Comparison of different methods of first-trimester screening for preterm pre-eclampsia: cohort study.

OBJECTIVE: To compare the predictive performance of three different mathematical models for first-trimester screening of pre-eclampsia (PE), which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), and two risk-scoring systems. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancy and a non-malformed live fetus attending their routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were converted into multiples of the median (MoM). Risks for term PE, preterm PE (< 37 weeks' gestation) and early PE (< 34 weeks' gestation) were calculated according to the FMF competing-risks model, the Crovetto et al. logistic regression model and the Serra et al. Gaussian model. PE classification was also performed based on the recommendations of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). We estimated detection rates (DR) with their 95% CIs at a fixed 10% screen-positive rate (SPR), as well as the area under the receiver-operating-characteristics curve (AUC) for preterm PE, early PE and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 32 (0.3%) that developed early PE, 72 (0.7%) that developed preterm PE and 230 (2.3%) with any PE. At a fixed 10% SPR, the FMF, Crovetto et al. and Serra et al. models detected 82.7% (95% CI, 69.6-95.8%), 73.8% (95% CI, 58.7-88.9%) and 79.8% (95% CI, 66.1-93.5%) of early PE; 72.7% (95% CI, 62.9-82.6%), 69.2% (95% CI, 58.8-79.6%) and 74.1% (95% CI, 64.2-83.9%) of preterm PE; and 55.1% (95% CI, 48.8-61.4%), 47.1% (95% CI, 40.6-53.5%) and 53.9% (95% CI, 47.4-60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUC of 0.911 (95% CI, 0.879-0.943), a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3-58.0%) of preterm PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4-76.4%) of preterm PE at 33.8% SPR. CONCLUSIONS: The best performance of screening for preterm PE is achieved by mathematical models that combine maternal factors with MAP, UtA-PI and PlGF, as compared to risk-scoring systems such as those of NICE and ACOG. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at an individual level. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of first-trimester combined screening for preterm pre-eclampsia: findings from cohort of 10 110 pregnancies in Spain.

OBJECTIVE: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing-risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11-13 weeks' gestation of preterm pre-eclampsia (PE) in a Spanish population. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non-malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient-specific risks for term and preterm PE were calculated according to the FMF competing-risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen-positive rate (SPR). Risk calibration of the model was assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA-PI MoM were significantly higher, and median serum PlGF MoM and PAPP-A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA-PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9-82.6%). An alternative strategy of replacing PlGF with PAPP-A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8-77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). CONCLUSIONS: The FMF model is effective in predicting preterm PE in the Spanish population at 11-13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high-quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome.

OBJECTIVE: To investigate the potential value of biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. METHODS: This was a screening study in 8268 singleton pregnancies at 30-34 weeks' gestation. Estimated fetal weight (EFW), uterine artery (UtA) pulsatility index (PI), umbilical artery (UA) PI, fetal middle cerebral artery (MCA) PI, mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured. The detection rate (DR) and false-positive rate (FPR) of screening by each biomarker were estimated for stillbirth, pre-eclampsia, delivery of small-for-gestational-age (SGA) neonate, Cesarean section for fetal distress before or during labor, umbilical arterial cord blood pH ≤7.0 or umbilical venous cord blood pH ≤7.1, 5-min Apgar score < 7 and admission to the neonatal unit (NNU). RESULTS: Multivariable regression analysis demonstrated that significant prediction of PE was provided by PlGF, sFlt-1, MAP and MCA-PI, with a DR of 98% for PE delivering < 37 weeks' gestation and 56% for those delivering ≥ 37 weeks, at a 10% FPR. Prediction of SGA was provided by EFW, PlGF, sFlt-1, UtA-PI, UA-PI and MCA-PI, with a DR of 88% for SGA delivering < 37 and 51% for those delivering ≥ 37 weeks' gestation, at a 10% FPR. Prediction of stillbirth was provided by EFW, UtA-PI and MCA-PI, with DR of 30% at 10% FPR. Prediction of Cesarean section for fetal distress before labor was provided by EFW, sFlt-1, UtA-PI and UA-PI, with a DR of 90% at a 10% FPR. Prediction of fetal distress in labor was provided by EFW and sFlt-1, with a DR of 16% at a 10% FPR. There were no significant differences from the normal outcome group in any of the biomarkers for low cord blood pH, low Apgar score or NNU admission for cases other than those with PE and/or SGA. CONCLUSION: At 30-34 weeks' gestation, biomarkers of impaired placentation and fetal hypoxemia provide good prediction of PE, SGA and fetal distress before labor, but poor or no prediction of stillbirth and adverse events in labor or after birth.

Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.

OBJECTIVE: To investigate the potential value of biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. METHODS: This was a screening study in 3953 singleton pregnancies at 35-37 weeks' gestation. Estimated fetal weight (EFW), uterine artery pulsatility index (UtA-PI), umbilical artery (UA)-PI, fetal middle cerebral artery (MCA)-PI, mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured. The detection rate (DR) and false-positive rate (FPR) of screening by each biomarker were estimated for pre-eclampsia (PE), delivery of small-for-gestational-age (SGA) neonates, Cesarean section for fetal distress before or during labor, umbilical arterial cord blood pH ≤ 7.0 or umbilical venous cord blood pH ≤ 7.1, 5-min Apgar score < 7 and admission to the neonatal unit (NNU). RESULTS: Multivariable regression analysis demonstrated that significant prediction of PE was provided by PlGF, sFlt-1 and MAP, with a DR of 73% at a 10% FPR. Prediction of SGA was provided by EFW, PlGF and UtA-PI, with a DR of 63% at a 10% FPR. Prediction of Cesarean section for fetal distress before labor was provided by EFW and UA-PI with DR of 100% at 10% FPR. Prediction of fetal distress in labor was provided by EFW and sFlt-1, with a DR of 15% at a 10% FPR. There were no significant differences between those with a normal outcome and those with low cord blood pH, low Apgar score or NNU admission for any of the biomarkers assessed. CONCLUSION: At 35-37 weeks' gestation biomarkers of impaired placentation and fetal hypoxemia provide good prediction of PE, SGA and fetal distress before labor, but poor or no prediction of adverse events in labor or after birth.

Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome.

OBJECTIVE: To investigate the potential value of uterine artery (UtA) Doppler at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. METHODS: This was a screening study in 30 780 singleton pregnancies at 30-34 weeks. UtA pulsatility index (UtA-PI) was measured and the values were converted to multiples of the median (MoM) after adjustment for variables relating to maternal characteristics and medical history that affect the measurements. Multivariable logistic regression analysis was used to determine if measuring UtA-PI improved the prediction of adverse perinatal outcome provided by screening with maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by UtA-PI were estimated for stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH ≤ 7.0 or umbilical venous cord blood pH ≤ 7.1 and 5-min Apgar score < 7. RESULTS: The incidence of adverse perinatal outcome was higher in small-for-gestational-age (SGA) fetuses than in non-SGA fetuses, but the majority of cases with each adverse outcome were in the non-SGA group, including about 70% of stillbirths and more than 80% with Cesarean section for fetal distress, low cord blood pH and low Apgar score. The performance of UtA-PI > 95(th) percentile in screening for each adverse outcome was poor with DR of 6-16% and a FPR of 5-6%. The DR of adverse outcome when screening by high UtA-PI was greater in pregnancies complicated by SGA than in non-SGA pregnancies; 24% vs 13% for stillbirth, 15% vs 5% for Cesarean section for fetal distress, 30% vs 9% for low cord blood pH and 20% vs 3% for low 5-min Apgar score, respectively. CONCLUSION: High UtA-PI at 30-34 weeks' gestation may be useful in the prediction of adverse perinatal outcome in pregnancies with a SGA fetus, however, in the absence of SGA, UtA-PI is a poor predictor of adverse outcome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.