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August 1966, Vol 112, No. 2 >
Article | August 1966

Malformations Caused by Drugs in Pregnancy FREE

W. LENZ
[+] Author Affiliations

Received for publication Jan 20, 1966.

Read before the 11th International Congress of Pediatrics, Tokyo, Nov 8, 1965.

Reprint requests to Institut fur Humangenetik der Universitat Munster, Vesaliusweg 12/14, 44 Munster/Westf, Germany.


Am J Dis Child. 1966;112(2):99. doi:10.1001/archpedi.1966.02090110043001.
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References
Comments

UP TO 1961, only a few cases of malformations in man have been attributed to drugs, notably aminopterin (Thiersch, 1952;1 and 1960;2 Meltzer, 1956;3 and Warkany et al, 19594), busulfan (Diamond et al 19605), androgens and progestogens (Wilkins, 19606), cortisone (Bongiovanni and McPadden, 19607), quinine (Grebe, 1952,8 Uhlig, 1957;9 and Windorfer, 195310), insulin (Wickes, 195411), and tolbutamide (Larsson and Sterky, 196012).

A causal relationship has been well established only for aminopterin and for the androgenic and gestagenic hormones. A few cases of cleft palate following high doses of cortisone administered in early pregnancy are suggestive of a causative effect in view of similar results in animal experiments.

A connection between quinine intake for artificial abortion and malformations has been assumed in selected cases. However, no unbiased study is available. The malformations attributed to quinine have not shown any

