Caffeine Intake and the Risk of First-Trimester Spontaneous Abortion
Sven Cnattingius, M.D., Ph.D., Lisa B. Signorello, Sc.D., Göran Annerén, M.D., Ph.D., Britt Clausson, M.D., Anders Ekbom, M.D., Ph.D., Elisabeth Ljunger, M.D., William J. Blot, Ph.D., Joseph K. McLaughlin, Ph.D., Gunnar Petersson, B.Sc., Anders Rane, M.D., Ph.D., and Fredrik Granath, Ph.D.
Background Some epidemiologic studies have suggested that theingestion of caffeine increases the risk of spontaneous abortion,but the results have been inconsistent.
Methods We performed a population-based, case–controlstudy of early spontaneous abortion in Uppsala County, Sweden.The subjects were 562 women who had spontaneous abortion at6 to 12 completed weeks of gestation (the case patients) and953 women who did not have spontaneous abortion and were matchedto the case patients according to the week of gestation (controls).Information on the ingestion of caffeine was obtained from in-personinterviews. Plasma cotinine was measured as an indicator ofcigarette smoking, and fetal karyotypes were determined fromtissue samples. Multivariate analysis was used to estimate therelative risks associated with caffeine ingestion after adjustmentfor smoking and symptoms of pregnancy such as nausea, vomiting,and tiredness.
Results Among nonsmokers, more spontaneous abortions occurredin women who ingested at least 100 mg of caffeine per day thanin women who ingested less than 100 mg per day, with the increasein 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 confidenceinterval, 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 ofspontaneous abortion. When the analyses were stratified accordingto the results of karyotyping, the ingestion of moderate orhigh levels of caffeine was found to be associated with an excessrisk of spontaneous abortion when the fetus had a normal orunknown karyotype but not when the fetal karyotype was abnormal.
Conclusions The ingestion of caffeine may increase the riskof an early spontaneous abortion among nonsmoking women carryingfetuses with normal karyotypes.
Source Information
From the Department of Medical Epidemiology (S.C., B.C., A.E., G.P., F.G.) and the Department of Laboratory Science and Technique (A.R.), Karolinska Institute, Stockholm, Sweden; the International Epidemiology Institute, Rockville, Md. (L.B.S., W.J.B., J.K.M.); and the Department of Genetics and Pathology (G.A.) and the Department of Women's and Children's Health (B.C., E.L.), Uppsala University, Uppsala, Sweden.
Address reprint requests to Dr. Cnattingius at the Department of Medical Epidemiology, P.O. Box 281, Karolinska Institute, SE-171 77 Stockholm, Sweden.
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