Maternal Folic Acid Supplementation, Perinatal Factors, and Pre-Adolescent Asthma: Findings from the Healthy Growth Study

<b>Background:</b> While the importance of folic acid supplementation during pregnancy in the prevention of neural tube defects in offspring is well established, its potential role in pediatric asthma development remains unclear, with limited evidence to date. <b>Objective:</b> To identify perinatal and environmental factors that modify the association between maternal folic acid intake and pre-adolescent asthma. <b>Methods:</b> Cross-sectional analysis of the Healthy Growth Study that consisted of 2332 pre-adolescents (mean age 11 years; asthma <i>n</i> = 451); 50% boys attending elementary schools in Greece. Questionnaires were used to collect data on sociodemographic, perinatal, and environmental characteristics as well as asthma prevalence and maternal folic acid supplementation during pregnancy (trimesters 1, 2, and 3). Logistic regression models explored the association between maternal folic acid supplementation and pre-adolescent asthma, accounting for perinatal and environmental exposures. <b>Results:</b> Adjusted regression models showed that maternal folic acid supplementation during the third trimester was associated with 34% increased odds of pre-adolescent asthma. Stratified analyses per perinatal and environmental factors revealed significantly higher asthma odds with folic acid supplementation during the second and third trimesters among pre-adolescents born < 37 weeks; non-smoking mothers; in pre-adolescents attending schools of low socioeconomic level; and in neighborhoods having less traffic and more parks. Contrastingly, in appropriate for gestational age (AGA), an infant's first-trimester supplementation increased asthma odds. <b>Conclusions:</b> Maternal folic acid supplementation, particularly in later trimesters, was modestly associated with increased odds of pre-adolescent asthma, modified by perinatal and environmental factors. Future research should explore whether continued folic acid supplementation beyond the first trimester carries differential risks or benefits in asthma.