First-Trimester Systemic Immune-Inflammation Index, APRI and FIB-4 Scores in Women Who Later Develop Intrahepatic Cholestasis of Pregnancy: Association with the Disease and with Perinatal Outcomes in a Retrospective Case–Control Study

Objective: To examine 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 routine first-trimester tests, are associated with subsequent intrahepatic cholestasis of pregnancy (ICP) and, within ICP, with adverse perinatal outcomes. Materials and Methods: This retrospective case–control study included 115 women with ICP and 64 controls with normal liver tests. Indices were derived from 11- to 14-week values. The two primary hypotheses concerned APRI and SII (Bonferroni α = 0.025); all other analyses were exploratory, with false discovery rate (FDR) adjustment. Within ICP, the co-primary outcomes were a composite of preterm birth, meconium-stained amniotic fluid, fetal distress, neonatal intensive care admission or 1-min Apgar score < 7, and the same composite excluding preterm birth, because delivery timing was protocol-driven by bile acids. Results: APRI (AUC 0.786; 95% CI 0.718–0.852; p < 0.001) and SII (AUC 0.615; 0.530–0.697; p = 0.011) were higher in women who later developed ICP; FIB-4 was not. ALT alone discriminated better (AUC 0.895; DeLong p = 0.003), APRI and SII added no discrimination beyond ALT (AUC 0.904; p = 0.465), and when cases were restricted to the transaminase range of controls (ALT ≤ 31 U/L), the AUC of APRI fell to 0.644. Within ICP, no index demonstrated an association with either composite outcome (all FDR-adjusted q > 0.15), although power was only ~45% for an AUC of 0.60. Bile acids were associated with the composite excluding preterm birth (AUC 0.681; adjusted OR 1.43 per 10 µmol/L; 1.16–1.76); the stronger association with the full composite (AUC 0.754) is partly definitional. Conclusions: First-trimester APRI and SII carry a group-level signal in women who later develop ICP, but this signal largely reflects transaminases and is inflated by control selection. The indices did not demonstrate an association with perinatal outcomes, although small effects cannot be excluded; surveillance and delivery timing should continue to rely on bile acids.