Breast Milk Micronutrients and Infant Neurodevelopmental Outcomes: A Systematic Review

Francesca Lockyer, Samantha McCann, Sophie E Moore, Francesca Lockyer, Samantha McCann, Sophie E Moore

Abstract

Micronutrients are fundamental for healthy brain development and deficiencies during early development can have a severe and lasting impact on cognitive outcomes. Evidence indicates that undernourished lactating individuals may produce breast milk containing lower concentrations of certain vitamins and minerals. Exclusively breastfed infants born to mothers deficient in micronutrients may therefore be at risk of micronutrient deficiencies, with potential implications for neurodevelopment. This systematic review aims to consider current knowledge on the effects of breast milk micronutrients on the developmental outcomes of infants. The databases Medline, Global Health, PsychInfo, Open Grey, and the Web of Science were searched for papers published before February 2021. Studies were included if they measured micronutrients in breast milk and their association with the neurodevelopmental outcomes of exclusively breastfed infants. Also, randomised control trials investigating neurocognitive outcomes following maternal supplementation during lactation were sought. From 5477 initial results, three observational studies were eligible for inclusion. These investigated associations between breast milk levels of vitamin B6, carotenoids, or selenium and infant development. Results presented suggest that pyroxidal, β-carotene, and lycopene are associated with infant neurodevelopmental outcomes. Limited eligible literature and heterogeneity between included papers prevented quantitative synthesis. Insufficient evidence was identified, precluding any conclusions on the relationship between breast milk micronutrients and infant developmental outcomes. Further, the evidence available was limited by a high risk of bias. This highlights the need for further research in this area to understand the long-term influence of micronutrients in breast milk, the role of other breast milk micronutrients in infant neurodevelopmental outcomes, and the impact of possible lactational interventions.

Keywords: breastfeeding; human; infants; micronutrients; milk; neurodevelopment; nutrition.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of study selection.

References

    1. Krebs N.F., Lozoff B., Georgieff M.K. Neurodevelopment: The Impact of Nutrition and Inflammation During Infancy in Low-Resource Settings. Pediatrics. 2017;139:S50–S58. doi: 10.1542/peds.2016-2828G.
    1. Cusick S.E., Georgieff M.K. The Role of Nutrition in Brain Development: The Golden Opportunity of the “First 1000 Days”. J. Pediatr. 2016;175:16–21. doi: 10.1016/j.jpeds.2016.05.013.
    1. Martorell R. Improved nutrition in the first 1000 days and adult human capital and health. Am. J. Hum. Biol. 2017;29 doi: 10.1002/ajhb.22952.
    1. Fox S.E., Levitt P., Nelson C.A., III How the timing and quality of early experiences influence the development of brain architecture. Child. Dev. 2010;81:28–40. doi: 10.1111/j.1467-8624.2009.01380.x.
    1. Schwarzenberg S.J., Georgieff M.K. Advocacy for Improving Nutrition in the First 1000 Days to Support Childhood Development and Adult Health. Pediatrics. 2018;141:e20173716. doi: 10.1542/peds.2017-3716.
    1. da Cunha A.J.L.A., Leite Á.J.M., de Almeida I.S. The pediatrician’s role in the first thousand days of the child: The pursuit of healthy nutrition and development. J. Pediatr. 2015;91:S44–S51. doi: 10.1016/j.jped.2015.07.002.
    1. Bailey R.L., West K.P., Jr., Black R.E. The epidemiology of global micronutrient deficiencies. Ann. Nutr. Metab. 2015;66:22–33. doi: 10.1159/000371618.
    1. Georgieff M.K., Ramel S.E., Cusick S.E. Nutritional influences on brain development. Acta Paediatr. 2018;107:1310–1321. doi: 10.1111/apa.14287.
    1. Semba R.D., Delange F. Iodine in Human Milk: Perspectives for Infant Health. Nutr. Rev. 2001;59:269–278. doi: 10.1111/j.1753-4887.2001.tb05512.x.
    1. Adamo A.M., Oteiza P.I. Zinc deficiency and neurodevelopment: The case of neurons. Biofactors. 2012;36:117–124. doi: 10.1002/biof.91.
    1. Saher G., Brügger B., Lappe-Siefke C., Möbius W., Tozawa R.-I., Wehr M.C., Wieland F., Ishibashi S., Nave K.-A. High cholesterol level is essential for myelin membrane growth. Nat. Neurosci. 2005;8:468–475. doi: 10.1038/nn1426.
