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

Abstract

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. 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). 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. 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.