Advertisement

Embryotoxicity of Drugs in Man

  • James G. Wilson

Abstract

The subject of possible adverse effects on development of drugs and en­vironmental chemicals has been reviewed with some regularity (Cahen, 1966; Cohlan, 1964; Lenz, 1964; Nishimura, 1964; Palmisano and Polhill, 1972; Slater, 1965; Tuchmann-Duplessis, 1965; and others). Until more effective systems for prior testing and later surveillance for possible teratogenic effects of chemicals are in operation, however, frequent scrutiny in the form of surveys and reviews may serve to maintain a degree of alertness, if not provide the needed safeguard. Table 1 summarizes available information on known causes in man. It is apparent that only a very small percentage of the total burden of human developmental defects can at present be attributed to drugs and chemicals. Such percentages, however, must not be taken literally because they are only crude estimates based on the relatively few individual entities positively identified as human teratogens to date. Nevertheless, it appears unlikely that a majority of infants born with or diagnosed as having develop­mental defects will ever be assigned to any single category of environmental causation.

Keywords

Congenital Malformation Biliary Atresia Cleft Palate Congenital Heart Defect Teratogenic Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aarskog, D., 1975, Association between maternal intake of diazepam and oral cleft, Lancet 2: 921.CrossRefGoogle Scholar
  2. Aeppli, V. L., 1969, Teratologische Studien mit Imipramin an Ratte und Kaninchen, Arzneim. Forsch. 19: 1617–1640.Google Scholar
  3. Andrew, F. D., and Staples, R. E., 1974, Comparative embryotoxicity of medroxyprogesterone acetate, Teratology 9: A13.Google Scholar
  4. Andrew, F. D., Williams, T. L., Gidley, J. T., and Wall, M. E., 1972, Teratogenicity of contraceptive steroids in mice, Teratology 5: 249.Google Scholar
  5. Andrew, F. D., Christensen, H. D., Williams, T. L., Thompson, M. G., and Wall, M. E., 1973, Comparative teratogenicity of contraceptive steroids in mice and rats, Teratology 7: A11–A12.CrossRefGoogle Scholar
  6. Anon., 1975, Some anticoagulants can have teratogenic effect, J. Am. Med. Assoc. 234: 1015.Google Scholar
  7. Appelt, H., Gerken, H., and Lenz, W., 1966, Tetraphocomelie mit Lippen-Kiefer-gauminspalte und Clitorishypertrophie ein Syndrom, Paediatr. Paedol. 2: 119–124.Google Scholar
  8. Askrog, V. F., and Harvald, B., 1970, Teratogen effekt of inhalations anaestetika, Nord. Med. 83: 498–500.Google Scholar
  9. Bacic, M., Wesselius de Casparis, A., and Diczfalusy, E., 1970, Failure of large doses of ethinyl estradiol to interfere with early embryonic development in human species, Am. J. Obstet. Gynecol. 107: 531–534.Google Scholar
  10. Balci, S., Say, B., Pirnar, T., and Hiesönmez, A., 1973, Birth defects and oral contraceptives, Lancet 2: 1098.CrossRefGoogle Scholar
  11. Banerjee, B. N., Galbreath, C., and Sofia, R. D., 1975, Teratologic evaluation of synthetic A9tetrahydrocannabinol in rats, Teratology 11: 99–102.CrossRefGoogle Scholar
  12. Barr, M., Poznanski, A. K., and Schmickel, R. D., 1974, Digital hypoplasia and anticonvulsants during gestation: A teratogenic syndrome, J. Pediatr. 84: 254–256.CrossRefGoogle Scholar
  13. Barry, J. E., and Danks, D. M., 1974, Anticonvulsants and congenital abnormalities, Lancet 2: 48–49.CrossRefGoogle Scholar
  14. Barson, A. J., 1972, Malformed infant, Br. Med. J. 2: 45.CrossRefGoogle Scholar
  15. Basford, A. B., and Fink, B. R., 1968, The teratogenicity of halothane in the rat, Anesthesiology 29: 1167–1173.CrossRefGoogle Scholar
  16. Bateman, A. J., and Epstein, S. S., 1971, Dominant lethal mutations in mammals, in: Chemical Mutagens. Principles and Methods for Their Detection ( A. Hollaender, ed.), pp. 541–568, Plenum Press, New York.CrossRefGoogle Scholar
  17. Beall, J. R., 1972, Teratogenic study of chlorpromazine, orphenadrine, perphenazine, and LSD-25 in rats, Toxicol. Appl. Pharmacol. 21: 230–236.CrossRefGoogle Scholar
  18. Becker, M. H., Genieser, N. B., Finegold, M., Miranda, D., and Spackman, T., 1975, Chondrodysplasia punctata. Is maternal warfarin therapy a factor?, Am. J. Dis. Child. 129: 356–359.Google Scholar
  19. Bertelli, A., Polani, P. E., Spector, R., Seller, M. J., Tuchmann-Duplessis, H., and Mercier-Parot, L., 1968, Retentissement d’un neuroleptique, l’halopéridol, sur la gestation et le développment prénatal des rongeurs, Arzneim. Forsch. 18: 1420–1424.Google Scholar
  20. Bird, A. V., 1969, Anticonvulsant drugs and congenital abnormalities, Lancet 1: 311.CrossRefGoogle Scholar
  21. Boletti, M., and Croatto, L., 1958, Deafness in a 5-year old girl resulting from streptomycin therapy during pregnancy, Acta Pediatr. 11: 1.Google Scholar
  22. Bongiovanni, A. M., and McFadden, A. J., 1960, Steroids during pregnancy and possible fetal consequences, Fertil. Steril. 11: 181–186.Google Scholar
  23. Bongiovanni, A. M., DiGeorge, A. M., and Grumbach, M. M., 1959, Masculinzation of the female infant associated with estrogenic therapy alone during gestation, J. Clin. Endocrinol. Metab. 19: 1004–1010.CrossRefGoogle Scholar
  24. Borgen, L. A., Davis, W. M., and Pace, H. B., 1971, Effects of synthetic A9-tetrahydrocannabinol on pregnancy and offspring in the rat, Toxicol. Appl. Pharmacol. 20: 480–486.CrossRefGoogle Scholar
  25. Boué, J., Boué, A., and Lazar, P., 1975, Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions, Teratology 12: 11–26.CrossRefGoogle Scholar
  26. Brandner, M., and Nusslé, D., 1969, Foetopathie due a l’aminopterine avec sténose congénitale de l’espace médullaire des os tubulaires longs, Ann. Radiol. 12: 703–710.Google Scholar
  27. Briggs, G. G., Samson, J. H., and Crawford, D. J., 1975, Lack of abnormalities in a newborn exposed to amphetamines during gestation, Am. J. Dis. Child. 129: 249–250.Google Scholar
  28. Brock, N., and von Kreybig, T., 1964, Experimenteller Beitrag zur Prüfung teratogener Wirkungen von Arzneimitteln an der Laboratoriumsratte, Naunyn Schmiedebergs Arch. Pharmakol. 249: 117–145.CrossRefGoogle Scholar
  29. Cahen, R. L., 1964, Evaluation of the teratogenicity of drugs, Clin. Pharmacol. Ther. 5: 480–514.Google Scholar
  30. Cahen, R. L., 1966, Experimental and clinical chemoteratogenesis, in: Advances in Pharmacology ( S. Garottini and P. A. Shore, eds.), pp. 263–334, Academic Press, New York.Google Scholar
  31. Cahen, R., Sautai, M., Montagne, J., and Pessonnier, J., 1964, Recherche de l’effet teratogene de la 2-diethylaminopropiophenone, Med. Exp. 10: 201–224.Google Scholar
  32. Caldera, R., 1970, Carbutamide et malformations chez l’enfant, Ann. Pediatr. 17: 432–436.Google Scholar
  33. Campbell, G. D., 1961, Possible teratogenic effect of tolbutamide in pregnancy, Lancet 1: 891–892.CrossRefGoogle Scholar
  34. Campbell, G. D., 1963, Chlorpropamide and foetal damage, Br. Med. J. 1: 59–60.CrossRefGoogle Scholar
  35. Carr, D. H., 1970, Chromosome studies in selected spontaneous abortions. 1. Conception after oral contraceptives, Can. Med. Assoc. J. 103: 343–348.Google Scholar
  36. Carter, M. P., 1965, Discussion of a paper by B. C. S. Slater, in: Embryopathic Activity of Drugs ( J. M. Robson, F. M. Sullivan, and R. L. Smith, eds.), pp. 253–260, Little, Brown, Boston.Google Scholar
