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Placental HSD11B2 protects the fetus from excess glucocorticoids and may influence fetal programming during maternal metabolic stress. The present study assessed maternal overweight and GWG effects on stress axis and fetal development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective study of 175 singleton pregnancies at Charit\u00e9 University Berlin, recruited by pre\u2010pregnancy body mass index (BMI: normal, overweight, obese). Maternal weight, hair and serum cortisol, neonatal anthropometrics, and placental HSD11B2 expression and methylation were analyzed during pregnancy, at delivery, and\/or 6\u2009months postpartum. Linear regression and correlation analyses were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Excessive gestational weight gain (GWG) was more common in obese women, who also showed higher postpartum weight retention. First\u2010trimester hair cortisol and cortisone, reflecting chronic stress, were elevated in overweight and obese groups. While serum cortisol levels were similar, obese women showed a greater increase from the second to third trimester. Neonatal means did not differ consistently, yet macrosomia and small for gestational age rates were higher in offspring of obese mothers. Elevated maternal cortisol in late pregnancy and postpartum correlated with altered infant growth. Placental HSD11B2 was not GWG\u2010dependent but varied by sex and BMI. Promoter methylation was linked to infant body composition and growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Maternal overweight may relate to chronic hypothalamic\u2013pituitary\u2013adrenal (HPA) axis activation and altered placental HSD11B2, with sex\u2010specific placental adaptations affecting fetal glucocorticoid exposure and offspring development. These findings support integrated perinatal strategies targeting nutrition and stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ijgo.71165","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:26:31Z","timestamp":1782923191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal overweight and obesity during pregnancy and sex\u2010dependent dysregulation of the materno\u2010fetal stress axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-9920","authenticated-orcid":false,"given":"Thorsten","family":"Braun","sequence":"first","affiliation":[{"name":"Clinic of Obstetrics Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health  Berlin Germany"},{"name":"Division of Experimental Obstetrics 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