Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study.

STUDY QUESTION: Are low serum concentrations of human chorionic gonadotrophin (hCG) in very early pregnancy associated with pre-eclampsia risk? SUMMARY ANSWER: Low hCG concentrations in very early pregnancy are associated with increased risk of severe pre-eclampsia. WHAT IS KNOWN ALREADY: Low maternal serum concentrations of hCG early in pregnancy may indicate impaired proliferation or invasion of trophoblast cells, and thus low hCG concentrations may serve as a marker for impaired placental development. Impaired placental development is assumed to be a cause of pre-eclampsia, but there is little prospective evidence to support this hypothesis. STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study of pregnancies after IVF at Oslo University Hospital 1996-2010 with linkage to the Medical Birth Registry of Norway to obtain information on pre-eclampsia development. PARTICIPANTS/MATERIALS, SETTING,
METHODS: We included 2405 consecutive singleton pregnancies and examined the association of maternal serum hCG concentrations (measured using Elecsys, Roche) on Day 12 after embryo transfer with the risk of any pre-eclampsia and of mild and severe pre-eclampsia. MAIN RESULTS AND THE ROLE OF CHANCE: HCG concentrations were inversely associated with pre-eclampsia risk in a dose-dependent manner (Ptrend 0.02). Compared with women with hCG ≥150 IU/l, women with hCG <50 IU/l were at 2-fold higher overall risk of pre-eclampsia [absolute risk 6.4 versus 2.8%; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.7]. The inverse association was restricted to severe pre-eclampsia (Ptrend 0.01), thus, women with hCG <50 IU/l were at 4-fold higher risk of severe pre-eclampsia than women with hCG ≥150 IU/l (absolute risk 3.6 versus 0.9%; OR 4.2, 95% CI 1.4-12.2). For mild pre-eclampsia, there was no corresponding association (Ptrend 0.36). LIMITATIONS, REASONS FOR CAUTION: Results for IVF pregnancies may not be generalizable to spontaneously conceived pregnancies. WIDER IMPLICATIONS OF THE
FINDINGS: Plausible causes of low maternal hCG concentrations very early in pregnancy include impaired placental development and delayed implantation. Thus, these results provide prospective evidence to support the hypothesis that impaired placental development may be associated with subsequent development of severe pre-eclampsia. STUDY FUNDING/COMPETING INTEREST: The study was financially supported by the Research Council of Norway. None of the authors has any conflict of interest to declare.