TY - JOUR
T1 - Increased circulating Endothelin-1 is a risk factor for ECMO use and mortality in neonates with congenital diaphragmatic hernia
T2 - a prospective observational study
AU - Lemloh, Lotte
AU - de Vadder, Aster
AU - Melaku, Tamene
AU - Bo, Bartolomeo
AU - Patel, Neil
AU - Holdenrieder, Stefan
AU - Mueller, Andreas
AU - Kipfmueller, Florian
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
KW - Congenital diaphragmatic hernia
KW - Endothelin-1
KW - Extracorporeal membrane oxygenation
KW - Pulmonary hypertension
UR - http://www.scopus.com/inward/record.url?scp=105000540318&partnerID=8YFLogxK
U2 - 10.1186/s12931-025-03188-8
DO - 10.1186/s12931-025-03188-8
M3 - Article
AN - SCOPUS:105000540318
SN - 1465-9921
VL - 26
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 110
ER -