Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomised controlled trial.

BACKGROUND: Evidence linking prenatal maternal vitamin D supplementation with the offspring's risk of atopic eczema is inconsistent, with most data coming from observational studies. OBJECTIVE: To examine the influence of maternal cholecalciferol supplementation during pregnancy on risk of atopic eczema in the offspring at ages 12, 24 and 48 months. METHODS: Within the UK Maternal Vitamin D Osteoporosis Study (MAVIDOS) double-blind, randomised, placebo-controlled trial, we examined the relation of maternal vitamin D supplementation during pregnancy with offspring atopic eczema at ages 12, 24 and 48 months. In MAVIDOS, pregnant women were allocated to either cholecalciferol 1000 IU/day or matched placebo, taken from around 14 weeks' gestation until delivery, with the primary outcome of neonatal whole-body bone mineral content. The prevalence of atopic eczema in the offspring was ascertained at ages 12 (n=635), 24 (n=610) and 48 (n=449) months, based on the UK Working Party Criteria for the Definition of Atopic Dermatitis. RESULTS: Mothers and offspring characteristics were similar between the intervention and placebo groups, apart from longer breastfeeding duration in the intervention group. Adjusting for breastfeeding duration, offspring of mothers who received 1000 IU cholecalciferol daily had a lower odds ratio (OR) of atopic eczema at age 12 months (OR (95%CI) 0.55 (0.32-0.97), p=0.04); this effect weakened and was not statistically significant at ages 24 and 48 months (OR 0.76 (0.47-1.23) and 0.75 (0.37-1.52), respectively. The statistical interaction of intervention and breastfeeding duration in relation to eczema at age 12 months was not significant (p=0.41), but stratification showed a reduced infantile eczema risk in intervention group infants breastfed for ≥1 month (OR 0.48 (0.24,0.94), p=0.03) and not in those breastfed for <1 month (OR 0.80 (0.29,2.17), p=0.66). CONCLUSION: Our data provide the first randomised controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on risk of infantile atopic eczema, with the effect potentially being via increased breast milk cholecalciferol levels. The findings support a developmental influence on atopic eczema, and point to a potentially modifiable perinatal influence on atopic eczema.