REFERENCES

1 +
Thiersch, J.B.:  Therapeutic Abortions With a Folic Acid Antagonist, 4-Aminopteroylglutamic Acid (4-Amino P.G.A.) Administered by the Oral Route , Amer J Obstet Gynec 63:1298-1304, 1952;.
2 +
Thiersch, J.B.: Discussion in: CIBA Foundation Symposium on Congenital Malformations , London: J. & A. Churchill Ltd, 1960;, pp 152-154.
3 +
Meltzer, H.J.:  Congenital Anomalies Due to Attempted Abortion With 4-Aminopteroglutamic Acid , JAMA 161:1253, 1956;.
4 +
Warkany, J.; Beaudry, P.H.; and Hornstein, S.:  Attempted Abortion With Aminopterin (4-Amino-Pteroylglutamic Acid) , Amer J Dis Child 97: 274-281, 1959;.
5 +
Diamond, I.; Anderson, M.M.; and McCreadie, S.R.:  Transplacental Transmission of Busulfan (Myleran) in a Mother With Leukemia: Production of Fetal Malformation and Cytomegaly , Pediatrics 25:85-90, 1960;.
6 +
Wilkins, L.P.:  Masculinization of Female Fetus Due to Use of Orally Given Progestins , JAMA 172:1028-1032, 1962;.
7 +
Bongiovanni, A.M., and McPadden, A.J.:  Steroids During Pregnancy and Possible Fetal Consequences , Fertil Steril 11:181, 1960;.
8 +
Grebe, H.:  Können Abtreibungsversuche zu Missbildungen führen? Geburtsh Frauenheilk 12: 333-339, 1952;.
9 +
Uhlig, H.:  Missbildungen unerwünschter Kinder , Ärztl Wschr 12:61-64, 1957;.
10 +
Windorfer, A.:  Zum Problem der Missbildungen durch bewusste Keimund Fruchtschädigund , Med Klin 48:293-297, 1953;.
11 +
Wickes, I.G.:  Foetal Defects Following Insulin Coma Therapy in Early Pregnancy , Brit Med J 2:1029-1030, 1954;.
12 +
Larsson, Y., and Sterky, G.:  Possible Teratogenic Effect of Tolbutamide in a Pregnant Pediabetic Lancet 2:1424-1425, 1960;.
13 +
Ingalls, T.H., and Prindle, R.A.:  Esophageal Atresia With Tracheoesophageal Fistula , New Eng J Med 240:987-995, 1949;.
14 +
Ferrier, P.; Widgren, S.; and Ferrier, S.:  Nonspecific Pseudohermaphroditism: Report of Two Cases With Cytogenetic Investigation , Helv Paediat Acta 19:1-12, 1964;.
15 +
Fuhrmann, W.:  Genetische und peristatische Ursachen angeborener Angiokardiopathien , Ergebn Inn Med Kinderheilk 18:79-81, 1962;.
16 +
Kucera, J., and Benesová, D.:  Poruchy Nitrodelozniho VyVoje Cloveka Zpusobené Pokusem o Potrat , Cesk Pediat 17:483-489, 1962;.
17 +
Maier, W.:  Unser derzeitiges Wissen über äussere schädigende Einflüsse auf den Embryo und angeborene Missbildungen , Deutsch Z Ges Gerichtl Med 55:156-172, 1964;.
18 +
Mellin, G.W.:  Drugs in the First Trimester of Pregnancy and the Fetal Life of Homo Sapiens , Amer J Obstet Gynec 90:1169-1180, 1964;.
19 +
Taylor, H.M.:  Prenatal Medication as a Possible Etiologic Factor of Deafness in the New-born , Arch Otolaryng 20:790-803, 1934;.
20 +
Taylor, H.M.:  Further Observations on Prenatal Medication as a Possible Etiologic Factor of Deafness in the New-born , State Med J Nashville 28:125-129, 1935;.
21 +
Kinney, M.D.:  Hearing Impairments in Children , Laryngoscope 63:220, 1953;.
22 +
Robinson, G.C.; Brummitt, J.R.; and Miller, J.R.:  Hearing Loss in Infants and Preschool Children: II. Etiological Considerations , Pediatrics 32: 115-124, 1963;.
23 +
West, R.A.:  Effect of Quinine Upon Auditory Nerve , Amer J Obstet Gynec 36:241-248, 1938;.
24 +
Pedersen, L.M.; Tygstrup, I.; and Pedersen, J.:  Congenital Malformations in Newborn Infants of Diabetic Women: Correlation With Maternal Diabetic Vascular Complications , Lancet 1:1124-1126, 1964;.
25 +
Sobel, D.E.:  Fetal Damage Due to ECT, Insulin Coma, Chlorpromazine, or Reserpine , Arch Gen Psych 2:606-611, 1960;.
26 +
Sterne, J., and Lavieuville, M.:  Enquete clinique sur les effets tératogènes éventuels des antidiabétiques oraux sur le foetus humain , Thérapie 19:165-170, 1964;.
27 +
McBride, W.G.:  The Teratogenic Action of Drugs , Med J Aust 2:689-693, 1963;.
28 +
Biering-Sørensen, K.:  Congenital Malformations and Antihistaminic Drugs , Bull Soc Roy Belg Gynec Obstet 33:87-93, 1963;.
29 +
Carter, M.P., and Wilson, F.W.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1609, 1962;.
30 +
Diggory, P.L.C., and Tomkinson, J.S.:  Meclozine and Foetal Abnormalities , Lancet 2:1222, 1962;.
31 +