    1. Grantham-McGregor S. A review of studies of the effect of severe malnutrition on mental development. J. Nutr. 1995;125:2233S–2238S. doi: 10.1093/jn/125.suppl_8.2233S.
    1. Delange F. Iodine deficiency as a cause of brain damage. Postgrad. Med. J. 2001;77:217–220. doi: 10.1136/pmj.77.906.217.
    1. Georgieff M.K. Long-term brain and behavioral consequences of early iron deficiency. Nutr. Rev. 2011;69:S43–S48. doi: 10.1111/j.1753-4887.2011.00432.x.
    1. Bhutta Z.A. Prevention of Micronutrient Deficiencies: Tools for Policy Makers and Public Health Workers. BMJ. 1998;317:1460. doi: 10.1136/bmj.317.7170.1460.
    1. Elmadfa I., Meyer A.L. Vitamins for the first 1000 days: Preparing for life. Int. J. Vitam. Nutr. Res. 2012;82:342–347. doi: 10.1024/0300-9831/a000129.
    1. Victora C.G., Bahl R., Barros A.J.D., França G.V.A., Horton S., Krasevec J., Murch S., Sankar M.J., Walker N., Rollins N.C. Breastfeeding in the 21st century: Epidemiology, mechanisms, and lifelong effect. Lancet. 2016;387:475–490. doi: 10.1016/S0140-6736(15)01024-7.
    1. Deoni S.C.L., Douglas D.C., Piryatinsky I., O’Muircheartaigh J., Waskeiwicz N., Lehman K., Han M., Dirks H. Breastfeeding and early white matter development: A cross-sectional study. Neuroimage. 2013;82:77–86. doi: 10.1016/j.neuroimage.2013.05.090.
    1. Belfort M.B., Anderson P.J., Nowak V.A., Lee K.J., Molesworth C., Thompson D.K., Doyle L.W., Inder T.E. Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks’ Gestation. J. Pediatr. 2016;177:133–139. doi: 10.1016/j.jpeds.2016.06.045.
    1. Der G., Batty G.D., Deary I.J. Effect of breast feeding on intelligence in children: Prospective study, sibling pairs analysis, and meta-analysis. BMJ. 2006;333:945. doi: 10.1136/bmj.38978.699583.55.
    1. Jacobson S.W., Carter R.C., Jacobson J.L. Breastfeeding as a Proxy for Benefits of Parenting Skills for Later Reading Readiness and Cognitive Competence. J. Pediatr. 2014;164:440–442. doi: 10.1016/j.jpeds.2013.11.041.
    1. Klaus M. Mother and infant: Early emotional ties. Pediatrics. 1998;102:1244–1246.
    1. Lucas A., Morley R., Cole T.J., Lister G., Leeson-Payne C. Breast milk and subsequent intelligence quotient in children born preterm. Lancet. 1992;339:261–264. doi: 10.1016/0140-6736(92)91329-7.
    1. Harit D., Faridi M.M.A., Aggarwal A., Sharma S.B. Lipid profile of term infants on exclusive breastfeeding and mixed feeding: A comparative study. Eur. J. Clin. Nutr. 2008;62:203–209. doi: 10.1038/sj.ejcn.1602692.
    1. Isaacs E.B., Fischl B.R., Quinn B.T., Chong W.K., Gadian D.G., Lucas A. Impact of Breast Milk on Intelligence Quotient, Brain Size, and White Matter Development. Pediatr. Res. 2010;67:357–362. doi: 10.1203/PDR.0b013e3181d026da.
    1. Cunnane S.C., Francescutti V., Brenna J.T., Crawford M.A. Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexaenoate. Lipids. 2000;35:105–111. doi: 10.1007/s11745-000-0501-6.
    1. Dror D.K., Allen L.H. Overview of nutrients in human milk. Adv. Nutr. 2018;9:278S–294S. doi: 10.1093/advances/nmy022.
    1. Allen L.H. Maternal micronutrient malnutrition: Effects on breast milk and infant nutrition, and priorities for intervention. SCN News. 1994;11:21–24.
    1. World Health Organization Essential Nutrition Actions: Improving Maternal, Newborn, Infant and Young Child Health and Nutrition. 2013. [(accessed on 29 February 2021)]. Available online: .
    1. Picciano M.F. Nutrient Composition of Human Milk. Pediatr. Clin. N. Am. 2001;48:53–67. doi: 10.1016/S0031-3955(05)70285-6.
    1. Dorea J.G. Iodine nutrition and breast feeding. J. Trace Elem. Med. Biol. 2002;16:207–220. doi: 10.1016/S0946-672X(02)80047-5.
