The Significance of YKL-40, a Marker Involved in Extracellular Matrix Remodeling, in Preterm Prelabor Rupture of Membranes: A Prospective Observational Study

Objective: Our objectives were to evaluate maternal serum YKL-40 levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM), compare them with healthy gestational age-comparable controls, and assess the association between YKL-40 levels and subsequent composite adverse neonatal outcomes (CANOs). Methods: This prospective observational study included 44 women with PPROM and 44 healthy pregnant controls between 24 and 37 weeks of gestation. Maternal serum YKL-40 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA), with concentrations corrected for the manufacturer-specified 5-fold sample dilution. Multivariable Firth’s penalized logistic regression was used to evaluate the independent association of YKL-40 with PPROM and, within the PPROM cohort only, subsequent CANO. Exploratory receiver operating characteristic (ROC) analysis was performed to assess the ability of YKL-40 to discriminate established PPROM cases from healthy controls. The study was powered a priori only for the primary between-group comparison of YKL-40; the ROC and CANO analyses were not separately powered and are reported as exploratory. Results: Maternal serum YKL-40 levels were significantly higher in the PPROM group than in the control group (5.87 ± 2.64 vs. 2.44 ± 0.96 ng/mL, p < 0.001). In multivariable analysis, YKL-40 remained independently associated with PPROM (adjusted odds ratio 5.61, 95% CI 2.07–15.23, p < 0.001 per 1 ng/mL increase). Within the PPROM cohort, YKL-40 was not independently associated with CANO (p = 0.775). Exploratory ROC analysis yielded an AUC of 0.935 (95% CI 0.881–0.989); a ROC-derived cut-off of >3.3 ng/mL provided 86.4% sensitivity and 84.1% specificity for discriminating established PPROM cases from healthy controls. Conclusions: Maternal serum YKL-40 levels were significantly elevated in women with established PPROM and remained independently associated with PPROM status, but were not associated with subsequent CANO. Because YKL-40 was measured after PPROM diagnosis, the observed ROC performance reflects case–control discrimination rather than prospective prediction or established diagnostic utility. Larger prospective studies using clinically relevant comparison groups and independently validated assays are required to determine the potential clinical value of YKL-40 in PPROM.