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Preeclampsia and related hypertensive disorders of pregnancy are estimated to cause &gt;75\u2009000 maternal and 500\u2009000 infant deaths globally each year. Because of rising rates of risk factors such as obesity, in\u00a0vitro fertilization and advanced maternal age, the incidence of preeclampsia is going up with rates ranging from 5% to 10% of all pregnancies worldwide. A major discovery in the field was the realization that the clinical phenotypes related to preeclampsia, such as hypertension, proteinuria, and other adverse maternal\/fetal events, are due to excess circulating soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101, also referred to as sVEGFR\u20101). sFlt\u20101 is an endogenous anti\u2010angiogenic protein that is made by the placenta and acts by neutralizing the pro\u2010angiogenic proteins vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). During the last decade, this work has spawned a new era of molecular diagnostics for early detection of this condition. Antagonizing sFlt\u20101 either by reducing production or blocking its actions has shown salutary effects in animal models. Further, in early\u2010stage human studies, the therapeutic removal of sFlt\u20101 from maternal circulation has shown promise in delaying disease progression and improving outcomes. Recently, the FDA approved the first molecular test for preterm preeclampsia (sFlt\u20101\/PlGF ratio) for clinical use in the United States. Measuring serum sFlt\u20101\/PlGF ratio in the acute hospital setting may aid short\u2010term management, particularly regarding step\u2010up or step\u2010down of care, decision to transfer to settings better equipped to manage both the mother and the preterm neonate, appropriate timing of administration of steroids and magnesium sulfate, and in expectant management decisions. The test itself has the potential to save lives. Furthermore, the availability of a molecular test that correlates with adverse outcomes has set the stage for interventional clinical trials testing treatments for this disorder. In this review, we will discuss the role of circulating sFlt\u20101 and related factors in the pathogenesis of preeclampsia and specifically how this discovery is leading to concrete advances in the care of women with preeclampsia.<\/jats:p>","DOI":"10.1096\/fj.202301808r","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T10:35:44Z","timestamp":1706783744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Translation of mechanistic advances in preeclampsia to the clinic: Long and winding road"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8315-9938","authenticated-orcid":false,"given":"Ravi","family":"Thadhani","sequence":"first","affiliation":[{"name":"Woodruff Health Sciences Center Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Departments of Medicine and Biomedical Sciences Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-3537","authenticated-orcid":false,"given":"Ana Sofia","family":"Cerdeira","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women's Health and Reproductive Research University of Oxford  Oxford UK"},{"name":"Fetal Maternal Medicine Unit Queen Charlotte's and Chelsea Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-6831","authenticated-orcid":false,"given":"S. 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