Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status

Abstract

Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women <14 wk of gestation in Bangalore, India, were randomly assigned to receive daily oral supplementation with vitamin B-12 (50 μg) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P < 0.001) and third (median: 184 vs. 105 pmol/L, P < 0.001) trimesters. At 6 wk postpartum, median breast milk vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P < 0.0005). Among vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862.

Conflict of interest statement

Author disclosures: C. Duggan, K. Srinivasan, T. Thomas, T. Samuel, R. Rajendran, S. Muthayya, J. L. Finkelstein, A. Lukose, W. Fawzi, L. H. Allen, R. J. Bosch, and A. V. Kurpad, no conflicts of interest.

Figures

FIGURE 1

Summary of screening, recruitment, and randomization.

FIGURE 2

Effect of dietary supplementation with vitamin B-12 in pregnant Indian women compared with placebo on maternal plasma concentrations of vitamin B-12 (A), MMA (B), and homocysteine (C). Values are median and interquartile range, n = 182 to 102. *B12 different from P, P < 0.001 by Mann-Whitney U test. B12, Vitamin B-12 group; Hcy, homocysteine; MMA, methylmalonic acid; P, placebo group.

FIGURE 3

Effect of dietary supplementation with vitamin B-12 in pregnant Indian women compared with placebo on infant plasma concentrations of vitamin B-12 (A), MMA (B), and Hcy (C) at 6 wk after birth. Values are medians and IQRs, n = 43 in the vitamin B-12 group and 34 in the placebo group. *B-12 different from P, P < 0.001 by Mann-Whitney U test. B12, Vitamin B-12 group; Hcy, homocysteine; MMA, methylmalonic acid; P, placebo group.