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.
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).
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.
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.)
Infants who are small for gestational age or have impaired postnatal linear growth continue to be of major concern with regard to public health in low- and middle-income countries.1,2 However, environmental and dietary regulation of fetal and infant growth remain inadequately understood. Observational studies have shown numerous early-life risk factors for later anthropometric outcomes,3,4 but there is limited evidence of benefit of prenatal micronutrient interventions on childhood linear growth.5
Vitamin D may influence fetal and postnatal growth through effects on calcium absorption,6parathyroid hormone expression,7 phosphate metabolism,8 growth-plate function,9,10 and regulation of the insulin-like growth factor axis.11 Meta-analyses of observational studies12 and clinical trials13 have suggested that vitamin D may have a beneficial effect on fetal growth, but most previous trials have had methodologic limitations.13 In a previous small trial in Bangladesh, we found that early postnatal linear growth was higher in infants born to women who had received vitamin D supplementation as compared with those who had not received supplementation.14
In Bangladesh, approximately 30% of newborns are small for gestational age,1 and the growth of 36% of children younger than 5 years of age is stunted (height-for-age z score, <−2).15 Vitamin D deficiency is common in Bangladeshi women of reproductive age.16 In the Maternal Vitamin D for Infant Growth (MDIG) trial conducted in Dhaka, Bangladesh, we evaluated the dose-dependent effects of prenatal vitamin D supplementation, with and without postpartum supplementation, on infant growth and other maternal, newborn, and infant outcomes.
Reference: N Engl J Med 2018; 379:535-546