Neurology, vol.66, no.3, pp.354-360, 2006 (SCI-Expanded)
Objective: To analyze seizure control and treatment in pregnant women with epilepsy. Methods: Seizure control and treatment were recorded prospectively in 1,956 pregnancies of 1,882 women with epilepsy participating in EURAP, an international antiepileptic drugs (AEDs) and pregnancy registry. Results: Of all cases, 58.3% were seizure-free throughout pregnancy. Occurrence of any seizures was associated with localization-related epilepsy (OR: 2.5; 1.7 to 3.9) and polytherapy (OR: 9.0; 5.6 to 14.8) and for tonic-clonic seizures, with oxcarbazepine monotherapy (OR: 5.4; 1.6 to 17.1). Using first trimester as reference, seizure control remained unchanged throughout pregnancy in 63.6%, 92.7% of whom were seizure-free during the entire pregnancy. For those with a change in seizure frequency, 17.3% had an increase and 15.9% a decrease. Seizures occurred during delivery in 60 pregnancies (3.5%), more commonly in women with seizures during pregnancy (OR: 4.8; 2.3 to 10.0). There were 36 cases of status epilepticus (12 convulsive), which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. AED treatment remained unchanged in 62.7% of the pregnancies. The number or dosage of AEDs were more often increased in pregnancies with seizures (OR: 3.6; 2.8 to 4.7) and with monotherapy with lamotrigine (OR: 3.8; 2.1 to 6.9) or oxcarbazepine (OR: 3.7; 1.1 to 12.9). Conclusions: The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported. Copyright © 2006 by AAN Enterprises, Inc. Indications:Unspecified number of patients with epilepsy. AuthorsConclusions:The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported. FreeText:Study endpoints included occurrence of seizures, occurrence of convulsive seizures (expressed as present or absent), changes in AED load (number of AEDs or change in dosage), and changes in seizure frequency (expressed as increase or decrease, using seizure frequency in the first trimester as reference). Patients:1882 patients (1956 pregnancies), age range 15.3 to 43.5 years (mean age 29.3 years). AED monotherapy: 1367 pregnancies (498 Tegretol, 238 lamotrigine, 41 oxcarbazepine, 117 phenobarbital, 44 phenytoin, 345 valproic acid and 84 other AED). AED polytherapy: 369 pregnancies. TypeofStudy:An open study investigating the seizure control and treatment strategies during pregnancy in patients with epilepsy treated with AEDs including Tegretol, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, and valproic acid. The EURAP (epilepsy pregnancy registry) study. DosageDuration:Dosage and duration not stated. Results:1,013 (58.3%) were seizure-free throughout pregnancy, but 723 (41.6%) had seizures. 406 (23.4%) cases had nonconvulsive seizures and 317 had convulsive seizures but could also in addition have nonconvulsive seizures. 503/736 (68.3%) pregnancies with generalized epilepsies were completely controlled compared to 451/913 (49.4%) of those with localization-related epilepsies. Polytherapy was associated with a greater risk for occurrence of any seizures (5.6 to 14.8) and of convulsive seizures (2.5 to 7.0). Occurrence of all seizures was associated with localization-related epilepsy (1.7 to 3.9) and oxcarbazepine monotherapy with a greater risk for occurrence of convulsive seizures (1.6 to 17.1). Using first trimester as reference, seizure control did not change in 1093/1718 (63.6%), 1013 (92.7%) of whom were seizure-free during the entire pregnancy. Of the remaining 625 pregnancies, 273 (15.9%) had a decrease in seizure frequency in the 2nd or 3rd trimester (or both), and 298 (17.3%; 86 had higher frequency both in 2nd and 3rd trimesters than in the 1st, 100 in the 2nd trimester, 110 in 3rd trimester and 2 had deterioration in the 2nd trimester) had an increase. In 54 pregnancies (3.1%), seizure frequency category changed in opposite directions in the 2nd and 3rd trimesters. Seizure occurred in 60 (3.5%;28 single primary or secondary generalized tonic-clonic seizures, 31 other seizure types, and 1 convulsive status epilepticus) patients during delivery, more commonly in patients with seizures during pregnancy (2.3 to 10). 14/60 patients with seizures during delivery had been seizure-free in the entire pregnancy and 5/29 patients with tonic-clonic seizures at delivery had only had nonconvulsive seizures during pregnancy. 36/1956 (1.8%; 12 convulsive) pregnancies had status epilepticus, which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. 19 of the pregnancies with status were in patients with generalized epilepsy and 17 with localization-related epilepsy. 34/36 pregnancies associated with status had a delivery of live born offspring. 1 patient with nonconvulsive status during the 1st trimester had a spontaneous abortion. AED treatment was not changed in 1089 pregnancies (62.7%). In 1/12 pregnancies, AED was switched to another. The number of AEDs was decreased in 57 pregnancies and increased in 51. AED dosages were reduced in 137 and increased in 390/1616 pregnancies with constant AED type and number. Treatment was altered more often in pregnancies with seizures (383/715) compared in those with complete seizure control (264/1013). The number of AEDs or their dosages was greater in 37.5% of uncontrolled pregnancies and reduced in 15%; seizure-free pregnancies were 17.7% and 8.6%. In the 639 pregnancies with constant AED type and number and with seizures, AED dosage was decreased in 10.9%, increased 35.8%, and unchanged in 53.2%. The number or dosages of AEDs were more often increased or reduced in pregnancies with incomplete seizure control (2.8 to 4.7) and 1.5 to 3.0). Increased in AED load was associated with lamotrigine (2.1 to 6.9) or oxcarbazepine (1.1 to 12.9) monotherapy. Increase (1.7 to 3.7) or decrease (2.5 to 4.3) in AED dosage occurred more frequently in pregnancies with incomplete seizure control. Increased in dosage of AEDs remained independently associated with lamotrigine (2.3 to 7.8) and oxcarbazepine (1.1 to 14.6) monotherapy.AdverseEffects:No adverse effects were mentioned.