Fetal Outcomes of Anti-epileptic Drug Use in Pregnancy: Teratologic Approach

Abstract

Objective: To examine the fetal effects of valproic acid (VPA) and carbamazepine (CBZ) used as monotherapy during pregnancy, to determine the anomalies, and to compare them with a control group and previous literature.

Materials and Methods: The data of 10,562 pregnant women who presented to our outpatient clinic between 2009 and 2018 for teratologic consultation were reviewed retrospectively. The study group consisted of 95 pregnant women (VPA: n=49, CBZ: n=46) who were followed up with the diagnosis of epilepsy and who used VPA or CBZ only as monotherapy during pregnancy. The control group was composed of 88 pregnant women in the same age group, who had no chronic disease, were not expected to cause an increased risk in the first trimester, and used short-term risk group B drugs due to different health problems.

Results: The difference between the prevalence of major, minor anomalies, and behavioral defects between pregnant women using VPA and the control group was statistically significant (p<0.044, p<0.001, p<0.001, respectively). The frequency of minor anomalies was statistically significant between pregnant women using CBZ and the control group, but there was no statistically significant relationship between major anomalies and behavioral defects (p=0.116, p<0.018, p=0.116, respectively). Despite receiving anti-epileptic treatment during pregnancy, the frequency of major and minor anomalies in pregnant women who had two or more seizures compared to the control group.

Conclusion: Increasing the anomaly frequency of both epileptic attacks and anti-epileptic treatment constitutes a severe handicap for pregnant women. In teratologic counseling in patients with epilepsy, especially in the first trimester of pregnancy, combined treatment should be avoided if possible and a single antiepileptic drug with the least adverse effects should be chosen. If this is not medically possible, dose adjustment should be made to the most effective and lowest dose and it is recommended to continue mono/combination therapy.