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.