Antiepileptic monotherapy does not increase intrauterine death risk

By Lucy Piper, Senior medwireNews Reporter

Neither type nor dosage of antiepileptic drug (AED) affects the risk of intrauterine death among pregnant women with epilepsy when given as monotherapy, suggests research.

The only treatment-related factor found to increase the risk was the use of polytherapy, which the researchers, led by Torbjörn Tomson (Karolinska Institutet, Stockholm, Sweden), note “is best avoided to also reduce other teratogenic risks”.

The team reports in Neurology that the strongest predictor of intrauterine death was the presence of major congenital malformations (MCMs) in at least one of the parents, and suggests that “fetal loss is related more to intrinsic and possibly genetic parental or maternal transplacental factors than to epilepsy or its treatment.”

Indeed, “[f]ive of these pregnancies involved maternal MCMs of the uterus, which is an established risk factor for miscarriage in the general population”, they add.

The findings are based on data from the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) on 7055 pregnancies in epileptic women, of whom 1910 were taking lamotrigine, 1713 carbamazepine, 1171 valproic acid, 324 levetiracetam, 262 oxcarbazepine, 260 phenobarbital and 1415 polytherapy.

Intrauterine deaths occurred in 632 of the pregnancies (592 spontaneous abortions and 40 stillbirths) and rates were similar across the six monotherapies, ranging from 7.9% with lamotrigine to 8.6% with levetiracetam. The dose level at time of conception also had no effect on the risk of intrauterine death among the three AEDs for which the sample size was big enough to test – lamotrigine, carbamazepine and valproic acid.

For the women receiving polytherapy, however, the rate of intrauterine death was increased, at 12.1%, and the associated risk was increased by a significant 38% compared with monotherapy after accounting for confounding and prognostic factors.

A parental history of MCMs increased the risk by 92%, and they were present in 15 (2.4%) of the 632 pregnancies that ended in intrauterine death compared with 72 (1.1%) of the pregnancies that ended with a healthy delivery.

Other factors that were associated with an increased risk of intrauterine death, but to a lesser extent, were older maternal age, previous intrauterine deaths and undetermined or unclassified epilepsy compared with idiopathic generalised epilepsy.

Experiencing convulsions during pregnancy did not have an identifiable effect on intrauterine death, observe the researchers, with only one of the 32 cases of convulsive status epilepticus ending in a stillbirth. This is consistent with earlier data “suggesting that the rate of spontaneous abortions is not increased among women with epilepsy”, they say.

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