title: PP059. Angiogenic factors and risk of preeclampsia related adverse outcomes in twin pregnancies.
abstract: BACKGROUND
  Preeclampsia (PE) is a pregnancy specific hypertensive disorder with an overall incidence of 5-8% among all pregnancies.Incidence of PE in twins is about 2-4 fold higher compared to singletons.Angiogenic factors are implicated in pathogenesis of PE and related adverse outcomes.No studies exist evaluating angiogenic factor assessment in twin pregnancies complicated by PE or use of these proteins for prediction of PE-related adverse outcomes in twins.
  
  
  OBJECTIVE
  Our objective was to evaluate whether angiogenic factor levels correlate with the diagnosis of PE and predict adverse maternal and perinatal outcomes in women with twin pregnancy.
  
  
  METHODS
  This was a prospective cohort study of women with suspected PE and twin pregnancy from July 2009-August 2011.Antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) were measured at presentation on an automated platform.Diagnosis of hypertension PE during pregnancy was based on ACOG criteria.All diagnoses and outcomes were recorded 2 weeks later.An adverse outcome was defined as hemolysis elevated liver enzymes and low platelets (HELLP) syndrome; disseminated intravascular coagulation (DIC); abruption; pulmonary edema; cerebral hemorrhage; maternal, fetal and neonatal death; eclampsia; acute renal failure; small for gestational age; and indicated delivery.Data are presented as median (interquartile range).We computed the area under the curve (AUC) from the receiver operating characteristic curves to evaluate the ability of clinical values to discriminate between women who would and would not develop an adverse outcome within 2 weeks.
  
  
  RESULTS
  There were 79 women with twin gestation who presented to triage for evaluation of PE. The median gestational age at enrollment was 33.9 (31.9-36.0) weeks.The incidence of PE was 58.2%, of which 60.9% was mild and 39.1% was severe.The median sFlt1/PlGF ratio was 72.2 (42.5-111.9) in women with PE compared to 47.4 (5.5-82.2) in women with no hypertensive disorder (P=0.052).Among the 52 (65.8%) women who experienced an adverse outcome within 2 weeks, the median sFlt1/PlGF ratio at presentation was elevated [74.2 (43.5-110.5)] compared to the 27 (34.2%) women without an adverse outcome [36.2 (7.1-71.3); P=0.0003].Among those presenting at <34 weeks (n=40), the difference in sFlt1/PlGF ratio was more striking [97.7 (76.6-178.1) versus 31.7 (6.5-48.7); P=0.001].When using only the highest systolic blood pressure at presentation and proteinuria the AUC was 0.61.Adding the sFlt1/PlGF ratio significantly improved the AUC to 0.77 (P=0.01).When restricting to women who presented at <34 weeks, a similar, although not statistically significant, improvement was seen when adding the sFlt1/PlGF ratio (AUC=0.85) compared with blood pressure and proteinuria alone(AUC=0.69;P=0.08).
  
  
  CONCLUSIONS
  In women with twin pregnancy and suspected PE, the sFlt1/PlGF ratio at the time of initial evaluation is associated with subsequent diagnosis of PE and, more importantly, PE-related adverse maternal and perinatal outcomes. These findings are similar to singleton pregnancies and may implicate similar pathogenic pathways.
authors.affiliation: Obstetrics and Gynecology, Beth Israel Deaconess Medical Center/Harvard Medical Center, Boston, United States.
authors.forename: S
authors.initials: S
authors.lastname: Rana
authors.affiliation: Obstetrics and Gynecology, Beth Israel Deaconess Medical Center/Harvard Medical Center, Boston, United States.
authors.forename: M
authors.initials: M
authors.lastname: Hacker
authors.affiliation: Obstetrics and Gynecology, Beth Israel Deaconess Medical Center/Harvard Medical Center, Boston, United States.
authors.forename: A
authors.initials: A
authors.lastname: Merport
authors.affiliation: Obstetrics and Gynecology, Beth Israel Deaconess Medical Center/Harvard Medical Center, Boston, United States.
authors.forename: S
authors.initials: S
authors.lastname: Salahuddin
authors.affiliation: Department of Obstetrics, Campus Virchow-Clinic, Charité University Medicine, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Verlohren
authors.affiliation: Department of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Charité University Medicine, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Perschel
authors.affiliation: Obstetrics and Gynecology, Beth Israel Deaconess Medical Center/Harvard Medical Center, Boston, United States; Medicine, Beth Israel Deaconess Medical Center/Harvard Medical Center, Boston, United States.
authors.forename: S A
authors.initials: SA
authors.lastname: Karumanchi