Drugs in Pregnancy

Source Information

From the Motherisk Program, Division of Clinical Pharmacology and Toxicology (G.K., A.P., S.I.), the Departments of Pediatrics and Population Health Sciences (G.K., S.I.), and the Research Institute (G.K., S.I.), Hospital for Sick Children; and the Departments of Pediatrics (G.K., S.I.), Pharmacology (G.K., S.I.), and Medicine (G.K.), University of Toronto — both in Toronto.

Address reprint requests to Dr. Koren at the Division of Clinical Pharmacology, Hospital for Sick Children, 555 University Ave., Toronto, ON M5G 1X8, Canada.


  1. Better news on population. Lancet 1992;339:1600-1600.
  2. Koren G, Bologa M, Long D, Feldman Y, Shear NH. Perception of teratogenic risk by pregnant women exposed to drugs and chemicals during the first trimester. Am J Obstet Gynecol 1989;160:1190-1194. [Medline]
  3. Koren G, Pastuszak A. Prevention of unnecessary pregnancy termination by counselling women on drug, chemical, and radiation exposure during the first trimester. Teratology 1990;41:657-661. [Medline]
  4. Newton ER, ed. Medical problems in pregnancy. Med Clin North Am 1989;73:517-752.
  5. Moore KL. The developing human: clinically oriented embryology. 4th ed. Philadelphia: W.B. Saunders, 1988:131.
  6. Schardein JL. Chemically induced birth defects. 2nd ed. rev. New York: Marcel Dekker, 1993.
  7. Lenz W, Knapp K. Die Thalidomid-Embryopathie. Dtsch Med Wochenschr 1962;87:1232-1242.
  8. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 4th ed. Baltimore: Williams & Wilkins, 1994.
  9. Saxen I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemiol 1975;4:37-44. [Free Full Text]
  10. Rosenberg L, Mitchell AA, Parsells JL, Pashayan H, Luvik C, Shapiro S. Lack of relation of oral clefts to diazepam use during pregnancy. N Engl J Med 1983;309:1282-1285. [Abstract]
  11. Shiono PH, Mills JL. Oral clefts and diazepam use during pregnancy. N Engl J Med 1984;311:919-920. [Medline]
  12. Czeizel A. Lack of evidence of teratogenicity of benzodiazepine drugs in Hungary. Reprod Toxicol 1987;1:183-188. [Medline]
  13. Nora JJ, Nora AH, Blu J, et al. Exogenous progestogen and estrogen implicated in birth defects. JAMA 1978;240:837-843. [Abstract]
  14. Schardein JL. Congenital abnormalities and hormones during pregnancy: a clinical review. Teratology 1980;22:251-270. [CrossRef][Medline]
  15. Bracken MB. Oral contraception and congenital malformations in offspring: a review and meta-analysis of the prospective studies. Obstet Gynecol 1990;76:552-557. [Medline]
  16. Raman-Wilms L, Tseng AL, Wighardt S, Einarson TR, Koren G. Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis. Obstet Gynecol 1995;85:141-149. [Abstract]
  17. Jick H, Walker AM, Rothman KJ, et al. Vaginal spermicides and congenital disorders. JAMA 1981;245:1329-1332. [Abstract]
  18. Einarson TR, Koren G, Mattice D, Schechter-Tsafriri O. Maternal spermicide use and adverse reproductive outcome: a meta-analysis. Am J Obstet Gynecol 1990;162:655-660. [Medline]
  19. Walker BE. Induction of cleft palate in rats with antiinflammatory drugs. Teratology 1971;4:39-42. [Medline]
  20. Werler MM, Mitchell AA, Shapiro S. The relation of aspirin use during the first trimester of pregnancy to congenital cardiac defects. N Engl J Med 1989;321:1639-1642. [Abstract]
  21. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Aspirin and congenital malformations. Lancet 1976;1:1373-1375. [Medline]
  22. Dickson JH. Congenital deformities associated with Bendectin. Can Med Assoc J 1977;117:721-721. [Medline]
  23. Donnai D, Harris R. Unusual fetal malformations after antiemetics in pregnancy. BMJ 1978;1:691-692.
