Vitamin D prenatal programming of respiratory and allergic outcomes in childhood: What are observational studies telling us?

Introduction Prenatal vitamin D status may influence offspring's respiratory and allergic outcomes; however, evidence is inconclusive. A systematic review and meta-analysis was conducted on the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or cord blood at birth with the risk of offspring's respiratory and allergic conditions. Methods Two independent researchers conducted systematic searches for observational studies published using defined keywords on vitamin D and health outcomes, including respiratory tract infections (RTIs), wheeze, asthma, atopic eczema, allergic rhinitis, allergic sensitization and lung function. Random-effects meta-analyses were conducted. Heterogeneity among studies was tested by using the Cochran Q test and quantified by using the I2 statistic. Publication bias was examined by using Funnel plot and Egger's regression asymmetry test. Modification of effects by selected factors was assessed, including time at exposure assessment, offspring's age at health endpoint, outcome assessment, optimal 25(OH)D blood levels (30 ng/mL or greater) versus all the rest and geographical location. Results A total of 34 from 547 retrieved articles were included. Articles were based on 26 separate study populations, including 25 longitudinal birth cohorts and one case control study, from 16 different countries (latitude ranging from 55°N to 31°S). Increased prenatal exposure to 25(OH)D was inversely associated with risk of RTIs. Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratio was 0.64 (95% CI 0.47, 0.87). A positive borderline association was found for lung function at school age (FEV1 z-score coefficient 0.07, 95% CI −0.01, 0.15). No associations were found for wheeze, asthma, atopic eczema, allergic rhinitis and allergic sensitization. After subgroup analysis, stronger inverse associations were found between prenatal vitamin D and risk of RTIs within the first 6 months of life, and between cord blood vitamin D levels and RTIs. A stronger inverse association was found for asthma occurrence within the first 5 years of life, but no later in childhood. A stronger association between prenatal vitamin D levels and risk of atopic eczema during childhood was detected at higher latitude. Conclusions Current evidence from observational studies indicates that exposure to higher levels of vitamin D in utero may protect against early-life respiratory tract infections in offspring during childhood. However, epidemiological evidence from observational studies does not support an impact of prenatal vitamin D status in offspring's risk of asthma and allergic manifestations. Additional studies are warranted to confirm the potential benefits for lung function development.