  37. Carter, M. P., and Wilson, F. W., 1963, Antibiotics and congenital malformations, Lancet 1: 1267.CrossRefGoogle Scholar
  38. Carter, M. P. and Wilson, F., 1965, Antibiotics in early pregnancy and congenital malformations, Dev. Med. Child. Neurol. 7: 353–359.CrossRefGoogle Scholar
  39. Cervantes, A., Monter, H. M., and Campos, J. L., 1973, Clinical and genetic studies of children born of hormonal contraceptives users, in: 4th International Conference on Birth Defects ( A. G. Motulsky and F. J. G. Ebling, eds.), p. 53, Excerpta Medica, Amsterdam.Google Scholar
  40. Chang, L. W., Dudley, A. W., Katz, J., and Martin, A. H., 1974, Nervous system development following in utero exposure to trace amounts of halothane, Teratology 9: A15.Google Scholar
  41. Chaube, S., and Murphy, M. L., 1968, The teratogenic effects of the recent drugs active in cancer chemotherapy, in: Advances in Teratology ( D. H. M. Woollam, ed.), pp. 181–237, Academic Press, New York.Google Scholar
  42. Chernoff, G. F., 1975, A mouse model of the fetal alcohol syndrome, Teratology 11: 14A.Google Scholar
  43. Christenson, R. K., Schafer, J. H., Teague, H. S., and Grifo, A. P., 1971, Influence of methallibure on early pregnancy in swine, J Anim. Sci. 33: 1156.Google Scholar
  44. Christoffel, K. K., and Salafsky, I., 1975, Fetal alcohol syndrome in dizygous twins, J. Pediatr. 87: 963–967.CrossRefGoogle Scholar
  45. Cohen, E. N., Bellville, J. W., and Brown, B. W., 1971, Anesthesia, pregnancy and miscarriage: A study of operating room nurses and anesthetists, Anesthesiology 35: 343–347.CrossRefGoogle Scholar
  46. Cohlan, S. Q., 1964, Fetal and neonatal hazards from drugs administered during pregnancy, N.Y. Med. J. 64: 493–499.Google Scholar
  47. Coopersmith, H., and Kerbel, N. C., 1962, Drugs and congenital anomalies, Can. Med. Assoc. J. 87: 193.Google Scholar
  48. Corbett, T. H., 1972, Anesthetics as a cause of abortion, Fertil. Steril. 23: 866–869.Google Scholar
  49. Corbett, T. H., Cornell, R. G., Endres, J. L., and Lieding, K., 1974a, Birth defects among children of nurse-anesthetists, Anesthesiology 41: 341–344.CrossRefGoogle Scholar
  50. Corbett, T. H., Beaudoin, A. R., Cornell, R. G., Endres, J. L., and Page, A., 1974b, Effects of low concentrations of methoxyflurane on rat pregnancy, Teratology 9: A15–A16.Google Scholar
  51. Coté, C. J., Meuwissen, H. J., and Pickering, R. J., 1974, Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy, J Pediatr. 85: 324–328.CrossRefGoogle Scholar
  52. Courtney, K. D., and Valerio, D. A., 1968, Teratology in the Macaca mulatta, Teratology 1: 163–172.CrossRefGoogle Scholar
  53. Crombie, D. L., Pinsent, R. J. F. H., Slater, B. C., Fleming, D., and Cross, K. W., 1970, Teratogenic drugs—R. C. G. P. Survey, Br. Med. J. 4: 178–179.Google Scholar
  54. Crombie, D. L., Pinsent, R. J. F. H., and Fleming, D., 1972, Imipramine in pregnancy, Br. Med. J. 1: 745.CrossRefGoogle Scholar
  55. de Alvarez, R., 1962, Discussion of a paper by C. Goetsch, Am. J. Obstet. Gynecol. 83: 1474–1477.Google Scholar
  56. De Costa, E. J., and Abelman, M. A., 1952, Cortisone and pregnancy. An experimental and clinical study of the effects of cortisone on gestation, Am. J. Obstet. Gynecol. 64: 746–767.Google Scholar
  57. de Rothschild, B., and Levy, G., 1950, Action dé la quinacrine sur la gestation chez le rate, C.R. Soc. Biol. 144: 1350–1352.Google Scholar
  58. Diamond, I., Anderson, M. M., and McCreadie, S. R., 1960, Transplacental transmission of busulfan (Myleran) in a mother with leukemia: Production of fetal malformation and cytomegaly, Pediatrics 25: 85–90.Google Scholar
  59. Dieulangard, P., Coignet, J., and Vical, J. C., 1966, Sur un cas d’ectro-phocomelia, peut-etre d’origine medicamenteuse, Bull. Fed. Gynecol. Obstet. 18: 85–87.Google Scholar
  60. DiPaolo, J. A., and Kotin, P., 1966, Teratogenesis-oncogenesis: A study of possible relationships, Arch. Pathol. 81: 3–23.Google Scholar
  61. DiSaia, P. J., 1966, Pregnancy and delivery of a patient with a Starr-Edwards mitral valve prosthesis: Report of a case, Obstet. Gynecol. 28: 469–472.Google Scholar
  62. Dishotsky, N. I., Loughman, W. D., Mogar, R. E., and Lipscomb, W. R., 1971, LSD and genetic damage. Is LSD chromosome damaging, carcinogenic, mutagenic, or teratogenic?, Science 172: 431–440.CrossRefGoogle Scholar
  63. Dluzniewski, A., and Gastol-Lewinska, K., 1971, Search for teratogenic activity of some tuberculostatic drugs, Diss. Pharm. Pharmacol. 23: 383–392.Google Scholar
  64. Doig, R. K., and Coltman, O. McK., 1956, Cleft palate following cortisone therapy in early pregnancy, Lancet 2: 730.CrossRefGoogle Scholar
  65. Dolger, H., Baskman, J. J., and Nechemias, C., 1969, Tolbutamide in pregnancy and diabetes, J. Mt. Sinai Hosp. 36: 471–474.Google Scholar
  66. Duke, D. I., 1975, Prenatal effects of the cancer chemotherapeutic drug ICRF 159 in mice, rats, and rabbits, Teratology 11: 119–126.CrossRefGoogle Scholar
  67. Dumars, K. W., 1971, Parental drugs usage: Effect upon chromosomes of progeny, Pediatrics 47: 1037–1941.Google Scholar
  68. Einer-Jensen, N., and Secher, N. J., 1970, Diminished weight of rat foetuses after treatment of pregnant rats with haloperidol, J. Reprod. Fertil. 22: 591–594.CrossRefGoogle Scholar
  69. Elshove, J., 1969, Cleft palate in the offspring of female mice treated with phenytoin, Lancet 2: 1074.CrossRefGoogle Scholar
  70. Elshove, J., and van Eck, J. H. M., 1971, Aangeboren misvormingen, met name gespleten lip met of zonder gespleten verhemelte, bij kinderen van moeders met epilepsie, Ned. Tijdschr. Geneeskd. 115: 1371–1375.Google Scholar
  71. Emerson, D. J., 1962, Congenital malformations due to attemped abortion with aminopterin, Am. J. Obstet. Gynecol. 84: 356–357.Google Scholar
  72. Filippi, B., 1967, Antibiotics and congenitcal malformations: Evaluation of the teratogenicity of antibiotics, in: Advances in Teratology (D. H. M. Woollam, ed.), pp. 239–256, Logos Press and Academic Press, London and New York.Google Scholar
  73. Fillmore, S. J., and McDevitt, E., 1970, Effects of coumarin compounds on the fetus, Ann. Intern. Med. 73: 731–735.CrossRefGoogle Scholar
  74. Finnerty, J. J., and Mackay, B. R., 1962, Antepartum thrombophlebitis and pulmonary embolism, Obstet. Gynecol. 19: 405–410.Google Scholar
  75. Fishbein, L., Flamm, W. G., and Falk, H. L., 1970, Chemical Mutagens. Environmental Effects on Biological Systems, Academic Press, New York.Google Scholar
  76. Fleischman, R. W., Hayden, D. W., Rosenkrantz, H., and Braude, M. C., 1975, Teratologic evaluation of L19-tetrahydrocannabinol in mice, including a review of the literature, Teratology 12: 47–50.CrossRefGoogle Scholar
  77. Forfar, J. O., and Nelson, M. M., 1973, Epidemiology of drugs taken by pregnant women: Drugs that may affect the fetus adversely, Clin. Pharmacol. Ther. 14: 632–642.Google Scholar
  78. Fraser, F. C., and Fainstat, T. D., 1951, Production of congenital defects in the offspring of pregnant mice treated with cortisone, Pediatrics 8: 527–533.Google Scholar
  79. Gabler, W. L., 1968, The effect of 5,5-diphenylhydantoin on the rat uterus and its fetuses, Arch. Int. Pharmacodyn. Ther. 175: 141–152.Google Scholar
  80. Gal, I., Kirman, B., and Stern, J., 1967, Hormonal pregnancy tests and congenital malformations, Nature 216: 83.CrossRefGoogle Scholar