  24. Einarson TR, Leeder JS, Koren G. A method for meta-analysis of epidemiological studies. Drug Intell Clin Pharm 1988;22:813-824. [Abstract]
  25. McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects. I. A meta-analysis of the epidemiologic studies. Teratology 1994;50:27-37. [Medline]
  26. Neutel CI, Johansen HL. Measuring drug effectiveness by default: the case of Bendectin. Can J Public Health 1995;68:66-70.
  27. Ornstein M, Einarson A, Koren G. Bendectin/Diclectin for morning sickness: a Canadian follow-up of an American tragedy. Reprod Toxicol 1995;9:1-6. [Medline]
  28. Mazzota P, Magee L, Koren G. Therapeutic abortions due to morning sickness: unacceptable combination. Can Fam Physician 1997;43:1055-1057. [Medline]
  29. Fantel AG, Shepard TH, Newell-Morris LL, Moffett BC. Teratogenic effects of retinoic acid in pigtail monkeys (Macaca nemestrina). I. General features. Teratology 1977;15:65-71. [CrossRef][Medline]
  30. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med 1985;313:837-841. [Abstract]
  31. A nation of illiterates. US News and World Report. May 17, 1982:1.
  32. Pastuszak AL, Koren G, Rieder MJ. Use of the Retinoid Pregnancy Prevention Program in Canada: patterns of contraception use in women treated with isotretinoin and etretinate. Reprod Toxicol 1994;8:63-68. [Medline]
  33. Koren G. The children of neverland: the silent human disaster. Toronto: Kid In Us, 1997.
  34. Jones GR. Thalidomide: 35 years on and still deforming. Lancet 1994;343:1041-1041.
  35. Polaneczky M, Slap G, Forke C, Rappaport A, Sondheimer S. The use of levonorgestrel implants (Norplant) for contraception in adolescent mothers. N Engl J Med 1994;331:1201-1206. [Free Full Text]
  36. Glasier A. Emergency postcoital contraception. N Engl J Med 1997;337:1058-1064. [Free Full Text]
  37. Pipkin FB, Turner SR, Symonds EM. Possible risk with captopril in pregnancy: some animal data. Lancet 1980;1:1256-1256.
  38. Rosa FW, Bosco LA, Graham CF, et al. Neonatal anuria with maternal angiotensin-converting enzyme inhibition. Obstet Gynecol 1989;74:371-374. [Free Full Text]
  39. Sullivan FM, McElhatton PR. A comparison of the teratogenic activity of the antiepileptic drugs carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin, and primidone in mice. Toxicol Appl Pharmacol 1977;40:365-378. [CrossRef][Medline]
  40. Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991;324:674-677. [Medline]
  41. Wood JR Jr, Plessinger MA, Clark KE. Effect of cocaine on uterine blood flow and fetal oxygenation. JAMA 1987;257:957-961. [Abstract]
  42. Fantel AG, Macphail BJ. The teratogenicity of cocaine. Teratology 1982;26:17-19. [CrossRef][Medline]
  43. Weathers WT, Crane MM, Sauvain KJ, Blackhurst DW. Cocaine use in women from a defined population: prevalence at delivery and effects on growth in infants. Pediatrics 1993;91:350-354. [Free Full Text]
  44. Lutiger B, Graham K, Einarson TR, Koren G. Relationship between gestational cocaine use and pregnancy outcome: a meta-analysis. Teratology 1991;44:405-414. [CrossRef][Medline]
  45. Chasnoff IJ. Cocaine, pregnancy, and the growing child. Curr Probl Pediatr 1992;22:302-321. [CrossRef][Medline]
  46. Ellis FW, Pick JR. An animal model of the fetal alcohol syndrome in beagles. Alcohol Clin Exp Res 1980;4:123-134. [Medline]
  47. Shoemaker WJ, Koda LY, Shoemaker CA, Bloom FE. Ethanol effects in chick embryos: cerebellar Purkinje neurons. Neurobehav Toxicol 1980;2:239-242.
  48. Sulik KK, Johnston MC, Webb MA. Fetal alcohol syndrome: embryogenesis in a mouse model. Science 1981;214:936-938. [Free Full Text]
