First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study

BACKGROUND To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. METHODS Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. RESULTS Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis < 37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis < 34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (%hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, %hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699-0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750-0.988) for early-onset pre-eclampsia. Without %hCG-h the AUC values were 0.756 (95% CI 0.651-0.861) and 0.810 (95% CI 0.682-0.938) respectively. For prediction of gestational hypertension, the AUC for %hCG-h was 0.708 (95% CI 0.608-0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women. CONCLUSIONS First trimester maternal serum %hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.