin E as TE (alpha- + gammatocopherols) (mean ± SD): 3.36 ± 2.46 mg/L 28 (28) 47 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (Jewell, Mayes et al. 2004) (Schweigert, Bathe et al. 2004) Study performed in Ireland, Irish women mothers of both term and preterm infants Study performed in Germany, mothers of term infants Not reported No Not reported Not reported Mature milk: 19 days analyses Mixed: 1-41 days Yes: Few information on population and lack of information on specific supplementation Modified version of the step gradientHPLC methods No HPLC Colostrum: 4 ± 2 days Vitamin E as TE (alpha- + gammatocopherols) (mean ± SD): 3.23 ± 2.46 mg/L 28 (28) Median (range): 13 (28) alpha-tocopherol: 6.04 (1.2 – 41.05) µmol/g of fat gammatocopherol:0.52 (0.01 – 2.61) µmol/g of fat Mature milk: 19 ± 2 days Alpha-tocopherol (colostrum) (mean ± SD): 22.01 ± 13.40 mg/L 21 (21) Alpha-tocopherol (mature milk) (mean ± SD): 5.69 ± 2.20 mg/L (Quiles, Ochoa et al. 2006) Spanish women mothers of pre-term infants No supplement containing antioxidant vitamins or coenzyme Q Preterm group: Vitamin E daily intake: 6.1 ± 2.4 mg Colostrum: 3 days No HPLC alpha-tocopherol (mean): 16.37 mg/L Preterm group: 15 (15) delta-tocopherol (mean): 0.10 mg/L gamma-tocopherol (mean): 0.63 mg/L EFSA supporting publication 2014:EN-629 48 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Transitional milk: 8 days alpha-tocopherol (mean): 9.04 mg/L delta-tocopherol (mean): 0.10 mg/L gamma-tocopherol (mean): 0.54 mg/L Mature milk: 30 days alpha-tocopherol (mean): 5.17 mg/L delta-tocopherol (mean): 0.08 mg/L gamma-tocopherol (mean): 0.46 mg/L Spanish women mothers of term infants Full-term group: Colostrum: 3 days Vitamin E daily intake: 6.1 ± 0.9 mg alpha-tocopherol (mean): 24.55 mg/L Full-term group: 15 (15) delta-tocopherol (mean): 0.12 mg/L gamma-tocopherol (mean): 0.88 mg/L Transitional milk: 8 days alpha-tocopherol (mean): 16.37 mg/L delta-tocopherol (mean): 0.12 mg/L gamma-tocopherol (mean): 0.79 mg/L EFSA supporting publication 2014:EN-629 49 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Mature milk: 30 days alpha-tocopherol (mean): 8.61 mg/L delta-tocopherol (mean): 0.10 mg/L gamma-tocopherol (mean): 0.75 mg/L (Romeu-Nadal, Morera-Pons et al. 2006) Spanish women mothers of term infants Not reported Not reported Mature milk (no data about number of days) Yes: Few information on population and lack of information on specific supplementation Method I* Method II* Method III* Alpha-tocopherol: Method I* (mean ± SD): 4.72 ± 0.17 mg/L Not reported Method II* (mean ± SD): 3.71 ± 0.16 mg/L Method III* (mean ± SD): 3.72 ± 0.18 mg/L Gamma-tocopherol: Method I (mean ± SD): 0.43 ± 0.01mg/L Method II (mean ± SD): 0.33 ± 0.01 mg/L (Romeu-Nadal, Castellote et al. 2008) Spanish women Not reported EFSA supporting publication 2014:EN-629 Not reported Mature milk (no data about number of days) Yes: Few information on population and lack of information on specific supplementation HPLC Alpha-tocopherol (mean ± SD): 4.41 ± 0.16 mg/L 10 (20) Gamma-tocopherol ( mean ± SD): 0.47 ± 0.02 mg/L 50 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (Romeu-Nadal, Castellote et al. 2008) Spanish women Not reported Not reported Mature milk (no data about number of days) Yes: Few information on population and lack of information on specific supplementation HPLC Alpha-tocopherol ( mean ± SD): 3.85 ± 0.16 mg/L 10 (20) Gamma-tocopherol ( mean ± SD): 0.37 ± 0.02 mg/L (Michalski, Calzada et al. 2008) French women Not reported Not reported Mature milk (mean ± SD): 6.1 ± 4.0 months Yes: No information on supplementation HPLC Vitamin E as TE (alpha- + gammatocopherols) ( mean ± SD): 1.14 ± 0.52 mg/L 4 (4) (Tokusoglu, Tansug et al. 2008) Turkish women mothers of term infants Not reported Not reported Mature milk: 60-90 days Yes: lack of information on specific supplementation HPLC Alpha-tocopherol (mean ± SD): 9.84 ± 2.13 mg/L 92 (92) (Tijerina-Saenz, Innis et al. 2009) Canadian women (Caucasian 73%) mothers of term infants Yes, with unspecified nutrients: all women reported taking multivitamin supplements Not reported Mature milk: 1 month postpartum Yes: lack of information on specific supplementation HPLC alpha-tocopherol (mean ± SE): 2.32 ± 0.11 mg/L 60 (60) delta-tocopherol (mean ± SE): 0.11 ± 0.01 mg/L gamma-tocopherol (mean ± SE): 0.46 ± 0.03 mg/L EFSA supporting publication 2014:EN-629 51 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (Duda, NogalaKalucka et al. 2009) Polish women Not reported Intake of vitamin E (mean ± SD): 7.7 ± 3.4 mg/day. Mature milk (~96% of the inquired women were breast feeding for 2.5 month on the average, range: 112 months) Yes: lack of information on specific supplementation HPLC Mean ± SD: 30 (30) alpha-tocopherol: 4.11 ± 3.48 mg/L beta-tocopherol: 0.03 ± 0.02 mg/L gamma-tocopherol: 0.31 ± 0.25 mg/L alpha-tocopherol equivalent (alpha-TE (µg) = alphatocopherol (µg) + 0.5 beta-tocopherol (µg) + 0.25 gamma tocopherol (µg) (Olafsdottir et al., 2001)): 4.13 ± 1.94 mg/L (Sziklai-Laszlo, Majchrzak et al. 2009) Hungarian women mothers of term infants No Not reported Transitional milk: 5-10 days Yes: Few information on population and lack of information on dietary micronutrients intake HPLC Transitional milk (mean ± SD): alphatocopherol: 4.14 ± 2.17 mg/L Transitional milk group: 12 (12) gamma-tocopherol: 0.53 ± 0.28 mg/L alpha-TE (α-TE (mg) = α-tocopherol (mg) + 0.25 γ-tocopherol (mg)): 4.27 ± 2.18 mg/L EFSA supporting publication 2014:EN-629 52 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Mature milk: 2-40 weeks Mature milk (mean ± SD): alpha-tocopherol: 3 ± 1.16 mg/L Mature milk group: 18 (18) gamma-tocopherol: 1.17 ± 0.44 mg/L alpha-TE (tocopherol equivalents): 3.3 ± 1.13 mg/L (Molto-Puigmarti, Castellote et al. 2009) Spanish women Not reported Not reported Colostrum Yes: lack of information on specific supplementation and population Ultra Performance Liquid Chromatograp hic System Colostrum (mean ± SD): 10 (10) alpha-tocopherol: 37.84 ± 24.52 mg/L beta + gamma tocopherols: 0.9 ± 0.53 mg/L delta-tocopherol: 0.14 ± 0.09 mg/L Mature milk Mature milk (mean ± SD): alpha-tocopherol: 3.39 ± 2.12 mg/L beta + gamma tocopherol: 0.23 ± 0.17 mg/L delta-tocopherol: 0.03 ± 0.03 mg/L EFSA supporting publication 2014:EN-629 53 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (Orhon, Ulukol et al. 2009) (Molto-Puigmarti, Permanyer et al. 2011) Non-smoker Turkish women mothers of term infants No Total “vitamin A + retinol” (mean (SEM)): 4965.2 (538.5) IU/day Transitional milk (7 days) No HPLC alpha-tocopherol (mean ± SEM): 13.27 ± 0.69 mg/L 20 (20) Smoker Turkish women mothers of term infants No Total “vitamin A + retinol” (mean (SEM)): 4669.0 (358.3) IU/day Transitional milk (7 days) No HPLC alpha-tocopherol (mean ± SEM): 9.99 ± 1.08 mg/L 20 (20) Spanish women Not reported Not reported Mature milk Yes: lack of information on specific supplementation and population UHPLC alpha-tocopherol (mean ± SD): 7.17 ± 2.6 mg/L 10 (10) delta-tocopherol (mean ± SD): 0.1 ± 0.09 mg/L gamma-tocopherol (mean ± SD): 0.48 ± 0.28 mg/L (Antonakou, Chiou et al. 2011) Greek women mothers of term infants No (mothers were not receiving any vitamin E supplements during their pregnancy or postpartum) EFSA supporting publication 2014:EN-629 Dietary intake of vitamin E (mean ± SD): 7.2 ± 3.7 mg/day Mature milk at several time points post-partum: group I: 1 month (20-30 days) Yes: lack of information on specific supplementation As this calculation method for vitamin E as TE (sum of alpha-, (beta- and gamma-) and delta- tocopherol) is used only once, results were not included in the weighted mean HPLC Group I (mean ± SD): I group: 64 (64) alpha-tocopherol: 3.57 ± 1.46 mg/L beta- and gammatocopherol: 0.25 ± 0.14 mg/L delta-tocopherol: 0.01 ± 0.02 mg/L total vitamin E (sum of alpha-, (beta and gamma)- and deltatocopherol): 3.83 ± 1.55 mg/L 54 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk group II: 3 months analyses Group II (mean ± SD): II group: 39 (39) alpha-tocopherol: 3.49 ± 1.81 mg/L beta- and gammatocopherol: 0.32 ± 0.20 mg/L delta-tocopherol: 0.01 ± 0.01 mg/L total vitamin E (sum of alpha-, (beta and gamma)- and deltatocopherol): 3.75 ± 1.55 mg/L group III: 6 months Group III (mean ± SD): III group: 23 (23) alpha-tocopherol: 3.66 ± 2.02 mg/L beta- and gammatocopherol: 0.43 ± 0.52 mg/L delta-tocopherol: 0.01 ± 0.01 mg/L total vitamin E (sum of alpha-, (beta and gamma)- and deltatocopherol): 4.09 ± 2.41 mg/L EFSA supporting publication 2014:EN-629 55 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (Elisia and Kitts 2011) Canadian women Not reported Not reported Mature milk: > 2 weeks HPLC alpha-tocopherol (mean ± SD): 2.11 ± 0.66 mg/L 30 (30) delta-tocopherol (mean ± SD): 0.14 ± 0.07 mg/L gamma-tocopherol (mean ± SD): 0.8 ± 0.28 mg/L (Kasparova, Plisek et al. 2012) Czech women Not reported Not reported Mature milk: 1-2 months Yes: No information on supplementation HPLC Alpha-tocopherol (mean ± SD): 12 (12) Mature milk (1-2 months) group: 3.96 ± 1.42 mg/L EFSA supporting publication 2014:EN-629 Mature milk: 3-4 months Mature milk (3-4 months) group: 3.75 ± 1.68 mg/L Mature milk: 5-6 months Mature milk (5-6 months) group: 3.62 ± 1.51 mg/L Mature milk: 9-12 months Mature milk (9-12 months) group: 4.01 ± 1.34 mg/L 56 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (SzlagatysSidorkiewicz, Zagierski et al. 2012) (MartysiakZurowska, SzlagatysSidorkiewicz et al. 2013) Polish women mothers of term infants Polish women Yes: vitamin supplementation Not reported Colostrum: 3rd day Mature milk: 30th32nd day postpartum Yes: vitamin E daily intake from supplementation (mean ± SD (range)): 7.32 ± 8.34 (0 – 30) mg/day Colostrum group: no data Colostrum: 2nd day postpartum Yes: lack of details on vitamin supplementation HPLC As the calculation for “vitamin E” was not reported, values were not included in the weighted mean analyses. No “Vitamin E” (calculation not reported) (median (range)): 49 (49) Colostrum: 8.86 (5.2212.0) mg/L Transitional milk: 1.1 (0.74-3.94) mg/L HPLC Alpha-tocopherol (mean ± SD): 9.99 ± 1.51 mg/L Colostrum group: 17 (17) Gamma-tocopherol (mean ± SD): 0.57 ± 0.21 mg/L TE (alpha-tocopherol equivalents defined as TE (mg) = alphatocopherol (mg) + 0.25 gamma-tocopherol (mg)) ( mean ± SD): 10.13 ± 1.5 mg/L EFSA supporting publication 2014:EN-629 57 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Transitional milk group: Daily intake of alpha-tocopherol equivalents (mean ± SD (range)): 8.20 ± 3.40 (4.24 - 16.67) mg/day Transitional milk: 14th day postpartum Alpha-tocopherol (mean ± SD): 4.45 ± 0.95 mg/L Transitional milk group: 30 (30) Gamma-tocopherol (mean ± SD): 0.6 ± 0.21 mg/L TE (alpha-tocopherol equivalents defined as TE (mg) = alphatocopherol (mg) + 0.25 gamma-tocopherol (mg)) ( mean ± SD): 4.59 ± 0.93 mg/L Mature milk group (30 days): Daily intake of alpha-tocopherol equivalents (mean ± SD (range)): 8.41 ± 3.48 (3.43 - 16.08) mg/day Mature milk: 30th day postpartum Alpha-tocopherol (mean ± SD): 2.92 ± 0.84 mg/L Mature milk group (30 days): 27 (27) Gamma-tocopherol (mean ± SD): 0.3 ± 0.14 mg/L TE (alpha-tocopherol equivalents defined as TE (mg) = alphatocopherol (mg) + 0.25 gamma-tocopherol (mg)) ( mean ± SD): 3.0 ± 0.85 mg/L EFSA supporting publication 2014:EN-629 58 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Mature milk group (90 days): Daily intake of alpha-tocopherol equivalents (mean ± SD (range)): 9.33 ± 3.80 (4.00 - 15.76) mg/day Mature milk: 90th day postpartum Alpha-tocopherol (mean ± SD): 2.07 ± 0.66 mg/L Mature milk group (90 days): 19 (19) Gamma-tocopherol (mean ± SD): 0.22 ± 0.1 mg/L TE (alpha-tocopherol equivalents defined as TE (mg) = alphatocopherol (mg) + 0.25 gamma-tocopherol (mg)) ( mean ± SD): 2.13 ± 0.67 mg/L (Vahamiko, Isolauri et al. 2013) Finnish women (Caucasian) mothers of term infants Yes: Vitamin E from supplements (mean (95% CI)): 4.91 (3.23 - 6.58) mg Vitamin E from diet (mean (95% CI)): 11.83 (10.93 - 12.73) mg Colostrum Mature milk: 1 month Vitamin E from supplements (mean (95% CI)): 5.65 (3.95-7.34) mg EFSA supporting publication 2014:EN-629 Vitamin E from diet (mean (95% CI)): 9.88 (8.99 – 10.77) mg Colostrum Population allergy (fever, asthma, atopic eczema or food allergy) in the family (mother, father or sibling of unborn child). As the calculation for “vitamin E” was not reported, values were not included in the weighted mean analyses. HPLC “Vitamin E” (calculation not reported) (mean (95% CI)): 16.54 (13.71 – 19.98) mg/L Intervention group - with individual dietary counselling: 44 (44) “Vitamin E” (calculation not reported) (mean (95% CI)): 3.56 (3.05 – 4.16) mg/L “Vitamin E” (calculation not reported) (mean (95% CI)): 12.96 (9.96 – 16.87) mg/L Control group: 45 (45) 59 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Mature milk: 1 month EFSA supporting publication 2014:EN-629 “Vitamin E” (calculation not reported) (mean (95% CI)): 3.41 (2.92 – 3.98) mg/L 60 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Weighted mean analysis for total vitamin E expressed as tocopherol-equivalent (TE (mg) = alpha-tocopherol (mg) + 0.25 gamma-tocopherol (mg)) in women milk (5 studies): Mothers of term infants (weighted mean ± SE (95% CI)): 3.51 ± 1.00 mg/L (1.54 – 5.47) (1 study) Transitional milk (weighted mean ± SE (95% CI)): 4.27 ± 2.18 mg/L (0.01 – 8.54) (1 study) Mature milk (weighted mean ± SE (95% CI)): 3.30 ± 1.13 mg/L (1.09 – 5.51) (1 study) Supplemented women (weighted mean ± SE (95% CI)): 3.59 ± 0.44 mg/L (2.73 – 4.45) (1 study) All samples (weighted mean ± SE (95% CI)): 3.87 ± 0.18 mg/L (3.53 – 4.22) (5 studies) Weighted mean analysis for alpha-tocopherol in women milk (18 studies): Mothers of preterm infants (weighted mean ± SE (95% CI)): 6.84 ± 0.43 mg/L (5.99 – 7.69) (1 study) Mothers of term infants (weighted mean ± SE (95% CI)): 3.45 ± 0.07 mg/L (3.31 – 3.59) (8 studies) Colostrum (weighted mean ± SE (95% CI)): 24.11 ± 5.58 mg/L (13.17 – 35.05) (2 studies) Transitional milk (weighted mean ± SE (95% CI)): 11.86 ± 0.56 mg/L (10.77 – 12.95) (3 studies) Mature milk (weighted mean ± SE (95% CI)): 3.30 ± 0.07 mg/L (3.16 – 3.44) (7 studies) Non supplemented women (either mothers of term and preterm infants) (weighted mean ± SE (95% CI)): 8.28 ± 0.32 mg/L (7.65 – 8.90) (4 studies) Supplemented women (weighted mean ± SE (95% CI)): 3.46 ± 0.44 mg/L (2.61 – 4.32) (1 study) All samples (weighted mean ± SE (95% CI)): 3.74 ± 0.06 mg/L (3.63 – 3.85) (18 studies) (a) Concentrations of individual forms alpha-, beta-, delta-, gamma-tocopherol are reported. Total vitamin E concentration in Tocopherol Equivalents (TE) is reported when available (with definition and formulas applied). When papers reported “Vitamin E” concentration without specifying the definition or formulas, values are reported in italics. *Method I: the rapid direct method for measuring alpha- and gamma-tocopherol in human milk using reversed-phase high performance liquid chromatography with ultraviolet/visible (UV–vis) detection. Method II: saponification with ultraviolet/visible detection. Method III: saponification with evaporative light scattering detection. EFSA supporting publication 2014:EN-629 61 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Vitamin E breast milk concentration was assessed in 24 publications (23 studies) via the quantitation of alpha-tocopherol, beta-tocopherol, delta-tocopherol, gamma-tocopherol (or sum of some of them), or total vitamin E (defined in most of cases as alpha-tocopherol + 0.25 gamma-tocopherol). Five studies were free of confounders (Gossage, Deyhim et al. 2002; Schweigert, Bathe et al. 2004; Quiles, Ochoa et al. 2006; Orhon, Ulukol et al. 2009; Martysiak-Zurowska, SzlagatysSidorkiewicz et al. 2013). The analytical method employed was HPLC-MS/MS (23 studies). Composition data for milks of mothers who gave birth to term infants were available for colostrum (5 studies), transitional milk (5 studies), mature milk (9 studies). Milks were collected from mothers who gave birth to term (11 studies) or preterm infants (1 study), mixed term and preterm infants (1 study), or not specified (11 studies). Vitamin E supplementation of the mothers was mentioned in 2 studies (forms not specified, range: 0 - 30 mg/day) (Martysiak-Zurowska, Szlagatys-Sidorkiewicz et al. 2013; Vahamiko, Isolauri et al. 2013). Maternal vitamin E intake was reported in seven studies (range from 3.43 to 16.47 mg/day) (Gossage, Deyhim et al. 2002; Olafsdottir, Wagner et al. 2001; Quiles, Ochoa et al. 2006; Duda, Nogala-Kalucka et al. 2009; Antonakou, Chiou et al. 2011; Martysiak-Zurowska, Szlagatys-Sidorkiewicz et al. 2013; Vahamiko, Isolauri et al. 2013); 3 studies reported data on status (as plasmatic alpha-tocopherol concentration, sum of plasmatic alpha- and gamma-tocopherols, or “total vitamin E” concentration (with no precision on the tocopherol(s) considered)) (Thijssen, Drittij et al. 2002; Schweigert, Bathe et al. 2004; Vahamiko, Isolauri et al. 2013). Five studies reported total vitamin E expressed as tocopherol-equivalent (TE, TE (mg) = alpha-tocopherol (mg) + 0.25 gamma-tocopherol (mg)). The weighted mean and 95% CI for TE concentration from all samples was 3.87 (3.53 – 4.22) mg/L. Weighted means and 95% CIs for TE at different stages of lactation were as follows: transitional milk (1 study) = 4.27 (0.01 – 8.54) mg/L; mature milk (1 study) = 3.30 (1.09 – 5.51) mg/L. When specified, milk samples were collected from mothers who gave birth to term infants. Mothers of term infants presented TE concentration of 3.51 (1.54 – 5.47) mg/L. When women were supplemented with “vitamin E”, weighted mean and 95% CI for TE was 3.59 (2.73 – 4.45) mg/L. Nineteen studies reported alpha-tocopherol concentration in women milk. The weighted mean and 95% CI for alpha-tocopherol concentration from all samples was 3.74 (3.63 – 3.85) mg/L. Weighted means and 95% CIs at different stages of lactation were as follows: colostrum (2 studies) = 24.11 (13.17 – 35.05) mg/L; transitional milk (3 studies) = 11.86 (10.77 – 12.95) mg/L; mature milk (7 studies) = 3.30 (3.16 – 3.44) mg/L. Milk samples were collected from mothers who gave birth to both term or pre-term infants. Weighted mean and 95% CI was 6.84 (5.99 – 7.69) mg/L) for breast milk of mothers of preterm infants and 3.45 (3.31 – 3.59) mg/L for breast milk of mothers of term infants. The weighted mean and 95% CI were 8.28 (7.65 – 8.90) mg/L for milk from non-supplemented women vs. 3.46 (2.61 – 4.32) mg/L for milk from women supplemented with “vitamin E”. Two studies showed a correlation between the concentration of vitamin E (alpha-TE as the sum of alpha- and gamma-tocopherols) in the milk and its intake (forms not specified, range 6 – 9 mg/day) (Olafsdottir, Wagner et al. 2001; Duda, Nogala-Kalucka et al. 2009), whereas 3 other studies did not find correlation between breast milk vitamin E concentration (alpha-TE as the sum of alpha- and gamma-tocopherols) and intake (forms not specified, 3.43 – 16.67 mg/day) (Antonakou, Chiou et al. 2011; Martysiak-Zurowska, Szlagatys-Sidorkiewicz et al. 2013). One study failed to show correlation between maternal plasma alpha-tocopherol and TE (alpha- + gamma-tocopherol) milk concentrations (Thijssen, Drittij et al. 2002). One study showed that plasma levels of alpha-tocopherol were significantly lower later in lactation (day 19) than shortly after birth (P<0.01), and that levels of carotenoids, alpha-tocopherol