    1. Dijkhuizen M.A., Wieringa F.T., West C.E., Muherdiyantiningsih, Muhilal. Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia. Am. J. Clin. Nutr. 2001;73:786–791. doi: 10.1093/ajcn/73.4.786.
    1. Bellows A.L., Smith E.R., Muhihi A., Briegleb C., Noor R.A., Mshamu S., Sudfeld C., Masanja H., Fawzi W.W. Micronutrient Deficiencies among Breastfeeding Infants in Tanzania. Nutrients. 2017;9:1258. doi: 10.3390/nu9111258.
    1. Stelle I., Venkatesan S., Edmond K., Moore S.E. Acknowledging the gap: A systematic review of micronutrient supplementation in infants under six months of age. Wellcome Open Res. 2020;5:238. doi: 10.12688/wellcomeopenres.16282.1.
    1. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:71. doi: 10.1136/bmj.n71.
    1. The EndNote Team . EndNote. Clarivate; Philadelphia, PA, USA: 2013. EndNote 20.
    1. Cochrane Developmental, Psychosocial and Learning Problems Data Collection Form for Intervention Reviews: RCTs and Non-RCTs Version 3. 2014. [(accessed on 10 March 2021)]. Available online: .
    1. Critical Appraisal Skills Programme CASP Checklists. 2019. [(accessed on 17 March 2021)]. Available online:
    1. Christian P., Shamim A., Shaikh S., Ali H., Mehra S., Lee W., Labrique A., Schulze K., Klemm R., West K., Jr. Antenatal multiple micronutrient supplementation and growth in the first two years of life and cognitive function at 24 months in rural Bangladesh. FASEB J. 2014;28:256. doi: 10.1096/fasebj.28.1_supplement.256.5.
    1. Boylan L.M., Hart S., Driskell J.A. Neonatal behavioral development: Impact of pyridoxal content of mothers milk. FASEB J. 2000;14:A232.
    1. Latifah L., Nurcahyani Y.D., Yunitawati D., Kusrini I., Mulyantoro D.K. Breastmilk iodine level and infant development in replete and non replete iodine area. Ann. Nutr. Metab. 2019;75:98–99. doi: 10.1159/000501751.
    1. Cheatham C., Stegall J., Sheppard K., Armer A., Millsap G., Wernimont S., Zeisel S. The relation of human milk lutein, choline, and docosahexaenoic acid content to recognition memory abilities of 6-month-old breastfed infants. FASEB J. 2014;28:247. doi: 10.1096/fasebj.28.1_supplement.247.4.
    1. Gebreegziabher T., Woltamo T., Thomas D.G., Kennedy T.S., Stoecker B.J. Iodine supplementation of lactating women and assessment of infant visual information processing and maternal and infant thyroid function: A randomized trial. PLoS ONE. 2019;14:e0223348. doi: 10.1371/journal.pone.0223348.
    1. McCullough A.L., Kirksey A., Wachs T.D., McCabe G.P., Bassily N.S., Bishry Z., Galal O.M., Harrison G.G., Jerome N.W. Vitamin B-6 status of Egyptian mothers: Relation to infant behavior and maternal-infant interactions. Am. J. Clin. Nutr. 1990;51:1067–1074. doi: 10.1093/ajcn/51.6.1067.
    1. Neumann C.G., Oace S.M., Chaparro M.P., Herman D., Drorbaugh N., Bwibo N.O. Low vitamin B-12 intake during pregnancy and lactation and low breastmilk vitamin B-12 content in rural Kenyan women consuming predominantly maize diets. Food Nutr. Bull. 2013;34:151–159. doi: 10.1177/156482651303400204.
    1. Wu M., Wu D., Wu W., Li H., Cao L., Xu J., Yu X., Bian X., Yan C., Wang W. Relationship between Iodine Concentration in Maternal Colostrum and Neurobehavioral Development of Infants in Shanghai, China. J. Child. Neur. 2016;31:1108–1113. doi: 10.1177/0883073816639378.
    1. Cheatham C.L., Sheppard K.W. Synergistic Effects of Human Milk Nutrients in the Support of Infant Recognition Memory: An Observational Study. Nutrients. 2015;7:9079–9095. doi: 10.3390/nu7115452.
    1. Gebreegziabher T.A.O., Stoecker B.J. Comparison of two sources of iodine delivery on breast milk iodine and maternal and infant urinary iodine concentrations in southern Ethiopia: A randomized trial. Food Sci. Nutr. 2017;5:921–928. doi: 10.1002/fsn3.477.
