Skip to main content

Advertisement

SpringerLink
Log in

Maternal epilepsy- perinatal outcome and long-term neurological morbidity of the offspring: a population-based cohort study

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The current study was aimed to assess whether maternal epilepsy is linked to long-term neurological morbidity of the offspring, and to examine whether maternal epilepsy is associated with adverse pregnancy outcomes.

Methods

A population-based cohort study was conducted comparing perinatal outcomes of women with and without epilepsy, including long-term neurological morbidity of the offspring. Both the exposed and unexposed groups were followed up to 18 years of age for neurological-related morbidity. To assess perinatal outcomes of women with epilepsy, generalized estimation equation (GEE) models were used to control for confounders. To compare the cumulative incidence of long-term neurological morbidity a Kaplan–Meier survival curve was used. A Cox proportional hazards model was built to control for confounders.

Results

During the study period, 243,682 deliveries met the inclusion criteria; 711 (0.29%) were of mothers with epilepsy. Maternal epilepsy was noted as an independent risk factor for preterm delivery, cesarean delivery, and low birth weight using GEE models controlling for maternal age and parity. Offspring born to mothers with epilepsy had higher rates of long-term neurological morbidity (Kaplan–Meier log-rank test, p < 0.001). A Cox proportional hazards model, controlled for maternal age, hypertensive disorders, gestational age, and diabetes mellitus, demonstrated that being born to a mother with epilepsy was an independent risk factor for long-term neurological morbidity of the offspring (adjusted HR 2.7, 95% CI 2.12–3.56, p < 0.001).

Conclusions

The pregnancy of epileptic women is independently associated with the adverse perinatal outcome as well as a higher risk for long-term neurological morbidity of the offspring.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

SUMC:

Soroka University Medical Center

ICD-9:

International Classification of Diseases nine

GEE:

Generalized estimation equation

ADHD:

Attention deficit hyperactivity disorder

SGA:

Small for gestational age

AGA:

Appropriate for gestational age

LGA:

Large for gestational age

References

  1. Behr C, Goltzene MA, Kosmalski G et al (2016) Epidemiology of epilepsy. Rev Neurol (Paris) 172:27–36. https://doi.org/10.1016/j.neurol.2015.11.003

    Article  CAS  Google Scholar 

  2. Laskowska M, Leszczyńska-Gorzelak B, Oleszczuk J (2001) Pregnancy in women with epilepsy. Gynecol Obstet Invest 51:99–102. https://doi.org/10.1159/000052902

    Article  CAS  PubMed  Google Scholar 

  3. Katz O, Levy A, Wiznitzer A, Sheiner E (2006) Pregnancy and perinatal outcome in epileptic women: a population-based study. J Matern Fetal Neonatal Med 19:21–25. https://doi.org/10.1080/14767050500434096

    Article  PubMed  Google Scholar 

  4. Stafstrom CE, Carmant L (2015) Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect.a022426

    Article  PubMed  PubMed Central  Google Scholar 

  5. Poduri A, Lowenstein D (2011) Epilepsy genetics–past, present, and future. Curr Opin Genet Dev 21:325–332. https://doi.org/10.1016/j.gde.2011.01.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meador KJ (2014) Epilepsy: pregnancy in women with epilepsy–risks and management. Nat Rev Neurol 10:614–616. https://doi.org/10.1038/nrneurol.2014.179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Viale L, Allotey J, Cheong-See F et al (2015) Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis. Lancet 386:1845–1852. https://doi.org/10.1016/S0140-6736(15)00045-8

    Article  PubMed  Google Scholar 

  8. MacDonald SC, Bateman BT, McElrath TF, Hernández-Díaz S (2015) Mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the United States. JAMA Neurol 72:981–988. https://doi.org/10.1001/jamaneurol.2015.1017

    Article  PubMed  PubMed Central  Google Scholar 

  9. Swartjes JM, van Geijn HP (1998) Pregnancy and epilepsy. Eur J Obstet Gynecol Reprod Biol 79:3–11. https://doi.org/10.1016/s0301-2115(98)00027-x

    Article  CAS  PubMed  Google Scholar 

  10. Wilhelm J, Morris D, Hotham N (1990) Epilepsy and pregnancy–a review of 98 pregnancies. Aust N Z J Obstet Gynaecol 30:290–295. https://doi.org/10.1111/j.1479-828x.1990.tb02013.x

    Article  CAS  PubMed  Google Scholar 

  11. de Onis M, Habicht JP (1996) Anthropometric reference data for international use: recommendations from a World Health Organization Expert Committee. Am J Clin Nutr 64(4):650–658. https://doi.org/10.1093/ajcn/64.4.650

    Article  PubMed  Google Scholar 

  12. Schlaudecker EP, Munoz FM, Bardají A, Boghossian NS, Khalil A, Mousa H, Nesin M, Nisar MI, Pool V, Spiegel HML, Tapia MD, Kochhar S, Black S, Brighton Collaboration Small for Gestational Age Working Group (2017) Small for gestational age: case definition & guidelines for data collection, analysis, and presentation of maternal immunisation safety data. Vaccine 35:6518–6528. https://doi.org/10.1016/j.vaccine.2017.01.040