Döring, G.K., and Hossfeld, C.:  Über die Gefahren einer übertriebenen Medikamentenfurcht in der Schwangerschaft , Deutsch Med Wschr 89:1069-1072, 1964;.
32 +
Lask, S.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1609, 1962;.
33 +
Macleod, M.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1609, 1962;.
34 +
Meyberg, J.:  Meclizin und Foetale Missbildungen , Med Welt 2:2414-2417, 1963;.
35 +
Morandi, E., and Marchesoni, M.:  Incidence of Congenital Malformations Following Meclizine Therapy in the First Three Months of Pregnancy: A Report About the Trento Civil Hospital (1960-1962) , Bull Soc Roy Belg Gynec Obstet 33:139-142, 1963;.
36 +
Pettersson, F.:  Meclizine and Congenital Malformations , Lancet 1:675, 1964;.
37 +
Rosa, P.:  Les craintes émises à propos d'une éventuelle action tératogène de la méclizine sontelles fondées? Bull Roy Soc Belg Gynec Obstet 33: 149-162, 1963;.
38 +
Salzmann, K.D.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 1:471, 1963;.
39 +
Sjövall, A., and Ursing, I.:  A Rapid Retrospective Analysis Concerning the Supposed Terato- genicity of "Postafene" (Meclozine) , Bull Roy Soc Belg Gynec Obstet 33:95-105, 1963;.
40 +
Smithells, R.W., and Chinn, E.R.:  Meclozine and Foetal Abnormalities , Brit Med J 1:1678-1679, 1963;.
41 +
Smithells, R.W., and Chinn, E.R.:  Meclozine and Foetal Malformations: A Prospective Study , Brit Med J 1:217-218, 1964;.
42 +
Villumsen, A.L., and Zachau-Christiansen, B.:  Incidence of Malformations in the New-Born in a Prospective Child Health Study , Bull Roy Soc Belge Gynec Obstet 33:95-105, 1963;.
43 +
Woodall, J.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1681-1682, 1962;.
44 +
King, C.T.G.:  Teratogenic Effects of Meclizine Hydrochloride on the Rat , Science 14:353-355, 1963;.
45 +
Winberg, J.:  Utredning rörande det eventuella sambandet mellan fosterskador och läkemedel , Svensk Läkartidn 61:722-814, 1964;.
46 +
Curtis, E.J., and Walker, N.F.: Unpublished data.
47 +
Stark, R.B., et al:  Investigation of Possible Causative Factors Producing Human Maldevelopment , Plast Reconstr Surg 30:543-553, 1962;.
48 +
Janz, D., and Fuchs, U.:  Sind antiepileptische Medikamente während der Schwangerschaft schädlich? Deutsch Med Wschr 89:241-243, 1964;.
49 +
Jentgens, H.:  Tuberkulostatische Behandlung in der Gravidität und angebliche fetale Schäden , Med Welt 29:1576-1583, 1964;.
50 +
Lowe, C.R.:  Congenital Defects Among Children Born to Women Under Supervision or Treatment for Pulmonary Tuberculosis , Brit J Prev Soc Med 18:14, 1964;.
51 +
Varpela, E.:  On the Effect Exerted by First-Line Tuberculosis Medicines on the Foetus , Acta Tuberc Scand 35:53-69, 1964;.
52 +
Greenberg, L.H., and Tanaka, K.R.:  Congenital Anomalies Probably Induced by Cyclophosphamide , JAMA 188:423-426, 1964;.
53 +
Kunz, W.; Keller, H.; and Muckter, H.:  N-phthalylglutaminsäureimid: Experimentelle Untersuchungen an einem neuen synthetischen Produkt , Arzneimittelforschung 6:426, 1956;.
54 +
Jung, H.:  Klinische Erfahrungen mit einem neuen Sedativum , Arzneimittelforschung 6:430-436, 1956;.
55 +
Krueger, R.: Die Phocomelie und ihre Ubergänge , Berlin: Aug Hirschwalt, 1906;.
56 +
Wepler, W.:  Die sogenannte Phokomelie , Deutsch Med Wschr 63:1302-1308, 1937;.
57 +
Veiel, A.F.: Über mangelhafte Bildung der Extremitäten , Tübingen: Inaug.-Diss, 1829;.
58 +
Goerttler, K.:  Was wissen wir über die Entstehung von Missbildungen? Schleswig-Holsteinisches Ärzteblatt 16:207-221, 1963;.
59 +
Jurczok, F., and Schollmeyer, R.:  Zur Frage des gehäuften Auftretens von Extremitätenmissbildungen bei Neugeborenen , Geburtsh Frauenheilk 22: 400-421, 1962;.
60 +
Hepp, O.:  Die Häufung der angeborenen Defektmissbildungen der oberen Extremitäten in der Bundesrepublik Deutschland , Med Klin 57:419-426, 1962;.
61 +
Kucera, J.; Lenz, W.; and Maier, W.:  Missbildungen der Beine und der kaudalen Wirbelsäule bei Kindern diabetischer Mütter , Deutsch Med Wschr 90:901-905, 1965;.
62 +
Nowack, E.:  Die sensible Phase bei der Thalidomid-Embryopathie , Humangenetik 1:516-536, 1965;.
63 +
Delahunt, C.S.: Personal communication to the author, 1965.

