169: Are twin to twin transfusion syndrome and selective intra-uterine growth restriction a continuum? Evidence from a longitudinal study of circulating angiogenic factors

Abstract

intra-uterine growth restriction a continuum? Evidence from a longitudinal study of circulating angiogenic factors Yoav Yinon, Elad Ben Meir, Boaz Weisz, Eyal Schiff, Shali Mazaki-Tovi, Shlomo Lipitz Sheba Medical Center, Tel-Aviv University, Obstetrics and Gynecology, TelHashomer, Israel OBJECTIVE: To determine maternal plasma levels of soluble fms-like tyrosine kinase-1(sFlt-1), placental growth factor (PLGF) and soluble endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin to twin transfusion syndrome (TTTS) or selective intra-uterine growth restriction (sIUGR). STUDY DESIGN: A longitudinal cohort study of pregnant women with MC/DA twins who were classified into 3 groups: 1. Uncomplicated MC/DA twins (n 22) 2. TTTS (n 23) and 3. sIUGR (n 15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sFlt-1, PLGF and sEng were measured by ELISA. RESULTS: sFlt-1 and sEng levels were significantly higher in TTTS at the early (13-20 weeks) and late (21-28 weeks) second trimester compared to normal monochorionic pregnancies (p 0.01). In contrast, sFlt-1 and sEng levels were significantly higher in the sIUGR group only at the late second trimester (p 0.05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and sIUGR compared to controls (p 0.01). Plasma concentrations of sFlt-1 were significantly higher among TTTS pregnancies compared to sIUGR at the late second trimester (p 0.027). Within TTTS pregnancies who underwent fetoscopic laser ablation, the procedure resulted in elevation of PLGF levels and reduction of sFlt-1 levels. Cord blood analysis revealed significantly higher levels of sFlt-1 in the smaller IUGR twin compared to the normal co-twin. CONCLUSION: Monochorionic pregnancies complicated by TTTS and sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the anti-angiogenic state between TTTS and sIUGR suggests that these two conditions may represent a continuum. Collectively, the findings reported herein shed new light on the pathophysiologic mechanisms of these severe complications of pregnancy.