Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth

Abstract

Background: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common.

Methods: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group).

Results: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose.

Conclusions: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

Figure 1: Trial flow diagram

Figure 2: Study design and CONSORT diagram

Maternal, venous cord, and infant 25-hydroxyvitamin D (25(OH)D) [nmol/L], and maternal iPTH [pmol/L] concentrations, by vitamin D supplementation group. (A) Mean maternal 25(OH)D at baseline (n=1285), delivery (n=656; delivery specimens were collected within -19 days to 11 days of delivery [median: 0 days]), 3 months postpartum (n=581), and 6 months postpartum (n=590). Bars denote 95% confidence intervals (CI); (B) Mean 25(OH)D concentrations in venous cord (n=507), infants at 3 months (n=345), infants at 6 months (n=254), and infants at 12 months (n=182). Bars denote 95% CI; (C) Geometric means of maternal iPTH concentrations [pmol/L] at baseline (n=608), delivery (n=551; delivery specimens were collected within -19 days to 11 days of delivery [median: 0 days]), and 6 months postpartum (n=588). Bars denote 95% CI.