Effectiveness of A Package of Folate-oriented Tertiary Interventions on Incidence of Fetus and Birth Defects: protocol for a single blind cluster randomized controlled trial

Background: Birth defects are the main cause of fetal death, infant mortality and morbidity, as well as long-term disability in China. Though the etiology of birth defects remains unknown, many studies indicated that maternal key nutrition factors, especially maternal folate status during periconception period, played an important role in organogenesis, the incidence of neural tube defects, congenital heart diseases and some other birth defects. The aim of this trial is to evaluate the effectiveness of package of folate-oriented interventions during periconception on incidence reduction of fetus and birth defects. Methods: This is a two-arm single-blind cluster randomized controlled trial (cRCT) in clinical settings. Twenty-two tertiary community health care centers will be randomly allocated to the intervention arm or control arm. Eligible women will be recruited before conception and receive folate-oriented tertiary intervention procedures in addition to the routine perinatal care (intervention arm), or only routine perinatal care (control arm) according to the national recommendation and guideline. The difference was the procedures to aware and ensure sufficient folate levels before conception in the intervention arm. The participants will be blinded to the allocation. Participants of the control arm will not be offered any information about the intervention procedures during the study period to prevent contamination. The composite primary outcome is defined as occurrence of fetus defects, still birth, and neonatal birth defects identified from the confirmation of pregnancy to 28 days after birth. Secondary outcomes include abortions, financial burden of fetus and birth defects, gestational diabetes, gestational hypertension, pregnancy weight gain (entire and early gestation), maternal body weight and HbA1c at and after 6 months of delivery and neonatal development. Discussion: This trial will provide important evidence on the effectiveness of a package of folate-oriented tertiary interventions on the reduction of the incidence of fetus and birth defects compared to routine periconceptional and antenatal health care. This evidence is expected to impact policy making about improving primary prevention of birth defects in China. Trial registration: ClinicalTrials.gov, NCT03725878，Registered on 24 October 2018, https://www.clinicaltrials.gov/ct2/show/NCT03725878?term=Huang+guoying&rank=2