  49. Clarren SK. Recognition of fetal alcohol syndrome. JAMA 1981;245:2436-2439. [CrossRef][Medline]
  50. Streissguth AP, Aase JM, Clarren SK, Randels SP, LaDue RA, Smith DF. Fetal alcohol syndrome in adolescents and adults. JAMA 1991;265:1961-1967. [Abstract]
  51. Wilby OK, Tesh SA, Ross FW, Tesh JM. Effects of lithium on development in vitro and in vivo in the rat. Teratology 1987;35:69-69.abstract
  52. Nora JJ, Nora AH, Toews WH. Lithium, Ebstein’s anomaly, and other congenital heart defects. Lancet 1974;2:594-595. [CrossRef]
  53. Jacobson SJ, Jones K, Johnson K, et al. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992;339:530-533. [CrossRef][Medline]
  54. Tatetsu M. Experimental manifestation of “congenital Minamata disease.” Psychiatr Neurol Jpn 1968;70:162.
  55. Dougherty WJ, Coulston F, Golberg L. Toxicity of methylmercury in pregnant rhesus monkeys. Toxicol Appl Pharmacol 1974;29:138-138.abstract
  56. Matsumoto H, Koya G, Takeuchi T. Fetal Minamata disease: a neuropathological study of two cases of intrauterine intoxication by a methyl mercury compound. J Neuropathol Exp Neurol 1965;24:563-574. [Medline]
  57. McClain RM, Langhoff L. Teratogenicity of diphenylhydantoin in New Zealand white rabbits. Toxicol Appl Pharmacol 1979;48:A32-A32.abstract
  58. Finnell RH. Phenytoin-induced teratogenesis: a mouse model. Science 1981;211:483-484. [Free Full Text]
  59. Harbison RD. Studies on the mechanism of teratogenic action and neonatal pharmacology of diphenylhydantoin. (Ph.D. thesis. Iowa City: State University of Iowa, 1969.)
  60. Hanson JW, Smith DW. The fetal hydantoin syndrome. J Pediatr 1975;87:285-290. [CrossRef][Medline]
  61. Scolnik D, Nulman I, Rovet J, et al. Neurodevelopment of children exposed in utero to phenytoin and carbamazepine monotherapy. JAMA 1994;271:767-770. [Abstract]
  62. Fratta ID, Sigg EB, Maiorana K. Teratogenic effects of thalidomide in rabbits, rats, hamsters, and mice. Toxicol Appl Pharmacol 1965;7:268-286.
  63. McBride WG. Thalidomide and congenital abnormalities. Lancet 1961;2:1358-1358.
  64. Nau H. Species differences in pharmacokinetics and drug teratogenesis. Environ Health Perspect 1986;70:113-129. [Medline]
  65. Finnel RH, Bennett GD, Karras SB, Mohl VK. Common hierarchies of susceptibility to the induction of neural tube defects in mouse embryos by valproic acid and its 4-propyl-4-pentenoic acid metabolite. Teratology 1988;38:313-320. [CrossRef][Medline]
  66. Jager-Roman E, Deichi A, Jakob S, et al. Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid. J Pediatr 1986;108:997-1004. [CrossRef][Medline]
  67. Lammer EJ, Sever LE, Oakley GP Jr. Teratogen update: valproic acid. Teratology 1987;35:465-473. [CrossRef][Medline]
  68. Howe AM, Webster WS. The warfarin embryopathy: a rat model showing maxillonasal hypoplasia and other skeletal disturbances. Teratology 1992;46:379-390. [CrossRef][Medline]
  69. Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980;68:122-140. [CrossRef][Medline]
  70. Baxter H, Fraser FC. The production of congenital defects in the offspring of female mice treated with cortisone. McGill Med J 1950;19:245-9.
  71. Fainstat T. Cortisone-induced congenital cleft palate in rabbits. Endocrinology 1954;55:502-508.
  72. Buresh JJ, Urban TJ. The teratogenic effect of the steroid nucleus in the rat. J Dent Res 1970;43:548-554.
  73. Wilson JG, Fradkin R, Schumacher HJ. Influence of drug pretreatment on the effectiveness of known teratogenic agents. Teratology 1970;3:210-211.abstract
