Presumed etiology of preterm birth: brain injury and neurodevelopmental outcomes.

Aim: To determine the relationship between presumed preterm birth (PTB) etiology and the incidence of brain injury, and neurodevelopmental outcomes at 3 and 4.5 years.

Subjects and methods: Prospective cohort study including 222 neonates born at 24-32 weeks' gestation. The presumed PTB etiology was defined by placental histopathology and other clinical features. Outcome measures included brain injury defined on MRI, neurodevelopmental outcomes using the Bayley Scales of Infant and Toddler Development, the Movement Assessment Battery for Children, Wechsler Preschool and Primary Scale of Intelligence, Beery Buktenica Developmental Test of Visual-Motor Integration.

Results: Presumed PTB etiology was inflammatory in 85 (38%), vascular in 57 (25%), multiple gestation in 56 (25%) and idiopathic in 24 (11%) neonates. Cognitive outcome at 3 years was marginally lower in the inflammatory group (Beta = -6.2, P = 0.05) relative to multiple gestation. At 4.5 years, white matter injury was associated with significantly lower motor scores (P = 0.004) and there were no significant associations between PTB etiology and WPPSI-III IQ scales or MABC-2 scores.

Conclusions: The lack of association between presumed PTB etiology (using integrated clinical phenotype and placental pathology) and cognitive/motor outcomes suggests that postnatal morbidities and brain injury are pivotal in the neurodevelopmental trajectory of these infants.

Impact: The presumed etiology of preterm birth (PTB), based on placental histopathology and clinical features, does not predict long-term neurodevelopmental outcomes, such as cognitive scores at 4.5 years. Postnatal factors, including neonatal morbidities (e.g., bronchopulmonary dysplasia, retinopathy of prematurity, brain injury), are more significant in determining neurodevelopmental outcomes than the initial PTB cause. Placental histopathology helps identify PTB causes but shows no direct link to brain injury or neurodevelopmental outcomes. Infants with "idiopathic" PTB (no clear cause) have the greatest white matter injury burden, suggesting genetic or unrecognized factors.