Epilepsy and pregnancy: Report of an Epilepsy Research Foundation Workshop

Epilepsy Research

Volumn 52, Issue 3, 2003, Pages 147-187

  Barrett, Camilla ^a   Richens, Alan ^a  

^a Epilepsy Research Foundation   (United Kingdom)

Author keywords

Antiepileptic drugs; Congenital malformations; Epilepsy; Pregnancy; Teratogenicity

Indexed keywords

ANTICONVULSIVE AGENT; ANTIOXIDANT; BENZODIAZEPINE; CARBAMAZEPINE; CISAPRIDE; CYTOCHROME P450; DOFETILIDE; ENZYME; FOLIC ACID; IRON CHELATE; LIPOXYGENASE; PHENOBARBITAL; PHENYTOIN; POTASSIUM ION; PRIMIDONE; PROSTAGLANDIN SYNTHASE; REACTIVE OXYGEN METABOLITE; VALPROIC ACID;

ANTICONVULSANT THERAPY; ARRHYTHMOGENESIS; CHILDHOOD; COGNITIVE DEFECT; COGNITIVE DEVELOPMENT; CONFERENCE PAPER; CONGENITAL HEART DISEASE; CONGENITAL MALFORMATION; DOWN SYNDROME; DRUG EFFECT; DRUG WITHDRAWAL; EMBRYO DEVELOPMENT; EPILEPSY; EPILEPTIC STATE; FACE MALFORMATION; FOLATE METABOLISM; GENE; GENE MUTATION; GENETIC DISORDER; HEART ARRHYTHMIA; HEART MUSCLE ISCHEMIA; HUMAN; HYPOXIA; INTELLIGENCE QUOTIENT; LABOR; LONG TERM EXPOSURE; MATERNAL MORTALITY; METABOLIC DISORDER; NEURAL TUBE DEFECT; NONHUMAN; PREGNANCY; PRENATAL DRUG EXPOSURE; PRENATAL EXPOSURE; PRIORITY JOURNAL; PSYCHOMOTOR DEVELOPMENT; REGISTER; RISK FACTOR; SEIZURE; TERATOGENESIS;

ABNORMALITIES; ABNORMALITIES, DRUG-INDUCED; ANTICONVULSANTS; EPILEPSY; FEMALE; HUMANS; INFANT, NEWBORN; PREGNANCY; PREGNANCY COMPLICATIONS;

EID: 0037236359     PISSN: 09201211     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0920-1211(02)00237-1     Document Type: Conference Paper

References (136)

