Effects of Folate and Vitamin B 12 Deficiencies During Pregnancy on Fetal, Infant, and Child Development
Abstract
The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects (NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B 12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B 12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B 12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B 12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B 12 status have not been sufficiently researched.
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Folic acid is necessary for human survival and is involved in essential cellular events: synthesis of DNA and cell proliferation, erythrocyte formation, vitamin B12-dependent remethylation of homocysteine to methionine, DNA and histone methylation.
“Folic acid is a micronutrient necessary for human survival and is involved in essential cellular events: synthesis of DNA and cell proliferation, erythrocyte formation, the vitamin B12-dependent remethylation of homocysteine to methionine, DNA and histone methylation.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [109]
Folic acid is a key regulator of DNA synthesis, methylation processes, and epigenetic programming during early development, making it central to fetal organogenesis and long-term metabolic and neurocognitive health.
“In summary, folic acid is a key regulator of DNA synthesis, methylation processes, and epigenetic programming during early development, making it central to fetal organogenesis and long-term metabolic and neurocognitive health [109,110].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [109]
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Green, R., Allen, L. H., Bjørke-Monsen, A.-L., Brito, A., Guéant, J.-L., Miller, J. W., Molloy, A. M., Nexo, E., Stabler, S., Toh, B.-H., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.40 · Cited by 970 · see citing works
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- Authors
- Molloy, A. M., Kirke, P. N., Brody, L. C., Scott, J. M., & Mills, J. L.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Molloy, Anne M.
- Venue
- Food and Nutrition Bulletin
- Publisher
- SAGE Publications
- Published
- 2008-06
- Volume
- 29
- Issue
- 2_suppl1
- Pages
- S101-S111
- ISSN
- 0379-5721 (ISSN-L)
- 1564-8265
- OpenAlex
- W120235536
- Cited by
- 308
- References
- 4
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 15 · 2023: 34 · 2022: 19 · 2021: 30 · 2020: 20 · 2019: 19 · 2018: 15 · 2017: 22 · 2016: 19 · 2015: 13 · 2014: 12 · 2013: 18 · 2012: 14
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food and Nutrition Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- folate deficiency, vitamin B12 deficiency, pregnancy, maternal nutrition, fetal development, infant development, birth weight, neural tube defects, megaloblastic anemia, recurrent pregnancy loss, preterm birth, lactation, breast milk, childhood anemia, congenital malformations
- MeSH terms
- Congenital Abnormalities, Abortion, Spontaneous, Child Development, Child Nutritional Physiological Phenomena, Child, Preschool, Female, Folic Acid, Folic Acid Deficiency, Humans, Infant, Infant, Low Birth Weight, Infant, Newborn, Neural Tube Defects, Nutritional Status, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Vitamin B 12, Vitamin B 12 Deficiency, Women's Health, Maternal Nutritional Physiological Phenomena, Prenatal Nutritional Physiological Phenomena
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