{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:06:39Z","timestamp":1788876399209,"version":"build-2803163510"},"reference-count":142,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Non-communicable diseases remain the dominant cause of adult morbidity and mortality, yet cardiometabolic, vascular and renal risk may originate before birth. This structured narrative review critically evaluates human evidence linking pregnancy-related exposures, placental pathophysiology and later offspring health within a maternal\u2013placental\u2013fetal\u2013life-course framework. Evidence published from 2020 to 2026 was emphasised, while seminal earlier cohorts were retained when they provided uniquely long follow-up or direct placental measurements. The most consistent associations concern maternal obesity, gestational diabetes, excessive gestational weight gain and hypertensive disorders, which are linked with higher offspring blood pressure, greater adiposity and adverse glucose\u2013insulin profiles. Human placental studies implicate vascular malperfusion, altered nutrient transport, inflammatory and oxidative signalling, endocrine function and epigenetic regulation. Few studies, however, have measured the prenatal exposure, a specific placental phenotype and a long-term offspring outcome within the same longitudinal design; most proposed placental pathways are supported by convergent evidence or biological plausibility rather than demonstrated mediation. Preterm birth and fetal growth restriction are clinically observable, etiologically heterogeneous sentinel phenotypes, not obligatory mediators. Placental and offspring epigenetic signatures, telomere biology and mitochondrial function represent distinct domains of biological embedding; their causal and prognostic significance remains uncertain. Longitudinal studies integrating maternal exposures, placental histopathology and molecular phenotypes, fetal organ development, childhood cardiometabolic trajectories and adult clinical outcomes are needed to determine whether, and under what circumstances, the placenta plays an intermediary role rather than merely serving as a marker of an adverse pregnancy environment.<\/jats:p>","DOI":"10.3390\/pathophysiology33030067","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:51:48Z","timestamp":1788871908000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5846-388X","authenticated-orcid":false,"given":"Eleftherios","family":"Panteris","sequence":"first","affiliation":[{"name":"Department of Neonatology\/Neonatal Intensive Care Unit, University Hospital of Heraklion, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5375-4197","authenticated-orcid":false,"given":"Ioanna","family":"Kakatsaki","sequence":"additional","affiliation":[{"name":"Department of Neonatology\/Neonatal Intensive Care Unit, University Hospital of Heraklion, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoi","family":"Koukou","sequence":"additional","affiliation":[{"name":"School of Health Sciences, International Hellenic University (IHU), Sindos, 57400 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5398-1103","authenticated-orcid":false,"given":"Charalambos","family":"Kolvatzis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Styliani","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"Department of Neonatology\/Neonatal Intensive Care Unit, University Hospital of Heraklion, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-3309","authenticated-orcid":false,"given":"Eleftheria","family":"Hatzidaki","sequence":"additional","affiliation":[{"name":"Department of Neonatology\/Neonatal Intensive Care Unit, University Hospital of Heraklion, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/S0140-6736(25)01637-X","article-title":"Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990\u20132023: A systematic analysis for the Global Burden of Disease Study 2023","volume":"406","author":"Simon","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Freihat, O., Sipos, D., Aamir, M., and Kovacs, A. 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