Caffeine intake and the risk of first-trimester spontaneous abortion.

Background: Some epidemiologic studies have suggested that the ingestion of caffeine increases the risk of spontaneous abortion, but the results have been inconsistent. Methods: We performed a population-based, case-control study of early spontaneous abortion in Uppsala County, Sweden. The subjects were 562 women who had spontaneous abortion at 6 to 12 completed weeks of gestation (the case patients) and 953 women who did not have spontaneous abortion and were matched to the case patients according to the week of gestation (controls). Information on the ingestion of caffeine was obtained from in-person interviews. Plasma cotinine was measured as an indicator of cigarette smoking, and fetal karyotypes were determined from tissue samples. Multivariate analysis was used to estimate the relative risks associated with caffeine ingestion after adjustment for smoking and symptoms of pregnancy such as nausea, vomiting, and tiredness. Results: Among nonsmokers, more spontaneous abortions occurred in women who ingested at least 100 mg of caffeine per day than in women who ingested less than 100 mg per day, with the increase in risk related to the amount ingested (100 to 299 mg per day: odds ratio, 1.3; 95 percent confidence interval, 0.9 to 1.8; 300 to 499 mg per day: odds ratio, 1.4; 95 percent confidence interval, 0.9 to 2.0; and 500 mg or more per day: odds ratio, 2.2; 95 percent confidence interval, 1.3 to 3.8). Among smokers, caffeine ingestion was not associated with an excess risk of spontaneous abortion. When the analyses were stratified according to the results of karyotyping, the ingestion of moderate or high levels of caffeine was found to be associated with an excess risk of spontaneous abortion when the fetus had a normal or unknown karyotype but not when the fetal karyotype was abnormal. Conclusions: The ingestion of caffeine may increase the risk of an early spontaneous abortion among nonsmoking women carrying fetuses with normal karyotypes. (N Engl J Med 2000;343:1839-45.) (C) 2000, Massachusetts Medical Society.