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(Hypertension. 2007;50:137.)
© 2007 American Heart Association, Inc.

Original Articles

Sequential Changes in Antiangiogenic Factors in Early Pregnancy and Risk of Developing Preeclampsia

Sarosh Rana; S. Ananth Karumanchi; Richard J. Levine; Shivalingappa Venkatesha; Jose Alejandro Rauh-Hain; Hector Tamez; Ravi Thadhani

From the Maternal Fetal Medicine Division (S.R.), Women and Infants Hospital, Brown University, Providence, RI; the Departments of Medicine, Obstetrics, and Gynecology (S.A.K., S.V.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass; the Division of Epidemiology, Statistics and Prevention Research (R.J.L.), National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Md; and the Department of Medicine (J.A.R.-H., H.T., R.T.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Ravi Thadhani, MD, MPH, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. E-mail rthadhani{at}partners.org

Concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) increase in maternal blood with the approach of clinical preeclampsia. Although alterations in these circulating antiangiogenic factors herald the signs and symptoms of preeclampsia, in vitro studies suggest they may also play a role in regulating early placental cytotrophoblast functions. Early pregnancy changes in sFlt1 and sEng may thus identify women destined to develop preeclampsia. We performed a nested case-control study of 39 women who developed preeclampsia and 147 contemporaneous normotensive controls each with serum collected in the first (11 to 13 weeks of gestation) and second (17 to 20 weeks) trimesters. Whereas levels of sFlt1 and sEng at 11 to 13 weeks were similar between cases and controls (sFlt1: 3.5±0.3 ng/mL versus 3.0±0.1, P=0.14; sEng 6.9±0.3 ng/mL versus 6.6±0.2, P=0.37, respectively), at 17 to 20 weeks both were elevated in the women destined to develop preeclampsia (sFlt1: 4.1±0.5 ng/mL versus 3.1±0.1, P<0.05; sEng, 6.4±0.4 ng/mL versus 5.2±0.1, P<0.01). Women who developed preterm (<37 weeks) preeclampsia demonstrated even greater sequential changes: difference [delta{d}] between second and first trimester levels: dsFlt1, 0.63±0.91 ng/mL in preterm PE versus 0.05±0.15 in controls; dsEng, 0.73±0.77 ng/mL versus –1.32±0.18, P<0.01. Similar findings were noted in a cross-sectional analysis of specimens collected from the Calcium for Preeclampsia Prevention Study. In conclusion, sequential changes in antiangiogenic factors during early pregnancy may be useful for predicting preterm preeclampsia.

Key Words: antiangiogenic factors • sFlt1 • soluble endoglin • preeclampsia • predictive test

Related Article:

Emerging Roles of Antiangiogenic and Angiogenic Proteins in Pathogenesis and Prediction of Preeclampsia

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