Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial

Abstract

Background: Maternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development.

Objectives: The aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh.

Methods: In a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n = 1300) were recruited at 17-24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs.

Results: Total-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [-10.90, 12.13], 0.0004 g/cm2 [-0.0089, 0.0097], and 0.02 kg [-0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P = 0.11).

Conclusions: Maternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively.

Keywords: areal bone mineral density; bone mineral content; grip strength; randomized controlled trial; vitamin D.

FIGURE 1

TBLH BMC (A) and aBMD (B) by intervention group (0/0, n = 114; 4200/0, n = 126; 16,800/0, n = 120; 28,000/0, n = 121; 28,000/28,000, n = 118). Intervention group reflects the vitamin D dose provided in IU/week, represented as a prenatal/postpartum supplementation regimen assigned to the child's mother from randomization (17–24 weeks’ gestation) to 6 mo postpartum. Means and 95% CIs for each intervention group are represented by the solid black circles and vertical lines. aBMD, areal bone mineral density; BMC, bone mineral content; BMD, bone mineral density; TBLH, total-body-less-head.