  81. Ganguin, G., 1971, Auswirkungen einer antituberkulösen Chemotherapie bei tuberkulösen Schwangeren auf die Frucht, Z. Erkr. Atmungsorgane 134: 95–103.Google Scholar
  82. Gardner, L. I., Assemany, S. R., and Neu, R. R., 1970, 46XY female: Antiandrogenic effect of oral contraceptive?, Lancet 2: 667–668.Google Scholar
  83. Gaunt, R., Renzi, A. A., Antonchak, N., Miller, G. J., and Gilman, M., 1959, Endocrine aspects of the pharmacology of reserpine, Ann. N.Y. Acad. Sci. 59: 22–35.CrossRefGoogle Scholar
  84. Geber, W. F., and Schramm, L. C., 1969a, Effects of marihuana extracts on fetal hamsters and rabbits, Toxicol. Appl. Pharmacol. 14: 247.CrossRefGoogle Scholar
  85. Geber, W. F., and Schramm, L. C., 1969b, Heroin teratogenic and behavioral activity in hamsters, Fed. Proc. 28: 262.Google Scholar
  86. Geber, W. F., and Schramm, L. C., 1969c, Comparative teratogenicity of morphine, heroin and methadone in the hamster, Pharmacologist 11: 248.Google Scholar
  87. German, J., Kowal, A., and Ehlers, K. H., 1970, Trimethadione and teratogenesis, Teratology 3: 349–362.CrossRefGoogle Scholar
  88. Ghanem, M. H., 1961, Possible teratogenic effect of tolbutamide in the pregnant prediabetic, Lancet 1: 1227.CrossRefGoogle Scholar
  89. Gibson, J. E., and Becker, B. A., 1968, Teratogenic effects of diphenylhydantoin in Swiss-Webster and AO- mice, Proc. Soc. Exp. Biol. Med. 128: 905–909.Google Scholar
  90. Gibson, J. P., and Newberne, J. W., 1973, Teratology and reproduction studies with metiapine, Toxicol. Appl. Pharmacol. 25: 212–219.CrossRefGoogle Scholar
  91. Girotti, M., and Schaer, A.-E., 1973, Malformations after anti-ovulatory drugs, in: 4th International Conference on Birth Defects, ( A. G. Motulsky and F. J. G. Ebling, eds.), pp. 52–53, Excerpta Medica. Amsterdam.Google Scholar
  92. Giroud, A., and Martinet, M., 1950, Action de la sulfaguanidine sur le développement de l’embryon, Arch. Fr. Pediatr. 7: 180–184.Google Scholar
  93. Giroud, A., and Tuchmann-Duplessis, H., 1962, Malformations congénitales. Role des facteurs exogènes, Pathol. Biol. 10: 119–151.Google Scholar
  94. Goetsch, C., 1962, An evaluation of aminopterin as an abortifacient, Am. J. Obstet. Gynecol. 83: 1474–1477.Google Scholar
  95. Goldfield, M. D., and Weinstein, M. R., 1973, Lithium carbonate in obstetrics: Guidelines for clinical use, Am. J. Obstet. Gynecol. 116: 15–22.Google Scholar
  96. Grabowsky, J. R., 1966, Açâo do Tofranil sóbre o embriâo humano, Rev. Brasil. Med. 23: 220.Google Scholar
  97. Gralla, E. J., and Mcllhenny, H. M., 1972, Studies in pregnant rats, rabbits and monkeys with lithium carbonate, Toxicol. Appi. Pharmacol. 21: 428–433.CrossRefGoogle Scholar
  98. Grebe, H., 1952 Können Abtreibungsversuche zu Missibildungen fuhren?, Geburtshilfe Frauenheilkd. 12: 333–339.Google Scholar
  99. Green, H. G., 1974, Infants of alcoholic mothers, Am. J. Obstet. Gynecol. 118: 713–716.Google Scholar
  100. Greenberg, G., Inman, W. H. W., Weatherall, J. A. C., and Adelstein, A. M., 1975, Hormonal pregnancy tests and congenital malformations, Br. Med. J. 2: 191–192.Google Scholar
  101. Greenberg, L. H., and Tanaka, K. R., 1964, Congenital anomalies probably induced by cyclophosphamide, J. Am. Med. Assoc. 188: 423–426.CrossRefGoogle Scholar
  102. Greenwald, P., Barlow, J. J., Nasca, P. C., and Burnett, W. S., 1971, Vaginal cancer after maternal treatment with synthetic estrogens, N. Engl. J. Med. 285: 390–392.CrossRefGoogle Scholar
  103. Grosse, K.-P., Schwanitz, G., Rott, H.-D., and Wissmüller, H. F., 1972, Chromosomenuntersuchungen bei Behandlung mit Anticonvulsiva, Humangenetik 16: 209–216.CrossRefGoogle Scholar
  104. Grumbach, M. M., and Ducharme, J. R., 1960, The effects of androgens on fetal sexual development; androgen-induced female pseudohermaphroidism, Fertil. Steril. 11: 157–180.Google Scholar
  105. Guilbeau, J. A., 1953, Effects of cortisone on the fetus, Am. J. Obstet. Gynecol. 65: 227.Google Scholar
  106. Hanson, J. W., and Smith, D. W., 1975, The fetal hydantoin syndrome, J. Pediatr. 87: 285–290.CrossRefGoogle Scholar
  107. Harbison, R. D., and Mantilla-Plata, B., 1972, Prenatal toxicity, maternal distribution, and placental transfer of tetrahydrocannabinol, J. Pharmacol. Exp. Ther. 180: 446–453.Google Scholar
  108. Harlap, S., Prywes, R., and Davies, A. M., 1975, Birth defects and oestogens and progesterones in pregnancy, Lancet 1: 682–683.CrossRefGoogle Scholar
  109. Harpel, H. S., and Gautieri, R. F., 1968, Morphine-induced fetal malformations, J. Pharm. Sci. 57: 1590–1597.CrossRefGoogle Scholar
  110. Harper, K. H., Palmer, A. K., and Davies, R. E., 1965, Effect of imipramine upon the pregnancy of laboratory animals, Arzneim. Forsch. 15: 1218–1221.Google Scholar
  111. Harris, J. W., and Ross, I. P., 1956, Cortisone therapy in early pregnancy: Relation to cleft palate, Lancet 1: 1045–1047.CrossRefGoogle Scholar
  112. Hartz, S. C., Heinonen, O. P., Shapiro, S., Siskind, V., and Slone, D., 1975, Antenatal exposure to meprobamate and chlordiazepoxide in relation to malformations, mental development, and childhood mortality, N. Engl. J. Med. 292: 726–728.CrossRefGoogle Scholar
  113. Hendrickx, A. G., 1975, Teratologic evaluation of imipramine hydrochloride in bonnet (Macaca radiata) and rhesus monkeys (Macaca mulatta), Teratology 11: 219–222.CrossRefGoogle Scholar
  114. Herbst, A. L., and Scully, R. E., 1970, Adenocarcinoma of the vagina in adolescents—A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas), Cancer 25: 745–761.CrossRefGoogle Scholar
  115. Herbst, A. L., Ulfelder, H., and Poskanzer, D. C., 1971, Adenocarcinoma of the vagina, N. Engl. J. Med. 284: 878–881.CrossRefGoogle Scholar
  116. Herbst, A. L., Robboy, S. J., Scully, R. E., and Poskanzer, D. C., 1974, Clear-cell adenocarcinoma of the vagina and cervix in girls: Analysis of 170 registry cases, Am. J. Obstet. Gynecol. 119: 713–724.Google Scholar
  117. Herbst, A. L., Poskanzer, D. C., Robboy, S. J., Friedlander, L., and Scully, R. E., 1975, Prenatal exposure to stilbestrol. A prospective comparison of exposed female offspring with unexposed controls, N. Engl. J. Med. 292: 334–339.CrossRefGoogle Scholar
  118. Herrmann, J., Feingold, M., Tuffli, G. A., and Opitz, J. M., 1969, A familial dysmorphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: The “pseudothalidomide” or “SC-syndrome”, Birth Defects: Orig. Art. Ser. 5: 81–89.Google Scholar
  119. Hirsh, J., Cade, J. F., and O’Sullivan, E. F., 1970, Clinical experience with anticoagulant therapy during pregnancy, Br. Med. J. 1: 270–273.CrossRefGoogle Scholar
  120. Hoffeld, D. R., Webster, R. L., and McNew, J., 1967, Adverse effects on offspring of tranquilizing drugs during pregnancy, Nature 215: 182–183.CrossRefGoogle Scholar
  121. Holmes, B., Moser, H. W., Haldórsson, S., et al.,1972, Mental Retardation: An Atlas of Disease with Associated Physical Abnormalities, Macmillan, New York.Google Scholar
  122. Holmes, L. B., and Borden, S., 1974, Phocomelia, flexion deformities and absent thumbs: A new hereditary upper limb malformation, Pediatrics 54: 461–465.Google Scholar
  123. Hook, E. B., Heinonen, O. P., Shapiro, S., and Slone, D., 1974, Maternal exposure to oral contraceptives and other female sex hormones: Relation to birth defects in a prospectively ascertained cohort of 50,282 pregnancies, Teratology 9: A21–A22.CrossRefGoogle Scholar
