Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta-Analysis

BACKGROUND Chorioamnionitis has recently been reported as a risk factor for various neonatal diseases, including cerebral palsy, bronchopulmonary dysplasia, and necrotizing enterocolitis, but its effect on patent ductus arteriosus (PDA) is unclear. We performed a systematic review and meta-analysis to evaluate the effect of chorioamnionitis on PDA. METHODS We searched PubMed, EMBASE, Cochrane Library, and KoreaMed databases using the terms: "intrauterine infection" or "maternal infection" or "antenatal infection" or "chorioamnionitis" or "placenta inflammation" or "placenta pathology" or "neonatal outcome" or "neonatal morbidity" or "PDA or patent ductus arteriosus" or "ductus arteriosus," and "prematurity" or "very low birth weight infant." Studies were included if they were randomized controlled trials, case-control studies, or cohort studies that included information relating to chorioamnionitis and PDA. RESULTS Among 1,571 studies, a total of 23 studies (17,708 cases) were included in the meta-analysis to analyze the relationship between chorioamnionitis and PDA, except one study that only included PDA requiring surgical ligation. The association between chorioamnionitis and PDA was statistically significant (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.19, 1.72; P < 0.0001). In subgroup analysis, clinical chorioamnionitis was not associated with PDA (OR 1.28; 95% CI 1.00, 1.64, 1.790; P = 0.05), whereas histologic chorioamnionitis (OR 1.54; 95% CI 1.10, 2.15; P = 0.01) and chorioamnionitis diagnosed from both clinical and histologic findings (OR 1.75; 95% CI 1.07, 2.86; P = 0.03) showed significant associations with PDA. Chorioamnionitis did not increase the risk of PDA requiring surgical ligation (OR 1.23; 95% CI 0.69, 2.17; P = 0.48), and antenatal steroid use reduced the risk of PDA (OR 0.62; 95% CI 0.42, 0.90; P = 0.01) after chorioamnionitis. CONCLUSIONS The results from this meta-analysis support an association between maternal chorioamnionitis and PDA in offspring.