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Commentary on: Razaz N, Tomson T, Wikström AK, et al. Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurol. 2017;74(8):983–991.
Implications for practice and research
Epilepsy in pregnancy can increase the risk of adverse outcomes for the mother but treatment for epilepsy with medication does not appear to increase these risks.
Research must focus on the clinical nuances of the individual patient and take into account disease severity, antiepileptic drug (AED) type and dose and type and other adverse events (eg, miscarriage and malformations) that are not accounted for by administrative data.
Epilepsy is one of the most common neurological conditions in pregnancy. Up to 1% of all pregnant women may be epileptic1 and both seizures and the treatment for seizures, antiepileptic drugs (AEDs), have the potential to cause harm to the woman as well as the fetus. Whether AEDs increase the risk of harm is unclear, especially with newer AEDs where there is little short-term and long-term information. Obtaining information is important because up to 40% of pregnant women may be incompliant with AED treatment2 because of concerns for drug effects.
Razaz et al 3 used linked administrative data to determine perinatal outcomes for women diagnosed with epilepsy from hospital inpatient and outpatient records in Sweden between 1997 and 2011. A subset of women who were treated with AEDs 30 days before the estimated date of conception to birth between 2005 and 2011 were also identified from the Prescribed Drug Registry and their outcomes were assessed with propensity scoring to optimise adjustment for covariates such as maternal habitus and physical and psychiatric comorbidities.
Of the 1 429 652 singleton births >22 weeks gestation, 5373 infants were born to 3586 women with epilepsy. There were 3231 births between 2005 and 2011, of which 1363 (42.2%) were exposed to AEDs at least 1 month before and/or during pregnancy. The most commonly used AEDs were lamotrigine (n=628, 46.1%) and carbamazepine (n=418, 30.7%) and 181 (13.3%) were exposed to multiple agents. Women with epilepsy were at an increased risk of almost all perinatal complications. Compared with other epileptic women, those who were treated with AEDs were not at increased risk of complications, including major congenital malformations, one of the most prevailing concerns for women requiring AED during pregnancy.
Administrative data provide cost-effective, valuable and contemporary information on many conditions that would otherwise be difficult, if not impossible, to obtain by other means. In this study, Razaz et al demonstrate through linked data analysis that AEDs did not increase the risk of complications in live births >22 weeks gestation, including congenital malformations.3 Artama et al used data from the Finnish National Health Register (1996–2008) to examine the outcomes of 4867 live and still births of women with epilepsy and exposed to AEDs (3067, 63%) and found that AED treatment (n=1800) only slightly increased the risk of admission into a neonatal care unit.4 Importantly though, women with epilepsy are at higher risk of external problems that may be caused by seizures (eg, accidents) which may be worse if the women are left untreated.5
It must be recognised that administrative data cannot provide many of the important clinical nuances for practice for example, the aetiology of epilepsy, the types or doses of AED. In a meta-analyses of 22 prospective cohort studies including six registry-based studies of neurodevelopmental outcomes of children exposed to various AEDs, Bromley et al noted a dearth of information on new AEDS but found a strong association, especially at higher doses, between valproate in particular, with reduced childhood IQ. This emphasises the need to consider the implications of administrative data research on the individual patient and to take into account the risks and benefits between uncontrolled epilepsy and AED.6
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.