Patent Ductus Arteriosus and Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension: A Bayesian Meta-Analysis

IMPORTANCE: Bronchopulmonary dysplasia (BPD) is often associated with pulmonary vascular disease and secondary pulmonary hypertension (PH). The pathogenesis of BPD-associated PH (BPD-PH) is complex and involves prenatal and postnatal factors that disrupt pulmonary vascular development, and patent ductus arteriosus (PDA) is a factor potentially associated with risk of BPD-PH that has been identified in very recent studies. OBJECTIVE: To explore the association of PDA with BPD-PH using a bayesian model-averaged (BMA) meta-analysis of studies. DATA SOURCES: PubMed and Embase were searched up to April 2023. Key search terms included BPD and PH. STUDY SELECTION: Studies examining infants with gestational age 32 weeks or less and reporting data on PDA and risk of BPD-PH. DATA EXTRACTION AND SYNTHESIS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. Two independent reviewers extracted data, with a third reviewer checking for accuracy and completeness. Data pooling and effect size calculations were performed by BMA. MAIN OUTCOMES AND MEASURES: The primary outcome was BPD-PH. BMA was used to calculate Bayes factors (BFs). The BF(10) is the ratio of the probability of the data under the alternative hypothesis (H(1), association of PDA with BPD-HP) over the probability of the data under the null hypothesis (H(0)). RESULTS: A total of 32 studies (8513 infants) were included. BMA showed that the evidence in favor of H(1) was weak for any PDA (BF(10) = 2.90; 10 studies), moderate for hemodynamically significant PDA (BF(10) = 3.77; 3 studies), and extreme for surgically ligated or catheter-occluded PDA (BF(10) = 294.9; 16 studies). In contrast, the evidence in favor of H(0) was weak for medically treated PDA (BF(10) = 0.55; 6 studies). In addition, BMA found strong evidence in favor of H(1) when prolonged exposure to PDA was analyzed as a dichotomous variable (BF(10) = 11.80; 6 studies) and extreme evidence (BF(10) = 113.60; 3 studies) when PDA exposure time was analyzed as a continuous variable. CONCLUSIONS AND RELEVANCE: In this bayesian meta-analysis, the data suggest that prolonged exposure to PDA might be associated with increased risk of pulmonary vascular disease in extremely preterm infants. This highlights the need to monitor for PH in high-risk preterm infants with prolonged exposure to PDA and to incorporate PH risk into clinical decisions regarding PDA management.