title: Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia.
abstract: 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.
authors.affiliation: Maternal Fetal Medicine Division, Women and Infants Hospital, Brown University, Providence, RI, USA.
authors.forename: Sarosh
authors.initials: S
authors.lastname: Rana
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levine
authors.forename: Shivalingappa
authors.initials: S
authors.lastname: Venkatesha
authors.forename: Jose Alejandro
authors.initials: JA
authors.lastname: Rauh-Hain
authors.forename: Hector
authors.initials: H
authors.lastname: Tamez
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
mesh_terms: D000328:Adult; D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000097:blood*; D015703:Antigens, CD / Q000097:blood*; D016022:Case-Control Studies; D000071063:Endoglin; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000209:etiology*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1