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

Abstract

OBJECTIVE: To investigate whether the rate of caffeine metabolism influences spontaneous abortion risk. METHODS: We studied 101 women with normal karyotype spontaneous abortions and 953 pregnant women at 6–12 gestational weeks. Participants reported on caffeine intake and provided urine for phenotyping cytochrome P4501A2 (CYP1A2) activity and blood for genotyping N-acetylation (NAT2) status. We calculated odds ratios (OR) and 95% confidence intervals (CI) to evaluate the association between each of the two metabolic indices and spontaneous abortion risk and also the potential interaction between caffeine intake and metabolic activity on such risk. In calculating the associations between the metabolic 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 spontaneous abortion (OR 1.36, 95% CI 0.84, 2.21) and recurrent spontaneous abortion (OR 2.51, 95% CI 0.81, 7.76). In contrast, low CYP1A2 activity was associated 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 among 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, among women with high CYP1A2 activity). CONCLUSION: The findings indicate that high CYP1A2 activity may increase the 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.