Epilepsy, Pregnancy, and the Child
Sunao Kaneko
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorSunao Kaneko
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan
Search for more papers by this authorAbstract
Women with epilepsy have many legitimate concerns regarding the effects of their condition and the use of antiepileptic drugs (AEDs) on their unborn children. These concerns fall into 4 areas: increased seizure frequency during pregnancy, risk of birth defects, risks associated with breast- feeding, and psychomotor retardation in offspring. Studies have shown that many of these risks can be minimized with appropriate management and counseling. Data also show that psychomotor retardation in offspring of mothers with epilepsy is generally transitory. In this article, associations between maternal use of AEDs, birth defects, intrauterine growth retardation, and the psychomotor development are discussed together with how best to alter AED therapy to minimize them.
References
- 1 Kaneko, S, Kondo, T. Antiepileptic agents and birth defects. Incidence, mechanisms and prevention. CNS Drugs 1995; 3: 41–55.
- 2 Ogawa, Y, Fukushi, A, Nomura, Y, et al. Complications of pregnancy, labor and delivery in women with epilepsy. In: T Sato, S. Shinagawa eds. Antiepileptic drugs and pregnancy. Amsterdam : Excerpta Medica, 1984: 87–97.
- 3 Kaneko, S. Antiepileptic drug therapy and reproductive consequence: Functional and morphologic effects. Reprod Toxicol 1991; 5: 179–198.
- 4 Nau, H, Rating, D, Koch, S, Hauser, I, Helge, H. Valproic acid and its metabolites: Placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in nconates of epileptic mothers. J Pharmacol Exp Ther 1981a; 291: 768–777.
- 5 Kojima, S, Ogura, H, Yokoyama, M, Ookawa, S. The effect of di-azepam on neonatal neurobehavioral response. Acta Obstet Gynecol Jpn 1985; 37: 2784–90.
- 6 de Vinsky, O, Yerby, MS. Women with epilepsy. Neurol Clin 1994; 16: 479–496.
- 7 Mattson, RH, Cramer, JA, Darney, PD, Naftolin, F. Use of oral contraceptives by women with epilepsy. JAMA 1986; 256: 238–240.
- 8 Kaneko, S. Responses to antiepileptic drugs: Effects and unwanted effects. [In Japanese.] Jpn J Neuropsychopharmacol 1995; 12: 873–883.
- 9 O'Brien, MD, Gilmour-White S. Epilepsy and pregnancy. BMJ 1993; 307: 492–495.
- 10 Kaneko, S, Battino, D, Andermann, E, et al. International collaborative study on mechanisms of teratogenesis of antiepileptic drugs (A preliminary report) [in Japanese, abstract in English]. Ann Rep Jpn Epil Res Found 1993; 5: 191–199.
- 11 Kaneko, S. Pregnancy and quality of life in women with epilepsy. Clinical Therapeutics 1998; 20 (Suppl A): 30–47.
- 12 Lander, SM, Eadie, MJ. Plasma antiepileptic drug concentrations during pregnancy. Epilepsia 1991; 32: 257–266.
- 13 Tomson, T, Lindbom, U, Ekqvist, B, Sundqvist, A. A prospective study of seizure control in relation to free and total plasma concentrations of carbamazepine and phenytoin. Epilepsia 1994; 325: 122–130.
- 14 Kaneko, S, Battino, D, Andermann, E, et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999; 33: 145–158.
- 15 Kaneko, S, Otani, K, Fukushima, Y, et al. Teratogenicity of antiepileptic drugs: analysis of possible risk factors. Epilepsia 1988; 29: 459–467.
- 16 Kaneko, S, Otani, K, Kondo, T, et al. Malformation in infants of mothers with epilepsy receiving antiepileptic drugs. Neurology 1992; 42(Suppl 5): 68.
- 17 Hanson, JW, Smith, DW. The fetal hydantoin syndrome. J Pediatr 1975; 87: 285–290.
- 18 Di Liberti, JM, Farndon, PA, Dennis, NR. The fetal valproate syndrome. Am J Med Genet 1984; 19: 473–481.
- 19 Gaily, E, Granstrom, ML, Hiilesmaa, V, Bardy, A. Minor anomalies in offspring of epileptic mothers. J Pediatr 1988; 112: 520–529.
- 20 Jager-Roman, E, Deichl, A, Jacob, S, et al. Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid. J Pediatr 1986; 108: 997–1004.
- 21 Lindhout, D, Schmidt, D. In-utero-exposure to valproate and neural tube defects. Lancet 1986; 1: 1392–1393.
- 22 Rosa, FW. Spina bifida in infants of women treated with carba-mazepine during pregnancy. N Engl J Med 1991; 342: 674–677.