Figures

Tables

Interactive Graphics

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

1 +
Thiersch, J.B.:  Therapeutic Abortions With a Folic Acid Antagonist, 4-Aminopteroylglutamic Acid (4-Amino P.G.A.) Administered by the Oral Route , Amer J Obstet Gynec 63:1298-1304, 1952;.
2 +
Thiersch, J.B.: Discussion in: CIBA Foundation Symposium on Congenital Malformations , London: J. & A. Churchill Ltd, 1960;, pp 152-154.
3 +
Meltzer, H.J.:  Congenital Anomalies Due to Attempted Abortion With 4-Aminopteroglutamic Acid , JAMA 161:1253, 1956;.
4 +
Warkany, J.; Beaudry, P.H.; and Hornstein, S.:  Attempted Abortion With Aminopterin (4-Amino-Pteroylglutamic Acid) , Amer J Dis Child 97: 274-281, 1959;.
5 +
Diamond, I.; Anderson, M.M.; and McCreadie, S.R.:  Transplacental Transmission of Busulfan (Myleran) in a Mother With Leukemia: Production of Fetal Malformation and Cytomegaly , Pediatrics 25:85-90, 1960;.
6 +
Wilkins, L.P.:  Masculinization of Female Fetus Due to Use of Orally Given Progestins , JAMA 172:1028-1032, 1962;.
7 +
Bongiovanni, A.M., and McPadden, A.J.:  Steroids During Pregnancy and Possible Fetal Consequences , Fertil Steril 11:181, 1960;.
8 +
Grebe, H.:  Können Abtreibungsversuche zu Missbildungen führen? Geburtsh Frauenheilk 12: 333-339, 1952;.
9 +
Uhlig, H.:  Missbildungen unerwünschter Kinder , Ärztl Wschr 12:61-64, 1957;.
10 +
Windorfer, A.:  Zum Problem der Missbildungen durch bewusste Keimund Fruchtschädigund , Med Klin 48:293-297, 1953;.
11 +
Wickes, I.G.:  Foetal Defects Following Insulin Coma Therapy in Early Pregnancy , Brit Med J 2:1029-1030, 1954;.
12 +
Larsson, Y., and Sterky, G.:  Possible Teratogenic Effect of Tolbutamide in a Pregnant Pediabetic Lancet 2:1424-1425, 1960;.
13 +
Ingalls, T.H., and Prindle, R.A.:  Esophageal Atresia With Tracheoesophageal Fistula , New Eng J Med 240:987-995, 1949;.
14 +
Ferrier, P.; Widgren, S.; and Ferrier, S.:  Nonspecific Pseudohermaphroditism: Report of Two Cases With Cytogenetic Investigation , Helv Paediat Acta 19:1-12, 1964;.
15 +
Fuhrmann, W.:  Genetische und peristatische Ursachen angeborener Angiokardiopathien , Ergebn Inn Med Kinderheilk 18:79-81, 1962;.
16 +
Kucera, J., and Benesová, D.:  Poruchy Nitrodelozniho VyVoje Cloveka Zpusobené Pokusem o Potrat , Cesk Pediat 17:483-489, 1962;.
17 +
Maier, W.:  Unser derzeitiges Wissen über äussere schädigende Einflüsse auf den Embryo und angeborene Missbildungen , Deutsch Z Ges Gerichtl Med 55:156-172, 1964;.
18 +
Mellin, G.W.:  Drugs in the First Trimester of Pregnancy and the Fetal Life of Homo Sapiens , Amer J Obstet Gynec 90:1169-1180, 1964;.
19 +
Taylor, H.M.:  Prenatal Medication as a Possible Etiologic Factor of Deafness in the New-born , Arch Otolaryng 20:790-803, 1934;.
20 +
