Single versus longitudinal scans in the third trimester: a multicenter randomized clinical trial on screening for late-onset intrauterine fetal growth restriction (The RELAIS Study)

Abstract

Background: Undiagnosed fetal smallness is strongly associated with adverse perinatal outcomes. Despite robust evidence that late third trimester ultrasound improves small for gestational age detection the question of whether routine ultrasound assessment in late pregnancy can improve perinatal outcome remains unresolved.

Objective: The objective of the study was to assess whether the addition of a 35-37 week scan in low-risk pregnancy would improve the detection of small for gestational age at birth without increasing cesarean section rates or neonatal morbidity.

Study design: Open label multicentric randomized trial recruiting nulliparous low-risk pregnant women in ten Italian centers between Jan 2021 and March 2023. Patients were randomly assigned at mid-trimester scan to either routine care (single scan at 28-32 weeks) or intervention (routine care plus additional scan at 35-37 weeks). The primary end point was prenatal detection of small for gestational age neonate with birthweight <10^th centile. Pre-defined secondary outcomes included detection of severe fetal smallness defined as birthweight <3^rd centile, cesarean section rate, composite mild/severe adverse neonatal outcome and intact neonatal survival. The study is registered at ClinicalTrials.gov (NCT05787054) on the 1st of March 2023.

Results: The antenatal detection of small for gestational age birth was significantly higher in the intervention (9/46, sensitivity 19·5%) versus routine care (0/28, sensitivity 0%) arms of the trial (p=0·011). False positive rate for the intervention for the routine care arms were 1·7% and 2·0%, respectively. The total cesarean section rate was unchanged (OR 0·89, 95% CI 0·63-1·26) and the neonatal intensive care unit admission rate was significantly lower for patients allocated to have a scan at 35-37 weeks (3·8% versus 1·0%; OR 0·27 [95%CI 0·09 - 0·80]). Composite adverse neonatal outcomes and intact neonatal survival rates were not significantly different between two groups.

Conclusion: In a low-risk population performing an additional ultrasound scan at 35-37 weeks increases the detection of small for gestational age at birth and reduces the rate of neonatal intensive care unit admission without affecting rates of labor induction or total cesarean birth.

Keywords: fetal smallness; intrauterine growth restriction; late fetal growth restriction; third trimester screening.