Circulating angiogenic factors and risk of adverse maternal and perinatal outcomes in twin pregnancies with suspected preeclampsia

Abstract

To evaluate whether angiogenic factor levels correlate with preeclampsia-related adverse maternal and perinatal outcomes in women with twin pregnancy, we studied 79 women with suspected preeclampsia in the 3rd trimester. Antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and proangiogenic placental growth factor (PlGF) were measured at presentation on an automated platform. An adverse outcome was defined as hemolysis, elevated liver enzymes, and low platelets syndrome; disseminated intravascular coagulation; abruption; pulmonary edema; cerebral hemorrhage; maternal, fetal, and neonatal death; eclampsia; acute renal failure; small for gestational age; and indicated delivery. All outcomes were ascertained 2 weeks after initial evaluation. Comparing the 52 women (65.8%) who experienced an adverse outcome with the 27 women (34.2%) without an adverse outcome, the median sFlt-1 was elevated (11461.5 pg/mL [8794.0-14847.5] versus 7495.0 pg/mL [3498.0-10482.0; P=0.0004]), PlGF was reduced (162.5 pg/mL [98.0-226.5] versus 224.0 pg/mL [156.0-449.0]; P=0.005), and sFlt-1/PlGF ratio was elevated (74.2 [43.5-110.5] versus 36.2 [7.1-71.3]; P=0.0005). Among those presenting <34 weeks (n=40), the difference in sFlt-1/PlGF ratio was more striking (97.7 [76.6-178.1] versus 31.7 [6.5-48.7]; P=0.001). Addition of sFlt-1/PlGF to the highest systolic blood pressure and proteinuria improved prediction of adverse outcomes. We conclude that in women with twin pregnancy and suspected preeclampsia, the sFlt-1/PlGF ratio at the time of initial evaluation is associated with subsequent adverse maternal and perinatal outcomes. These findings are similar to those in singleton pregnancies and may implicate common pathogenic pathways.

Figure 1. Angiogenic factors at Presentation

Shows median angiogenic factor levels at presentation stratified by adverse outcome. Adverse outcomes were ascertained 2 weeks after presentation. None- No adverse outcome (N= 27), Indicated del: Indicated delivery represents iatrogenic delivery indicated for hypertensive complications of pregnancy (N=47), SGA: small for gestational age (N=13), HELLP: hemolysis, elevated liver enzymes and low platelets (N=6) The extremes of the box represent the interquartile range; the bottom of the box represents the 25^th percentile and top of the box represents the 75^th percentile. The horizontal line across the box represents the median. The ends of the whiskers correspond to the lowest and highest values within 1.5 interquartile range below and above the interquartile range. Panel A shows sFlt1 levels. The median [IQR] sFlt1 for each group were as follows: None =7495.0 [3498.0– 10482.0], Indicated del= 12286.0 [8975.0–14981.0], SGA =14714.0 [8096.0–18205.0], HELLP =13633.5 [5623.0–15117.0]. Panel B shows PlGF levels. The median [IQR] PlGF for each group were as follows: None =224.0 [156.0–449.0], Indicated del =174.0 [99.0–229.0], SGA =104.0 [96.0–187.0], HELLP= 141.0 [98.0–185.0]. Panel C shows sFlt1/PlGF levels. The median [IQR] sFlt1/PlGF for each group were as follows: None =36.2 [7.1–71.3], Indicated del= 71.8 [43.3–112.3], SGA= 105.1 [67.5–233.6], HELLP= (84.4 [55.6–104.1].