- 23 Kaneko, S, Otani, K, Kondo, T, et al. Teartogenicity of antiepileptic drugs and drug specific malformations. Jpn J Psychiatr Neurol 1993; 47: 306–308.
- 24 Kondo, T, Kaneko, S, Amano, Y, Egawa, I. Preliminary report on teratogenic effects of zonisamide in the offspring treated women with epilepsy. Epilepsia 1996; 27: 1242–1244.
- 25 Dansky, L, Andermann, E, Andermann, F. Maternal epilepsy and congenital malformations: correlation with maternal plasma anti-convulsant levels during pregnancy. In: D Janz, D Dam, A Richens, L Bossi, H Helge, D. Schmidt eds. Epilepsy, Pregnancy, and the Child. New York : Raven Press, 1982: 251–258.
- 26 Kaneko, S. Major malformations in children of mothers with epilepsy. Eur J Neurol 1995: 2(Suppl 4): 51–63.
- 27 Lindhout, D, Hoppener, RJEA, Meinardi, H. Teratogenicity of anti-epileptic drug combinations with special emphasis on epoxidation (of carbamazepine). Epilepsia 1984; 25: 77–83.
- 28 Kitay, DZ. Folic acid and reproduction. Clin Obstet Gynecol 1979; 22: 809–817.
- 29 Meadow, SR. Anticonvulsant drugs and congenital abnormalities. Lancet 1968; 2: 1296.
- 30 Dansky, LV, Andermann, E, Rosenblatt, D, Sherwin, AL, Andermann, F. Anticonvulsants, folate levels, and pregnancy outcome: A prospective study. Ann Neurol 1987; 21: 176–182.
- 31 Ogawa, Y, Kaneko, S, Otani, K, Fukushima, Y. Serum folic acid levels in epileptic mothers and their relationship to congenital malformations. Epilepsy Res 1991; 8: 75–78.
- 32 Netzloff, ML, Streiff, RR, Frias, JL, Rennert, DM. Folate antagonism following teratogenic exposure to diphenylhydantoin. Teratology 1979; 9: 45–50.
- 33 Wells, PG, Harbison, RD. Significance of the phenytoin reactive arene oxide intermediate, its oxepin tautomer, and clinical factors modifying their roles in phenytoin-induced teratology. In: TH Hassell, MC Johnston, KH. Dudley eds. Phenytoin-induced teratology and gingival pathology. New York : Raven Press, 1980: 83–112.
- 34 Gaily, E, Granstrom, M-L. A transient retardation of early postnatal growth in drug exposed children of epileptic mothers. Epilepsy Res 1989; 4: 147–155.
- 35 Ogawa, Y, Shinagawa, S, Kaneko, S, et al. Physical development in offspring born to treated epileptic mothers, with reference to various hormone levels. Advances in epileptology 1989; 17: 237–241.
- 36 Battino, D, Kaneko, S, Aandermann, E, et al. Intrauterine growth in the offspring of epileptic women: a prospective multicenter study. Epilepsy Res 1999; 36: 53–60.
- 37 Kaneko, S, Hirano, T, Muramatsu, E and Nomura, Y. Fetal and neonatal effects of antiepileptic drugs-the physical and psychomo-tor developments in the offspring of epileptic parents. In: T Fujii and PM Adams eds. Functional teratologenesis. Tokyo : Teikyo University Press. 1987; 205–214.
- 38 Kaneko, S, Otani, K, Fukushima, Y, et al. Effects of antiepileptic drugs on hGH, TSH and thyroid hormone concentrations during pregnancy. Biol Res in Pregn 1982; 3: 148–151.
- 39 Kaneko, S. Antiepileptic drug therapy of women with epilepsy of childbearing age: functional effects in offspring and developmental measures. In: T Seki ed. Brain damage associated with prenatally environmental factors. Tokyo : Organizing committee of the 6th International symposium on developmental disabilities. 1994; 113–122.
- 40 Gluckmann, PD and Liggins, GC. Regulation of fetal growth. In: RW Beard and PW Nathanielsz, eds. Productive medicine. No 6. New York : Marcel Dekker, 1984; 511–557.
- 41 Liggins, GC, Kitterman, JA and Forster, CS. Fetal maturation related to parturition. Anim Reprod Sci 1979; 2: 193–207.
- 42 Hirano, T, Okada, M, Mihara, K, et al. Antiepileptic drug therapy and folic acid supplementation. In: Y Fukushima and S Kaneko eds. Treatment of women with epilepsy of childbearing age. (in Japanese) Tokyo : Iwasaki Gakujyutu shuppan, 1993; 49–58.