Skip to main content

Seizure control during pregnancy and postpartum period in women with epilepsy: an Egyptian prospective study

Abstract

Background

Proper seizure control during pregnancy and postpartum is essential to optimize the outcome of women with epilepsy (WWE). The current work aimed to address factors related to seizure occurrence during pregnancy and postpartum.

Methods

One hundred twenty-five WWE, compliant with their anti-seizure medications (ASMs) regimen, were prospectively evaluated for seizure control and ASMs changes all through the pregnancy up to 4 weeks postpartum.

Results

Most of the patients, 73 (58.4%), completed their pregnancy without seizures, while 52 (41.6%) had seizures. Only one case developed one episode of convulsive status epilepticus in the third trimester. Due to breakthrough seizures, the ASM dose was increased from the first to the third trimester in 19.2% of pregnancies, while another ASM was added in 8 pregnancies. Uncontrolled seizures during the six months before pregnancy were associated with a four-fold increase in the risk of seizures during pregnancy (95% CI 2.476–6.695). The latter nearly doubled the risk of seizures during the postpartum period (RR 1.978) (95% CI 1.44 -2.717). Furthermore, genetic etiology would increase the risk of seizures during the postpartum period by 2.7 times more than the unknown etiology (RR 2.778, 95%CI 1.156–6.679).

Conclusion

Women with epilepsy should be counselled that proper seizure control six months before pregnancy is necessary to pass their pregnancy and the postpartum period without seizures.

Peer Review reports

Introduction

In the Arab world, the estimated prevalence of epilepsy ranged from 0.9/1000 to 6.5/1000 [1]. Egypt is ranked among the most prevalent Arab countries with epilepsy, where the prevalence of epilepsy was estimated to be 6.9 cases per 1000 [2].

Epilepsy is associated with an overall increased risk of maternal deaths, both during and after pregnancy, and an increased risk of Sudden Unexpected Death in Epilepsy (SUDEP) specifically [3]. Uncontrolled seizures during pregnancy add another risk factor for epilepsy-related deaths [3, 4]. In addition, Y-H Chen et al. [5] found that uncontrolled seizures can partially contribute to adverse pregnancy outcomes in women with epilepsy (WWE), such as preterm delivery and low birth weight. The postpartum period is considered another vulnerable time for seizures, as stress increases and sleep is disturbed [6]. Taken together, every attempt should be made to prevent seizures during pregnancy and postpartum.

That's why several studies have been interested in revealing predictors of seizures during pregnancy [7,8,9] as well as postpartum seizures in WWE [10, 11].

In this work, Egyptian WWE adhering to the treatment were prospectively followed during the entire pregnancy and up to 4 weeks postpartum to assess seizure control during pregnancy and the postpartum period concerning pre-pregnancy control, age, age at onset, seizure type, etiology, and treatment regimen.

Methods

The present study was a part of the Egyptian Registry of Anti-seizure medications and Pregnancy system, in which 211 pregnant WWE were prospectively evaluated from November 2018 to November 2020 [12].

Out of 211 pregnancies included in that study, 27 ended prematurely due to intrauterine deaths, five patients started their seizures for the first time during pregnancy, and 54 were noncompliant with their anti-seizure medications (ASMs) regimen. Hence, only 125 WWE were included in the current analysis of seizure control. Only one woman was excluded from the analysis of seizure control during the postpartum period because she delivered a stillbirth.

Data for these patients regarding seizure control and treatment changes during the entire pregnancy and up to four weeks postpartum were prospectively registered into the Egyptian Registry of Anti-seizure medications and Pregnancy system.

Seizure control was verified six months before pregnancy, during each trimester, at the time of delivery, and during the four postpartum weeks. Treatment changes regarding the type or dose of ASMs in each of these previous periods were also documented. Additionally, the occurrence of status epilepticus (SE), either convulsive or non-convulsive, was evaluated.

Ethical statement

All the participants signed their informed consent to the study. The study was performed following the Helsinki declaration. The ethical committee of the Faculty of Medicine, Cairo University, approved the study (approval number is D-39–2019).

Statistical analysis

Data were summarized using mean and standard deviation for quantitative data and count and percentages for categorical data. Comparisons between categorical data were made using the Chi-square test. Relative risk (RR) for seizures occurring during pregnancy and postpartum was estimated. P-values less than 0.05 were considered statistically significant.

