First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia

Objective To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta subunit of human chorionic gonadotrophin (f beta-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia. Design Nested case-control study. Setting Routine first-trimester screening for trisomy 21 in the Netherlands. Population Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls. Methods PP13, PlGF and ADAM12 were measured in stored first-trimester serum, previously tested for PAPP-A and f beta-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination. Main outcome measures Development of pre-eclampsia or HELLP syndrome. Results PP13 and PlGF were reduced in women with pre-eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and f beta-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except f beta-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate. Conclusion This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.