Spontaneous abortion and the use of sugar substitutes (saccharin) JENNIE KLINE, PH.D. ZENA A. STEIN, M.A., M.B., B.CH. MERVYN SUSSER, M.B., B.CH., F.R.C.P.(E.) DOROTHY WARBURTON, PH.D. h’tw York, New York The hypothesis that the use of saccharin may increase the risk of spontaneous abortion was tested in a case-control study. Women who had had spontaneous abortions were compared with women who had been delivered after 28 weeks’ gestation. Women with a history of diabetes were excluded from the analysis. The use of sugar substitutes during pregnancy was similar in cases and controls: 5.5 per cent of cases and 5.8 per cent of controls reported using sugar substitutes. The power of the analysis to detect a twofold increase in the frequency of use of sugar substitutes in cases as compared to controls was approximately 81 per cent. The analysis effectively controlled for all known potentially confounding variables: that is, age at last menstrual period, history of previous spontaneous abortions, smoking during pregnancy, and usual weight were controlled in the analysis. (AM. J. OBSTET. GYNECOL. 130: 708, 1978.) SACCHARIN may soon be prohibited by the United States Food and Drug Administration because, in ex- periments recently reported from Canada, heavy doses administered to rats were found to be associated with bladder cancer. There are two aspects of these experi- ments which bear on the present study: (1) in the Canadian experiments, saccharin was not only car- cinogenic but also mutagenic: (2) the bladder cancers were found predominantly in the offspring exposed in utero. In view of these findings, it seems prudent in human beings to search for signs of mutagens, and also for signs of teratogens resulting from in utero expo- sure. From the Epidemiology oj Bruzr~ Disorders Department, New York State Ps?lchiatric Institute; the Diuision of Epidemiology, the Department of Human Genetic.r and Development and Clinical Pediatrics, and the Gertrude H. Srrgievsky Center, College of Phykans and Surgeon\. Columbia lI?2iwysity. Supported by grants from the New York State Department of Mental Hveiene and from the National Institutes of health h’o. ikOl-HD-68838 and No. 1 T32-HD-0?010. Rvcezved for publication August 1, 1977. Accepted October 1, 1977. Reprint requests: Zena Stein, Columbia University Faculty of Medicine, 600 W’. 168th St., New York, New York 10032. 708 Spontaneous abortions provide a means of detecting both mutagens and teratogens. An association between saccharin and spontaneous abortion would suggest that saccharin had acted either before conception as a mutagen or after conception as a teratogen. In either case, the effects are likely to be seen in morphologic and chromosomal anomalies, and these are highly con- centrated in spontaneous abortions as compared with live births. About 40 per cent of abortuses at 8 to 28 weeks’ gestation are chromosomally and/or morpho- logically abnormal: this concentration is IOO-fold the incidence of such defects at term. At least 95 per cent of all chromosomally abnormal conceptions are lost through spontaneous abortion and cannot be observed at birth. Given the attrition of anomalies between con- ception and birth, a factor which causes an increase in anomalies is more readily detectable in spontaneous abortions than at birth. A factor which causes such an increase is likely also to lead to an increased rate of spontaneous abortion. Thus an association of a suspect factor with spontaneous abortions, as compared with births, serves as a first approach to identifying potential mutagens and teratogens. In this paper. we seek an association of saccharin with spontaneous abortions. In a case-control study, we compare the frequency of the use of sugar substitutes during pregnancy in women who have had spontane- 0002-Y378/78/06130-0708$00.40/O 0 1978 The C. V. Mceb) Co.