Increased circulating Endothelin-1 is a risk factor for ECMO use and mortality in neonates with congenital diaphragmatic hernia: a prospective observational study
Increased circulating Endothelin-1 is a risk factor for ECMO use and mortality in neonates with congenital diaphragmatic hernia: a prospective observational study

Increased circulating Endothelin-1 is a risk factor for ECMO use and mortality in neonates with congenital diaphragmatic hernia: a prospective observational study

Respir Res. 2025 Mar 21;26(1):110. doi: 10.1186/s12931-025-03188-8.

ABSTRACT

BACKGROUND: Elevated levels of Endothelin-1 (ET-1), a vasoactive peptide, have been associated with adverse outcomes in neonates with congenital diaphragmatic hernia (CDH). However, the relationship between ET-1 levels and clinical outcomes remains poorly understood. This study aimed to investigate the kinetics of ET-1 levels in CDH neonates from birth to 48 h postnatally and assess its association with clinical comorbidities, the need for extracorporeal membrane oxygenation (ECMO), and mortality.

METHODS: A prospective single-center study was conducted, including 107 newborns with CDH from 2014 to 2022. Blood samples for ET-1 measurement were collected at birth, 6 h, and 48 h postnatally. The need for ECMO and mortality served as primary and secondary clinical endpoints. Based on the ET-1 values patients were assigned to ET-1 high, intermediate, and low groups. Statistical analyses, including ROC curve analysis and multivariate logistic regression, were performed to determine the predictive value of ET-1 levels.

RESULTS: Among the 107 CDH neonates 41 (38.3%) required ECMO and the overall mortality rate was 19.6%. Higher ET-1 levels at 0 and 48 h correlated significantly with the need for ECMO (p = 0.028 and p < 0.001) and mortality (p = 0.016 and p < 0.001). The high ET-1 group had a significantly higher rate of ECMO use (63.2%) and higher mortality (42.1%) compared to the ET-1 low group (15.4% and 0%). Furthermore, elevated ET-1 levels were associated with more severe disease characteristics including severe PH and biventricular dysfunction.

CONCLUSIONS: Elevated ET-1 levels during the first 48 h of life in CDH neonates are significantly associated with increased rates of ECMO and mortality. These findings underline the potential of ET-1 as a predictive biomarker for poor outcomes in CDH and highlight its relevance in guiding therapeutic interventions.

TRIAL REGISTRATION: DKRS00034329.

PMID:40119427 | DOI:10.1186/s12931-025-03188-8