Results

One hundred twenty-five WWE were prospectively followed during pregnancy. Their ages ranged from 17 to 41 years, with a mean age of 27.3 ± 5.4.

Overall seizure control and treatment changes during pregnancy

Most of the patients, 73 (58.4%), successfully completed their pregnancy without seizures, while 52 (41.6%) had seizures. Seizure frequency was unchanged in 97 cases (77.6%), of which 73 (75.2%) were seizure-free during the entire pregnancy. Of the remaining 28 pregnancies, six patients (4.8%) had a reduction in seizure frequency in the second and \ or third trimester, and 22 patients (17.6%) had deteriorated.

Only one case developed one episode of convulsive SE in the third trimester. This case was diagnosed as preeclampsia during the third trimester.

Seizure control during pregnancy in relation to different ASMs is illustrated in Table 1. Due to breakthrough seizures, the ASM dose was increased from the first to the third trimester in 19.2% of pregnancies (24/125), while another ASM was added in 8 pregnancies (6.4%).

Table 1 Anti-seizure medications used by eligible patients in relation to seizure control during pregnancy

Seizures occurred during delivery in 7 (5.6%) patients, two on monotherapy (one on levetiracetam and another on valproate) and five on polytherapy.

Risk estimation for seizures occurring during pregnancy

Univariate analysis showed that seizure freedom six months before pregnancy was significantly associated with seizure freedom during pregnancy (P < 0.001) (Table 2).

Table 2 Comparison between patients who had seizures versus who had no seizures during pregnancy

Uncontrolled seizures during the six months before pregnancy were associated with a four-fold increase in the risk of seizures during pregnancy (95% CI 2.476–6.695) (Table 3).

Table 3 Risk estimation of seizures occurring during the entire pregnancy

Risk estimation for seizures occurring during the postpartum period

By univariate analysis, genetic and structural etiology were significantly associated with seizure occurrence during the postpartum period compared to those with unknown etiology. Moreover, Seizure occurrence during pregnancy was significantly associated with seizure occurrence during the postpartum period (Table 4).

Table 4 Comparison between patients who had seizures and who had no seizures during the postpartum period

Seizure occurrence during pregnancy nearly doubled the risk of seizures during the postpartum period (RR 1.978) (95% CI 1.44 -2.717). Additionally, genetic etiology would increase the risk of seizures during the postpartum period by 2.7 times more than the unknown etiology (RR 2.778, 95%CI 1.156–6.679) (Table 5).

Table 5 Risk estimation of seizures occurring during the postpartum period

Discussion

The current study showed that most of the patients (58.4%) successfully passed their pregnancy without breakthrough seizures in a ratio slightly similar to that found in the 2006 EURAP study (58.3%) [13] but less than EURAP 2013 study (66.6%) [14]. The later EURAP analysis excluded women on polytherapy, who are known to be less likely to have complete seizure control [14]. In the Australian register of ASMs in pregnancy, only 50.3% of WWE remained seizure-free throughout the entire pregnancy [8]. Compared with other developing countries, our ratio was higher than the KREP study in which 47.8% of WWE remained seizure-free throughout the entire pregnancy [9]. However, PB Pennell et al. [15] found that the rate of seizure worsening in WWE during and after pregnancy was similar when compared to WWE who were not pregnant and observed over the same time period.

Seizure frequency was unchanged in 77.6% of our study population. This proportion was higher than those reported by EURAP study 2013 [14] and EURAP study 2006 [13] (70.5% and 63.6%), respectively. In addition, the percent of worsening in seizure control in our study population from the first to second or third trimesters was similar to those reported by the EURAP study (17.6% in ours, 17.3% in EURAP 2006 [13] and 15.8% in EURAP 2013 [14].

In this study, SE occurred in only one case (0.8%) with no maternal mortality. According to KR Rajiv and A Radhakrishnan [16], SE occurs in 1–2% of pregnancies in WWE and does not seem to be more frequent than in other periods of life. This finding contrasts with earlier estimates that suggest high maternal mortality rates in SE during pregnancy [17].

In the EURAP study, the drug dose was increased, or a second ASM was added in almost one-third of the pregnancies. These changes in treatment schedule were not limited to patients who had breakthrough seizures but also to patients who were taking ASMs whose levels had decreased during the second and third trimesters of pregnancy to prevent breakthrough seizures [14]. In our study, increases in doses and/or number of ASMs occurred in 25.6% of pregnancies. They were almost in pregnancies with breakthrough seizures, which may be due to the lack of serum level of those AEDs known to be affected during pregnancy (levetiracetam, lamotrigine, oxcarbazepine) [18].

