Intrahepatic Cholestasis of Pregnancy Is Associated with Reduced Nitric Oxide Synthase (iNOS) in Plasma and Placentas: A Pilot Study

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a condition specific to pregnancy, leading to increased fetal morbidity and mortality. Nitric oxide synthase (iNOS) may be a factor regulating the vasodilation of blood vessels, which are relevant to ischemic-hypoxic conditions. We aimed to explore the potential relationship between iNOS and ICP. MATERIAL/METHODS: A prospective, case-control study was conducted including 77 pregnant women with ICP and 80 healthy pregnant women as controls. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS levels. The placenta mRNA levels and cell-specific localization of iNOS were determined by quantitative polymerase chain reaction, western blotting, and immunohistochemical analysis. A multivariate linear regression model was used to identify the independent factors of serum total biliary acids (TAB) in ICP. RESULTS: Compared with controls, the expression of iNOS was significantly lower in maternal serum and placentas with ICP (P<0.001). Maternal plasm iNOS levels were negatively correlated with TAB (r=−0.450, P<0.001), cholyglycine (r=−0.367, P<0.001), alanine aminotransferase (r=−.359, P<0.001), and aspartate aminotransferase (r=−0.329, P<0.001). iNOS level was an indicator for ICP by multivariate linear regression analysis (β=−0.505, P<0.001). The ROC curve indicated the optimal cut-off level for iNOS was 2865.43 pg/mL (sensitivity, 85.71%; specificity, 63.75%). The ROC curve area for iNOS was 0.793 (95% CI 0.722–0.864). CONCLUSIONS: iNOS plays an important role in poor fetoplacental vascular perfusion and adverse pregnancy outcomes. iNOS can provide complementary information in predicting the extent and severity of ICP.