Rethinking Seizure Care Blog

Antiseizure Drug for Newborns Shows Promise

Posted by RSC Diagnostics on Apr 22, 2022

Newborn baby in hospital with identification bracelet tag name-2

Seizures in newborns can cause major problems for the baby including motor disabilities, cognitive problems, epilepsy, and death. Unfortunately, seizures that occur in infants are often difficult to treat. They are often resistant to certain types of treatments because the seizures in neonates are different from seizures in adults and even older children. However, doctors often treat them the same way they do with other patients.

There is no question that improved treatment options for infants are needed, and there is the possibility that help could be on the horizon according to a recent retrospective study. Janet Soul, MD is the director of the Fetal-Neonatal Neurology Program at Boston Children’s Hospital. She and her colleagues from other centers looked at information from newborns who had electrographic or clinically suspected seizures.

An Old Drug with a New Purpose

There were 426 infants included in the study, and 64% of them had seizures that were nonresponsive to initial antiseizure medications. 16% of the newborns had status epilepticus, while 17% of them died in the NICU. Those who were found to have higher seizure severity had worse outcomes.

Dr. Soul has focused her efforts on finding ways to improve treatment and outcomes for these patients with neonatal seizures. It was about a decade ago that she started to look into a drug called bumetanide. This is not a new drug. It’s been around for many decades, and it has been used with infants as a diuretic.

Dr. Soul said, “There was some interesting basic science work showing that one of the reasons newborns have seizures is because their chloride gradient goes in the opposite direction from that in older children and adults. The big finding was that a chloride transporter called NKCC1 is very abundant in newborns’ brains. So, their neurons have such a much higher chloride concentration than older children and adults.”

The drug that is most commonly used with seizures in adults is benzodiazepines. Phenobarbital is used with babies. These drugs can work well to treat seizures in older patients, as they open the chloride channels. This helps make it easier for chloride to flow into the cells, which can reduce seizures. However, phenobarbital works differently in babies because of their “higher intracellular chloride concentrations.” It could end up causing the chloride to flow out of the cell, which could increase the seizures.

The Trial

However, bumetanide blocks NKCC1 in the kidneys. In animals, it was shown to block NKCC1 in the brain, which helped to stop seizures. The drug is considered safe, so she and her colleagues started a pilot randomized test in 2009.

Dr. Soul said, “Our trial was the first to test a novel drug with an age-specific mechanism of action — a drug uniquely suited to the newborn brain. It was also the first trial to employ a standard-therapy control group, which was key to measuring drug efficacy and safety.”

In the trial, one group with 27 newborns was to receive the drug bumetanide “added to standard phenobarbital therapy in a dose-escalation design.” The control group had 16 newborns that receive phenobarbital and a placebo of saline. The investigators who were evaluating the newborns were unaware of which treatment the infants received.

The results of the study were published in the Annals of Neurology. They found that the bumetanide helped to reduce seizure burden when compared with those who were in the control group. Higher doses of bumetanide resulted in better effects. Spurred on by the success, Boston Children's Hospital is going to be starting an even larger trial to see what the results will be.




Topics: Infant Epilepsy