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    Editorial: Incremental progress in predicting preeclampsia


    However, as an accompanying editorial notes, these findings apply only to a high-risk, mostly white population with singleton gestations and cannot be extended to the general population of mixed racial composition or patients with multifetal gestations.15 In addition, the study was sponsored by the maker of the diagnostic platform. We also have no idea whether use of sFlt-1/PlGF would actually improve maternal and perinatal outcomes or reduce costs (ie, add value to obstetrical care). Nonetheless, this approach represents the first practical application of our improved understanding of the pathogenesis of the disease.

    Take-home message

    Our understanding of the etiology and pathogenesis of preeclampsia is increasing. As we continue to unravel the pathogenesis of this ancient obstetrical nemesis unique to humans, additional markers will no doubt be discovered. For example, we have recently reported that high concentrations of the NK cell chemokine interferon-gamma-inducible protein 10 (IP-10) may paradoxically impede uterine NK cell recruitment and that first-trimester elevations in maternal serum IP-10 may predict subsequent development of preeclampsia.4  This study suggests that agents that facilitate uterine NK cell recruitment could prove a powerful approach to preventing the disease.

    I predict that an intensive study of the pathogenesis of the disorder will permit development of a battery of such markers and allow us not only to identify women at risk early but also to bring to bear novel preventative agents.

    Next: How much does it cost to have a baby in the US?



    1. Redman C. Pre-eclampsia: A complex and variable disease. Pregnancy Hypertens. 2014;4(3):241–242.

    2. Preeclampsia Foundation. New Guidelines in Preeclampsia Diagnosis and Care Include Revised Definition of Preeclampsia. December 4, 2013. http://www.preeclampsia.org/the-news/1-latest-news/299-new-guidelines-in-preeclampsia-diagnosis-and-care-include-revised-definition-of-preeclampsia. Accessed March 14, 2016.

    3. Brosens I, Pijnenborg R, Vercruysse L, Romero R. The "Great Obstetrical Syndromes" are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011;204(3):193–201 Review.

    4. Lockwood CJ, Huang SJ, Chen CP, et al. Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia. Am J Pathol. 2013;183(3):841–856.

    5. Lockwood CJ, Matta P, Krikun G, et al. Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: implications for preeclampsia. Am J Pathol. 2006;168(2):445–452.

    6. Clark DE, Smith SK, He Y, et al. A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol Reprod. 1998;59(6):1540–1548.

    7. Vuorela P, Helske S, Hornig C, Alitalo K, Weich H, Halmesmäki E. Amniotic fluid--soluble vascular endothelial growth factor receptor-1 in preeclampsia. Obstet Gynecol. 2000;95(3):353–357.

    8. Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A, Kalluri R. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem. 2003;278(15):12605–12608.

    9. Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–683.

    10. Karumanchi SA, Bdolah Y. Hypoxia and sFlt-1 in preeclampsia: the "chicken-and-egg" question. Endocrinology. 2004;145(11):4835–4837.

    11. Brinda BJ, Viganego F, Vo T, Dolan D, Fradley MG. Anti-VEGF-induced hypertension: a review of pathophysiology and treatment options. Curr Treat Options Cardiovasc Med. 2016;18(5):33.

    12. Kleinrouweler CE, Wiegerinck MM, Ris-Stalpers C, et al; EBM CONNECT Collaboration. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis. BJOG. 2012;119(7):778–787.

    13. Leaños-Miranda A, Campos-Galicia I, Isordia-Salas I, et al. Changes in circulating concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor measured by automated electrochemiluminescence immunoassays methods are predictors of preeclampsia. J Hypertens. 2012;30(11):2173–2181.

    14. Zeisler H, Llurba E, Chantraine F, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13–22.

    15. Seely EW, Solomon CG. Improving the prediction of preeclampsia. N Engl J Med. 2016;374(1):83–84.

    Charles J. Lockwood, MD, MHCM
    Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South ...


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