The Role of Maternal Serum Cadherin-6 Levels in Early Second Trimester Prediction of Preeclampsia: A Prospective Cohort Study

Background: Preeclampsia (PE) is a multisystem disease that can affect all pregnant women and lead to numerous feto-maternal complications. Currently, early prediction of this condition remains challenging. In this study, we aimed to evaluate the potential of maternal serum cadherin-6 (CDH-6) levels measured between 15 and 20 weeks of gestation, to predict the subsequent development of PE later in pregnancy. Methods: In this prospective cohort study, 75 pregnant women, diagnosed with PE during the follow-up period, and 75 healthy pregnant women at matching gestational weeks were included. Blood samples from all 150 participants were first centrifuged and stored, and serum CDH-6 levels were analysed by enzyme-linked immunosorbent assay (ELISA). Results: Serum CDH-6 levels, measured in the second trimester, were significantly higher in pregnancies that later developed PE compared with controls (375.3 vs. 93.1 ng/mL, p < 0.001), with the highest levels observed in early-onset cases. CDH-6 showed an excellent diagnostic performance for PE (area under the curve [AUC] = 0.983) and a good accuracy in distinguishing early- from late-onset disease (AUC = 0.801). Conclusions: High CDH-6 levels, detected in the second trimester, may serve as an early warning marker for the development of PE. This finding may contribute to clinical practice by enabling timely diagnosis of high-risk pregnancies. Clinical Trial Registration: The study is registered on the National Clinical Trial (NCT) at https://clinicaltrials.gov/study/NCT07467226?cond=NCT07467226&viewType=Card&rank=1 (registration number: NCT07467226).