PREGNANCY OUTCOME AND EARLY DEVELOPMENT OF OFFSPRING IN WOMEN WITH EPILEPSY

Authors

  • BEENA VASANTHY Department of Neurology, Government Medical College Hospital, Gandhinagar, P.O. Kottayam, Kerala, India.
  • MARIA ROSE DOMINIC Research Associate in Central Kerala Pregnancy Epilepsy Registry.
  • VIJAYAN CHANDRATHIL PARAMESWARAN NAIR Department of Obstetrics and Gynecology, Pro Vice Chancellor, Kerala University of Health Sciences, Thrissur, Kerala, India.

DOI:

https://doi.org/10.22159/ajpcr.2022.v15i10.45575

Keywords:

Women, Epilepsy, Antiepileptic drugs, Oxcarbazepine, Clobazam, Pregnancy, Developmental outcome, Malformation

Abstract

Objectives: The aim of the study was to evaluate the outcome of pregnancy and early development of offspring, in women with epilepsy (WWE) who were receiving and not receiving anti-epileptic drugs (AED).

Methods: Women with epilepsy who delivered in a teaching hospital (n=60), between November 2017 and October 2018, were identified from the delivery records (n=5202) and their infants (n=39) underwent developmental assessment by Baroda development screening test. Maternal epilepsy syndrome, AEDs during pregnancy, and other details were obtained from medical records and interview.

Results: Fourteen mothers received monotherapy, 15 polytherapy and 10 mothers were not taking any AED. There were four major congenital malformations (MCM) among 39 babies. Two were cardiac malformations; one was complex anomaly, caused death in neonate and other was ventricular septal defect (VSD). Both occurred in babies of mothers receiving clobazam in combination with oxcarbazepine and levetiracetam, respectively. There were two urological anomalies in babies unexposed to AEDs. When mothers were receiving monotherapy (14), normal Development Quotient score (DQ score) was observed in 11 babies, but low DQ score was observed in three. In the polytherapy group (15), normal DQ scores were found in five and low DQ in nine (one baby died neonatally). Among the group who were unexposed to AED (10), normal DQ score was found in eight, but low DQ in two (in the antenatal period mother of one of the low DQ babies reported frequent major seizures).

Conclusion: Clobazam therapy is a risk factor for developing MCM in babies of WWE. Oxcarbazepine, monotherapy or polytherapy, and Clobazam polytherapy are risk factors for low DQ scores in the offspring of WWE. Polytherapy and frequent seizures during pregnancy are also risk factors for low DQ scores. Widely used drugs which were considered safe demonstrated adverse effects in offspring. Even though sample size is small, it is a matter of concern and curiosity.

Downloads

Download data is not yet available.

References

Koch S, Jäger-Roman E, Lösche G, Nau H, Rating D, Helge H. Antiepileptic drug treatment in pregnancy: Drug side effects in the neonate and neurological outcome. Acta Paediatr 1996;85:739-46. doi: 10.1111/j.1651-2227.1996.tb14137.x, PMID 8816215

Thomas SV, Ajaykumar B, Sindhu K, Nair MK, George B, Sarma PS. Motor and mental development of infants exposed to antiepileptic drugs in utero. Epilepsy Behav 2008;13:229-36. doi: 10.1016/j. yebeh.2008.01.010, PMID 18346940

Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009;360:1597-605

Thomas SV, Jose M, Divakaran S, Sarma PS. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India. Epilepsia 2017;58:274-81. doi: 10.1111/epi.13632, PMID 28084641

Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010;362:2185-93. doi: 10.1056/ NEJMoa0907328, PMID 20558369

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. doi: 10.1016/j. seizure.2017.05.004, PMID 28641176

Whelehan A, Delanty N. Therapeutic strategies for treating epilepsy during pregnancy. Expert Opin Pharmacother 2019;11;20:323-32. doi: 10.1080/14656566.2018.1550073, PMID 30526135

Sveberg L, Svalheim S, Taubøll E. The impact of seizures on pregnancy and delivery. Seizure 2015;28:35-8. doi: 10.1016/j.seizure.2015.02.020, PMID 25746572

Phatak AT, Khurana B. Baroda development screening test for infants. Indian Pediatr 1991;28:31-7. PMID 1711514

Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: A practical clinical definition of epilepsy. Epilepsia 2014;55:475-82. doi: 10.1111/epi.12550, PMID 24730690

Kjøller M, Thoning H. Characteristics of non-response in the Danish health interview surveys, 1987-1994. Eur J Public Health 2005;15:528-35. doi: 10.1093/eurpub/cki023, PMID 16051660

Chen YH, Chiou HY, Lin HC, Lin HL. Affect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 2009;66:979-84. doi: 10.1001/archneurol.2009.142, PMID 19667219

