Prostaglandins versus transcervical balloon for induction of labor for fetal growth restriction: study protocol for a randomized, multicenter, open-label, superiority trial (PROBIN)

Fetal growth restriction (FGR) is associated with an increased risk of perinatal morbidity and mortality. The risk of labor induction-related cesarean delivery is estimated around 30%. Although comparative studies suggest a transcervical balloon catheter may reduce the incidence of uterine tachysystole and fetal heart rate abnormalities over prostaglandins (all indications combined), this remains insufficiently studied for FGR. The mechanical effects of the balloon catheter might reduce the incidence of uterine tachysystole, the frequency of nonreassuring fetal status and fetal distress during labor, and thus the cesarean risk in this high-risk population. This trial’s primary objective is to assess if transcervical balloon catheter compared with prostaglandins lowers the cesarean rate among women with FGR and induction of labor between 34+0 and 41+0 weeks’ gestation. PROBIN (PROstaglandins versus Balloon catheter for INduction of labor in fetal growth restriction) is a multicenter, open-label, randomized controlled trial conducted in 16 French maternity units. Eligible participant will be women with FGR, defined as a fetus with an abdominal circumference and/or estimated fetal weight below the 10th percentile, in cephalic presentation, between 34+0 and 41+0 weeks’ gestation; requiring induction of labor according to the practitioners and with a Bishop score < 6. They will be randomized to cervical ripening by either a transcervical balloon catheter or prostaglandins. Women aged < 18 years, with no health insurance, a previous cesarean, multiple pregnancy, or fetal congenital malformation will be excluded. Randomization will be stratified by center and parity. The primary outcome will be the cesarean delivery incidence, regardless of indication. Secondary outcomes include maternal and neonatal morbidity and maternal birth experience. Assuming an alpha-risk of 0.05 and beta-risk of 0.20 (statistical power of 80%), a total of 774 women (387 per arm) is required to demonstrate a relative reduction of at least 30% in the primary endpoint — from 30% (prostaglandin group) to 21% (transcervical balloon catheter group) — with a potential loss-to-follow-up rate of 5%. If the reduction in cesarean delivery rates is confirmed with labor induction by transcervical balloon catheter in pregnancies with FGR, this method should be considered over prostaglandins. The short- and long-term maternal and neonatal morbidity associated with cesarean delivery makes reducing its incidence a major public health challenge. ClinicalTrials.gov identifier: NCT05674487, registered April 27th, 2023. The first participant was recruited April 9th, 2024.