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).

Methods
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 the TTTS at the early (13-20 weeks of gestation) 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.

Conclusions
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.

 

Authors:

Yoav Yinon, Elad Ben Meir, Boaz Weisz,

Eyal Schiff, Shali Mazaki-Tovi, Shlomo Lipitz

Fetal Medicine Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Aviv University