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

  • 2026-06
  • Bone 207
    • Charlotte Maden
    • Stefania D'Angelo
    • Leo D Westbury
    • Elizabeth M Curtis
    • Sarah R Crozier
    • Keith M Godfrey
    • Kate A Ward
    • Cyrus Cooper
    • Nicholas C Harvey
    • Rebecca J Moon

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 222
Population
222 children (placebo n = 110, cholecalciferol n = 112) born to mothers who participated in the MAVIDOS trial
Methods
Post hoc analysis of a randomised placebo-controlled trial of 1000 IU/day cholecalciferol from 14 to 17 weeks' gestation until delivery; offspring tibial bone microarchitecture assessed at age 6-7 years using HR-pQCT
Blinding
Double-blind
Duration
from 14 to 17 weeks' gestation until delivery
  • Large Human Trial

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 to 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), rs2282679 (GC)] 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 = 1.0).

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.

Research Insights

  • Vitamin D→Increased Bone Mineral Density

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Cortical Thickness

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Cortical Volumetric Bone Mineral Density

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Cross-sectional Area

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Tibial Cross-sectional Area

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Trabecular Number

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Trabecular Thickness

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Increased Trabecular Volumetric Bone Mineral Density

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
  • Vitamin D→Reduced Cortical Porosity

    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

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU/day
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