Advertisement

Improved pregnancy outcome in epileptic women in the last decade: Relationship to maternal anticonvulsant therapy

      This paper is only available as a PDF. To read, Please Download here.
      The prevalence of abnormal pregnancy outcomes in the offspring of 103 epileptic women, followed prospectively during pregnancy between 1982 and 1989, was compared with that in the previous study of 119 pregnancies by Dansky et al from the same institution. Our results have shown a significant decrease in the prevalence of major malformations, as compared with the previous study: 8.8% vs 24.1% (P< 0.01). Monotherapy was more frequent and the mean number of drugs used during pregnancy was significantly smaller in the present study. Phenytoin, phenobarbital and primidone were prescribed less frequently in the present study, whereas carbamazepine and valproic acid were used more frequently. Plasma levels of valproic acid during pregnancy were higher in mothers of malformed babies. In the present study, plasma folate levels were significantly higher, and more patients were taking folate supplements during pregnancy. In conclusion, the type and number of drugs used during pregnancy, as well as the plasma concentrations and serum folate levels, may determine the frequency of abnormal outcomes.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Janz D
        Antiepileptic drugs and pregnancy: altered utilization patterns and teratogenesis.
        Epilepsia. 1982; 23: S53-S63
        • Kelly TE
        • Rein M
        • Edwards P
        Teratogenicity of anticonvulsant drugs IV: the association of clefting and epilepsy.
        Am J Med Genet. 1984; 19: 451-458
        • Shapiro S
        • Slone D
        • Hartz SC
        • et al.
        Anticonvulsants and parental epilepsy in the development of birth defects.
        Lancet. 1976; i: 272-275
        • Dansky L
        • Andermann E
        • Andermann F
        Major congenital malformations in the offspring of epileptic patients: genetic and environmental risk factors.
        in: Janz D Dam M Richens A Bossi L Helge H Schmidt D Epilepsy, pregnancy, and the child. Raven Press, New York1982: 223-233
        • Dansky L
        • Andermann E
        • Sherwin AL
        • Andermann F
        • Kinch RA
        Maternal epilepsy and birth defects: a prospective study with monitoring of plasma anticonvulsant levels during pregnancy.
        in: Dam M Gram L Penry JK Advances in epileptology: XIIth Epilepsy International Symposium. Raven Press, New York1981: 607-612
        • Dansky L
        • Andermann E
        • Andermann F
        • Sherwin AL
        • Kinch RA
        Maternal epilepsy and congenital malformations: correlation with maternal plasma anticonvulsant levels during pregnancy.
        in: Janz D Dam M Richens A Bossi L Helge H Schmidt D Epilepsy, pregnancy, and the child. Raven Press, New York1982: 251-258
        • Lindhout D
        • Hoppener RJEA
        • Meinardi H
        Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation (of carbamazepine).
        Epilepsia. 1984; 25: 77-83
        • Kaneko S
        • Otani K
        • Fukushima Y
        • et al.
        Teratogenicity of antiepileptic drugs: analysis of possible risk factors.
        Epilepsia. 1988; 29: 459-467
        • Strickler SM
        • Dansky L
        • Miller MA
        • Seni MH
        • Andermann E
        • Spielberg SP
        Genetic predisposition to phenytoin-induced birth defects.
        Lancet. 1985; ii: 746-749
        • Dansky L
        • Andermann E
        • Rosenblatt D
        • Sherwin AL
        • Andermann F
        Anticonvulsants, folate levels, and pregnancy outcome: a prospective study.
        Ann Neurol. 1987; 21: 176-182
        • Hiilesmaa VK
        • Teramo K
        • Granstrom M-L
        • Bardy AH
        Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures and fetal outcome.
        Br Med J. 1983; 287: 577-579
        • Gjerde IO
        • Strandjord RE
        • Ulstein M
        The course of epilepsy during pregnancy: a study of 78 cases.
        Acta Neurol Scand. 1988; 78: 198-205
        • Dansky L
        Outcome of pregnancy in epileptic women.
        in: PhD thesis. McGill University, Montreal1989
        • Dansky L
        • Wolfson C
        • Andermann E
        • Andermann F
        • Sherwin A
        A multivariate analysis of risk factors for major congenital malformations in offspring of epileptic women (abstr).