1. Adab N., Jacoby A., Smith D., Chadwick D. Additional educational needs in children born to mothers with epilepsy. J. Neurol. Neurosurg. Psychiatry. 70:(1):2001;15-21.
2. Aggarwal P., Chaudhari S., Bhave S., Pandit A., Barve S. Clinical predictors of outcome in hypoxic ischaemic encephalopathy in term neonates. Ann. Trop. Paediatr. 18:1998;117-121.
3. Anderson R.C. Cardiac defects in children of mothers receiving anticonvulsant therapy during pregnancy. J. Pediatr. 89:1976;318-319.
4. Andrews J.E., Ebron McCoy M.T., Bojic U., Nau H. Stereoselective dysmorphogenicity of the enantiomers of the valproic acid analogue 2-n-propyl-4-pentynoic acid (4-yn-VPA): cross species evaluation in whole embryo culture. Teratology. 55:1997;314-318.
5. Annegers J.F., Elveback L.R., Hauser W.A., Kurland L.T. Do anticonvulsants have ateratogenic effect. Arch. Neurol. 31:1974;364-373.
6. Arnon J., Shechtman S., Ornoy A. The use of psychiatric drugs in pregnancy and lactation. Isr. J. Psychiatry Relat. Sci. 37:2000;205-222.
7. Azarbayjani F., Danielsson B.R. Pharmacologically induced embryonic dysrhythmia and episodes of hypoxia followed by reoxygenation: a common teratogenic mechanism for antiepileptic drugs. Teratology. 57:1998;117-126.
8. Azarbayjani F., Danielsson B.R. Phenytoin-induced cleft palate: evidence for embryonic cardiac bradyarrhythmia due to inhibition of delayed rectifier K+ channels resulting in hypoxia-reoxygenation damage. Teratology. 63:2001;152-160.
9. Azarbayjani F., Danielsson B.R. Embryonic arrhythmia by inhibition of HERG channels: a common hypoxia-related teratogenic mechanism for antiepileptic drugs. Epilepsia. 43:2002;457-468.
10. Battino, D., 2001. Assessment of teratogenic risk. Epilepsy Res. 45(1-3), 171-173; Discussion 175-176.
11. Battino D., Kaneko S., Andermann E., Avanzini G., Canevini M.P., Canger R., Croci D., Fumarola C., Guidolin L., Mamoli D., Molteni F., Pardi G., Vignoli A., Fukushima Y., Kan R., Takeda A., Nakane Y., Ogawa Y., Dansky L., Oguni M., Lopez-Ciendas I., Sherwin A., Andermann F., Seni M.H., Goto M., et al. Intrauterine growth in the offspring of epileptic women: a prospective multicenter study. Epilepsy Res. 36:(1):1999;53-60.
12. Baum M., Chinnock R., Ashwal S., Peverini R., Trimm F., Bailey L. Growth and neurodevelomental outcome in infants undergoing heart transplantation. J. Hearth Lung Transplant. 12:1993;211-217.
13. Bayley N. Manual for the Bayley Scales of Infant Development. 1969;The Psychological Corporation, New York.
14. Beghi E., Annegers J.F. Pregnancy registries in epilepsy. Epilepsia. 42:2001;1422-1425.
15. Berg, K, Lindhout, D. Antiepileptic drugs in pregnancy: options for prevention of congenital abnormalities. Commun. Genet. (in press).
16. Berry R.G., et al. Prevention of neural tube defects with folic acid in China. China-US collaborative project for neural tube defect prevention. New Engl. J. Med. 341:(20):1999;1485-1490.
17. Bertollini R., Kallen B., Mastroiacovo P., Robert E. Anticonvulsant drugs in monotherapy. Effect on the foetus. Eur. J. Epidemiol. 3:(2):1987;164-171.
18. Bjerkedal T. Janz D., Dam M., Bossi L., Helge H., Richens A., Schmidt D. Epilepsy, Pregnancy, and the Child. 1982;317-323 Raven Press, New York.
19. Blaheta R.A., Nau H., Michaelis M., Cinatl J. Valproate and valproate-analogues: potent tools to fight against cancer. Curr. Med. Chem. 9:2002;1417-1433.
20. Bojic U., Ehlers K., Ellerbeck U., Bacon C.L., O'Driscoll E., O'Connell C., Berezin V., Kawa A., Lepekhin E., Bock E., Regan C.M., Nau H. Studies on the teratogen pharmacophore of valproic acid analogues: evidence of interactions at hydrophobic center. Eur. J. Pharmacol. 354:(2-3):1998;289-299.
21. Botto L.D., Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am. J. Epidemiol. 151:2000;862-877.
