Attempted Abortion with Aminopterin (4-Amino-Pteroylglutamic Acid): Malformations of the Child FREE

JOSEF WARKANY, M.D.; PIERRE H. BEAUDRY, M.D.; STEPHEN HORNSTEIN, M.D.

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Submitted for publication July 28, 1958.

Research Fellow supported by Grant RG 5099, National Institutes of Health, V. S. Public Health Service (Dr. Beaudry).

AMA Am J Dis Child. 1959;97(3):274-281. doi:10.1001/archpedi.1959.02070010276003.

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ABSTRACT

ABSTRACT | REFERENCES

Pteroylglutamic acid (PGA, folic acid) plays an important role in many biological reactions, and PGA deficiency may lead to death of mammalian embryos. Nelson and Evans¹ demonstrated reproductive failure in rats kept on a PGA-deficient diet containing succinylsulfathiazole and a crude PGA antagonist. Thiersch and Philips² induced fetal death in rodents kept on an adequate diet by administration of aminopterin (4-amino-pteroylglutamic acid), a powerful PGA antagonist. Later Giroud and Lefebvres-Boisselot³ and Nelson, Asling, and Evans⁴ produced multiple congenital abnormalities by maternal PGA deficiencies during gestation.

Aminopterin has also been used to induce therapeutic abortions in women with tuberculosis or cancer. In 10 out of 12 cases reported by Thiersch⁵ oral doses of 6 to 12 mg. aminopterin induced fetal death in the first trimester of pregnancy, followed by spontaneous delivery of the products of conception. The doses lethal to the embryo had only mild effects

REFERENCES

ABSTRACT | REFERENCES

Nelson, M. M., and Evans, H. M.: Pteroylglutamic Acid and Reproduction in the Rat , J. Nutrition 38:11, 1949;.

Thiersch, J. B., and Philips, F. S.: Effect of 4-Amino-Pteroylglutamic Acid (Aminopterin) on Early Pregnancy , Proc. Soc. Exper. Biol. & Med. 74:204, 1950;.

Giroud, A., and Lefebvres-Boisselot, J.: Influence tératogène de la carence en acide folique , Compt. rend. Soc. biol. 145:526, 1951;.

Nelson, M. M.; Asling, C. W., and Evans, H. M.: Production of Multiple Congenital Abnormalities in Young by Maternal Pteroylglutamic Acid Deficiency During Gestation , J. Nutrition 48:61, 1952;.

Thiersch, J. B.: Therapeutic Abortions with a Folic Acid Antagonist, 4-Aminopteroylglutamic Acid (4-Amino P. G. A.) Administered by the Oral Route , Am. J. Obst. & Gynec. 63:1298, 1952;.

Thiersch, J. B.: The Control of Reproduction in Rats with the Aid of Antimetabolites and Early Experiments with Antimetabolites as Abortifacient Agents in Man , Acta Endocrinol. ( (Supp. 28) ) 23:37, 1956;.

Meltzer, H. J.: Congenital Anomalies Due to Attempted Abortion with 4-Aminopteroglutamic Acid , J. A. M. A. 161:1253, 1956;.

Apgar, V.: A Proposal for a New Method of Evaluation of the Newborn Infant , Anesth. & Analg. 32:260, 1953;.

Patten, B. M.: Human Embryology , Ed. 2, New York, The Blakiston Company (division of McGraw-Hill Book Company, Inc.), 1953;.

Whitehouse, D. B., and McKeown, T.: A Note on the Significance of Attempted Abortion in the Aetiology of Congenital Abnormalities , J. Obst. & Gynaec. Brit. Emp. 63:224, 1956;.

Warkany, J.: Can the Origin of Congenital Malformations Be Dated by Their Morphological Characteristics? A. M. A. J. Dis. Child . 94:434, 1957;.

Gruenwald, P.: Malformations Caused by Necrosis in the Embryo: Illustrated by the Effect of Selenium Compounds on Chick Embryos , Am. J. Path. 34:77, 1958;.

Fulton, J. T.: Closure of the Human Palate in Embryo , Am. J. Obst. & Gynec. 74:179, 1957;.

Streeter, G. L.: Development of the Auricle in the Human Embryo , in Carnegie Contributions to Embryology , Vol. 14, Washington, D. C., Carnegie Institution of Washington, 1922;, p. 111.

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