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This has led to the term \u2018the great obstetrical syndromes\u2019 being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10\u201318\u2009weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low\u2010dose aspirin, which affects the COX\u20101 receptor (thrombosis) and the COX\u20102 receptor (inflammation), prevents not just pre\u2010eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low\u2010dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre\u2010eclampsia, and further study of them may offer therapeutic options beyond low\u2010dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation.<\/jats:p>","DOI":"10.1111\/1471-0528.17613","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T12:40:57Z","timestamp":1690980057000},"page":"8-15","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["The great obstetrical syndromes and the placenta"],"prefix":"10.1111","volume":"130","author":[{"given":"Matthew K.","family":"Hoffman","sequence":"first","affiliation":[{"name":"Departments of Obstetrics and Gynecology Christiana Care Health Services  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(18)30451-0"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(21)00311-4"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31593-8"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706475"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.08.009"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0639"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080995"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1A0815-351R"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-210310"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1067\/S0002-9378(03)00838-X"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1977.tb12676.x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1992.tb13848.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0225-CC"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.06.001"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.09.003"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1007"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181016"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114092"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","unstructured":"MendesS Tim\u00f3teo\u2010FerreiraF AlmeidaH SilvaE.New insights into the process of placentation and the role of oxidative uterine microenvironment.2019;2019:1\u201318.","DOI":"10.1155\/2019\/9174521"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01661"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000015080"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9111139"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3MR0615-272RR"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900621"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2004.12.027"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)91367-3"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)91996-2"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136985"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704559"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32973-3"},{"issue":"10","key":"e_1_2_12_32_1","article-title":"Antiplatelet agents for preventing pre\u2010eclampsia and its complications","volume":"2019","author":"Duley L","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-0528.2003.02096.x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12088"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000736"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1998.tb10088.x"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1998.tb10089.x"},{"issue":"1","key":"e_1_2_12_38_1","first-page":"39","article-title":"Randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. 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