Maternal and Neurodevelopmental Outcomes of in Utero Antiepileptic Drug (AED) Exposure (MONEAD)

• Changes in seizure frequency over pregnancy vs. post-partum (comparable time periods for non-pregnant women with epilepsy). [ Time Frame: Pregnant women with epilepsy:1st Trimester through 9 months post-partum; Nonpregnant women with epilepsy: Study enrollment through 18 months participation ] [ Designated as safety issue: No ]
  Change in seizure frequency during pregnancy vs postpartum as measured by subject completed daily electronic seizure diaries
  
  
• C-section Rate [ Time Frame: Pregnant women with epilepsy & Pregnant women without epilepsy at child's birth ] [ Designated as safety issue: No ]
  rate of C-sections in pregnant women without epilepsy vs pregnant women with epilepsy
  
  
• Rate of Depression [ Time Frame: Pregnant women: 1st Trimester through 9 months post partum, again when child is 2 and 3 Years of age. Nonpregnant women with epilepsy: Study enrollment through 6months participation, then 12 months until 18 months participation ] [ Designated as safety issue: Yes ]
  Rate of depression during pregnancy in pregnant women with epilepsy vs pregnant women without epilepsy screened by the Beck Depression Inventory and confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual-IV.
  
  
• Child Verbal Intellectual Ability [ Time Frame: When child is 2, 3, 4.5 and 6 Years of age ] [ Designated as safety issue: No ]
  Child verbal intellectual ability as measured by the Language Scale of the Bayley Scales of Infant Development -III at visit 9 (2Yo) and by the Differential Abilities Scale-II at visit 10 (3Yo)and 4.5YO and 6YO.
  
  
• Small for Gestational Age Rate [ Time Frame: Child's birth ] [ Designated as safety issue: No ]
  Rate of children considered small for gestational age (<10%tile)born to women with epilepsy vs women without epilepsy
  
  
• Breastfeeding Effects on verbal intellectual ability in children [ Time Frame: Birth until the child is 2 Years of age, although we anticipate not all children will breastfeed until 2 Years ] [ Designated as safety issue: No ]
  Measuring difference in verbal intellectual ability in breastfed children vs non-breastfed children born to women on aeds via the Bayley Scales of Infant Development III Language scale at 2 years of age and Differential Abilities Scale III at 3, 4.5 and 6 Years of age.
  
  

There is a compelling need for prospective, properly controlled studies in women with epilepsy (WWE) during pregnancy to improve maternal and child outcomes. The proposed investigations are pertinent to the National Institute of Neurological Disorders and Stroke Epilepsy Research Benchmarks and will address multiple gaps in our knowledge noted by the recent American Academy of Neurology guidelines. This multicenter investigation will employ a prospective, observational, parallel-group, cohort design with an established research team.

The specific aims are to:

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;
4. Determine the long-term effects of in utero antiepileptic drug exposure on verbal intellectual abilities and other neurobehavioral outcomes in the children of women with epilepsy;
5. Determine if small for gestation age and other adverse neonatal outcomes are increased in children of women with epilepsy;
6. Determine if breastfeeding when taking antiepileptic drugs impairs the child's verbal intellectual and other cognitive abilities.

An overall goal of the proposed research 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.

Anticonvulsant blood levels (ABLs) and area-under-the-concentration-time-curves (AUCs) will be used as direct measures of drug exposure. The results will enable clinicians to prospectively calculate individual dosing regimens for the mother in order to optimize dosing and limit unnecessary drug exposure to the child. In addition, genetic samples will be collected, which will provide a valuable resource for future pharmacogenetics studies to further delineate individual variability across patients.