Placental Matrix Metalloproteinase-9 Expression as a Biomarker of Preterm Birth in COVID-19–Positive Pregnancies: A Cross-Sectional Study

Background & Objective: Preterm birth is a major contributor to neonatal morbidity and mortality, with dysregulation of extracellular matrix remodeling implicated in its pathogenesis. Matrix metalloproteinase-9 (MMP-9), a key enzyme in placental tissue degradation, has been proposed as a potential biomarker. This study was conducted with aim to evaluate that elevated placental MMP-9 expression is associated with preterm birth.Materials & Methods: This single-center cross-sectional study was conducted using placental tissue samples from 48 pregnant women who delivered in Central Java, Indonesia. Since the study was conducted during the COVID-19 pandemic, all participants were incidentally positive for SARS-CoV-2. Placental MMP-9 expression was assessed via immunohistochemistry using an anti-MMP-9 antibody and quantified with the Immunoreactive Score (IRS). Data were analyzed using the Shapiro- Wilk test, Levene’s test, independent t-test, Mann-Whitney test, and chi-square test, with significance set at P<0.05.Results: Placental MMP-9 expression was significantly higher in women with preterm birth compared to those with term birth (P=0.017). A cut-off IRS value of >5.5 yielded 75% sensitivity and 54.2% specificity, with an odds ratio of 3.55 (P=0.039), indicating a significant association with preterm birth.Conclusion: Elevated placental MMP-9 expression is associated with preterm birth, suggesting its potential role as a predictive biomarker. Although all subjects were coincidentally SARS-CoV-2 positive, this factor did not alter the primary findings. Further studies are warranted to confirm the generalizability of the results in broader populations.