Early life vitamin D status and asthma and wheeze: a systematic review and meta-analysis

Background: Vitamin D deficiency has been linked to an increased risk of asthma. This study aimed to quantify the effect of early life vitamin D status on asthma and wheeze later in life.

Methods: PubMed, Embase, CINAHL, and CNKI databases, the Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to July 2017. We included randomized controlled trials (RCTs) and cohort studies with vitamin D level in blood (maternal or cord or infant) or intake (maternal intake during pregnancy or infant intake) and asthma and/or wheeze. Two reviewers independently extracted data. Fixed- and random-effects models were used to summarize the risk estimates of comparisons between highest vs. lowest vitamin D categories.

Results: Of the 1485 studies identified, three RCTs and 33 cohort studies were included. We did not include the RCTs (1619 participants) in the meta-analysis as the comparators and outcome definitions were heterogenous. Three RCTs reported a non-statistically significant effect of vitamin D supplementation during pregnancy on offspring wheeze/asthma at 3 years of age. Pooled estimates of cohort studies suggest no association between antenatal blood vitamin D levels or vitamin D intake and offspring asthma assessed either > 5 years or ≤ 5 years. The estimate for blood vitamin D remained unchanged when two studies assessing asthma in adulthood were excluded, but a significant inverse association emerged between vitamin D intake and childhood asthma. We found no association between antenatal vitamin D level and wheeze. On the other hand, vitamin D intake during pregnancy may have a protective effect against wheeze.

Conclusions: The pooled estimates from cohort studies show no association between antenatal blood vitamin D level and asthma/wheeze in later life. Whereas, the pooled estimates from cohort studies suggest that antenatal vitamin D intake may have an effect on childhood asthma > 5 years or childhood wheeze. The inconsistent results from studies assessing vitamin D either in blood or intake may be explained by previously reported non-linear association between blood vitamin D₃ and childhood asthma. Further trials with enough power and longer follow-up time should be conducted to confirm the results.