  124. Hoskins, D., 1948, Some effects of nitrogen mustard on the development of external body form in the rat, Anat. Rec. 102: 493–512.CrossRefGoogle Scholar
  125. Iuliucci, J. D., and Gautieri, R. F., 1971, Morphine-induced fetal malformations. II. Influence of hystamine and diphenylhydramine, J. Pharm. Sci. 60: 420–425.CrossRefGoogle Scholar
  126. Jackson, A. V., 1948, Toxic effects of salicylate on the foetus and mother, J. Pathol. Bacterial. 60: 587–593.CrossRefGoogle Scholar
  127. Janerich, D. T., Piper, J. M., and Glebatis, D. M., 1974, Oral contraceptives and congenital limb-reduction defects, N. Engl. J. Med. 291: 697–700.CrossRefGoogle Scholar
  128. Janz, D., and Fuchs, U., 1964, Sind antiepileptische Medikamente während der Schwangerschaft schädlich?, Dtsch. Méd. Wochenschr. 89: 241–243.CrossRefGoogle Scholar
  129. Jentgens, H., 1968, Ethionamid and teratogene Wirkung, Prax. Pneumol. 22: 699–704.Google Scholar
  130. Johansen, K. T., 1971, Lithium teratogenicity, Lancet 1: 1026–1027.CrossRefGoogle Scholar
  131. Joneja, M. G., 1975, Effects of A9-tetrahydrocannabinol (THC) on fetuses of Swiss Webster mice, Anat. Rec. 181: 387–388.Google Scholar
  132. Jones, K. L., 1974, Fetal alcohol syndrome, Paper presented at 14th Annual Teratology Society Meeting, Vancouver, British Columbia.Google Scholar
  133. Jones, K. L., and Smith, D. W., 1973, Recognition of the fetal alcohol syndrome in early infancy, Lancet 2: 999–1001.CrossRefGoogle Scholar
  134. Jones, K. L., and Smith, D. W., 1975, The fetal alcohol syndrome, Teratology 12: 1–10.CrossRefGoogle Scholar
  135. Jones, K. L., Smith, D. W., Ulleland, C. N., and Streissguth, A. P., 1973, Pattern of malformation in offspring of chronic alcoholic mothers, Lancet 1: 1267.CrossRefGoogle Scholar
  136. Jones, K. L., Smith, D. W., Streissguth, A. P., and Myrianthopoulos, N. C., 1974, Outcome in offspring of chronic alcoholic women, Lancet 1: 1076–1078.CrossRefGoogle Scholar
  137. Jordan, R. L., and Shiel, F. O’M., 1972, Preliminary observations on the response of the rat embryo to dextroamphetamine sulfate, Anat. Rec. 172: 338.Google Scholar
  138. Jurand, A., 1973, Teratogenic activity of methadone hydrochloride in mouse and chick embryos, J. Embryol. Exp. Morphol. 30: 449–458.Google Scholar
  139. Kalter, H., 1972a, Nonteratogenicity of isoniazid in mice, Teratology 5: 259.CrossRefGoogle Scholar
  140. Kalter, H., 1972b, Teratogenicity, embryolethality and mutagenicity of drugs of dependence, in: Chemical and Biological Aspects of Drug Dependence ( S. J. Mulé and H. Brill, eds.), pp. 413–445, CRC Press, Cleveland, Ohio.Google Scholar
  141. Kaplan, N. M., 1959, Male pseudohermaphrodism. Report of a case with observations and pathogenesis, N. Engl. J. Med. 261: 641.CrossRefGoogle Scholar
  142. Kasirsky, G., and Tansy, M. T., 1971, Teratogenic effects of methamphetamine in mice and rabbits, Teratology 4: 131–134.CrossRefGoogle Scholar
  143. Kato, T., Jarvik, L. F., Roizin, L., and Moralishvili, E., 1970, Chromosome studies in pregnant rhesus macaque given LSD-25, Dis. Nero. Syst. 31: 245–250.Google Scholar
  144. Kato, T., and Kitagawa, S., 1973, Production of congenital skeletal anomalies in the fetuses of pregnant rats and mice treated with various sulfonamides, Congenital Anomalies 13: 17–23.Google Scholar
  145. Kato, T., and Kitagawa, S., 1974, Effects of a new antibacterial sulfonamide (CS-61) on mouse and rat fetuses, Toxicol. Appi. Pharmacol. 27: 20–27.CrossRefGoogle Scholar
  146. Kaufman, R. L., 1973, Birth defects and oral contraceptives, Lancet 1: 1396.CrossRefGoogle Scholar
  147. Kerber, I. J., Warr, O. S., and Richardson, C., 1968, Pregnancy in a patient with a prosthetic mitral valve: Associated with a fetal anomaly attributed to warfarin sodium, J. Am. Med. Assoc. 203: 223–225.CrossRefGoogle Scholar
  148. Kernis, M. M., Pashayan, H. M., and Pruzansky, S., 1973, Dilantin-induced teratogenicity and folic acid deficiency, Teratology 7: A19–A20.Google Scholar
  149. Kimmel, C. A., Wilson, J. G., and Schumacher, H. J., 1971, Studies on metabolism and identification of the causative agent in aspirin teratogenesis in the rat, Teratology 4: 15–24.CrossRefGoogle Scholar
  150. King, C. T. G., Weaver, S. A., and Narrod, S. A., 1965, Antihistamines and teratogenicity in the rat, J. Pharmacol. Exp. Ther. 147: 391–398.Google Scholar
  151. Knill-Jones, R. P., Moir, D. D., Rodrigues, L. V., and Spence, A. A., 1972, Anaesthetic practice and pregnancy: a controlled survey of women anaesthetists in the United Kingdom, Lancet 2: 1326.CrossRefGoogle Scholar
  152. Kopelman, A. E., McCullar, F. W., and Heggeness, L., 1975, Limb malformations following maternal use of haloperidol, J. Am. Med. Assoc. 231: 62–64.CrossRefGoogle Scholar
  153. Koppe, J. G., Bosman, W., Oppers, V. M., Spaans, F., Kloosterman, G. J., and De Bruijne, J. I., 1973, Epilepsy and congenital malformations, in: 4th International Conference on Birth Defects ( A. G. Motulsky and F. J. G. Ebling, eds.), p. 52, Excerpta Medica, Amsterdam.Google Scholar
  154. Kronick, J., Phelps, N. E., McCallion, D. J., and Hirsch, J., 1974, Effects of sodium warfarin administered during pregnancy in mice, Am. J. Obstet. Gynecol. 118: 819–823.Google Scholar
  155. Kuenssberg, E. V., and Knox, J. D. E., 1972, Imipramine in pregnancy, Br. Med. J. 2: 1972.CrossRefGoogle Scholar
  156. Kuenssberg, E. V., and Knox, J. D. E., 1973, Teratogenic effect of anticonvulsants, Lancet 1: 198.CrossRefGoogle Scholar
  157. Landauer, W., and Wakasugi, N., 1968, Teratological studies with sulphonamides and their implications, J Embryol. Exp. Morphol. 20: 261–284.Google Scholar
  158. Larsson, K. S., Bostrom, H., and Erickson, B., 1963, Salicylate-induced malformations in mouse embryos, Acta Pediatr. 52: 36.CrossRefGoogle Scholar
  159. Larsson, Y., and Sterky, G., 1961, Possible teratogenic effect of tolbutamide in a pregnant pre-diabetic, Lancet 2: 1424.Google Scholar
  160. Laurence, M., Miller, M., Vowles, M., Evans, K., and Carter, C., 1971, Hormonal pregnancy tests and neural tube malformations, Nature 233: 495–496.CrossRefGoogle Scholar
  161. Lejour Jeanty, M., 1966, Becs-de-lièvre provoqués chez le rat par un dérivé de la pénicilline, l’hadacidine, J. Embryol. Exp. Morphol. 15: 193–211.Google Scholar
  162. Lemoine, P., Harousseau, H., and Borteyru, J., 1968, Les enfants de parents alcooliques. Anomalies observées, Quest. Med. 21: 476–482.Google Scholar
  163. Lenz, W., 1962, Drugs and congenital abnormalities, Lancet 1: 45.CrossRefGoogle Scholar
  164. Lenz, W., 1964, Chemicals and malformations in man, in: Congenital Malformations ( M. Fishbein, ed.), pp. 263–276, International Medical Congress, New York.Google Scholar
  165. Lenz W., 1966, Malformations caused by drugs in pregnancy, Am. J. Dis. Child. 112: 99–106.Google Scholar
  166. Lenz, W., 1972, Genetic diagnosis: molecular diseases and others, in: Human Genetics ( J. de Grouchy, F. J. G. Ebling, and I. W. Henderson, eds.), pp. 2–5, Excerpta Medica, Amsterdam.Google Scholar
  167. Levin, J. N., 1971, Amphetamine ingestion with biliary atresia, J. Pediatr 79: 130–131.CrossRefGoogle Scholar
  168. Levy, E. P., Cohen, A., and Fraser, F. C., 1973, Hormone treatment during pregnancy and congenital heart defects, Lancet 1: 611.CrossRefGoogle Scholar
