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.

Keywords: bone mineral density; cholecalciferol; developmental programming; pregnancy; randomized controlled trial; vitamin D.

FIGURE 1

Participant flow diagram. DXA, dual-energy X-ray absorptiometry; LS, lumbar spine; WB, whole body; WBLH, whole-body-less-head. (a) Offspring born preterm in Southampton in the control group. DXA at birth—WB: n = 15 and LS: n = 12; 4 y—WBLH: N = 12 and LS: N = 12; 6–7 y—WBLH: N = 13 and LS: N = 13; (b) Offspring born preterm in Southampton in the intervention group. DXA at birth—WB: n = 12 and LS n = 9; 4 y—WBLH: N = 6 and LS: N = 6; and 6–7 y—WBLH: N = 9 and LS: N = 10.

FIGURE 2

The effect of maternal pregnancy cholecalciferol supplementation compared with placebo on offspring WBLH (n = 384) and LS (n = 384 for BA and 382 for other outcomes) BA, BMC, BMD, and BMAD at ages 6–7 y. The point estimate shows the beta coefficient (95% CI) for the cholecalciferol group compared with placebo (effectively the mean difference in the measure between the 2 groups). A CI that does not cross y = 0 demonstrates a statistically significant (P < 0.05) difference between the 2 randomly assigned groups. Beta coefficients for standardized variables have been generated using linear regression and including adjustment for age at DXA, sex, height, weight, use of vitamin D supplementation at ages 6–7 y, and the duration of consumption of human milk. ∗ P < 0.05. BA, bone area; BMAD, bone mineral apparent density; BMC, bone mineral content; BMD, bone mineral density; CI, confidence interval; DXA, dual-energy X-ray absorptiometry; LS, lumbar spine; WBLH, whole-body-less-head.

FIGURE 3

The effect of maternal pregnancy cholecalciferol supplementation compared with placebo on BA, BMC, BMD, and BMAD in children who had a DXA assessment at birth, 4, and 6–7 y for (A) whole body (birth)/whole-body-less head (4 and 6–7 y) (n = 263) and (B) lumbar spine (n = 236). Shown as beta (95% CI) for the cholecalciferol group compared with placebo. Beta coefficients for standardized variables have been generated using linear regression and including adjustment for age at DXA, sex, height (length at birth), weight at all ages, and additionally the use of vitamin D supplementation at time of DXA and the duration of consumption of human milk at ages 4 and 6–7 y. BA, bone area; BMAD, bone mineral apparent density; BMC, bone mineral content; BMD, bone mineral density; CI, confidence interval; DXA, dual-energy X-ray absorptiometry.