Follow‐Up of Children Born to Mothers in Folic Acid Clinical Trial (FACT 4 Child): A Prospective Cohort Study Based on a Double‐Blinded Randomised Controlled Trial

To assess the impact of high-dose folic acid supplementation (4.0-5.1 mg), started between 8+0 and 16+6 weeks of gestation and continued until delivery, on social impairments associated with Autism Spectrum Disorders, deficiencies in executive function, and emotional and behavioural problems in children. FACT 4 Child is a follow-up of mothers and their children born during the Folic Acid Clinical Trial (FACT), an international multi-centre double-blinded randomised trial to assess the effect of high-dose folic acid supplementation on preventing preeclampsia in women with increased risk. Multi-centre international follow-up study. Mothers and their children enrolled in FACT, among them 664 completed the follow-up. Mothers reported on social and executive function and emotional and behavioural problems in their children aged 4-9 years using standardised, validated questionnaires. The proportion of children with at least one score > 1.5 SD above expected mean. Among 319 children in the intervention group, 43 (13.5%) had a score in the elevated range, compared with 51/345 (14.8%) in the placebo group (RR = 0.91; 95% CI: 0.63 to 1.33; p = 0.63). In children born to women at risk for preeclampsia, rates of neurodevelopmental outcomes were not different between high-dose folic acid and control groups in this study. Our finding suggests that a high dose of folic acid supplementation may not be needed in pregnant women with increased risk. A larger-scale study is needed to determine neurodevelopmental outcomes associated with different dosages and timing of folic acid supplementation during pregnancy.