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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.

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

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SUBMITTER: Behere RV

PROVIDER: S-EPMC8074968 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundVitamin B12 deficiency during pregnancy has been associated with adverse maternal and infant health outcomes. Few prospective studies have investigated vitamin B12 status early in pregnancy, and its links to infant vitamin B12 status, particularly in India where the burden of vitamin B12 deficiency is estimated to be the highest globally. The objective of this study was to examine the associations of maternal vitamin B12 biomarkers with neonatal vitamin B12 status.MethodsPregnant women (~12 weeks' gestation) were enrolled in a perinatal cohort study in Bangalore, India. Total vitamin B12, methylmalonic acid (MMA), and homocysteine concentrations were evaluated in maternal samples at enrollment and in neonates at birth using cord blood. Linear and binomial regression models were used to evaluate the associations of maternal vitamin B12 biomarkers with neonatal vitamin B12 status and perinatal outcomes.ResultsA total of 63.2% of women had vitamin B12 deficiency (<148 pmol/L), 87.2% had vitamin B12 insufficiency (<221 pmol/L), and 47.3% had impaired vitamin B12 status (vitamin B12<148 pmol/L and MMA>0.26μmol/L) at enrollment; 40.8% of neonates had vitamin B12 deficiency, 65.6% were insufficiency, and 38.1% had impaired vitamin B12 status at birth. Higher maternal vitamin B12 concentrations at enrollment were associated with increased neonatal vitamin B12 concentrations (β(SE): 0.40 (0.05); p<0.0001) and lower risk of neonatal vitamin B12 deficiency (Risk Ratio [RR]: 0.53; 95% CI: [0.43, 0.65]; p<0.0001). Maternal vitamin B12 deficiency (RR: 1.97 [1.43, 2.71]; p<0.001), insufficiency (RR: 2.18 [1.23, 3.85]; p = 0.007), and impaired vitamin B12 status (RR: 1.49 [1.13, 1.97]; p = 0.005) predicted a two-fold increase in the risk of neonatal vitamin B12 deficiency at birth.ConclusionsThe prevalence of vitamin B12 deficiency was high early in pregnancy and predicted neonatal vitamin B12 status. Future research is needed to determine the role of vitamin B12 in the development of pregnancy and infant outcomes, and to inform screening and interventions to improve maternal and child health.

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