Antiepileptic drugs and intrauterine death: A prospective observational study from EURAP

Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John J Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V Thomas, Frank Vajda, EURAP Study Group

59 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalNeurology
Volume85
Issue number7
Pages (from-to)580-8
Number of pages9
ISSN0028-3878
DOIs
Publication statusPublished - 18 Aug 2015

Keywords

  • Abortion, Spontaneous
  • Adolescent
  • Adult
  • Anticonvulsants
  • Congenital Abnormalities
  • Drug Therapy, Combination
  • Epilepsy
  • Female
  • Humans
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications
  • Prospective Studies
  • Registries
  • Risk Factors
  • Stillbirth
  • Young Adult

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