Preeclampsia (PE) is a significant obstetrical and perinatal problem, affecting 2% to 8% of all pregnancies. Research has shown some treatments are effective for reducing the incidence of PE when started early in pregnancy and when risk factors for PE have been identified. Identification of the risk of developing PE has mainly focused on maternal risk factors, but this method is not always successful. Although there has been an increased focus on identifying and preventing this disorder, the incidence of preterm PE has remained unchanged for the last 10 years in Denmark. This study was designed to assess the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester combined screening algorithm for PE and to compare it with the current strategy of using major maternal risk factors.

This study (PRESIDE [Pre-eclampsia Screening in Denmark]) was a prospective, noninterventional multicenter study from 6 hospitals in Denmark. Patients with a singleton pregnancy undergoing first-trimester screening between 11 weeks and 2 days and 14 weeks and 1 day of gestation from May 2019 to December 2020 were recruited. Exclusion criteria were age younger than 18 years, a multiple gestation pregnancy, or an inability to understand Danish or English. Primary outcomes were gestational age at delivery and PE diagnosis.

Final analysis included 8156 patients, with a median age of 30.8 years. Complete risk assessment included maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF), and serum pregnancy-associated plasma protein A (PAPP-A). Of the final population, 303 developed PE, with 16 at less than 34 weeks' gestation, 55 at less than 37 weeks' gestation, and 248 at greater than 37 weeks' gestation. The FMF algorithm combined screening detected 77.4% of cases (95% confidence interval [CI], 57.6%–97.2%) at less than 34 weeks, 66.8% of cases (95% CI, 54.4%–79.1%) at less than 37 weeks, and 44.1% of cases (95% CI, 38.5%–49.7%) at greater than 37 weeks. In contrast, the strategy of screening with just maternal risk factors detected 25% of women with PE with delivery at less than 34 weeks and 19.6% of women with PE with delivery at less than 37 weeks at a screen-positive rate (SPR) of 3.4%. Analysis was adjusted for patients who were on treatment to prevent PE due to risk factors. Prediction models showed the area under the receiver operating characteristic curve of 0.93 (95% CI, 0.87–0.98) for PE at less than 34 weeks and an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.85–0.93) for PE at less than 37 weeks.

These results indicate that the detection rate (DR) for the FMF algorithm is substantially higher than the current Danish strategy of maternal characteristics alone. The results have a few major implications, including that this study provides independent validation of the FMF algorithm, that the FMF algorithm had a higher DR for preterm PE than current strategies, that this study contributes to growing evidence that biomarkers are more reliable in detecting preterm PE, and that this study supports screening for preterm PE as applicable in a public health care setting. Further research should be done to address the limitations of this study; future studies should focus on implementing this intervention in a more representative sample, as well as expanding to groups of individuals who were originally excluded from this analysis such as multiple gestations or individuals from other countries.