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Potential biological mechanisms that link maternal depression with poor breastfeeding outcomes have not been investigated. This study examined associations between lifetime history of depression (LHD), prenatal oxytocin receptor gene (\n                      <jats:italic>OXTR<\/jats:italic>\n                      ) DNA methylation, and breastfeeding outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Longitudinal observational data from the Norwegian Mother, Father and Child Cohort Study (MoBa) were analysed (N\u2009=\u20093607). LHD was self-reported during pregnancy (week 15). Blood samples were collected at 16\u201318\u00a0weeks of pregnancy, and DNA methylation was measured using the Illumina Methylation EPIC BeadChip 850\u00a0K array. This array includes 22 CpG sites on the\n                      <jats:italic>OXTR<\/jats:italic>\n                      gene, which were used in analyses. Mothers self-reported breastfeeding initiation (breastmilk given to child in first month), breastfeeding maintenance (breastmilk given to child for 6\u00a0months or more) and breastfeeding problems. Maternal LHD was not associated with\n                      <jats:italic>OXTR<\/jats:italic>\n                      DNA methylation. There was some evidence that prenatal\n                      <jats:italic>OXTR<\/jats:italic>\n                      DNA methylation was associated with breastfeeding outcomes. There was an association between CpG cg26455676 and breastfeeding maintenance to 6\u00a0months (odds ratio\u2009=\u20091.59, 95% confidence intervals\u2009=\u20091.11\u20132.27, raw\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01, adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). Higher levels of DNA methylation at CpG cg26455676 was associated with a greater likelihood of maintaining breastfeeding to 6\u00a0months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This highly novel study highlights the intriguing possibility that maternal prenatal DNA methylation at genes important for breastfeeding may be associated with breastfeeding experiences. Further understanding of vastly differing breastfeeding experiences would assist with the targeting efforts to support breastfeeding women, particularly those who are vulnerable, such as mothers who have depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13148-025-02030-8","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T13:15:09Z","timestamp":1767100509000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations between lifetime history of depression, prenatal OXTR DNA methylation and breastfeeding outcomes"],"prefix":"10.1186","volume":"18","author":[{"given":"Elizabeth C.","family":"Braithwaite","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine","family":"Haftorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurora","family":"Oftedal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziada","family":"Ayorech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Kaasen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Murgatroyd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Lyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian M.","family":"Page","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Bekkhus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"2030_CR1","unstructured":"WHO. 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