Prediction of preterm pre‐eclampsia and preterm small‐for‐gestational‐age at 24–28 weeks of gestation using ultrasound and biochemical markers in high‐risk pregnancies treated with aspirin: A secondary analysis of the StopPRE trial

OBJECTIVES: To evaluate the predictive value of second-trimester clinical ultrasound and biochemical markers for preterm pre-eclampsia and small for gestational age (SGA) in a high-risk population. STUDY DESIGN: This secondary analysis included 943 singleton pregnancies from the StopPRE trial. Women classified as high risk for preterm pre-eclampsia based on first-trimester combined screening and receiving aspirin 150 mg daily from 12 to 28 weeks of gestation were randomized to continue or discontinue aspirin treatment. Predictive models were developed using clinical risk factors, mean arterial pressure (MAP), uterine artery Doppler, estimated fetal weight (EFW) percentile, and the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio. Model performance was assessed using receiver operating characteristic curves and area under the curve (AUC) analysis. MAIN OUTCOME MEASURES: The primary outcomes were preterm pre-eclampsia and SGA. RESULTS: Among the 943 included women, 30 (3.1%) developed preterm pre-eclampsia or delivered a SGA neonate. A model combining MAP, EFW percentile, mean uterine artery Doppler pulsatility index, and the sFlt-1/PlGF ratio showed the highest predictive accuracy for preterm pre-eclampsia and/or SGA neonate (AUC 0.915, 95% confidence interval [CI] 0.867-0.963). For preterm pre-eclampsia alone, the combination of MAP, EFW percentile, first-trimester risk, and the sFlt-1/PlGF ratio performed best (AUC 0.927, 95% CI 0.850-1.00). For preterm SGA, the strongest predictor was the combination of EFW percentile and uterine artery Doppler (AUC 0.857, 95% CI 0.741-0.972). CONCLUSIONS: Combined second-trimester ultrasound and angiogenic assessment improves identification of women at risk of preterm pre-eclampsia and SGA despite aspirin treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03741179; October 25, 2018. First patient enrolled: March 5, 2019. https://clinicaltrials.gov/study/NCT03741179.