Screening for pre-eclampsia using pregnancy-associated plasma protein-A or placental growth factor measurements in blood samples collected at 8–14 weeks' gestation

Objectives: To assess the value of pregnancy-associated plasma protein-A (PAPP-A) in screening for preterm pre-eclampsia (PE) (delivery < 37 weeks' gestation) measured in maternal blood samples collected before 11 weeks, and to compare the screening performance of PAPP-A with that of placental growth factor (PlGF) from blood samples collected at 8–14 weeks. Methods: This study analyzed data from women who participated in the PRESIDE (Pre-eclampsia Screening in Denmark) study, a prospective, non-interventional multicenter study investigating the predictive performance of the Fetal Medicine Foundation first-trimester screening algorithm for PE in a Danish population. As part of combined first-trimester screening, a routine blood sample was collected at 8–14 weeks' gestation and PAPP-A was measured. Excess serum was stored at −80°C and analyzed for PlGF in batches after delivery. Most women in the PRESIDE study had an extra blood sample collected at the time of the first-trimester scan at 11–14 weeks, which was also analyzed for PlGF and PAPP-A in batches after all the participants had delivered. Screening performance was assessed in terms of the detection rate at a 10% screen-positive rate (SPR) for a combination of PAPP-A or PlGF with maternal factors alone and for a combination of each of these biomarkers with maternal factors, mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI). Results: The study population comprised 8386 women who had a routine combined first-trimester aneuploidy screening blood sample collected at 8–14 weeks' gestation. In pregnancies that developed preterm PE, the median PAPP-A multiples of the median from routine blood samples were 0.78 (95% CI, 0.67–0.90) before 10 weeks, 0.80 (95% CI, 0.58–1.10) at 10 weeks and 0.64 (95% CI, 0.53–0.78) at 11–14 weeks. In women with samples collected before 10 weeks, there was no significant improvement in the detection rate of preterm PE when PAPP-A or PlGF was combined with maternal factors alone or when combined with maternal factors, MAP and UtA-PI. In routine samples collected at or after 10 weeks, PAPP-A only increased the detection rate of preterm PE slightly. However, PlGF in samples collected at or after 10 weeks increased the detection rate from 31.3% (95% CI, 16.1–50.0%) to 56.3% (95% CI, 37.7–73.6%) at a 10% SPR, i.e. an increase in the detection rate of 25.0% (95% CI, 4.3–44.4%), when combined with maternal factors alone. When PlGF collected from the PRESIDE sample at 11–14 weeks was combined with maternal factors, MAP and UtA-PI, there was an increase in the detection rate from 50.9% (95% CI, 37.1–64.6%) to 67.3% (95% CI, 53.3–79.3%), i.e. an increase of 16.4% (95% CI, 5.6–29.0%) at a 10% SPR. Conclusions: PAPP-A has limited value in first-trimester screening for PE, whereas PlGF adds significantly to the detection rate of preterm PE at 10–14 weeks' gestation.