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Drug Safety
Published in: Drug Safety 3/2004

01-03-2004 | Original Research Article

Malformation Rates in Children of Women with Untreated Epilepsy

A Meta-Analysis

Authors: Shawn Fried, Eran Kozer, Irena Nulman, Thomas R. Einarson, Dr Gideon Koren

Published in: Drug Safety | Issue 3/2004

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Abstract

Background: It is widely quoted that women with epilepsy have a higher than baseline risk for giving birth to a child with malformations, independent of the effects of antiepileptic drugs.
Objective: To determine, based on available evidence, if epilepsy per se represents a teratogenic risk. To systematically review all studies investigating the occurrence of major malformation rates among children of treated or untreated women with epilepsy and non-exposed controls who do not have epilepsy.
Methods: A meta-analysis, using a random effects model, was conducted of all cohort and case-control studies reporting malformation rates in children of women with epilepsy exposed or unexposed to antiepileptic drugs compared with that of children of nonepileptic women. Medline (1966–2001), EMBASE, the Cochrane database as well as REPROTOX (an information system on environmental hazards to human reproduction and development) databases were accessed.
Results: We found ten studies reporting results of untreated epilepsy (n = 400) and their non-epileptic healthy controls (n = 2492). Nine out of ten studies also reported results on 1443 patients exposed to antiepileptic drugs and their 2526 unexposed healthy controls. The risk for congenital malformations in the offspring of women with untreated epilepsy was not higher than among nonepileptic controls (odds ratio [OR] = 1.92; 95% CI 0.92–4.00). There was evidence of publication bias, thus with bias removed the OR was 0.99 (95% CI 0.49–2.01). In contrast, the offspring of epileptic women who received antiepileptic drugs had higher incidences of malformation than controls (OR 3.26; 95% CI 2.15–4.93).
Conclusion: Our study does not support the commonly held view that epilepsy per se represents a teratogenic risk. Our study suggests that this view is the result of a publication bias, with several small (<100 participants) positive studies leading to a premature conclusion.
Literature
1.
Devinsky O, Yerby M. Women with epilepsy: reproduction and effects of pregnancy on epilepsy. Neurol Clin 1994; 12: 479–95PubMed
2.
3.
Martin PJ, Millac PAH. Pregnancy, epilepsy, management and outcome: a 10-year perspective. Seizure 1993; 2: 277–80PubMedCrossRef
4.
Janz D. On major malformations and minor anomalies in the offspring of parents with epilepsy: review of the literature. In: Janz D, Dam M, Richens A, et al., editors. Epilepsy, pregnancy, and the child. New York: Raven Press, 1982: 211–22
5.
Majewski F, Steger M, Richter B, et al. The teratogenicity of hydantoins and barbiturates in humans, with considerations on the etiology of malformations and cerebral disturbances in the children of epileptic parents. Int J Biol Res Pregnancy 1981; 2(1): 37–45PubMed
6.
Dansky LV, Finnell RH. Parental epilepsy, anticonvulsant drugs, and reproductive outcome: epidemiologic and experimental findings spanning three decades. 2: human studies. Reprod Toxicol 1991; 5(4): 301–35PubMedCrossRef
7.
8.
Jones KL, Lacro RV, Johnson K, et al. Patterns of malformations in the children of women treated with carbamazepine during pregnancy. N Engl J Med 1989; 320: 1661–6PubMedCrossRef
9.
10.
Nulman I, Scolnik D, Chitayat D, et al. Findings in children exposed in utero to phenytoin and carbamazepine monotherapy: independent effects of epilepsy medications. Am J Med Genet 1997; 68: 18–24PubMedCrossRef
11.
Koch S, Gopfert-Geyer I, Jager-Roman E, et al. Antiepileptika wahrend der schwangerschaft. Dtsch Med Wochenschr 1983; 108: 250–7PubMedCrossRef
12.
International League Against Epilepsy, Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1990; 30: 389–99
13.
Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001; 344: 1132–8PubMedCrossRef
14.
Spiedel BD, Meadow SR. Maternal epilepsy and abnormalities of the fetus and newborn. Lancet 1972; 21: 839–43CrossRef
15.
Jick SS, Terris BZ. Anticonvulsants and congenital malformations. Pharmacotherapy 1997; 17: 561–4PubMed
16.
Holmes LB, Rosenberger PB, Harvey EA, et al. Intelligence and physical features of children of women with epilepsy. Teratology 2000; 61: 196–202PubMedCrossRef
17.
Koch S, Losche G, Jager-Roman E, et al. Major and minor birth malformations and antiepileptic drugs. Neurology 1992; 42Suppl. 5: 83–8PubMed
18.
Fedrick J. Epilepsy and pregnancy: a report from the Oxford Record Linkage Study. BMJ 1973; 2: 442–8PubMedCrossRef
19.
Koch S, Hartmann A, Jager-Roman E, et al. Major malformations in children of epileptic parents: due to epilepsy or its therapy? In: Janz D, Dam M, Richens A, et al., editors. Epilepsy, pregnancy and the child. New York: Raven Press, 1982: 313-5
20.
Van der Pol MC, Hadders-Algra M, Huisjes HJ, et al. Antiepileptic medication in pregnancy: late effects on the children’s central nervous system development. Am J Obstet Gynecol 1991; 164: 121–8PubMed
21.
Fabris C, Licata D, Stasiowska B, et al. Il neonato da madre epilettica: rischio malformativo ed auxologico. Pediatr Med Chir 1989; 11: 27–32PubMed
22.
Yerby M. Pregnancy, teratogenesis and epilepsy. Neurol Clin 1994; 12: 749–71PubMed
23.
Kaneko S, Otani K, Fukushima J, et al. Teratogenicity of antiepileptic drugs: analysis of possible risk factors. Epilepsia 1988; 29: 459–67PubMedCrossRef
24.
Kaneko S, Fukushima Y, Sato T, et al. Teratogenicity of antiepileptic drugs: a prospective study. Jpn J Psychiatry Neurol 1986; 40: 447–50
25.
Byrne B. Epilepsy and pregnancy. Ir Med J 1997; 90: 173–4
26.
Lopes-Cendes I, Andermann E, Candes F, et al. Risk factors for changes in seizure frequency during pregnancy of epileptic women: a cohort study [abstract]. Epilepsia 1992; 33Suppl. 3: 57
27.
Donaldson JO. Neurologic disorders of pregnancy. In: Reece EA, Hobbins JC, Mahoney MJ, et al., editors. Medicine of the fetus and mother. Philadelphia (PA): JB Lippincott, 1992: 1097–102
Metadata
Title
Malformation Rates in Children of Women with Untreated Epilepsy
A Meta-Analysis
Authors
Shawn Fried
Eran Kozer
Irena Nulman
Thomas R. Einarson
Dr Gideon Koren
Publication date
01-03-2004
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 3/2004
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200427030-00004

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