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However, evidence for placental DNA methylation as a mediator is limited, with prior studies focusing narrowly on HPA\u2010axis genes. This study aimed to examine the impact of prenatal maternal stress on offspring allergic diseases and placental DNA methylation's mediating role from an epigenome\u2010wide perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Within the Shanghai Parent\u2013Child Cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093883 pairs), maternal stress and childhood allergic diseases were assessed via questionnaires and medical records. Latent class analysis identified allergic trajectories. Specific CpG sites were identified using genome\u2010wide placental DNA methylation analysis and bisulfite pyrosequencing validation. Associations were examined using multivariate log\u2010binomial regression, linear regression, and logistic regression; mediation effects were assessed using causal mediation analysis with nonparametric bootstrapping.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Maternal total stress in early pregnancy was associated with increased risks of atopic dermatitis (RR: 1.23, 95% CI: 1.04\u20131.45), asthma (RR: 1.42, 95% CI: 1.07\u20131.88) and persistent allergy (RR: 1.36, 95% CI: 1.13\u20132.84), while late\u2010pregnancy total stress associated with atopic dermatitis (RR: 1.39, 95% CI: 1.10\u20131.77), allergic rhinitis (RR: 1.56, 95% CI: 1.16\u20132.11) and persistent allergy (RR: 1.30, 95% CI: 1.03\u20131.45). Genome\u2010wide analysis and pyrosequencing validation identified specific placental CpG site hypermethylation associated with both prenatal maternal stress and childhood allergic outcomes. Stress effects on persistent allergic trajectory were partially mediated through\n                      <jats:italic>HLA\u2010DRA<\/jats:italic>\n                      methylation, with a mediation proportion of 8.89%, and on asthma through\n                      <jats:italic>IPCEF1<\/jats:italic>\n                      methylation (12.8%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Prenatal maternal stress may adversely impact childhood allergy outcomes, partially mediated by alterations in placental DNA methylation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70331","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T05:11:47Z","timestamp":1775452307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental DNA 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