Prenatal Depression and Anxiety Disrupt Infant Sleep Through Two Distinct Biological Pathways
Prenatal psychological distress is a known risk factor for infant sleep problems, but the mechanisms have remained unclear. A large prospective study published in Sleep now provides evidence that depression and anxiety disrupt infant sleep through entirely different biological routes: one involving the stress hormone axis, the other involving the gut microbiome and serotonin metabolism.
What they found
Researchers led by Liu and colleagues at Ningxia Medical University in China followed 2,288 mother-infant pairs from pregnancy through the first year of life. They measured maternal anxiety and depression during pregnancy, then tracked infant sleep patterns up to 12 months of age. A sub-cohort of 112 pairs underwent detailed multi-omics analysis, including meconium microbiota sequencing (16S rRNA) and cord blood metabolomics for tryptophan pathway metabolites.
The results revealed two distinct pathways:
Prenatal depression alone increased the risk of infant sleep disturbance by 53% (fully adjusted odds ratio 1.53, 95% CI 1.04 to 2.25). The effect was stronger in female infants, where the risk more than doubled (OR 2.11, p = 0.022). Cord blood cortisol levels partially mediated this link, pointing to the hypothalamic-pituitary-adrenal (HPA) axis as the key mechanism.
Prenatal anxiety, by contrast, operated through the gut-brain axis. Anxious mothers had infants with reduced meconium microbial diversity, lower levels of Bifidobacterium, and decreased concentrations of 3-hydroxyanthranilic acid (3-HAA) and serotonin in cord blood. Serial mediation analysis confirmed the chain: anxiety altered the neonatal gut microbiome, which disrupted tryptophan metabolism, which in turn affected sleep.
A machine learning model (XGBoost) incorporating microbial diversity, Streptococcus abundance, dopamine, and 3-HAA achieved an AUC of 0.727 for classifying infant sleep disturbance.
Why it matters
The finding that depression and anxiety act through distinct biological pathways has direct implications for intervention. Infants exposed to prenatal depression may benefit from interventions targeting cortisol regulation or HPA axis function. Those exposed to prenatal anxiety may respond better to approaches that modulate the gut microbiome or tryptophan metabolism such as probiotic supplementation.
This is among the first studies to demonstrate separable mediating roles for the neonatal gut microbiome and HPA axis in linking different types of prenatal psychological distress to infant sleep outcomes. The dual-pathway framework opens the door to more personalized, mechanism-based interventions.
Limits
The study is observational, and residual confounding cannot be excluded. The multi-omics sub-cohort was relatively small (112 pairs), and the machine learning model, while promising, requires external validation. All measures were taken at a single Chinese site, and generalizability to other populations remains to be tested.
Bottom line
Prenatal depression and anxiety disrupt infant sleep through different biological channels: the HPA axis for depression, the gut-brain axis for anxiety. These distinct pathways suggest that personalized interventions tailored to the type of maternal distress may be more effective than one-size-fits-all approaches.
Source
Liu C, Lin Y, Li Y, et al. Differential Effects of Prenatal Depression and Anxiety on Infant Sleep: Dual-Pathway Mechanisms Involving the HPA Axis and the Gut-Brain Axis. Sleep. 2026 Jun 27:zsag171. doi: 10.1093/sleep/zsag171. PMID: 42364158.