22. Buehler B.A., Delimont D., van Waes M., Finnell R.H. Prenatal prediction of risk of the foetal hydantoin syndrome. New Engl. J. Med. 322:1990;567-572.
23. Craig J., Morrison P., Morrow J., Patterson V. Failure of pre-conceptual folic acid to prevent a neural tube defect in the offspring of a mother taking sodium valproate. Seizure. 8:1999;153-254.
24. Crawford P., Appleton R., Betts T., Duncan J., Guthrie E., Morrow J.I. Best practice guidelines for the management of women with epilepsy. Seizure. 8:1999;201-217.
25. Czeizel A.E. Reduction of urinary tract and cardiovascular defects by periconceptual multivitamin supplementation. Am. J. Med. Genet. 62:1996;179-183.
26. Danielsson B.R., Sköld A.C., Azarbayjani F. Class III antiarrhythmics and phenytoin: teratogenicity due to embryonic cardiac dysrhythmia and reoxygenation damage. Curr. Pharm. Design. 7:2001;787-802.
27. Dean J.C.S., Moore S.J., Osborne A., Howe J., Turnpenny P.D. Foetal anticonvulsant syndrome and mutation in the maternal MTHFR gene. Clin. Genet. 56:1999;216-220.
28. Dean J.C.S., Hailey H., Moore S.J., Lloyd D.J., Turnpenny P.D., Little J. Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth. J. Med. Genet. 39:2002;251-259.
29. Delassio D.J. Seizure disorders and pregnancy. New Engl. J. Med. 312:1985;55-63.
30. Dessens A.B., Boer K., Koppe J.G., van de Poll N.E., Cohen-Kettenis P.T. Studies on long-lasting consequences of prenatal exposure to anticonvulsant drugs. Acta Paediatr. Suppl. 404:1994;54-64.
31. Dessens A.B., Cohen-Kettenis P.T., Mellenbergh G.J., van de Poll N.E., Koppe J.G., Boer K. Prenatal exposure to anticonvulsants and psychosexual development. Arch. Sex. Behav. 28:1999;31-44.
32. Dessens A.B., Cohen-Kettenis P.T., Mellenbergh G.J., Koppe J.G., van de Poll N.E., Boer K. Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems. Acta Paediatr. 89:2000;533-541.
33. Dessens A.B., Cohen-Kettenis P.T., Mellenbergh G.J., Koppe J.G., van de Poll N.E., Boer K. Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders. Teratology. 64:2001;181-188.
34. Di Liberti J.R., Farndon P.A., Dennis N.R., Curry C.J.R. The foetal valproate syndrome. Am. J. Med. Genet. 19:1984;483-491.
35. Dolk H., McElhatton P. Assessing epidemiological evidence for the teratogenic effects of anticonvulsant medications. J. Med. Genet. 39:(4):2002;243-244.
36. Dronamraju K.R. Epilepsy and cleft lip and palate. Lancet. ii:1970;876-877.
37. D'Souza S.W., Roberston I.G., Donnai D., Mawer G. Foetal phenytoin exposure, hypoplastic nails and jitterness. Arch. Dis. Child. 66:(3):1990;320-324.
38. Ehlers K., Stürje H., Merker H.-J., Nau H. Valproic acid-induced spina bifida: a mouse model. Teratology. 45:1992;145-151.
39. Erickson J.D., Oakley G.P. Seizure disorder in mothers of children with orofacial clefts: a case-control study. J. Pediatr. 84:1974;244-246.
40. Faiella A., Wernig M., Consalez G.G., Hostick U., Hofmann C., Hustert E., Boncinelli E., Balling R., Nadeau J.H. A mouse model for valproate teratogenicity: parental effects, homeotic transformations, and altered HOX expression. Hum. Mol. Genet. 9:(2):2000;227-236.
41. Finnell R.H., Dansky L.V. Parental epilepsy, anticonvulsant drugs, and reproductive outcome: epidemiological and experimental findings spanning three decades; 1:animal studies. Reprod. Toxicol. Rev. 5:1991;281-299.
42. Fogh-Andersen, P., 1942. Inheritance of harelip and cleft palate (Thesis). Nyt Nordisk Forlag, Arnold Busck, Copenhagen.
43. Frankenburg, W.K., Dodds, J.B., Fandal, A.W., 1970. Denver Developmental Screening Test Revised. University of Colorado Medical Center, Denver.
44. Friis M.L. Epilepsy among parents of children with facial clefts. Epilepsia. 20:1979;69-76.
45. Friis M.X., Hauge M. Congenital heart defects in love-born children of epileptic parents. Arch. Neurol. 42:1985;374-376.
46. Friis M.L., Broeng-Nielsen B., Sindrup E.H., Lund M., Fogh-Andersen P., Hauge M. Facial clefts among epileptic patients. Arch. Neurol. 38:1981;227-229.
