Relationship between maternal folic acid supplementation during pregnancy and risk of childhood asthma: Systematic review and dose-response meta-analysis

Systematic review and dose-response meta-analysis of 18 observational studies (13 cohort, 5 case-control) in pregnant women and their children from Europe, North America, Asia, and Australia. The pooled dataset included 252,770 participants and 50,248 children with asthma.

Maternal folic acid supplementation during pregnancy was evaluated, with contributing cohorts commonly reporting 400 µg/day taken daily; exposure was assessed by trimester and across the whole pregnancy. Route was not stated.

Maternal folic acid supplementation during pregnancy was associated with a modestly higher risk of childhood asthma. Across included studies, the pooled OR was 1.07 (95% CI 1.04-1.11); the association was also present for first trimester exposure (OR 1.09, 95% CI 1.05-1.12), third trimester exposure (OR 1.15, 95% CI 1.04-1.26), and whole-pregnancy exposure (OR 1.13, 95% CI 1.10-1.16). Dose-response analysis suggested no association below 581 µg/day, but increased risk at 581 µg/day or more. The association persisted in high- and middle-income economies.

The evidence was observational, so residual confounding and other biases cannot be excluded. Dose estimation was challenging, dose-response data were limited, and offspring ages varied widely across studies, which may reduce comparability and generalizability.