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Cardiac Malformations Are Increased in Infants of Mothers with Epilepsy

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Abstract

We aimed to ascertain the prevalence of cardiac malformation (CM) and its association with antenatal exposure to an antiepileptic drug (AED) in infants of mothers with epilepsy (IMEs). Women with epilepsy (WWE) are enrolled in Kerala Registry of Epilepsy and Pregnancy (KREP) in the prepregnancy or early pregnancy period and are followed up with a standard protocol until the IMEs are 6 years old. At 3 months postpartum, a cardiologist, blinded to the AED exposure, carried out a clinical examination and echocardiography on all live-born babies. Patent foramen ovale (PFO) and interatrial septal defects of < 5 mm in size were excluded from CM. Details of maternal epilepsy, folate usage, AED exposure in the first trimester, and newborn characteristics were abstracted from the records of the KREP. We examined 462 babies. Maternal epilepsy was generalized in 201 (43.50%) or localization related in 241 (52.2%). The AED exposure was monotherapy in 262 (56.7%)—carbamazepine (112), valproate (71), phenobarbitone (43), phenytoin (31), and clonazepam (2)—and polytherapy in 126 (27.3%). Seventy-four infants (16.01%) had no AED exposure. There were 36 infants with CM (7.8%; 95% confidence interval: 5.5–10.6). CMs included atrial septal defect (26; 72.2%), tetrology of Fallot (3; 8.3%), patent ductus arteriosus and pulmonic stenosis (2 each; 5.6%), and ventricular septal defect, tricuspid regurgitation, transposition of great arteries (1 each; 2.8%). CMs were significantly more for IMEs with premature birth (p < .003). There was no association between CM and maternal age, epilepsy syndrome, seizure frequency during pregnancy, and folate use. CMs were more frequent with polytherapy (13; 10.3%) compared to monotherapy (17; 6.5%). Those with valproate exposure had a trend (not statistically significant) toward higher frequency of CM compared to IMEs on other AEDs as monotherapy.

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References

  1. American Academy of Pediatrics Committee on Drugs, Anticonvulsants and Pregnancy (1979) Pediatrics 63:331–333

    Google Scholar 

  2. Artama M, Auvinen A, Raudaskoski T, Isojarvi I, Isojarvi J (2005) Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology 64:1874–1878

    Article  PubMed  CAS  Google Scholar 

  3. Bertollini R, Mastroiacovo P, Segni G (1985) Maternal epilepsy and birth defects: a case-control study in the Italian Multicentric Registry of Birth Defects (IPIMC). Eur J Epidemiol 1:67–72

    Article  PubMed  CAS  Google Scholar 

  4. Brent RL (2004) Environmental causes of human congenital malformations: the pediatrician's role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics 113(4 Suppl):957–968

    PubMed  Google Scholar 

  5. Carlgren L-E, Ericson A, Kallen B (1987) Monitoring of congenital cardiac defects. Paediatr Cardiol 8:247–256

    Article  CAS  Google Scholar 

  6. Craig J, Morrison P, Morrow J, Patterson V (1999) Failure of periconceptual folic acid to prevent a neural tube defect in the offspring of a mother taking sodium valproate. Seizure 8:253–254

    Article  PubMed  CAS  Google Scholar 

  7. Friis ML, Hauge M (1985) Congenital heart defects in live-born children of epileptic parents. Arch Neurol 42:374–376

    PubMed  CAS  Google Scholar 

  8. Hanna EJ, Nevin NC, Nelson J (1994) Genetic study of congenital heart defects in Northern Ireland (1974–1978). J Med Genet 31:858–863

    PubMed  CAS  Google Scholar 

  9. Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA (2000) Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 343:1608–1614

    Article  PubMed  CAS  Google Scholar 

  10. Hoffman JI, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardol 39:1890–1900

    Article  Google Scholar 

  11. Hoffman JIE (2002) Incidence, mortality and natural history. In Anderson RH, Baker EJ, Macartney FJ, Rigby ML, Shinebourne EA, Tynan MJ (eds), Paediatric cardiology, 2nd ed. Churchill Livingstone, Edinburgh, Vol, I, pp 111–139

  12. Izukawa T (1992) Lightfoot NE trends in neonatal congenital heart disease: the Toronto experience. In Freedom RM, Benson LN, Smallhorn JF (eds), Neonatal heart disease. Springer-Verlag, London, pp 31–33