47. Friis M.L., Holm N.V., Sindrup E.H., Fogh-Andersen P., Hauge M. Facial clefts in sibs and children of epileptic patients. Neurology. 36:1986;346-350.
48. Gaily E., Kantola-Sorsa E., Granström M.L. Intelligence of children of epileptic mothers. J. Ped. 113:1988;677-684.
49. Gorman K.S., Lourie A.E., Choudhury N. Differential patterns of development: the interaction of birth weight, temperament and maternal behavior. J. Dev. Behav. Pediatr. 22:2001;366-375.
50. Govaert P., Smets K., Matthys E., Oostra A. Neonatal focal temporal lobe or atrial wall haemorrhagic infarction. Arch. Dis. Child Fetal Neonatal Ed. 81:1999;211-216.
51. Grandjean P., Weihe P., Burse V.W., Needham L.L., Storr-Hansen E., Heinzow B., Debes F., Murata K., Simonson H., Ellefsen P., Budtz-Jorgensen E., Keiding N., White R.F. Neurobehavioural deficits associated with PCB in 7-year old children prenatally exposed to seafood neurotoxicants. Neurotoxicol. Teratol. 23:2001;305-317.
52. Granström M.-L., Gaily E. Psychomotor development in children of mothers with epilepsy. Neurology. 42:(suppl 5):1992;144-148.
53. Greenberg G., Inman W.H.W., Weatherall J.A.C., Adelstein A.M., Haskey J.C. Maternal drug histories and congenital abnormalities. Br. Med. J. 2:1977;853-856.
54. Grunau R.E., Whitfield M.F., Davis C. Pattern of learning disabilities in children with extremely low birth weight and broadly average intelligence. Arch. Pediatr. Adolesc. Med. 156:2002;615-620.
55. Gupta C., Sonawane B.R., Yaffe S.J., Shapiro B.H. Phenobarbital exposure in utero: alterations in female reproductive function in rats. Science. 208:1980;508-510.
56. Gupta C., Yaffe S.J., Shapiro B.H. Prenatal exposure to phenobarbital permanently decreases testosterone and causes reproductive dysfunction. Science. 216:1982;640-641.
57. Hansen J.M., Harris K.K., Philbert M.A., Harris C. Thalidomide modulates nuclear redox status and preferentially depletes glutathione in rabbit limb versus rat limb. J. Pharmacol. Exp. Ther. 300:(3):2002;768-776.
58. Hanson J.W., Smith D.W. The foetal hydantoin syndrome. J. Pediatr. 87:1975;285-290.
59. Hanson J.W., Myrianthopoulos N.C., Harvey M.A.S., Smith D.W. Risks to the offspring of women treated with hydantoin anticonvulsants with emphasis on the foetal hydantoin syndrome. J. Pediatr. 89:1976;662-668.
60. Hauck R.-S., Elmazar M.M.A., Plum C., Nau H. The enantioselective teratogenicity of 2-n-propyl-4-pentinoic acid (4-yn-VPA) is due to stereoselective intrinsic activity and not differences in pharmacokinetics. Toxicol. Lett. 60:1992;145-153.
61. Hernandez-Diaz S., Werler M.M., Walker A.M., Mitchell A.A. Folic acid antagonists during pregnancy and the risk of birth defects. New Engl. J. Med. 343:(22):2000;1608-1614.
62. Hernandez-Diaz S., Werler M.M., Walker A.M., Mitchell A.A. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am. J. Epidemiol. 153:(10):2001;961-968.
63. Hiilesmaa V.K. Pregnancy and birth in women with epilepsy. Neurology. 42:(suppl 5):1992;8-11.
64. Hiilesmaa, V., 1997. Effects of maternal seizures on the foetus. Epilepsy and Pregnancy, Wrightson Biomedical Publishing Ltd. P135-141.
65. Hill R.M., Willie M., Verniaud M. Infants exposed in utero to antiepileptic drugs. Am. J. Dis. Child. 127:1974;645-653.
66. Hill R., Verniaud W., Rettig G., Tennyson L., Craig J. Relationship between antiepileptic drug exposure of the infant and development potential. Epilepsy and the Child. 1982;409-417 Raven press, New York.
67. Holmes L.B., Harvey E.A., Coull B.A., Huntington K.B., Khoshbin S., Hayes A.M., Ryan L.M. The teratogenicity of anticonvulsant drugs. New Engl. J. Med. 344:2001;1132-1138.
68. Huth H.G., Steinhausen H.C., Helge H. Mental development in children of epileptic parents. Epilepsy, Pregnancy and the Child. 1982;Raven Press, New York.
