Neonatal seizures occur in an average of 2.6 per 1,000 newborn babies, usually (although not always) due to damage to the brain before or during birth. This damage can be caused by a number of things, such as lack of oxygen, infection, or haemorrhage. Other causes of neonatal seizures include low levels of glucose, magnesium or calcium in the blood. In rare cases, a lack of vitamin B may also cause seizures in newborns.

The current treatment of choice for neonatal seizures is the anti-epileptic drug (AED) phenobarbital; however research has increasingly shown that this drug has limited efficacy and that it carries a risk of cognitive side-effects in infants and toddlers. Animal studies have also shown that phenobarbital triggers neuronal death, and this can have serious implications for development.

Levetiracetam, another AED, has been shown to be safe and well-tolerated by children aged four years and above, in the treatment of partial seizures. It does not appear to interact with other drugs in any significant way, or trigger neuronal death (in animal models). Researchers in Germany have completed a small pilot study, looking at whether levetiracetam might be suitable treatment option for neonatal seizures.

With formal consent from the mothers, the team recruited newborn babies, who had a birth weight over 2Kg and who were born after 30 weeks of pregnancy, and who presented with neonatal seizures. Babies whose seizures were due to low glucose / magnesium / calcium or to a vitamin B deficiency were excluded, along with who had received more than two single doses of phenobarbital or treatment with any other AED. A total of six babies went on to take part in the study after exclusions.

Each child was given levetiracetam orally over three days, increasing the dose by 10mg per Kg of body weight each day. Levetiracetam treatment was stopped after three days if it alone failed to control the seizures and other AEDs were required. Additional treatment with single daily doses of phenobarbital was permitted between days one and three, if required. In cases where seizures were successfully controlled after three days, levetiracetam treatment was continued for three months. At this point decisions regarding further treatment were taken on an individual basis, and all babies were followed-up to eight months.

All of the babies were seizure free after six days, and four of the six remained seizure free during the three month study period. One child suffered a single seizure at the age of four weeks, and was given an increased dose of levetiracetam, which proved successful. Another baby suffered from seizures after two months and has not responded to any AED since.

After the full eight months, five infants remained seizure free; two without any medication, and one with levetiracetam in combination with another AED. The remaining two babies became seizure free having discontinued levetiracetam and started other AEDs.

The team observed no severe side-effects of levetiracetam, but one child did become slightly drowsy during the initial three days.

These results are promising, but a note of caution is needed. Although all of the babies became seizure free during the first six days of the study, we cannot say for sure that this was due to the levetiracetam. For example, for some it could have been spontaneous recovery and nothing to do with treatment. A control group of untreated neonatal seizures would have given an idea of the rate of spontaneous recovery, but this was ethically unviable. In addition, the effects of the single doses of phenobarbital, which were permitted between days one and three (and in the event were administered to all of the babies), cannot be ruled out. Could the levetiracetam and phenobarbital have acted together to produce seizure freedom? Another point is that the study was very small, and a much larger trial would need to be carried out in order to confirm the benefits of levetiracetam, and whether or not it causes adverse side-effects in newborns.

Despite these reservations, the findings are still positive, because they could direct further research. They might form the basis of a much larger randomized controlled trial, to further assess the potential of levetiracetam as an effective treatment option for neonatal seizures.

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