and vitamin A were highest in colostrum and declined (P<0.01) (Schweigert, Bathe et al. 2004). EFSA supporting publication 2014:EN-629 62 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.3.3. Choline As described in the study flow diagram, 5 publications, from Europe (4 studies) and the US (1 study), were included from the comprehensive literature search on choline (free and/or total choline, phosphatidylcholine, phosphocholine, glycerophosphocholine, phospholipid-bound choline) (January 2000 – January 2014). Details are reported in the following Table 6. Table 6: Publication (Holmes, Snodgrass et al. 2000) Summary of the included studies for choline Population main characteristics British women Supplementation Not reported Maternal micronutrients intake Not reported Stage of lactation Confounding factors Mixed: 2-6 days vs 7-22 days postpartum Yes: The lack of information on specific supplementation and population Analytical method “Choline” concentration in breast milk (a) Proton nuclear magnetic resonance spectroscopy Colostrum/ Transitional milk (2-6 days) (mean ± SD): Free choline : 11.46 ± 2.08 mg/L Number of women (number of samples) 8 (8) Total choline (sum of free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): 62.50 ± 9.38 mg/L Transitional/Mature milk (7-22 days) (mean ± SD): Free choline (7-22 days): 21.88 ± 5.21 mg/L Total choline (sum of EFSA supporting publication 2014:EN-629 63 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Choline” concentration in breast milk (a) Number of women (number of samples) free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): 133.34 ± 14.58 mg/L (Ilcol, Ozbek et al. 2005) Turkish women Not reported Not reported Colostrum: 0-2 days Yes: lack of information on specific supplementation and population Modification of the enzymatic radiochemical method Colostrum (mean ± SEM): total choline (sum of free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): 70.42 ± 3.65 mg/L Colostrum group: Not reported (21) free choline: 13.75 ± 2.19 mg/L Mature milk: 12-28 days EFSA supporting publication 2014:EN-629 Mature milk (12-28 days) (mean ± SEM): total choline (sum of free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): 166.15 ± 8.54 mg/L Mature milk group (12-28 days): Not reported (14) 64 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Choline” concentration in breast milk (a) Number of women (number of samples) free choline: 31.15 ± 3.75 mg/L Mature milk: 75-90 days Mature milk (75-90 days) (mean ± SEM): total choline (sum of free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): 150.11 ± 8.75 mg/L Mature milk group (75-90 days): Not reported (12) free choline: 29.79 ± 2.19 mg/L Mature milk: 165180 days Mature milk group (165-180 days) (mean ± SEM): total choline (sum of free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): : 140.53 ± 10.94 mg/L Mature milk group (165180 days): Not reported (11) free choline: 13.75 ± 1.56 mg/L Mature milk: 12EFSA supporting publication 2014:EN-629 Mature milk group Mature milk 65 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method 180 days “Choline” concentration in breast milk (a) Number of women (number of samples) (12-180 days) (mean ± SEM): total choline (sum of free choline, phosphocholine, glycerolphosphocholine, phosphatidylcholine, sphingomyelin): 153.76 ± 5.00 mg/L group (12-180 days): Not reported (95) free choline: 23.75 ± 1.04 mg/L (Fischer, Da Costa et al. 2010) American (89%), African-American (3%), Asian (6%), American Indian (1%), other (1%) Yes: Supplemented group with 750 mg choline/day No: Placebo group Supplemented group: Dietary choline (mean ± SE (range)) 338 ± 14 (124 - 622 ) mg/day; Total choline for diet and supplement (mean ± SE): 1088 ± 14 mg/day Placebo group: Dietary choline (mean ± SE (range)): 364 ± 18 (139 671) mg/day Mature milk: 45 days No Liquid chromatograp hy/mass spectrometry Supplemented group (mean ± SE): Supplemente d group: 51 (51) free choline: 11.04 ± 1.04 mg/L phosphatidylcholine: 11.77 ± 0.52 mg/L Placebo group (mean ± SE): Placebo group: 48 (48) free choline: 8.65 ± 0.83 mg/L phosphatidylcholine: 11.15 ± 0.73 mg/L EFSA supporting publication 2014:EN-629 66 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication (Ozarda, Cansev et al. 2014) Population main characteristics Turkish women Supplementation Not reported Maternal micronutrients intake Not reported Stage of lactation Colostrum: 3 days Transitional milk: 6-14 days Confounding factors Analytical method Yes: Few information on population and lack of information on specific supplementation Not reported “Choline” concentration in breast milk (a) Colostrum group (median, as determined graphically): Free choline: 50 mg/L Number of women (number of samples) Colostrum group: 67 (67) Total choline (no details on the forms taken into account): 425 mg/L As values were very high compared to the other papers, we did not include them in the weighted mean analyses Transitional milk group (median, as determined graphically): Free choline: 120 mg/L Transitional milk group: 47 (47) Total choline (no details on the forms taken into account): 2 250 mg/L Mature milk: 28178 days Mature milk group (median, as determined graphically): Free choline: 100 mg/L Mature milk group: 71 (71) Total choline(no details on the forms taken into account): 2 050 mg/L Ozarda, Cansev et Turkish women No EFSA supporting publication 2014:EN-629 Not reported Colostrum: 1-3 No HPLC for free Median (1st-3rd 67 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication al. 2014 Population main characteristics Supplementation mothers of term infants Maternal micronutrients intake Stage of lactation days Confounding factors Analytical method “Choline” concentration in breast milk (a) choline, phosphorcholine, glycerolphosphocholine and total choline quartiles) Enzymatic colorimetric method for phospholipidbound choline Glycerophosphocholine: 24.69 (10.29 – 50.67) mg/L Number of women (number of samples) Free choline: 7.40 (2.19 – 13.65) mg/L Phosphocholine: 7.00 (2.39 – 20.62) mg/L Phospholipid-bound choline: 20.21 (18.44 – 22.61) mg/L Total choline: 42.40 (31.36 – 72.09) mg/L Mature milk: 22180 days Median (1st-3rd quartiles) Free choline: 9.69 (6.98 – 13.85) mg/L Phosphocholine: 64.64 (48.06 – 96.49) mg/L Glycerophosphocholine: 246,42 (194.46 – 293.49) mg/L EFSA supporting publication 2014:EN-629 68 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Choline” concentration in breast milk (a) Number of women (number of samples) Phospholipid-bound choline: 19.38 (17.60 – 22.92) mg/L Total choline: 159.59 (130.21 – 176.57) mg/L Weighted mean analysis for choline total/free concentration in women milk (4 studies): Supplemented women (weighted mean ± SE (95% CI)): NA*/11.63 ± 0.47 mg/L (10.71 – 12.54) (1 study) Non supplemented women (weighted mean ± SE (95% CI)): 56.90 ± 8.99 mg/L (39.29 – 74.51)/10.01 ± 0.53 mg/L (8.97 – 11.05) (2 studies) Mothers of term infants (weighted mean ± SE (95% CI)): 56.90 ± 8.99 mg/L (39.29 – 74.51)/8.97 ± 1.95 mg/L (5.14 – 12.79) (1 study) Colostrum (weighted mean ± SE (95% CI)): 42.40 ± 9.60 mg/L (23.58 – 61.22)/7.40 ± 3.47 mg/L (0.59 – 14.21) (1 study) Mature milk (weighted mean ± SE (95% CI)): 159.59 ± 25.55 mg/L (109.52 – 209.66)/9.69 ± 2.36 mg/L (5.07 – 14.31) (1 study) All samples (weighted mean ± SE (95% CI)): 105.71 ± 2.36 mg/L (101.08 – 110.35)/12.82 ± 0.31 mg/L (12.21 – 13.44) (4 studies) (a) Total and free choline concentrations are reported. When available, phosphatidylcholine concentration is also reported. *NA: not applicable, total choline was not measured. Five studies deal with choline breast milk concentration (free and/or total choline, phosphatidylcholine, phosphocholine, glycerophosphocholine, phospholipidbound choline). Two studies were free of confounders (Fischer, Da Costa et al. 2010; Ozarda, Cansev et al. 2014). Free choline (5 studies), total choline (4 studies), phosphatidylcholine (1 study), phosphocholine (1 study), glycerophosphocholine (1 study) and phospholipid-bound choline (1 study) were measured via HPLCMS/MS (2 studies), enzymatic method (2 studies) or proton nuclear magnetic resonance spectroscopy (1 study). One study (Ozarda, Cansev et al. 2014) did not report the analytical method for choline analysis. Composition data were available for colostrum (1 study) and mature milk (1 study). The gestational age of the EFSA supporting publication 2014:EN-629 69 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk infants (term/preterm) was specified only in one study where mothers of term infants were involved. One study reported data on choline intake from diet and supplementation (mean dietary intake was 351 mg/day and mean total intake for supplemented women was 1088) (Fischer, Da Costa et al. 2010). The weighted mean and 95% CI from all samples was 12.82 (12.21 – 13.44) mg/L for free choline and 105.71 (101.08 – 110.35) mg/L for total choline concentrations, respectively. Weighted means and 95% CIs at different stages of lactation were as follows (free choline/total choline): colostrum = 7.40 (0.59 – 14.21)/ 42.40 (23.58 – 61.22) mg/L; mature milk = 9.69 (5.07 – 14.31)/159.59 (109.52 – 209.66) mg/L. When specified, milk samples were collected from mothers who gave birth to term infants (weighted mean and 95% CI for free choline/total choline: 8.97 (5.14 – 12.79)/56.90 (39.29 – 74.51) mg/L). Free choline breast milk concentration was (weighted mean and 95% CI): 11.63 (10.71 – 12.54) mg/L in women supplemented with choline and (weighted mean and 95% CI): 10.01 (8.97 – 11.05) mg/L in women non-supplemented. Total choline concentration was only reported for non-supplemented women (weighted mean and 95% CI): 56.90 (39.29 – 74.51) mg/L. Two studies investigated choline status (defined by free choline plasma concentration) and found a correlation between choline status and breast milk free choline concentration (Ilcol, Ozbek et al. 2005; Fischer, Da Costa et al. 2010). Breast milk concentrations of choline, phosphatidylcholine and phosphocholine were significantly correlated with total choline intake (1088 mg/day) in one study (Fischer, Da Costa et al. 2010). One study investigated changes with time according to breast milk “choline” concentration (Ilcol, Ozbek et al. 2005). They showed that, in mature milk, free choline, phosphocholine and glycerophosphocholine concentrations were significantly higher than the observed concentrations in colostrum, but that total phospholipid-bound choline, phosphatidylcholine and sphingomyelin contents of mature milk and colostrum were similar. Then, free choline contents in mature breast milk decreased with time with a significant inverse relationship between free choline concentrations in breast milk and lactating days; on the contrary, there were no significant relationships between the lactation days and total choline, phosphocholine, glycerophosphocholine, phosphatidylcholine or sphingomyelin contents of breast milk. EFSA supporting publication 2014:EN-629 70 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.3.4. Phosphorus As described in the study flow diagram, 5 publications were included from the comprehensive literature search on phosphorus (January 2000 – January 2014). Details are reported in the following Table 7. Table 7: Publication Summary of the included studies for phosphorus Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method Phosphorus concentration in breast milk Number of women (number of samples) (SanchezHidalgo, FloresHuerta et al. 2000) Mexican women Not reported Not reported Not reported Yes: lack of information on specific supplementation and population Not reported Phosphorus: 140 mg/L Not reported (Gulson, Mizon et al. 2001) 6 Australians and 31 migrants Not reported Phosphorus daily intake (mean): 606 mg (nonpregnant migrants), 788 mg (pregnant migrants), 940 mg (Australian pregnant subjects). Not reported Yes: No information on supplementation Not reported Mean ± SD (median): 17 (78) No Not reported Phosphorus:117.8 ± 16.94 (120) mg/L Potassium daily intake (mean): 1392 mg (nonpregnant migrants), 1710 mg (pregnant migrants), 1938 mg (Australian pregnant subjects) (Nickkho-Amiry, Prentice et al. Arab women (14) No vitamin D supplements EFSA supporting publication 2014:EN-629 Dietary phosphorus intake (median (range)): 745 (179 - 915) mg/day Mature milk: 9-13 weeks Phosphorus (median (range)): 124.62 (74.40 Arab women: 14 (14) 71 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method Phosphorus concentration in breast milk Number of women (number of samples) – 186.93) mg/L 2008) White Caucasian women (10) from United Kingdom (Witczak and Jarnuszewska 2011) Polish women (Bjorklund, Vahter et al. 2012) Swedish women Dietary phosphorus intake (median (range)): 841 (764 - 987) mg/day Not reported Not reported Not reported Not reported Mature milk: 5-6 months Mature milk: 14-21 days Yes: lack of information on specific supplementation and population ICP-AES Yes: No information on supplementation ICP-MS Phosphorus (median (range)): 123.69 (76.88 – 159.65) mg/L White Caucasian women: 10 (10) Mean: Not reported (9) Phosphorus:13 mg/100g (conversion undoable, data was not included in the analyses) Phosphorus (mean ± SD): 172 ± 23 mg/L 60 (840) Weighted mean analysis for phosphorus concentration in women milk: All samples (weighted mean ± SE (95% CI)): 131.71 ± 7.12 mg/L (117.75 – 145.67) (4 studies) Five studies reported phosphorus breast milk concentration. One study was free of confounders (Nickkho-Amiry, Prentice et al. 2008). Phosphorus concentration was quantified via the ICP-MS analytical method (2 studies). Three studies did not report the analytical method for phosphorus dosage. Three studies were performed on mature milk samples and 2 other studies did not precise the stage of lactation. The involvement of mothers of term or preterm infants was not specified. Two studies reported on phosphorus intakes (range: 179 – 987 mg/day) (Gulson, Mizon et al. 2001; Nickkho-Amiry, Prentice et al. 2008). Phosphorus status, as defined by phosphorus plasma concentration, was reported in one study (Nickkho-Amiry, Prentice et al. 2008). The weighted mean and 95 % CI phosphorus concentration from all samples was 131.71 (117.75 – 145.67) mg/L. There was no information from available studies on the relationship between phosphorus intake (including supplementation) or status and breast milk concentration. EFSA supporting publication 2014:EN-629 72 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.3.5. Potassium As described in the study flow diagram, 3 publications were included from the comprehensive literature search on potassium (October 2010 – January 2014). Details are reported in the following Table 8. Table 8: Publication Summary of the included studies for potassium Population main characteristics (Witczak and Jarnuszewska 2011) Polish women (Bauer and Gerss 2011) German mothers of pre-term infants German mothers of term infants Supplementation Not reported Not reported Not reported EFSA supporting publication 2014:EN-629 Maternal micronutrients intake Not reported Not reported Not reported Stage of lactation Mature milk: 5-6 months Mixed (1-8 weeks) Mixed (1-8 weeks) Confounding factors Analytical method Potassium concentration in breast milk Yes: lack of information on specific supplementation and population ICP-AES Mean: Yes: No information on supplementation Absorption spectrometer and colorimetric assay with endpoint determination Mean ± SD: Yes: No information on supplementation Absorption spectrometer and colorimetric Mean ± SD: Number of women (number of samples) Not reported (9) Potassium:52 mg/100g (conversion undoable, these results were not included in the analyses) Potassium: Preterm group (<28 weeks) 547.38 ± 86.02 mg/L; Preterm group (28-31 weeks) 512.19 ± 97.75 mg/L; Preterm group (32-33 weeks) 473.09 ± 70.38 mg/L Potassium: 449.63 ± Total number of subjects: 102 (no data) Total number of subjects: 102 (no data) 73 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication (Bjorklund, Vahter et al. 2012) Population main characteristics Swedish women Supplementation Not reported Maternal micronutrients intake Not reported Stage of lactation Mature milk: 14-21 days Confounding factors Yes: No information on supplementation Analytical method Potassium concentration in breast milk assay with endpoint determination 74.29 mg/L ICP-MS Potassium (mean ± SD): 633 ± 4 mg/L Number of women (number of samples) 60 (840) Weighted mean analysis for potassium concentration in women milk (2 studies): Mothers of preterm infants (weighted mean ± SE (95% CI)): 505.09 ± 47.58 mg/L (411.82 – 598.35) (1 study) Mothers of term infants (weighted mean ± SE (95% CI)): 449.63 ± 74.29 mg/L (304.02 – 595.24) (1 study) All samples (weighted mean ± SE (95% CI)): 561.10 ± 28.31 mg/L (505.62 – 616.58) (2 studies) Three studies reported potassium breast milk concentration. No study was free of confounders. Potassium concentration was quantified via the ICP-MS analytical method (3 studies). Analyses were performed on mature milk samples (2 studies) or mixed milk samples (transitional/mature milk, 1 study. When reported, milks were collected from mothers who gave birth to both term and preterm infants (1 study). None of the studies reported intake and/or status data. The weighted mean and 95% CI potassium concentration from all samples was 561.10 (505.62 – 616.58) mg/L. Mothers of preterm infants presented potassium breast milk concentration of (weighted mean and 95% CI): 505.09 (411.82 – 598.35) mg/L, mothers of term infants presented potassium breast milk concentration of (weighted mean and 95% CI): 449.63 (304.02 – 595.24) mg/L. There was no information from these studies on the relationship between potassium intake (including supplementation) or status and breast milk concentration. EFSA supporting publication 2014:EN-629 74 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.4. Vitamin A, Vitamin B1, chloride, copper, magnesium, sodium 4.4.1. Vitamin A As described in the study flow diagram, 19 publications (18 studies) were recorded from the comprehensive literature search on vitamin A (January 2000 – January 2014). Details are reported in the following Table 9. Table 9: Summary of the included studies for vitamin A Publication Population main characteristics Sanchez-Hidalgo, Flores-Huerta et al. 2000 Mexican women mothers of preterm infants Not reported Not reported Olafsdottir, Wagner et 2001 Icelandic women Yes: cod liver oil (no other supplements); Cod liver oil Daily intakes: vit ± 1.5 mg/day, vit specified): 3653 mg/day al. Supplementation No: no cod liver oil group Maternal micronutrients intake group: E: 9.0 A (not ± 645 No cod liver oil group: Daily intake: vit E: 6.0 ± 0.5 mg/day, vit A (not specified): 1165 ± 124 mg/day EFSA supporting publication 2014:EN-629 Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) Not reported Yes: no information on type of milk nor on women details; besides, there is a strong suspicion of a mistake in the article for the recording of the value (this measure has been excluded from the calculations) Not reported “Vitamin A” (not specified): 223 IU/dl Not reported Mature milk: 2-4 months Yes: lack of information on supplementation of the nutrients of interest (In the article are described only data about cod liver oil supplementation) HPLC Mean ± SE: 18 (18) Vitamin A (retinol equivalents RE calculated as follows: RE (µg) = all-trans retinol (µg) + 0.546 retinylpalmitate (µg) + 1/6 ß-carotene + 1/12 α-carotene + 1/12 cryptoxanthin): 618 ± 59 (59) The results for all subjects (77(77 samples)) are also presented. 75 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) 35 µg/L Vitamin A (alltransretinol): 87 ± 12 µg/L Vitamin A (retinylpalmitate): 965 ± 55 µg/L Median (range): Vitamin A (RE): 584 (177-1 889) µg/L Vitamin A (alltransretinol): 55 (17651) µg/L Vitamin A (retinylpalmitate): 868 (264-2 876) µg/L Gossage, Deyhim et al. 2002; Gossage, Deyhim et al. 2000 European American (n=17), Hispanic (n=2), African American (n=2) Yes: Beta-carotene group: betacarotene 30 mg/day; No: Placebo group Beta-carotene group: dietary intakes (mean ± SD): vit A: 2149 ± 1141 µg RE (formula not reported); vit E: 7.0 ± 4.5 mg; total carotenoids: 12060 ± 2934 µg; betacarotene: 4942 ± 2429 µg; alpha-carotene: 844 ± 683 µg Colostrum: 4 days Mature days milk: 32 No but strong suspicion of error according to units, not included in the calculations. HPLC Mean ± SD (data for all subjects): Vitamin A (retinol): 1 416 208.8 ± 154 396.6 µg/L Beta-carotene group: 10 (80) Placebo group: 9 (72) Mean ± SD (data for all subjects): Vitamin A (retinol): 595 529.6 ± 595 529.6 µg/L Placebo group: dietary intakes (mean ± SD): vit A: 2378 ± 1008 µg RE; EFSA supporting publication 2014:EN-629 76 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) vit E: 7.0 ± 3.8 mg; total carotenoids: 16733 ± 12586 µg; betacarotene: 6490 ± 4455 µg; alpha-carotene: 1491 ± 1186 µg Canfield, Clandinin et al. 2003 Australian women, Canadian women, Mexican women, British women, American women mothers of term infants No: Mothers who were taking vitamins or other supplements containing carotenoids or vitamin A > 8000 IU/day were excluded. Not reported Mature milk (1-12 months) No HPLC Mean ± SE (Australia, Canda, Mexico, United Kingdom, United States): Alpha-carotene: 18.25 ± 1.61 µg/L 19.33 ± 1.61 µg/L 16.64 ± 1.07 µg/L 16.64 ± 1.61 µg/L 8.59 ± 1.07 µg/L 48 (48) 53 (53) 47 (47) 49 (49) 41 (41) Beta-carotene: 32.21 ± 3.76 µg/L 19.33 ± 1.61 µg/L 27.38 ± 2.68 µg/L 25.77 ± 1.61 µg/L 19.86 ± 2.15 µg/L 53 (53) 55 (55) 50 (50) 49 (49) 49 (49) Retinol: 311.09 ± 15.75 µg/L 340.30 ± 18.91 µg/L 378.40 ± 24.92 µg/L 301.46 ± 14.32 µg/L EFSA supporting publication 2014:EN-629 53 (53) 55 (55) 50 (50) 50 (50) 77 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Jewell, Mayes et al. 2004 Irish women mothers of both term and preterm infants Not reported Schweigert, Bathe et al. 2004 German mothers infants No supplements containing carotenoids or vitamin A of women term Maternal micronutrients intake Not reported Not reported Stage of lactation Mixed: 1-41 days Colostrum: 4 ± 2 days Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) 351.74 ± 24.92 µg/L 49 (49) 13 (28) Yes: Few information on population and lack of information on specific supplementation Modified version of the step gradientHPLC methods Median (range): No HPLC Vitamin A (retinol) (colostrum) (mean ± SD): 1 532.51 ± 724.72 µg/L Vitamin A (retinol): 1.49 (0.28 – 7.96) µmol/g of fat Vitamin A (alphacarotene): 12.77 (0.063.14) nmol/g of fat Vitamin A (betacarotene): 1.7 (0.05.07) nmol/g of fat 21 (21) Alpha-carotene (colostrum) (mean ± SD): 91.48 ± 79.19 µg/L Beta-carotene (colostrum) (mean ± SD): 227.31 ± 175.34 µg/L Mature milk: 19±2 days Vitamin A (retinol) (mature milk) (mean ± SD): 830.71 ± 320.82 µg/L Alpha-carotene (mature milk) (mean ± EFSA supporting publication 2014:EN-629 78 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) SD): 11.38 ± 7.68 µg/L Beta-carotene (mature milk) (mean ± SD): 41.98 ± 24.80 µg/L Schulz, Engel et al. 2007 Aurvag, Henriksen et al. 2007 German mothers infants of women term Norwegian women mothers of preterm infants Tokusoglu, Tansug et al. 2008 Turkish mothers infants Tijerina-Saenz, Innis et al. 2009 Canadian women (Caucasian 73%) mothers of term of women term No Exclusion criteria: intake beta-carotene (2gm/d) or vitamin A (>2000 IU/d) Retinol intake (mean ± SD): 0.95 ± 0.64 mg/d; Total vit A (not specified, mean ± SD): 2.11 ± 0.89 mg/d Colostrum (2 days) Yes: Multivitamins with 750 µg retinol equivalents/day regardless of infant weight for the reference protocol; human milk fortifier corresponding to 513 to 1026 µg retinol equivalents/day according to infant weight Not reported Infants in the modified group received significantly more vitamin A than infants in the reference group during three out of the four periods. The difference in vitamin A intake was greatest in the last period (gestational age > 37 weeks): 578 versus 316 g/kg/day (p = 0.02). Mixed Not reported Mature milk: 60-90 days Yes: The lack of information on specific supplementation HPLC Vitamin A (retinol) (mean ± SD): 815 ± 120.6 µg/L 92 (92) Yes: All women reported taking multivitamin Not reported Mature month No HPLC Mean ± SE (range): Vitamin A (all-transretinol): 80 ± 10 (10- 60 (60) EFSA supporting publication 2014:EN-629 No HPLC Mean ± SD: Retinol: 1105.70 850.76 µg/L ± Retinol: 27 (27) Beta-carotene: 26 (26) Beta-carotene: 365.07 ± 327.49 µg/L No HPLC “Vitamin (unspecified) However, due to the uncertainty of the value for vitamin A concentration, it was not included in the weighted mean analyses. milk: 1 Mean: A” Mixed milks from reference and modified protocols: 540 µg/L Reference protocol: 23 (31 – total number of samples); Modified protocol: 30 (31 – total number of samples) 79 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics infants Tacken, Vogelsang et al. 2009 Women Netherlands mothers of infants Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method supplements in term Yes: 6 women used multivitamin supplements containing 1440 µg β-carotene per day “Vitamin A” concentration in breast milk (a) Number of women (number of samples) 200) µg/L Not reported Mature milk (mean ± SD: 4.2 ± 1.2 months) No HPLC Median quartile): (1st, 3rd Beta-carotene: (0-8.59) µg/L 5.37 30 (30) Alpha-carotene: 15.57 (11.81-25.77) µg/L Duda, NogalaKalucka et al. 2009 Polish women Not reported The mean intake of vitamin E was 7.7 ± 3.4 mg/day. The mean vitamin A equivalent concentration (formula not given) in daily food rations (DFR) was 1012 ± 735 μg/day. Orhon, Ulukol et al. 2009 Non-smoker Turkish women mothers of term infants No Total “vitamin A + retinol” (mean (SEM)): 4965.2 (538.5) IU/day Mature milk (~96% of the inquired women were breast feeding for 2.5 month on the average-this period ranged from 1-12 months) Yes: The lack of information on specific supplementation HPLC Mean ± SD: vitamin A (all-trans retinol): 570.70 ± 500.30 µg/L; Median (range) vitamin A (all-trans retinol): 293.8 µg/L (157.2-1424.1 µg/L) 30 (30) Transitional milk (7 days) No HPLC β –carotene (mean ± SEM): 536.9 ± 80.6 µg/L 20 (20) Retinol (mean ± SEM): 2 463.5 ± 200.5 µg/L Smoker Turkish women mothers of term infants No Total vitamin A + retinol (mean (SEM)): 4669.0 (358.3) IU/day Transitional milk (7 days) No HPLC β –carotene (mean ± SEM): 483.2 ± 64.4 µg/L 20 (20) Retinol (mean ± SEM): 2 320.3 ± 171.9 µg/L Schweigert, Raila German women Not reported EFSA supporting publication 2014:EN-629 Not reported Not reported Yes: No HPLC Vitamin A No data (25) 80 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation et al. 2011 Confounding factors Analytical method information on supplementation and population “Vitamin A” concentration in breast milk (a) Number of women (number of samples) (unspecified) (Mean ± SD): Standard procedure of the extraction (A): 493 ± 327 µg/L Due to the uncertainty of the value for vitamin A concentration, it was not included in the weighted mean analyses Vitamin A (unspecified) (Mean ± SD): Ready-to-use extraction (B): 507 ± 367 µg/L Vitamin A (unspecified) (Mean ± SD): Disposable vial measured in the portable fluorophometer, iCheck (C): 493 ± 332 µg/L Kasparova, Plisek et al. 2012 Czech mothers women Not reported EFSA supporting publication 2014:EN-629 Not reported Mature milk: 1-2 months Yes: No information on supplementation HPLC Vitamin A (retinol) (mean ± SD): 12 (12) Mature milk (1-2 months) group: 458.32 ± 286.45 µg/L Mature milk: 3-4 months Mature milk (3-4 months) group: 315.10 ± 257.81 µg/L Mature milk: 5-6 Mature milk (5-6 months) group: 229.16 81 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics SzlagatysSiodorkiewicz, Zagierski et al. 2012 Vähämiko, Isolauri et 2013 al. Polish mothers infants women of term Finnish women (Caucasian) Supplementation Maternal micronutrients intake Yes: Among 63.18% and 52% women it was recorded use of vitamin supplementation, whose milk samples were examined on the 3rd and 30th32nd days after delivery. Not reported Yes: Vit. A (retinol) from supplements mean (95% CI): 35.6 (5.46 - 65.74) µg Vit. A (RE, formula not specified) from diet mean (95% CI): 1164 (985-1 344) RE Stage of lactation EFSA supporting publication 2014:EN-629 A (retinol) Vit. A (RE, formula not Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) months ± 114.58 µg/L Mature milk: 9-12 months Mature milk (9-12 months) group: 171.87 ± 114.58 µg/L Colostrum: 3rd day No Transitional milk: 30th-32nd day However, due to the uncertainty of the value for vitamin A concentration, it was not included in the weighted mean analyses. Colostrum Mature month Vit. Confounding factors milk: Colostrum Population allergy (fever, asthma, atopic eczema or food allergy) in the family (mother, father or sibling of unborn child). 1 Due to the uncertainty of the value for vitamin A concentration, it was not included in the weighted mean analyses. HPLC Median (1st, 3rd quartile): Vitamin A (unspecified): 126.15 (79.12-158.63) µg/L 49 (49) Median (1st, 3rd quartile): Vitamin A (unspecified): 84.7 (51.45-134.68) µg/L HPLC Mean (95% CI): Vitamin A (unspecified) (Intervention group with individual dietary counselling): 1372.10 (1214.55-1552.56) µg/L Intervention group - with individual dietary counseling: 44 (44); Control group: 45 (45) Vitamin A (unspecified) (Intervention group with individual dietary counselling): 492.69 (429.68-564.31) µg/L Vitamin A 82 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Song, Jouni et al. 2013 Population main characteristics American women mothers of term infants Supplementation Maternal micronutrients intake from supplements mean (95% CI): 42.01 (11.5-72.52) µg specified) from diet mean (95% CI): 969 (792-1147) RE Not reported Not reported Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) (unspecified) (Control group): 1051.27 (859.35-1283.30) µg/L Mature month milk: 1 Transitional milk (1 week) Vitamin A (unspecified) (Control group): 466.91 (409.60-529.93) µg/L Yes: No information on supplementation Liquid chromatograp hy-diode array detector Mean ± SE (range): Alpha-carotene: 31.68 ± 7.25 (6.44-118.43) µg/L; Beta-carotene: 88.21 ± 13.53 (9.29-175.99) µg/L Mature weeks) milk (4 16 14 15 17 16 16 (16) (16) (14) (15) (17) (16) Alpha-carotene: 10.31 ± 1.61 (3.92-24.96) µg/L; Beta-carotene: 56.05 ± 14.87 (5.74-202.61) µg/L Mature weeks) milk (13 Alpha-carotene: 12.46 ± 2.58 (1.99-43.06) µg/L; Beta-carotene: 47.24 ± 12.51 (4.56-189.30) µg/L EFSA supporting publication 2014:EN-629 83 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) Weighted mean analysis for retinol concentration in women milk (8 studies): Mothers of term infants (weighted mean ± SE (95% CI)): 233.74 ± 6.32 µg/L (221.36 – 246.12) (6 studies) Colostrum (weighted mean ± SE (95% CI)): 1 353.03 ± 551.69 µg/L (271.72 – 2434.34) (2 studies) Transitional milk (weighted mean ± SE (95% CI)): 2 380.97 ± 130.50 µg/L (2 125.18 – 2 636.75) (1 study) Mature milk (weighted mean ± SE (95% CI)): 228.55 ± 6.32 µg/L (216.15 – 240.94) (4 studies) Non supplemented women (weighted mean ± SE (95% CI)): 333.13 ± 8.17 µg/L (317.12 – 349.15) (3 studies) All samples (weighted mean ± SE (95% CI)): 206.06 ± 5.57 µg/L (195.14 – 216.97) Weighted mean analysis for alpha-carotene concentration in women milk (4 studies): Mothers of term infants (weighted mean ± SE (95% CI)): 14.30 ± 0.53 µg/L (13.26 – 15.34) (4 studies) Colostrum (weighted mean ± SE (95% CI)): 91.48 ± 79.19 µg/L (13.73 – 246.69) (1 study) Transitional milk (weighted mean ± SE (95% CI)): 31.68 ± 7.25 µg/L (17.47 – 45.88) (1 study) Mature milk (weighted mean ± SE (95% CI)): 14.20 ± 0.53 µg/L (13.16 – 15.25) (4 studies) Non supplemented women (weighted mean ± SE (95% CI)): 14.80 ± 0.59 µg/L (13.65 – 15.95) (1 study) Supplemented women (weighted mean ± SE (95% CI)): 15.57 ± 3.89 µg/L (7.94 – 23.20) (1 study) All samples (weighted mean ± SE (95% CI)): 14.30 ± 0.53 µg/L (13.26 – 15.34) EFSA supporting publication 2014:EN-629 84 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method “Vitamin A” concentration in breast milk (a) Number of women (number of samples) Weighted mean analysis for beta-carotene concentration in women milk (6 studies): Mothers of term infants (weighted mean ± SE (95% CI)): 18.11 ± 0.75 µg/L (16.64 – 19.58) (6 studies) Colostrum (weighted mean ± SE (95% CI)): 258.00 ± 154.58 µg/L (14.97 – 560.98) (2 studies) Transitional milk (weighted mean ± SE (95% CI)): 116.25 ± 13.07 µg/L (90.65 – 141.86) (2 studies) Mature milk (weighted mean ± SE (95% CI)): 17.78 ± 0.75 µg/L (16.30 – 19.25) (5 studies) Non supplemented women (weighted mean ± SE (95% CI)): 23.36 ± 0.91 µg/L (21.56 – 25.15) (3 studies) Supplemented women (weighted mean ± SE (95% CI)): 5.37 ± 1.34 µg/L (2.74 – 8.00) (1 study) All samples (weighted mean ± SE (95% CI)): 18.11 ± 0.75 µg/L (16.64 – 19.58) (a) Concentrations in retinol, alpha-carotene and beta-carotene are reported. When reported in the paper, total vitamin A concentrations, in retinol equivalent (RE) are reported, with the conversion formula applied. When analysed forms were unspecified in the paper, “vitamin A” concentrations are reported. Vitamin A breast milk concentration was assessed in 19 publications (18 studies) via the quantitation of retinol (8 studies), alpha-carotene (4 studies), beta-carotene (6 studies). One study also calculated total vitamin A concentration in retinol equivalents (RE) (Olafsdottir, Wagner et al. 2001). Five studies reported “vitamin A” concentration without specifying the analysed forms (Sanchez-Hidalgo, Flores-Huerta et al. 2000; Aurvag, Henriksen et al. 2007; Schweigert, Raila et al. 2011; Szlagatys-Siodorkiewicz, Zagierski et al. 2012; Vähämiko, Isolauri et al. 2013). Nine studies were free of confounders (Gossage, Deyhim et al. 2002; Canfield, Clandinin et al. 2003; Schweigert, Bathe et al. 2004; Schulz, Engel et al. 2007; Aurvag, Henriksen et al. 2007; Tijerina-Saenz, Innis et al. 2009; Tacken, Vogelsang et al. 2009; Orhon, Ulukol et al. 2009; Szlagatys-Siodorkiewicz, Zagierski et al. 2012). The analytical method employed is HPLC (17 studies). One study did not record the analytical method. Data are available for colostrum (2 studies), transitional milk (2 studies) or mature milk (6 samples). Milks were collected from mothers who gave birth to both term (8 studies) and pre-term infants (1 study). In 4 of the studies, mothers were taking vitamin A supplement (as beta-carotene ranging 1 to 30 mg/day (Gossage, Deyhim et al. 2002; Tacken, Vogelsang et al. 2009), retinol ranging 5.46 to 72.52 µg/day (Vähämiko, Isolauri et al. 2013) or 750 µg RE (Aurvag, Henriksen et al. 2007)). Seven studies reported intake data (retinol from 792 to 4 965 µg, alpha-carotene 844 to 1 491 µg, beta-carotene 4 942 to 6 490 µg) (Olafsdottir, Wagner et al. 2001; Gossage, Deyhim et al. 2002; Schulz, Engel et al. 2007; Aurvag, Henriksen et al. 2007; Duda, Nogala-Kalucka et al. 2009; Orhon, Ulukol et al. 2009; Vähämiko, EFSA supporting publication 2014:EN-629 85 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Isolauri et al. 2013); 6 studies reported data on status as alpha-carotene, beta-carotene or retinol plasma concentration (Schweigert, Bathe et al. 2004; Schulz, Engel et al. 2007; Aurvag, Henriksen et al. 2007; Tokusoglu, Tansug et al. 2008; Orhon, Ulukol et al. 2009; Vähämiko, Isolauri et al. 2013). The weighted mean and 95% CI for retinol concentration from all samples was 206.06 (195.14 – 216.97) µg/L. Weighted means and 95% CIs at different stages of lactation were the followings: colostrum = 1 353.03 (271.72 – 2434.34) µg/L; transitional milk = 2 380.97 (2 125.18 – 2 636.75) µg/L; mature milk = 228.55 (216.15 – 240.94) µg/L. Weighted mean and 95% CI was 233.74 (221.36 – 246.12) µg/L for milk of mothers of term infants. The weighted mean and 95% CI were 333.13 (317.12 – 349.15) µg/L for milk from non-supplemented women. There was no data on breast milk retinol concentration from supplemented women. One study showed a correlation between the concentration of retinol in the milk and the intake of cod liver (Olafsdottir, Wagner et al. 2001), 1 study showed a positive correlation between maternal vitamin A intakes (as measured by total vitamin A + retinol) and milk retinol levels and between maternal plasma and milk beta-carotene levels in non-smoker mothers, but not in smoker ones (Orhon, Ulukol et al. 2009). Another study did not find correlation between breast milk vitamin A concentration (not specified) and intake of beta-carotene (30 mg/day) (Gossage, Deyhim et al. 2000; Gossage, Deyhim et al. 2002). Two studies showed correlation between maternal plasma retinol and milk concentrations (Schulz, Engel et al. 2007; Tokusoglu, Tansug et al. 2008). One study showed that levels of carotenoids and vitamin A were highest in colostrum and declined (P<0.01) (Schweigert, Bathe et al. 2004). EFSA supporting publication 2014:EN-629 86 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.4.2. Vitamin B1 As described in the study flow diagram, 2 publications were recorded from the comprehensive literature search on vitamin B1 (January 2000 – January 2014). Details are reported in the following Table 10. Table 10: Summary of the included studies for vitamin B1 Publication Ortega, Martinez et al. 2004 Population main characteristics Spanish mothers infants of women term Supplementation Maternal micronutrients intake Stage of lactation Vitamin B1 intake < recommended intake (RI) group: Vitamin B1 supplied by supplements: 0 mg/d; Vitamin B1 intake <RI group: Total intake (diet): 0.87 ± 0.13 mg/d; Transitional milk (13-14 days); Vitamin B1 intake ≥ recommended intake (RI) group: Vitamin B1 supplied by supplements: 1.57 mg/d Hampel, York et al. 2012 Caucasian women (from USA) Not reported EFSA supporting publication 2014:EN-629 Mature days) milk Confounding factors No Analytical method Fluorimetry Vitamin B1 concentration in breast milk Number of women (number of samples) Mean ± SD: vitamin B1 238.82 ± 273.32 µg/L; Vitamin B1 intake <RI group: 13 (20); Vitamin B1 intake ≥RI group: 38 (21) (40 Mean ± SD: vitamin B1 66.34 ± 18.6 µg/L; Vitamin B1 intake ≥RI group: Total intake (supplements + diet): 1.45 ± 0.38 mg/d Transitional milk (13-14 days); Mean ± SD: vitamin B1 233.51 ± 151.25 µg/L Mature days) Mean ± SD: vitamin B1 156.56 ± 116.76 µg/L Not reported Mature milk: 4-12 weeks milk (40 Yes: Few information on population and lack of information on specific supplementation UPLC– MS/MS Mean (range): Vitamin B1: 37 (5-66) µg/L 28 (28) 87 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Publication Population main characteristics Supplementation Maternal micronutrients intake Stage of lactation Confounding factors Analytical method Vitamin B1 concentration in breast milk Number of women (number of