Antiseizure medications linked with many obstetrical, perinatal complications, review finds
Women who took antiseizure medication had a more than doubled risk of spontaneous miscarriage, but separating the effects of the medical conditions necessitating these medications from those of the medications themselves is difficult, a meta-analysis of 75 studies found.
Antiseizure medications are associated with increased risk of obstetrical and perinatal complications, according to results of a systematic review and meta-analysis.
The review included studies of pregnant women taking the medications for any indication and untreated pregnant women. All studies investigated obstetric complications and fetal/neonatal complications other than congenital malformations and impaired neurodevelopment. A total of 75 studies with 16,941,373 pregnancies or live births (14,437,221 pregnancies with maternal outcome data and 14,938,972 live births with fetal/neonatal outcome data) were included. Findings were published by Neurology on Jan. 7.
Compared with pregnancies in women without conditions treated with antiseizure medication, pregnancies exposed to the treatments had increased odds of preterm birth (odds ratio [OR], 1.30; 95% CI, 1.09 to 1.54), cesarean section (OR, 1.43; 95% CI, 1.13 to 1.81), gestational diabetes (OR, 1.44; 95% CI, 1.07 to 1.94), induction of labor (OR, 1.46; 95% CI, 1.15 to 1.86), preeclampsia (OR, 1.33; 95% CI, 1.02 to 1.72), spontaneous miscarriage (OR, 1.42; 95% CI, 1.01 to 2.01), and spontaneous fetal loss (OR, 2.54; 95% CI, 1.04 to 6.24).
When researchers compared women who had the same indications but didn't received antiseizure medications versus those treated with the medications and unaffected women, they found that some of the differences in outcomes, including preterm birth, cesarean section, gestational diabetes, and preeclampsia, were largely attributable to the underlying condition, particularly epilepsy. The odds of spontaneous miscarriage, spontaneous fetal loss, elective cesarean section, five-minute APGAR score, and admission to the neonatal ICU were significantly higher with exposure to the medications than with the same conditions and no exposure, but the study authors noted that the results could have been confounded by differences in disease severity.
Polytherapy was associated with higher risk of the adverse outcomes, and the risk of small-for-gestational age differed across medications, with signals pointing to particular risks with clonazepam, oxcarbazepine, topiramate, and zonisamide, the study found.
The study authors cautioned that all included studies were observational and many were retrospective. They were also unable to account for the influence of dose, which may change depending on indication.
“Although some of these adverse outcomes are attributable to the underlying condition, particularly epilepsy, exposure to [antiseizure medication] seems to be associated with additional risks,” the authors wrote, noting that the findings can be incorporated into routine patient counseling. “Further studies are needed to better characterize relevant risk factors, including the role played by the severity of the underlying disease,” they concluded.