Abstracts

RATIONALE: Many women with epilepsy who become pregnant women need to take antiepileptic drugs (AED) to prevent the potentially harmful effects of seizures. However, retrospective studies have demonstrated an increased chance of having a child with a birth defect (BD) in these women. It is uncertain how much of this risk is directly caused by the AEDs and whether certain drugs or drug combinations are associated with a greater risk.
METHODS: An Australia-wide, prospective, voluntary, telephone-interview based, observational register enrolled three groups of women: those with epilepsy taking AEDs, those with epilepsy not taking AEDs, and those taking AEDs for a non-epileptic indication. The pregnancy outcomes are evaluated by follow-up interviews and by reference to hospital and treating doctors records.
RESULTS: In the first 30 months of the study (till December 2001) 333 eligible women have been enrolled, with all states and territories being represented. 293 pregnancies had been completed, of which 254 (86.7%) have been a healthy live birth, 19 (6.5%) a live birth with a birth defect, four an induced abortion because of a detected malformation on ultrasound, one a premature labour with a stillbirth and 11 (3.8%) a spontaneous abortion. Of completed pregnancies, 269 were exposed to at least one AED during the first trimester (carbamazepine - 124, valproate - 96, lamotrigine - 52, clonazepam - 20, phenytoin - 19, vigabatrin - 7, gabapentin - 9, topiramate - 6, tiagabine - 2, primidone - 2, acetazolamide and diazepam - 1). The incidence of birth defects in relation to each specific AED was: valproate (16.7%), phenytoin (10.5%), lamotrigine (7.7%) and carbamazepine (3.2%), none of which were significantly different from women with epilepsy not taking an AED (4.3%, p[gt]0.05). However, multivariate logistic regression analysis found valproate exposure to be independently associated with the occurrence of BD (O.R = 4.6, p=0.03). Additionally, the dose of valproate taken was higher in pregnancies with BD compared to those without (mean 2081 mg vs. 1146 mg, p[lt]0.0001). The incidence of folate supplementation being taken prior to conception did not differ for pregnancies with or without BD (69.6% vs. 66.4%, p[gt]0.05).
CONCLUSIONS: The model for the Australian Pregnancy Register has proved successful, with strong enrollment from all regions. The study is prospective and includes reference to all new AEDs approved in Australia over the past decade. Results to date provide evidence that exposure to valproate during the first trimester may be independently associated with a higher risk of an infant/fetus with a birth defect, particularly at higher doses.
[Supported by: Unrestricted grants from the The Epilepsy Foundation of Victoria, The Epilepsy Society of Australia, Pfizer Pharmaceuticals, Aventis Pharma, Sanofi-Synthelabo, Novartis Pharmaceuticals, Janssen-Cilag, Galaxo Smith Kline and UCB (Belgium).]; (Disclosure: Grant - Study supported by unrestricted grants from the The Epilepsy Foundation of Victoria, The Epilepsy Society of Australia, Pfizer Pharmaceuticals, Aventis Pharma, Sanofi-Synthelabo, Novartis Pharmaceuticals, Janssen-Cilag, Galaxo Smith Kline and UCB)