        Epilepsia. 1989; 30: 678
        • Dellaportas DI
        • Shorvon SD
        • Galbraith AW
        • et al.
        Chronic toxicity in epileptic patients receiving single-drug treatment.
        Br Med J. 1982; 285: 409-410
        • Kutt H
        The use of blood levels of antiepileptic drugs in clinical practice.
        Pediatrics. 1974; 53: 557-560
        • Perucca E
        • Richens A
        Interpretation of drug levels: relevance of protein binding.
        in: Drug concentration in neuropsychiatry, Ciba Foundation Symposium 74. Excerpta Medica, Amsterdam1981: 51-58
        • Gray SW
        • Skandalakis VE
        The anterior body wall.
        in: Gray SW Skandalakis VE Embryology for surgeons: the embryological basis for the treatment of congenital defects. WB Saunders Company, Philadelphia-London-Toronto1972: 387-441
        • Bergsma D
        Birth defects compendium. 2nd ed. Alan R. Liss, New York1979
        • Lovell WW
        • Price CT
        • Meehan PL
        The foot.
        in: Conell WW Winter RB Pediatric orthopedics. 2nd ed. WB Lippincott Company, Philadelphia1986: 895-977
        • Carter CO
        Genetics of common disorders.
        Br Med Bull. 1969; 25: 52-57
        • Lindsay WK
        Cleft Up.
        in: Ravitch MM Welch KJ Benson CE Aberdeen E Randolph VG Pediatric surgery. 3rd ed. Year Book Medical Publishers, Inc, Chicago-London1979: 262-272
        • Lindsay WK
        Cleft palate.
        in: Ravitch MM Welch KJ Benson CE Aberdeen E Randolph VG Pediatric surgery. 3rd ed. Year Book Medical Pub-Ushers, Inc., Chicago London1979: 272-281
        • MacEwen GD
        • Bunnell WP
        • Ramsey PL
        The hip.
        in: Conell W Winter RB Pediatric orthopedics. 2nd ed. WB Lippincott Company, Philadelphia1986: 703-780
        • Friis ML
        • Broeng-Nielsen B
        • Sindrup EH
        • Lund M
        • Fogh-Andersen P
        • Hauge M
        Increased prevalence of cleft lip and/ or cleft palate among epileptic patients.
        in: Janz D Bossi L Dam M Helge H Richens A Schmidt D Epilepsy, pregnancy, and the child. Raven Press, New York1982: 297-298
        • Friis ML
        • Hauge M
        Congenital heart defects in live-born children of epileptic parents.
        Arch Neurol. 1985; 42: 374-376
        • Friis ML
        Epilepsy among parents of children with facial clefts.
        Epilepsia. 1979; 20: 69-76
        • Friis ML
        Facial clefts and congenital heart defects in children of parents with epilepsy: genetic and environmental etiologic factors.
        Acta Neurol Scand. 1989; 79: 433-459
        • Knight AH
        • Rhind EG
        Epilepsy and pregnancy: a study of 153 pregnancies in 59 patients.
        Epilepsia. 1975; 16: 99-110
        • Hill RM
        • Tennyson LM
        Significant anomalies in the anti-epileptic drug syndrome: comment (1982).
        in: Janz D Dam M Richens A Bossi L Helge H Schmidt D Epilepsy, pregnancy, and the child. Raven Press, New York1982: 309-311
        • Kaneko S
        • Fukushima Y
        • Sato T
        Hazards of fetal exposure to antiepileptic drugs: a preliminary report.
        in: Sato T Shinagawa S Antiepileptic drugs and pregnancy. Excerpta Medica, Amsterdam1984: 132-138
        • Jager-Roman E
        • Koch S
        Major malformations and minor anomalies in infants exposed to different antiepileptic drugs during pregnancy.
        in: Wolf P Dam M Janz D Dreifuss FE Advance in epileptology. Vol 16. Raven Press, New York1987: 561-565
        • Millar JHD
        • Nevin NC
        Congenital malformations and anticonvulsant drugs.