We agreed with all previous studies that pre-pregnancy uncontrolled seizure predicts breakthrough seizure during pregnancy, but the period studied before pregnancy varied from one study to another. While we studied the effect of the six months as a preconception period, J Allotey et al. [7] studied the effect of 3 months, SV Thomas et al. [9] studied the effect of one month before pregnancy, PE Voinescu et al. [10] studied the effect of 9 months and one year was evaluated by FJ Vajda et al. [8].

Therefore, WWE should be counselled to postpone pregnancy until seizures are controlled to avoid breakthrough seizures during pregnancy.

The present study showed that age, age at onset, seizure type, etiology, or treatment regimen were not significantly associated with seizures during pregnancy, in contrast to other registries that found that seizures affected pregnancies occurred in younger mothers, with earlier onset, with focal seizures, and who were exposed to polytherapy [7,8,9,10, 14].

In this study, the type of ASM was not studied concerning seizure occurrence during pregnancy due to the limited number of our patients. Larger registries found that the serum level of some ASMs drooped during pregnancy; oxcarbazepine in the EURAP 2006 [13] and lamotrigine in the EURAP 2013 study [14].

The postpartum period is considered physically and emotionally stressful for WWE [6]. Therefore, detecting predictors of seizure occurrence during this vulnerable period is crucial to keep the nursing mother and her baby safe. In agreement with the Australian registry [8], this study showed that seizure occurrence during pregnancy was associated with seizure occurrence during the postpartum period. Therefore, WWE who were controlled during pregnancy should be reassured that they would most likely be safe during the postpartum period.

The present study showed that genetic etiology was associated with seizure occurrence during the postpartum period than those with unknown etiology (RR = 2.778). Sleep deprivation, a feature of the postpartum phase, is a known seizure trigger for those with genetic etiology [19]. Therefore, family help and support to assist with night feeding were recommended [6].

Finally, the relatively small size of the study population is the main noteworthy limitation of this study that impeded the analysis of each ASM individually in relation to seizure occurrence during pregnancy. Lack of drug serum level monitoring during pregnancy was another limitation.

Conclusion

To conclude, most of our patients successfully completed their pregnancy without seizures. Seizure occurrence six months before pregnancy was associated with an increased risk of breakthrough seizure during pregnancy, and the latter was associated with seizure occurrence during the postpartum period.

Availability of data and materials

Authors report that the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Benamer HT, Grosset DG. A systematic review of the epidemiology of epilepsy in Arab countries. Epilepsia. 2009;50(10):2301–4. https://doi.org/10.1111/j.1528-1167.2009.02058.x.

    Article  Google Scholar 

  2. Hashem S, Al-Kattan M, Ibrahim SY, Shalaby NM, Shamloul RM, Farrag M. Epilepsy prevalence in Al-Manial Island, Egypt. A door-to-door survey. Epilepsy Res. 2015;117:133–7. https://doi.org/10.1016/j.eplepsyres.2015.08.003.

    Article  Google Scholar 

  3. Edey S, Moran N, Nashef L. SUDEP and epilepsy-related mortality in pregnancy. Epilepsia. 2014;55(7):e72–4. https://doi.org/10.1111/epi.12621.

    Article  CAS  Google Scholar 

  4. Leach JP, Smith PE, Craig J, Bagary M, Cavanagh D, Duncan S, et al. Epilepsy and Pregnancy: For healthy pregnancies and happy outcomes. Suggestions for service improvements from the Multispecialty UK Epilepsy Mortality Group. Seizure. 2017;50:67–72. https://doi.org/10.1016/j.seizure.2017.05.004.

    Article  CAS  Google Scholar 

  5. Chen Y-H, Chiou H-Y, Lin H-C, Lin H-L. Affect of Seizures During Gestation on Pregnancy Outcomes in Women With Epilepsy. Arch Neurol. 2009;66(8):979–84. https://doi.org/10.1001/archneurol.2009.142.

    Article  Google Scholar 

  6. Klein A. The postpartum period in women with epilepsy. Neurol Clin. 2012;30(3):867–75. https://doi.org/10.1016/j.ncl.2012.06.001.

