Browsing by Author "Lindhout, D"

Now showing 1 - 4 of 4
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    Antiepileptic drugs and intrauterine death A prospective observational study from EURAP
    (NEUROLOGY, 2015) Tomson, T; Battino, D; Bonizzoni, E; Craig, JJ; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Vajda, F
    Objective:To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs).Methods:The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint.Results:Of 7,055 pregnancies exposed to monotherapy with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar across the different monotherapies (8.2%; 95% confidence interval [CI] 7.5%-8.9%), higher with polytherapy (12.1%; 95% CI 10.5%-13.9%), but showed no relationship with AED dose in monotherapy at conception. Multivariable analysis including 11 covariates in addition to the different AED exposures showed that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased with later gestational week at enrollment (RR 0.84; 0.82-0.86).Conclusions:The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents.
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    Dose-dependent teratogenicity of valproate in mono- and polytherapy An observational study
    (NEUROLOGY, 2015) Tomson, T; Battino, D; Bonizzoni, E; Craig, J; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Vajda, F
    Objective: To assess the risk of major congenital malformations (MCMs) in association with maternal use of valproic acid (VPA) in monotherapy or adjunctive therapy, and its relationship with dose. Methods: The analysis was based on prospectively acquired data from EURAP, a registry enrolling women treated with antiepileptic drugs (AEDs) in early pregnancy, in which the primary outcome is presence of MCMs at 1 year after birth. Exposure was defined as type and dose of AEDs at time of conception. A comparison was made among 3 exposure types: (1) VPA monotherapy (n = 1,224); (2) VPA combined with lamotrigine (LTG) (n=159); and (3) VPA combined with another AED but not LTG (n=205). Results: The frequency of MCMs at 1 year after birth was 10.0% for VPA monotherapy, 11.3% for exposures to VPA and LTG, and 11.7% for exposures to VPA + another (non-LTG) AED. Regardless of exposure group, the frequency of MCMs increased with dose of VPA, being highest at doses >= 1,500 mg/d (24.0% for monotherapy, 31.0% for VPA + LTG, and 19.2% for VPA + other AEDs), and was similar across treatment groups at the lowest VPA dose level of,700 mg/d (5.9% for monotherapy, 7.0% for VPA + LTG, and 5.4% for VPA + other AEDs). Conclusions: The risk of MCMs associated with VPA exposure increases with increasing VPA dose, both in the presence and in the absence of one concomitant AED, and appears to be related primarily to the dose of VPA.
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    EURAP, an international anti-epileptic drugs and pregnancy registry.
    (PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, 2015) Craig, J; Tomson, T; Battino, D; Bonizzoni, E; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Vajda, F
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    Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP
    (EPILEPSIA, 2016) Tomson, T; Battino, D; Bonizzoni, E; Craig, J; Lindhout, D; Perucca, E; Sabers, A; Thomas, SV; Vajda, F
    Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesian statistics, we compared seizure control in pregnancies where VPA was withdrawn (withdrawal group, n = 93), switched to another AED (switch group, n = 38), or maintained (maintained-therapy group, n = 1,588) during the first trimester. The probability of primarily or secondarily generalized tonic-clonic seizures (GTCS) was lower in the maintained-therapy group compared with the other two groups, both in the first trimester and for the entire duration of pregnancy. GTCS were twice as common during pregnancy in the withdrawal (33%) and switch groups (29%) compared with the maintained-treatment group (16%). Limitations in the data and study design do not allow to establish a causeeffect relationship between treatment changes and seizure outcome, but these observations provide a signal that withdrawal of, or switch from, VPA during the first trimester could lead to loss of seizure control, and highlight the need for a specifically designed prospective observational study.