Discussion
death, hypothermia, NDI, brain injury, HIE, white matter lesions
MRS
In this large, prospective cohort of infants with HIE who underwent harmonized neuroimaging in the first week of age, we found several imaging biomarkers that were associated with 2-year neurodevelopmental outcomes including MRI severity of the injury, presence of central gray, peripheral white matter or global patterns of injury, and elevated lactate/NAA and lower NAA/creatine ratios on MRS. Although severe injury was strongly correlated with adverse outcomes, infants with mild or moderate brain injury exhibited rates of NDI and Bayley-III scores that were similar to infants with no apparent brain injury on MRI.Clinicians frequently rely on brain MRI findings to counsel families on their infant’s future prognosis following HIE. Neonatal neuroimaging retains its predictive value even after infants have undergone therapeutic hypothermia, and MRS measurement of lactate/NAA in the thalamus has been shown to outperform MRI findings in predicting adverse outcomes after HIE.Like others,Punctate white matter lesions were seen in 12% of infants enrolled in a large MRI study of healthy term newborns who had a normal exam and normal neurodevelopmental outcome.The ideal timing of brain MRI for predicting future neurodevelopment is unknown. Although some studies suggest an MRI performed in the first week of age may be most predictive,The fact that a static image of the brain obtained during the first week of age fails to accurately discriminate between milder forms of impairment is not surprising, as it does not measure the long trajectory of development that will continue to occur within the highly plastic newborn brain. It is well-known that maternal education is positively associated with better outcomes and that a disadvantaged socioeconomic status is associated with worse neurodevelopment after injury in both the termStrengths of our study include the large sample size, prospective study design, harmonized neuroimaging protocol, short time window within which neuroimaging was performed, and the use of a validated MRI scoring system that could detect lesions in most regions of the brain.In conclusion, several features on neonatal brain MRI and MRS were associated with worse neurodevelopmental outcomes after HIE. Although the finding of severe or global injury strongly predicts death or severe NDI, for infants with milder forms of brain injury, a range of outcomes are possible. Additional studies may improve prognostication by incorporating multiple modalities of biomarkers of brain injury.