Vitamin D supplementation during pregnancy and offspring bone microarchitecture: a post hoc analysis of the MAVIDOS randomised controlled trial

Abstract

Background: randomised trials have shown that pregnancy vitamin D supplementation results in greater offspring bone mineral density (BMD) in childhood. The effect of this intervention on bone microarchitecture, a further determinant of bone strength, and possible interactions with genetic variation in vitamin D metabolism, have not previously been investigated. We investigated these in a post hoc analysis of a randomised controlled trial.

Methods: MAVIDOS was a randomised placebo-controlled trial of 1000 IU/day cholecalciferol from 14-17 weeks’ gestation until delivery. Offspring tibial bone microarchitecture was assessed at age 6-7 years using high resolution peripheral quantitative computed tomography (HR-pQCT; Stratec Xtreme CTII). Maternal and child genotype at four single nucleotide polymorphisms (SNPs) [rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1)] was determined using serum samples.
Differences in bone microarchitecture by randomisation were assessed using linear regression, and additionally across clusters of bone microarchitecture phenotypes generated using cluster analysis approaches.

Results: 222 children (placebo n=110, cholecalciferol n=112) were included. No significant differences in cross-sectional area, cortical thickness or porosity, trabecular thickness or number, or volumetric BMD (total, cortical or trabecular) were found using linear regression, and there was no interaction with either maternal or offspring SNP genetic variants.
Three phenotypic bone clusters were generated. Differences in child anthropometry were evident across clusters, but the proportion of mothers randomised to cholecalciferol was similar across the clusters (p=1.00).

Conclusion: in this subset of children born to mothers participating in a trial of vitamin D supplementation in pregnancy, no effect of the supplementation on tibial microarchitecture was observed.

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Identifiers

ORCID for Rebecca Moon: orcid.org/0000-0003-2334-2284

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

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

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

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

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

ORCID for Elaine Dennison: orcid.org/0000-0002-3048-4961

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