Maternal prenatal stress and its neuropsychological sequelae in infants and mother–infant dyadic quality: A systematic review and meta-analysis protocol

<ns5:p>Background Prenatal maternal stress represents a significant public health concern within the Developmental Origins of Health and Disease (DOHaD) framework. Unlike transient adaptive stress, chronic prenatal stress triggers sustained hypothalamic–pituitary–adrenal (HPA) axis dysregulation, elevating maternal glucocorticoid levels and enabling cortisol transfer across the placenta. Reduced placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity — potentiated by epigenetic silencing of the NR3C1 glucocorticoid receptor gene — amplifies fetal cortisol exposure and disrupts neurodevelopmental programming. Hair cortisol concentration (cHCC), recognised as the gold standard for retrospective assessment of chronic HPA activation, provides an integrated, non-invasive measure applicable to both mothers and neonates. Methods This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. We will search seven electronic databases (PubMed/MEDLINE, PsycINFO, Web of Science, Scopus, CINAHL, LILACS/BVS, and EBSCO Academic Search Ultimate), supplemented by grey literature and citation tracking. Prospective cohort and case-control studies including pregnant women (≥18 years) with validated assessments of chronic prenatal stress — via psychometric instruments (PSS-10, EPDS, STAI, PRAQ-R) or HPA biomarkers (cHCC, salivary/serum cortisol, CAR) — and reporting neurodevelopmental outcomes in infants at 6, 12, or 24 months will be eligible. Risk of bias will be assessed with the ROBINS-E tool. Quantitative synthesis will employ random-effects models (DerSimonian–Laird estimator; Hedges’s g; Fisher’s r-to-z) in R (meta and metafor packages). Statistical heterogeneity, meta-biases (Egger’s test; trim-and-fill), and certainty of evidence (GRADE framework) will be formally evaluated. Registration This protocol is published in Open Research Europe. The formal pre-registration is deposited in OSF (https://doi.org/10.17605/OSF.IO/2Y3RC).</ns5:p>