Clinical and placental correlates of high- versus low-grade Villitis of unknown etiology: a retrospective study from Kuwait, 2014–2024

Villitis of unknown etiology (VUE) is a chronic inflammatory placental lesion associated with adverse pregnancy outcomes, particularly in severe disease. Previous studies have mainly compared VUE-positive with VUE-negative placentas or examined selected outcomes; direct evidence on whether routine maternal, obstetric, fetal, and placental features distinguish high-grade from low-grade VUE remains limited. This retrospective case-only comparative study included all 128 placentas with a histologically confirmed diagnosis of VUE identified at a single institution (Maternity Hospital, Ministry of Health, State of Kuwait) between 2014 and 2024, comprising 64 high-grade and 64 low-grade cases. Maternal demographic and obstetric characteristics, pregnancy outcomes, and concurrent placental lesions were extracted from clinical and pathology records. Because no VUE-negative comparison group was included, the analyses evaluated correlates of VUE grade and could not identify risk factors for the occurrence of VUE. Group comparisons used Welch t tests, chi-square tests, or Fisher exact tests as appropriate. Univariable and multivariable logistic regression estimated odds ratios (ORs) for high-grade VUE with 95% confidence intervals (CIs). No statistically significant associations were identified in the present dataset. Mean maternal age was 30.61 years in the high-grade group and 29.69 years in the low-grade group (mean difference 0.92 years, 95% CI − 0.96 to 2.80; p = 0.334). Parity category ( p = 0.952) and gravidity category ( p = 0.817) were not associated with grade. In the adjusted model, none of the prespecified predictors was independently associated with high-grade VUE. Estimates included maternal age (adjusted OR 1.03 per year, 95% CI 0.95–1.10), parity (adjusted OR 1.05 per birth, 95% CI 0.83–1.33), any pregnancy complication (adjusted OR 1.12, 95% CI 0.51–2.46), and any additional placental pathology (adjusted OR 1.72, 95% CI 0.72–4.13). In this selected case-only cohort of placentas with VUE, the measured maternal, fetal, obstetric, and concurrent placental characteristics did not clearly distinguish high-grade from low-grade disease. The study addresses variation in grade among VUE-positive placentas and does not identify risk factors for developing VUE. The adjusted model had modest discrimination (c-statistic = 0.60), and limited precision, sparse subgroups, possible misclassification, and multiple testing constrain interpretation. The null findings do not establish equivalence or biological independence, and clinically relevant associations may have been missed.