Abstract
BackgroundThere is increasing evidence that neonatal seizures in term neonates with stroke, asphyxia or brain haemorrhage might be associated with adverse neurodevelopment and development of epilepsy. The extent of this association is not known. The objective of this study was to assess the possible impact of neonatal seizures on these outcomes and if possible calculate a relative risk.MethodsA systematic review and meta-analysis was performed (study period January 2000–June 2015). PubMed, Medline and Embase were searched for cohort studies evaluating neurodevelopmental outcome at the age of at least 18 months or development of epilepsy in surviving term neonates with or without neonatal seizures. The methodological quality of included studies was assessed and data extractions were performed in a standardized manner by independent reviewers. Pooled Relative Risks (RR) with 95% confidence intervals for adverse outcome were calculated if possible.ResultsOut of 1443 eligible studies 48 were selected for full text reading leaving 9 cohort studies for the final analyses (4 studies on stroke, 4 on perinatal asphyxia and one on cerebral hemorrhage). For all cases with stroke or asphyxia combined the pooled risk ratio (RR) for adverse outcome when suffering neonatal seizures was 7.42 (3.84–14.34); for neonates with perinatal asphyxia: 8.41 (4.07–17.39) and for neonates with stroke: 4.95 (1.07–23.0). The pooled RR for development of late onset epilepsy could only be determined for infants suffering from stroke: 1.48 (0.82–2.68). Results were biased and evidence sparse.ConclusionsThe presence of neonatal seizures in term newborns with vascular or hypoxic brain injury may have an impact on or be a predictor of neurodevelopmental outcome. The biased available data yield insufficient evidence about the true size of this association.
Highlights
There is increasing evidence that neonatal seizures in term neonates with stroke, asphyxia or brain haemorrhage might be associated with adverse neurodevelopment and development of epilepsy
We followed the guidelines from the Meta-analysis of Observational Studies in Epidemiology (MOOSE) [11], Preferred Reporting Items for Systematic Reviews and Meta-Analyses the (PRISMA) statements [12], and the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy
A total of 48 articles were selected for full text reading. From these 48 articles 39 studies were excluded as data could not be reliably extracted, leaving 9 studies for the final analyses: 4 studies on stroke, [14,15,16,17], 4 studies on hypoxic ischemic encephalopathy (HIE), [18,19,20,21] and one study on cerebral hemorrhage [22]
Summary
There is increasing evidence that neonatal seizures in term neonates with stroke, asphyxia or brain haemorrhage might be associated with adverse neurodevelopment and development of epilepsy. The extent of this association is not known. The developing brain is highly vulnerable to hypoxic–ischemic insults and these insults often result in neonatal seizures [3, 4]. The most important causes of neonatal seizures are hypoxic ischemic encephalopathy (HIE) due to perinatal asphyxia (50–60%), stroke (10%), and cerebral haemorrhage (10%) [3, 6]. There is increasing evidence that neonatal seizures are associated with adverse neurodevelopmental outcome, defined as cerebral palsy, psychomotor retardation and It has been hypothesized that this hyper excitability of the brain is caused by interplay between a high density synaptic network, an abundance of glutaminergic neurons, paradoxical neonatal excitatory actions of primary inhibitory networks and differences in membrane potentials in the immature dendrites [1, 3, 5].
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