Examining the complex intersection between extreme prematurity, chronic lung disease, neonatal brain maturation, and early language development

Introduction: Survival rates for extremely preterm (EP) neonates (those born at 28 weeks of gestation or less) have rapidly increased due to advancements in perinatal and neonatal medicine. However, despite improvements in gentler ventilation methods and greater utilization of antenatal steroids, the incidence of chronic lung disease of prematurity, or bronchopulmonary dysplasia (BPD)—characterized by alveolar simplification, alveolar fibrosis, airway hyperinflation, and vascular changes, often resulting from inflammation partly due to mechanical ventilation and supplemental oxygen—has not improved. While BPD is known to impact development, including poorer cognitive outcomes and academic success, clarifying its specific relation to neonatal brain maturation is critical for advancing risk detection and intervention strategies within this high-risk population. This study examined the influence of BPD severity on neonatal brain maturation and assessed whether incorporating postnatal brain size and growth metrics enhanced our current understanding of the association between BPD and early language development. Methods: This study utilized prospectively collected data from the University of Iowa as part of the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) General Database Study, which includes information on neonatal morbidities, such as BPD, and the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) expressive and receptive communication subscores at 18 to 26 months corrected age. Linear measurements of brain regions and cerebrospinal fluid (CSF) spaces were performed on previously collected non-invasive and nonsedating clinical two-dimensional head ultrasonography (2D HUS) examinations conducted around day of life seven and again around 36 weeks postmenstrual age. Results: These findings showed that moderate and severe BPD were linked to smaller, less developed brains, as reflected by reduced volumes in extra-axial and ventricular spaces, as well as smaller sizes of deep and midline structures at 36 weeks postmenstrual age, in addition to impaired brain growth in these regions from the first week of life to term-equivalent age. Furthermore, the study found that moderate and severe BPD were strongly associated with poor expressive and receptive communication skills at 18 to 26 months corrected age. However, neonatal brain size and growth metrics were not significantly associated with the variability in language skills. Conclusion: By utilizing neuroimaging techniques routinely employed in the neonatal intensive care unit (NICU), such as 2D HUS, this study aimed to lay the groundwork for a more multidisciplinary approach to clinical care by accurately identifying which areas of the brain are most crucial to monitor through serial 2D HUS exams in the presence of BPD. Furthermore, this study highlighted the need for continued investigation into additional mechanisms linking chronic lung disease of prematurity with language outcomes.