Predictive value of inflammatory indices for disease severity and perinatal outcomes in intrahepatic cholestasis of pregnancy

Abstract

Background: The etiology of intrahepatic cholestasis of pregnancy (ICP) is not fully understood; however, genetic, hormonal, environmental factors, and inflammation are believed to contribute to its development. This study aimed to investigate the relationship between systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and neutrophil-to-monocyte ratio (NMR) levels with disease severity in ICP and to evaluate their potential in predicting adverse perinatal outcomes.

Materials and methods: A total of 240 pregnant women who delivered at Bursa City Hospital between 2019 and 2024 were retrospectively analyzed. Based on fasting serum bile acid (SBA) levels, patients were divided into three groups: control (SBA < 10 µmol/L), mild (SBA 10-40 µmol/L), and severe (SBA ≥ 40 µmol/L) cholestasis. Inflammatory indices were calculated using complete blood count. Blood samples had been collected at the time of diagnosis, between 28 and 36 weeks of gestation during the third trimester, and prior to the initiation of any treatment. Intergroup comparisons and correlation analyses were conducted. The predictive value of these indices was assessed using receiver operating characteristic (ROC) analysis.

Results: No significant differences were found between groups in WBC and other complete blood count parameters. Only NMR was significantly higher in the severe cholestasis group compared to the control group (p = 0.0057). SII and SIRI levels did not differ significantly among the groups. Gestational age at delivery, birth weight, Apgar scores, and neonatal intensive care unit (NICU) admission rates were significantly worse in the cholestasis groups than in controls (p < 0.001). SII showed a negative correlation with gestational age and 5th-minute Apgar score. In ROC analysis, SII predicted preterm birth with an AUC of 0.600 (cut-off: 897.35; sensitivity: 57%; specificity: 67%) and predicted low 5th-minute Apgar scores with an AUC of 0.669 (cut-off: 1248.38; sensitivity: 75%; specificity: 83%).

Conclusion: The SII and the SIRI may not be reliable markers for the diagnosis or severity assessment of ICP. However, the SII may serve as a potential predictor for preterm birth and low Apgar scores. NMR was significantly elevated in severe ICP patients, suggesting its potential diagnostic value, which should be supported by further studies.

Keywords: Intrahepatic cholestasis of pregnancy (ICP); Neutrophil-to-Monocyte ratio (NMR); Systemic immune-inflammation index (SII); Systemic inflammatory response index (SIRI).

Fig. 1

ROC curve of SII for predicting preterm birth and low 5th minute apgar score AUC for preterm birth = 0.600 (cut-off: 897.35; sensitivity: 57%; specificity: 67%). AUC for low 5th-minute Apgar score = 0.669 (cut-off: 1248.38; sensitivity: 75%; specificity: 83%) Abbreviations: SII– Systemic immune-inflammation index; ROC– Receiver operating characteristics; AUC– Area under the curve