Exploring the Association of Male Sex With Adverse Outcomes in Severe Bronchopulmonary Dysplasia

Background Bronchopulmonary dysplasia (BPD) is a significant contributor to morbidity and death in infants who are born premature. Male sex is an independent risk factor for the development of BPD. However, whether male sex is associated with adverse outcomes that occur after formal diagnosis of severe BPD prior to hospital discharge remains unclear. Research Question Is male sex associated with a higher risk of adverse outcomes in infants with established severe BPD? Study Design and Methods A retrospective, multicenter cohort study of infants enrolled in the BPD Collaborative Registry from January 1, 2015, to June 29, 2022, was performed. Demographics, clinical characteristics, and outcomes were stratified by sex (ie, 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. Results We identified 1,156 infants with severe BPD, defined at 36 weeks postmenstrual age by the National Institutes of Health 2001 consensus definition. The cohort was predominantly male (59% male infants, 41% female infants). However, rates of mechanical ventilation at 36 weeks postmenstrual age (ie, type 2 severe BPD) did not differ by sex. Overall mortality rates within the cohort were low (male infants, 5.3%; female infants, 3.6%). The OR of death or tracheostomy for male-to-female infants was 1.0 (95% CI, 0.7-1.5). Interpretation Our results lead us to speculate that, although sex is an important variable that contributes 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 the development of severe BPD and its progression during the neonatal ICU 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. Bronchopulmonary dysplasia (BPD) is a significant contributor to morbidity and death in infants who are born premature. Male sex is an independent risk factor for the development of BPD. However, whether male sex is associated with adverse outcomes that occur after formal diagnosis of severe BPD prior to hospital discharge remains unclear. Is male sex associated with a higher risk of adverse outcomes in infants with established severe BPD? A retrospective, multicenter cohort study of infants enrolled in the BPD Collaborative Registry from January 1, 2015, to June 29, 2022, was performed. Demographics, clinical characteristics, and outcomes were stratified by sex (ie, 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. We identified 1,156 infants with severe BPD, defined at 36 weeks postmenstrual age by the National Institutes of Health 2001 consensus definition. The cohort was predominantly male (59% male infants, 41% female infants). However, rates of mechanical ventilation at 36 weeks postmenstrual age (ie, type 2 severe BPD) did not differ by sex. Overall mortality rates within the cohort were low (male infants, 5.3%; female infants, 3.6%). The OR of death or tracheostomy for male-to-female infants was 1.0 (95% CI, 0.7-1.5). Our results lead us to speculate that, although sex is an important variable that contributes 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 the development of severe BPD and its progression during the neonatal ICU 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.