Midtrimester urine human chorionic gonadotropin β-subunit core fragment levels and the subsequent development of preeclampsia

OBJECTIVE: Our purpose was to determine whether midtrimester maternal urine human chorionic gonadotropin β-subunit core fragment predicts later pre-eclampsia. STUDY DESIGN: Urine β-core fragment levels standardized to spot creatinine concentration and expressed as multiples of the median were prospectively determined in 347 midtrimester singleton pregnancies undergoing genetic amniocentesis. All women considered in the analysis were white and nonsmokers. Obstetric chart review was undertaken after delivery to identify cases in which pre-eclampsia developed. The risk of pre-eclampsia at different threshold levels of β-core fragment of human chorionic gonadotropin was determined. RESULTS: The median maternal age was 36.0 years, with a median gestational age at urine collection of 16.0 weeks. The median level of the β-core fragment of human chorionic gonadotropin was 1385.5 ng/mg of creatinine in those with pre-eclampsia, whereas that in those without pre-eclampsia was 1061.2 ng/mg. The difference was significant (Mann- Whitney U test, P = .03). A significant linear association was found between the β-core fragment concentration and the risk of pre-eclampsia (Mantel- Haenszel test of linear association, P = .03). The relative risk and 95% confidence interval of subsequent pre-eclampsia increased from 2.07 (1.06 to 4.05) at β-core fragment levels of human chorionic gonadotropin >2.0 multiples of the median to 5.17 (1.95 to 13.7) at ≤4.0 multiples of the median. CONCLUSION: Clinically normal patients with elevated midtrimester levels of urine β-core fragment of human chorionic gonadotropin are at increased risk for the subsequent development of pre-eclampsia. The clinical value of this urine analyte as a marker for pre-eclampsia needs to be further investigated.