samples) Weighted mean analysis for vitamin B1 (vitamin B1) concentration in women milk (2 studies): Mothers of term infants (weighted mean ± SE (95% CI)): 71.70 ± 18.17 µg/L (36.08 – 107.31) (1 study) Transitional milk (weighted mean ± SE (95% CI)): 234.76 ± 132.34 µg/L (24.63 – 494.14) (1 study) Mature milk (weighted mean ± SE (95% CI)): 68.57 ± 18.34 µg/L (32.61 – 104.52) (1 study) Non supplemented women (weighted mean ± SE (95% CI)): 67.13 ± 18.53 µg/L (30.81 – 103.45) (1 study) Supplemented women (weighted mean ± SE (95% CI)): 185.29 ± 92.42 µg/L (4.14 – 366.44) (1 study) All samples (weighted mean ± SE (95% CI)): 44.73 ± 8.58 µg/L (27.92 – 61.54) (2 studies) Vitamin B1 breast milk concentration was assessed in 2 studies. One study was free of confounders (Ortega, Martinez et al. 2004). The analytical method employed was either HPLC (1 study) or fluorimetry (1 study). Data were available for colostrum (1 study), transitional milk (1 study), mature milk (1 study). Milks were collected from mothers who gave birth to term infants in one study, while in the other study the gestation stage was not specified. In 1 of the studies, mothers were taking vitamin B1 supplement (1.57 mg/day) (Ortega, Martinez et al. 2004). One study reported intake and status data (vitamin B1 status assessed by erythrocyte transketolase activation assay) (Ortega, Martinez et al. 2004). The weighted mean and 95% CI for vitamin B1 concentration from all samples was 44.73 (27.92 – 61.54) µg/L. Weighted means and 95% CIs at different stages of lactation are the followings: transitional milk = 234.76 (24.63 – 494.14); mature milk = 68.57 (32.61 – 104.52). Milk from mothers of term infants presented weighted mean and 95% CI concentration of 71.70 (36.08 – 107.31) µg/L. The weighted means and 95% CIs were 67.13 (30.81 – 103.45) µg/L for milk from nonsupplemented women vs. 185.29 (4.14 – 366.44) µg/L for milk from women supplemented with vitamin B1. One study showed a correlation between the concentration of vitamin B1 in the mature milk and its intake (Ortega, Martinez et al. 2004). The relationship between vitamin B1 intake/status and breast milk concentration was not investigated in the other study. EFSA supporting publication 2014:EN-629 88 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.4.3. Chloride As described in the study flow diagram, 1 publication was recorded from the comprehensive literature search on chloride (January 2000 – January 2014). Details are reported in the following Table 11. Table 11: Summary of the included study for chloride Publication Population main characteristics Bauer, Gerss 2011 German women mothers of both term and preterm infants Supplementation Not reported Maternal micronutrients intake Not reported Stage of lactation Confounding factors Mixed (1-8 weeks) Yes: No information on supplementation Analytical method Absorption spectrometer and colorimetric assay Chloride concentration in breast milk Number of women (number of samples) Mean ± SD: Chloride: Preterm group (<28 weeks) 361.62 ± 81.54 mg/L Total number of subjects: 102 (no data) Mean ± SD: Chloride: Preterm group (28-31 weeks) 443.16 ± 106.36 mg/L Mean ± SD: Chloride: Preterm group (32-33 weeks) 361.62 ± 53.18 mg/L Mean ± SD: Chloride: Term group 386.44 ± 35.45 mg/L Weighted mean analysis for chloride concentration in women milk (1 study): Mothers of preterm infants (weighted mean ± SE (95% CI)): 373.79 ± 41.09 mg/L (293.26 – 454.32) Mothers of term infants (weighted mean ± SE (95% CI)): 386.44 ± 35.45 mg/L (316.95 – 455.93) All samples (weighted mean ± SE (95% CI)): 381.04 ± 26.84 mg/L (328.43 – 433.65) EFSA supporting publication 2014:EN-629 89 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Chloride breast milk concentration was assessed in 1 study. The analytical method employed is spectrometric absorption. Milks samples were collected between 1 and 8 weeks post partum, from mothers who gave birth to both term and pre-term infants. There was no information on chloride intake/status in this study. The weighted mean and 95% CI for chloride concentration from all samples was 381.04 (328.43 – 433.65) mg/L. Weighted means and 95% CIs were 373.79 (293.26 – 454.32) mg/L for mothers of preterm infants and 386.44 (316.95 – 455.93) mg/L for milk of mothers of term infants, respectively.The relationship between chloride intake/status and breast milk concentration was not investigated in this study. EFSA supporting publication 2014:EN-629 90 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.4.4. Copper As described in the study flow diagram, 3 publications were recorded from the comprehensive literature search on copper (January 2011 – January 2014). Details are reported in the following Table 12. Table 12: Summary of the included studies for copper Publication Population main characteristics Supplementation Örün, Yalcin et al. 2012 Turkish women mothers of both term and preterm infants Not reported Björklund, Vahter et al. 2012 Swedish women Not reported Maternal micronutrients intake Stage of lactation Confounding factors Not reported Mature milk (52-60 days postpartum) Yes: No information on supplementation Not reported Mature milk: 14-21 days Yes: No information on supplementation Analytical method Copper concentration in breast milk Number of women (number of samples) ICP-MS Median (1st, 3rd quartile): Copper: 239 (200; 296) µg/L 142 (no data) ICP-MS Mean ± SD: 60 (840) Copper: 471 ± 75 µg/L Median (range): Copper: 471 (327 670) µg/L WiniarskaMieczan, 2014 Polish women Not reported Not reported Mature milk (1-12 months) Yes: No information on supplementation FAAS Mean ± SD (range): 323 (323) Copper: 137 ± 92 (25455) µg/L Weighted mean analysis for copper concentration in women milk (3 studies): All samples (weighted mean ± SE (95% CI)): 264.05 ± 29.29 µg/L (206.64 – 321.46) (3 studies) Copper breast milk concentration was assessed in 3 studies. None of the studies was free of confounders. The analytical method employed is ICP-MS (2 studies) or FAAS (1 study). All milk samples included mature milk. Samples from mothers of term and preterm infants were combined in 1 study (Örün, Yalcin et al. 2012); the stage of gestation was not specified in the 2 other studies. There was no information on mothers’ supplementation with copper. None of the study reported copper intake or status data. The weighted mean and 95% CI for copper concentration from all samples was 264.05 (206.64 – 321.46) µg/L. None of the studies investigated the relationship between chloride intake/status and breast milk concentration. EFSA supporting publication 2014:EN-629 91 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.4.5. Magnesium As described in the study flow diagram, 3 publications were included from the comprehensive literature search on magnesium (October 2010 – January 2014). Details are reported in the following Table 13. Table 13: Summary of the included studies for magnesium Publication Population main characteristics Bauer, Gerss 2011 German women mothers of term and preterm infants Supplementation Not reported Maternal micronutrients intake Not reported Stage of lactation Confounding factors Analytical method Mixed (1-8 weeks) Yes: No information on supplementation Absorption spectrometer and colorimetric assay with endpoint determination Magnesium concentration in breast milk Mean ± SD: Magnesium: Preterm group (<28 weeks) 38.89 ± 7.29 mg/L Number of women (number of samples) Total number of subjects: 102 (no data) Magnesium: Preterm group (28-31 weeks) 36.46 ± 7.29 mg/L Magnesium: Preterm group (32-33 weeks) 41.32 ± 4.86 mg/L Magnesium: Term group 31.60 ± 4.86 mg/L Witczak, Jarnuszewska al. 2011 Polish women Not reported Not reported et Björklund, Vahter et al. 2012 Swedish women Not reported EFSA supporting publication 2014:EN-629 Not reported Mature milk: 5-6 months Yes: lack of information on specific supplementation and population ICP-AES Mature milk: 14-21 days Yes: No information on supplementation ICP-MS Mean: Magnesium: 40 mg/L Mean ± SD: Not (9) reported 60 (840) Magnesium: 28 ± 4.8 mg/L 92 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Median (range): Magnesium: 28 (2143) mg/L Weighted mean analysis for magnesium concentration in women milk (3 studies): Mothers of preterm infants (weighted mean ± SE (95% CI)): 39.60 ± 3.54 mg/L (32.67 – 46.54) (1 study) Mothers of term infants (weighted mean ± SE (95% CI)): 31.60 ± 4.86 mg/L (22.07 – 41.12) (1 study) All samples (weighted mean ± SE (95% CI)): 34.83 ± 2.39 mg/L (30.15 – 39.51) (3 studies) Magnesium breast milk concentration was assessed in 3 studies. None of the studies was free of confounders. The analytical method employed was absorption spectrometry (1 study), ICP-AES (1 study) and ICP-MS (1 study). Milk samples included mature milk (2 studies) or mixed samples (1-8 weeks post partum; 1 study). One study provided milk concentrations from milk of mothers who gave birth to term vs. pre-term infants (Bauer, Gerss 2011); the other studies did not specify the gestational age for the infants. There was no information on mothers’ supplementation with magnesium. None of the studies reported intake or status data. The weighted mean and 95% CI for magnesium concentration from all samples was 34.83 (30.15 – 39.51) mg/L. Weighted means and 95% CIs was 39.60 (32.67 – 46.54) mg/L for milk of mothers of preterm infants and 31.60 (22.07 – 41.12) mg/L for milk of mothers of term infants, respectively. None of the studies investigated the relationship between magnesium intake/status and breast milk concentration. EFSA supporting publication 2014:EN-629 93 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 4.4.6. Sodium As described in the study flow diagram, 13 publications were included from the comprehensive literature search on sodium (January 2000 – January 2014). Details are reported in the following Table 14. Table 14: Summary of the included studies for sodium Publication Population main characteristics Gulson, Mizon et al. 2001 6 Australian and 31 migrants selected at the start of the study, 17 women were finally included Supplementation Not reported Maternal micronutrients intake Sodium - no data Stage of lactation Not reported Daily intakes (mean): P: 606 mg (nonpregnant migrants), 788 mg (pregnant migrants), 940 mg (Australian pregnant subjects). Confounding factors Yes: No information on supplementation Analytical method Not reported Sodium concentration in breast milk Mean ± SD: Number of women (number of samples) 17 (78) Sodium: 167 ± 62.37 mg/L; Median: Sodium: 170 mg/L Daily intakes (mean): K: 1392 mg (nonpregnant migrants), 1710 mg (pregnant migrants), 1938 mg (Australian pregnant subjects). Kumral, Duman et al. 2002 Turkish mothers infants of women term Not reported Not reported Transitional milk (5 days) Transitional milk (7 days) Yes: The lack of information on specific supplementation Not reported Sodium values): (Individual 1 (2) Transitional milk (5 days): 1908.17 mg/L (right breast); 1793.22 mg/L (left breast) Sodium values): (Individual 1 (2) Transitional milk (7 days): 1586.31 mg/L EFSA supporting publication 2014:EN-629 94 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk (right breast); 1632.29 (left breast) mg/L Tarcan, Tiker et al. 2005 Savilahti, Saarinen et 2007 al. Turkish mothers infants Finnish mothers infants of of women term women term Not reported Not reported Not reported Not reported Mixed (group 3-20 days) 1: Mixed (group 3-17 days) 2: Mixed (group 3-12 days) 3: Colostrum days) Yes: Few information on population and lack of information on specific supplementation Not reported Mean ± SD (range): Sodium Group 1*: 581.65 ± 337.95 (91.96-1793.22) mg/L Sodium Group 2*: 540.27 ± 268.98 (137.941034.55) mg/L Sodium Group 3*: 866.72 ± 262.09 (436.811379.40) mg/L (1-5 Yes: Population asthma (18 vs 13%) and symptoms of atopy (48%). No information on supplementation Not reported Mean: Sodium Mothers who either breast-fed their infants exclusively less than 0.5 months: 597.74 mg/L Sodium Mothers who either breast-fed their infants exclusively longer than 3.5 months: 459.80 mg/L EFSA supporting publication 2014:EN-629 group 1: 58 (58) group 2: 18 (18) group 3: 10 (10) Mothers who either breastfed their infants exclusively less than 0.5 months: 96 (96) Mothers who either breastfed their infants exclusively longer than 3.5 months: 106 (106) 95 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Manganaro, Marseglia et al. 2007 Italian mothers infants women term Not reported Not reported Colostrum (3 days) Yes: No information on supplementation Flame photometer IL943 Mean ± SD (95% CI): Sodium: 540.27 ± 25.29 (479.80-580.50) mg/L 208 (208) of Ozbek. Kumral et al. 2008 Turkish mothers infants women term Not reported Not reported Mixed (mean ± SD: 4.48 ± 1.63 days) Yes: No information on supplementation Ion selective method in Hitachi Modular Analytics ISE 1900 module Mean ± SD: of Hypernatremic dehydration group: 21 (21); Sodium Hypernatremic dehydration group: 1040.76 ± 435.20 mg/L (for information, not taken into account in the analyses) Sodium Control group: 283.47 ± 91.27 mg/L Powe, Puopolo et al. 2010 Campbell-Yeo, Allen et al. 2010 American women mothers of preterm infants Canadian women mothers of preterm infants Not reported Not reported Not reported Not reported Mature milk (4-39 weeks) Colostrum (day 0) Transitional (day 14) Orgun, Atlihan et al. 2010 Turkish mothers infants of women term Not reported EFSA supporting publication 2014:EN-629 Not reported Not reported milk Yes: Few information on population and lack of information on specific supplementation Flame photometry Yes: Few information on population and lack of information on specific supplementation Not reported Yes: Few information on population and lack of Not reported Mean: Control group: 43 (43) 2 (4) Sodium Baseline: days 1 and 2: 183.92 mg/L Pooled data from days 7 and 8: 160.93 mg/L Mean ± SD: Sodium: 363.24 374.74 mg/L ± Sodium: 395.43 446.01 mg/L ± Mean ± SD: Sodium Placebo group: 24 (48) Hypernatremic dehydration group: 50 (50) Hypernatremic 96 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk information on specific supplementation dehydration group: 558.66 ± 466.7 mg/L (for information, not taken into account in the analyses) Sodium Control group: 278.18 ± 193.12 mg/L Bauer, Gerss 2011 German women mothers of term and preterm infants Not reported Not reported Mixed (1-8 weeks) Yes: No information on supplementation Absorption spectrometer and colorimetric assay with endpoint determination Mean ± SD: Sodium: Preterm group (<28 weeks) 243.69 ± 43.68 mg/L Control group: 72 (72) Total number of subjects: 102 (no data) Sodium: Preterm group (28-31 weeks) 243.69 ± 50.58 mg/L Sodium: Preterm group (32-33 weeks) 239.10 ± 43.68 mg/L Sodium: Term group 257.49 ± 48.28 mg/L Galipeau, Goulet et al. 2012 North American: 91; European: 11; Asian: 6; African: 14; Central/South American: 6; Caribbean: 11; Middle East: 2 (in Canada) Women of Not reported Not reported Mixed: colostrum (3 days) and transitional milk (2 weeks) Yes: No information on supplementation Gasometry apparatus Mean ± SD (range): Sodium: 982.36 ± 508.54 (333.362758.80) mg/L 151 (151) term EFSA supporting publication 2014:EN-629 97 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk infants Björklund, Vahter et al. 2012 Swedish women Not reported Not reported Mature milk: 14-21 days Yes: No information on supplementation ICP-MS Mean ± SD: 60 (840) Sodium: 0.217±0.077 mg/L Median (range): Sodium: 0.192 (0.1360.48) mg/L Weighted mean analysis for sodium concentration in women milk (12 studies): Mothers of preterm infants (weighted mean ± SE (95% CI)): 183.58 ± 11.00 mg/L (162.02 – 205.13) (3 studies) Mothers of term infants (weighted mean ± SE (95% CI)): 850.35 ± 17.15 mg/L (816.73 – 883.98) (8 studies) Colostrum (weighted mean ± SE (95% CI)): 538.18 ± 24.37 mg/L (490.42 – 585.94) (2 studies) Transitional milk (weighted mean ± SE (95% CI)): 1642.60 ± 30.19 mg/L (1583.43 – 1701.76) (1 study) All samples (weighted mean ± SE (95% CI)): 371.07 ± 9.09 mg/L (353.25 – 388.89) (12 studies) *Group 1: babies who exhibited <10% weight loss or had regained to reach birthweight (minimum) in the period up to postnatal day 10; Group 2: babies who showed >10% weight loss or had not regained enough to reach birthweight by postnatal day 10, and whose serum Na levels were <146 mEq/L; Group 3: babies with the same weight status as group 2 (severe weight loss), but whose serum Na levels were ≥146 mEq/L. Sodium breast milk concentration was assessed in 12 publications. None of the studies was free of confounders. The analytical method employed is flame photometry (2 studies), absorption spectrometry (1 study), gasometry (1 study), ICP-MS (1 study) and ion selective method (1 study). Six studies did not record the analytical method. Milk samples included colostrum (3 studies), transitional milk (2 studies), mature milk (2 studies) or mixed/unspecified samples (6 studies) (weighed mean analysis according to stage of lactation was only performed when it was specified that women gave birth to term infants). Milk concentrations were available from mothers who gave birth to term infants (8 studies) or pre-term infants (3 studies); the stage of gestation was not specified in 2 studies. None of the studies reported mothers’ sodium intake or status data. The weighted mean and 95% CI for sodium concentration from all samples was 371.07 (353.25 – 388.89) mg/L. Weighted means and 95% CIs at different stages of lactation are the followings: colostrum = 538.18 (490.42 – 585.94) mg/L; transitional milk = 1642.60 (1583.43 – 1701.76) mg/L. Weighted means and 95% CIs were 183.58 (162.02 – 205.13) mg/L in milks from mothers of preterm infants and 850.35 (816.73 – 883.98) mg/L in milks from mothers of term infants, respectively. None of the studies investigated the relationship between sodium intake/status and breast milk concentration. EFSA supporting publication 2014:EN-629 98 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk CONCLUSIONS Articles have been systematically searched and reviewed using a standard protocol, with the aim of collating data on breast milk concentrations of folate, zinc, vitamin B6, vitamin E, choline, phosphorus, vitamin A, vitamin B1, chloride, sodium (from January 2000), potassium, magnesium (from October 2010) and copper (from January 2011). The searches resulted in the inclusion of eight studies on folate, 41 studies on zinc, four studies on vitamin B6, 23 studies on vitamin E, five studies on choline, five studies on phosphorus, three studies on potassium, 18 studies on vitamin A, two studies on vitamin B1, one study on chloride, three studies on copper, three studies on magnesium and 12 studies on sodium. Weighted mean breastmilk concentrations for each individual micronutrient were calculated by combining results from “all samples” available. The characteristics of the breast milk samples assessed in these studies were diverse (i.e. samples from mothers of term vs. preterm infants; colostrum, transitional milk or mature milk samples; samples from mothers supplemented with the micronutrient of interest or not). This heterogeneity should be kept in mind when interpreting the results of the pooled analyses. A number of studies were assessed as being at moderate risk of bias due to uncertainties regarding the characteristics of the breast milk samples (i.e. mothers’ supplementation with the micronutrient of interest, infants’ gestational age at birth and/or lactation stage not reported). Overall, two out of eight studies on folate, six out of 41 studies on zinc, three out of four studies on vitamin B6, five out of 23 studies on vitamin E, two out of five studies on choline, one out of five studies for phosphorus, none out of three studies for potassium, nine out of 18 studies for vitamin A, one out of two studies on vitamin B1, none out of three studies for copper, none out of three studies on magnesium, and none out of 12 studies on sodium were assessed as “free of confounders” and provided adequate characterisation of the breast milk samples. The results of the other studies could not be used in refined weighted mean analyses performed according to stages of lactation, gestational age at birth, and use or not of the supplement of interest. The lack of information on the characteristics of breast milk samples in most studies limit the exploration of heterogeneity among results. The reliability of analytical methods applied was assessed for each study according to the presence of quality controls and sufficient details on the validation. No technical issue was identified and there was sufficient information on the methods used to consider them as reliable. When several methods were used for dosing the same micronutrient, data recorded from the studies did not allow estimating the relevancy/usefulness of one method compared to another. For some studies, there were strong doubts with respect to the units recorded in the publication; results from these studies were reported in the database but were not included in the analyses. EFSA supporting publication 2014:EN-629 99 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk REFERENCES INCLUDED Folates Alvarez-Sanchez, B., Priego-Capote, F. et al. (2010). "Automated determination of folate catabolites in human biofluids (urine, breast milk and serum) by on-line SPE-HILIC-MS/MS." Journal of Chromatography A 1217(28): 4688-4695. Buttner, B. E., Witthoft, C. M. et al. (2014). "Effect of type of heat treatment of breastmilk on folate content and pattern." Breastfeeding Medicine 9(2): 86-91. Houghton, L. A., Yang, J. et al. (2009). 