223 - Impact of Sex as a Biological Variable in Infants with Congenital Diaphragmatic Hernia

Poster Number: 223
Publication Number: 223.221

JD Hammond, Baylor College of Medicine, Houston, TX, United States; Oluyinka O. Olutoye, Baylor College of Medicine, Houston, TX, United States; Jamie Gilley, Texas Children’s Hospital, Houston, TX, United States; Joseph Hagan, Baylor College of Medicine, Houston, TX, United States; Jason P. Gleghorn, University of Delaware, Newark, DE, United States; Krithika Lingappan, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Sundeep Keswani, Baylor College of Medicine, Houston, TX, United States

Background: The male disadvantage in neonatal mortality and morbidity has been well described, and male neonates are more likely to suffer from adverse pulmonary outcomes than females. Congenital diaphragmatic hernia (CDH) is a complex congenital anomaly characterized by pulmonary hypoplasia and severe pulmonary hypertension (PH) with a higher incidence in male neonates than females. Despite reported similarities in overall survival between males and females, the impact of biological sex on pulmonary hypertension outcomes in males with CDH compared to females remains unclear. We hypothesized that female sex would be protective against PH related outcomes in infants with CDH.

Objective: Investigate the association of biological sex on pulmonary hypertension outcomes in infants with CDH, stratified by disease severity.

Design/Methods: A single-center retrospective cohort study was performed on all infants with CDH presenting for prenatal surgical consult from January 1st, 2008 to December 31st, 2020 at Texas Children’s Hospital. Patients who underwent prenatal intervention were excluded. Chart review was performed. Abstracted data included demographics, clinical characteristics, and echocardiograms at birth and one year of age. Infants were stratified by severity (1=mild, 2=moderate, 3=severe) using TOTAL trial definitions. Logistic regression was used to determine association of CDH severity and biological sex with inhaled nitric oxide (iNO), extracorporeal membrane oxygenation (ECMO) and tracheostomy at discharge.

Results: 291 infants were included. The cohort was predominantly male (n=167, 57%). There were no differences in overall survival between biological sex. Increased CDH severity was associated with increased risk of iNO use (OR 1.66 95% CI (1.07-2.57), p=0.023), ECMO (OR 1.93 95% CI (1.28-2.91), p=0.002), and tracheostomy at discharge (OR 2.01 95% CI (1.13-3.56) p=0.017). Female sex was associated with lower risk of ECMO (OR 0.38 95% CI (0.18-0.80), p=0.010), and this difference persisted after controlling for severity (adjusted OR 0.408 95% CI (0.18-0.92), p=0.030). Amongst 89 infants with available ECHO data, females were more likely to have resolution of PH on echocardiogram (49.1% vs 25.0%, p = 0.028). Conclusion(s): Females were more likely to have resolution of PH on ECHO by one year of life and less likely to require ECMO. This is the first time that biological sex has been implicated in modulating PH-related outcomes amongst infants with CDH. The results highlight the need to investigate the mechanisms underlying the protective role female sex appears to play in infants with CDH-PH.
Outcomes Associated with Female SexTable 1: A. When biological sex was the sole predictor, females had significantly lower odds of ECMO. B. Females also had lower odds of ECMO after controlling for CDH severity.