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We conducted a systematic review with meta‐analytic elements using publicly available Gene Expression Omnibus (GEO) datasets to determine the role of epigenetic mechanisms in prenatal alcohol exposure (PAE)‐induced hypothalamic–pituitary–adrenal (HPA) axis dysfunctions in offspring. Several studies have demonstrated that PAE has long‐term consequences on HPA axis functions in offspring. Some studies determined that alcohol‐induced epigenetic alterations during fetal development persist in adulthood. However, additional research is needed to understand the major epigenetic events leading to alcohol‐induced teratogenesis of the HPA axis. Our network analysis of GEO datasets identified key pathways relevant to alcohol‐mediated histone modifications, DNA methylation, and miRNA involvement associated with PAE‐induced alterations of the HPA axis. Our analysis indicated that PAE perturbated the epigenetic machinery to activate corticotrophin‐releasing hormone, while it suppressed opioid, glucocorticoid receptor, and circadian clock genes. These results help to further our understanding of the epigenetic basis of alcohol's effects on HPA axis development. [ABSTRACT FROM AUTHOR]