69. Irl C., Hasford J. Assessing the safety of drugs in pregnancy: the role of prospective cohort studies. Drug Saf. 22:(3):2000;169-177.
70. Janz D., Fuchs U. Sind antiepileptische medikamente während der schwangerschaft schädlich. Dtsch. Med. Wochenschr. 89:1964;241-243.
71. Jones K.L., Lacro R.V., Johnson K.A. Pattern of malformations in the children of women treated with carbamazepine during pregnancy. New Eng. J. Med. 320:(25):1989;1661-1666.
72. Kelly T.E. Teratogenicity of anticonvulsant drugs I: review of the literature. Am. J. Med. Genet. 19:1984;413-434.
73. Kelly T.E., Rein M., Edwards P. Teratogenicity of anticonvulsant drugs IV. The association of clefting and epilepsy. Am. J. Med. Genet. 19:1984;451-458.
74. Klepel H., Freitag G. Spina bifida occulta in epilepsy syndromes. Neurology. 42:(Suppl. 5):1992;126-127.
75. Klip H., Verloop J., van Gool J.D., Koster M.E., Burger C.W., van Leeuwen F.E. Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study. Lancet. 359:2002;1102-1107.
76. Koch S., Titze K., Zimmerman R.B., Schroder M., Lehkuhl U., Rauh H. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. Epilepsia. 40:1999;1237-1243.
77. Lampen A., Siehler S., Ellerbeck U., Göttlicher M., Nau H. New molecular bioassays for the estimation of the teratogenic potency of valproic acid derivatives in vitro: activation of the peroxisomal proliferator-activated receptor (PPARδ). Toxicol. Appl. Pharmacol. 160:1999;238-249.
78. Lampen A., Carlberg C., Nau H. Peroxisome proliferator-activated receptor δ is a specific sensor for teratogenic valproic acid derivatives. Euro. J. Pharmacol. 431:2001;25-33.
79. Leavitt A.M., Yerby M.D., Robinson N., Sells C., Erickson D.M. Epilepsy in pregnancy: developmental outcome of offspring at 12 months. Neurology. 42:(Suppl. 5):1992;141-143.
80. Lejarraga H., Pascucci M.C., Krupitzky S., Kelmansky D., Bianco A., Martinez E., Tibaldi F., Cameron N. Psychomotor development in Argentinean children aged 0-5 years. Paediatr. Perinat. Epidemiol. 16:2002;47-60.
81. Lindhout D. Pharmacogenetics and drug interactions: role in antiepileptic drug induced teratogenesis. Neurology. 42:(Suppl. 5):1992;43-47.
82. Lindhout D., Meinardi H., Meijer J., Nau H. Antiepileptic drugs and teratogenesis in two consecutive cohorts: changes in prescription prescription policy paralleled by changes in pattern of malformations. Neurology. 42:(Suppl. 5):1992;94-110.
83. Lindhout D., Omtzigt J.G.C., Cornel M.C. Spectrum of neural-tube defects in 34 infants prenatally exposed to antiepileptic drugs. Neurology. 42:(Suppl. 5):1992;111-118.
84. Lo W., Friedman J. Teratogenicity of recently introduced medications in human pregnancy. Obstet. Gynecol. 100:(3):2002;465.
85. Maneru C., Junque C., Botet F., Tallada M., Guardia J. Neuropsychological long-term sequelae of perinatal asphyxia. Brain Inj. 15:2001;1029-1039.
86. Mawer, G., Clayton-Smith, J., Coyle, H., Kini, U., 2002. Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated with higher doses of sodium Valproate. Seizure, in press.
87. McCarthy D. McCarthy scales of children's abilities. Manual. 1972;The Psychological Corporation, New York.
88. Meador K.J. Cognitive effects of epilepsy and of antiepileptic medications. Wyllie E. third ed. The Treatment of Epilepsy: Principles and Practice. 88:2001;1215-1225 Lippincott Williams & Wilkins, Philadelphia, PA.
89. Meadow S.R. Anticonvulsant drugs and congenital abnormalities. Lancet. ii:1968;1296.
90. Moore S., Turnpenny P., Quinn A., Lloyd D., Montgomery T., Dean J. A Clinical study of 57 children with foetal anticonvulsant syndromes. J. Med. Genet. 37:2000;489-497.
91. Morrow J.I., Craig J.J., Russell A.J.C., Parsons L., Morrison P., Robertson I., Guthrie E. The UK epilepsy and pregnancy register. Epilepsia. 41:(suppl. 142):2000;168.
