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

Eur J Nutr. 2016 Feb;55(1):281-93. doi: 10.1007/s00394-015-0845-x. Epub 2015 Feb 4.


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-month postpartum along with 60 mg iron + 400 μg folate. Women were immunized with pandemic influenza A (H1N1) vaccine at 26- to 28-week gestation. Blood from mothers (baseline, 72-h post-delivery, 3-month postpartum), newborns and infants (3-month) was analyzed for hemoglobin, B12, methylmalonic acid (MMA), total homocysteine (tHcy), ferritin and serum transferrin receptor, 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, colostrums and breast milk (p < 0.05) and lowered MMA in neonates, mothers and infants at 3 months (p < 0.05). B12 supplementation significantly increased H1N1-specific IgA responses in plasma and colostrums in mothers and reduced 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.

Keywords: Breast milk B12; Methylmalonic acid; Vaccine response; Vitamin B12 supplementation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bangladesh
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Female
  • Ferritins / blood
  • Folic Acid / administration & dosage
  • Folic Acid / blood
  • Hemoglobins / metabolism
  • Homocysteine / blood
  • Humans
  • Immunoglobulin A / blood
  • Infant
  • Influenza A Virus, H1N1 Subtype
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control
  • Lactation
  • Maternal Nutritional Physiological Phenomena
  • Methylmalonic Acid / blood
  • Milk, Human
  • Orosomucoid / metabolism
  • Postpartum Period / drug effects*
  • Postpartum Period / metabolism
  • Pregnancy
  • Receptors, Transferrin / blood
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / blood
  • Young Adult


  • Biomarkers
  • Hemoglobins
  • Immunoglobulin A
  • Influenza Vaccines
  • Orosomucoid
  • Receptors, Transferrin
  • Homocysteine
  • Methylmalonic Acid
  • C-Reactive Protein
  • Ferritins
  • Folic Acid
  • Vitamin B 12