Association between volumes of preterm brain structures, neurodevelopmental outcomes, and neonatal morbidities

Abstract Purpose : Premature infants are prone to impaired neurodevelopmental outcomes due to brain injury or underdevelopment. However, these outcomes may be present without any brain lesions. The association between neonatal morbidities and the volume of segmentalbrain structures is not fully understood. Therefore, we analyzed the association between brain structure volumes, neonatal morbidities, and neurodevelopmental outcomesin extremepreterm infants. Methods : This retrospective cohort study included 158 extreme preterm infants, in whom brain magnetic resonance imaging at term equivalent age (TEA-MRI) and neurodevelopmental evaluation wereperformed at a corrected age of 18–24 months.Patients with congenital anomalies or significant brain lesions, such as high-grade intraventricular hemorrhage and periventricular leukomalacia were excluded. Medical records, including the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III), of preterm infants were reviewed and analyzed. FreeSurfer infant software was used to evaluatebrain structures, while volumes of specific brain regions were adjusted for gestational age and postmenstrual age on MRI using multivariate regression analysis. Results : Preterm infants with neurodevelopmental impairment had smaller midbrain (aOR 0.804, 95% CI 0.647–0.998). Neonatal morbidities of preterm infants included respiratory distress syndrome (RDS), which was associated with a smaller volume of the medulla (aOR 0.593, 95% CI 0.387–0.908), ventral diencephalon (aOR 0.730, 95% CI 0.572–0.932), and putamen (aOR 0.874, 95% CI 0.788–0.969). Patent ductus arteriosus (PDA) requiring surgery was associated with a smaller volume of the pons (aOR 0.727, 95% CI 0.594–0.889) and vermis (aOR 0.766, 95% CI 0.646–0.907). Retinopathy of prematurity (ROP) requiring surgery was associated with a smaller pons volume (aOR 0.729, 95% CI 0.600–0.886). Necrotizing enterocolitis (NEC) requiring surgery was associated with a smaller volume of the pons (aOR 0.751, 95% CI 0.661–0.854), vermis (aOR 0.832, 95% CI 0.745–0.930), and cerebellum (aOR 0.974, 95% CI 0.960–0.989). Conclusions : Among preterm infants without significant brain injuries, smaller volume of midbrain was associated with impaired neurodevelopment. RDS and morbidities requiring surgery such as PDA, ROP, and NEC were associated with reduced segmental volumes of the brain in preterm infants.