Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother-child pairs

Authors: SIDDIQUA, TOWFIDA - International Centre For Diarrhoeal Disease Research; AKHTAR, EVANA - International Centre For Diarrhoeal Disease Research; HAQ, MD AHSANUL - International Centre For Diarrhoeal Disease Research; Shahab-Ferdows, Setareh; HAMPEL, DANIELA - University Of California, Davis; ISLAM, SHARMIN - International Centre For Diarrhoeal Disease Research; AHMED, TAHMEED - International Centre For Diarrhoeal Disease Research; Allen, Lindsay; RAQIB, RUBHANA - International Centre For Diarrhoeal Disease Research

Submitted to: BMC Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2023
Publication Date: 1/3/2024
Citation: Siddiqua, T.J., Akhtar, E., Haq, M., Shahab-Ferdows, S., Hampel, D., Islam, S., Ahmed, T., Allen, L.H., Raqib, R. 2024. Effects of vitamin B12 supplementation on oxidative stress markers and pro-inflammatory cytokines during pregnancy and postpartum among Bangladeshi mother-child pairs. BMC Nutrition. 10. Article 3.
DOI: https://doi.org/10.1186/s40795-023-00785-y

Interpretive Summary: Vitamin B12 is important for the immune system but little is known about the effects of maternal B12 supplementation on stress and inflammation during pregnancy and lactation, and whether these possible effects are transferred from a lactating women to the breastfeeding infant. We determined the impact of maternal B12 supplementation during pregnancy and lactation on maternal and infant stress biomarkers (8-hydroxy-2-deoxyguanosine [8-OH-dG]) and pro-inflammatory cytokine levels, and examined the relationships between maternal plasma, breastmilk and infant B12 status as well as immune function markers. Bangladeshi women (n=68, 18–35 years, hemoglobin <110 g/L, gestational weeks 11–14) received either 250 µg/day B12 or placebo throughout pregnancy up to 3-months after birth. Samples were collected from mothers at baseline and 3-months postpartum and infants at 3-months to measure B12 status indicators, 8-OH-dG, and proinflammatory cytokines. Mothers consuming the B12 supplement also showed decreased concentrations of 8-OH-dG concentrations at 3-months, which was also true for their infants. Further, B12 supplementation increased plasma TNF-a and IL-6 levels (p<0.05) among mothers and IL-10 and IFN-' levels among infants. Maternal B12 at 3 months postpartum and breastmilk B12 were both related to infant plasma B12. Milk B12 also correlated with infant total homocysteine. Thus,, B12 supplementation during pregnancy and postpartum may influence 8-OH-dG and several cytokine concentrations and therefore aid in the protection against immune response-induced oxidative stress. Both, milk and maternal plasma B12 at 3 months were associated with infant plasma B12.

Technical Abstract: Background: Vitamin B12 (B12) is essential for the efficient functioning of the immune system. However, there is limited research to determine whether B12 supplementation during pregnancy and lactation is protective against oxidative stress and pro-inflammatory cytokines, and whether this effect is transferred to the breastfed infant, via milk. In addition the associations among maternal plasma/breastmilk and infant B12 levels and such immune function markers are poorly characterized. Objectives: To evaluate the effects of maternal B12 supplementation during pregnancy and postpartum on maternal and infant 8-hydroxy-2'-deoxyguanosine (8-OH-dG; oxidative stress marker) and proinflammatory cytokine levels, and examine the associations between maternal plasma, breastmilk and infant B12 status as well as immune function markers. Method: In a blinded, placebo-controlled trial, Bangladeshi women (n=68, 18–35 years, hemoglobin <110 g/L, gestational weeks 11–14) received either 250 µg/day B12 or placebo throughout pregnancy up to 3-months postpartum. Samples were collected from mothers at baseline and 3-months postpartum and infants at 3-months to measure B12 status indicators, 8-OH-dG, and proinflammatory cytokines. Results: Maternal B12 supplementation significantly reduced 8-OH-dG concentrations among postpartum mothers and infants at 3-months compared to placebo group. Nine months of maternal B12 supplementation increased plasma TNF-a and IL-6 levels (p<0.05) among mothers and IL-10 and IFN-' levels among infants. Maternal B12 at 3 months postpartum was associated with infant plasma B12. Maternal breastmilk B12 levels were associated with infant plasma B12 (beta (ß)=277, 95% confidence interval (CI)=(132, 423), p'0.001) and total homocysteine (tHcy) (ß =-7.63, 95% CI=(-12.40,-2.86), p=0.002). Conclusion: B12 supplementation during pregnancy and postpartum modulates 8-OH-dG and several cytokines to protect against immune response-induced oxidative stress. Both milk and maternal plasma B12 at 3 months were associated with infant plasma B12 (clinicaltrials.gov: NCT01795131).