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Caffeine Associated with Spontaneous Abortion Only in Subgroup of Women

Researchers from Sweden have found that, in women with a daily intake of 300 mg or more of caffeine, those with high cytochrome P4501A2 activity had a higher risk for miscarriage than did those with low activity.

Studies that investigated whether caffeine intake during pregnancy causes spontaneous abortion have conflicting results. Investigators attempted to explain these discordant findings by measuring caffeine metabolism during early pregnancy in this case-control study at a university hospital in Sweden. Of 652 women who had spontaneous abortions at 6 to 12 weeks' gestation, 101 women with normal fetal karyotypes in the products of conception were matched with 953 women who were 6 to 12 weeks pregnant. Subjects were asked to recall their weekly caffeine intake from 4 weeks before pregnancy until they were identified for the study. The main metabolic enzymes for caffeine, cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2), were measured in urine and blood, respectively. CYP1A2 breaks caffeine down into its primary metabolites; NAT2 determines whether individuals are slow or fast acetylators of these metabolites.

Low CYP1A2 activity was associated with a significantly lower risk for spontaneous abortion (odds ratio, 0.35; 95% CI, 0.20-0.63). Caffeine intake of 300 mg or more was a risk factor for spontaneous abortion only in women with high CYP1A2 activity (OR, 3.17; 95% CI, 1.22-8.22). NAT2 status was not significantly associated with an increased risk for spontaneous abortion.

Comment: This study illustrates an ideal method for establishing the effect of a toxin on risk for spontaneous abortion, because it excludes the 60% of spontaneous abortions that are caused by genetic abnormalities in the fetus. By focusing only on abortuses with normal karyotypes, the investigators were able to determine that caffeine may be a risk factor in only a subset of pregnant women. In a separate report, the authors found that caffeine intake did not differ among patients with aneuploid fetuses, suggesting that recall bias may not play an important role in this group. Patients may be advised that some women are sensitive to caffeine and that, by limiting their daily caffeine intake to no more than 3 cups of coffee (60-100 mg/cup), they can reduce their risk for spontaneous abortion.

— Sandra Ann Carson, MD

Published in Journal Watch Women's Health January 18, 2002

Citation(s):

Signorello LB et al. Caffeine metabolism and the risk of spontaneous abortion of normal karyotype fetuses. Obstet Gynecol 2001 Dec; 98:1059-66.

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