    1. Honzik T., Adamovicova M., Smolka V., Magner M., Hruba E., Zeman J. Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B12 deficiency—What have we learned? Eur. J. Paediatr. Neurol. 2010;14:488–495. doi: 10.1016/j.ejpn.2009.12.003.
    1. Blackwell R.Q., Chow B.F., Chinn K.S.K., Blackwell B.N., Hsu S.C. Prospective Maternal Nutrition Study in Taiwan—Rationale, Study Design, Feasibility, and Preliminary Findings. Nutr. Rep. Int. 1973;7:517–532.
    1. Osei J., Baumgartner J., Rothman M., Matsungo T.M., Covic N., Faber M., Smuts C.M. Iodine status and associations with feeding practices and psychomotor milestone development in six-month-old South African infants. Matern. Child. Nutr. 2017;13:e12408. doi: 10.1111/mcn.12408.
    1. Park S., Bellinger D.C., Adamo M., Bennett B., Choi N.K., Baltazar P.I., Ayaso E.B., Monterde D.B.S., Tallo V., Olveda R.M., et al. Mechanistic pathways from early gestation through infancy and neurodevelopment. Pediatrics. 2016;138:e20161843. doi: 10.1542/peds.2016-1843.
    1. Prado E.L., Abbeddou S., Adu-Afarwuah S., Arimond M., Ashorn P., Ashorn U., Bendabenda J., Brown K.H., Hess S.Y., Kortekangas E., et al. Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso. J. Child. Psychol. Psychiatry. 2017;58:1264–1275. doi: 10.1111/jcpp.12751.
    1. Bhargava A. Modeling the effects of maternal nutritional status and socioeconomic variables on the anthropometric and psychological indicators of Kenyan infants from age 0-6 months. Am. J. Phys. Anthropol. 2000;111:89–104. doi: 10.1002/(SICI)1096-8644(200001)111:1<89::AID-AJPA6>;2-X.
    1. Al-Saleh I., Al-Mohawes S., Al-Rouqi R., Elkhatib R. Selenium status in lactating mothers-infants and its potential protective role against the neurotoxicity of methylmercury, lead, manganese, and DDT. Environ. Res. 2019;176:108562. doi: 10.1016/j.envres.2019.108562.
    1. Arakawa T., Mizuno T., Honda Y. Brain function of infants fed on milk from mothers with low serum folate levels. Tohoku J. Exp. Med. 1969;97:391–397. doi: 10.1620/tjem.97.391.
    1. Matias S.L., Mridha M.K., Tofail F., Arnold C.D., Khan M.S.A., Siddiqui Z., Ullah M.B., Dewey K.G. Home fortification during the first 1000 d improves child development in Bangladesh: A cluster-randomized effectiveness trial. Am. J. Clin. Nutr. 2017;105:958–969. doi: 10.3945/ajcn.116.150318.
    1. Boylan L.M., Hart S., Porter K.B., Driskell J.A. Vitamin B-6 content of breast milk and neonatal behavioral functioning. J. Am. Diet. Assoc. 2002;102:1433–1438. doi: 10.1016/S0002-8223(02)90317-2.
    1. Zielinska M.A., Hamulka J., Grabowicz-Chadrzynska I., Brys J., Wesolowska A. Association between Breastmilk LC PUFA, Carotenoids and Psychomotor Development of Exclusively Breastfed Infants. Int. J. Environ. Res. Public Health. 2019;16:1144. doi: 10.3390/ijerph16071144.
    1. Castriotta L., Rosolen V., Biggeri A., Ronfani L., Catelan D., Mariuz M., Bin M., Brumatti L.V., Horvat M., Barbone F. The role of mercury, selenium and the Se-Hg antagonism on cognitive neurodevelopment: A 40-month follow-up of the Italian mother-child PHIME cohort. Int. J. Hyg. Environ. Health. 2020;230:113604. doi: 10.1016/j.ijheh.2020.113604.
    1. Zielinska M.A., Hamulka J., Wesolowska A. Carotenoid Content in Breastmilk in the 3rd and 6th Month of Lactation and Its Associations with Maternal Dietary Intake and Anthropometric Characteristics. Nutrients. 2019;11:193. doi: 10.3390/nu11010193.
    1. Albers C.A., Grieve A.J. Test review: Bayley, N. (2006). Bayley scales of infant and toddler development–third edition. San Antonio, TX: Harcourt assessment. J. Psychoeduc. Assess. 2007;25:180–190. doi: 10.1177/0734282906297199.