  74. Pinsky L, DiGeorge AM. Cleft palate in the mouse: a teratogenic index of glucocorticoid potency. Science 1965;147:402-403. [Free Full Text]
  75. Fraser FC, Sajoo A. Teratogenic potential of corticosteroids in humans. Teratology 1995;51:45-46. [CrossRef][Medline]
  76. Shepard TH. Catalog of teratogenic agents. 7th ed. Baltimore: Johns Hopkins University Press, 1994.
  77. Miller RP, Becker BA. Teratogenicity of oral diazepam and diphenylhydantoin in mice. Toxicol Appl Pharmacol 1975;32:53-61. [CrossRef][Medline]
  78. Klein KL, Scott WJ, Wilson JG. Aspirin-induced teratogenesis: a unique pattern of cell death and subsequent polydactyly in the rat. J Exp Zool 1981;216:107-112. [CrossRef][Medline]
  79. Wilson JG, Ritter EJ, Scott WJ, Fradkin R. Comparative distribution and embryotoxicity of acetylsalicylic acid in pregnant rats and rhesus monkeys. Toxicol Appl Pharmacol 1977;41:67-78. [Medline]
  80. Beall JR, Klein MF. Enhancement of aspirin-induced teratogenicity by food restriction in rats. Toxicol Appl Pharmacol 1977;39:489-495. [Medline]
  81. Mastroiacovo P, Corchia C, Botto LD, Lanni R, Zampino G, Fusco D. Epidemiology and genetics of microtia-anotia: a registry based study on over one million births. J Med Genet 1995;52:453-457.
  82. Herbst AL, Scully RE. Adenocarcinoma of the vagina in adolescence: a report of 7 cases including 6 clear-cell carcinomas. Cancer 1970;25:745-757. [CrossRef][Medline]
  83. Rosa FW. Teratogenicity of isotretinoin. Lancet 1983;2:513-513. [Medline]
  84. Koren G, Pastuszak A. Teratogen information services. In: Koren G, ed. Maternal-fetal toxicology: a clinician’s guide. 2nd ed. rev. New York: Marcel Dekker, 1994:683-705.
  85. Pastuszak A, Schick-Boschetto B, Zuber C, et al. Pregnancy outcome following first-trimester exposure to fluoxetine. JAMA 1993;269:2246-2248. [Abstract]
  86. Goldstein DJ, Corbin LA, Sundell KL. Effects of first-trimester fluoxetine exposure on the newborn. Obstet Gynecol 1997;89:713-718. [Abstract]
  87. Adams J. Neural and behavioral pathology following prenatal exposure to retinoids. In: Koren G, ed. Retinoids in clinical practice: the risk-benefit ratio. New York: Marcel Dekker, 1993:111-28.
  88. Gonen R, Shilalukey K, Magee L, Koren G, Shime J. Maternal disorders leading to increased reproductive risk. In: Koren G, ed. Maternal-fetal toxicology: a clinician’s guide. 2nd ed. rev. New York: Marcel Dekker, 1994:641-82.
  89. Feldman Y, Koren G, Mattice K, Shear H, Pellegrini E, MacLeod SM. Determinants of recall and recall bias in studying drug and chemical exposure in pregnancy. Teratology 1989;40:37-45. [CrossRef][Medline]
  90. Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA 1993;269:1257-1261. [Abstract]
  91. McCall RB. The development of intellectual functioning in infancy and the prediction of later I.Q. In: Osofsky JD, ed. Handbook of infant development. New York: John Wiley, 1979:707-41.
  92. Teratology Society Public Affairs Committee. FDA classification of drugs for teratogenic risk. Teratology 1994;49:446-447. [CrossRef][Medline]
  93. Smith J, Taddio A, Koren G. Drugs of choice for pregnant women. In: Koren G, ed. Maternal-fetal toxicology: a clinician’s guide. 2nd ed. rev. New York: Marcel Dekker, 1994:115-28.
  94. Loebstein R, Lalkin A, Koren G. Pregnancy induced pharmacokinetic changes and their clinical relevance. Clin Pharmacokinet 1997;33:328-343. [Medline]
  95. Theis JGW. Acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy: are they safe? Can Fam Physician 1996;42:2347-2349. [Medline]

Gideon Koren, M.D., Anne Pastuszak, M.Sc., and Shinya Ito, M.D.

Page 7 of 7« First 5 6 7

Provided by ArmMed Media