92. Morrow J.I., Russell A.J.C., Craig J.J., Morrison P., Robertson I., Guthrie E., Parsons L. Major malformations in the offspring of women with epilepsy: a comprehensive prospective study. Epilepsia. 42:(suppl 2):2001;125.
93. Morrow P.J.A., Morrow J.I., Bingham E. An Audit of a newly established free-phone advice line for women with epilepsy contemplating pregnancy. Epilepsia. 41:(Suppl):2000;168.
94. Müller-Küppers M. Zur Frage der Fruchtschädigung in der Schwangerschaft durch Einnahtme von Antiepileptika. Acta Paedopsychiatr. 30:1963;401-405.
95. Nau H., Hauck R.S., Ehlers K. Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacol. Toxicol. 69:1991;310-321.
96. Nelson K., Ellenberg J. Maternal seizure disorder, outcome of pregnancy, and neurological abnormalities in the children. Neurology. 32:(11):1982;1247-1254.
97. Nicol C.J., Zielenski J., Tsui L.-C., Wells P.G. An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis. FASEB J. 14:2000;111-127.
98. Normura, Y., Takebe, Y., Nomura, Y., Shinagawa, S., Kaneko Sato, T., 1984. The physical and mental development of infants born to mothers treated with antiepileptic drugs. Antiepileptic drugs and pregnancy, Excerpta Medica. Amsterdam, 187-195.
99. Omtzigt J.G.C., Los F.J., Grobbee D.E., Pijpers L., Jahoda M.G.J., Brandenburg H., Stewart P.A., Gaillard H.I.J., Sachs E.S., Wladimiroff J.W., Lindhout D. The risk of spina bifida aperta after first trimester exposure to valproate in a pre-natal cohort. Neurology. 42:1992;119-125.
100. Orringer C.E., Eustace J.C., Wunsch C.D., Gardner L.B. Natural history of lactic acidosis after grand mal seizures. A model of the study of an anion-gap acidosis not associated with hyperkalemia. New Engl. J. Med. 297:1977;796-799.
101. Parman T., Wells P.G. Embryonic prostaglandin H synthase-2 (PHS-2) expression and benzo[a]pyrene teratogenicity in PHS-2 knockout mice. FASEB J. 16:2002;1001-1009.
102. Parman T., Chen G., Wells P.G. Free radical intermediates of phenytoin and related teratogens: prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry and photochemical product analysis. J. Biol. Chem. 273:1998;25079-25088.
103. Parman T., Wiley M.J., Wells P.G. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat. Med. 5:1999;582-585.
104. Pashayan H., Pruzansky D., Pruzansky S. Are anticonvulsants teratogenic. Lancet. ii:1971;702-703.
105. Pinto W., Gardner L.I., Rosenbaum P. Abnormal genitalia as a presenting sign in two male infants with hydantoin embryopathy syndrome. Am. J. Dis. Child. 131:1977;452-455.
106. Reiff-Eldridge R., Heffner C.R., Ephross S.A., Tennis P.S., White A.D., Andrews E.B. Monitoring pregnancy outcomes after prenatal drug exposure through prospective pregnancy registries: a pharmaceutical company commitment. Am. J. Obstet. Gynecol. 182:2000;159-163.
107. Reinisch J.M., Sanders S.A. Early barbiturate exposure: the brain, sexually dimorphic behavior and learning. Neurosci. Biobehav. Rev. 6:1982;311-319.
108. Reinisch J.M., Sanders S.A., Mortensen E.L., Rubin D.B. In utero exposure to phenobarbital and intelligence deficits in adult men. J. Am. Med. Assoc. 274:1995;1518-1525.
109. Robert E. Handling surveillance types of data on birth defects and exposures during pregnancy. Reprod. Toxicol. 6:1992;205-209.
110. Robert E., Guibaud P. Maternal valproic acid and congenital neural tube defects. Lancet. ii:1982;937.
111. Rosa F.W. Spina bifida in infants of women treated with carbamazepine during pregnancy. New Engl. J. Med. 324:1991;674-677.
112. Rovet J., Cole S., Nulman I., Scolnik D., Altmann. Effects of maternal epilepsy on children's neurodevelopment. Child Neuropsychol. 1:1995;150-157.
113. Samren E.B., van Duijn C.M., Christiaens G.C., Hofman A., Lindhout D. Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann. Neurol. 46:1999;739-746.
114. Shankaran S., Papile L.A., Wright L.L., Ehrenkranz R.A., Mele L., Lemons J.A., Korones S.B., Stevenson D.K., Donovan E.F., Stoll B.J., Fanaroff A.A., Oh W., Verter J. Am. J. Obstet. Gynecol. 187:2002;171-177.
