Exploring the Association of Male Sex With Adverse Outcomes in Severe Bronchopulmonary Dysplasia: A Retrospective, Multicenter Cohort Study

Abstract

Background and ObjectiveBronchopulmonary dysplasia (BPD) is a significant contributor to morbidity and mortality in infants born premature. Male sex is an independent risk factor for the development of BPD. However, whether male sex is associated with adverse outcomes occurring after formal diagnosis of severe BPD prior to hospital discharge remains unclear. Research QuestionIs male sex associated with a higher risk of adverse outcomes in infants with established severe BPD? Study Design and MethodsA retrospective, multi-center cohort study of infants enrolled in the BPD Collaborative Registry from January 1, 2015, to June 29th, 2022 was performed. Demographics, clinical characteristics, and outcomes were stratified by sex (i.e., male vs. female). Regression modeling was used to estimate the association of sex with the primary composite outcome of death or tracheostomy at hospital discharge. ResultsWe identified 1156 infants with severe BPD, defined at 36 weeks’ postmenstrual age (PMA) by the National Institutes of Health 2001 consensus definition. The cohort was predominantly male (59% males, 41% females). However, rates of mechanical ventilation at 36 weeks’ PMA (i.e. type 2 severe BPD) did not differ by sex. Overall mortality within the cohort was low (5.3% males, 3.6 % females). The odds ratio of death or tracheostomy for males to females was 1.0 (95%CI: 0.7, 1.5). InterpretationOur results lead us to speculate that while sex is an important variable contributing to the development and pathogenesis of severe BPD, it does not appear to be associated with adverse outcomes in this cohort of infants with established disease. The surprising results raise important questions surrounding the temporal role of biological sex in developing severe BPD and its progression during the NICU stay. As we explore the phenotypes and endotypes of BPD, it is imperative to consider how sex modulates the disease from birth through hospital discharge.