Abstract
Sir, We read with interest the article by D'Anna et al. (1). In their study mid-trimester inhibin-A concentrations were not elevated among women with pregnancy-induced hypertension or preeclampsia. In contrast with D'Anna et al. we studied the possible role of inhibin-A as an early predictor of preeclampsia during the first trimester of pregnancy and not as a marker of disease. It has been suggested that increased inhibin-A serum levels in early pregnancy are associated with the development of preeclampsia and that elevated levels in the second trimester are helpful in prediction of preeclampsia (2,3). Nineteen women destined to develop preeclampsia and/or hemolysis elevated liver enzymes low platelets (HELLP) syndrome and 36 women who remained normotensive throughout pregnancy were included. Preeclampsia was defined as a diastolic blood pressure above 90 mmHg on two occasions more than 4 h apart with proteinuria of more than 0.3 g/L. Blood was drawn by vene puncture at the first prenatal visit, between 6 and 15 weeks amenorrhea. Serum inhibin-A concentrations were determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit (4). Statistical analyses to compare serum inhibin-A concentrations between the patient and the control groups were performed using Student's t-test. A p-value below 0.05 was considered to indicate statistical significance. Subsequently, receiver-operating characteristic (ROC) analysis was performed to assess the best cut-off value and discriminating capacity of inhibin-A. Sensitivity, specificity, predictive values and likelihood ratio of a positive and negative test were calculated in order to consider the predictive efficacy of first trimester serum inhibin-A concentrations. Median (range) serum inhibin-A concentrations were significantly (p < 0.05) higher in patients compared to controls; 281 (82–2300) pg/mL vs. 234 (26–455) pg/mL, respectively. Placental protein leakage due to syncytiotrophoblast alteration might cause the elevated inhibin-A serum concentrations (5). Another possibility might be reactive hyperplasia of cytotrophoblastic cells due to reduced oxygen supply, as has been suggested for increased human chorionic gonadotropin (hCG) concentrations in early trimester of pregnant women who subsequently develop preeclampsia (6). Both proposed mechanisms are possibly present long before onset of disease. Despite the significantly higher median inhibin-A concentrations early in pregnancy of the cases, the sensitivities and predictive values of a positive and negative test for the two cut-off values were too low to provide a reliable predictor of disease (Table I). Furthermore, considering the likelihood ratio of 3.2, the capacity of increased inhibin-A concentrations as a predictive marker for developing preeclampsia appears to be low. In conclusion, our results indicate that first trimester serum inhibin-A concentration cannot be used as a single predictor for development of preeclampsia. Combination models with other biochemical and clinical markers have to be studied and future studies should also elucidate the optimal sampling time. E. A. P. Steegers Department of Obstetrics and Gynecology Erasmus University Medical Center PO Box 2040 3000 CA Rotterdam the Netherlands e-mail: [email protected]
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