115. Shanks M.J., Wiley M.J., Kubow S., Wells P.G. Phenytoin teratogenicity: role of enzymatic bioactivation in a murine embryo culture model. Teratology. 40:1989;311-320.
116. Shapiro S., Slone D., Hartz S.C., Rosenberg L., Siskind V., Monson R., Mitchell A.A., Heinonen O.P. Anticonvulsants and parental epilepsy in the development of birth defects. Lancet. I:1976;272-275.
117. Shorvon S. Antiepileptic drug therapy during pregnancy: the neurologist's perspective. J. Med. Genet. 39:(4):2002;248-250.
118. Kr-blocker cisapride: relation to embryonic cardiac arrhythmia. Reprod. Toxicol., In press.
119. Sommerfelt K., Sonnander K., Skranes J., Andersson H.W., Ahlsten G., Ellertsen B., Markestad T., Jacobsen G., Hofiman H.J., Bakketeig L.S. Neuropsychologic and motor function in small-for-gestation preschoolers. Pediatr. Neurol. 26:2002;186-191.
120. Spiedel, B.D., Meadow, S.R., 1972. Maternal epilepsy and abnormalities of the foetus and newborn. The Lancet ii, 839-843.
121. Teramo K., Hiilesmaa V., Bardy A., Saarikoski S. Foetal heart rate during a maternal grand mal epileptic seizure. J. Perinat. Med. 7:1979;3-6.
122. Tomson T., Battino D., Beaussart M., Bonizzoni E., Craig J., Lindhout D., Perucca E., Vajda F. EURAP: an international pregnancy registry for the evaluation of the comparative teratogenic effects of antiepileptic drugs. Epilepsia. 42:(suppI 7):2001;293. Abstract.
123. Ueland P.M., Hustad S., Schneede J., Refsum H., Vollset S.E. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol. Sci. 22:2001;195-201.
124. Van der Pol M.C., Hadders-Algra M., Huisjes H.J., Touwen B.C. Antiepileptic medication in pregnancy: late effects on the children's central nervous system development. Am. J. Obstet. Gynecol. 164:1991;121-128.
125. Wald N. MRC vitamin study research group. Prevention of neural tube defects: results of the medical research council vitamin study. Lancet. 338:1991;131-137.
126. Webster R., Leishman D., Walker D. Towards a drug concentration effect relationship for QT prolongation and torsade de pointes. Curr. Opin. Drug Discov. Dev. 5:2002;116-126.
127. Wells P.G., Winn L.M. Biochemical toxicology of chemical teratogenesis. Crit. Rev. Biochem. Mol. Biol. 31:1996;1-40.
128. Wells P.G., Kim P.M., Laposa R.R., Nicol C.J., Parman T., Winn L.M. Oxidative damage in chemical teratogenesis. Mutat. Res. 396:(1-2):1997;65-78.
129. Werling U., Siehler S., Litfin M., Nau H., Göttlicher M. Induction of differentiation in F9 cells and activation of peorxisome proliferator-activated receptor-δ by valproic acid and its teratogenic derivates. Mol. Pharmacol. 59:2001;1.
130. Wide K., Winbladh B., Tomson T., Kallen B. Body dimensions of infants exposed to antiepileptic drugs in utero: observations spanning 25 years. Epilepsia. 41:(7):2000;854-861.
131. Wide K., Winbladh B., Tomson T., Sars-Zimmer K., Berggren E. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study. Dev. Med. Child Neurol. 42:(2):2000;87-92.
132. Wide K., Hening E., Tomson T., Winbladh B. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Acta Paediatr. 91:2002;409-414.
133. Williams G., Cunningham M., Stephen M., Kerr B., Hersh J.H. Foetal valproate syndrome and autism: additional evidence of an association. Dev. Med. Child Neurol. 43:2001;201-206.
134. Wilson J.G. Current status of teratology: general principles and mechanisms derived from animal studies. Wilson J.G., Clarke Fraser F. Handbook of Teratology (I) General Principles and Etiology. 1977;47-74 Plenum Press, New York and London.
135. Winn L.M., Wells P.G. Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity. Free Rad. Biol. Med. 26:1999;266-274.
136. Winn, LM., Wells, PG., 2002. Evidence for Ras-dependent signal transduction in phenytoin teratogenicity. Toxicol. Appl. Pharmacol., 184, in press.