The Contribution of Serum Netrin-1 Levels in Early-Onset Preeclampsia Detection

Abstract

Background: Netrin-1 is a laminin-related protein involved in angiogenesis, vascular remodeling, trophoblast invasion, endothelial protection, and inflammatory regulation, making it a promising candidate biomarker for early prediction of preeclampsia.
Aim: To evaluate the role of maternal serum Netrin-1 measured during the first trimester as an early biomarker for predicting early-onset preeclampsia and to assess its relationship with maternal and neonatal outcomes.
Patients and Methods: A hospital-based case-control study was conducted at the Department of Obstetrics and Gynecology, Tikrit Teaching Hospital, Salah Al-Din Governorate, Iraq, between October 2025 and June 2026. Ninety pregnant women with singleton pregnancies were enrolled during the first trimester (11–13+6 weeks of gestation). Forty-five women who subsequently developed early-onset preeclampsia constituted the case group, while forty-five normotensive pregnant women served as controls..
Results: Maternal serum Netrin-1 concentrations were markedly lower among women who developed EOPE than among controls (286.4±71.8 vs. 468.9±84.6 pg/mL, P<0.001). Women with EOPE experienced significantly poorer maternal outcomes, including earlier delivery, increased cesarean section rate, higher ICU admission, and increased incidence of HELLP syndrome. Neonatal outcomes were also significantly worse, with lower birth weight, lower Apgar scores, higher preterm birth, and increased NICU admission. Serum Netrin-1 demonstrated significant negative correlations with maternal body mass index (r=−0.311), systolic blood pressure (r=−0.671), diastolic blood pressure (r=−0.642), serum creatinine (r=−0.514), AST (r=−0.488), and ALT (r=−0.451), while significant positive correlations were observed with gestational age at delivery (r=0.557), birth weight (r=0.602), and platelet count (r=0.463) (all P<0.05). Multivariable logistic regression analysis showed that serum Netrin-1 remained an independent predictor of EOPE after adjustment for maternal risk factors (adjusted OR=0.982, 95% CI=0.974–0.990, P<0.001).
Conclusions: Maternal serum Netrin-1 measured during the first trimester is significantly reduced in women who subsequently develop early-onset preeclampsia. Lower serum Netrin-1 concentrations are associated with adverse maternal and neonatal outcomes and remain an independent predictor of disease development. Serum Netrin-1 demonstrates excellent diagnostic accuracy and represents a promising biomarker for early prediction and risk stratification of early-onset preeclampsia.