Study Outline

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Sponsored by:

National Institute of Neurological Disorders and Stroke (NINDS)

and

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)




Objectives

The overall goal of this study is to determine risks that are increased in women with epilepsy during pregnancy and in their children, and to examine the key contributing factors.

Adult women with epilepsy will be monitored during pregnancy and postpartum to measure maternal outcomes, and their children will be monitored from birth through age 6 years to measure their health and developmental outcomes. Two control groups will be enrolled for comparison, which include 1) healthy pregnant women without epilepsy and 2) non-pregnant women with epilepsy.

For the women with epilepsy, we will measure the following primary outcomes:

  1. Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors
  2. Determine if C-section rate is increased in women with epilepsy and delineate contributing factors
  3. Determine if women with epilepsy have an increased risk for depression during pregnancy and post-partum period and characterize risks factors

For the children born to women with epilepsy, we will measure the following primary outcomes:
  1. Determine the long-term effects of in utero antiepileptic drug exposure on verbal intellectual abilities and other neurobehavioral outcomes
  2. Determine if small for gestational age and other adverse neonatal outcomes are increased
  3. Determine if breastfeeding when taking AEDs impairs the child’s ultimate verbal and other cognitive outcomes.

An overall goal of this study is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response. The results will enable clinicians to better manage women with epilepsy during pregnancy.


Design and Outcomes

baby holding adult's hand     

This multicenter investigation will employ a prospective, observational, parallel-group, cohort design to monitor clinical outcomes in the mothers with epilepsy and the outcomes in their children.

The specific outcomes in the mother that will be measured include: Seizure frequency and type; Obstetrical complications, including C-section rate; and Depression.

The specific outcomes in the children that will be measured include: Neurodevelopmental outcomes measured by the Language Scale of the Bayley Scales of Infant Development-III (BSID-3) at age 2 and Verbal Index at age 6 as well as other cognitive outcomes; Neonatal outcomes including birth weight; and Breastfeeding outcomes measured by the Language Scale of the BSID-3 at age 2 years and Verbal Index at age 6 years. Additional cognitive and behavioral measures for the child will be obtained age 2, 3, 4.5 and 6 years.

AED blood levels will be used as direct measures of drug exposure and to estimate individual drug exposure.


Interventions and Duration

This study will compare pregnant women with epilepsy, non-pregnant women with epilepsy, and pregnant women without epilepsy. This observational study will not employ any interventions; however, antiepileptic drug treatment for WWE will be recorded throughout the duration of the study.

Non-pregnant women with epilepsy will be followed for 18 months.

Pregnant women (with or without epilepsy) will be followed throughout pregnancy and until their child is 6 years old. Children of the pregnant women will ultimately be followed until they are 6 years old.

The child’s father and a first degree relative of each mother will be invited to participate in the study to provide additional family information.


Sample Size and Population

Subjects will include mother/child pairs enrolled during pregnancy (including approximately 100 healthy women and 350 women with epilepsy) and approximately 100 non-pregnant women with epilepsy. Children are classified into 4 groups with healthy mothers or mothers diagnosed with epilepsy on antiepileptic drug (AED) monotherapy, polytherapy, or no antiepileptic drug treatment.

The study will recruit and target of 550 women, as detailed in the table below.

Study Group* Target Sample Size Monotherapy
(LTG, LEV, CBZ, Other)**
Polytherapy No AED***
Pregnant women with epilepsy 350 280
(n=70/ AED group)
35 35
Non-pregnant women with epilepsy 100 80 10 10
Healthy pregnant women 100 N/A N/A 100

*Additionally, group proportions for key demographic factors such as age, race, education, and socioeconomic status will be monitored and assessed.
**CBZ=carbamazepine, LEV=levetiracetam, LTG=lamotrigine
***AED=antiepileptic drug
n=number; N/A=not applicable