The role of prenatal vitamin D on the development of childhood asthma and wheeze: An umbrella review of systematic reviews and meta-analyses

Background & objective: It has been suggested that prenatal vitamin D plays a role in the development of childhood asthma and wheeze. Several systematic reviews have been conducted, but the results are inconsistent, and the methodological quality has not been studied. Therefore, the objective of this umbrella review was to assess the internal validity of the evidence base and the evidence for an association between prenatal vitamin D and asthma or wheezing in the offspring. Methods: We searched the electronic databases Embase, PubMed, and Cochrane Library for studies on prenatal vitamin D using search words such as vitamin D, 25-hydroxyvitamin D, calcidiol, fetal, and neonatal. The search was conducted in June 2020, and the databases were searched from their date of establishment. We included systematic reviews and/or meta-analyses of experimental and observational studies assessing the association between prenatal vitamin D or asthma and wheeze. We excluded narrative reviews, commentaries, and other umbrella reviews. The methodological quality of systematic reviews was assessed using AMSTAR 2 tool. PROSPERO reg. no. CRD42020151329. Results: We identified 22 eligible systematic reviews (17 on asthma and 20 on wheeze). Using the AMSTAR 2 quality assessment tool, the methodological quality was rated as critically low in 21 out of 22 systematic reviews, suggesting that previous reviews and meta-analyses did not provide accurate and comprehensive summaries of the included studies and that conclusions reached were potentially flawed. The majority of the included reviews reported that prenatal vitamin D reduces the risk of wheeze in the offspring. Conclusion: Prior to informing public guidelines, high-quality systematic reviews of the current evidence are greatly warranted.