Prenatal vitamin D supplementation and child respiratory health: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Systematic review and meta-analyses of observational studies on maternal vitamin D status and risk of respiratory allergic conditions indicated that mothers who had supplementation during pregnancy could decrease the risk of recurrent wheeze or asthma in their offspring.

Objectives: We conducted this meta-analysis of Randomized Controlled Trials with the primary intention of detecting the effect of prenatal vitamin D supplementation on the offspring's asthma. Secondary outcomes under respiratory health include eczema, lower respiratory tract infections, Immunoglobulin E positive test, upper respiratory tract infections, and allergic rhinitis.

Methods: A comprehensive search of PubMed, ScienceDirect, Google Scholar, and Cochrane Library databases was performed to retrieve randomized controlled trials. Risk Ratio with 95% confidence intervals was computed from dichotomous data using a random-effects model, with I² >50% representing notable heterogeneity.

Results: Six clinical trials met the inclusion criteria, involving a total of 2898 subjects (1461 experimental group and 1437 control group). There was non-significant inverse relationship between vitamin D intake during pregnancy and the occurrence of asthma in offspring (pooled RR = 0.89, 95% CI = 0.69-1.15, I ² = 46% and Z-static = 0.90, P-value = 0.37). There is no significant difference in the risk of assessed childhood respiratory problems due to maternal supplementation of vitamin D during pregnancy.

Conclusion and implications: Currently, there is no fertile evidence to promote vitamin D supplementation in pregnancy for childhood respiratory health. Future clinical trials should emphasize early initiation of vitamin D supplementation, consider 6 weeks to 6 months postnatal critical window for vitamin D deficiency for offspring, lower risk dose of vitamin D, and identify different phenotypes of asthma and response to vitamin D supplementation.

Keywords: Allergy; Asthma; Childhood; IU, International unit; IgE, Immunoglobulin E; LRTI, Lower respiratory tract infection; Meta-analysis; PRISMA, preferred reporting items for systematic reviews and meta-analysis; Prenatal; RCT, randomized controlled trial; RR, relative risk; URTI, Upper respiratory tract infection; Vitamin D.

Fig. 1

Literature search results and study selection

Fig. 2

Forest plot showing: A) the pooled effect of prenatal vitamin D supplementation on offspring's risk of asthma, B) the pooled effect of prenatal vitamin D supplementation on offspring's risk of eczema, C) the pooled effect of prenatal vitamin D supplementation on offspring's LRTIs, D) the pooled effect of prenatal vitamin D supplementation on offspring's IgE; subgroup analysis performed on infant's postnatal vitamin D status, E) the pooled effect of prenatal vitamin D supplementation on offspring's URTIs, F) the pooled effect of prenatal vitamin D supplementation on the offspring's status of allergic rhinitis.