Abstracts

Rationale:
For many women with epilepsy worldwide, seizures are affected by neuroactive steroids (NAS), which are sex hormones and their neurosteroid metabolites. Allopregnanolone (ALLO), a progesterone (PROG) metabolite, has the richest evidence for an anticonvulsant role, while 17β-estradiol (EST) is mostly proconvulsant. It was previously shown that circulating NAS concentrations dramatically increase during pregnancy, far above the non-pregnant state; yet not all pregnant WWE (PWWE) experience the same seizure control. With the hypothesis that seizures are likely affected by circulating neuroactive steroids (NAS) during pregnancy, we aimed to determine whether PROG, ALLO and EST levels correlate with seizure control during pregnancy.  
Method:
Women with epilepsy were enrolled preconception or early in pregnancy from the Emory Epilepsy Program (Atlanta, GA). Detailed information was collected about their seizure types and frequency, including baseline frequency over the past year. They were prospectively followed throughout pregnancy and the first postpartum year with daily diaries of seizures, AED doses, and adherence. Study visits with blood sampling occurred every 1-3 months. A subset of plasma samples was assayed through a GC–MS method, which was developed to simultaneously measure nine NAS, including ALLO, estradiol, progesterone (Pennell KD et al, Steroids 95, 24–31 (2015)). The Wilcoxon rank sum test was used to compare NAS levels by trimester and seizure frequency. The Bonferroni-Holm method was used to correct for multiple comparisons.
Results:
NAS concentrations were obtained for 101 patients, but 19 patients were excluded because of inadequate seizure information, miscarriages or only one blood sample analyzed. Out of the 83 patients included, there were 15 women who experienced seizure worsening in the first trimester, 18 in the second trimester and 10 in the third. The ALLO concentration, but not the PROG concentration, was significantly higher (p=0.00046) in women with stable seizure frequency compared to those with an increase in their seizure frequency in the third trimester. A similar trend was notices for ALLO concentrations in the first trimester, but significance was not reached (p=0.076). Although the difference in the EST concentrations did not reach significance, a trend was observed for higher EST concentrations in the second trimester (p= 0.17) for women who experienced an increase in their seizure frequency.
Conclusion:
In this prospective study from a single epilepsy, the findings suggest that higher ALLO concentrations help maintain a stable seizure frequency during the third trimester of pregnancy. Higher EST concentrations may play contribute to an increase in seizure frequency during the second trimester. Validation of these finding in a larger cohort is necessary.
Funding:
:Supported by an NIH Specialized Center of Research (P50 MH 68036) (ZNS, DJN, JR, PBP), NCRR M01-RR00039, NINDS and NICHD (U01 NS038455) (ZNS, PBP).