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

STUDY OBJECTIVES: Prenatal psychological distress is associated with adverse offspring outcomes, including infant sleep disturbances and altered gut microbiota, yet the mediating roles of neonatal gut microbiome and tryptophan metabolism remain underexplored. METHODS: This prospective birth cohort study enrolled 2288 mother-infant pairs, using questionnaires to assess prenatal anxiety/depression and infant sleep patterns up to 12 months. A 112-pair sub-cohort underwent multi-omics analyses: meconium microbiota profiling via 16S rRNA sequencing and cord blood tryptophan metabolite quantification via LC-MS/MS. LASSO regression, mediation analyses, and XGBoost modeling were applied. RESULTS: Results showed prenatal depression-only was a significant risk factor for infant sleep disturbance (fully adjusted OR = 1.53, 95% CI:1.04-2.25), with a stronger effect in female infants (OR = 2.11, p = 0.022). Cord blood cortisol partially mediated this link (ACME = -7.47, 95% CI: [-14.82, -0.12], p = 0.048). Prenatal anxiety correlated with reduced meconium microbial alpha-diversity, lower Bifidobacterium abundance, and decreased 3-HAA/serotonin levels, which were associated with sleep disturbance; serial mediation confirmed the gut microbiota-tryptophan metabolism pathway. The XGBoost predictive model achieved an AUC of 0.727, with microbial diversity, Streptococcus abundance, dopamine, and 3-HAA as top contributors. CONCLUSIONS: This study identifies distinct mediating pathways for depression and anxiety, providing targets for personalized infant sleep health interventions.