Differential Effects of Prenatal Depression and Anxiety on Infant Sleep: Dual-Pathway Mechanisms Involving the HPA

Can Liu1,2, Yuan Lin3, Ye Li1,2

  • 1School of Public Health, Ningxia Medical University, Yinchuan 750004, Ningxia, China.

Sleep
|June 27, 2026
PubMed

Insights

Prenatal depression increases infant sleep problems, partly mediated by cortisol. Prenatal anxiety impacts infant gut microbes and tryptophan, affecting sleep via a gut-brain axis pathway.

Area of Science:

  • Perinatal mental health
  • Infant sleep science
  • Gut microbiome research
  • Tryptophan metabolism

Background:

  • Prenatal psychological distress is linked to adverse infant outcomes, including sleep disturbances and altered gut microbiota.
  • The specific mediating roles of the neonatal gut microbiome and tryptophan metabolism in these associations are not well understood.

Purpose of the Study:

  • To investigate the mediating roles of neonatal gut microbiome and tryptophan metabolism in the relationship between prenatal psychological distress (anxiety and depression) and infant sleep disturbances.
  • To identify distinct pathways linking maternal prenatal mental health to infant sleep outcomes.

Main Methods:

  • Prospective birth cohort study of 2288 mother-infant pairs.
  • Assessment of prenatal anxiety/depression and infant sleep via questionnaires up to 12 months.
  • Multi-omics analyses (16S rRNA sequencing for meconium microbiota, LC-MS/MS for cord blood tryptophan metabolites) in a 112-pair sub-cohort.
  • Statistical analyses including LASSO regression, mediation analyses, and XGBoost modeling.

Main Results:

  • Prenatal depression was a significant risk factor for infant sleep disturbance (OR=1.53), with a stronger effect in female infants.
  • Cord blood cortisol partially mediated the link between prenatal depression and infant sleep disturbance.
  • Prenatal anxiety was associated with reduced gut microbial diversity and Bifidobacterium, and decreased 3-HAA/serotonin levels, which were linked to sleep disturbance.
  • Serial mediation analysis confirmed a pathway involving gut microbiota and tryptophan metabolism influencing sleep.
  • XGBoost model predicted sleep disturbance with an AUC of 0.727, highlighting microbial diversity, Streptococcus, dopamine, and 3-HAA as key predictors.

Conclusions:

  • Distinct mediating pathways link prenatal depression (via cortisol) and anxiety (via gut microbiome and tryptophan metabolism) to infant sleep disturbances.
  • These findings offer potential targets for developing personalized interventions to improve infant sleep health.
Abstract

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