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 spont aneous 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 matc hed to the case patients according to the week of gestation (controls). Inf ormation on the ingestion of caffeine was obtained from in-person interview s. Plasma cotinine was measured as an indicator of cigarette smoking, and f etal 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, vomi ting, 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 le ss than 100 mg per day, with the increase in risk related to the amount ing ested (100 to 299 mg per day: odds ratio, 1.3; 95 percent confidence interv al, 0.9 to 1.8; 300 to 499 mg per day: odds ratio, 1.4; 95 percent confiden ce interval, 0.9 to 2.0; and 500 mg or more per day: odds ratio, 2.2; 95 pe rcent confidence interval, 1.3 to 3.8). Among smokers, caffeine ingestion w as not associated with an excess risk of spontaneous abortion. When the ana lyses were stratified according to the results of karyotyping, the ingestio n 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 sp ontaneous abortion among nonsmoking women carrying fetuses with normal kary otypes. (N Engl J Med 2000;343:1839-45.) (C) 2000, Massachusetts Medical So ciety.