Abstracts

Rationale: Ideal treatment of women with epilepsy (WWE) during pregnancy involves achieving an optimal balance between maintaining seizure control and minimizing fetal exposure to AEDs. Sex steroid hormones and the metabolic byproducts that are capable of modifying neural activity are classified as neuroactive steroids (NAS). Fluctuations in NAS have been implicated in seizure control in the non-pregnant state (catamenial epilepsy). 17β-Estradiol (EST) is considered proconvulsant and progesterone (PROG) anticonvulsant. There has been limited investigation of these phenomena during pregnancy, although the magnitude of increases in most of the NAS far exceeds fluctuations at any other time of the life cycle. Methods: After providing informed consent, 110 WWE enrolled and completed a prospective observational study during pregnancy with clinic visits qmonth-qtrimester (TM) with review of seizure diaries and collection of blood samples. Plasma samples from a subset of 26 women on non-enzyme-inducing AEDs, and at least 3 samples during pregnancy, were assayed for concentrations of EST and PROG, to provide pilot data regarding their potential role in seizure control during pregnancy. Baseline preconception seizure frequency (SF) over the past year was obtained for each subject; the most severe seizure type that occurred within the past year or during pregnancy for each woman was used for assessment of change in SF for this study. Since enrollment time was variable in the 1st TM, we analyzed SF during the 2nd and 3rd TMs of pregnancy for comparison to the nonpregnant baseline. Each subject’s SF was categorized as Increased (≥ ↑25%), No change, or Decreased (≥↓ 25%). Hormone values were log-transformed, and the rate of increase was computed for each pregnancy by fitting a regression line through the data points. The rate of increase in gestational EST and PROG levels were compared across the 3 groups. Results: The 3 groups are comparable in their demographic characteristics (Table 1). The rate of increase of EST during pregnancy is similar across the 3 groups. However, there is some indication that the PROG rate of increase might be slower for the group with Increased SF, though it did not reach statistical significance. Conclusions: This pilot data on 26 patients suggest that worsening of SF during pregnancy may be associated with a slower rate of increase of PROG during pregnancy, but SF may not be influenced by the rate of increase of EST. While we work on validating this finding in a larger cohort of patients, we will also begin to examine other NAS compounds during pregnancy such as allopregnanolone. Positive identification of a role for NAS in seizure control during pregnancy could result in novel therapeutic approaches (e.g., supplemental progesterone), thereby potentially reducing amount of fetal exposure to AEDs in utero and improving maternal and fetal outcomes. Acknowledgements: Supported in part by the National Institutes of Health, P50 MH-068036, NCRR M01-RR00039, and PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Center for Research Resources.