Taylor, H.M.:  Further Observations on Prenatal Medication as a Possible Etiologic Factor of Deafness in the New-born , State Med J Nashville 28:125-129, 1935;.
21 +
Kinney, M.D.:  Hearing Impairments in Children , Laryngoscope 63:220, 1953;.
22 +
Robinson, G.C.; Brummitt, J.R.; and Miller, J.R.:  Hearing Loss in Infants and Preschool Children: II. Etiological Considerations , Pediatrics 32: 115-124, 1963;.
23 +
West, R.A.:  Effect of Quinine Upon Auditory Nerve , Amer J Obstet Gynec 36:241-248, 1938;.
24 +
Pedersen, L.M.; Tygstrup, I.; and Pedersen, J.:  Congenital Malformations in Newborn Infants of Diabetic Women: Correlation With Maternal Diabetic Vascular Complications , Lancet 1:1124-1126, 1964;.
25 +
Sobel, D.E.:  Fetal Damage Due to ECT, Insulin Coma, Chlorpromazine, or Reserpine , Arch Gen Psych 2:606-611, 1960;.
26 +
Sterne, J., and Lavieuville, M.:  Enquete clinique sur les effets tératogènes éventuels des antidiabétiques oraux sur le foetus humain , Thérapie 19:165-170, 1964;.
27 +
McBride, W.G.:  The Teratogenic Action of Drugs , Med J Aust 2:689-693, 1963;.
28 +
Biering-Sørensen, K.:  Congenital Malformations and Antihistaminic Drugs , Bull Soc Roy Belg Gynec Obstet 33:87-93, 1963;.
29 +
Carter, M.P., and Wilson, F.W.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1609, 1962;.
30 +
Diggory, P.L.C., and Tomkinson, J.S.:  Meclozine and Foetal Abnormalities , Lancet 2:1222, 1962;.
31 +
Döring, G.K., and Hossfeld, C.:  Über die Gefahren einer übertriebenen Medikamentenfurcht in der Schwangerschaft , Deutsch Med Wschr 89:1069-1072, 1964;.
32 +
Lask, S.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1609, 1962;.
33 +
Macleod, M.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1609, 1962;.
34 +
Meyberg, J.:  Meclizin und Foetale Missbildungen , Med Welt 2:2414-2417, 1963;.
35 +
Morandi, E., and Marchesoni, M.:  Incidence of Congenital Malformations Following Meclizine Therapy in the First Three Months of Pregnancy: A Report About the Trento Civil Hospital (1960-1962) , Bull Soc Roy Belg Gynec Obstet 33:139-142, 1963;.
36 +
Pettersson, F.:  Meclizine and Congenital Malformations , Lancet 1:675, 1964;.
37 +
Rosa, P.:  Les craintes émises à propos d'une éventuelle action tératogène de la méclizine sontelles fondées? Bull Roy Soc Belg Gynec Obstet 33: 149-162, 1963;.
38 +
Salzmann, K.D.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 1:471, 1963;.
39 +
Sjövall, A., and Ursing, I.:  A Rapid Retrospective Analysis Concerning the Supposed Terato- genicity of "Postafene" (Meclozine) , Bull Roy Soc Belg Gynec Obstet 33:95-105, 1963;.
40 +
Smithells, R.W., and Chinn, E.R.:  Meclozine and Foetal Abnormalities , Brit Med J 1:1678-1679, 1963;.
41 +
Smithells, R.W., and Chinn, E.R.:  Meclozine and Foetal Malformations: A Prospective Study , Brit Med J 1:217-218, 1964;.
42 +
