Cumulative Hydrocortisone Exposure and Early Brain Volumetrics in Very Low Birth Weight Infants: Associations with Neurodevelopmental Outcomes

<b>Background/Objectives</b>: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. <b>Methods</b>: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18-24 months. <b>Results</b>: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, <i>p</i> = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, <i>p</i> = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, <i>p</i> < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, <i>p</i> = 0.016) and reduced head circumference (aOR 4.45, <i>p</i> = 0.016). <b>Conclusions</b>: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks.