Ultrasound prediction of adverse outcome and perinatal complications at diagnosis of late-onset fetal growth restriction: a cohort study

Background: Abnormal umbilical, cerebral and uterine artery Doppler findings and fetal biometry below the 3rd percentile have been proposed as risk factors for perinatal complications in late-onset fetal growth restriction (FGR). Recent evidence has allowed to reach a consensus on the clinical use of Doppler ultrasound for the monitoring and timing of delivery in early-onset FGR, however there is limited data on the relationship between abnormal Doppler and severity of the growth restriction and adverse outcome when a diagnosis of late-onset FGR is made. Objective: To evaluate the relationship between the ultrasound parameters measured at diagnosis and perinatal adverse outcome within a cohort of late-onset FGR fetuses. Methods: This is a multicentre retrospective study between 2014 and 2019 including non-anomalous singleton pregnancies complicated by late-onset FGR, which was defined either by abdominal circumference (AC), estimated fetal weight (EFW) <10th percentile for the gestation or by a reduction of the longitudinal growth of the AC by over 50 percentiles compared to an ultrasound scan performed between 18 and 32 weeks of gestation. Sonographic findings at diagnosis were compared between fetuses with and without adverse outcomes including stillbirth, obstetric intervention due to intrapartum distress, neonatal acidaemia, transfer to neonatal intensive care unit (NICU) and composite adverse perinatal outcome (CAO), which was defined by either stillbirth or the combination of at least two adverse perinatal outcomes. Results: Overall, 468 cases with full biometry and umbilical, middle cerebral, and uterine artery (UtA) Doppler data were included, among whom CAO was recorded in 53 (11.3%). At logistic regression analysis, only the EFW percentile proved to be independently associated with CAO (p=0.01) and NICU admission (p<0.01), while the mean UtA pulsatility index (PI) MoM >95th percentile at diagnosis proved to be independently associated with obstetric intervention due to intrapartum distress (p<0.01). The model including baseline pregnancy characteristics and the EFW percentile was associated with an area under the curve of 0.889, 95%CI (0.813-0.966), p<0.001 for CAO. A cut-off value corresponding to the 3.95th percentile was found to better discriminate between cases with and without CAO yielding a 58.5% sensitivity [95% confidence interval (CI) (44.1-71.9)], a 69.6% specificity [95%CI (65.0-74.0)], a 19.8% positive predictive value [95%CI (13.8-26.8)], and a 92.9% negative predictive value [95%CI (89.5-95.5)]. Conclusions: Retrospective data on a large cohort of late-onset FGR fetuses shows that at diagnosis the EFW is the only sonographic parameter independently associated with the occurrence of adverse perinatal outcomes, while a mean UtA PI MoM >95th percentile at diagnosis is independently associated with intrapartum distress leading to obstetric intervention.