Effects of a five-day neuroprotective care bundle on severe intraventricular hemorrhage and mortality in extremely low birth weight neonates: a retrospective evaluation across three practice eras

Background Neuroprotective bundles of care (BoC) aim to reduce intraventricular hemorrhage (IVH) in extremely preterm infants, but optimal duration and interaction with physiologic risk factors such as hypercapnia remain uncertain. Methods We performed a single-center retrospective cohort study of infants born ≤28 weeks of gestation or with extremely low birth weight (<1,000 g, ELBW) across three practice eras: pre-intervention, 3-day BoC, and 5-day BoC. The bundle emphasized midline head positioning and cerebral hemodynamic stability. The primary outcome was death or severe IVH (Papile grade 3 or 4). Multivariable logistic regression adjusted for illness severity (CRIB II), antenatal steroids, and maximum arterial carbon dioxide (CO 2 ). CO 2 /outcome relationships were examined by era. Results Among 285 infants, unadjusted outcomes were similar across eras; however, after adjustment for measured differences in illness severity and physiologic risk factors, the 5-day BoC era was associated with lower odds of death and the composite outcome. Higher maximum arterial CO 2 was associated with increased predicted risk of severe IVH and the composite outcome across eras. Conclusions The 5-day BoC era was associated with improved adjusted outcomes despite similar unadjusted IVH rates. Because implementation coincided with other evolving neonatal practices, including higher use of noninvasive respiratory support these findings should be interpreted as an era-associated effect rather than an isolated effect of bundle duration. Prospective studies are needed to determine the independent contribution and optimal duration of neuroprotective bundles.