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To better understand placental physiology and its disruption in disease, we employ a multiomics approach (transcriptomics, metabolomics, and proteomics) combined with clinical data and histopathology from 321 placentas across conditions: severe fetal growth restriction (FGR), FGR with hypertension (FGR\u2009+\u2009HDP), severe\u00a0preeclampsia (PE), and spontaneous\u00a0preterm delivery (PTD). Cellular deconvolution reveals FGR\u2009+\u2009HDP placentas have more extravillous trophoblasts than controls (p\u2009&lt;\u20090.0001). After adjusting for fetal sex and gestational age, we build condition-specific interomics networks and detect communities (a.k.a. subnetworks). In a control community,\n                    <jats:italic>miR-365a-3p<\/jats:italic>\n                    is the most connected node, whereas in FGR\u2009+\u2009HDP placentas, it is hypoxia-induced\n                    <jats:italic>miR-210-3p<\/jats:italic>\n                    . From this community, we identify a signature containing mRNAs implicated in placental dysfunction (e.g.\n                    <jats:italic>FLT1<\/jats:italic>\n                    ,\n                    <jats:italic>FSTL3<\/jats:italic>\n                    ,\n                    <jats:italic>HTRA4<\/jats:italic>\n                    ,\n                    <jats:italic>LEP<\/jats:italic>\n                    , and\n                    <jats:italic>PHYHIP<\/jats:italic>\n                    ), which distinguishes FGR\u2009+\u2009HDP placentas from those with other conditions, illustrating the power of interomics in understanding obstetric syndromes.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-08631-6","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T10:28:49Z","timestamp":1755512929000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Placental network differences among obstetric syndromes identified with an integrated multiomics approach"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8119-6724","authenticated-orcid":false,"given":"Samantha N.","family":"Piekos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren","family":"Barak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Baumgartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-3277","authenticated-orcid":false,"given":"W. Tony","family":"Parks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-7606","authenticated-orcid":false,"given":"Jennifer","family":"Hadlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leroy","family":"Hood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4157-0267","authenticated-orcid":false,"given":"Nathan D.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2969-6737","authenticated-orcid":false,"given":"Yoel","family":"Sadovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"8631_CR1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","volume":"204","author":"I Brosens","year":"2011","unstructured":"Brosens, I., Pijnenborg, R., Vercruysse, L. & Romero, R. The \u201cgreat obstetrical syndromes\u201d are associated with disorders of deep placentation. Am. J. Obstet. Gynecol. 204, 193\u2013201 (2011).","journal-title":"Am. J. Obstet. Gynecol."},{"key":"8631_CR2","doi-asserted-by":"crossref","unstructured":"Burton G. J., Fowden A. L. & Thornburg, K. L. Placental origins of chronic disease. Physiol. Rev. 96, 1509\u20131565 (2016).","DOI":"10.1152\/physrev.00029.2015"},{"key":"8631_CR3","doi-asserted-by":"publisher","first-page":"e37","DOI":"10.1016\/S2214-109X(18)30451-0","volume":"7","author":"S Chawanpaiboon","year":"2019","unstructured":"Chawanpaiboon, S. et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob. Health. 7, e37\u2013e46 (2019).","journal-title":"Lancet Glob. Health."},{"key":"8631_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-021-03809-2","volume":"21","author":"W Wang","year":"2021","unstructured":"Wang, W. et al. 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The company is not associated with this study or any of the findings. NDP is the Chief Science Officer of Thorne HealthTech and has equity. Y.S. is a consultant at Bio-Rad Laboratories, Inc. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"We confirm that all collaborators in this study meet the Nature Portfolio journals\u2019 criteria for authorship. Their invaluable contributions to the study\u2019s design, implementation, and intellectual output are reflected in their inclusion as authors. Roles and responsibilities were clearly defined and agreed upon by all collaborators prior to the commencement of the research. The research conducted is of significant local relevance, a determination made in close collaboration with our local partners. This study was not severely restricted or prohibited in the primary researchers\u2019 setting, and it does not pose any risk of stigmatization, incrimination, discrimination, or personal risk to participants. Local and regional research have been considered and cited appropriately within this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"1239"}}