Maternal Tryptophan and Kynurenine Pathway Metabolites and Risk of Preeclampsia

OBJECTIVE: To estimate the association of maternal plasma concentrations of tryptophan and six kynurenine pathway metabolites with the risk of preeclampsia. METHODS: The study was based on a subsample of 2,936 pregnant women who delivered singleton neonates in the Norwegian Mother and Child Cohort Study in 2002-2003. Maternal blood plasma was obtained at approximately gestational week 18 and was measured for tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, and 3-hydroxyanthranilic acid. RESULTS: Of the 2,936 pregnant women included in this study, 116 (4.0%, 95% confidence interval [CI] 3.2-4.7) had preeclampsia subsequently diagnosed. The prevalence of preeclampsia was significantly higher among women with plasma kynurenic acid concentrations greater than the 95th percentile than among those with concentrations in the 25th-75th percentile (11.0% compared with 3.3%, P<.001; adjusted odds ratio 3.6, 95% CI 1.9-6.8). This association was significantly stronger in women with prepregnancy body mass index of 25 or more (P for interaction=.03; 20.4% compared with 4.2%; P<.001). No statistically significant associations of preeclampsia with other tryptophan metabolites were found. CONCLUSION: Elevated maternal plasma kynurenic acid concentrations in early pregnancy are associated with a substantial increased risk of preeclampsia in obese women. (Obstet Gynecol 2012;119:1243-50) DOI: 10.1097/AOG.0b013e318255004e