Term-equivalent functional brain maturational measures predict neurodevelopmental outcomes in premature infants

Background: Term equivalent age (TEA) brain MRI identifies preterm infants at risk for adverse neurodevelopmental outcomes. But some infants may experience neurodevelopmental impairments even in the absence of neuroimaging abnormalities. Objective: Evaluate the association of TEA amplitude-integrated EEG (aEEG) measures with neurodevelopmental outcomes at 24–36 months corrected age. Methods: We performed aEEG recordings and brain MRI at TEA (mean post-menstrual age of 39 (±2) weeks in a cohort of 60 preterm infants born at a mean gestational age of 26 (±2) weeks. Forty-four infants underwent Bayley Scales of Infant Development, 3rd Edition (BSID-III) testing at 24–36 months corrected age. Developmental delay was defined by a score greater than one standard deviation below the mean (<85) in any domain. An ROC curve was constructed and a value of SEF₉₀ < 9.2, yielded the highest sensitivity and specificity for moderate/severe brain injury on MRI. The association between aEEG measures and neurodevelopmental outcomes was assessed using odds ratio, then adjusted for confounding variables using logistic regression. Results: Infants with developmental delay in any domain had significantly lower values of SEF₉₀. Absent cyclicity was more prevalent in infants with cognitive and motor delay. Both left and right SEF₉₀ < 9.2 were associated with motor delay (OR left: 4.7(1.2–18.3), p = 0.02, OR right: 7.9 (1.8–34.5), p < 0.01). Left SEF₉₀ and right SEF₉₀ were associated with cognitive delay and language delay respectively. Absent cyclicity was associated with motor and cognitive delay (OR for motor delay: 5.8 (1.3–25.1), p = 0.01; OR for cognitive delay: 16.8 (3.1–91.8), p < 0.01). These associations remained significant after correcting for social risk index score and confounding variables. Conclusions: aEEG may be used at TEA as a new tool for risk stratification of infants at higher risk of poor neurodevelopmental outcomes. Therefore, a larger study is needed to validate these results in premature infants at low and high risk of brain injury.