  169. Levy, G., 1965, Pharmacokinetics of salicylate elimination in man, J. Pharm. Sci. 54: 959–967.CrossRefGoogle Scholar
  170. Little, W. A., 1966, Personal communication.Google Scholar
  171. Long, S. Y., 1972, Does LSD induce chromosomal damage and malformations? A review of the literature, Teratology 6: 75–90.CrossRefGoogle Scholar
  172. Loughnan, P. M., Gold, H., and Vance, J. C., 1973, Phenytoin teratogenicity in man, Lancet 1: 70–72.CrossRefGoogle Scholar
  173. Lowe, C. R., 1964, Congenital defects among children born to women under supervision or treatment of pulmonary tuberculosis, Br. J. Prey. Soc. Med. 18: 14–16.Google Scholar
  174. Lowe, C. R., 1973, Congenital malformations among infants born to epileptic women, Lancet 1: 9–10.CrossRefGoogle Scholar
  175. Malius, J. M., Cooke, A. M., Pyke, D. A., and Fitzgerald, M. G., 1964, Sulphonylurea drugs in pregnancy, Br. Med. J. 2: 187.Google Scholar
  176. Markham, J. K., Emmerson, J. L., and Owen, N. V., 1971, Teratogenicity studies of methadone HCl in rats and rabbits, Nature 233: 342–343.CrossRefGoogle Scholar
  177. Marsh, L., and Fraser, F. C., 1973, Studies on dilantin-induced cleft palate in mice, Teratology 7: A23.Google Scholar
  178. Martin, P. A., Thorburn, M. I., and Bryant, S. A., 1974, In vivo and in vitro studies of the cytogenetic effects of Cannabis sativa in rats and men, Teratology 9: 81–86.CrossRefGoogle Scholar
  179. Massey, K. M., 1966, Teratogenic effects of diphenylhydantoin sodium, J. Oral Ther. Pharmacol. 2: 380–385.Google Scholar
  180. Matera, R. F., Zabala, H., and Jiminez, A. P., 1967, Bifid exencephalia, teratogenic action of amphetamine, Int. Surg. 50: 79–85.Google Scholar
  181. Matsumoto, N., Iijima, S., and Katsunuma, H., 1974, Placental transfer of LiC1 and its effects on foetal growth development in mice, Teratology 10: 89.Google Scholar
  182. McBride, W. G., 1972, The teratogenic effects of imipramine, Teratology 5: 262.Google Scholar
  183. McDonald, A. D., 1961, Maternal health in early pregnancy and congenital defect. Final report on a prospective injury, Br. J. Prey. Soc. Med. 15: 154–166.Google Scholar
  184. McNiel, J. R., 1973, The possible teratogenic effect of salicylates on the developing fetus, Clin. Pediatr. 12: 347–350.Google Scholar
  185. Meadow, S. R., 1968, Anticonvulsant drugs and congenital abnormalities, Lancet 2: 1296.CrossRefGoogle Scholar
  186. Meadow, S. R., 1970, Congenital abnormalities and anticonvulsant drugs, Proc. R. Soc. Med. 63: 12–13.Google Scholar
  187. Melchoir, J. C., Svensmark, O., and Trolle, D., 1967, Placental transfer of phenobarbitone in epileptic women, and elimination in newborns, Lancet 2: 860–861.CrossRefGoogle Scholar
  188. Mellin, G. W., 1963, Fetal life study: A prospective epidemiologic study of prenatal influences on fetal development: meclizine and other drugs, Bull. Soc. R. Belge Gynecol. Obstet. 33: 79.Google Scholar
  189. Mellin, G. W., 1964, Drugs in the first trimester of pregnancy and the fetal life of Homo sapiens, Am. J. Obstet. Gynecol. 90: 1169–1180.Google Scholar
  190. Mellin, G. W., and Katzenstein, M., 1964, Increased incidence of malformations-chance or change?, J. Am. Med. Assoc. 187: 570–573.CrossRefGoogle Scholar
  191. Meltzer, H. J., 1956, Congenital anomalies due to attempted abortion with 4-aminopteroylglutamic acid, J. Am. Med. Assoc. 161: 1253.CrossRefGoogle Scholar
  192. Mercier-Parot, L., and Tuchmann-Duplessis, H., 1974, Action of diphenylhydantoin in pregnant rats and mice, Teratology 9: A28.Google Scholar
  193. Milkovich, L., and van den Berg, B. J., 1974, Effects of prenatal meprobamate and chlordiazepoxide hydrochloride on human embryonic and fetal development, N. Engl. J. Med. 291: 1268–1271.CrossRefGoogle Scholar
  194. Miller, R. P., and Becker, B. A., 1975, Teratogenicity of oral diazepam and diphenylhydantoin in mice, Toxicol. Appl. Pharmacol. 32: 53–61.CrossRefGoogle Scholar
  195. Milunsky, A., Graef, J. W., and Gaynor, M. T., 1968, Methotrexate-induced congenital malformations, with a review of the literature, J. Pediatr. 72: 790–795.CrossRefGoogle Scholar
  196. Mirkin, B. L., 1971, Placental transfer and neonatal elimination of diphenylhydantoin, Am. J. Obstet. Gynecol. 109: 930–933.Google Scholar
  197. Monnet, P., Kalb, J.-C., and Pujol, M., 1967, De l’influence nocive de l’isoniazide sur le produit de conception, Lyon Med. 217: 431–455.Google Scholar
  198. Monson, R. R., Rosenberg, L., Hartz, S. C., Shapiro, S., Heinonen, O. P., and Slone, D., 1973, Diphenylhydantoin and selected congenital malformations, N. Engl. J. Med. 289: 1049–1052.CrossRefGoogle Scholar
  199. Morearity, A. J., and Nance, H. R., 1963, Trifluoperazine and congenital malformations, Can. Med. Assoc. J. 88: 375.Google Scholar
  200. Moss, P. D., 1962, Phenmetrazine and foetal abnormality, Br. Med. J. 2: 1610.CrossRefGoogle Scholar
  201. Mulvihill, J. J., Mulvihill, C. G., and Neill, C. A., 1974, Prenatal sex-hormone exposure and cardiac defects in man, Teratology 9: A30.Google Scholar
  202. Murphy, M. L., Dagg, C. P., and Karnofsky, D., 1957, Comparison of teratogenic chemicals in the rat and chick embryos, Pediatrics 19: 701–714.Google Scholar
  203. Murray, F. J., 1974, Implications for teratogenic hazard to epileptic women taking diphenylhydantoin as indicated by animal studies, Ph. D. dissertation, University of Cincinnati College of Medicine, Cincinnati, Ohio.Google Scholar
  204. Naranjo, P., and de Naranjo, E., 1968, Embryotoxic effects of antihistamines, Arzneim. Forsch. 18: 188–195.Google Scholar
  205. Nelson, M. M., 1963, Teratogenic effects of pteroylglutamic acid deficiency in the rat, in: Ciba Foundation Symposium on Congenital Malformations ( G. E. W. Wolstenholme and C. M. O’Connor, eds.), pp. 134–151, Little, Brown, Boston.Google Scholar
  206. Nelson, M. M., and Forfar, J. O., 1971, Associations between drugs administered during pregnancy and congenital abnormalities of the fetus, Br. Med. J. 1: 523–527.CrossRefGoogle Scholar
  207. Nelson, M. M., Wright, H. V., Asling, C. W., and Evans, H. M., 1955, Multiple congenital abnormalities resulting from transitory deficiency of pteroylglutamic acid during gestation in the rat, J. Nutr. 56: 349–370.Google Scholar
  208. Nichols, M. M., 1973, Fetal anomalies following maternal trimethadione ingestion, J. Pediatr. 82: 885–886.CrossRefGoogle Scholar
  209. Nicholson, H. O., 1968, Cytotoxic drugs in pregnancy, J. Obstet. Gynaecol. Br. Commonw. 75: 307–312.CrossRefGoogle Scholar
  210. Nishimura, H., 1963, Interstrain differences in susceptibility to the teratogenic effects of Mitomycin C in mice, Abstracts of papers presented at 3rd Annual Teratology Society Meeting, Ste. Adele, Quebec.Google Scholar
  211. Nishimura, H., 1964, Chemistry and Prevention of Congenital Anomalies, Charles C. Thomas, Springfield, Illinois.Google Scholar
  212. Nishimura, H., and Kuginuki, M., 1958, Congenital malformations induced by ethyl-urethan in mouse embryos, Okajimas Folia Anat. Jpn. 31: 1.Google Scholar
  213. Nishimura, H., Uwabe, C., and Semba, R., 1974, Examination of teratogenicity of progestogens and/or estrogens by observation of the induced abortuses, Teratology 10: 93.CrossRefGoogle Scholar
  214. Niswander, J. D., and Wertelecki, W., 1973, Congenital malformations among offspring of epileptic women, Lancet 1: 1062.CrossRefGoogle Scholar