    1. Brazelton T.B., Nugent J.K. Neonatal Behavioral Assessment Scale. Cambridge University Press; Cambridge, UK: 1995.
    1. Paluch P., Kochański B., Ganc M., Cieśla K., Milner R., Pluta A., Lewandowska M. Early general development and central auditory system maturation in children with cochlear implants—A case series. Int. J. Pediatr. Otorhinolaryngol. 2019;126:109625. doi: 10.1016/j.ijporl.2019.109625.
    1. Abe S.K., Balogun O.O., Ota E., Takahashi K., Mori R. Supplementation with multiple micronutrients for breastfeeding women for improving outcomes for the mother and baby. Cochrane Database Syst. Rev. 2016;2:CD010647. doi: 10.1002/14651858.CD010647.pub2.
    1. Oliveira J.M., Allert R., East C.E. Vitamin A supplementation for postpartum women. Cochrane Database Syst. Rev. 2016;3:CD005944. doi: 10.1002/14651858.CD005944.pub3.
    1. Jensen C.L., Voigt R.G., Prager T.C., Zou Y.L., Fraley J.K., Rozelle J.C., Turcich M.R., Llorente A.M., Anderson R.E., Heird W.C. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants. Am. J. Clin. Nutr. 2005;82:125–132. doi: 10.1093/ajcn/82.1.125.
    1. Berger P.K., Plows J.F., Jones R.B., Alderete T.L., Yonemitsu C., Poulsen M., Ryoo J.H., Peterson B.S., Bode L., Goran M.I. Human milk oligosaccharide 2′-fucosyllactose links feedings at 1 month to cognitive development at 24 months in infants of normal and overweight mothers. PLoS ONE. 2020;15:e0228323. doi: 10.1371/journal.pone.0228323.
    1. Allen L.H. B vitamins in breast milk: Relative importance of maternal status and intake, and effects on infant status and function. Adv. Nutr. 2012;3:362–369. doi: 10.3945/an.111.001172.
    1. Walker S.P., Wachs T.D., Grantham-McGregor S., Black M.M., Nelson C.A., Huffman S.L., Richter L. Inequality in early childhood: Risk and protective factors for early child development. Lancet. 2011;378:1325–1338. doi: 10.1016/S0140-6736(11)60555-2.
    1. Prendergast A.J., Humphrey J.H. The stunting syndrome in developing countries. Paediatr. Int. Child. Health. 2014;34:250–265. doi: 10.1179/2046905514Y.0000000158.
    1. Kramer M.S., Kakuma R. The optimal duration of exclusive breastfeeding: A systematic review. Adv. Exp. Med. Biol. 2004;554:63–77. doi: 10.1007/978-1-4757-4242-8_7.
    1. Butte N.F., Lopez-Alarcon M.G., Garza C. Nutrient Adequacy of Exclusive Breastfeeding for the Term Infant during the First Six Months of Life. World Health Organization; Geneva, Switzerland: 2002.
    1. Horta B.L., De Mola C.L., Victora C.G. Breastfeeding and intelligence: A systematic review and meta-analysis. Acta Paediatr. 2015;104:14–19. doi: 10.1111/apa.13139.
    1. Victora C.G., Horta B.L., De Mola C.L., Quevedo L., Pinheiro R.T., Gigante D.P., Gonçalves H., Barros F.C. Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: A prospective birth cohort study from Brazil. Lancet Glob. Health. 2015;3:e199–e205. doi: 10.1016/S2214-109X(15)70002-1.
    1. Krol K.M., Grossmann T. Psychological effects of breastfeeding on children and mothers. Bundesgesundheitsblatt Gesundh. Gesundh. 2018;61:977–985. doi: 10.1007/s00103-018-2769-0.
    1. Perrone L., Di Palma L., Di Toro R., Gialanella G., Moro R. Interaction of trace elements in a longitudinal study of human milk from full-term and preterm mothers. Biol. Trace Elem. Res. 1994;41:321–330. doi: 10.1007/BF02917432.
    1. Da Cunha R.D.E.S., Fernando L.F., Rafael E.V., Lamy Z.C., De Queiroz A.L.G. Breast milk supplementation and preterm infant development after hospital discharge: A randomized clinical trial. J. Pediatr. 2016;92:136–142. doi: 10.1016/j.jped.2015.04.004.
    1. Lucas A., Fewtrell M.S., Morley R., Lucas P.J., Baker B.A., Lister G., Bishop N.J. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Am. J. Clin. Nutr. 1996;64:142–151. doi: 10.1093/ajcn/64.2.142.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe