Pregnancy vitamin D supplementation and offspring bone mineral density in childhood follow-up of a randomized controlled trial

Abstract

Background: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 y. Demonstrating the persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health.

Objectives: we investigated whether gestational vitamin D supplementation increases offspring BMD at ages 6–7 y in an exploratory post-hoc analysis of an existing trial.

Methods: in the MAVIDOS randomized controlled trial, pregnant females <14 wk’ gestation with a singleton pregnancy and serum 25-hydroxyvitamin D 25–100nmol/l at 3 United Kingdom hospitals (Southampton, Sheffield, and Oxford) were randomly assigned to either 1000 IU/d cholecalciferol or placebo from 14 to 17-wk gestation until delivery. Offspring born at term to participants recruited in Southampton were invited to the childhood follow-up at ages 4 and 6–7 y. 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, bone mineral content (BMC), BMD, and bone mineral apparent density (BMAD) were derived. Linear regression was used to compare the 2 groups adjusting for age, sex, height, weight, duration of consumption of human milk, and vitamin D use at 6–7 y.

Results: a total of 454 children were followed up at ages 6–7 y, of whom 447 had a usable DXA scan. Gestational cholecalciferol supplementation resulted in higher WBLH BMC [0.15 SD, 95% confidence interval (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 with placebo. The effect of pregnancy cholecalciferol on bone outcomes was similar at ages 4 and 6–7 y.

Conclusions: supplementation with cholecalciferol 1000 IU/d during pregnancy resulted in greater offspring BMD and lean mass in mid-childhood compared with 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 number: this trial was registered at the ISRCTN (https://doi.org/10.1186/ISRCTN82927713) as 82927713 and EUDRACT (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001716-23/results) as 2007-001716-23.

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Identifiers

ORCID for Stefania D'Angelo: orcid.org/0000-0002-7267-1837

ORCID for Elizabeth M. Curtis: orcid.org/0000-0002-5147-0550

ORCID for Kate A. Ward: orcid.org/0000-0001-7034-6750

ORCID for Sarah R. Crozier: orcid.org/0000-0002-9524-1127

ORCID for Keith M. Godfrey: orcid.org/0000-0002-4643-0618

ORCID for Cyrus Cooper: orcid.org/0000-0003-3510-0709

ORCID for Nicholas C. Harvey: orcid.org/0000-0002-8194-2512

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