The efficacy of seizure control prior to pregnancy in predicting seizures during pregnancy and pregnancy outcomes_Journal of Epilepsy

Authors：

HAN Yenan ¹ ,  YU Qing ¹ , REN Mengruo ¹ , PANG Jie ² , YANG Weidong ³ , CHEN Ying ¹ , LV Hui ¹ , YAO Xiaojuan ¹ , CHEN Zhijuan ³

1. Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, China;
2. Department of Neurology, Zhengzhou Central Hospital, Zhengzhou 450000, China;
3. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China;

Corresponding author：

YU Qing, Email: yq_yuqing@163.com

Keywords：

Epilepsy; Pregnancy; Seizure control; Preconceptional counseling; Prognosis factors

DOI：

10.7507/2096-0247.20210002

Video：

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Objective To explore the predictors of seizures during pregnancy, and to explore whether seizure control in the 6 months and 1 year prior to pregnancy can predict the risk of seizures during pregnancy and the occurrence of adverse maternal and infant outcomes, so as to guide the choice of the best fertility timing for women with epilepsy (WWE).Methods A total of 46 WWE with 48 pregnancies were enrolled in Epilepsy Clinics of Tianjin Medical University from August 2016 to January 2020. Retrospective analysis was used to analyze the risk factors of epileptic seizures in pregnancy. The patients were grouped according to the time of absence of seizures during pregnancy. To analyze the influence of epileptic seizure, pregnancy complications and pregnancy outcome.Results Among 48 pregnancies, the risk of premature rupture of membranes was significantly higher in patients with epilepsy than those without epilepsy (34.6% vs. 0.0%), and the difference was statistically significant (P<0.01). There was no significant difference in the risk of PIH, GDM, gestational anemia and pregnancy complications (P>0.05). For women who had seizure during pregnancy, the mean birth weight of the offspring was slightly lower, and the incidence of low birth weight and fetal distress was higher, but the difference was not statistically significant (P>0.05); Seizures in the 6 months before pregnancy were significantly associated with seizures during pregnancy [RR=4.28, 95%CI (2.10, 8.74), P<0.01]. Further, the risk of adverse pregnancy outcomes increased significantly [RR=2.00, 95%CI (1.10, 3.65), P<0.05] for WWE who had seizure in 6 month before pregnancy; The rates of seizures during pregnancy in the two groups were 25.0% and 20.0%, but the difference was not statistically significant (P>0.05). Compared with the 6-months, the ≥1 year group had a lower risk of PIH and gestational anemia, and the offspring had a lower risk of low birth weight, premature delivery and fetal distress, but the difference was not statistically significant (P>0.05).Conclusion Ensuring seizure-free at least 6 months before pregnancy will significantly reduce the probability of seizures during pregnancy, and is significantly associated with a lower incidence of adverse pregnancy outcomes. Women of childbearing age with epilepsy are advised to plan pregnancy after reaching seizure-free at least 6 months.

Citation： HAN Yenan, YU Qing, REN Mengruo, PANG Jie, YANG Weidong, CHEN Ying, LV Hui, YAO Xiaojuan, CHEN Zhijuan. The efficacy of seizure control prior to pregnancy in predicting seizures during pregnancy and pregnancy outcomes. Journal of Epilepsy, 2021, 7(1): 12-20. doi: 10.7507/2096-0247.20210002 Copy

