The role of hyperglycosylated hCG in trophoblast invasion and the prediction of subsequent pre-eclampsia

Objective: Hyperglycosylated hCG (HhCG) is the predominant form of chorionic gonadotrophin in states characterized by aggressive trophoblast invasion such as early pregnancy or choriocarcinoma. Pre-eclampsia may be the result of failed or inadequate trophoblast invasion. We investigated whether low levels of maternal urine HhCG levels would predict subsequent pre-eclampsia. Study design: Mid-trimester urine (14-21 weeks) was collected and frozen from non-hypertensive women undergoing genetic amniocentesis. Inclusion criteria were: normal singleton pregnancies without a prior history of pre-eclampsia, hypertension, diabetes or other vascular disorders. The specimens were subsequently thawed, and HhCG levels standardized to urine creatinine were measured. Maternal charts were reviewed after delivery to determine the development of pre-eclampsia. There were a total of 568 study subjects. Results: Pre-eclampsia developed in 26 (4.6%) women. There was a significant correlation between low urine HhCG and subsequent pre-eclampsia (Mantel-Haenszel test of linear association: Chi-square 10.52, p=0.001). The mean HhCG level (ng/mg creatinine) was significantly greater in normals than in those destined to develop pre-eclampsia: 42.7 versus 20.3, p=0.002 (Mann-Whitney U-test). There was a progressive increase in the risk of subsequent pre-eclampsia as HhCG levels fell: HhCG ≤ 0.9 MoM RR (95% CI) = 1.51 (1.15-1.98) compared with ≤ 0.1 MoM 10.42 (2.0-54.3). Conclusion: Low maternal mid-trimester urine HhCG predicted subsequent pre-eclampsia. This appears to support the view that pre-eclampsia results at least in part from poor trophoblast invasion. Thus, HhCG may play a role in trophoblast invasion and measurement of this in urine identifies women at high risk for developing pre-eclampsia.