P2.I179: Prostaglandins as Vasodilatory Agent Therapy for Pulmonary Hypertension in Postnatal Period in Patients with Congenital Diaphragmatic Hernia: A Systematic Review and Meta-Analysis

Background: Congenital diaphragmatic hernia (CDH) is a life-threatening condition that causes severe respiratory distress shortly after birth due to pulmonary hypoplasia. [1-2] Commonly, inhaled nitric oxide (NOi) has been used to treat Pulmonary hypertension (PH) in those patients. [11,12] However, studies have shown that using NOi in neonates with CDH did not reduce the mortality rates and the demand for extracorporeal membrane oxygenation (ECMO). [11,12] Than, the administration of prostacyclins (PGI)/prostaglandins (PG) was recently introduced as a therapy option for PH in children with CDH. [6] Nevertheless, there is still a lack of information regarding the use of those medications in the management of PH in children with CDH. [6]
Several retrospective studies suggested that PGE1 may improve circulatory function, as it has been associated with a reduction in B-type natriuretic peptide, leading to a decrease in pulmonary artery pressure (PAP). [13–15] Furthermore, PGE1 offers a dual action, both vasodilating pulmonary arteries locally to reduce PAP and helping to maintain the patency of the ductus arteriosus. [13–15] Additionally, one advantage of prostacyclin therapy is its versatility in administration, with options including intravenous, subcutaneous, inhaled, and oral routes. [6] While small retrospective cohorts have explored PGE1 and PGI as a treatment for PH in CDH, comprehensive studies and meta-analyses evaluating their impact on the prognosis of newborns with CDH and PH are lacking.
The study aimed to perform a meta-analysis on the efficacy and safety of prostaglandins as vasodilatory agent therapy for Pulmonary Hypertension (PH) in postnatal period in patients with Congenital Diaphragmatic Hernia.

Methods: A systematic search of PubMed, EMBASE, and Cochrane was conducted to identify randomized controlled trials (RCT) and cohorts analyzing the use of PGE1 and PGI versus placebo in CDH patients with PH born after 37 weeks of gestation. The primary outcomes of interest were mortality and ECMO utilization. Statistical analysis followed the Cochrane Collaboration guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. Heterogeneity was assessed by using Cochrane's Risk of Bias 1 (ROBINS-I), Cochran Q test, and I2 statistics.

Results: The meta-analysis, comprising four cohorts totaling 6873 patients, revealed that prostaglandins (PG) did not significantly decrease mortality rates as anticipated (RR 1.44; 95% CI 0.89 - 2.32; p = 0.134; I2=64%). However, the confidence interval and p-value indicated a lack of statistical significance.

Conclusion: This meta-analysis has its limitations; we do not establish conclusively the efficacy of PGI and PGE in reducing mortality in CDH patients. However, it may have indicated an association between the use of PGE1 and a reduction in the duration of mechanical ventilation dependency. Further, RCT is imperative to comprehensively assess the utilization of PGI and PGE1 in treating PH in CDH patients.