Caffeine metabolism and the risk of spontaneous abortion of normal karyotype fetuses

Objective: To investigate whether the rate of caffeine metabolism influence s spontaneous abortion risk. Methods: We studied 101 women with normal karyotype spontaneous abortions a nd 953 pregnant women at 6-12 gestational weeks. Participants reported on c affeine intake and provided urine for phenotyping cytochrome P4501A2 (CYP1A 2) activity and blood for genotyping N-acetylation (NAT2) status. We calcul ated odds ratios (OR) and 95% confidence intervals (CI) to evaluate the ass ociation between each of the two metabolic indices and spontaneous abortion risk and also the potential interaction between caffeine intake and metabo lic activity on such risk. In calculating the associations between the meta bolic indices and risk of spontaneous abortion, we had 80% power to detect an OR of 2.1, with a Type I error of 0.05. Results: Slow acetylators had a nonsignificantly increased risk for spontan eous abortion (OR 1.36, 95% CI 0.84, 2.21) and recurrent spontaneous aborti on (OR 2.51, 95% CI 0.81, 7.76). In contrast, low CYP1A2 activity was assoc iated with a significantly decreased risk for spontaneous abortion (OR 0.35 , 95% CI 0.20, 0.63). Caffeine was a risk factor for spontaneous abortion a mong women with high, but not low, CYP1A2 activity (OR 2.42,95% CI 1.01, 5. 80 for 100-299 mg/day; OR 3.17, 95% CI 1.22, 8.22 for 300 mg/day or more, a mong women with high CYP1A2 activity). Conclusion: The findings indicate that high CYP1A2 activity may increase th e risk of spontaneous abortion, independently or by modifying the effect of caffeine. The results regarding NAT2 are less conclusive but suggest that slow acetylators may be at elevated risk of spontaneous abortion. (Obstet G ynecol 2001;98:1059-66. (C) 2001 by the American College of Obstetricians a nd Gynecologists.).