Soluble fms-like Tyrosine Kinase 1
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Soluble fms-like tyrosine kinase 1 (sFlt1), a splice variant of the vascular endothelial growth factor receptor Flt1 and a potent inhibitor of vascular endothelial growth factor, has been shown to be elevated in pregnant women with preeclampsia.1 A clinical study showed that increased plasma concentrations of sFlt1 are detectable about five weeks before the onset of the disorder.2 We wondered whether abnormal uterine perfusion in the second trimester is associated with increased sFlt1 levels, since disturbed uterine perfusion can identify high-risk pregnancies that are later complicated by preeclampsia or intrauterine growth retardation. However, the finding of abnormal uterine perfusion on Doppler ultrasonography has limited, predictive value, since these complications only sometimes develop in women with this finding.3 Because the increase in sFlt1 antedates preeclampsia, this marker could be a clinically useful adjunct to Doppler ultrasonography, serving to differentiate between women who later have pregnancy complications and those who do not.
We report a pilot cohort study involving 20 women in the 20th week of pregnancy with abnormal uterine perfusion (Figure 1). Gestation proceeded normally in 12 women, whereas preeclampsia developed in 4, and intrauterine growth retardation developed in 4. Ten women with clinically evident preeclampsia and nine with intrauterine growth retardation and without hypertension were also studied. The women with abnormal perfusion and an adverse pregnancy outcome (preeclampsia or intrauterine growth retardation) had significantly higher sFlt1 values than did those with normal outcomes (2313.0 vs. 339.4 pg per milliliter, P<0.01). As expected, patients with evidence of preeclampsia had high sFlt1 values (7247.5 pg per milliliter). Surprisingly, the women with intrauterine growth retardation and normotension were also characterized by a marked increase in the plasma sFlt1 concentration (5072.4 pg per milliliter). The documented excess of sFlt1 seems not to be specific to preeclampsia since it was also observed in women with intrauterine growth retardation. A prospective study will be needed to clarify whether the concurrent measurement of uterine perfusion and sFlt1 levels might be an early screening test for severe complications of pregnancy.
Figure 1. Plasma Concentration of sFlt1.
In Panel A, the sFlt1 concentrations in pregnant women with abnormal uterine perfusion (mean duration of gestation, 20 weeks) and a normal pregnancy outcome are compared with those in women who had an adverse pregnancy outcome (mean, 22 weeks). In Panel B, the sFlt1 concentrations in pregnant women with clinically evident preeclampsia (mean duration of gestation, 31 weeks) are compared with those in women with intrauterine growth retardation (IUGR) (mean, 31 weeks). I bars represent standard deviations.
Holger Stepan, M.D.
Anne Geide
Renaldo Faber, M.D.
University of Leipzig
04103 Leipzig, Germany
steh@medizin.uni-leipzig.de
References
Maynard SE, Min Y, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003;111:649-658.
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672-683.
Chien PF, Arnott N, Gordon A, Owen P, Khan KS. How useful is uterine artery Doppler flow velocimetry in the prediction of pre-eclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG 2000;107:196-208.
We report a pilot cohort study involving 20 women in the 20th week of pregnancy with abnormal uterine perfusion (Figure 1). Gestation proceeded normally in 12 women, whereas preeclampsia developed in 4, and intrauterine growth retardation developed in 4. Ten women with clinically evident preeclampsia and nine with intrauterine growth retardation and without hypertension were also studied. The women with abnormal perfusion and an adverse pregnancy outcome (preeclampsia or intrauterine growth retardation) had significantly higher sFlt1 values than did those with normal outcomes (2313.0 vs. 339.4 pg per milliliter, P<0.01). As expected, patients with evidence of preeclampsia had high sFlt1 values (7247.5 pg per milliliter). Surprisingly, the women with intrauterine growth retardation and normotension were also characterized by a marked increase in the plasma sFlt1 concentration (5072.4 pg per milliliter). The documented excess of sFlt1 seems not to be specific to preeclampsia since it was also observed in women with intrauterine growth retardation. A prospective study will be needed to clarify whether the concurrent measurement of uterine perfusion and sFlt1 levels might be an early screening test for severe complications of pregnancy.
Figure 1. Plasma Concentration of sFlt1.
In Panel A, the sFlt1 concentrations in pregnant women with abnormal uterine perfusion (mean duration of gestation, 20 weeks) and a normal pregnancy outcome are compared with those in women who had an adverse pregnancy outcome (mean, 22 weeks). In Panel B, the sFlt1 concentrations in pregnant women with clinically evident preeclampsia (mean duration of gestation, 31 weeks) are compared with those in women with intrauterine growth retardation (IUGR) (mean, 31 weeks). I bars represent standard deviations.
Holger Stepan, M.D.
Anne Geide
Renaldo Faber, M.D.
University of Leipzig
04103 Leipzig, Germany
steh@medizin.uni-leipzig.de
References
Maynard SE, Min Y, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003;111:649-658.
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672-683.
Chien PF, Arnott N, Gordon A, Owen P, Khan KS. How useful is uterine artery Doppler flow velocimetry in the prediction of pre-eclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG 2000;107:196-208.