Infant Respiratory Tract Infections or Wheeze and Maternal Vitamin D in Pregnancy: A Systematic Review

Backgrounds: Respiratory tract infections (RTIs) are a common cause of morbidity and mortality in young children and can be associated with wheeze. Vitamin D can have a protective role against RTI. Materials and Methods: A systematic search of PubMed, Embase and the Cochrane library was performed. Titles and abstracts were evaluated, and selected articles were reviewed by 2 authors. We included randomized controlled trials (RCTs) investigating the effect of vitamin D supplementation during pregnancy on RTIs or wheeze in children of 5 years of age or younger. Observational studies on the association between serum 25-hydroxyvitamin D during pregnancy, or at birth, and RTIs and/or wheeze were included. The protocol was registered on PROSPERO (Registration number: CRD42015019183). Results: Of 4 RCTs, 1 showed a protective effect of a high daily dose (2000 IU) of vitamin D during pregnancy on offspring RTI doctor visits (P = 0.004; the RCT also included 800 IU/d supplement to the infants until 6 months). Meta-analysis of 3 RCTs showed a reduced relative risk for offspring wheeze when mothers were supplemented with vitamin D during pregnancy [relative risk: 0.81 (95% confidence interval: 0.68-0.97), P = 0.025]. In 3 of 4 strong-quality, and 5 of 10 moderate-quality observational studies, an inverse association between pregnancy and cord 25-hydroxyvitamin D and subsequent wheeze and/or RTI was seen. Conclusion: Growing evidence supports a preventive role of vitamin D during pregnancy on offspring wheeze and/or RTI. Recommendations in future intervention studies may need to exceed current recommendations of vitamin D supplementation during pregnancy to show benefit against childhood wheeze or infections.