The impact of vitamin D in pregnancy on extraskeletal health in children: a systematic review.

The impact of maternal vitamin D status in pregnancy on the extraskeletal health of the offspring has become a "hot topic" with a potential for cost-beneficial prevention. The objective of this study was to systematically review the level I and II evidence. PubMed, Embase and Cochrane databases were searched using the MeSH terms "vitamin D" AND "pregnancy" until 1 January 2012. The search was limited to randomized controlled trials (evidence level I) and observational studies (evidence level II) in humans and in the English language. Papers reporting on vitamin D supplementation in combination with other supplements, or not reporting on 25OHD or outcomes of the offspring were excluded. Six randomized controlled trials and 24 observational studies were finally included. In randomized controlled studies, vitamin D supplementation resulted in increased birthweight in one study, but showed no effect in five other studies. In cohort and case-control studies, higher vitamin D intake, or higher 25OHD, was associated with increased birthweight in large studies only, and modified by vitamin D receptor polymorphisms and by race (U-shaped in Caucasians in one unconfirmed study). The risks of HIV mother-to-child transmission, rhinitis symptoms and eczema were lower. Data were conflicting on the effect on respiratory infections and wheezing, whereas U-shaped associations to inhalant allergen-specific IgE at five years and to schizophrenia were reported in unconfirmed studies. The risk of type 1 diabetes at 15 years was lower or unchanged. It is concluded that observational studies suggest an effect of vitamin D on several outcomes. U-Shaped associations warrant caution.