1.	Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
2.	Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology, 2009, 73(2): 133-141.
3.	Battino D, Tomson T, Bonizzoni E, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia, 2013, 54(9): 1621-1627.
4.	Thomas SV, Syam U, Devi JS. Predictors of seizures during pregnancy in women with epilepsy. Epilepsia, 2012, 53(5): e85-e88.
5.	Vajda FJE, O'Brien TJ, Graham JE, et al. Predicting epileptic seizure control during pregnancy. Epilepsy Behav, 2018: 7891-7895.
6.	Jiménez M, Grau-López L, Ciurans J, et al. Epilepsy and pregnancy. Factors associated with epileptic seizures during pregnancy. Neurologia, 2020, 7: S0213-4853(20)30135-3.
7.	Shahla M, Hijran B, Sharif M. The course of epilepsy and seizure control in pregnant women. Acta Neurol Belg, 2018, 118(3): 459-464.
8.	Vajda FJE, O'Brien TJ, Graham JE, et al. Antiepileptic drug polytherapy in pregnant women with epilepsy. Acta Neurol Scand, 2018, 138(2): 115-121.
9.	Ding Y, Tan X, Zhang S, et al. Pharmacokinetic changes and therapeutic drug monitoring of lamotrigine during pregnancy. Brain Behav, 2019, 9(7): e01315.
10.	Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications. Epilepsia, 2013, 54(3): 405-414.
11.	Öhman I, Beck O, Vitols S, et al. Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy. Epilepsia, 2008, 49(6): 1075-1080.
12.	Pennell PB, Peng L, Newport DJ, et al. Lamotrigine in pregnancy: Clearance, therapeutic drug monitoring, and seizure frequency. Neurology, 2007, 70(Issue 22, Part 2): 2130-2136.
13.	Reimers A, Brodtkorb E. Second-generation antiepileptic drugs and pregnancy: a guide for clinicians. Expert Review of Neurotherapeutics, 2014, 12(6): 707-717.
14.	Polepally AR, Pennell PB, Brundage RC, et al. Model‐based lamotrigine clearance changes during pregnancy: clinical implication. Annals of Clinical and Translational Neurology, 2014, 1(2): 99-106.
15.	Reisinger TL, Newman M, Loring DW, et al. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav, 2013, 29(1): 13-18.
16.	Garrity LC, Turner M, Standridge SM. Increased levetiracetam clearance associated with a breakthrough seizure in a pregnant patient receiving once/day extended-release levetiracetam. Pharmacotherapy, 2014, 34(7): e128-e132.
17.	Cappellari AM, Cattaneo D, Clementi E, et al. Increased levetiracetam clearance and breakthrough seizure in a pregnant patient successfully handled by intensive therapeutic drug monitoring. Ther Drug Monit, 2015, 37(3): 285-287.
18.	Westin AA, Reimers A, Helde G, et al. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure, 2008, 17(2): 192-198.
19.	Watila MM, Beida O, Kwari S, et al. Seizure occurrence, pregnancy outcome among women with active convulsive epilepsy: one year prospective study. Seizure, 2015: 267-211.
20.	Cummings C, Stewart M, Stevenson M, et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child, 2011, 96(7): 643-647.

1. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
2. Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology, 2009, 73(2): 133-141.
3. Battino D, Tomson T, Bonizzoni E, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia, 2013, 54(9): 1621-1627.
4. Thomas SV, Syam U, Devi JS. Predictors of seizures during pregnancy in women with epilepsy. Epilepsia, 2012, 53(5): e85-e88.
5. Vajda FJE, O'Brien TJ, Graham JE, et al. Predicting epileptic seizure control during pregnancy. Epilepsy Behav, 2018: 7891-7895.
6. Jiménez M, Grau-López L, Ciurans J, et al. Epilepsy and pregnancy. Factors associated with epileptic seizures during pregnancy. Neurologia, 2020, 7: S0213-4853(20)30135-3.
7. Shahla M, Hijran B, Sharif M. The course of epilepsy and seizure control in pregnant women. Acta Neurol Belg, 2018, 118(3): 459-464.
8. Vajda FJE, O'Brien TJ, Graham JE, et al. Antiepileptic drug polytherapy in pregnant women with epilepsy. Acta Neurol Scand, 2018, 138(2): 115-121.
9. Ding Y, Tan X, Zhang S, et al. Pharmacokinetic changes and therapeutic drug monitoring of lamotrigine during pregnancy. Brain Behav, 2019, 9(7): e01315.
10. Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications. Epilepsia, 2013, 54(3): 405-414.
11. Öhman I, Beck O, Vitols S, et al. Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy. Epilepsia, 2008, 49(6): 1075-1080.
12. Pennell PB, Peng L, Newport DJ, et al. Lamotrigine in pregnancy: Clearance, therapeutic drug monitoring, and seizure frequency. Neurology, 2007, 70(Issue 22, Part 2): 2130-2136.
13. Reimers A, Brodtkorb E. Second-generation antiepileptic drugs and pregnancy: a guide for clinicians. Expert Review of Neurotherapeutics, 2014, 12(6): 707-717.
14. Polepally AR, Pennell PB, Brundage RC, et al. Model‐based lamotrigine clearance changes during pregnancy: clinical implication. Annals of Clinical and Translational Neurology, 2014, 1(2): 99-106.
15. Reisinger TL, Newman M, Loring DW, et al. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav, 2013, 29(1): 13-18.
16. Garrity LC, Turner M, Standridge SM. Increased levetiracetam clearance associated with a breakthrough seizure in a pregnant patient receiving once/day extended-release levetiracetam. Pharmacotherapy, 2014, 34(7): e128-e132.
17. Cappellari AM, Cattaneo D, Clementi E, et al. Increased levetiracetam clearance and breakthrough seizure in a pregnant patient successfully handled by intensive therapeutic drug monitoring. Ther Drug Monit, 2015, 37(3): 285-287.
18. Westin AA, Reimers A, Helde G, et al. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure, 2008, 17(2): 192-198.
19. Watila MM, Beida O, Kwari S, et al. Seizure occurrence, pregnancy outcome among women with active convulsive epilepsy: one year prospective study. Seizure, 2015: 267-211.
20. Cummings C, Stewart M, Stevenson M, et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child, 2011, 96(7): 643-647.

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