Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?

Background: Previous studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort.

Methods: In total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks' gestation) and/or 28-32 weeks' gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002-2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample.

Results: Data were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24).

Conclusions: While our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.