ABSTRACT
BACKGROUND: Findings from the MAVIDOS trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 years. Demonstrating persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health. OBJECTIVE: We investigated whether gestational vitamin D supplementation increases offspring BMD at 6-7 years in an exploratory post-hoc analysis of an existing trial. METHODS: In the MAVIDOS randomised controlled trial, pregnant females <14 weeks' gestation with a singleton pregnancy and serum 25-hydroxyvitamin D [25(OH)D] 25-100nmol/l at three UK hospitals (Southampton, Sheffield and Oxford) were randomised to either 1000 IU/day cholecalciferol or placebo from 14-17 weeks gestation until delivery. Offspring born at term to participants recruited in Southampton were invited to the childhood follow-up at 4 and 6-7 years. The children had a dual-energy X-ray absorptiometry (DXA, Hologic discovery) scan of whole-body-less-head (WBLH) and lumbar spine, from which bone area [BA], bone mineral content [BMC], BMD and bone mineral apparent density [BMAD]) were derived. Linear regression was used to compare the two groups adjusting for age, sex, height, weight, duration of consumption of human milk and vitamin D use at 6-7 years. RESULTS: 454 children were followed up at age 6-7 years, of whom 447 had a usable DXA scan. Gestational cholecalciferol supplementation resulted in higher WBLH BMC (0.15 SD, 95%CI 0.04, 0.26), BMD (0.18 SD, 95%CI 0.06,0.31), BMAD (0.18 SD, 95%CI 0.04,0.32) and lean mass (0.09 SD, 95%CI 0.00,0.17) compared to placebo. The effect of pregnancy cholecalciferol on bone outcomes was similar at ages 4 and 6-7 years. CONCLUSIONS AND RELEVANCE: Supplementation with cholecalciferol 1000 IU/day during pregnancy resulted in greater offspring BMD and lean mass in mid-childhood versus placebo in this exploratory post-hoc analysis. These findings suggest that pregnancy vitamin D supplementation may be an important population health strategy to improve bone health. TRIAL REGISTRATION: ISRCTN:82927713 https://doi.org/10.1186/ISRCTN82927713; EUDRACT:2007-001716-23 https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001716-23/results.