    Google Scholar 

  13. Kaneko S, Battino D, Andermann E, Wada K et al. (1999) Congenital malformations due to antiepileptic drugs. Epilepsy Res 33:145–158

    Article  PubMed  CAS  Google Scholar 

  14. Kaneko S, Otani K, Kondo T et al. (1992) Malformations in infants of mothers with epilepsy receiving antiepileptic drugs. Neurology 42(4 Suppl 5):68–74

    PubMed  CAS  Google Scholar 

  15. Kaplan PW (2004) Reproductive health effects and teratogenicity of antiepileptic drugs. Neurology 63(10 Suppl 4):S13–S23

    PubMed  CAS  Google Scholar 

  16. Lindhout D, Omtzigt JG (1994) Teratogenic effects of antiepileptic drugs: implications for the management of epilepsy in women of childbearing age. Epilepsia 35(Suppl 4):S19–S28

    Article  PubMed  Google Scholar 

  17. Mitchell SC, Korones SB, Berendes HW (1971) Congenital heart disease in 56,109births; incidence and natural history. Circulation 43:323–332

    PubMed  CAS  Google Scholar 

  18. Mo CN Ladusans EJ (1999) Anomalous right pulmonary artery origins in association with fetal valproate syndrome. J Med Genet 36:83–84

    Google Scholar 

  19. Morrow J, Russell A, Guthrie E, Parsons L et al. (2006) Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 77:193–198

    Article  PubMed  CAS  Google Scholar 

  20. O’Brien MD, Gilmour-White S (1993) Epilepsy and pregnancy Br Med J 307:492–495

    CAS  Google Scholar 

  21. Ooshima A, Fukushige J, Ueda K (1995) Incidence of structural cardiac disorders in neonates: an evaluation by color Doppler echocardiography and the results of a 1-year follow-up. Cardiology 86:402–406

    PubMed  CAS  Google Scholar 

  22. Pradat P, Francannet C, Harris JA, Robert E (2003) The epidemiology of cardiovascular Defects, Part I: A study based on data from three large registries of congenital malformations. Pediatr Cardiol 24:195–221

    Article  PubMed  CAS  Google Scholar 

  23. Perucca E (2005) Birth defects after prenatal exposure to antiepileptic drugs. Lancet Neurol 4:781–786

    Article  PubMed  CAS  Google Scholar 

  24. Samanek M, Goetzova J, Benesova D (1986) Causes of death in neonates born with a heart malformation. Int J Cardiol 11:63–74

    Article  PubMed  CAS  Google Scholar 

  25. Sindhu K, Thomas SV, Ajaykumar B, Sylaja PN, Sulekhadevi PB, Jacob S (2005) Complications of pregnancy and delivery in women with epilepsy. Epilepsia 46(Suppl 6):84

    Google Scholar 

  26. Sodhi P, Poddar B, Parmar V (2001) Fatal cardiac malformation in fetal valproate syndrome. Indian J Pediatr 68:989–990

    Article  PubMed  CAS  Google Scholar 

  27. Ten Berg K, van Oppen AC, Nikkels PG et al. (2005) Complex cardiac defect with hypoplastic right ventricle in a fetus with valproate exposure. Prenat Diagn 25:156–158

    Article  PubMed  CAS  Google Scholar 

  28. Thisted E, Ebbesen F (1993) Malformations, withdrawal manifestations and hypoglycemia after exposure to valproate in utero. Arch Dis Child 69:288–291

    Article  PubMed  CAS  Google Scholar 

  29. Thomas SV, Indrani L, Devi GC, Jacob S et al. (2001) Pregnancy in women with epilepsy: preliminary results of Kerala Registry of Epilepsy and Pregnancy. Neurol India 49:60–66

    PubMed  CAS  Google Scholar 

  30. Venugopalan P, Agarwal AK, Johston WJ, Riveia E (2002) Spread of heart diseases seeen in an open access pediatric echocardiography clinic. Int J Cardiol 84:211–216

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The Kerala Registry of Epilepsy and Pregnancy is supported by a grant-in-aid from the Kerala Council of Science Technology and Environment, the Indian Epilepsy Society, and the Indian Council of Medical Research.

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Correspondence to S. V. Thomas.

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Thomas, S.V., Ajaykumar, B., Sindhu, K. et al. Cardiac Malformations Are Increased in Infants of Mothers with Epilepsy. Pediatr Cardiol 29, 604–608 (2008). https://doi.org/10.1007/s00246-007-9161-4

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  • DOI: https://doi.org/10.1007/s00246-007-9161-4

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