title: Sequential plasma angiogenic factors levels in women with suspected preeclampsia.
abstract: BACKGROUND
  Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester.
  
  
  OBJECTIVE
  Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia.
  
  
  METHODS
  We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate.
  
  
  RESULTS
  During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 and 14 (0-39) below a ratio of 85 (P < .001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004).
  
  
  CONCLUSIONS
  Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.
authors.affiliation: Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Kedak
authors.initials: K
authors.lastname: Baltajian
authors.affiliation: Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Surichhya
authors.initials: S
authors.lastname: Bajracharya
authors.affiliation: Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Saira
authors.initials: S
authors.lastname: Salahuddin
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Berg
authors.affiliation: Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Carl
authors.initials: C
authors.lastname: Geahchan
authors.affiliation: Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Wenger
authors.affiliation: Division of Nephrology/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; Division of Nephrology/Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Division of Maternal Fetal Medicine/Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; Maternal Fetal Medicine/Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois. Electronic address: srana@bsd.uchicago.edu.
authors.forename: Sarosh
authors.initials: S
authors.lastname: Rana
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third / Q000097:blood*
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers
keywords: adverse outcomes; angiogenic factors; preeclampsia; sequential changes