Vitamin B12 Supplementation during Pregnancy and Postpartum of Bangladeshi Women: Effects on Oxidative Stress, Pro‐Inflammatory Cytokines and Global DNA Methylation
Authors: Siddiqua Towfida Jahan , Akhtar Evana , Hossain Mohammad Bakhtiar , Allen Lindsay H , Ahmed Tahmeed , Raqib Rubhana 
Published: November 2023

BackgroundVitamin B12 (B12) deficiency is highly prevalent in women of reproductive age, particularly amongst populations with limited intake of animal source foods. Genetic and cellular studies of oxidative stress indicate that B12 might function as a possible scavenger of reactive oxygen species. In addition, adequate maternal folate and B12 status during pregnancy is crucial for maintaining one‐carbon metabolism cycle which provides methyl groups for CpG (cytosine‐guanine) methylation and epigenetic regulation. There are no studies evaluating the role of exclusive B12 supplementation on DNA methylation and inflammatory oxidative stress responses among mother‐infant pairs.ObjectivesTo evaluate effects of maternal B12 supplementation during pregnancy and postpartum on (a) maternal and infant 8‐hydroxy‐2′‐deoxyguanosine (8‐OH‐dG), a marker of oxidative stress; (b) concentrations of pro‐inflammatory cytokines (IL‐1, IL‐6, IL‐8, IL‐10, IFN‐γ, and TNF‐α); and (c) global DNA methylation among mother‐infant pairs.MethodsThe parent study was a blinded, placebo‐controlled trial; Bangladeshi women (n=68, 18–35 years, hemoglobin <110 g/L, gestational weeks 11–14) were randomized to receive either 250 μg/day B12 or placebo throughout pregnancy up to 3‐mo postpartum. Stored plasma samples from blood collected from mothers at baseline and 3‐mo postpartum, and infants at 3‐mo were used to measure 8‐OH‐dG and pro‐inflammatory cytokines using commercially available ELISA kit. DNA extracted from peripheral blood mononuclear cell was assessed to determine global DNA methylation status using commercially available ELISA kit.ResultsAt baseline demographic variables did not differ significantly between the groups. Analysis of covariance showed that maternal vitamin B12 supplementation significantly reduced 8‐OH‐dG concentrations (ng/mL) among postpartum mothers (3.8 ± 1.5 vs. 5.8 ±3.0) and infants (3.6 ± 1.6 vs. 5.4 ± 2.6) at 3‐month compared to the placebo group. Concentration of 8‐OH‐dG decreased significantly from baseline to 3‐month postpartum in the supplemented group compared to the placebo group. The cytokine profile did not differ between the study groups among postpartum mothers. However, infants from supplemented mothers at 3 months showed significantly higher IFN‐γ response compared to placebo group (p<0.01). Global DNA methylation level (% 5‐hmC) was significantly higher in infants born to B12 supplemented mothers compared to the placebo in a sub‐sample assessed (n = 28). Interestingly, a trend for association (r=0.36, p=0.06) was observed between infant DNA methylation and maternal vitamin B12 status at 3 month postpartum.ConclusionMaternal B12 supplementation during pregnancy and postpartum may influence immune and epigenetic responses positively in the mother and infant.Support or Funding InformationSwedish International Development Cooperation Agency (Sida)