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nahum Sacks K, Friger M, Shoham-Vardi I et al (2019) Long-term neuropsychiatric morbidity in children exposed prenatally to preeclampsia. Early Human Dev 130:96–100. https://doi.org/10.1016/j.earlhumdev.2019.01.016

    Article  Google Scholar 

  14. Nahum Sacks K, Friger M, Shoham-Vardi I et al (2016) Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring. Am J Obstet Gynecol 215:380.e1-380.e7. https://doi.org/10.1016/j.ajog.2016.03.030

    Article  Google Scholar 

  15. Kullmann DM (2002) Genetics of epilepsy. J Neurol Neurosurg Psychiatry 73(Suppl 2):II32-35. https://doi.org/10.1136/jnnp.73.suppl_2.ii32

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gauffin H, Flensner G, Landtblom A-M (2015) Being parents with epilepsy: thoughts on its consequences and difficulties affecting their children. Neuropsychiatr Dis Treat 11:1291–1298. https://doi.org/10.2147/NDT.S74222

    Article  PubMed  PubMed Central  Google Scholar 

  17. Halmøy A, Klungsøyr K, Skjærven R, Haavik J (2012) Pre- and perinatal risk factors in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 71:474–481. https://doi.org/10.1016/j.biopsych.2011.11.013

    Article  PubMed  Google Scholar 

  18. Gaily E, Kantola-Sorsa E, Granström ML (1990) Specific cognitive dysfunction in children with epileptic mothers. Dev Med Child Neurol 32:403–414. https://doi.org/10.1111/j.1469-8749.1990.tb16959.x

    Article  CAS  PubMed  Google Scholar 

  19. Perucca E (2005) Birth defects after prenatal exposure to antiepileptic drugs. Lancet Neurol 4:781–786. https://doi.org/10.1016/S1474-4422(05)70224-6

    Article  CAS  PubMed  Google Scholar 

  20. Brikell I, Ghirardi L, D’Onofrio BM et al (2018) Familial liability to epilepsy and attention-deficit/hyperactivity disorder: a nationwide cohort study. Biol Psychiatry 83:173–180. https://doi.org/10.1016/j.biopsych.2017.08.006

    Article  PubMed  Google Scholar 

  21. Chen Y-H, Chiou H-Y, Lin H-C, Lin H-L (2009) Affect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 66:979–984. https://doi.org/10.1001/archneurol.2009.142

    Article  PubMed  Google Scholar 

  22. Adab N, Kini U, Vinten J et al (2004) The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 75:1575–1583. https://doi.org/10.1136/jnnp.2003.029132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pariente G, Leibson T, Shulman T et al (2017) Erratum to: pregnancy outcomes following in utero exposure to lamotrigine: a systematic review and meta-analysis. CNS Drugs 31:451. https://doi.org/10.1007/s40263-017-0439-7

    Article  PubMed  Google Scholar 

  24. Tomson T, Landmark CJ, Battino D (2013) Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia 54:405–414. https://doi.org/10.1111/epi.12109

    Article  CAS  PubMed  Google Scholar 

  25. Schmitz T (2016) Prevention of preterm birth complications by antenatal corticosteroid administration. J Gynecol Obstet Biol Reprod (Paris) 45:1399–1417. https://doi.org/10.1016/j.jgyn.2016.09.008

    Article  CAS  Google Scholar 

  26. Wapner RJ (2013) Antenatal corticosteroids for periviable birth. Semin Perinatol 37:410–413. https://doi.org/10.1053/j.semperi.2013.06.024

    Article  PubMed  Google Scholar 

  27. Crowther CA, Hiller JE, Doyle LW et al (2003) Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA 290:2669–2676. https://doi.org/10.1001/jama.290.20.2669

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Not applicable.

Author information

Author notes

  1. Mor Marsel Sarusi and Tamar Wainstock equally contributed to the article.

Authors and Affiliations

  1. Joyce and Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Mor Marsel Sarusi

  2. Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Eyal Sheiner & Gali Pariente

  3. The Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Tamar Wainstock

Authors
  1. Mor Marsel Sarusi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamar Wainstock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eyal Sheiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gali Pariente
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MMS: conceptualization, investigation, material preparation, literature review, methodology, and writing (original draft); TW: material preparation, data collection, methodology, data analysis and writing (review/edits); ES: conceptualization, supervision, intellectual input and writing (review/edits); GP: conceptualization, supervision, intellectual input and writing (review/edits); All authors have read and agreed to the final version of the manuscript.

Corresponding author

Correspondence to Eyal Sheiner.

Ethics declarations

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

This study was conducted in accordance with the standards and approved by the local institutional ethics committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All subjects provided informed written consent prior to their inclusion in the study.

Disclosure

This study was conducted as part of the requirements for Mor Marsel Sarusi MD degree from the Goldman Medical School at the Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

(DOCX 43 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sarusi, M.M., Wainstock, T., Sheiner, E. et al. Maternal epilepsy- perinatal outcome and long-term neurological morbidity of the offspring: a population-based cohort study. Arch Gynecol Obstet 305, 55–62 (2022). https://doi.org/10.1007/s00404-021-06114-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-021-06114-7

Keywords

Search

Navigation