Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye

Abstract

ObjectiveThe present study was aimed at investigating the effects of anti‐seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE).MethodsPWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow‐up of PWWE was conducted using structured, general pregnant follow‐up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum.ResultsOf the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31‐fold (95% confidence interval (CI): 1.48–4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high‐dose ASMs.SignificanceBirth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

Comparative analysis of three decades' experience in the management of pregnant women with epilepsy: a real-life scenario

“…WWE's live births were 91.7%. As a matter of fact, 91.7% of the WWE in this study delivered live babies; this finding is similar to that from a Turkish study ( 10 ). Remarkably, more pregnancies ended with live births over time.…”

“…Unfortunately, there were some patients, even in the regular care group I, in whom VPA could not be discontinued, but the dosage could be reduced (<600 mg). Although the effects of VPA on the fetus have been discussed in a recent publication ( 10 ), a study from 1999 reported that VPA might have a negative impact on pregnancy in a dose-dependent manner ( 15 ). Therefore, we decreased the dose of VPA as much as we could to reduce the risk of side effects already in the early treatment groups (even in G2).…”

“…Many studies have shown that the risk is higher with VPA. In a recent study conducted at 21 centers, VPA was associated with a significantly higher risk of congenital malformations, whereas LTG had the weakest association ( 10 ). Other older agents, such as phenobarbital (PB) or phenytoin (PHT), have also been shown to have higher risks of teratogenicity compared with newer-type ASMs such as lamotrigine (LTG) and levetiracetam (LEV) ( 11 , 12 ).…”