The SAVE FGR study: Short term variation Analysis versus Visual Evaluation of cardiotocography in early-onset Fetal Growth Restriction to trigger expedited birth - study protocol for a stepped wedge cluster randomized trial

Early-onset fetal growth restriction (eoFGR) is associated with high risks of adverse outcomes and a key dilemma in clinical obstetrical practice in determining the optimal timing of birth. Cardiotocography (CTG) is an important tool for antepartum fetal surveillance and typically assessed visually. Computerised CTG including short term variation (STV) analysis offers an objective analysis by quantifying the beat-to-beat variation in the fetal heart rate. Currently, there is a lack of randomized studies of sufficient power that examine whether birth intervention based on such quantified STV improves outcomes by ensuring timely intervention. The aim of this study is to compare perinatal and long-term outcomes up to two years of corrected age, from birth based on monitoring the fetal condition using visual evaluation of the CTG only versus CTG supported by computerised STV analysis. This study is a multicenter stepped wedge cluster randomized trial including women with singleton pregnancies between 24 and 32 weeks of gestation with eoFGR (abdominal circumference or estimated fetal weight below p10 AND umbilical artery pulsatility index above p95) with an indication for fetal CTG monitoring. In the control period, CTG monitoring is performed through visual evaluation and birth is expedited when the CTG exhibits signs of hypoxia, such as a reduced heart rate variability or repetitive, unprovoked decelerations. In the intervention period, visual evaluation of the CTG is supported by STV analysis, with birth expedited if the STV is below 3.5 ms (below 29 weeks’ gestation) or 4.0 ms (between 29 and 32 weeks’ gestation), or if other signs of hypoxia are observed visually. The intended sample size is at least 16 clusters and 800 participants. Coprimary outcomes are perinatal death and neurodevelopmental impairment at two years of corrected age based on the Ages and Stages Questionnaire. Secondary outcomes include mode of birth, neonatal morbidity, maternal health and infant health outcomes until two years CA. Analysis will be intention-to-treat and per-protocol. This study will provide insight if STV-analysis in the timing of birth in pregnancies complicated by eoFGR improves perinatal outcomes and neurodevelopmental outcomes until two years of corrected age. Prospectively registered at August 24, 2023. ClinicalTrials.gov: NCT06010238.