Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia

Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury by increasing cerebral metabolic demand, causing fluctuations in oxygenation and perfusion, and triggering the release of excitatory neurotransmitters. Anticonvulsant therapy has been used in infants with perinatal asphyxia in order to prevent seizures. However, long term anticonvulsant therapy may lead to inhibition of brain development. Therefore, the routine use of anticonvulsant therapy to prevent seizures following perinatal asphyxia needs to be evaluated.

To assess the effect of administering anticonvulsants to infants of 37 weeks gestation or more following perinatal asphyxia on death or subsequent severe neurodevelopmental disability and/or the prevention of seizures.

Relevant randomised controlled trials were identified using a combination of electronic database searches, hand searches and a search of the Cochrane Controlled Trials Registry.

All randomised or quasi-randomised controlled clinical trials that reported data comparing the following outcomes: mortality, neurodevelopmental disability, neonatal seizures and adverse events, following anticonvulsant therapy in term infants (37 weeks or more) compared to controls (with or without placebo) following perinatal asphyxia.

Methodological quality and validity of studies were assessed without consideration of the results. Data relevant to the outcome were extracted and analysed.

Seven randomised or quasi-randomised controlled trials that met the selection criteria were included. No studies were of sufficient methodological quality and size to demonstrate a valid, clinically significant change in the risk of mortality or severe neurodevelopmental disability. A meta-analysis combining five studies comparing barbiturates with conventional therapy following perinatal asphyxia demonstrated no difference in risks of death, severe neurodevelopmental disability, or the combined outcome of death or severe neurodevelopmental disability.

At the present time, anticonvulsant therapy to term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice, other than in the treatment of prolonged or frequent clinical seizures. Any future studies should be of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability.