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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

Leaños-Miranda, Alfredo; Campos-Galicia, Inova; Isordia-Salas, Irma; Rivera-Leaños, Roxana; Romero-Arauz, Juan Fernando; Ayala-Méndez, José Antonio; Ulloa-Aguirre, Alfredo

doi: 10.1097/HJH.0b013e328357c0c9

Objective: Preeclampsia is characterized by an imbalance in angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). We herein assessed whether these factors measured by a newly developed automated electrochemiluminescence immunoassay are associated with risk to develop preeclampsia.

Methods: We performed a nested case–control study within a cohort of 230 women with singleton pregnancies. The study included all 37 women who eventually developed preeclampsia and 29 normotensive controls. Serum samples were collected at 4-week intervals (from weeks 20th to 36th). sFlt-1 and PlGF were measured using a commercial automated immunoassay (Elecsys).

Results: Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 levels and sFlt-1/PlGF ratio than women with normal pregnancies. These changes became significant at 20 weeks in women destined to develop early preeclampsia (<34 weeks, P ≤ 0.003), and at 24–28 weeks in women who later developed preeclampsia (P ≤ 0.024). The risk for developing preeclampsia was higher among women with PlGF concentration values in the lowest quartile or with sFlt-1 levels and sFlt-1/PlGF ratio in the highest quartile of the control distribution. The odds ratios were higher and appeared earlier in women destined to develop early preeclampsia than in women who presented preeclampsia later. The sFlt-1/PlGF ratio was more tightly associated with risk of preterm or term preeclampsia than either angiogenic factor alone.

Conclusion: Changes in circulating concentrations of PlGF, sFlt-1, and in the sFlt-1/PlGF ratio precede the onset of preeclampsia. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested at preterm or term.

aResearch Unit in Reproductive Medicine

bClinic of Hypertensive Diseases of Pregnancy, UMAE-Hospital de Ginecología y Obstetricia ‘Luis Castelazo Ayala’

cResearch Unit in Thrombosis, Hemostasia and Atherogenesis, Hospital Gabriel Mancera, Instituto Mexicano del Seguro Social, México D.F., Mexico

Correspondence to Dr Alfredo Leaños-Miranda, Research Unit in Reproductive Medicine, Don Luis # 111, Col. Nativitas, México 03500 D.F., México. Tel/fax: +52 55 56 16 22 78; e-mail:

Abbreviations: PlGF, placental growth factor; sFlt-1, soluble fms-like tyrosine kinase-1

Received 1 December, 2011

Revised 20 May, 2012

Accepted 4 July, 2012

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.