VIRGINIA /APGAR Since the thalidomide tragedy of 1960 to 1962, pregnant women have been in a quandry about taking com- mon medications on their own in- itiative, and physicians have been troubled about prescribing drugs for them. Peckham and King have shown recently that 92 percent of women have at least one drug prescribed by their physicians during pregnancy, and 3.9 percent are given 10 or more (1). There is no count of babies who have survived because of drugs ad- ministered during pregnancy, infants who escaped birth defects because their mothers were given certain drugs, or full-term babies who might have been born prematurely without drugs. Both physicians and patients rightly demand to know what infor- mation is available about drugs and human pregnancy. Very little is known that can actu- ally be applied to all pregnancies. According to Lenz, 80 percent of the ‘mothers who took thalidomide dur- ing the period of fetal sensitivity had normal infants (2). What was it in the genetic background of the mother or the father that caused the serious anomalies that occurred in 20 per- cent of the infants? What environ- mental associations were related? The answers to these questions are a long way off. This past year, two useful reviews appeared, by Cohlan and Lucey, about the effect of medication ad- ministered during pregnancy on the fetus and newborn infant, from which these comments are largely drawn (3,4). Two other reviews, which dis- cuss in detail the problems of human teratogenesis, were written by Wark- any and Kalter and by Fraser. All are DR. APGAR is a member of the pediatrics panel of the American Medical Association Registry on Adverse Reactions. DRUGS IN PREGNANCY highly recommended (5,6). The table lists some relationships observed between maternal medica- tion and fetal or neonatal changes. Only a few are proved beyond a shad- ow of doubt, but until further data are collected, caution should be exer- cised in administering these sub- stances to pregnant women. The best way to determine a post hoc ergo propter hoc relationship between maternal medication and changes in the fetus and newborn infant is to conduct a prospective study in a population of women who enter the study by the eighth week of pregnancy. They should be frequent- ly observed and interrogated by only one, two, or three astute clinicians, and the data should be entered and analyzed within a few hours’ time. Such-a study, a continuation of the Fetal Life Study of McIntosh and Merritt begun in 1947, is being con- ducted by Mellin(8). Routine ques- tioning about the intake of certain drugs formed the basis of their re- port that meclizine hydrochloride (Bonadettes, Bonine Hydrochloride) was not under suspicion as a terato- genic agent(9). Other prospective studies, such as that of the Kaiser Permanente group, and the Collabo- rative Study of the National Institute of Neurological Disease and Blind- ness can be expected to show certain relationships between medication ad- ministered during pregnancy and fe- tal and neonatal changes, But these studies lack the accuracy achieved by a small, closely controlled group of pregnant women, observed by the same professional team. The greatest danger of inducing malformations is in the first trimester of pregnancy. Since this includes the period before a woman may be aware that she is pregnant, and since we know very little about the effects of drugs on the fetus, physicians are AMERICAN JOURNAL OF NURSING urged to exercise great restraint in rescribing medications for women of childbearing age, and self-medica- strongly discouraged. Dr. Emest Page’s doublet, “Don’t make a of the afterbirth,” i is cer- rplacentation is established. However, is : Cohlan suggests, “placental panic” Fences that terminate in a viable peaby, the placenta has performed REFERENCES “1, PECKHAM, Cc. H., AND KING, R. W. ” Study of intercurrent conditions observed during pregnancy. Amer.J.Obstet.Gynec. 87:609-620, Nov. 1, 1963. 2. LENZ, W. Personal communication to the author. .38. COHLAN, S. Q. Fetal and neonatal haz- “ards from drugs administered during preg- _mancy. New York J.Med. 64:493-499, c. Feb. 15, 1964. . 4. LUCEY, J. F. Fetal effects of drugs given . to mothers during pregnancy, symposium ‘on the placenta, New York, March 6, 1964, J.Pediat. (To be published) BS. WARKANY, J.. AND KALTER, H. Con- genital malformations. New Eng.J.Med. 265:993-1001; 1046-1052, Nov. 16, 23, 1961. bi FRASER, F. C. Experimental Teratogens ' 4m Relation to Congenital Malformations in _Men, eeiteat Comune of the Second Inter- national Congress on Congenital Malfor- ‘mations, New York, July 6 to 19, 1963. “(To be published ) ‘y:RODRIQUEZ, S. U., AND OTHERS. ‘Neonatal thrombocytopenia associated with | “ante-partum administration of thiazide ‘drugs, New Eng J.Med. 270: 881-884, Apr. 23, 1964. .8. MELLIN, G. Fetal Life Study: Prospectice : "iB pidemiological Study of Prenatal Influ- cle on Fetal. Development end. Syrvical. ‘Conference ‘on ‘Research Methodology and (Needs in Perinatal Studies, Chapel Hill, x; Sept. 9. to.11, 2963, ory, wl gg a . \ Mate“ ~ - : eT | | article is reprinted from The Journal of ©. American Medical Association, November MEDICATION AND CHANGES PRODUCED MATERNAL MEDICATION FETAL OR NEONATAL EFFECT i. 0, : 1964, Vol. 190, pp. 840-841. Copyright py: Be Oral progestogens Androgens Estrogens Cortisone Acetate (Cortogen Acetate, Cortone Acetate) Potassium iodide Propyithiouracil Methimazoile (Tapazole) lophenoxic acid (Teridax) Sodium aminopterin Methotrexate (Amethopterin) Chiorambucil (Leukeran) Bishydroxycoumarin (Dicumaro!) Ethy! bicoumacetate (Tromexan Ethyi Acetate) Sodium warfarin (Coumadin Sodium, Panwarfin, Prothromadin) Salicylates (large amounts) - Streptomycin Sulfonamides Chloramphenicol (Chloromycetin) Sodium novobiocin (Albamycin Sodium, Cathomycin Sodium) Erythromycin (llesone) Nitrofurantoin (Furadantin) Tetracyclines Vitamin K Analogues (in excess) Ammonium chloride Intravenous fluids (in excess) Reserpine (Rauloydin, Raurine, Rau-Sed, Reserpoid, Sandril, Serfin, Serpasil, Serpate, Vio-Serpine) Hexamethonium bromide (Bistrium Bromide) Heroin and morphine Phenobarbital (in excess) Smoking : Sulphonylurea derivatives Phenformin hydrochloride (DBI) ‘Phenothiazines -Meprobamate (Equanil, Wyseats, ' “Meprospan, Meprotabs, _-FMiltewn). 2st: : Chloroquine. phosphate (ralen » Phosphate) - ad : “Quinine oe Jeditor) Lancet. 1829-293, Jan... 26, Thalidomide | ' Vaccination, ‘émaltpox Vaccination, influenza Antihistamines” Thiazide diuretics . Masculinization and advanced bone age Anomalies: cleft palate (?) Goiter and mental retardation Elevation of P.B.1. Anomalies and abortion Fetal death; hemorrhage Neonatal bleeding Possible 8th nerve deafness Kernicterus : “Grey” syndrome; death Hyperbilirubinemia Liver damage (?) Hemolysis Inhibition of bone growth Discoloration of teeth Hyperbilirubinemia Acidosis Electrolyte Abnormalities Stuffy nose; respiratory obstruction Neonatal ileus Neonatal death Neonatal bleeding; death Birth of small babies Anomalies (7) Lactic acidosis (7) Hyperbilirubinemia (?) Retarded development (?) Retinal damage or death (?) 2 Thrombocytopenia yo Phocomelia; death; hearing loss Fetal vaccinia Increased anti-A and 8 titers in mothers ~ Anomalies (2); infertility Thrombocytopenia q) MARCH 1965