Gestational kynurenine metabolites mediate effects of pregnancy adiposity on child negative affect

BACKGROUND: Mounting evidence links increased adiposity during pregnancy and offspring risk for mental health disorders. Yet the mechanisms underlying this association remain poorly understood, limiting our ability to design effective interventions. We hypothesize that alterations in the kynurenine system of the pregnant woman help to explain this association. METHODS: Participants were recruited during pregnancy with repeated assessments through 24 months postpartum. Maternal adiposity was assessed using air displacement plethysmography. Liquid chromatography tandem mass spectrometry was used to measure kynurenine system metabolites in maternal plasma. Child negative affect was assessed via maternal report at 6, 12, and 24 months. RESULTS: Participants (N = 302) included mother-child dyads (70% non-Hispanic White, 51% female). The ratio of picolinic to quinolinic acid (PA:QA) predicted child fear (β = -.15, 95% CI -0.27, -0.03, p = .02) and sadness (β = -.14, 95% CI -0.28, 0.003, p = .045) at 6 months. PA:QA mediated the effect of pregnancy adiposity on child fear (β = .03, bootstrapped 95% CI 0.009, 0.07) and sadness (β = .04, bootstrapped 95% CI 0.006, 0.08). Similar associations were observed when children were 12 and 24 months old, suggesting enduring effects. The ratio of kynurenic to quinolinic acid (KA:QA) was not associated with child negative affect. CONCLUSIONS: This is the first evidence reporting that alterations in the kynurenine system during pregnancy are associated with increased child negative affectivity, an early life risk factor for psychopathology. Results further suggest that these kynurenine metabolites are a mechanistic link between pregnancy adiposity and child negative affect. Though observed effect sizes were small, results suggest that picolinic and quinolinic acid during pregnancy may be novel biomarkers for offspring behavioral risk.