Second-trimester maternal serum paraxanthine, CYP1A2 activity, and the risk of severe preeclampsia

OBJECTIVE: To measure the association between second-trimester maternal caffeine intake and caffeine metabolism through the CYP1A2 system and the risk of subsequent severe preeclampsia. METHODS: This was a nested case-control study of women who had undergone second-trimester screening for fetal aneuploidy and had banked serum available for analysis. The outcome of interest was severe preeclampsia, and exposures were serum paraxanthine (1,7- dimethylxanthine), measured through high-performance liquid chromatography, and CYP1A2 activity, assessed by paraxanthine/caffeine ratios. RESULTS: We identified 51 cases of severe preeclampsia from our population of 3,992 women (1.3%), of whom 33 had sufficient serum for analysis. These were compared with 99 healthy women. Median paraxanthine concentrations were not significantly higher in women in the control group than women in the case group (96.4 ng/mL compared with 38.0 ng/mL, P=.12), and higher serum paraxanthine was not associated with lower odds of severe preeclampsia (odds ratio [OR] 0.72, confidence interval [CI] 0.48-1.08). However, we found a significantly higher paraxanthine/caffeine ratio in women in the control group than women in the case group (0.37 compared with 0.23, P=.02) and a decreased risk of preeclampsia per every log standard deviation increase in paraxanthine/caffeine ratio (OR 0.53, 95% CI 0.31-0.90). CONCLUSION: Faster caffeine metabolism in the second trimester, assessed by paraxanthine/caffeine ratios, is associated with a reduced risk of subsequent severe preeclampsia.