Seizure control and treatment changes in pregnancy: Observations from the EURAP epilepsy pregnancy registry

Authors

  • Dina Battino,

    Corresponding author
    1. Epilepsy Center, Department of Neurophysiology and Experimental Epileptology, I.R.C.C.S. Neurological Institute “Carlo Besta” Foundation, Milan, Italy
    • Address correspondence to Dina Battino, Epilepsy Center, Department of Neurophysiology and Experimental Epileptology, I.R.C.C.S. Neurological Institute “Carlo Besta” Foundation, Via Celoria 11 20133 Milan, Italy. E-mail: dbattino@istituto-besta.it

    Search for more papers by this author
  • Torbjörn Tomson,

    1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Erminio Bonizzoni,

    1. Department of Occupational Health “Clinica del Lavoro L. Devoto”, Section of Medical Statistics and Biometry “G.A. Maccacaro”, Faculty of Medicine and Surgery, University of Milan, Milan, Italy
    Search for more papers by this author
  • John Craig,

    1. Department of Neurology, Belfast Health and Social Care Trust, Belfast, Ireland
    Search for more papers by this author
  • Dick Lindhout,

    1. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
    2. SEIN – Epilepsy Institute in the Netherlands, Heemstede/Zwolle, The Netherlands
    Search for more papers by this author
  • Anne Sabers,

    1. The Epilepsy Clinic, Department of Neurology, Rigshospitalet University State Hospital, Copenhagen, Denmark
    Search for more papers by this author
  • Emilio Perucca,

    1. Department of Internal Medicine and Therapeutics, University of Pavia, and Clinical Trial Center, National Institute of Neurology IRCCS C. Mondino Foundation, Pavia, Italy
    Search for more papers by this author
  • Frank Vajda,

    1. Departments of Medicine and Neurology, University of Melbourne, Royal Melbourne Hospital, Melbourne, Victoria, Australia
    Search for more papers by this author
  • and for the EURAP Study Group

    Search for more papers by this author
    • The complete list of collaborators is provided in Appendix S1.

Summary

Purpose

To analyze seizure control, dose adjustments, and other changes of antiepileptic drug (AED) treatment during pregnancy in a large cohort of women with epilepsy entering pregnancy on monotherapy with carbamazepine, lamotrigine, phenobarbital, or valproate.

Methods

Seizure control and AED treatment were recorded prospectively in 3,806 pregnancies of 3,451 women with epilepsy taking part in European and International Registry of Antiepileptic Drugs and Pregnancy (EURAP), an international AED and pregnancy registry.

Key Findings

Of all cases, 66.6% remained seizure-free throughout pregnancy. Generalized tonic–clonic seizures (GTCS) occurred in 15.2% of the pregnancies. Women with idiopathic generalized epilepsies were more likely to remain seizure-free (73.6%) than women with localization-related epilepsy (59.5%; p < 0.0001). Worsening in seizure control from the first to second or third trimesters occurred in 15.8% of pregnancies. The AED dose was increased during pregnancy in 26.0% and a second AED added to the initial monotherapy in 2.6% of all pregnancies. Seizures were more likely to occur in the first trimester in pregnancies with an increased drug load (35%; increased dose and/or addition of another AED) than in pregnancies without an increased drug load (15.3%) (p < 0.0001). Compared with other monotherapies, pregnancies exposed to lamotrigine were less likely to be seizure-free, 58.2% (p < 0.0001); had more GTCS, 21.1% (p < 0.0001); had a greater likelihood of deterioration in seizure control from first to second or third trimesters, 19.9% (p < 0.01), and were more likely to require an increase in drug load, 47.7% (p < 0.0001). The mean dose increases from the first to third trimesters were 26% for lamotrigine, 5% for carbamazepine, 11% for phenobarbital, and 6% for valproate. There were 21 cases of status epilepticus (10 convulsive): none with maternal mortality and only one with a subsequent stillbirth.

Significance

Although the majority of women remain seizure-free throughout pregnancy, our data suggest that a more proactive approach to adjusting the dose of all AEDs in pregnancy should be considered, in particular for those pregnancies with seizures occurring in the first trimester and those exposed to lamotrigine, to reduce the risk of deterioration in seizure control.

Ancillary