Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh

Authors: SIDDIQUA, TOWFIDA - International Centre For Diarrhoeal Disease Research; AHMAD, SHAIKH - International Centre For Diarrhoeal Disease Research; AHSAN, KHALID - International Centre For Diarrhoeal Disease Research; RASHID, M - International Centre For Diarrhoeal Disease Research; ROY, ANJAN - International Centre For Diarrhoeal Disease Research; RAHMAN, SYED - International Centre For Diarrhoeal Disease Research; Shahab-Ferdows, Setti; HAMPEL, DANIELA - University Of California; AHMED, TAHMEED - International Centre For Diarrhoeal Disease Research; Allen, Lindsay - A; RAQIB, RUBHANA - International Centre For Diarrhoeal Disease Research

Submitted to: European Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/26/2015
Publication Date: 2/4/2015
Publication URL: download.springer.com/static/pdf/901/art%253A10.1007%252Fs00394-015-0845-x.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00394-015-0845-x&token2=exp=1439401404~acl=%2Fstatic%2Fpdf%2F901%2Fart%25253A10.1007%25252Fs00394-015-0845-x.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00394-015-0845-x*~hmac=563e65e414a300d3ac47d6ee51c2b66460ab19193bb33331fbd349353f0701e2
Citation: Siddiqua, T.J., Ahmad, S.M., Ahsan, K.B., Rashid, M., Roy, A., Rahman, S.M., Shahab-Ferdows, S., Hampel, D., Ahmed, T., Allen, L.H., Raqib, R. 2015. Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh. European Journal of Nutrition. 54:1-13. https://doi.org/10.1007/s00394-015-0845-x.
DOI: https://doi.org/10.1007/s00394-015-0845-x

Interpretive Summary: The effects of vitamin B12 supplementation on vitamin B12 status and immune function were measured in Bangladeshi women and their infants. In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, age 18–35 y, hemoglobin <110 g/L, 11–14 wk pregnant) were randomized to receive 250 µg/d B12 or a placebo throughout pregnancy and 3-mo postpartum along with 60 mg iron + 400 µg folic acid. Women were immunized with pandemic influenza A (H1N1) vaccine at 26- to 28-wk gestation. Blood from mothers (baseline, 72-h post-delivery, 3-mo postpartum), newborns and infants (3-mo) was analyzed for hemoglobin, B12 status (serum B12 and methylmalonic acid (MMA)), total homocysteine (tHcy), iron status (serum ferritin and serum transferrin receptors), inflammation (C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP)). Vitamin B12 was also assessed in breast milk. H1N1-specific antibodies were determined in plasma and colostrum/breast milk. At baseline, 26 % women were B12 deficient (<150 pmol/L), 40 % had marginal status (150–220 pmol/L), 43 % had elevated MMA (>271 nmol/L), and 31 % had elevated tHcy (>10 µmol/L). Supplementation improved B12 status shown by increased B12 in plasma, colostrum and breast milk (p < 0.05) and lower MMA in neonates, mothers and infants at 3 mo (p < 0.05). B12 supplementation also significantly increased H1N1-specific IgA responses in plasma and colostrum in mothers and reduced the proportion of infants with elevated AGP and CRP compared with placebo. We conclude that supplementation with 250 µg B12/d during pregnancy and lactation substantially improved maternal, infant and breast milk B12 status. Maternal supplementation improved H1N1 vaccine-specific responses in mothers only and may alleviate inflammatory responses in infants.

Technical Abstract: Purpose Poor vitamin B12 (B12) status is associated with adverse outcomes in pregnancy and infancy. Little is known about effects of B12 supplementation on immune function. The present study aimed to evaluate effects of pre- and postnatal B12 supplementation on biomarkers of B12 status and vaccine-specific responses in mothers and infants. Method In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, age 18–35 years, hemoglobin <110 g/L, 11–14 weeks pregnant) were randomized to receive 250 µg/day B12 or a placebo throughout pregnancy and 3-months postpartum along with 60 mg iron + 400 µg folic acid. Women were immunized with pandemic influenza A (H1N1) vaccine at 26- to 28-weeks gestation. Blood from mothers (baseline, 72-h post-delivery, 3-mo postpartum), newborns and infants (3-mo) was analyzed for hemoglobin, B12, methylmalonic acid (MMA), total homocysteine (tHcy), ferritin and serum transferrin receptors, C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP). Vitamin B12 was also assessed in breast milk. H1N1-specific antibodies were determined in plasma and colostrum/breast milk. Results At baseline, 26 % women were B12 deficient (<150 pmol/L), 40 % had marginal status (150–220 pmol/L), 43 % had elevated MMA (>271 nmol/L), and 31 % had elevated tHcy (>10 µmol/L). Supplementation increased B12 in plasma, colostrum and breast milk (p < 0.05) and lowered MMA in neonates, mothers and infants at 3 mo (p < 0.05). B12 supplementation significantly increased H1N1-specific IgA responses in plasma and colostrum in mothers and reduced the proportion of infants with elevated AGP and CRP compared with placebo. Conclusion Supplementation with 250 µg/day B12 during pregnancy and lactation substantially improved maternal, infant and breast milk B12 status. Maternal supplementation improved H1N1 vaccine-specific responses in mothers only and may alleviate inflammatory responses in infants.