    Article  Google Scholar 

  7. Allotey J, Fernandez-Felix BM, Zamora J, Moss N, Bagary M, Kelso A, et al. Predicting seizures in pregnant women with epilepsy: Development and external validation of a prognostic model. PLoS Med. 2019;16(5):e1002802. https://doi.org/10.1371/journal.pmed.1002802.

    Article  CAS  Google Scholar 

  8. Vajda FJ, Hitchcock A, Graham J, O’Brien T, Lander C, Eadie M. The Australian Register of Antiepileptic Drugs in Pregnancy: the first 1002 pregnancies. Aust N Z J Obstet Gynaecol. 2007;47(6):468–74. https://doi.org/10.1111/j.1479-828X.2007.00781.x.

    Article  Google Scholar 

  9. Thomas SV, Syam U, Devi JS. Predictors of seizures during pregnancy in women with epilepsy. Epilepsia. 2012;53(5):e85–8. https://doi.org/10.1111/j.1528-1167.2012.03439.x.

    Article  Google Scholar 

  10. Voinescu PE, Ehlert AN, Bay CP, Allien S, Pennell PB. Variations in Seizure Frequency During Pregnancy and Postpartum by Epilepsy Type. Neurology. 2022;98(8):e802–7. https://doi.org/10.1212/wnl.0000000000013056.

    Article  CAS  Google Scholar 

  11. Vajda FJ, O’Brien TJ, Hitchcock A, Graham J, Lander C. The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months. J Clin Neurosci. 2003;10(5):543–9. https://doi.org/10.1016/s0967-5868(03)00158-9.

    Article  CAS  Google Scholar 

  12. Hosny H, Elkattan M, Zaki MA, Ramzy GM, Magdy R, Abo Al-Azayem S. Risk factors of fetal deaths and major birth defects in newborns of women with epilepsy: An Egyptian prospective study. Epilepsy Behav. 2021;123:108251. https://doi.org/10.1016/j.yebeh.2021.108251.

    Article  Google Scholar 

  13. Pennell PB. EURAP Outcomes for Seizure Control during Pregnancy: Useful and Encouraging Data. Epilepsy Curr. 2006;6(6):186–8. https://doi.org/10.1111/j.1535-7511.2006.00140.x.

    Article  Google Scholar 

  14. Battino D, Tomson T, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia. 2013;54(9):1621–7. https://doi.org/10.1111/epi.12302.

    Article  CAS  Google Scholar 

  15. Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, et al. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. 2020;383 26:2547-56. https://doi.org/10.1056/NEJMoa2008663

  16. Rajiv KR, Radhakrishnan A. Status epilepticus in pregnancy: Etiology, management, and clinical outcomes. Epilepsy & behavior : E&B. 2017;76:114–9. https://doi.org/10.1016/j.yebeh.2017.07.002.

    Article  Google Scholar 

  17. Pennell PB. Antiepileptic drugs during pregnancy: what is known and which AEDs seem to be safest? Epilepsia. 2008;49 Suppl 9 0 9:43–55. https://doi.org/10.1111/j.1528-1167.2008.01926.x.

  18. Reimers A, Brodtkorb E. Second-generation antiepileptic drugs and pregnancy: a guide for clinicians. Expert Rev Neurother. 2012;12(6):707–17. https://doi.org/10.1586/ern.12.32.

    Article  CAS  Google Scholar 

  19. Lieblich S. Are Seizures in the setting of sleep deprivation provoked? 2009.

    Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

Author information

Authors and Affiliations

Authors

Contributions

HH participated in the concept, study design, collection, and interpretation of data. MM participated in study design and data interpretation and helped draft the manuscript. MZ participated in study design and data interpretation and helped draft the manuscript. GR participated in study design and data interpretation and helped draft the manuscript. SA participated in the study design, collection, and interpretation of data and helped to draft the manuscript. RM participated in the study design, collection, and interpretation of data and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rehab Magdy.

Ethics declarations

Ethics approval and consent to participate

All the participants signed their informed consent to the study. The study was performed in accordance with the Helsinki declaration. The ethical committee of the Faulty of Medicine, Cairo University, approved the study (approval number is D-39–2019).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hosny, H., Al Kattan, M.M., Zaki, M.A. et al. Seizure control during pregnancy and postpartum period in women with epilepsy: an Egyptian prospective study. BMC Neurol 23, 54 (2023). https://doi.org/10.1186/s12883-023-03086-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12883-023-03086-w

Keywords