Abstract
Objective: To assess whether the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) score, derived from first-trimester tests, discriminate intrahepatic cholestasis of pregnancy (ICP) and predict adverse perinatal outcomes within ICP. Materials and Methods: This retrospective case–control study included 115 women with ICP and 64 healthy controls. Indices were derived from 11–14-week values. The composite adverse outcome comprised preterm birth, meconium-stained amniotic fluid, fetal distress, neonatal intensive care admission or a 1-minute Apgar score <7. ROC analysis with DeLong comparisons and logistic regression adjusted for age and body mass index were used. Results: APRI (p < 0.001), NLR (p = 0.002) and SII (p = 0.011) were higher in ICP; FIB-4 was similar. Among derived markers, APRI had the highest area under the curve (AUC 0.786; 95% CI 0.718–0.851); however, ALT alone performed better (AUC 0.895; DeLong p = 0.003), and APRI and SII added nothing to ALT (AUC 0.904; p = 0.465). In the adjusted model, APRI (OR 3.36 per 0.1 unit; 2.16–5.25) and SII (OR 1.45 per 100 units; 1.08–1.96) remained independent. Within the ICP group, no index predicted adverse outcomes; only serum bile acids did (AUC 0.754; OR 2.39 per 10 µmol/L; 1.54–3.69), which persisted, though attenuated, after excluding the protocol-driven preterm component (AUC 0.681). Conclusion: First-trimester APRI and SII carry an early hepatocellular–inflammatory signal in women who later develop ICP, but add no diagnostic value beyond transaminases and do not predict perinatal risk; surveillance and delivery timing should continue to rely on bile acids.