ABSTRACT
Background
Babies affected by late fetal growth restriction are at risk of adverse perinatal outcomes, either due to placental insufficiency or the consequences of late iatrogenic prematurity. There is no randomized trial reporting the optimal timing of delivery and recommending delivery at 37 weeks can cause harm. Antenatal ultrasound parameters can be used to risk stratify late fetal growth restriction pregnancies at low risk of adverse outcomes who can be delivered at full term versus high-risk pregnancies who might benefit from early term delivery.
Objective
The objective of this study was to prospectively evaluate the performance of an antenatal risk stratification and management protocol, in reducing severe adverse perinatal outcome in fetuses with late fetal growth restriction.
Study Design
This was a prospective study of singleton pregnancies with non-anomalous fetuses ≥32 weeks of gestation with suspected late fetal growth restriction managed between 2018 and 2022 at University College London Hospital, UK. Pregnancies with unknown outcome or when a structural, chromosomal or genetic abnormality was diagnosed, were excluded (women with placenta praevia were included). Fetuses were classified at 36 weeks as low-risk if estimated fetal weight (EFW) 3-10th centile (normal Dopplers, no abdominal circumference (AC) drop), or EFW >10th centile with AC drop ≥50 centiles from previous scans +/- cerebroplacental ratio (CPR) <5th centile. The high-risk group included fetuses with EFW <3rd centile, umbilical artery Doppler pulsatility index (PI) >95th centile or EFW 3-10th centile with mean maternal uterine artery Doppler PI >95th centile in the 3rd trimester +/- AC drop ≥50 centiles +/- CRP <5th centile. Delivery was advised at 40–41 weeks in the low-risk group or 37–38 weeks in the high-risk group. The primary outcome was a composite of severe adverse perinatal outcomes (perinatal mortality and severe morbidity including acidosis at birth, ventilation, encephalopathy, use of inotropes and infections). After a consensus of experts, a sample size calculation was performed to achieve a meaningful clinical difference of 5% between the two groups, which resulted in 372 patients being required in each group (alpha 0.05, power 85%). Adverse maternal outcome was defined as operative delivery due to abnormal intrapartum fetal heart rate. Multiple logistic regression analysis and modelling to estimate the risk of severe adverse perinatal outcome at different gestational ages were performed.
Results
After exclusions, from 1065 a total of 1002 patients were included (594 in the low-risk and 408 in the high-risk groups respectively). There was a significant difference in gestational age at delivery between low- vs high-risk: 39+4 (interquartile range: 38+6-40+3) vs 38+0 (37+2-38+5), p<0.001. Neonates from pregnancies classified as low risk were less likely to have severe adverse perinatal outcomes (3.2 vs 8.3%, adjusted odds ratio: 2.1, 95% confidence interval: 1.2-3.9, p=0.02). There was no difference in adverse maternal outcome between the low and high-risk groups (20.5 vs 24.8%, adjusted odds ratio: 1.2, 95% confidence interval: 0.9-1.6, p=0.23). There were no cases of extended perinatal mortality (including stillbirth, neonatal death and infant death up to 6 months) in the low-risk group (4 cases in the high-risk group).
Conclusion
Our study demonstrated that appropriate risk stratification of singleton non-anomalous fetuses with late fetal growth restriction, allows pregnancies at low risk of adverse perinatal outcome to be managed conservatively at term, with lower adverse perinatal outcomes compared to high-risk late fetal growth restriction, with no increase in perinatal mortality and maternal interventions.
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