Origin and Timing of Brain Lesions in Term Infants With Neonatal Encephalopathy

Abstract

It is not clear whether intrapartum asphyxia is an important factor in neonatal encephalopathy and seizures in term infants. Antenatal factors have been implicated, but there is no firm evidence that brain damage occurs in utero. This study examined the proposal that neonatal encephalopathy and early postnatal seizures, or both, are sequelae of early adverse antenatal events. Cerebral magnetic resonance imaging (MRI) or autopsy was carried out in 351 full-term infants having encephalopathy and/or seizures within 72 hours of birth. Infants with major congenital malformations or known chromosomal disorders were excluded. The 261 infants placed in group 1 had a diagnosis of neonatal encephalopathy, with or without seizures, as well as evidence of perinatal asphyxia. The 90 group 2 infants presented with seizures but failed to meet diagnostic criteria for encephalopathy. Cerebral MRI disclosed evidence of acutely evolving lesions not related to established injury or atrophy in 80% of group 1 infants. These lesions, which usually were bilateral, were consistent with a hypoxic-ischemic insult. In addition to white matter, abnormalities were found in the basal ganglia, thalamus, or cortex. Only 2 group 1 infants, fewer than 1% of the total, had evidence of established injury. Three of 21 autopsies showed, in addition to an acutely evolving lesion, very small foci of established gliosis in the periventricular white matter. Acute ischemic or hemorrhagic lesions were found in 69% of group 2 infants. Two infants (3%) had, in addition, changes of antenatal injury. Thirteen of the 28 remaining group 2 infants had MRI findings of a specific nonhyoxic-ischemic condition. The other 15 infants had normal scans. Seven of 10 infants with no specific diagnosis continued to have seizures. Antenatal risk factors that were significantly more frequent in infants having apparent antenatal lesion or disorders of genetic or neurometabolic origin included a family history of seizures or neurologic disorder, low birth weight, head circumference below the 10th percentile, and low maternal age. In this study, more than 90% of term infants with neonatal encephalopathy and/or early seizures had evidence of a perinatally acquired insult. Established brain injuries acquired before birth were quite infrequent. The findings do not rule out the change that antenatal (or genetic) factors could predispose some infants to perinatal brain injury.