Association of First-Trimester Pan-Immune-Inflammation Value with Chronic Histiocytic Intervillositis and Villitis of Unknown Etiology

Background: Chronic histiocytic intervillositis (CHI) and villitis of unknown etiology (VUE) are immune-mediated placental disorders leading to adverse pregnancy outcomes. This study investigated whether first-trimester pan-immune-inflammation value (PIV), a novel systemic inflammation marker, is associated with these conditions. Methods: This retrospective case-control study (October 2022-August 2025) included 163 placentas (25 controls, 63 CHI, 75 VUE). First-trimester complete blood counts (<14 weeks) were used to calculate PIV = (neutrophil × platelet × monocyte)/lymphocyte. Histopathological examination followed Amsterdam criteria. Multivariable logistic regression and ROC analyses were performed. Results: PIV was significantly higher in cases versus controls (503.1 vs 381.3, P = .048). Across groups, PIV was highest in CHI (661.6), intermediate in VUE (446.4), and lowest in controls ( P < .001). CHI showed the worst perinatal outcomes: lowest gestational age (30.5 weeks), birth weight, and Apgar scores, and highest intrauterine fetal death (41.3%). After multivariable adjustment, first-trimester PIV remained independently associated with CHI (aOR 1.87, 95% CI 1.19-4.27, P = .005) but not with VUE (aOR 0.74, P = 0.103). Discriminatory performance was modest for CHI (AUC 0.677) and poor for VUE (AUC 0.434). Conclusion: Elevated first-trimester PIV is independently associated with CHI but not VUE, suggesting that systemic maternal inflammation may be detectable early in gestation, particularly in more severe placental immune pathology. PIV is not a standalone diagnostic test but may contribute to risk assessment when combined with clinical findings.