First trimester preeclampsia screening and prediction

Abstract

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. Early onset disease requiring preterm delivery is associated with a higher risk of complications in both mothers and babies. Evidence suggests that the administration of low dose aspirin initiated prior to 16 weeks' gestation significantly reduces the rate of preterm preeclampsia. Therefore, it is important to identify pregnant women at risk of developing preeclampsia during the first trimester of pregnancy, thus allowing timely therapeutic intervention. Several professional organizations such as American College of Obstetricians and Gynecologists (ACOG) and National Institute for Health and Care Excellence (NICE) have proposed screening for preeclampsia based on maternal risk factors. The approach recommended by the ACOG and NICE essentially treats each risk factor as a separate screening test with additive detection rate and screen positive rate. Evidence has shown that preeclampsia screening based on the NICE and ACOG approach has suboptimal performance as the NICE recommendation only achieves detection rates of 41% and 34%, at 10% false positive rate, for preterm and term preeclampsia, respectively. Screening based on the ACOG (2013) recommendation can only achieve detection rates of 5% and 2% for preterm and term preeclampsia, respectively, at 0.2% false positive rate. Various first trimester prediction models have been developed. Most of them have not undergone or failed external validation. However, it is worthy of note that the Fetal Medicine Foundation (FMF) first trimester prediction model (namely "the triple test"), which consists of a combination of maternal factors, and measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has undergone successful internal and external validation. The FMF triple test has detection rates of 90% and 75% for the prediction of early and preterm preeclampsia, respectively, at 10% false positive rate. Such performance of screening is superior to that of the traditional method by maternal risk factors alone. The use of the FMF prediction model, followed by the administration of low dose aspirin, has been shown to reduce the rate of preterm preeclampsia by 62%. Number needed to screen to prevent one case of preterm preeclampsia by the FMF triple test is 250. The key to maintain optimal screening performance is to establish standardized protocols for biomarker measurements and regular biomarker quality assessment as inaccurate measurement can affect screening performance. Tools frequently used to assess quality control include the cumulative sums and target plot. Cumulative sums is a sensitive method to detect small shifts over time and point of shift can be easily identified. Target plot is a tool to evaluate deviation from expected multiple of median and expected median of standard deviation. Target plot is easy to interpret and visualize. However, it is insensitive to detect small deviation. Adherence to well-defined protocols for the measurements of mean arterial pressure, uterine artery pulsatility index and placental growth factor is required. This article summarizes the existing literature on the different methods, recommendations by professional organizations, quality assessment of different components of risk assessment and clinical implementation of the first trimester screening for preeclampsia.