Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis.

Systematic review and meta-analysis of observational cohort and nested case-control studies from multiple countries; no randomized trials were identified. The included populations were pregnant women and their children, with folate exposure assessed around conception or during pregnancy and childhood outcomes including asthma, wheeze, atopy, eczema, and related allergic conditions.

Exposure was periconceptional or first-trimester folic acid-containing supplement use, generally around 400-500 mg/d where reported, versus no folic acid use. Some cohorts also examined pregnancy exposure at higher reported doses, such as 700 mg/d or a mean 497 ± 301 mg, and a few studies assessed folate biomarkers rather than supplement intake.

Periconceptional folic acid supplementation was not associated with an increased risk of childhood asthma. The pooled estimate for asthma was RR 1.01 (95% CI 0.78, 1.30), and when asthma and wheeze were combined the RR was 1.05 (95% CI 1.02, 1.09). Excluding one influential study changed the combined estimate to RR 1.04 (95% CI 0.92, 1.17). The authors concluded that more research is needed because of heterogeneity in exposures and outcomes and the limited number of studies, especially for non-asthma allergic outcomes.

Evidence came entirely from observational studies, so residual confounding and exposure misclassification remain possible. Exposure definitions, timing windows, and outcome definitions varied across studies, limiting comparability and pooling. The review also noted a limited number of studies for many folate measures and allergic outcomes, reducing certainty and generalizability.