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

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Main Authors: Hanna C. Gustafsson, Hanna R. Wright, Jorden E. Jacinto Schreeder, Joel T. Nigg, Elinor L. Sullivan
Format: Artículo Open Access
Published: Wiley 2025
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author Hanna C. Gustafsson
Hanna R. Wright
Jorden E. Jacinto Schreeder
Joel T. Nigg
Elinor L. Sullivan
author_facet Hanna C. Gustafsson
Hanna R. Wright
Jorden E. Jacinto Schreeder
Joel T. Nigg
Elinor L. Sullivan
Hanna C. Gustafsson
Hanna R. Wright
Jorden E. Jacinto Schreeder
Joel T. Nigg
Elinor L. Sullivan
collection Wiley Open Access
contents Gestational kynurenine metabolites mediate effects of pregnancy adiposity on child negative affect Hanna C. Gustafsson Hanna R. Wright Jorden E. Jacinto Schreeder Joel T. Nigg Elinor L. Sullivan Journal of Child Psychology and Psychiatry 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. 10.1111/jcpp.70071 http://creativecommons.org/licenses/by-nc-nd/4.0/
doi_str_mv 10.1111/jcpp.70071
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institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
publishDate 2025
publisher Wiley
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spellingShingle Gestational kynurenine metabolites mediate effects of pregnancy adiposity on child negative affect
Hanna C. Gustafsson
Hanna R. Wright
Jorden E. Jacinto Schreeder
Joel T. Nigg
Elinor L. Sullivan
Journal of Child Psychology and Psychiatry
Gestational kynurenine metabolites mediate effects of pregnancy adiposity on child negative affect Hanna C. Gustafsson Hanna R. Wright Jorden E. Jacinto Schreeder Joel T. Nigg Elinor L. Sullivan Journal of Child Psychology and Psychiatry 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. 10.1111/jcpp.70071 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Gestational kynurenine metabolites mediate effects of pregnancy adiposity on child negative affect
topic Journal of Child Psychology and Psychiatry
url https://acamh.onlinelibrary.wiley.com/doi/10.1111/jcpp.70071