        Lancet. 1973; i: 328
        • Lindhout D
        • Meinardi H
        • Barth PG
        Hazards of fetal exposure to drug combinations.
        in: Janz D Bossi L Dam M Helge H Richens A Schmidt D Epilepsy, pregnancy and the child. Raven Press, New York1982: 275-281
        • Robert E
        • Gibaud P
        Maternal valproic acid and congenital neural tube defects.
        Lancet. 1982; ii: 937
        • Bjerkedal T
        • Czeizel A
        • Goujard J
        Valproic acid and spina bifida.
        Lancet. 1982; ii: 1096-1097
        • Lindhout D
        • Schmidt D
        In-utero exposure to valproate and neural tube defects.
        Lancet. 1986; i: 1392-1393
      1. Data from Canadian congenital anomalies surveillance system, Surveillance and Risk Assessment Divison, Bureau of Chronic Disease Epidemiology, Health and Welfare Canada, Ottawa.

        • Bertollini R
        • Kallen B
        • Mastroiacovo P
        • Robert E
        Anticonvulsant drugs in monotherapy. Effect on the fetus.
        Eur J Epidemiol. 1987; 3: 164-171
        • Wladimiroff JW
        • Stewart PA
        • Reuss A
        • Swaay EV
        • Lindhout D
        • Sachs ES
        The role of ultrasound in the early diagnosis of fetal structural defects following maternal anticonvulsant therapy.
        Ultrasound in Med & Biol. 1988; 14: 657-660
        • Huot C
        • Gauthier M
        • Lebel M
        • Larbrisseau A
        Congenital malformations associated with maternal use of valproic acid.
        Can J Neurol Sci. 1987; 14: 290-293
        • Del Ser T
        • Bermejo F
        • Munoz-Garcia D
        • Portera A
        Psychological disturbances and folic acid in chronic epileptic outpatients.
        Epilepsia. 1983; 24: 558-596
        • Chanarin I
        • Rothman D
        • Ward A
        • Perry J
        Folate status and requirement in pregnancy.
        Br Med J. 1968; 2: 390-394
        • Willoughby MLN
        • Jewell FG
        Folate status throughout pregnancy and in the postpartum period.
        Br Med J. 1968; 4: 356-360
        • Nelson MM
        • Wright HV
        • Asling CW
        • Evans HM
        Multiple congenital abnormalities resulting from transitory deficiency of pteroylglutamic acid during gestation in the rat.
        J Nutr. 1955; 56: 349-363
        • Kinney CS
        • Morse LM
        Effect of a folic acid antagonist, aminopterin, on fetal development and nucleic acid metabolism in the rat.
        J Nutr. 1964; 84: 288-294
        • Jordan RL
        • Wilson JG
        • Schumacher HJ
        Embryotoxicity of the folate antagonist methotrexate in rats and rabbits.
        Teratology. 1977; 15: 73-80
      2. Crandall BF Brazier MAB Prevention of neural tube defects. Academic Press, New York1978: 163-205
        • Scott DE
        • Whalley PJ
        • Pritchard JA
        Maternal folate deficiency and pregnancy wastage. II. Fetal malformation.
        Obstet Gynecol. 1970; 36: 26-28
        • Milunsky A
        • Jick H
        • Jick SS
        • et al.
        Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects.
        JAMA. 1989; 262: 2847-2852
        • Baylis EM
        • Crowley JM
        • Preece JM
        • et al.
        Influence of folic acid on blood-phenytoin levels.
        Lancet. 1971; 1: 62-64
        • Ogawa Y
        • Shinagawa S
        • Munakata S
        • Nagasawa K
        Mechanism of teratogenicity of antiepileptic drugs. 2nd Report: maternal serum folic acid levels (abstr).
        in: Program of the 16 th Epilepsy International Congress, Hamburg1985
        • Andermann E
        • Andermann F
        • Dansky L
        Counseling for epileptic women of childbearing age.
        in: Dam M Gram L Penry JK Advances in epileptology: XIIth Epilepsy International Symposium. Raven Press, New York1981: 219-227