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Cited by 213Folate and B Vitamins ResearchBirth, Development, and HealthMaternal Mental Health During Pregnancy and Postpartum

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India

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Behere, Rishikesh V., Deshmukh, Anagha S., Otiv, Suhas, Gupte, Mohan D., Yajnik, Chittaranjan S.·2021·Frontiers in Endocrinology
DOI 10.3389/fendo.2021.619176PMC PMC8074968
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Abstract

Background: Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy. Methods: A systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Of the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT’s -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT’s) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring. Conclusion: In the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia. Systematic Review Registration: [website], identifier [registration number]

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  • These factors include hormones, vitamins, diet-derived metabolites and environmental chemicals.

    “These include hormones, vitamins, diet-derived metabolites and environmental chemicals [48,98,103,104].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [104]

    The Discussion section, “Mechanism for Effects of Maternal B12 and Folate on Fetal Growth” (page unavailable), discusses vitamins B12 and folate and the metabolites involved in their effects on fetal growth. It does not establish the full list attributed to it, particularly hormones and environmental chemicals. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Parental lifestyle factors including diet, obesity, smoking and endocrine-disrupting chemicals have all been shown to modulate disease risk later in life.

    “Parental lifestyle factors including diet, obesity, smoking and endocrine-disrupting chemicals, have all been shown to modulate disease risk later in life [104,108,109].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [104]

    The Results and Comments section, under “Later Life Health Outcomes in the Offspring” (page unavailable), links maternal undernutrition to increased later-life health risk and reports a role for maternal obesity in offspring outcomes. It does not substantiate the sentence’s claims about smoking or endocrine-disrupting chemicals, or extend its findings to parental factors generally; it also says causality for most long-term outcomes remains to be established. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Subsequent studies have confirmed that maternal exposure to either nutrient excess or deficit can have long-term consequences for the health of the progeny.

    “Subsequent studies have confirmed that maternal exposure to either nutrient excess or deficit, can have long-term consequences for the health of the progeny [104].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [104]

    In Results and Comments, under “Later Life Health Outcomes in the Offspring” (page not provided), the review reports associations of low maternal B12 and high maternal folate with offspring metabolic outcomes in childhood. It also says causality remains to be established for long-term outcomes other than neurocognitive function, so the claim that studies have confirmed consequences overstates the evidence. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Behere, R. V., Deshmukh, A. S., Otiv, S., Gupte, M. D., & Yajnik, C. S.
Affiliations
  • Manipal Academy of Higher Education (IN)
  • Indian Council of Medical Research (IN)
Corresponding author
Yajnik, Chittaranjan S.
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2021-04-12
Volume
12
Pages
619176-619176
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2021.619176
PMC
PMC8074968
OpenAlex
W3152829371
Cited by
213
References
3
Citations by year
2026: 25 · 2025: 36 · 2024: 28 · 2023: 65 · 2022: 26 · 2021: 7
FWCI
5.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • The Wellcome Trust DBT India Alliance (IA/CPHI/161502665)
  • Department of Biotechnology, Ministry of Science and Technology, India (BT/PR12629/MED/97/364/2016)
  • Biotechnology and Biological Sciences Research Council (BB/SO14020/1)
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 › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Keywords
pregnancy, maternal nutrition, neural tube defects, birth weight, gestational diabetes mellitus, preeclampsia, recurrent pregnancy loss, homocysteine, methylmalonic acid, vitamin B12 supplementation, offspring adiposity, insulin resistance, one-carbon metabolism, public health policy
MeSH terms
Female, Folic Acid, Humans, India, Pregnancy, Pregnancy Outcome, Vitamin B 12

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