Association between antenatal depression and maternal cortisol diurnal rhythm: A meta-analysis

Antenatal depression is prevalent and increases risks of adverse maternal and offspring outcomes. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, reflected in diurnal cortisol rhythm, is a proposed mechanism, but evidence remains inconsistent.

This meta-analysis quantified associations between antenatal depression and cortisol rhythmicity, including the cortisol awakening response (CAR), diurnal slope, and total output (AUCg). Observational studies were identified through systematic searches of five databases up to August 2025. Correlation coefficients were pooled using random-effects models.

Twelve studies were included. Significant negative associations were found between antenatal depression and both CAR (r = -0.33, 95% CI: -0.47 to -0.17, p < 0.001; k = 8, N = 584) and diurnal slope (r = -0.31, 95% CI: -0.52 to -0.07, p = 0.01; k = 7, N = 700), indicating a blunted CAR and a flattened slope. No significant association was found with AUCg (r = 0.04, p = 0.57; k = 7, N = 442). Subgroup analysis indicated that multi-day cortisol sampling attenuated the CAR effect size. Significant heterogeneity was observed for all outcomes.

Potential publication bias and residual heterogeneity suggest caution in interpretation.

Antenatal depression is associated with a specific "dynamic dysregulation" of the HPA axis, featuring impaired cortisol dynamics without altered total output. This phenotype may underlie adverse outcomes and inform biological strategies for identification and intervention.