title: First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia.
abstract: An imbalance of pro- and antiangiogenic factors may lead to preeclampsia (PE). In this prospective nested case-control study, we investigated whether first trimester serum levels of placental growth factor (PlGF), a potent angiogenic factor, and its soluble inhibitor, soluble fms-like tyrosine kinase 1 (sFlt1), distinguished women who developed PE (n = 40) from those who developed gestational hypertension (n = 40), delivered a small for gestational age (SGA) newborn (n = 40), or completed a full term normal pregnancy (n = 80). Compared with controls, serum PlGF levels were lower among women who developed PE (23 +/- 24 pg/ml vs. 63 +/- 145 pg/ml; P < 0.01) or gestational hypertension (27 +/- 19 pg/ml; P = 0.03), or who delivered a SGA newborn (21 +/- 16 pg/ml; P < 0.01). In contrast, serum sFlt1 levels did not markedly differ between the groups: PE, 1048 +/- 657 pg/ml; gestational hypertension, 942 +/- 437 pg/ml; SGA newborns, 1011 +/- 479 pg/ml; and normal controls, 973 +/- 490 pg/ml. Multivariable analysis adjusting for potential confounders and serum sFlt1 levels demonstrated a 3.7-fold (95% confidence interval, 1.2-12.5) increase in risk for PE for every log unit decrease in serum levels of PlGF compared with controls. Analyses for gestational hypertension and SGA were not significant. Examined in tertiles, the risk for PE was increased 28.7-fold (95% confidence interval, 2.3-351.0) in the third (<12 pg/ml) compared with the first (>39 pg/ml) PlGF tertile. First trimester serum levels of PlGF and sFlt1 may identify women at high risk for PE.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. thadhani.r@mgh.harvard.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.forename: Walter P
authors.initials: WP
authors.lastname: Mutter
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levine
authors.forename: Robert N
authors.initials: RN
authors.lastname: Taylor
authors.forename: Vikas P
authors.initials: VP
authors.lastname: Sukhatme
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ecker
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D015999:Multivariate Analysis; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy / Q000097:blood*; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D018570:Risk Assessment; D012995:Solubility; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1