Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands

Two parallel randomized, double-blind trials enrolling women of childbearing age intending to become pregnant within 12 months: Italian RCT (18–44 years) and Dutch RCT (18–45 years). Italian recruitment via obstetric/gynaecologic clinics; Dutch recruitment via community pharmacies.

Italian RCT: folic acid; 4 mg/day (treatment) or 0.4 mg/day (referent); peri-conceptional; taken daily; if pregnancy occurs, continue until end of the 12th completed gestational week; if not pregnant after 12 months, discontinue. Dutch RCT: four-arm regimen; start 4 weeks pre-conception; daily; from 4 weeks pre-conception to 12 weeks gestation; after 12 weeks, continue with 0.2 mg/day or 0.8 mg/day until end of pregnancy.

Recruitment difficulties due to lack of established pre-conception counselling and routine recruitment pathways; planned recruitment targets may be hard to meet.