Effect of Maternal Prenatal and Postpartum Vitamin D Supplementation on Offspring Bone Mass in Early Childhood: Follow-Up of a Randomized Controlled Trial

Abstract

ObjectivesMaternal vitamin D status has gained substantial attention as a modifiable contributor to offspring musculoskeletal health, yet there is a paucity of trial-derived data to corroborate effects of prenatal or postpartum vitamin D supplementation on offspring bone mass accrual. Among maternal-infant pairs in Bangladesh, we aimed to examine the hypothesized causal association of early life vitamin D exposure with musculoskeletal health in childhood. MethodsIn a double-blind dose-ranging trial of maternal vitamin D3 supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) were recruited at 17–24 weeks’ gestation and randomly assigned to receive a prenatal; postpartum regimen of 0;0,4200;0,16,800;0,28,000;0 or 28,000;28,000 IU vitamin D3/week until 26 weeks postpartum. In a follow-up study of offspring at 4 years of age (n = 642), bone mineral content (BMC) and bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry. Between-group differences were assessed by independent t-tests (28,000 IU/week prenatally vs placebo) and linear regression (each vitamin D treatment group vs placebo) with bootstrapping (1000 replications). ResultsWhole-body (WB), total-body-less-head (TBLH) and head-only BMC were similar in the combined high-dose prenatal and placebo groups (mean difference [95% CI] = 6.81g [–8.70, 22.32], 0.61g [–10.90, 12.13] and 1.71g [–3.54, 6.96], respectively). None of the mean values for WB or TBLH BMC or BMD in each vitamin D group were different from placebo (P > 0.05 for all comparisons). Although head BMD was slightly greater in offspring of women assigned to the 28,000;28,000 IU regimen compared to placebo (mean difference [95% CI] = 0.024g/cm2 [0.0009, 0.047], P = 0.042), the effect was attenuated and no longer significant upon adjustment for child height, weight, and sex (P = 0.11). ConclusionsIn a population with high prevalence of vitamin D deficiency, our findings do not support the use of maternal prenatal vitamin D supplementation, with or without postpartum supplementation, for improvement of child BMC or BMD at 4 years of age. Funding SourcesCanadian Institutes for Health Research and the Bill and Melinda Gates Foundation.