Objective: To assess the added value of maternal serum levels of IL-6 in women with preterm-prelabor rupture of membranes (PPROM) as a non-invasive test for the prediction of histological chorioamnionitis (HCA). Methods: This was a prospective cohort study of pregnant women between 20 + 0 and 36 + 6 weeks of gestation with a confirmed diagnosis of PPROM. Logistic regression models were created for the prediction of HCA and compared by assessing the improvement in their Naegelkerke R² as a measure of goodness of fit. Predictive performance of all models was assessed by receiver operating characteristics curve (ROC) analysis and compared by the DeLong method. Results: From 47 women with PPROM, 31 (66%) developed HCA. Maternal serum IL-6 ≥19.5 pg/dL was the best cut-off point for the prediction of HCA (OR = 15; 95% CI: 3.6–61; p < 0.01). A model comprising maternal characteristics and IL-6 ≥19.5 pg/dL showed an area under the curve of 0.85 (95% CI: 0.74–0.95), significantly improving the previous models of IL-6 ≥19.5 pg/dL (R²: 23.3 vs. 34.1%; p = 0.01) or maternal characteristics (R²: 8.4 vs. 34.1%; p < 0.01). Conclusions: A model comprising maternal serum levels of IL-6 plus maternal characteristics proves to be a good non-invasive predictor of HCA.

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