  215. Nora, A. H., and Nora, J. J., 1975, A syndrome of multiple congenital anomalies associated with teratogenic exposure, Arch Environ. Health 30: 17–21.Google Scholar
  216. Nora, J. J., and Nora, A. H., 1973, Preliminary evidence for a possible association between oral contraceptives and birth defects, Teratology 7: A24.Google Scholar
  217. Nora, J. J., and Nora, A. H., 1974, Can the pill cause birth defects?, N. Engl. J. Med. 291: 731–732.CrossRefGoogle Scholar
  218. Nora, J., Trasler, D. G., and Fraser, F. C., 1965, Malformations in mice induced by dexamphetamine sulphate, Lancet 2: 1021–1022.CrossRefGoogle Scholar
  219. Nora, J. J., Nora, A. H., Sommerville, R. J., Hill, R. M., and McNamara, D. G., 1967a, Maternal exposure to potential teratogens, J. Am. Med. Assoc. 202: 1065–1069.CrossRefGoogle Scholar
  220. Nora, J. J., McNamara, D. G., and Fraser, F. C., 19676, Dexamphetamine sulphate and human malformations, Lancet 1: 570–571.Google Scholar
  221. Nora, J. J., Sommerville, R. J., and Fraser, F. C., 1968, Homologies for congenital heart diseases: Murine models, influenced by dextroamphetamine, Teratology 1: 413–416.CrossRefGoogle Scholar
  222. Nora, J. J., Vargo, T. A., Nora, A. H., Love, K. E., and McNamara, D. G., 1970, Dexamphetamine: A possible environmental trigger in cardiovascular malformations, Lancet 1: 1290–1291.CrossRefGoogle Scholar
  223. Nora, J. J., Nora, A. H., and Toews, W. H., 1974, Lithium, Ebstein’s anomaly, and other congenital heart defects, Lancet 2: 594–595.CrossRefGoogle Scholar
  224. Notter, A., and Delande, M. F., 1962, Prophylaxie des excès de poids chez les gestantes d’apparence normale, Gynecol. Obstet. 61: 359–377.Google Scholar
  225. Olwin, J. H., and Koppel, J. L., 1969, Anticoagulant therapy during pregnancy, Obstet. Gynecol. 34: 847–852.Google Scholar
  226. Opitz, J. M., Grosse, F. R., and Haneberg, B., 1972, Congenital effects of bromism, Lancet 1: 91–92.CrossRefGoogle Scholar
  227. Pace, H. B., Davis, M. W., and Borgen, L. A., 1971, Teratogenesis and marijuana, Ann. N.Y. Acad. Sci. 191: 123–131.CrossRefGoogle Scholar
  228. Paget, G. E., and Thorpe, E., 1964, A teratogenic effect of a sulphonamide in experimental animals, Br. J. Pharmacol. 23: 305–312.Google Scholar
  229. Palacios-Macedo, X., Díaz-Devis, C., and Escudero, J., 1969, Fetal risk with the use of coumarin anticoagulant agents in pregnant patients with intracardiac ball valve prosthesis, Am. J. Cardiol. 24: 853–856.CrossRefGoogle Scholar
  230. Palmer, R. H., Oullett, E. M., Warner, L., and Leichtman, S. R., 1974, Congenital malformations in offspring of a chronic alcoholic mother, Pediatrics 53: 490–494.Google Scholar
  231. Palmisano, P. A., and Polhill, R. B., 1972, Fetal pharmacology, Pediatr. Clin. North AM. 19: 3–20.Google Scholar
  232. Papara-Nicholson, D., and Telford, I. R., 1957, Effects of alcohol on reproduction and fetal development in guinea pigs, Anat. Rec. 127: 438.Google Scholar
  233. Papp, Z., and Gardo, S., 1971, Effect of exogenous hormones on the fetus, Lancet 1: 753.CrossRefGoogle Scholar
  234. Pashayan, H., Pruzanksy, D., and Pruzansky, S., 1971, Are anticonvulsants teratogenic?, Lancet 2: 702–703.CrossRefGoogle Scholar
  235. Persaud, T. V. N., and Ellington, A. C., 1967, Ganja (Cannabis sativa) in early pregnancy, Lancet 2: 1306.CrossRefGoogle Scholar
  236. Persaud, T. V. N., and Ellington, A. C., 1968, Teratogenic activity of cannabis resin, Lancet 2: 406.CrossRefGoogle Scholar
  237. Persaud, T. V. N., and Henderson, W. M., 1969, The teratogenicity of barbital sodium in mice, Arzneim. Forsch. 19: 1309–1310.Google Scholar
  238. Peterson, W. F., 1969, Pregnancy following oral contraceptive therapy, Obstet. Gynecol. 34: 363–367.Google Scholar
  239. Pettersson, F., Olding, L., and Gustayson, K. H., 1970, Multiple severe malformations in a child of a diabetic mother treated with insulin and dibein during pregnancy, Acta Obstet. Gynecol. Scand. 49: 385–387.CrossRefGoogle Scholar
  240. Pettifor, J. M., and Benson, R., 1975, Congenital malformations associated with the administration of oral anticoagulants during pregnancy, J. Pediatr. 86: 459–462.CrossRefGoogle Scholar
  241. Poland, B. J., and Ash, K. A., 1973, The influence of recent use of an oral contraceptive on early intrauterine development, Am. J. Obstet. Gynecol. 116: 1138–1142.Google Scholar
  242. Popert, A. J., 1962, Pregnancy and adrenocortical hormones. Some aspects of their action in rheumatic disease, Br. Med. J. 1: 967–972.CrossRefGoogle Scholar
  243. Poswillo, D. E., 1972, Tridione and paradione as suspected teratogens, Ann. R. Coll. Surg. Engl. 50: 367–370.Google Scholar
  244. Potworowska, M., Sianozecka, E., and Szufladowicz, R., 1966, Ethionamide treatment and pregnancy (including drug induced abnormalities), Pol. Med. J. 5: 1152–1158.Google Scholar
  245. Powell, P. D., and Johnstone, J. M., 1962, Phenmetrazine and foetal abnormalities, Br. Med. J. 2: 1327.CrossRefGoogle Scholar
  246. Ravina, J. H., 1964, Les thérapeutiques dangereuses chez la femme enceinte, Presse Med. 72: 3057.Google Scholar
  247. Reilly, W. A., 1958, Hormone therapy during pregnancy: Effects on the fetus and newborn, Q. Rev. Pediatr. 13: 198–202.Google Scholar
  248. Report of Committee on Adverse Drug Reactions, 1971, Report (6th annual) of the New Zealand Committee on Adverse Drug Reactions, N.Z. Med. J. 74: 184–191.Google Scholar
  249. Report of Metropolitan Atlanta Congenital Malformations Surveillance, 1972, Reduction deformities and tricydic antidepressants, p. 9, (Jan.-Feb.).Google Scholar
  250. Richards, L. D. G., 1969, Congenital malformations and environmental influences in pregnancy, Br. J. Prey. Soc. Med. 23: 218–225.Google Scholar
  251. Robertson-Rintoul, J., 1974, Oral contraception: Potential hazards of hormone therapy during pregnancy, Lancet 2: 515–516.CrossRefGoogle Scholar
  252. Robinson, G. C., and Cambon, K. G., 1964, Hearing loss in infants of tuberculous mothers treated with streptomycin during pregnancy, N. Engl. J. Med. 271: 949–951.CrossRefGoogle Scholar
  253. Robinson, S. C., 1971, Pregnancy outcome following oral contraceptives, Am. J. Obstet. Gynecol. 109: 354–358.Google Scholar
  254. Robson, J. M., and Sullivan, F. M., 1963, The production of foetal abnormalities in rabbits by imipramine, Lancet 1: 638–639.CrossRefGoogle Scholar
  255. Rossiter, E. J. R., and Rendle-Short, J. T., 1972, Congenital effects of bromism, Lancet 2: 705.CrossRefGoogle Scholar
  256. Roux, C., 1959, Action tératogène de la prochlorpémazine, Arch. Fr. Pediatr. 16: 1–4.Google Scholar
  257. Rutman, J. Y., 1973, Anticonvulsants and fetal damage, N. Engl. J. Med. 289: 696–697.Google Scholar
  258. Safra, M. J., and Oakley, G. P., 1975, Association between cleft lip with or without cleft palate and prenatal exposure to diazepam, Lancet 2: 478–480.CrossRefGoogle Scholar
  259. Sandor, S., and Amels, D., 1971, The action of aethanol on the prenatal development of albino rats, Rev. Roum. Embryol. Cytol. 8: 37.Google Scholar
  260. Savini, E. C., Moulin, M. A., and Herrou, M. F., 1971, Experimental study of the effects of quinine on the rat, rabbit and dog fetus, Therapie 26: 563–574.Google Scholar
  261. Saxén, I., 1975, Associations between oral clefts and drugs taken during pregnancy, Int. J. Epidemiol. 4: 37–44.CrossRefGoogle Scholar
  262. Saxén, I., and Saxén, L., 1975, Association between maternal intake of diazepam and oral clefts, Lancet 2: 498.CrossRefGoogle Scholar
  263. Saxén, L., 1974, Cleft palate and maternal diphenhydramine intake, Lancet 1: 407–408.CrossRefGoogle Scholar
  264. Scanlon, F. J., 1969, Use of antidepressant drugs during the first trimester, Med. J. Aust. 2: 1077.Google Scholar
  265. Schardein, J. L., Hentz, D. L., Petrere, J. A., and Kurtz, S. M., 1971, Teratogenesis studies with diphenhydramine HCI, Toxicol. Appt. Pharmacol. 18: 971–976.CrossRefGoogle Scholar
  266. Schiff, D., Aranda, J. V., and Stern, L., 1970, Neonatal thrombocytopenia and congenital malformations associated with administration of tolbutamide to the mother, J. Pediatr. 77: 457–458.CrossRefGoogle Scholar
  267. Schou, M., Goldfield, M. D., Weinstein, M. R., and Villeneuve, A., 1973, Lithium.and pregnancy. I. Report from the register of lithium babies, Br. Med. J. 2: 135–136.CrossRefGoogle Scholar
  268. Seay, P. H., and Field, W. E., 1963, Toxicological studies on haloperidol, Int. J. Neuropsychiatry 3: 1–4.Google Scholar
  269. Setälä, K., and Nyyssönen, O., 1964, Hypnotic sodium pentobarbital as a teratogen for mice, Naturmissenchaften 51: 413.CrossRefGoogle Scholar
  270. Shaul, W. L., Emery, H., and Hall, J. G., 1975, Chondrodysplasia punctata and maternal warfarin use during pregnancy, Am. J. Dis. Child. 129: 360–362.Google Scholar
  271. Shaw, E. B., and Steinbach, H. L., 1968, Aminopterin-induced fetal malformation, Am. J. Dis. Child. 115: 477–482.Google Scholar
  272. Shelesnyak, M. C., and Davies, A. M., 1955, Disturbance of pregnancy in mouse and rat by systemic antihistamine treatment, Proc. Soc. Exp. Biol. 89: 629–632.Google Scholar
  273. Shepard, T. H., and Fink, B. R., 1968, Teratogenic activity of nitrous oxide in rats, in: Toxicity of Anesthetics ( B. R. Fink, ed.), pp. 308–323, Williams and Wilkins, Baltimore.Google Scholar
  274. Shotten, D., and Monie, I. W., 1963, Possible teratogenic effect of chlorambucil on a human fetus, J. Am. Med. Assoc. 186: 74–75.CrossRefGoogle Scholar
  275. Sim, M., 1972, Imipramine and pregnancy, Br. Med. J. 2: 45.CrossRefGoogle Scholar
  276. Sindair, J. G., 1950, A specific transplacental effect of urethane in mice, Tex. Rep. Biol. Med. 8: 623–632.Google Scholar
  277. Slater, B. C. S., 1965, The investigation of drug embryopathies in man, in: Embryopathic Activity of Drugs (J. M. Robson, F. M. Sullivan and R. L. Smith, eds.), pp. 241–260, Little, Brown, Boston.Google Scholar
  278. Smith, B. E., 1968, Teratogenic capabilities of surgical anaesthesia, in: Advances in Teratology ( D. H. M. Woollam, ed.), pp. 128–180, Academic Press, New York.Google Scholar
  279. Smith, B. E., Usubiaga, L. E., and Lehrer, S. B., 1971, Cleft palate induced by halothane anesthesia in C-57 black mice, Teratology 4: 242.Google Scholar
  280. Smithells, R. W., and Chinn, E. R., 1964, Meclozine and foetal malformations: A prospective study, Br. Med. J. 1: 217–218.CrossRefGoogle Scholar
  281. Sobel, D. E., 1960, Fetal damage due to ECT, insulin coma, chlorpromazine or reserpine, Arch. Gen. Psychiatry 2: 606–611.CrossRefGoogle Scholar
  282. Sokal, J. E., and Lessman, E. M., 1960, Effects of cancer chemotherapeutic agents on human fetus, J. Am. Med. Assoc. 172: 1765–1771.CrossRefGoogle Scholar
  283. Speidel, B. E., and Meadow, S. R., 1972, Maternal epilepsy and abnormalities of the fetus and newborn, Lancet 2: 839.CrossRefGoogle Scholar
  284. Spira, N., Goujard, J., Huel, G., and Rumeau-Rouquette, C., 1972, Etude du role teratogene des hormones sexuelles premiers résultats d’une enquète épidemiologique portant sur 20,000 femmes, Rev. Med. 41: 2683–2694.Google Scholar
  285. Staff, A., and Mattingly, R. F., 1974, Vaginal adenosis: A precancerous lesion?, Am. J. Obstet. Gynecol. 120: 666–677.Google Scholar
  286. Stalsberg, H., 1965, Antiemetics and congenital malformations—meclizine, cyclizine and chlorcydizine, Tidsskr. Nor. Laegeforen. 85: 1840–1841.Google Scholar
  287. Starreveld-Zimmerman, A. A. E., van der Kolt, W. J., Meinardi, H., and Elshove, J., 1973, Are anticonvulsants teratogenic? Lancet 2: 48–49.CrossRefGoogle Scholar
  288. Stenchever, M. A., and Parks, K. J., 1975, Some effects of diazepam on pregnancy in the Balb/C mouse, Am. J. Obstet. Gynecol. 121: 765–769.Google Scholar
  289. Stenchever, M. A., Kunysz, T. J., and Allen, M. A., 1974, Chromosome breakage in users of marihuana, Am. J. Obstet. Gynecol. 118: 106–113.Google Scholar
  290. Sterne, J., 1963, Antidiabetic drugs and teratogenicity, Lancet 1: 1165.CrossRefGoogle Scholar
  291. Sylvester, P. E., and Hughes, D. R., 1954, Congenital absence of both kidneys. A report of four cases, Br. Med. J. 1: 77–79.CrossRefGoogle Scholar
  292. Szabo, K. T., 1970, Teratogenic effect of lithium carbonate in the fetal mouse, Nature 225: 73–75.CrossRefGoogle Scholar
  293. Takano, K., 1964, The effect of several synthetic progestagens administered to pregnant animals upon their offspring, Proc. Cong. Anom. Res. Assoc. Jpn. 4: 3–4.Google Scholar
  294. Takano, K., Tanimura, T., and Nishimura, H., 1963, Effects of some psychoactive drugs administered to pregnant mice upon the development of their offspring, Proc. Cong. Anom. Res. Assoc. Jpn. 3: 2–3.Google Scholar
  295. Takano, K., Yamamura, H., Suzuki, M., and Nishimura, H., 1966, Teratogenic effect of chlormadinone acetate in mice and rabbits, Proc. Soc. Exp. Biol. Med. 121: 455–457.Google Scholar
  296. Tanimura, T., 1972, Effects on macaque embryos of drugs reported or suspected to be teratogenic in humans, in: Symposium on the Use of Non-Human Primates for Research in Problems of Human Reproduction ( E. Diczfalusy and C. C. Standley, eds.), pp. 293–308, WHO Research and Training Center on Human Reproduction, Stockholm.Google Scholar
  297. Tenbruick, M. L., and Buchin, S. Y., 1975, Fetal alcohol syndrome. Report of a case, J. Am. Med. Assoc. 232: 1144–1147.CrossRefGoogle Scholar
  298. Thiersch, J. B., 1952, Therapeutic abortions with a folic acid antagonist, 4-aminopteroylglutamic acid (4-amino P.G.A.) administered by the oral route, Am. J. Obstet. Gynecol. 63: 1298–1304.Google Scholar
  299. Thiersch, J. B., 1956, The control of reproduction in rats with the aid of antimetabolites and early experiments with antimetabolites as abortifacient agents in man, Acta Endocrinol. 23: 37–45.Google Scholar
  300. Thiersch, J. B., 1957, Effect of 2,4,6, triamino-“S”-triazine (TR) 2,4,6 “tris” (ethyleneimino)-“S”triazine (TEM) and N,N’,N“-triethylene-phosphoramide (TEPA) on rat litter in utero, Proc. Soc. Exp. Biol. Med. 94: 36–40.Google Scholar
  301. Trautner, E. M., Pennycuik, P. R., Morris, R. J. H., Gershon, S., and Shankly, K. H., 1958, The effect of prolonged sub-toxic lithium ingestion on pregnancy in rats, Aust. J. Exp. Biol. 36: 305–321.CrossRefGoogle Scholar
  302. Tsun-Yu, K. L., and Stiles, Q. R., 1975, Persistent fifth aortic arch in man, Am. J. Dis. Child. 129: 1229–1231.Google Scholar
  303. Tuchmann-Duplessis, H., 1965, Teratogenic Action of Drugs, Pergamon Press, New York; Czechoslovak Medical Press, Praha.Google Scholar
  304. Tuchmann-Duplessis, H., 1969, The action of anti-tumor drugs on gestation and on embryogenesis, in: Teratology, Proceedings of International Symposium at Como, Italy (A. Bertelli, ed.), pp. 75–86, Excerpta Medica, Amsterdam.Google Scholar
