Screening for pre-eclampsia using serum placental growth factor and endoglin with Down's syndrome Quadruple test markers

Objective To estimate the pre-eclampsia screening performance of placental growth factor (PlGF) and endoglin with second-trimester Quadruple test markers used for antenatal Down's syndrome screening. Methods A nested case-control study of 88 pregnant women with known early second-trimester Down's syndrome Quadruple test marker levels who subsequently developed pre-eclampsia and 275 unaffected controls. Frozen maternal serum samples were thawed and assayed for PlGF and endoglin. Monte Carlo simulation was used to estimate the pre-eclampsia screening performance of a pre-eclampsia detection algorithm using the Quadruple test markers with or without the addition of PlGF and/or endoglin. Results Median PlGF was 33% lower (95% confidence interval 24–41%) and endoglin 31% (20–43%) higher in pre-eclampsia than in unaffected pregnancies. Adding PlGF to the Quadruple test markers increased the pre-eclampsia detection rate from 34% to 45% at a 5% false-positive rate – it increased it to 43% with endoglin and to 50% with both. The corresponding estimates for early pre-eclampsia (before 36 weeks’ gestation) were a few percentage points higher (48%, 48% and 55% respectively). Including information on parity, pre-eclampsia in a previous pregnancy, family history (woman's mother) and assuming a pre-eclampsia prevalence of 2%, the detection rates for a 5% false-positive rate were 39% with the Quadruple test markers, 48% with addition of endoglin, 49% with addition of PlGF, and 54% with addition of both. Conclusions Adding PlGF to the Quadruple test Down's syndrome screening markers improves pre-eclampsia screening performance. There is a modest extra benefit in also adding the measurement of endoglin.