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Pediatria Wspolczesna Zawartosc cynku w mleku kobiet karmiacych piersia zamieszkalych na terenie Podlasia. 8: 121-125. Rodriguez Rodriguez, E. M., Sanz Alaejos, M. et al. (2000). "Concentrations of iron, copper and zinc in human milk and powdered infant formula." International Journal of Food Sciences and Nutrition 51(5): 373-380. Sanchez-Hidalgo, V. M., Flores-Huerta, S. et al. (2000). "A fortifier comprising protein, vitamins, and calcium-glycerophosphate for preterm human milk." Archives of Medical Research 31(6): 564570. Sievers, E. and Schaub, J. (2004). Zinc concentration in human milk: Longitudinal studies in consecutive lactation periods. Advances in Experimental Medicine and Biology. 554: 403-405. Silvestre, D., Martinez-Costa, C. et al. (2001). "Copper, iron, and zinc concentrations in human milk during the first three months of lactation: A longitudinal study." Biological Trace Element Research 80(1): 1-11. Silvestre, M., Lagarda, M. et al. (2000). "Copper, iron and zinc determinations in human milk using FAAS with microwave digestion." Food Chemistry 68: 95-99. EFSA supporting publication 2014:EN-629 102 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Silvestre, M. D., Lagarda, M. J. et al. (2000). "A study of factors that may influence the determination of copper, iron, and zinc in human milk during sampling and in sample individuals." Biological Trace Element Research 76(3): 217-227. Spevackova, V., Rychlik, S. et al. (2005). "Monitoring of trace elements in breast milk sampling and measurement procedures." Central European Journal of Public Health 13(2): 85-88. Stawarz, R., Formicki, G. et al. (2007). "Daily fluctuations and distribution of xenobiotics, nutritional and biogenic elements in human milk in Southern Poland." Journal of Environmental Science and Health - Part A Toxic/Hazardous Substances and Environmental Engineering 42(8): 1169-1175. Turan, S., Saygi, S. et al. (2001). "Determination of heavy metal concentrations in human colostrum samples by electrothermal atomic absorption spectrophotometry." Journal of Tropical Pediatrics 47(2): 81-85. Ustundag, B., Yilmaz, E. et al. (2005). "Levels of cytokines (IL-1(beta), IL-2, IL-6, IL-8, TNF(alpha)) and trace elements (Zn, Cu) in breast milk from mothers of preterm and term infants." Mediators of Inflammation 2005(6): 331-336. Wasowicz, W., Gromadzinska, J. et al. (2001). "Selenium, zinc, and copper concentrations in the blood and milk of lactating women." Biological Trace Element Research 79(3): 221-233. Winiarska-Mieczan, A. (2014). "Cadmium, lead, copper and zinc in breast milk in Poland." Biol Trace Elem Res 157(1): 36-44. Yalcin, S. S., Yurdakok, K. et al. (2010). "Maternal and environmental determinants of breast-milk mercury concentrations." Turkish Journal of Pediatrics 52(1): 1-9. Yalcn, S. S., Baykan, A. et al. (2009). "The factors that affect milk-to-serum ratio for iron during early lactation." Journal of Pediatric Hematology/Oncology 31(2): 85-90. Vitamin B6 Boylan, L., Hart, S. et al. (2002). "Vitamin B-6 concentration of breast milk and neonatal behavioral functioning." Journal of the American Dietetic Association 102: 1433-1438. Chang, S. and Kirksey, A. (2002). "Vitamin B-6 status of breast-fed infants in relation to pyridoxine center dot HCl supplementation of mothers." J Nutr Sci Vitaminol 48: 10-17. Hampel, D., York, E. R. et al. (2012). "Ultra-performance liquid chromatography tandem massspectrometry (UPLC-MS/MS) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk." Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 903: 7-13. Lovelady, C. A., Williams, J. P. et al. (2001). "Effect of energy restriction and exercise on vitamin B-6 status of women during lactation." Medicine and Science in Sports and Exercise 33(4): 512-518. EFSA supporting publication 2014:EN-629 103 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Vitamin E Antonakou, A., Chiou, A. et al. (2011). "Breast milk tocopherol concentration during the first six months in exclusively breastfeeding Greek women." European Journal of Nutrition 50(3): 195-202. Duda, G., Nogala-Kalucka, M. et al. (2009). "Influence of the lactating women diet on the concentration of the lipophilic vitamins in human milk." Pakistan Journal of Nutrition 8(5): 629634. Elisia, I. and Kitts, D. D. (2011). "Quantification of hexanal as an index of lipid oxidation in human milk and association with antioxidant components." Journal of Clinical Biochemistry and Nutrition 49(3): 147-152. Gossage, C., Deyhim, M. et al. (2000). "Effect of (beta)-carotene supplementation and lactation on carotenoid metabolism and mitogenic T lymphocyte proliferation." American Journal of Clinical Nutrition 71(4): 950-955. Gossage, C. P., Deyhim, M. et al. (2002). "Carotenoid composition of human milk during the first month postpartum and the response to (beta)-carotene supplementation." American Journal of Clinical Nutrition 76(1): 193-197. Jewell, V. C., Mayes, C. B. D. et al. (2004). "A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers." European Journal of Clinical Nutrition 58(1): 90-97. Kasparova, M., Plisek, J. et al. (2012). "Rapid sample preparation procedure for determination of retinol and alpha-tocopherol in human breast milk." Talanta 93: 147-152. Martysiak-Zurowska, D., Szlagatys-Sidorkiewicz, A. et al. (2013). "Concentrations of alpha- and gamma-tocopherols in human breast milk during the first months of lactation and in infant formulas." Maternal and Child Nutrition 9(4): 473-482. Michalski, M. C., Calzada, C. et al. (2008). "Oxidation products of polyunsaturated fatty acids in infant formulas compared to human milk--a preliminary study." Mol. Nutr. Food Res. 52: 14781485. Molto-Puigmarti, C., Castellote, A. I. et al. (2009). "Ultra-High-Pressure Liquid Chromatographic method for the analysis of tocopherols in human colostrum and milk." Journal of Chromatography A 1216(20): 4388-4394. Molto-Puigmarti, C., Permanyer, M. et al. (2011). "Effects of pasteurisation and high-pressure processing on vitamin C, tocopherols and fatty acids in mature human milk." Food Chemistry 124(3): 697-702. Olafsdottir, A. S., Wagner, K. H. et al. (2001). "Fat-soluble vitamins in the maternal diet, influence of cod liver oil supplementation and impact of the maternal diet on human milk composition." Annals of Nutrition and Metabolism 45(6): 265-272. Orhon, F. S., Ulukol, B., et al. (2009). "The influence of maternal smoking on maternal and newborn oxidant and antioxidant status." European Journal of Pediatrics 168(8): 975-981. EFSA supporting publication 2014:EN-629 104 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Quiles, J. L., Ochoa, J. J. et al. (2006). "Coenzyme Q concentration and total antioxidant capacity of human milk at different stages of lactation in mothers of preterm and full-term infants." Free Radical Research 40(2): 199-206. Romeu-Nadal, M., Castellote, A. I. et al. (2008). "Effect of pasteurisation on ascorbic acid, dehydroascorbic acid, tocopherols and fatty acids in pooled mature human milk." Food Chemistry 107(1): 434-438. Romeu-Nadal, M., Castellote, A. I. et al. (2008). "Effect of cold storage on vitamins C and E and fatty acids in human milk." Food Chemistry 106(1): 65-70. Romeu-Nadal, M., Morera-Pons, S. et al. (2006). "Determination of gamma- and alpha-tocopherols in human milk by a direct high-performance liquid chromatographic method with UV-vis detection and comparison with evaporative light scattering detection." Journal of Chromatography A 1114: 132-137. Schweigert, F. J., Bathe, K. et al. (2004). "Effect of the stage of lactation in humans on carotenoid levels in milk, blood plasma and plasma lipoprotein fractions." European Journal of Nutrition 43(1): 39-44. Sziklai-Laszlo, I., Majchrzak, D. et al. (2009). "Selenium and vitamin e concentrations in human milk and formula milk from Hungary." Journal of Radioanalytical and Nuclear Chemistry 279(2): 585590. Szlagatys-Sidorkiewicz, A., Zagierski, M. et al. (2012). "Longitudinal study of vitamins A, E and lipid oxidative damage in human milk throughout lactation." Early Human Development 88(6): 421-424. Thijssen, H. H. W., Drittij, M. J. et al. (2002). "Menaquinone-4 in breast milk is derived from dietary phylloquinone." British Journal of Nutrition 87(3): 219-226. Tijerina-Saenz, A., Innis, S. M. et al. (2009). "Antioxidant capacity of human milk and its association with vitamins A and e and fatty acid composition." Acta Paediatrica, International Journal of Paediatrics 98(11): 1793-1798. Tokusoglu, O., Tansug, N. et al. (2008). "Retinol and (alpha)-tocopherol concentrations in breast milk of Turkish lactating mothers under different socio-economic status." International Journal of Food Sciences and Nutrition 59(2): 166-174. Vahamiko, S., Isolauri, E. et al. (2013). "The impact of dietary counselling during pregnancy on vitamin intake and status of women and their children." International Journal of Food Sciences and Nutrition 64(5): 638-647. Choline Fischer, L. M., Da Costa, K. A. et al. (2010). "Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma." American Journal of Clinical Nutrition 92(2): 336-346. Holmes, H. C., Snodgrass, G. J. A. I. et al. (2000). "Changes in the choline concentration of human breast milk in the first 3 weeks after birth." European Journal of Pediatrics 159(3): 198-204. EFSA supporting publication 2014:EN-629 105 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Ilcol, Y. O., Ozbek, R. et al. (2005). "Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk." Journal of Nutritional Biochemistry 16(8): 489499. Ozarda, Y., Cansev, M., et al. (2014). "Breast milk choline contents are associated with inflammatory status of breastfeeding women." Journal of Human Lactation 30(2): 161-166. Ozarda, Y., Cansev, M., et al. (2014). "Relations of human breastmilk choline content with maternal hormonal status." Breastfeeding Medicine 9(1): 39-41. Phosphorus Bjorklund, K. L., Vahter, M. et al. (2012). "Metals and trace element concentrations in breast milk of first time healthy mothers: A biological monitoring study." Environmental Health: A Global Access Science Source 11(1): 92. Gulson, B. L., Mizon, K. J. et al. (2001). "Dietary intakes of selected elements from longitudinal 6-day duplicate diets for pregnant and nonpregnant subjects and elemental concentrations of breast milk and infant formula." Environmental Research 87(3): 160-174. Nickkho-Amiry, M., Prentice, A. et al. (2008). "Maternal vitamin D status and breast milk concentrations of calcium and phosphorus [1]." Archives of Disease in Childhood 93(2): 179. Sanchez-Hidalgo, V. M., Flores-Huerta, S. et al. (2000). "A fortifier comprising protein, vitamins, and calcium-glycerophosphate for preterm human milk." Archives of Medical Research 31(6): 564570. Witczak, A. and Jarnuszewska, A. (2011). "[The concentration of selected mineral nutrients in infant and follow-on formulae available at retail stores in Szczecin]." ROCZN. PZH 62(3): 257-262. Potassium Bauer, J. and Gerss, J. (2011). "Longitudinal analysis of macronutrients and minerals in human milk produced by mothers of preterm infants." Clin Nutr 30(2): 215-220. Bjorklund, K. L., Vahter, M. et al. (2012). "Metals and trace element concentrations in breast milk of first time healthy mothers: A biological monitoring study." Environmental Health: A Global Access Science Source 11(1): 92. Witczak, A. and Jarnuszewska, A. (2011). "[The concentration of selected mineral nutrients in infant and follow-on formulae available at retail stores in Szczecin]." ROCZN. PZH 62(3): 257-262. Vitamin A Aurvag, A. K., Henriksen, C. et al. (2007). "Improved vitamin A supplementation regimen for breastfed very low birth weight infants." Acta Paediatrica, International Journal of Paediatrics 96(9): 1296-1302. EFSA supporting publication 2014:EN-629 106 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Canfield, L. M., Clandinin, M. T. et al. (2003). "Multinational study of major breast milk carotenoids of healthy mothers." European Journal of Nutrition 42(3): 133-141. Duda, G., Nogala-Kalucka, M. et al. (2009). "Influence of the lactating women diet on the concentration of the lipophilic vitamins in human milk." Pakistan Journal of Nutrition 8(5): 629634. Gossage, C., Deyhim, M. et al. (2000). "Effect of (beta)-carotene supplementation and lactation on carotenoid metabolism and mitogenic T lymphocyte proliferation." American Journal of Clinical Nutrition 71(4): 950-955. Gossage, C. P., Deyhim, M. et al. (2002). "Carotenoid composition of human milk during the first month postpartum and the response to (beta)-carotene supplementation." American Journal of Clinical Nutrition 76(1): 193-197. Jewell, V. C., Mayes, C. B. D. et al. (2004). "A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers." European Journal of Clinical Nutrition 58(1): 90-97. Kasparova, M., Plisek, J. et al. (2012). "Rapid sample preparation procedure for determination of retinol and alpha-tocopherol in human breast milk." Talanta 93: 147-152. Olafsdottir, A. S., Wagner, K. H. et al. (2001). "Fat-soluble vitamins in the maternal diet, influence of cod liver oil supplementation and impact of the maternal diet on human milk composition." Annals of Nutrition and Metabolism 45(6): 265-272. Orhon, F. S., Ulukol, B., et al. (2009). "The influence of maternal smoking on maternal and newborn oxidant and antioxidant status." European Journal of Pediatrics 168(8): 975-981. Sanchez-Hidalgo, V. M., Flores-Huerta, S. et al. (2000). "A fortifier comprising protein, vitamins, and calcium-glycerophosphate for preterm human milk." Archives of Medical Research 31(6): 564570. Schulz, C., Engel, U. et al. (2007). "Vitamin A and beta-carotene supply of women with gemini or short birth intervals - A pilot study." European Journal of Nutrition 46: 12-20. Schweigert, F. J., Bathe, K. et al. (2004). "Effect of the stage of lactation in humans on carotenoid levels in milk, blood plasma and plasma lipoprotein fractions." European Journal of Nutrition 43(1): 39-44. Schweigert, F., Raila, J. et al. (2011). "Point of care measurements of Vitamin A in blood and breast milk for low resource settings." Annals of Nutrition and Metabolism 58: 382. Song, B. J., Jouni, Z. E. et al. (2013). "Assessment of phytochemical concentration in human milk during different stages of lactation." Nutrition 29(1): 195-202. Szlagatys-Sidorkiewicz, A., Zagierski, M. et al. (2012). "Longitudinal study of vitamins A, E and lipid oxidative damage in human milk throughout lactation." Early Human Development 88(6): 421-424. Tacken, K. J. M., Vogelsang, A. et al. (2009). "Loss of triglycerides and carotenoids in human milk after processing." Archives of Disease in Childhood: Fetal and Neonatal Edition 94(6): F447-F450. EFSA supporting publication 2014:EN-629 107 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Tijerina-Saenz, A., Innis, S. M. et al. (2009). "Antioxidant capacity of human milk and its association with vitamins A and e and fatty acid composition." Acta Paediatrica, International Journal of Paediatrics 98(11): 1793-1798. Tokusoglu, O., Tansug, N. et al. (2008). "Retinol and (alpha)-tocopherol concentrations in breast milk of Turkish lactating mothers under different socio-economic status." International Journal of Food Sciences and Nutrition 59(2): 166-174. Vahamiko, S., Isolauri, E. et al. (2013). "The impact of dietary counselling during pregnancy on vitamin intake and status of women and their children." International Journal of Food Sciences and Nutrition 64(5): 638-647. Vitamin B1 Hampel, D., York, E. R. et al. (2012). "Ultra-performance liquid chromatography tandem massspectrometry (UPLC-MS/MS) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk." Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 903: 7-13. Ortega, R. M., Martinez, R. M. et al. (2004). "Thiamin status during the third trimester of pregnancy and its influence on thiamin concentrations in transition and mature breast milk." British Journal of Nutrition 92(1): 129-135. Copper Bjorklund, K. L., Vahter, M. et al. (2012). "Metals and trace element concentrations in breast milk of first time healthy mothers: A biological monitoring study." Environmental Health: A Global Access Science Source 11(1): 92. Orun, E., Songul Yalcin, S. et al. (2012). "Zinc and copper concentrations in breastmilk at the second month of lactation." Indian Pediatrics 49(2): 133-135. Winiarska-Mieczan, A. (2014). "Cadmium, Lead, Copper and Zinc in Breast Milk in Poland." Biol Trace Elem Res 157: 36-44. Chloride Bauer, J. and Gerss, J. (2011). "Longitudinal analysis of macronutrients and minerals in human milk produced by mothers of preterm infants." Clinical Nutrition 30(2): 215-220. Magnesium Bauer, J. and Gerss, J. (2011). "Longitudinal analysis of macronutrients and minerals in human milk produced by mothers of preterm infants." Clinical Nutrition 30(2): 215-220. EFSA supporting publication 2014:EN-629 108 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Bjorklund, K. L., Vahter, M. et al. (2012). "Metals and trace element concentrations in breast milk of first time healthy mothers: A biological monitoring study." Environmental Health: A Global Access Science Source 11(1): 92. Witczak, A. and Jarnuszewska, A. (2011). "[The concentration of selected mineral nutrients in infant and follow-on formulae available at retail stores in Szczecin]." Roczn. Pzh 62(3): 257-262. Sodium Bauer, J. and Gerss, J. (2011). "Longitudinal analysis of macronutrients and minerals in human milk produced by mothers of preterm infants." Clinical Nutrition 30(2): 215-220. Bjorklund, K. L., Vahter, M. et al. (2012). "Metals and trace element concentrations in breast milk of first time healthy mothers: A biological monitoring study." Environmental Health: A Global Access Science Source 11(1): 92. Campbell-Yeo, M. L., Allen, A. C. et al. (2010). "Effect of domperidone on the composition of preterm human breast milk." Pediatrics 125(1): e107-e114. Galipeau, R., Goulet, C. et al. (2012). "Infant and maternal factors influencing breastmilk sodium among primiparous mothers." Breastfeeding Medicine 7(4): 290-294. Gulson, B. L., Mizon, K. J. et al. (2001). "Dietary intakes of selected elements from longitudinal 6-day duplicate diets for pregnant and nonpregnant subjects and elemental concentrations of breast milk and infant formula." Environmental Research 87(3): 160-174. Kumral, A., Duman, N. et al. (2002). "Hypernatraemic dehydration due to high sodium concentrations in breast milk: Possible relationship with unwanted pregnancy [1]." Acta Paediatrica, International Journal of Paediatrics 91(11): 1268-1269. Manganaro, R., Marseglia, L. et al. (2007). "Breast milk sodium concentration, sodium intake and weight loss in breast-feeding newborn infants." British Journal of Nutrition 97(2): 344-348. Orgun, L. T., Atlihan, F. et al. (2010). "Evaluation of breast milk sodium and neonatal hypernatremic dehydration." Early Human Development 86: S146. Ozbek, A., Kumral, A. et al. (2008). "Maternal psychosocial aspects in hypernatremic dehydration with high sodium concentrations in breast milk: A case-control study." Journal of Paediatrics and Child Health 44(1-2): 38-43. Powe, C. E., Puopolo, K. M. et al. (2011). "Effects of recombinant human prolactin on breast milk composition." Pediatrics 127(2): e359-e366. Savilahti, E. and Saarinen, K. M. (2007). "Colostrum TGF-(beta)-1 associates with the duration of breast-feeding." European Journal of Nutrition 46(4): 238-242. Tarcan, A., Tiker, F. et al. (2005). "Weight loss and hypernatremia in breast-fed babies: Frequency in neonates with non-hemolytic jaundice." Journal of Paediatrics and Child Health 41(9-10): 484-487. EFSA supporting publication 2014:EN-629 109 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk APPENDICES A. SEARCH STRATEGIES FOR FOLATES 1. Search strategies on Pubmed Search strategy Pubmed 1 “Folic Acid”[MeSH] OR “Folic Acid” OR “Folate”[MeSH] OR “Folates”[MeSH] OR folate OR folates OR “Vitamin B9” OR “Vitamin B 9” OR “Vitamin B-9” OR “Vitamin B(9)” 47 470 2 "Milk, Human"[Mesh] OR "Milk, Human" OR “human milk” OR "breast milk" OR breast milk OR “breast feeding”[MeSH] OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk” 44 002 3 1 AND 2 341 4 3 Limit 2000/01/01 161 5 4 “NOT (Animals NOT Humans)” 161 Date of search: 9th of December 2013 2. Search strategies on Embase Search strategy Embase 1 “Folic Acid”[emtree] OR “Folic Acid” OR “Folate”[emtree] OR “Folates”[emtree] OR folate OR folates OR “Vitamin B9” OR “Vitamin B 9” OR “Vitamin B-9” OR “Vitamin B(9)” 203896 2 "breast milk"[emtree] OR "breast feeding"[emtree] OR “lactation” [emtree] OR breast milk OR “women milk” OR “women’s milk” OR “mother’s milk” 80706 3 1 AND 2 1244 4 #3 Limit 2000/01/01 951 5 #4 Limit to Embase 890 6 #5 not (animal not human) [Limit to human] 836 Date of search: 6th of December 2013 EFSA supporting publication 2014:EN-629 110 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 3. Search strategies on Web of Science Search strategy Web Of Science 1 “Folic Acid” OR “Vitamin M” OR ”Pteroylglutamic Acid” OR ”Vitamin B9” OR ”B9, Vitamin” OR “Vitamin B 9” OR “Vitamin B-9” OR “Vitamin B(9)” OR ”Folate” OR ”Folic Acid, (D)-Isomer” OR ”Folic Acid, (DL)-Isomer” OR ”Folic Acid, Calcium Salt (1:1)” OR ”Folic Acid, Monosodium Salt” OR ”Folic Acid, Potassium Salt” OR ”Folic Acid, Sodium Salt” OR ”Folvite” OR ”Folacin” OR ”Folic Acid, Monopotassium Salt” OR “folate*” OR “Vitamin M” OR “Pteroylglutamic Acid” OR “Vitamin B9” OR “B9, Vitamin” OR “Folate” OR “Folic Acid, (D)-Isomer” OR “Folic Acid, (DL)-Isomer” OR “Folic Acid, Calcium Salt (1:1)” OR “Folic Acid, Monosodium Salt” OR “Folic Acid, Potassium Salt” OR “Folic Acid, Sodium Salt” OR “Folvite” OR “Folacin” OR “Folic Acid, Monopotassium Salt” OR "Folic Acid"[All Fields] OR ("folic" AND "acid") OR "folic acid" OR "folates" OR "Vitamin B9" OR "Vitamin B 9" OR "Vitamin B-9" OR "Vitamin B(9)" 34 278 2 "Milk, Human" OR “Breast Milk” OR “Breast Milks” OR “Milk, Breast” OR “human milk” OR “Breast milk” OR “Feeding, Breast” OR “Breastfeeding” OR “Breast Feeding, Exclusive” OR “Exclusive Breast Feeding” OR “Breastfeeding, Exclusive” OR “Exclusive Breastfeeding” OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk” 32 276 3 1 AND 2 267 4 3 Limit 2000/01/01 172 5 4 “NOT (Animals NOT Humans)” 172 Date of search: 10th of December 2013 4. Grey literature searches Grey literature was searched by hand, using relevant keywords, more or less specific according to the searched websites/databases (see the following table). Websites interface and structure were carefully screened for identifying any relevant information. EFSA supporting publication 2014:EN-629 111 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used "breast milk folic acid" , "breast milk folate", "breast milk folates" https://www.google.com/ 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" "breast milk folic acid" , "breast milk folate", "breast milk folates" http://scholar.google.fr/ 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" "breast milk folic acid" , "breast milk folate", "breast milk folates" http://books.google.com/ 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" http://www.nrv.gov.au/ http://www.codexalimentariu s.org/ 30.12.2013 30.12.2013 Search by hand Specific features Relevant reference? Reason for exclusion Period searched from 2000 http://www. drugs.com/p regnancy/fol ic-acid.html No reference Period searched from 2000 No more information than that yet retrieved from the databases Period searched from 2000 Information out of the range of selected dates Search in the “Nutrients” and “Ressources ” section Information out of the range of selected dates "breast milk folic acid" , "breast milk folate", "breast milk folates", “breast milk nutrients” "human milk folic acid" , "human milk folate", "human milk folates" “human milk nutrients” No relevant information Search by hand in the reports http://www.eurreca.org/ever yone/ 30.12.2013 Search by hand http://www.nutrition.org/ 30.12.2013 "breast milk folic acid" , "breast milk folate", "breast milk folates" "human milk folic acid" , "human milk EFSA supporting publication 2014:EN-629 Search in the “Scientific Publication section No more information than that yet retrieved from the databases No more information than that yet retrieved 112 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features folate", "human milk folates" Relevant reference? from the databases http://ndri.co m/article/co mposition_o f_breast_mil k_and_comp arison_with_ cows_and_st andard_form ula_milk425.html "breast milk folic acid" , "breast milk folate", "breast milk folates" http://scientific.thomsonweb plus.com/ 30.12.2013 http://clinicaltrials.gov/ 30.12.2013 "breast milk”, “human milk” “folic acid”, “folates" No relevant information http://www.oclc.org/ 30.12.2013 "breast milk”, “human milk” “folic acid”, “folates" No relevant information http://www.opengrey.eu/ 30.12.2013 "breast milk”, “human milk” “folic acid”, “folates" No relevant information http://www.efsa.europa.eu/ "human milk folic acid" , "human milk folate", "human milk folates" 30.12.2013 Reason for exclusion "breast milk”, “human milk” “folic acid”, “folates" No reference No relevant information Search by hand in the reports "breast milk”, “human milk” “folic acid”, “folates" http://www.anses.fr/ 30.12.2013 “lait maternel”, “acide folique”, “folates” French and English searches No relevant information Advanced search with restriction to articles published from 2000 No relevant information Search by hand in the reports "breast milk folic acid" , "breast milk folate", "breast milk folates" http://www.jstor.org/ 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" http://www.greylit.org/ 30.12.2013 EFSA supporting publication 2014:EN-629 "breast milk folic acid" , "breast milk No relevant 113 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features folate", "breast milk folates" Relevant reference? Reason for exclusion information "human milk folic acid" , "human milk folate", "human milk folates" "breast milk folic acid" , "breast milk folate", "breast milk folates" http://worldwidescience.org/ No relevant information 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" "breast milk folic acid" , "breast milk folate", "breast milk folates" http://www.science.gov/ No relevant information 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" http://www.collectionscanad a.gc.ca/thesescanada/ 30.12.2013 "breast milk”, “human milk” “folic acid”, “folates" “lait maternel”, “acide folique”, “folates” "breast milk folic acid" , "breast milk folate", "breast milk folates" http://trove.nla.gov.au/ 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" French and English searches No relevant information Advanced search with restriction to articles published from 2000 No relevant information "breast milk folic acid" , "breast milk folate", "breast milk folates" http://scienceresearch.com/ No relevant information 30.12.2013 "human milk folic acid" , "human milk folate", "human milk folates" http://www.sudoc.abes.fr/ 30.12.2013 "breast milk”, “human milk” “folic acid”, “folates" “lait maternel”, “acide folique”, “folates” https://www.google.pl/ 31.12.2013 EFSA supporting publication 2014:EN-629 "breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language French and English searches No relevant information Period searched from 2000; Polish No more information than that yet retrieved from the 114 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL http://scholar.google.pl/ http://books.google.com/?hl =pl http://www.ptzkd.org/ http://www.neonatologia.edu .pl/ http://www.ptp.edu.pl/ http://www.izz.waw.pl/pl/ Specific features Relevant reference? searches databases 3.01.2014 breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Period searched from 2000; Polish searches No more information than that yet retrieved from the databases 3.01.2014 breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Period searched from 2000; Polish searches No relevant information 3.01.2014 "breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information 3.01.2014 "breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information 3.01.2014 "breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information 3.01.2014 "breast/human milk folic acid" , "breast/human milk folate", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information Access date EFSA supporting publication 2014:EN-629 Search terms used Reason for exclusion 115 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk B. SEARCH STRATEGIES FOR ZINC 1. Search strategies on Pubmed Search strategy Pubmed 1 “Zinc”[MeSH] OR Zinc 104 762 2 "Milk, Human"[Mesh] OR "Milk, Human" OR “human milk” OR "breast milk" OR breast milk OR “breast feeding”[MeSH] OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk” 44 163 3 1 AND 2 728 4 3 Limit 2000/01/01 305 5 4 “NOT (Animals NOT Humans)” 300 Date of search: 3rd of January 2014 2. Search strategies on Embase Search strategy Embase 1 Zinc”[emtree] OR Zinc 161584 2 "breast milk"[emtree] OR "breast feeding"[emtree] OR “lactation” [emtree] OR breast milk OR “women milk” OR “women’s milk” OR “mother’s milk” 80834 3 1 AND 2 1468 4 #3 Limit 2000/01/01 875 5 #4 Limit to Embase 782 6 #5 not (animal not human) [Limit to human] 665 Date of search: 7th of January 2014 EFSA supporting publication 2014:EN-629 116 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk 3. Search strategies on Web of Science Web Of Science Search strategy 1 Topic=(zinc) 227 305 2 Topic=(“Milk, Human" OR “Breast Milk” OR “Breast Milks” OR “Milk, Breast” OR “human milk” OR “Breast milk” OR “Feeding, Breast” OR “Breastfeeding” OR “Breast Feeding, Exclusive” OR “Exclusive Breast Feeding” OR “Breastfeeding, Exclusive” OR “Exclusive Breastfeeding” OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk”) 32 991 3 1 AND 2 744 4 3 Timespan=2000-2014 457 5 4 “NOT (Animals NOT Humans)” 445 Date of search: 3rd of January 2014 4. Grey literature searches Grey literature was searched by hand, using relevant keywords, more or less specific according to the searched websites/databases (see the following table). Websites interface and structure were carefully screened for identifying any relevant information. URL Access date Search terms used "breast milk zinc" , "breast milk zinc", "breast milk zinc" https://www.go ogle.com/ 11.02.2014 http://scholar.go ogle.fr/ 11.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" "breast milk zinc" , "breast milk zinc", EFSA supporting publication 2014:EN-629 Specific features Relevant reference? Period searched from 2000 No more information than that yet retrieved from the databases Period searched from 2000 Reason for exclusion No more information than that yet 117 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features "breast milk zinc" Relevant reference? Reason for exclusion retrieved from the databases "human milk zinc" , "human milk zinc", "human milk zinc" http://books.goo gle.com/ http://www.nrv. gov.au/ http://www.cod exalimentarius. org/ "breast milk zinc" , "breast milk zinc", "breast milk zinc" 11.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" 11.02.2014 11.02.2014 Search by hand Period searched from 2000 Information out of the range of selected dates Search in the “Nutrients” and “Ressources” section Information out of the range of selected dates "breast milk zinc" , "breast milk zinc", "breast milk zinc", “breast milk nutrients” "human milk zinc" , "human milk zinc", "human milk zinc" “human milk nutrients” No relevant information Search by hand in the reports http://www.eurr eca.org/everyon e/ 11.02.2014 Search by hand EFSA supporting publication 2014:EN-629 Search in the “Scientific Publication section No more information than that yet retrieved from the databases 118 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL http://www.nutr ition.org/ Access date Search terms used Specific features "breast milk zinc" , "breast milk zinc", "breast milk zinc" Relevant reference? No more information than that yet retrieved from the databases 11.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" "breast milk zinc" , "breast milk zinc", "breast milk zinc" No more information than that yet retrieved from the databases http://scientific.t homsonwebplus .com/ 11.02.2014 http://clinicaltri als.gov/ 11.02.2014 "breast milk”, “human milk” “zinc”, “zinc" No relevant information http://www.oclc .org/ 11.02.2014 "breast milk”, “human milk” “zinc”, “zinc" No relevant information http://www.ope ngrey.eu/ 11.02.2014 "breast milk”, “human milk” “zinc”, “zinc" No relevant information http://www.efsa .europa.eu/ "human milk zinc" , "human milk zinc", "human milk zinc" 11.02.2014 Reason for exclusion "breast milk”, “human milk” “zinc”, “zinc" No relevant information Search by hand in the reports http://www.anse s.fr/ 11.02.2014 "breast milk”, “human milk” EFSA supporting publication 2014:EN-629 French and English No relevant information 119 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features “zinc”, “zinc" searches Relevant reference? Reason for exclusion “lait maternel”, “zinc”, “zinc” Search by hand in the reports http://www.jstor .org/ http://www.grey lit.org/ "breast milk zinc" , "breast milk zinc", "breast milk zinc" 11.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" "breast milk zinc" , "breast milk zinc", "breast milk zinc" 11.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" "breast milk zinc" , "breast milk zinc", "breast milk zinc" http://worldwid escience.org/ 11.02.2014 http://www.scie nce.gov/ 12.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" "breast milk zinc" , "breast milk zinc", "breast milk EFSA supporting publication 2014:EN-629 Advanced search with restriction to articles published from 2000 No relevant information No relevant information No relevant information No relevant information 120 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? French and English searches No relevant information Advanced search with restriction to articles published from 2000 No relevant information Reason for exclusion zinc" "human milk zinc" , "human milk zinc", "human milk zinc" http://www.coll ectionscanada.g c.ca/thesescana da/ http://trove.nla. gov.au/ http://scienceres earch.com/ http://www.sud oc.abes.fr/ 12.02.2014 "breast milk”, “human milk” “zinc”, “zinc" “lait maternel”, “zinc”, “zinc” "breast milk zinc" , "breast milk zinc", "breast milk zinc" 12.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" "breast milk zinc" , "breast milk zinc", "breast milk zinc" No relevant information 12.02.2014 "human milk zinc" , "human milk zinc", "human milk zinc" 12.02.2014 "breast milk”, “human milk” “zinc”, “zinc" “lait maternel”, “zinc”, “zinc” EFSA supporting publication 2014:EN-629 French and English searches No relevant information 121 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL https://www.go ogle.pl/ http://scholar.go ogle.pl/ http://books.goo gle.com/?hl=pl http://www.ptzk d.org/ http://www.neo natologia.edu.pl / Access date Search terms used Specific features Relevant reference? "breast/human milk zinc" ,“breast/human milk nutrients”, “breast/human milk composition” – in Polish language Period searched from 2000; Polish searches 06.02.2014 “breast/human milk zinc", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Period searched from 2000; Polish searches No more information than that yet retrieved from the databases 06.02.2014 “breast/human milk zinc", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Period searched from 2000; Polish searches No relevant information 06.02.2014 "breast/human milk zinc", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information Polish searches No relevant information 06.02.2014 06.02.2014 "breast/human milk zinc", “breast/human milk nutrients”, “breast/human milk EFSA supporting publication 2014:EN-629 No relevant information or no more information than that yet retrieved from the databases Reason for exclusion 1 secondary publication: Pawlus 2004 1 publication with data on other nutrients: Stasiuk 2012 1 duplicate: PiotrowskaDepta 2006 122 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Specific features Relevant reference? 