  305. Tuchmann-Duplessis, H., 1973, Teratogenic screening methods and their application to contraceptive products, in: Pharmacological Models in Contraceptive Development ( M. H. Briggs and E. Diczfalusy, eds.), pp. 203–223, WHO Reseach and Training Center on Human Reproduction, Stockholm.Google Scholar
  306. Tuchmann-Duplessis, H., and Mercier-Parot, L., 1956, Rèpercussions de la réserpine sur la gestation chez la ratte, C.R. Acad. Sci. 243: 410–412.Google Scholar
  307. Tuchmann-Duplessis, H., and Mercier-Parot, L., 1960, A propos de l’action tératogène de l’actinomycine, C.R. Soc. Biol. 153: 1697–1700.Google Scholar
  308. Tuchmann-Duplessis, H., and Mercier-Parot, L., 1961, Malformations foetales chez le rat traité par de fortes doses de deserpidine, C.R. Soc. Biol. 155: 2291.Google Scholar
  309. Tuchmann-Duplessis, H., and Mercier-Parot, L., 1963, Production de malformations chez le souris et le lapin par administration d’un sulfamide hypoglycemiant, la carbutamide, C.R. Soc. Biol. 158: 1193–1197.Google Scholar
  310. Tuchmann-Duplessis, H., and Mercier-Parot, L., 1964, Rèpercussions des neuroleptiques et des antitumoraux sur le développement prénatal, Bull. Acad. Suisse Sci. Med. 20: 490–526.Google Scholar
  311. Tuchmann-Duplessis, H., and Mercier-Parot, L., 1967, Delayed nidation under the influence of a neuroleptic agent R 1625 (haloperidol), C.R. Acad. Sci. 264: 114–117.Google Scholar
  312. Turner, G., and Collins, E., 1975, Fetal effects of regular salicylate ingestion in pregnancy, Lancet 2: 338–339.CrossRefGoogle Scholar
  313. Tze, W. J., and Lee, M., 1975, Adverse effects of maternal alcohol consumption on pregnancy and foetal growth in rats, Nature 257: 479–488.CrossRefGoogle Scholar
  314. Uhlig, H., 1957, Abnormalities in undesired children, Aerztl. Wochenschr. 12: 61.Google Scholar
  315. Uhlig, H., 1959, Fehlbildungen nach Follikel-hormonen beim Menschen, Geburtschilfe Frauenheilkd. 19: 346–352.Google Scholar
  316. Van Waes, A., and Van de Velde, E., 1969, Safety evaluation of haloperidol in the treatment of hyperemesis gravidarum, J. Clin. Pharmacol. 9: 224–227.Google Scholar
  317. van Wagenen, G., and Hamilton, J. B., 1943, The experimental production of pseudohermaphroditism in the monkey, Essays Bio. 583–607.Google Scholar
  318. Varpela, E., 1964, On the effect exerted by first-line tuberculosis medicines on the foetus, Acta Tuberc. Scand. 45: 53–69.Google Scholar
  319. Vevera, J., and Zatloukal, F., 1964, Pfipad vrozenÿch malformaci, zpusobenych pravdépodobné atebrinem, poddvanÿn vraném téhotenstvi, Cesk. Pediatr. 19: 211–212.Google Scholar
  320. Vichi, F., 1969, Neuroleptic drugs in experimental teratogenesis, in: Teratology ( A. Bertelli and L. Donati, eds.), pp. 87–101, Excerpta Medica, Amsterdam.Google Scholar
  321. Vichi, F., and Pierleoni, P., 1970, Effetti letali e teratogeni dell’haloperidol in embroni di topo, Riv. Ital. Stomatol. 25: 585–596.Google Scholar
  322. Voorhess, M. L., 1967, Masculinization of the female fetus associated with norethindrone mestranól therapy during pregnancy, J. Pediatr. 71: 128–131.CrossRefGoogle Scholar
  323. Warkany, J., 1975, A warfarin embryopathy?, Am. J. Dis. Child. 129: 287–288.Google Scholar
  324. Warkany, J., and Bofinger, M., 1975, Le rôle de la coumadin dans les malformations congénitales, Med. Hyg. 23: 1454–1457.Google Scholar
  325. Warkany, J., and Takacs, E., 1959, Experimental production of congenital malformations in rats by salicylate poisoning, Am. J. Pathol. 35: 315–331.Google Scholar
  326. Warkany, J., and Takacs, E., 1965, Congenital malformations in rats from streptonigrin, Arch. Pathol. 79: 65–79.Google Scholar
  327. Warkany, J., Beaudry, P. H., and Hornstein, S., 1959, Attempted abortion with aminopterin (4-aminopteroylglutamic acid), Am. J. Dis. Child. 97: 274–281.Google Scholar
  328. Warrell, D. W., and Taylor, R., 1968, Outcome for the foetus of mothers receiving prednisolone during pregnancy, Lancet 1: 117–118.CrossRefGoogle Scholar
  329. Wells, C. N., 1953, Treatment of hyperemesis gravidum with cortisone, Am. J. Obstet. Gynecol. 66: 598.Google Scholar
  330. Wickes, I. G., 1954, Foetal defects following insulin coma therapy in early pregnancy, Br. Med. J. 2: 1029.CrossRefGoogle Scholar
  331. Wild, J., Schorah, C. J., and Smithells, R. W., 1974, Vitamin A, pregnancy, and oral contraceptives, Br. Med. J. 1: 57–60.CrossRefGoogle Scholar
  332. Wilkins, L., 1960, Masculinization of female fetus due to use of orally given progestins, J. Am. Med. Assoc. 172: 1028–1032.CrossRefGoogle Scholar
  333. Wilson, J. G., 1964, Teratogenic interaction of chemical agents in the rat, J. Pharmacol. Exp. Ther. 144: 429–436.Google Scholar
  334. Wilson, J. G., 1966, Effects of acute and chronic treatment with actinomycin D on pregnancy and the fetus in the rat, Harper Hosp. Bull. 24: 109–118.Google Scholar
  335. Wilson, J. G., 1971, Use of rhesus monkeys in teratological studies, Fed. Proc. 30: 104–109.Google Scholar
  336. Wilson, J. G., 1972, Abnormalities of intrauterine development in nonhuman primates, in: The Use of Non-Human Primates in Research on Human Reproduction ( E. Diczfalusy and C. C. Standley, eds.), pp. 261–292, WHO Research and Training Center on Human Reproduction, Stockholm.Google Scholar
  337. Wilson, J. G., 1973a, An animal model of human disease: Thalidomide embryopathy in primates, Comp. Pathol. Bull. 5: 3–4.Google Scholar
  338. Wilson, J. G., 1973b, Environment and Birth Defects, Academic Press, New York.Google Scholar
  339. Wilson, J. G., 1974, Teratologic causation in man and its evaluation in non-human primates, in: Birth Defects ( A. G. Motulsky and W. Lenz, eds.), pp. 191–203, Excerpta Medica, Amsterdam.Google Scholar
  340. Wilson, J. G., Maren, T. H., Takano, K., and Ellison, A., 1968, Teratogenic action of carbonic anhydrase inhibitors in the rat, Teratology 1: 51–60.CrossRefGoogle Scholar
  341. Winckel, C. W. F., 1948, Quinine and congenital injuries of ear and eye of the foetus, J. Trop. Med. 51: 2.Google Scholar
  342. Windorfer, A., 1953, Zum problem du Missbildungen durch bewusste Keim-und Fruchtschadigung, Med. Klin. Berl. 48: 293.Google Scholar
  343. Wright, T. L., Hoffman, L. H., and Davies, J., 1971, Teratogenic effects of lithium in rats, Teratology 4: 151–156.CrossRefGoogle Scholar
  344. Yalom, I. D., Grau, R., and Fisk, N., 1973, Prenatal exposure to female hormones: Effect on psychosexual development in boys, Arch. Gen. Psychiatry 28: 554–561.CrossRefGoogle Scholar
  345. Yasuda, M., and Poland, B. J., 1974, A 63-mm human fetus with radial aplasia, tibial polydactyly, rib and vertebral fusions, and right aortic arch, Teratology 10: 119–124.CrossRefGoogle Scholar
  346. Yerushalmy, J., and Milkovich, L., 1965, Evaluation of the teratogenic effect of meclizine in man, Am. J. Obstet. Gynecol. 93: 553–562.Google Scholar
  347. Zackai, E. H., Mellman, W. J., Neiderer, B., and Hanson, J. W., 1975, The fetal trimethadione syndrome, J. Pediatr. 87: 280–284.CrossRefGoogle Scholar
  348. Zolcinski, A., Heimrath, T., and Ujec, M., 1965, Quinine as a cause of fetal malformation, Ginekol. Pol. 36: 935–938.Google Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • James G. Wilson
    • 1
  1. 1.Children’s Hospital Research FoundationCincinnatiUSA

Personalised recommendations