Less Life Support Use After Early Prostacyclin for Diaphragmatic Hernia

For newborns with pulmonary hypertension associated with congenital diaphragmatic hernia (CDH), early prostacyclin was associated with reduced need for extracorporeal life support (ECLS), researchers found based on a registry.

Babies with CDH who received prostacyclin during the first week of life were less likely to receive ECLS (23.3% vs 42.9%; adjusted OR 0.39, 95% CI 0.22-0.68) and had shorter mean duration of ECLS (8.6 vs 12.6 days; adjusted OR 0.43, 95% CI 0.19-0.96) in a propensity-matched analysis by Akila Ramaraj, MD, MPH, of UConn Health in Farmington, Connecticut, and colleagues of the CDH Study Group (CDHSG).

However, prostacyclin made no difference when it came to in-hospital mortality (29.9% vs 29.3%), according to the cohort study published in JAMA Pediatrics.

“The findings in this study demonstrate a potential benefit with early prostacyclin use in neonates with CDH,” Ramaraj and colleagues wrote. “The absolute decrease in ECLS use attributable to early prostacyclin therapy identifies a potential strategy to avoid resource-intensive care among this high-risk group of patients.”

A diaphragmatic hernia is a birth defect that can prevent the baby’s lungs from developing completely, causing breathing difficulties for the baby at birth. Approximately 1 in every 3,600 babies is born with diaphragmatic hernia, according to the CDC.

In practice, newborns with CDH who receive ECLS have 2.7 to 4 times higher mortality after accounting for disease severity, researchers noted.

Strategies to mitigate early cardiopulmonary deterioration and decrease ECLS use are important in terms of decreasing mortality. However, effective medical treatment of pulmonary hypertension associated with CDH presents a challenge, according to the researchers, because these patients respond to vasoactive agents differently than those with pulmonary hypertension secondary to other pathophysiologic processes.

“While medications such as sildenafil and inhaled nitric oxide have undergone retrospective evaluation, prostacyclins remain understudied,” Ramaraj and colleagues wrote. “Prostacyclins decrease pressure in the pulmonary arteriolar bed by vasodilation and may be titrated to clinical effect. Prior literature regarding prostacyclin therapy among CDH neonates is primarily limited to small-sample safety and feasibility studies.”

Researchers cited a prior study from the CDHSG registry that found users of epoprostenol, a synthetic analogue of prostacyclin, to have excess mortality. However, this finding was attenuated after adjustment for congenital comorbidities and 5-minute Apgar scores.

The CDHSG registry includes babies born from January 2007 to December 2019 and enrolled within the first week of life by one of 88 tertiary pediatric referral centers worldwide.

For the present analysis, the authors performed propensity score matching using estimated gestational age, birth weight, transfer status, 1-minute and 5-minute Apgar scores, highest and lowest partial pressure of arterial carbon dioxide in the first 24 hours of life, and degree of pulmonary hypertension as covariates to generate a matched cohort of exposed and unexposed patients.

Out of 6,227 infants with CDH who met inclusion criteria (mean gestational age 37.4 weeks, 42% girls), there were 3.3% (n=206) identified as receiving early prostacyclin therapy, with the remaining (n=6,021) not receiving prostacyclin in the first week or only after ECLS. Of those, ECLS was used in 22.2% and 27.9%, respectively.

After propensity score matching, there were 147 patients each in the treatment and control groups.

“This was one of the first studies to leverage the power of the CDHSG registry to evaluate outcomes associated with prostacyclin therapy and, to our knowledge, the only study focused on ECLS outcomes. The clinical significance of the association identified highlights the need for more investigation in this area to continue to improve outcomes for patients with CDH,” Ramaraj and colleagues wrote.

Commenting on the fact that in-hospital mortality was no different between the early treatment and control patients, the researchers suggested that “propensity score matching may have addressed the differences in disease severity that would otherwise contribute to mortality differences between these groups.”

Limitations of the study included that data were collected prospectively but studied retrospectively, and that management and care were not standardized among CDHSG institutions, researchers reported.

Additionally, there are currently no widely accepted guidelines for prostacyclin use in patients with CDH, the researchers said, so benefits seen in the study population were contingent on the initial decision to start the therapy early.