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Although epidemiological and clinical studies have consistently linked compromised placental function to neonatal respiratory, neurological, gastrointestinal, and infectious morbidity, the mechanisms through which placental insufficiency translates into organ\u2010specific neonatal vulnerability remain unclear. Increasing evidence from human observations and experimental animal models indicates that placental insufficiency disrupts coordinated fetal development through alterations in perfusion, vascular patterning, cellular differentiation, barrier maturation, and immune responsiveness, rather than through uniform growth failure. This review summarizes current progress in the understanding of organ\u2010specific mechanisms by which placental insufficiency shapes neonatal vulnerability, with a focus on the lung, brain, intestine, and immune system. We further discuss how these developmental perturbations interact with postnatal environmental exposures and highlight future perspectives for identifying at\u2010risk infants and developing targeted strategies to mitigate adverse neonatal outcomes.<\/jats:p>","DOI":"10.1111\/jog.70202","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T23:14:36Z","timestamp":1771370076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Placental Insufficiency and Neonatal Vulnerability: Organ\u2010Specific Mechanisms Shaping Early\u2010Life Health"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2974-9109","authenticated-orcid":false,"given":"Mari","family":"Ichinose","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Iriyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-9780","authenticated-orcid":false,"given":"Yasushi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.52"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00071.2020"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f6564"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.09.026"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641955.2013.842584"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000522202"},{"issue":"2","key":"e_1_2_11_8_1","first-page":"139","article-title":"Long\u2010Term Neurologic Consequences Following Fetal Growth Restriction: The Impact on Brain Reserve","volume":"47","author":"Shah D. 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