Maternal Folic acid Supplementation, Perinatal Factors and Preadolescent Asthma: Findings from the Healthy Growth Study

Background 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. Aim To identify perinatal and environmental factors that modify the association between maternal folic acid intake and pre-adolescent asthma. Methods Cross-sectional analysis of the Healthy Growth Study that consisted of 2332 preadolescents (mean age 11 years, asthma n = 451), 50% boys attending elementary schools in Greece. Questionnaires were used to collect data on sociodemographic, perinatal, and environmental characteristics, 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 preadolescent asthma accounting for perinatal and environmental exposures. Results Adjusted regression models showed that maternal folic acid supplementation during the 3rd-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 2nd- and 3rd-trimesters among pre-adolescents born < 37 weeks, non-smoking mothers, in pre-adolescents attending schools of low socio-economic level, in neighborhoods having less traffic and more parks. Contrastingly, in appropriate for gestational age (AGA), infant’s 1st -trimester supplementation increased asthma odds. Conclusions 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 1st-trimester carries differential risks or benefits in asthma.