Ozdemir O, Sarı ME, Ertuğrul FA, Kurt A, Selimova V, Atalay CR. The effects of a history of seizures during pregnancy on umbilical arterial blood gas values in pregnant women with epilepsy. J Turk Ger Gynecol Assoc 2014;15:135-9. doi: 10.5152/jtgga.2014.13118, PMID 25317039

Teramo K, Hiilesmaa V, Bardy A, Saarikoski S. Fetal heart rate during a maternal grand mal epileptic seizure. J Perinat Med 1979;7:3-6. doi: 10.1515/jpme.1979.7.1.3, PMID 106102

Faught E, Duh MS, Weiner JR, Guérin A, Cunnington MC. Nonadherence to antiepileptic drugs and increased mortality: Findings from the RANSOM Study. Neurology 2008;71:1572-8. doi: 10.1212/01. wnl.0000319693.10338.b9, PMID 18565827

Meador KJ, Baker G, Cohen MJ, Gaily E, Westerveld M. Cognitive/ behavioral teratogenetic effects of antiepileptic drugs. Epilepsy Behav 2007;11:292-302. doi: 10.1016/j.yebeh.2007.08.009, PMID 17996637

Adab N, Kini U, Vinten J, Ayres J, Baker G, Clayton-Smith J, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 2004;75:1575-83. doi: 10.1136/ jnnp.2003.029132, PMID 15491979

Rolnitsky A, Merlob P, Klinger G. In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia. Pediatr Neurol 2013;48:466-8. doi: 10.1016/j.pediatrneurol.2013.02.012, PMID 23668873

Veroniki AA, Cogo E, Rios P, Straus SE, Finkelstein Y, Kealey R, et al. Comparative safety of anti-epileptic drugs during pregnancy: A systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Med 2017;15:95. doi: 10.1186/s12916-017-0845-1, PMID 28472982

Montouris G. Oxcarbazepine safety of the newer antiepileptic drug during pregnancy. Curr Med Res Opin 2005;21:693-701.

Videman M, Stjerna S, Roivainen R, Nybo T, Vanhatalo S, Gaily E, et al. Evidence for spared attention to faces in 7-month-old infants after prenatal exposure to antiepileptic drugs. Epilepsy Behav 2016;64:62-8. doi: 10.1016/j.yebeh.2016.09.023, PMID 27732918

Buchanan N. Clobazam in the treatment of epilepsy: Prospective follow-up to 8 years. J R Soc Med 1993;86:378-80. doi: 10.1177/014107689308600703, PMID 8371242

Dean L. Clobazam therapy and CYP2C19 genotype. Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kane MS, Kattman BL, et al., editors. In: Medical Genetics Summaries. Bethesda: National Center for Biotechnology Information US; 2019. p. 2012.

National Center for Biotechnology Information. PubChem Compound Summary for Information CID2789, Clobazam; 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/clobazam [Last accessed on 2021 Jan 26].

Andrade C. Gestational exposure to benzodiazepines, 3: Clobazam and major congenital malformations. J Clin Psychiatry 2019;80:19f13151. doi: 10.4088/JCP.19f13151, PMID 31774946

Mawhinney E, Craig J, Morrow J, Russell A, Smithson WH, Parsons L, et al. Levetiracetam in pregnancy: Results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013;80:400-5. doi: 10.1212/WNL.0b013e31827f0874, PMID 23303847

Koc G, Guler SK, Karadas O, Yoldas T, Gokcil Z. Fetal safety of levetiracetam use during pregnancy. Acta Neurol Belg 2018;118:503-8. doi: 10.1007/s13760-018-0996-7, PMID 30056483

Shallcross R, Bromley RL, Irwin B, Bonnett LJ, Morrow J, Baker GA, et al. Child development following in utero exposure: Levetiracetam vs sodium valproate. Neurology 2011;76:383-9. doi: 10.1212/ WNL.0b013e3182088297, PMID 21263139, PMCID PMC3271390

Gerard EE, Meador KJ. An update on maternal use of antiepileptic medications in pregnancy and neurodevelopment outcomes. J Pediatr Genet 2015;4:94-110. doi: 10.1055/s-0035-1556741, PMID 27617120, PMCID PMC4918792

Hill DS, Wlodarczyk BJ, Palacios AM, Finnell RH. Teratogenic effects of antiepileptic drugs. Expert Rev Neurother 2010;10:943-59. doi: 10.1586/ern.10.57, PMID 20518610, PMCID PMC2970517

Published

07-10-2022

How to Cite

VASANTHY, B., M. R. DOMINIC, and V. C. PARAMESWARAN NAIR. “PREGNANCY OUTCOME AND EARLY DEVELOPMENT OF OFFSPRING IN WOMEN WITH EPILEPSY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 15, no. 10, Oct. 2022, pp. 79-83, doi:10.22159/ajpcr.2022.v15i10.45575.

Issue

Section

Original Article(s)