Elsevier

The Lancet

Volume 361, Issue 9359, 1 March 2003, Pages 736-742
The Lancet

Articles
Origin and timing of brain lesions in term infants with neonatal encephalopathy

https://doi.org/10.1016/S0140-6736(03)12658-XGet rights and content

Summary

Background

The role of intrapartum asphyxia in neonatal encephalopathy and seizures in term infants is not clear, and antenatal factors are being implicated in the causal pathway for these disorders. However, there is no evidence that brain damage occurs before birth. We aimed to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both result from early antenatal insults.

Methods

We used brain MRI or post-mortem examination in 351 fullterm infants with neonatal encephalopathy, early seizures, or both to distinguish between lesions acquired antenatally and those that developed in the intrapartum and early post-partum period. We excluded infants with major congenital malformations or obvious chromosomal disorders. Infants were divided into two groups: those with neonatal encephalopathy (with or without seizures), and evidence of perinatal asphyxia (group 1); and those without other evidence of encephalopathy, but who presented with seizures within 3 days of birth (group 2).

Findings

Brain images showed evidence of an acute insult without established injury or atrophy in 197 (80%) of infants in group 1, MRI showed evidence of established injury in only 2 infants (<1%), although tiny foci of established white matter gliosis, in addition to acute injury, were seen in three of 21 on post-mortem examination. In group 2, acute focal damage was noted in 62 (69%) of infants. Two (3%) also had evidence of antenatal injury.

Interpretation

Although our results cannot exclude the possibility that antenatal or genetic factors might predispose some infants to perinatal brain injury, our data strongly suggest that events in the immediate perinatal period are most important in neonatal brain injury.

Introduction

Until recently, hypoxic-ischaemic events in the perinatal period were assumed to be the main cause for early neonatal encephalopathy, seizures, or both. They were also thought to be a major cause of brain damage in infants with a clinical diagnosis of cerebral palsy. For the normally developed non-dysmorphic infant born at term who develops neonatal encephalopathy or early seizures after an uneventful pregnancy, an insult to the brain of perinatal origin seems the logical conclusion. Results from Hagberg and colleagues'1 study of the prevalence, cause, and timing of cerebral palsy in Sweden lend support to this view. These investigators reported a perinatal origin for cerebral palsy in 36% of affected term infants, and asphyxia of intrapartum onset was judged to be the cause of the disorder in most. However, there is often an absence of evidence of severe intrapartum asphyxia in infants with neonatal encephalopathy, and conversely, many infants who do have signs of fetal distress and asphyxia do not develop neurological sequelae.2, 3, 4, 5, 6 These observations, together with evidence that there is a higher incidence of maternal illness, antenatal complications, and adverse social factors in infants with neonatal encephalopathy, seizures, or both7 have led to the view that the main causes of such conditions occur before birth.

Our aim was to test the hypothesis that neonatal encephalopathy, early neonatal seizures, or both in the term infant are the result of early antenatal insults.

Section snippets

Patients

Between Jan 1, 1992, and Dec 31, 1998, we recruited 351 fullterm infants born in, or referred to, two tertiary referral intensive care units—Wilhelmina Children's Hospital, Utrecht, Netherlands, and Hammersmith and Queen Charlotte's Hospitals, London, UK. Both units provide a regional specialist service for the investigation of neurologically abnormal neonates.

All infants in the study were born after more than 36 weeks' gestation and presented within 72 h of birth with neonatal encephalopathy,

Results

We included 351 infants. 261 infants met our criteria for neonatal encephalopathy and 90 had seizures within 72 h of birth.

Discussion

Our findings show that more than 90% of term infants with neonatal encephalopathy, seizures, or both, but without specific syndromes or major congenital defects, had evidence of perinatally acquired insults, and there was a very low rate of established brain injury acquired before birth. Reasons for injuries of perinatal onset remain poorly understood. The frequency of risk factors in infants with and without established brain abnormality did not differ greatly, but the study was not designed

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