Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks.

OBJECTIVES: To develop a model for the prediction of stillbirth that is based on a combination of maternal characteristics and medical history with first-trimester biochemical and biophysical markers and to evaluate the performance of screening with this model for all stillbirths and those due to impaired placentation and unexplained causes. METHODS: This was a prospective screening study of 76 897 singleton pregnancies, including 76 629 live births and 268 (0.35%) antepartum stillbirths; 157 (59%) were secondary to impaired placentation and 111 (41%) were due to other or unexplained causes. Multivariable logistic regression analysis was used to determine if there was a significant contribution to prediction of stillbirth from the maternal factor-derived a-priori risk, fetal nuchal translucency thickness, ductus venosus pulsatility index for veins (DV-PIV), uterine artery pulsatility index (UtA-PI) and maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A (PAPP-A). The significant contributors were used to derive a model for first-trimester prediction of stillbirth. RESULTS: Significant contribution to prediction of stillbirth was provided by maternal factors, PAPP-A, UtA-PI and DV-PIV. A model combining these variables predicted 40% of all stillbirths and 55% of those due to impaired placentation, at a false-positive rate of 10%. Within the impaired-placentation group, the detection rate of stillbirth < 32 weeks' gestation was higher than that of stillbirth ≥ 37 weeks (64% vs 42%). CONCLUSIONS: A model based on maternal factors and first-trimester biomarkers can potentially predict more than half of subsequent stillbirths that occur due to impaired placentation. The extent to which such stillbirths could be prevented remains to be determined. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.