Screening for pre-eclampsia at 11-13 weeks' gestation: use of pregnancy-associated plasma protein-A, placental growth factor or both.

Objective: First-trimester screening for pre-eclampsia (PE) is useful because treatment of the high-risk group with aspirin reduces the rate of early PE with delivery at < 34 weeks' gestation by about 80% and that of preterm PE with delivery at < 37 weeks by 60%. In previous studies, we reported that the best way of identifying the high-risk group is by a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). An alternative biochemical marker is pregnancy-associated plasma protein-A (PAPP-A), which is used widely as part of early screening for trisomy. The objective of this study was to examine the additive value of PlGF and PAPP-A in first-trimester screening for preterm PE by maternal factors, MAP and UtA-PI and define the risk cut-off and screen-positive rate to achieve a desired detection rate of PE if PAPP-A rather than PlGF was to be used for first-trimester screening.

Methods: This was a non-intervention screening study. The data were derived from prospective screening for adverse obstetric outcomes in women with singleton pregnancy attending for a routine first-trimester hospital visit. Patient-specific risks of delivery with PE at < 37 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median (MoM) values of MAP, UtA-PI, PlGF and PAPP-A. The performance of screening in the total population and in subgroups of women of white and black racial origin was estimated. McNemar's test was used to compare the detection rate, for a fixed screen-positive rate, of screening with and without PlGF and PAPP-A. Risk cut-offs and screen-positive rates to achieve desired detection rates of preterm PE were determined in screening with and without PlGF and PAPP-A.

Results: The study population was composed of 60 875 singleton pregnancies, including 1736 (2.9%) that developed PE. There are three main findings of this study. First, the performance of first-trimester screening for PE by a combination of maternal factors, MAP, UtA-PI and PlGF is superior to that of screening by maternal factors, MAP, UtA-PI and PAPP-A; for example, in screening by maternal factors, MAP, UtA-PI and PlGF, at a screen-positive rate of 10%, the detection rate of PE with delivery at < 37 weeks' gestation was 74.1%, which was 7.1% (95% CI, 3.8-10.6%) higher than in screening by maternal factors, MAP, UtA-PI and PAPP-A. Second, addition of serum PAPP-A does not improve the prediction of PE provided by maternal factors, MAP, UtA-PI and PlGF. Third, the risk cut-off and screen-positive rate to achieve a given fixed detection rate of preterm PE vary according to the racial composition of the study population and whether the biomarkers used for screening are MAP, UtA-PI and PlGF or MAP, UtA-PI and PAPP-A. For example, in screening by a combination of maternal factors, MAP, UtA-PI and PlGF in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 136 and the screen-positive rate would be 14.1%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 29 and the screen-positive rate would be 12.5%. In screening by a combination of maternal factors, MAP, UtA-PI and PAPP-A in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 140 and the screen-positive rate would be 16.9%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 44 and the screen-positive rate would be 19.3%.

Conclusion: In first-trimester screening for PE, the preferred biochemical marker is PlGF rather than PAPP-A. However, if PAPP-A was to be used rather than PlGF, the same detection rate can be achieved but at a higher screen-positive rate. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.