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Grand Rounds

Adverse Perinatal Outcomes and Epilepsy: Is it the Disorder or the Treatment?

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BACKGROUND AND PURPOSE:

  • Most studies have focused on antiepileptic drugs (AEDs), birth defects and cognition in offspring
  • Some studies have looked at the effect of epilepsy itself on poor pregnancy outcomes, but few studies have looked at large population datasets required to sort out the contributions of epilepsy and AEDs
  • Razaz et al. (JAMA Neurology, 2017) investigated associations between epilepsy and adverse perinatal outcomes including the potential influence of AEDs

METHODS:

  • Population-based retrospective nationwide cohort study
  • Singleton births at 22 or more completed gestational weeks
  • Data on AED exposure was available in a subset of offspring
  • Researcher looked at both pregnancy outcomes (e.g., preeclampsia, chorioamnionitis, abruption), mode of delivery and perinatal outcomes (e.g., stillbirth, preterm birth, congenital malformations, small for gestational age [SGA])
  • Comparisons were made between outcomes of women with epilepsy who were receiving AEDs vs those with epilepsy not receiving medication
  • Analyzed consecutive births from the same mother, to adjust for confounders such as maternal preexisting conditions

RESULTS:

  • Final cohort set included 1,424,279 pregnancies, of 869,947 mothers
  • 5373 births were in 3586 women with epilepsy with a mean age of 30.54 years
  • Most common AEDs
    • Lamotrigine (46.1%)
    • Carbamazepine (30.7%)
    • Valproic acid (19.2%)
    • Topiramate (4.0%)
    • 13.3% were exposed to polytherapy
  • Pregnancy Outcomes: Compared with no-epilepsy pregnancies, women with epilepsy were at an increased risk of
    • Preeclampsia
    • Infection
    • Placental abruption
    • Induction
    • Elective cesarean section
    • Emergency cesarean section
  • Perinatal Outcomes: Infants of mothers with epilepsy were at increased risk of
    • SGA live birth
    • Neonatal infection
    • Any and major malformations
    • Asphyxia-related neonatal complications
    • Low 5-minute Apgar scores
    • Neonatal hypoglycemia and Respiratory distress
  • In women with epilepsy, using AEDs during did not increase the risks of pregnancy complications, except for a higher rate of labor induction
  • Increased perinatal complications were of borderline significance included respiratory distress (6.0% vs 4.5%); SGA live birth (9.5% vs 6.9%); and major malformations (6.7% vs 4.7%)
    • Valproic acid poses a greater risk for major malformation

CONCLUSION:

  • Epilepsy during pregnancy is associated with increased risks of adverse pregnancy and perinatal outcomes
  • AED use during pregnancy is generally not associated with adverse outcomes
    • Epilepsy and possible related conditions (autoimmune disorders) appear to be responsible for majority of adverse pregnancy and perinatal adverse outcomes
  • women with epilepsy should not be advised to discontinue clinically indicated treatment

Learn More – Primary Sources:

Association Between Pregnancy and Perinatal Outcomes Among Women With Epilepsy

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