06.02.2014 "breast/human milk zinc", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information 06.02.2014 "breast/human milk zinc", “breast/human milk nutrients”, “breast/human milk composition” – in Polish language Polish searches No relevant information Access date Search terms used Reason for exclusion composition” – in Polish language http://www.ptp. edu.pl/ http://www.izz. waw.pl/pl/ EFSA supporting publication 2014:EN-629 123 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk C. SEARCH STRATEGIES FOR VITAMIN B6, VITAMIN E, CHOLINE, PHOSPHORUS AND POTASSIUM 1. Search strategies on Pubmed Search strategy PubMed 1 “Vitamin E”[MeSH] OR “Vitamin E” OR “tocopherol”[MeSH] OR “tocopherol*” OR “tocotrienol”[MeSH] OR “tocotrienol*” OR “Choline”[MeSH] OR “Choline” OR “Vitamin B6”[MeSH] OR “Vitamin B6” OR “Vitamin B 6” OR “Vitamin B-6” OR “Vitamin B(6)” OR "pyridoxal phosphate”[MeSH] OR "Phosphorus, Dietary"[Mesh] OR “Phosphorus”[MeSH] OR “Phosphorus” 195 780 2 1 Limit 2000/01/01 70 597 3 “Potassium, Dietary” [MeSH] OR Potassium [MeSH] OR Potassium 222 067 4 3 Limit 2010/10/01 18 529 5 2 OR 4 88 356 6 "Milk, Human"[Mesh] OR "Milk, Human" OR “human milk” OR "breast milk" OR breast milk OR “breast feeding”[MeSH] OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk” 44 163 7 5 AND 6 244 8 7 “NOT (Animals NOT Humans)” 237 Date of search: 3rd of January 2014 2. Search strategies on Embase Search strategy Embase 1 “Vitamin E”[emtree] OR “Vitamin E“ OR “tocopherol”[emtree] OR tocopherol* OR “tocotrienol”[emtree] OR tocotrienol* OR “Choline”[emtree] OR Choline OR “Vitamin B6”[emtree] OR “Vitamin B6” OR “Vitamin B 6” OR “Vitamin B-6” OR “Vitamin B(6)” OR "pyridoxal phosphate”[emtree] OR pyridoxine [emtree] OR "Phosphorus, Dietary"[emtree] OR “Phosphorus”[emtree] OR Phosphorus 528194 2 "breast milk"[emtree] OR "breast feeding"[emtree] OR “lactation” [emtree] OR breast milk OR “women milk” OR “women’s milk” OR “mother’s milk” 80834 EFSA supporting publication 2014:EN-629 124 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Search strategy Embase 3 1 AND 2 2410 4 #3 Limit 2000/01/01 1254 5 #4 Limit to Embase 1041 6 "Potassium"[emtree] OR “potassium ion” [emtree] OR “potassium” 329193 7 2 AND 6 939 8 #7 Limit 2010/10/01 141 9 #8 Limit to Embase 127 10 5 OR 9 1144 11 #10 not (animal not human) [Limit to human] 936 Date of search: 7th of January 2014 3. Search strategies on Web of Science Search strategy 1 Topic=(“Vitamin E” OR “tocopherol” OR “tocopherol*” OR “Abortosan” OR “Aquasol E” OR “Auxina E Bio E” OR “Biopto-E” OR “Biosan” OR “Lasar” OR “Bioweyxin” OR “Davitamon” OR “Dermorelle” OR “Detulin” OR “E-ferol” OR “E ferol” OR “E-Mulsin” OR “E Mulsin” OR “E-Vicotrat” OR “E Vicotrat” OR “EVitamin-ratiopharm” OR “Ecoro” OR “Elex Verla” OR “Embial” OR “Evion” OR “Ephynal” OR “Eplonat” OR “Equivit E” OR “Antioxidans E-Hevert” OR “Eusovit” OR “Hydrovit E” OR “Micorvit E” OR “Malton E” OR “Vitazell” OR “Puncto E” OR “Richtavit E” OR “Sanavitan S” OR “Snow-E Muscle, Energy and Fertility” OR “Spondyvit” OR “Tocolion” OR “Tocopa” OR “Tocopharm” OR “Vibolex” OR “Vit E hydrosol” OR “Vitamin E Stada” OR “Vita-E” OR “Vita E” OR “VitaE” OR “Tocovital” OR “Unique E” OR “Uno-Vit” OR “Uno Vit” OR “UnoVit” OR “VitaPlus E” OR “Vita Plus E” OR “VitaPlus E” OR “Vitamin-E Dragees” OR “Dragees, Vitamin-E” OR “Vitamin-E EVI-MIRALE” OR “EVI-MIRALE, Vitamin-E” OR “Vitamine E GNR” OR “Dal-E” OR “Dal E” OR “tocotrienol” OR “tocotrienol*” OR “Choline” OR “2-Hydroxy-N,N,N-trimethylethanaminium” OR “Choline Citrate” OR “Citrate, Choline” OR “Choline Bitartrate” OR “Bitartrate, Choline” OR EFSA supporting publication 2014:EN-629 Web Of Science 149 755 125 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Search strategy Web Of Science “Bursine” OR “Vidine” OR “Choline Hydroxide” OR “Hydroxide, Choline” OR “Fagine” OR “Choline Chloride” OR “Chloride, Choline” OR “Choline O-Sulfate” OR “Choline O Sulfate” OR “O-Sulfate, Choline” OR “Vitamin B6” OR “Vitamin B 6” OR “Vitamin B-6” OR “Vitamin B(6)” OR "pyridoxal phosphate” OR “Phosphate, Pyridoxal” OR “Pyridoxal-P” OR “Pyridoxal P” OR “Pyridoxal 5Phosphate” OR “Pyridoxal 5 Phosphate” OR "Phosphorus, Dietary" OR “Dietary Phosphorus” OR “Phosphorus”) 2 1 Timespan=(2000-2014) 83 217 3 Topic=(“Potassium, Dietary” OR “Dietary Potassium” OR “Potassium” OR “Potassium Ion Level” OR “Ion Level, Potassium” OR “Level, Potassium Ion”) 205 835 4 3 Timespan=(2010.10.01-2014) 33 506 5 2 OR 4 114 129 6 Topic=(“Milk, Human" OR “Breast Milk” OR “Breast Milks” OR “Milk, Breast” OR “human milk” OR “Breast milk” OR “Feeding, Breast” OR “Breastfeeding” OR “Breast Feeding, Exclusive” OR “Exclusive Breast Feeding” OR “Breastfeeding, Exclusive” OR “Exclusive Breastfeeding” OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk”) 32 991 7 5 AND 6 121 8 7 “NOT (Animals NOT Humans)” 121 Date of search: 3rd of January 2014 4. Grey literature searches Grey literature was searched by hand, using relevant keywords, more or less specific according to the searched websites/databases (see the following table). Websites interface and structure were carefully screened for identifying any relevant information. EFSA supporting publication 2014:EN-629 126 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL https://www.go ogle.com/ http://scholar.go ogle.fr/ http://books.goo gle.com/ http://www.nrv. gov.au/ Access date Search terms used "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 17.02.2014 Search by hand EFSA supporting publication 2014:EN-629 Specific features Relevant reference? Period searched from 2000 No more information than that yet retrieved from the databases Period searched from 2000 No more information than that yet retrieved from the databases Period searched from 2000 Information out of the range of selected dates Search in the “Nutrients” and “Ressources” section Information out of the range of selected dates Reason for exclusion 127 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL http://www.cod exalimentarius. org/ Access date 17.02.2014 Search terms used Specific features "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient", “breast milk nutrients” "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" “human milk nutrients” Relevant reference? Reason for exclusion No relevant information Search by hand in the reports http://www.eurr eca.org/everyon e/ http://www.nutr ition.org/ http://scientific.t homsonwebplus .com/ 17.02.2014 Search by hand "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 17.02.2014 "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" Search in the “Scientific Publication section No more information than that yet retrieved from the databases No more information than that yet retrieved from the databases No more information than that yet retrieved from the databases "human milk spec micronutrient" , "human milk spec EFSA supporting publication 2014:EN-629 128 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? Reason for exclusion micronutrient", "human milk spec micronutrient" http://clinicaltri als.gov/ http://www.oclc .org/ http://www.ope ngrey.eu/ http://www.efsa .europa.eu/ 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" No relevant information 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" No relevant information 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" No relevant information 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" No relevant information Search by hand in the reports http://www.anse s.fr/ 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" French and English searches No relevant information “lait maternel”, “spec micronutrient”, “spec EFSA supporting publication 2014:EN-629 129 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? Advanced search with restriction to articles published from 2000 No relevant information Reason for exclusion micronutrient” Search by hand in the reports http://www.jstor .org/ http://www.grey lit.org/ http://worldwid escience.org/ "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" EFSA supporting publication 2014:EN-629 No relevant information No relevant information 130 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL http://www.scie nce.gov/ http://www.coll ectionscanada.g c.ca/thesescana da/ http://trove.nla. gov.au/ http://scienceres earch.com/ Access date Search terms used Specific features "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 17.02.2014 “lait maternel”, “spec micronutrient”, “spec micronutrient” "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 17.02.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 17.02.2014 "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" Reason for exclusion No relevant information 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" Relevant reference? French and English searches No relevant information Advanced search with restriction to articles published from 2000 No relevant information No relevant information "human milk spec micronutrient" , EFSA supporting publication 2014:EN-629 131 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? French and English searches No relevant information Reason for exclusion "human milk spec micronutrient", "human milk spec micronutrient" http://www.sud oc.abes.fr/ 17.02.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" “lait maternel”, “spec micronutrient”, “spec micronutrient” https://www.go ogle.pl/ 24.02.2014 http://scholar.go ogle.pl/ 24.02.2014 http://books.goo gle.com/?hl=pl 24.02.2014 "breast milk vitamin B6", “breast milk choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” – in Polish language Period searched from 2000 (vit B6, vit E, choline, P) and 2010 (K), Polish searches "breast milk vitamin B6", “breast milk choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” – in Polish language Period searched from 2000 (vit B6, vit E, choline, P) and 2010 (K), Polish searches "breast milk vitamin B6", “breast milk Period searched from 2000 (vit B6, vit E, EFSA supporting publication 2014:EN-629 1 secondary publication: Pawlus 2004 No more information than that yet retrieved from the databases 1 publication with data on other nutrients: Stasiuk 2017 1 duplicate: PiotrowskaDepta 2006 No relevant information No relevant information 132 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” – in Polish language http://www.ptzk d.org/ http://www.neo natologia.edu.pl / http://www.ptp. edu.pl/ Specific features Relevant reference? choline, P) and 2010 (K), Polish searches 24.02.2014 "breast milk vitamin B6", “breast milk choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information 06.02.2014 "breast milk vitamin B6", “breast milk choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information Polish searches No relevant information 24.02.2014 ""breast milk vitamin B6", “breast milk choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” EFSA supporting publication 2014:EN-629 Reason for exclusion 133 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? Polish searches No relevant information Reason for exclusion – in Polish language http://www.izz. waw.pl/pl/ 24.02.2014 "breast milk vitamin B6", “breast milk choline”, “breast milk vitamin E”, “breast milk potassium”, “breast milk phosphorus”, “breast milk nutrients”, “breast milk composition” – in Polish language EFSA supporting publication 2014:EN-629 134 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk D. SEARCH STRATEGIES FOR VITAMIN A, VITAMIN B1, CHLORIDE, COPPER, MAGNESIUM AND SODIUM 1. Search strategies on Pubmed Search strategy PubMed 1 “Vitamin A”[MeSH] OR “Vitamin A” OR “retinol”[MeSH] OR “retinol” OR “carotenoids”[MeSH] OR “carotenoid*” OR “retinoids”[MeSH] OR “retinoid*” OR “Vitamin B1”[MeSH] OR “Vitamin B1” OR “thiamin”[MeSH] OR “thiamin” OR “vitamin B1” OR “Vitamin B 1” OR “Vitamin B-1” OR “Vitamin B(1)” OR “Chloride” OR “Chloride”[MeSH] OR “Sodium, Dietary”[MeSH] OR “sodium”[MeSH] OR “Sodium” OR “electrolyte*” 690 819 2 1 Limit 2000/01/01 275 158 3 “Magnesium”[MeSH] OR “Magnesium” 89 951 4 3 Limit 2010/10/01 7 090 5 “Copper”[MeSH] OR “Copper” 91 634 6 5 Limit 2011/01/01 14 909 7 2 OR 4 OR 6 86 871 8 "Milk, Human"[Mesh] OR "Milk, Human" OR “human milk” OR "breast milk" OR breastmilk OR “breast feeding”[MeSH] OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk” 44 165 9 7 AND 8 172 9 “NOT (Animals NOT Humans)” 165 10 th Date of search 6 of January 2014 2. Search strategies on Embase Search strategy Embase 1 “Vitamin A”[emtree] OR “Vitamin A” OR “retinol[emtree] OR retinol OR “carotenoids”[ emtree] OR carotenoid* OR “retinoids”[ emtree] or retinoid* OR “Vitamin B1”[emtree] OR Vitamin B1 OR “thiamin”[emtree] OR thiamin OR “vitamin B1” OR “Vitamin B 1” OR “Vitamin B-1” OR “Vitamin B(1)” OR Chloride OR “Chloride”[emtree] OR “Sodium, Dietary”[emtree] OR “sodium”[emtree] OR Sodium OR electrolyte* 1266791 2 "breast milk"[emtree] OR "breast feeding"[emtree] OR “lactation” [emtree] OR breastmilk OR “women milk” OR “women’s milk” OR “mother’s milk” 80834 3 1 AND 2 4979 EFSA supporting publication 2014:EN-629 135 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Search strategy Embase 4 #3 Limit 2000/01/01 3054 5 #4 Limit to Embase 2733 6 "Copper"[emtree] OR “copper” 134112 7 2 AND 6 754 8 #7 Limit 2011/01/01 105 9 #8 Limit to Embase 93 10 "Magnesium"[emtree] OR “magnesium” 127805 11 2 AND 10 793 12 #11 Limit 2010/10/01 104 13 #12 Limit to Embase 94 14 5 OR 9 OR 13 2842 #14 not (animal not human) [Limit to human] 2308 15 th Date of search 7 of January 2014 3. Search strategies on Web of Science Search strategy Web Of Science 1 Topic=(“Vitamin A” OR “Aquasol A” OR “Retinol” OR “3,7-dimethyl-9-(2,6,6trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, (all-E)-Isomer” OR “AllTrans-Retinol” OR “All Trans Retinol” OR “Vitamin A1” OR “11-cis-Retinol” OR “carotenoids” OR “carotenoid*” OR “Carotenes” OR “Carotene” OR “retinoids” OR “retinoid*” OR “Vitamin B1” OR “thiamin” OR “vitamin B1” OR “Vitamin B 1” OR “Vitamin B-1” OR “Vitamin B(1)” OR “Aneurin” OR “Chloride” OR “Sodium, Dietary” OR “Dietary Sodium” OR “Sodium” OR “electrolyte*”) 898 633 2 1 Timespan=(2000-2014) 575 890 3 Topic=(“Magnesium”) 120 004 4 3 Timespan=(2010.10.01-2014) 26 061 5 Topic=(“Copper”) 333 639 6 5 Limit 2011/01/01 54 383 7 2 OR 4 OR 6 645 381 EFSA supporting publication 2014:EN-629 136 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Web Of Science Search strategy 8 Topic=(“Milk, Human" OR “Breast Milk” OR “Breast Milks” OR “Milk, Breast” OR “human milk” OR “Breastmilk” OR “Feeding, Breast” OR “Breastfeeding” OR “Breast Feeding, Exclusive” OR “Exclusive Breast Feeding” OR “Breastfeeding, Exclusive” OR “Exclusive Breastfeeding” OR “breast feeding” OR “women milk” OR “women’s milk” OR “mother’s milk”) 32 991 9 7 AND 8 1 324 10 9 “NOT (Animals NOT Humans)” 1 305 Date of search 6th of January 2014 4. Grey literature searches URL https://www.google .pl/ http://scholar.googl e.pl/ http://books.google. com/?hl=pl Access date Search terms used Specific features Relevant reference 27.03.2014 "breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu), Polish searches No more information than that yet retrieved from the databases 27.03.2014 ""breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu), Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu), Polish searches No relevant information EFSA supporting publication 2014:EN-629 137 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference 27.03.2014 "breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoids", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information language http://www.ptzkd.or g/ http://www.neonato logia.edu.pl/ http://www.ptp.edu. pl/ http://www.izz.waw .pl/pl/ EFSA supporting publication 2014:EN-629 138 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Grey literature was searched by hand, using relevant keywords, more or less specific according to the searched websites/databases (see the following table). Websites interface and structure were carefully screened for identifying any relevant information. URL https://www.go ogle.pl/ http://scholar.go ogle.pl/ http://books.goo gle.com/?hl=pl Access date Search terms used Specific features Relevant reference? 27.03.2014 "breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu), Polish searches No more information than that yet retrieved from the databases 27.03.2014 ""breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu), Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu), Polish searches No relevant information EFSA supporting publication 2014:EN-629 Reason for exclusion 139 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Specific features Relevant reference? 27.03.2014 "breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language Polish searches No relevant information 27.03.2014 "breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast Polish searches No relevant information Access date Search terms used Reason for exclusion milk composition” – in Polish language http://www.ptzk d.org/ http://www.neo natologia.edu.pl / http://www.ptp. edu.pl/ EFSA supporting publication 2014:EN-629 140 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? Polish searches No relevant information Reason for exclusion milk composition” – in Polish language http://www.izz. waw.pl/pl/ http://scientific.t homsonwebplus .com/ http://clinicaltri als.gov/ http://www.oclc .org/ 27.03.2014 "breast milk vitamin A/retinol/carotenoi ds", “breast milk vitamin B1/vitamin B 1”, “breast milk chloride”, “breast milk sodium”, “breast milk copper”, “breast milk magnesium“, “breast milk nutrients”, “breast milk composition” – in Polish language "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" No more information than that yet retrieved from the databases 18.04.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 18.04.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" 18.04.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" EFSA supporting publication 2014:EN-629 Period searched from 2000 (vit A, vit B1, sodium, chloride) and 2010 (Mg), and 2011 (Cu) No relevant information No relevant information 141 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL http://www.ope ngrey.eu/ http://www.efsa .europa.eu/ Access date Search terms used 18.04.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" 18.04.2014 Specific features Relevant reference? Reason for exclusion No relevant information "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" No relevant information Search by hand in the reports "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" http://www.anse s.fr/ 18.04.2014 “lait maternel”, “spec micronutrient”, “spec micronutrient” French and English searches No relevant information Advanced search with restriction to articles published from 2000 (vit A, vit B1, sodium, chloride); 2010 (Mg), and 2011 (Cu) No relevant information Search by hand in the reports http://www.jstor .org/ "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 18.04.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" EFSA supporting publication 2014:EN-629 142 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL http://www.grey lit.org/ http://worldwid escience.org/ http://www.scie nce.gov/ http://www.coll ectionscanada.g c.ca/thesescana da/ Access date Search terms used Specific features "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" No relevant information 18.04.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" No relevant information 18.04.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 18.04.2014 Reason for exclusion No relevant information 18.04.