Villumsen, A.L., and Zachau-Christiansen, B.:  Incidence of Malformations in the New-Born in a Prospective Child Health Study , Bull Roy Soc Belge Gynec Obstet 33:95-105, 1963;.
43 +
Woodall, J.:  "Ancoloxin" and Foetal Abnormalities , correspondence, Brit Med J 2:1681-1682, 1962;.
44 +
King, C.T.G.:  Teratogenic Effects of Meclizine Hydrochloride on the Rat , Science 14:353-355, 1963;.
45 +
Winberg, J.:  Utredning rörande det eventuella sambandet mellan fosterskador och läkemedel , Svensk Läkartidn 61:722-814, 1964;.
46 +
Curtis, E.J., and Walker, N.F.: Unpublished data.
47 +
Stark, R.B., et al:  Investigation of Possible Causative Factors Producing Human Maldevelopment , Plast Reconstr Surg 30:543-553, 1962;.
48 +
Janz, D., and Fuchs, U.:  Sind antiepileptische Medikamente während der Schwangerschaft schädlich? Deutsch Med Wschr 89:241-243, 1964;.
49 +
Jentgens, H.:  Tuberkulostatische Behandlung in der Gravidität und angebliche fetale Schäden , Med Welt 29:1576-1583, 1964;.
50 +
Lowe, C.R.:  Congenital Defects Among Children Born to Women Under Supervision or Treatment for Pulmonary Tuberculosis , Brit J Prev Soc Med 18:14, 1964;.
51 +
Varpela, E.:  On the Effect Exerted by First-Line Tuberculosis Medicines on the Foetus , Acta Tuberc Scand 35:53-69, 1964;.
52 +
Greenberg, L.H., and Tanaka, K.R.:  Congenital Anomalies Probably Induced by Cyclophosphamide , JAMA 188:423-426, 1964;.
53 +
Kunz, W.; Keller, H.; and Muckter, H.:  N-phthalylglutaminsäureimid: Experimentelle Untersuchungen an einem neuen synthetischen Produkt , Arzneimittelforschung 6:426, 1956;.
54 +
Jung, H.:  Klinische Erfahrungen mit einem neuen Sedativum , Arzneimittelforschung 6:430-436, 1956;.
55 +
Krueger, R.: Die Phocomelie und ihre Ubergänge , Berlin: Aug Hirschwalt, 1906;.
56 +
Wepler, W.:  Die sogenannte Phokomelie , Deutsch Med Wschr 63:1302-1308, 1937;.
57 +
Veiel, A.F.: Über mangelhafte Bildung der Extremitäten , Tübingen: Inaug.-Diss, 1829;.
58 +
Goerttler, K.:  Was wissen wir über die Entstehung von Missbildungen? Schleswig-Holsteinisches Ärzteblatt 16:207-221, 1963;.
59 +
Jurczok, F., and Schollmeyer, R.:  Zur Frage des gehäuften Auftretens von Extremitätenmissbildungen bei Neugeborenen , Geburtsh Frauenheilk 22: 400-421, 1962;.
60 +
Hepp, O.:  Die Häufung der angeborenen Defektmissbildungen der oberen Extremitäten in der Bundesrepublik Deutschland , Med Klin 57:419-426, 1962;.
61 +
Kucera, J.; Lenz, W.; and Maier, W.:  Missbildungen der Beine und der kaudalen Wirbelsäule bei Kindern diabetischer Mütter , Deutsch Med Wschr 90:901-905, 1965;.
62 +
Nowack, E.:  Die sensible Phase bei der Thalidomid-Embryopathie , Humangenetik 1:516-536, 1965;.
63 +
Delahunt, C.S.: Personal communication to the author, 1965.

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