225 - Is Early Inhaled Nitric Oxide Beneficial in the Treatment of Neonates with Congenital Diaphragmatic Hernia?

Poster Number: 225
Publication Number: 225.221

Caroline Yeon-Kyeong Noh, Stanford University School of Medicine, Palo Alto, CA, United States; Valerie Y. Chock, Stanford University School of Medicine, Sunnyvale, CA, United States; Shazia Bhombal, Stanford university, Palo Alto, CA, United States; Enrico Danzer, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Neil Patel, Royal Hospital for Children, Glasgow, Scotland, United Kingdom; Alex Dahlen, Stanford University School of Medicine, Stanford, CA, United States; Matthew T. Harting, University of Texas Medical School, Houston, Houston, TX, United States; Kevin P. Lally, McGovern Medical School at UTHouston, Houston, TX, United States; Ashley H. Ebanks, UTHealth, Houston, TX, United States; Krisa P. Van Meurs, Stanford University School of Medicine, Palo Alto, CA, United States

Background: Inhaled nitric oxide (iNO) has been widely used for the management of pulmonary hypertension (PH) in infants with congenital diaphragmatic hernia (CDH); however, there is limited evidence of its benefit.

Objective: To evaluate the impact of early use of iNO in the first 3 days of life on the outcomes of infants with CDH in relation to echocardiographic characteristics and to identify subgroups of infants who may or may not benefit from iNO. We hypothesized that a subgroup of infants with echocardiographic characteristics demonstrating severe PH with right ventricular (RV) dysfunction might benefit from iNO administration, while other infants with severe PH and impaired left ventricular (LV) function might not.

Design/Methods: This is a retrospective study of Congenital Diaphragmatic Hernia Study Group Registry data collected from 90 centers in 18 countries between 2015 and 2020. Echocardiographic characteristics from the first study prior to extracorporeal life support (ECLS) or repair were analyzed to determine the impact of iNO use in the first 3 days of life on mortality or ECLS use. A series of multivariate logistic regression models and subgroup analyses wherein patients were stratified by echocardiographic characteristics and defect size was performed.

Results: Out of 1777 infants included in the final analysis, 863 (48.6%) infants received early iNO treatment. Infants treated with iNO had lower birth weight, larger defect size, more severe PH, and abnormal ventricular size and function (Table 1). After controlling for these factors, early iNO use was associated with increased mortality (OR 2.08, 95% CI 1.06-4.06) and increased ECLS use (OR 3.36, 95% CI 2.07-5.45) (Figure 1). Subgroup analyses after stratification by echocardiographic characteristics and defect size failed to identify a subgroup of infants for which early iNO treatment was associated with decreased ECLS use or improved survival, including those with severe PH without LV dysfunction (Table 2). In addition, early iNO use when used in milder forms of disease with smaller defects and less severe echocardiographic parameters was also associated with significantly higher mortality.Conclusion(s): Use of iNO in the first 3 days of life prior to ECLS or repair was not associated with a reduction in mortality or ECLS use in any of the echocardiographic subgroups identified. Further study of iNO use is warranted in the CDH population.
Table 1. Cohort characteristics, echocardiographic characteristics, and outcomes by early iNO use group
Table 2. The impact of early iNO on death and ECLS use stratified by echocardiographic characteristics and defect size.