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" Relevant reference? French and English searches No relevant information “lait maternel”, EFSA supporting publication 2014:EN-629 143 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk URL Access date Search terms used Specific features Relevant reference? Advanced search with restriction to articles published from 2000 (vit A, vit B1, sodium, chloride); 2010 (Mg), and 2011 (Cu) No relevant information Reason for exclusion “spec micronutrient”, “spec micronutrient” http://trove.nla. gov.au/ http://scienceres earch.com/ http://www.sud oc.abes.fr/ "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" 18.04.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" "breast milk spec micronutrient" , "breast milk spec micronutrient", "breast milk spec micronutrient" No relevant information 18.04.2014 "human milk spec micronutrient" , "human milk spec micronutrient", "human milk spec micronutrient" 18.04.2014 "breast milk”, “human milk” “spec micronutrient”, “spec micronutrient" “lait maternel”, “spec micronutrient”, “spec micronutrient” EFSA supporting publication 2014:EN-629 French and English searches No relevant information 144 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk E. REFERENCES FOR STUDIES EXCLUDED ON THE BASIS OF THE COUNTRY 1. Data on folates Han, Y. H., Yon, M. et al. (2009). "Folate concentrations in human milk and casein-based and soyabased formulas, and folate status in Korean infants." British Journal of Nutrition 101(12): 17691774. Sakurai, T., Furukawa, M. et al. (2005). 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"Cord blood iron profile and breast milk micronutrients in maternal iron deficiency anemia." Pediatric Blood and Cancer 58(2): 233-238. Anastacio, A. D. S., Da Silveira, C. L. P. et al. (2004). "Distribution of lead in human milk fractions: Relationship with essential minerals and maternal blood lead." Biological Trace Element Research 102(1-3): 27-37. Azevedo, P. M. C., Gavazzoni-dias, M. F. R. et al. (2008). "Acrodermatitis enteropathica in a full-term breast-fed infant: Case report and literature review." International Journal of Dermatology 47(10): 1056-1057. Becquey, E. and Martin-Prevel, Y. (2010). "Micronutrient adequacy of women's diet in urban Burkina Faso is low." Journal of Nutrition 140(11): 2079S-2085S. Berger, J., Ninh, N. X. et al. (2006). "Efficacy of combined iron and zinc supplementation on micronutrient status and growth in Vietnamese infants." European Journal of Clinical Nutrition 60(4): 443-454. Choua, G., Atalhi, N. et al. (2011). "Determination the quantity of zinc in serum and maternal milk of Moroccan babies exclusively breastfeeding." Annals of Nutrition and Metabolism 58: 378-379. Cooper, J., Krebs, N. et al. (2006). "Low maternal dietary zinc intake and breast milk zinc concentrations in southern Ethiopia." Western abstracts 54(1): p S144. EFSA supporting publication 2014:EN-629 145 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Correia-Santos, A. M., Bolognini, P. et al. (2011). "Dietary supplements for the lactating adolescent mother: influence on plasma micronutrients." Nutrición Hospitalaria 26(2): 392-8. Cunha, A., Dorea, J. et al. (2001). "Intrauterine device and maternal copper metabolism during lactation." Contraception 63(1):37-9. da Costa, R., do Carmo, M. et al. (2002). "Trace elements concentration of colostrum milk in Brazil." JOURNAL OF FOOD COMPOSITION AND ANALYSIS 15(1): 27–33. da Costa, R. S. S., do Carmo, M. G. T. et al. (2003). "Characterization of iron, copper and zinc levels in the colostrum of mothers of term and pre-term infants before and after pasteurization." International Journal of Food Sciences and Nutrition 54(2): 111-117. De Mello Neto, J., De Carvalho Rondo, P. et al. (2011). "Effect of common supplements on status of micronutrients of lactants of a human milk bank." Annals of Nutrition and Metabolism 58: 136137. De Mello Neto, J., Rondo, P. H. C. et al. (2011). "Effect of mineral and/or vitamin supplements usually consumed on iron, copper and zinc status of lactating women at a Brazilian human milk bank." Tropical Medicine and International Health 16: 286. De Pee, S. and Hautvast, J. G. A. J. (2005). "Variation in mineral concentrations in breast milk of Guatemalan mothers and a tribute to Professor Clive E. West." Journal of Pediatric Gastroenterology and Nutrition 40(2): 120-121. Dewey, K. G., Cohen, R. J. et al. (2004). "Exclusive Breast-Feeding for 6 Months, with Iron Supplementation, Maintains Adequate Micronutrient Status among Term, Low-Birthweight, Breast-Fed Infants in Honduras." Journal of Nutrition 134(5): 1091-1098. Dhonukshe-Rutten, R. A. M., Vossenaar, M. et al. (2005). "Day-to-day variations in iron, zinc and copper in breast milk of Guatemalan mothers." Journal of Pediatric Gastroenterology and Nutrition 40(2): 128-134. Dijkhuizen, M. A., Wieringa, F. T. et al. (2001). "Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia." American Journal of Clinical Nutrition 73(4): 786-791. Dijkhuizen, M. A., Wieringa, F. T. et al. (2004). "Zinc plus (beta)-carotene supplementation of pregnant women is superior to (beta)-carotene supplementation alone in improving vitamin A status in both mothers and infants." American Journal of Clinical Nutrition 80(5): 1299-1307. Donangelo, C. M., Zapata, C. L. V. et al. (2005). "Zinc absorption and kinetics during pregnancy and lactation in Brazilian women." American Journal of Clinical Nutrition 82(1): 118-124. Dorea, J. G. (2002). "Zinc and copper in breast-milk and home-prepared milk fed to urban infants from low-income families." Journal of Trace Elements in Experimental Medicine 15(3): 123-129. Dumrongwongsiri, O., Suthutvoravut, U. et al. (2013). "Maternal zinc status is associated with breast milk zinc concentration and zinc status of 4-6 month old infants." Annals of Nutrition and Metabolism 63: 611-612. El Din, Z. M. E., El Ghaffar, S. A. et al. (2004). "Is stored expressed breast milk an alternative for working Egyptian mothers?" Eastern Mediterranean Health Journal 10(6): 815-821. EFSA supporting publication 2014:EN-629 146 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk El Fekih, N., Monia, K. et al. (2011). "Transient symptomatic zinc deficiency in a breast-fed infant: Relevance of a genetic study." Nutrition 27(10): 1087-1089. Eneroth, H., El Arifeen, S. et al. (2009). "Duration of exclusive breast-feeding and infant iron and zinc status in rural Bangladesh." Journal of Nutrition 139(8): 1562-1567. Goes, H. C. A., Torres, A. G. et al. (2002). "Nutrient composition of banked human milk in Brazil and influence of processing on zinc distribution in milk fractions." Nutrition 18(7-8): 590-594. Hannan, M. A., Dogadkin, N. N. et al. (2005). "Copper, selenium, and zinc concentrations in human milk during the first three weeks of lactation." Biological Trace Element Research 107(1): 11-20. Itsumura, N., Inamo, Y. et al. (2013). "Compound Heterozygous Mutations in SLC30A2/ZnT2 Results in Low Milk Zinc Concentrations: A Novel Mechanism for Zinc Deficiency in a Breast-Fed Infant." PLoS ONE 8(5). Khaghani, S., Ezzatpanah, H. et al. (2010). "Zinc and copper concentrations in human milk and infant formulas." Iranian Journal of Pediatrics 20(1): 53-57. Kim, S. Y., Park, J. H. et al. (2012). "Longitudinal study on trace mineral compositions (selenium, zinc, copper, manganese) in Korean human preterm milk." Korean Med Sci 27: 532-536. Kosanovic, M., Adem, A. et al. (2008). "Simultaneous determination of cadmium, mercury, lead, arsenic, copper, and zinc in human breast milk by ICP-MS/microwave digestion." Analytical Letters 41(3): 406-416. Mahdavi, R., Nikniaz, L. et al. (2010). "Association between zinc, copper, and iron concentrations in breast milk and growth of healthy infants in Tabriz, Iran." Biological Trace Element Research 135(1-3): 174-181. Maia, P. A., Figueiredo, R. C. B. et al. (2007). "Zinc and copper metabolism in pregnancy and lactation of adolescent women." Nutrition 23(3): 248-253. Mastroeni, S. S. B. S., Okada, I. A. et al. (2006). "Concentrations of Fe, K, Na, Ca, P, Zn and Mg in maternal colostrum and mature milk." Journal of Tropical Pediatrics 52(4): 272-275. Mello-neto, J., Rondo, P. H. et al. (2010). "Iron concentrations in breast milk and selected maternal factors of human milk bank donors." Journal of Human Lactation 15(1): 27–33. Mello-neto, J., Rondo, P. H. C. et al. (2009). "The influence of maternal factors on the concentration of vitamin A in mature breast milk." Clinical Nutrition 28(2): 178-181. Melnikov, P., Moura, A. J. D. C. et al. (2007). "Zinc and copper in colostrum." Indian Pediatrics 44(5): 355-357. Murthy, S. C., Udagani, M. M. et al. (2010). "Symptomatic zinc deficiency in a full-term breast-fed infant." Dermatology Online Journal 16(6). Nakamori, M., Ninh, N. X. et al. (2009). "Nutritional status of lactating mothers and their breast milk concentration of iron, zinc and copper in rural Vietnam." Journal of Nutritional Science and Vitaminology 55(4): 338-345. Nwosu, F., Adekola, F. et al. (2003). "Comparison of some preconcentration methods for certain metal ions in human milk and yogurts." Bull. Chem. Soc. Ethiop. 17(1): 1-9. EFSA supporting publication 2014:EN-629 147 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Rakicioglu, N., Samur, G. et al. (2006). "The effect of Ramadan on maternal nutrition and composition of breast milk." Pediatrics International 48(3): 278-283. Scheplyagina, L. A. (2005). "Impact of the mother's zinc deficiency on the woman's and newborn's health status." Journal of Trace Elements in Medicine and Biology 19(1 SPEC. ISS.): 29-35. Severi, C., Hambidge, M. et al. (2013). "Zinc in plasma and breast milk in adolescents and adults in pregnancy and pospartum, a cohort study in Uruguay." Nutr Hosp 28(1): 223-228. Shaaban, S. Y., El-Hodhod, M. A. A. et al. (2005). "Zinc status of lactating Egyptian mothers and their infants: Effect of maternal zinc supplementation." Nutrition Research 25(1): 45-53. Yang, W. L., Hsu, C. K. et al. (2012). "Transient zinc deficiency syndrome in a breast-fed infant due to decreased zinc in breast milk (type II hypozincemia of infancy): A case report and review of the literature." Dermatologica Sinica 30(2): 66-70. 3. Data on Vitamin B6, Vitamin E, choline, phosphorus, potassium Barkova, E. N., Nazarenko, E. V. et al. (2005). "Diurnal variations in qualitative composition of breast milk in women with iron deficiency." Bulletin of Experimental Biology and Medicine 140(4): 394396. Bishara, R., Dunn, M. S. et al. (2008). "Nutrient composition of hindmilk produced by mothers of very low birth weight infants born at less than 28 weeks' gestation." Journal of Human Lactation 24(2): 159-167. Braga, L. P. M. and Palhares, D. B. (2007). Effect of evaporation and pasteurization in the biochemical and immunological composition of human milk. Jornal de Pediatria Efeito da evaporacao e pasteurizacao na composicao bioquimica e imunologica do leite humano. 83: 59-63. de Azeredo, V. B. and Trugo, N. M. (2008). "Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations” Nutrition 24(2): 133-139." Kamao, M., Tsugawa, N. et al. (2007). "Quantification of fat-soluble vitamins in human breast milk by liquid chromatography-tandem mass spectrometry." Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 859(2): 192-200. Kodentsova, V. M. and Vrzhesinskaya, O. A. (2006). "Evaluation of the vitamin status in nursing women by vitamin concentration in breast milk." Bulletin of Experimental Biology and Medicine 141(3): 323-327. Kositamongkol, S., Suthutvoravut, U. et al. (2011). "Vitamin A and E status in very low birth weight infants." Journal of Perinatology 31(7): 471-476. Lietz, G., Mulokozi, G. et al. (2006). "Xanthophyll and hydrocarbon carotenoid patterns differ in plasma and breast milk of women supplemented with red palm oil during pregnancy and lactation." Journal of Nutrition 136(7): 1821-1827. Macias, C. and Schweigert, F. J. (2001). "Changes in the concentration of carotenoids, vitamin A, alpha-tocopherol and total lipids in human milk throughout early lactation." Annals of Nutrition and Metabolism 45(2): 82-85. EFSA supporting publication 2014:EN-629 148 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Martinez, F. E., Sieber, V. M. et al. (2002). "Effect of supplementation of preterm formula with long chain polyunsaturated Fatty acids on mineral balance in preterm.” Journal of Pediatric Gastroenterology and Nutrition infants 35(4): 503-7." Mastroeni, S. S. B. S., Okada, I. A. et al. (2006). "Concentrations of Fe, K, Na, Ca, P, Zn and Mg in maternal colostrum and mature milk." Journal of Tropical Pediatrics 52(4): 272-275. Mataloun, M. M. G. B. and Leone, C. R. (2000). "Human milk mineral intake and serum concentrations of calcium and phosphorus in newborn term infants: Influence of intrauterine growth restriction." Acta Paediatrica, International Journal of Paediatrics 89(9): 1093-1097. Nikniaz, L., Mahdavi, R. et al. (2013). "Effects of synbiotic supplementation on total antioxidant capacity of human breastmilk." Breastfeeding Medicine 8(2): 217-222. Qiao, Y., Feng, J. et al. (2013). "The relationship between dietary vitamin A intake and the levels of sialic acid in the breast milk of lactating women." Journal of Nutritional Science and Vitaminology 59(4): 347-351. Tanaka, A., Rugolo, L. M. et al. (2006). "Fractional sodium excretion, urinary osmolality and specific gravity in preterm infants fed with fortified donor human milk” Jornal de pediatria 82(5): 335-40. Thomaz, D. M. C., Serafim, P. O. et al. (2012). "Comparison between homologous human milk supplements and a commercial supplement for very low birth weight infants." Jornal de Pediatria 88(2): 119-124. Todoroki, Y., Tsukahara, H. et al. (2005). "Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk." Free Radical Research 39(3): 291-297. Turner, T. and Burri, B. J. (2012). "Rapid isocratic HPLC method and sample extraction procedures for measuring carotenoid, retinoid, and tocopherol concentrations in human blood and breast milk for intervention studies." Chromatographia 75(5-6): 241-252. Yagi, T., Iwamoto, S. et al. (2013). "Concentrations of all forms of vitamin B6, pyridoxine-(beta)glucoside and 4-pyridoxic acid in mature milk of Japanese women according to 4-pyridoxolactoneconversion high performance liquid chromatography." Journal of Nutritional Science and Vitaminology 59(1): 9-15. Zimmerman, D. R., Goldstein, L. et al. (2009). "Effect of a 24+ hour fast on breast milk composition." Journal of Human Lactation 25(2): 194-198. 4. Data on Vitamin A, Vitamin B1, chloride, copper, magnesium, sodium Ahmed, L., Islam, S. et al. (2004). "Antioxidant micronutrient profile (Vitamin E, C, A, copper, zinc, iron) of colostrum: Association with maternal characteristics." Journal of Tropical Pediatrics 50(6): 357-358. Ali El-Farrash, R., Rahman Ismail, E. A. et al. (2012). "Cord blood iron profile and breast milk micronutrients in maternal iron deficiency anemia." Pediatric Blood and Cancer 58(2): 233-238. Ali, S. (2000). "Hypernatrenic dehydration in a neonate due to high sodium concentration in breast milk and apparent lactation failure." Saudi Medical Journal 21(6): 593-595. EFSA supporting publication 2014:EN-629 149 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Atalhi, N., Choua, G. et al. (2011). "Impact of daily consumption of Vitamin A fortified oil on human milk Vitamin A concentration in lactating Moroccan women." Annals of Nutrition and Metabolism 58: 6. Bahl, R., Bhandari, N. et al. (2002). "Vitamin A supplementation of women postpartum and of their infants at immunization alters breast milk retinol and infant vitamin A status." Journal of Nutrition 132(11): 3243-3248. Bezerra, D., de Araujo, K. et al. (2010). "A Randomized Trial Evaluating the Effect of 2 Regimens of Maternal Vitamin A Supplementation on Breast Milk Retinol Levels." Journal of Human Lactation 26(2): 148-156. Bhaskaram, P., Balakrishna, N. et al. (2000). "Vitamin A deficiency in infants: Effects of postnatal maternal vitamin A supplementation on the growth and vitamin A status." Nutrition Research 20(6): 769-778. Bishara, R., Dunn, M. S. et al. (2008). "Nutrient composition of hindmilk produced by mothers of very low birth weight infants born at less than 28 weeks' gestation." Journal of Human Lactation 24(2): 159-167. Braga, L. P. M. and Palhares, D. B. (2007). Effect of evaporation and pasteurization in the biochemical and immunological composition of human milk. Jornal de Pediatria Efeito da evaporacao e pasteurizacao na composicao bioquimica e imunologica do leite humano. 83: 59-63. Caminha, M., Diniz, A. et al. (2008). "Serum retinol concentrations in hospitalized severe proteinenergy malnourished children." Journal of Tropical Pediatrics 54(4): 248-252. Correia-Santos, A. M., Bolognini, P. et al. (2011). "Dietary supplements for the lactating adolescent mother: influence on plasma micronutrients." Nutricion hospitalaria 26(2): 392-398. de Azeredo, V. and Trugo, N. (2008). "Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations." Nutrition 24: 133-139. Dijkhuizen, M. A., Wieringa, F. T. et al. (2004). "Zinc plus (beta)-carotene supplementation of pregnant women is superior to (beta)-carotene supplementation alone in improving vitamin A status in both mothers and infants." American Journal of Clinical Nutrition 80(5): 1299-1307. Estes, J., Craft, N. et al. (2002). "Analysis of vitamin A (VA) in breast milk (BM) and fortified sugar." Faseb Journal 16(4). Fernandes, T. F., Figueiroa, J. N. et al. (2011). "Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A." PEDIATRICS 129(4): e960-966. Fujita, M., Shell-Duncan, B. et al. (2011). "Vitamin A dynamics in breastmilk and liver stores: a life history perspective." AMERICAN JOURNAL OF HUMAN BIOLOGY 23: 664-673. Guimaraes, E., V, G. Schettino, et al. (2012). "Prevalence of Hyponatremia at Diagnosis and Factors Associated with the Longitudinal Variation in Serum Sodium Levels in Infants with Cystic Fibrosis." THE JOURNAL OF PEDIATRICS 161(2): 285-289. Hsairi, M., Ben Hamouda, H. et al. (2006). Hypernatremic dehydration and breast-feeding. Journal de Pediatrie et de Puericulture - Deshydratation hypernatremique et allaitement maternel. 19(7): 265267. EFSA supporting publication 2014:EN-629 150 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Vitamin and mineral content of breast milk Kamao, M., Tsugawa, N. et al. (2007). 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H. C. et al. (2006). Evaluation of retinol levels in the human colostrum and its relation with maternal vitamin A nourishing state. Revista Brasileira de Medicina Avaliaao dos niveis de retinol no colostro humano e a sua relacao com o estado nutricional materno em vitamina A. 63: 206-210. Ergin, H., Sahin, O. et al. (2013). Hypernatremic dehydration in breastfed infants. Guncel Pediatri Anne sutuyle beslenen yenidoganlarda hipernatremik dehidratasyon. 11: 51-56. Penalver Giner, O., Gisbert Mestre, J. et al. (2004). Hypernatremic dehydration associated with breastfeeding. Anales de Pediatria Deshidratacion hipernatremica asociada a lactancia materna. 61: 340343. Queiroz Bortolozo, E. A. F., Borges Tiboni, E. et al. (2004). Milk from human milk banks for low birthweight newborns: Nutritional concentrations and supplementation. Revista Panamericana de Salud Publica/Pan American Journal of Public Health Leite humano processado em bancos de leite para o recem-nascido de baixo peso: Analise nutricional e proposta de um novo complemento. 16: 199-205. EFSA supporting publication 2014:EN-629 154 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.