{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:32Z","timestamp":1791229652722,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>A low circulating placental growth factor (PlGF) concentration is considered a marker of placental dysfunction, the predominant cause of preeclampsia and fetal growth restriction. Besides iatrogenic delivery, there are no effective treatments, potentially due to its heterogeneity. We hypothesize that more than one subtype of placental dysfunction exists in pregnancies with a low circulating PlGF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Matched placental villous and maternal plasma samples (low PlGF &lt;5th, n=19; normal PlGF \u22655th centile, n=20) were collected from uncomplicated pregnancies and those complicated by one or a combination of preeclampsia, fetal growth restriction, or chronic hypertension. Transcriptomic and metabolomic data sets were obtained from villous samples and used to perform cluster-of-cluster analysis. Clinical outcomes were compared between clusters, as well as subsequent pathway analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>Multi-\u2019omic cluster-of-cluster analysis resulted in three molecular clusters. Cluster one predominantly consisted of those with a low PlGF (9\/10); PlGF results in cluster two varied (low, n=8\/20; normal, n=12\/20), while cluster three mainly comprised of those with a normal PlGF result (n=7\/9). Birthweight was significantly lower in cluster one, as well as an increased incidence of early-onset preeclampsia. However, pathways commonly associated with placental dysfunction were only identified in cluster two.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Multi-\u2019omic analysis revealed two potential subtypes of placental dysfunction associated with a low circulating PlGF. These results support previous studies suggesting the existence of preeclampsia subtypes. Clinical outcome comparisons indicate cluster one as the severe subtype; however, pathway analysis contradicted this. Improved understanding of subtype etiology could enable a more personalized therapeutic approach for pregnancies complicated by placental dysfunction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.24440","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T05:01:23Z","timestamp":1747803683000},"page":"1249-1260","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Assessing Placental Dysfunction Subtypes in Pregnancies With a Low PlGF Centile"],"prefix":"10.1161","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-4527","authenticated-orcid":true,"given":"Kirsty M.M.","family":"Vincent","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-9730","authenticated-orcid":true,"given":"Terence","family":"Garner","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1950-7325","authenticated-orcid":true,"given":"Adam","family":"Stevens","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-4707","authenticated-orcid":true,"given":"Elizabeth C.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0913-2096","authenticated-orcid":true,"given":"Jenny E.","family":"Myers","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.)."},{"name":"Manchester University Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, United Kingdom (J.E.M., L.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-497X","authenticated-orcid":true,"given":"Lucy E.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.)."},{"name":"Manchester University Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, United Kingdom (J.E.M., L.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.02.010"},{"key":"e_1_3_3_3_2","first-page":"332","article-title":"Intrauterine Growth Retardation (IUGR): epidemiology and etiology.","volume":"6","author":"Romo A","year":"2009","unstructured":"Romo A, Carceller R, Tobajas J. Intrauterine Growth Retardation (IUGR): epidemiology and etiology. Pediatr Endocrinol Rev. 2009;6:332\u2013336.","journal-title":"Pediatr Endocrinol Rev"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2018.05.004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.15884"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003215"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2020.10.005"},{"key":"e_1_3_3_8_2","unstructured":"NICE. PLGF-based testing to help diagnose suspected preterm pre-eclampsia (DG49). NICE; 2022. https:\/\/www.nice.org.uk\/guidance\/dg49"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2016.03.010"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16683"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.21061"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.05445"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)80010-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08408"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09741"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509819"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2010.02879.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1831"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.07.019"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(06)68433-x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908056"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-4642(17)30173-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116508"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07293"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62236"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep03202"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2013.01.004"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12942-015-0017-5"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac008"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1613\/jair.953"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i11"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01661"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2022.03.009"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2016.06.032"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2019.11.006"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.02.011"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-97799-y"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.592689"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.17772\/gp\/59240"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2019.06.384"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jogoh.2021.102179"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031884"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/HYPERTENSIONAHA.124.24440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:54:00Z","timestamp":1760709240000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/HYPERTENSIONAHA.124.24440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1161\/HYPERTENSIONAHA.124.24440"],"URL":"https:\/\/doi.org\/10.1161\/hypertensionaha.124.24440","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2024-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}