Selective Intrauterine Growth Restriction in Monochorionic Twin Pregnancies: Markers of Endothelial Damage and Metabolomic Profile

Abstract

The aim of this study was to assess the aorta-intima thickness (aIT) and serum metabolomic profile in selective intrauterine growth-restricted (sIUGR) monochorionic diamniotic (MCDA) twin fetuses presenting Doppler velocimetry alterations. Fetal abdominal aIT was measured by ultrasound at 32 weeks of gestation, enrolling 24 MCDA twin fetuses (8 sIUGR and 16 controls). sIUGR twin fetuses were classified into two groups: Group 1 consisted of sIUGR with abnormal umbilical artery (UA) Doppler waveforms and Group 2 included sIUGR with normal UA Doppler. Group 3 were control fetuses appropriate for gestational age (AGA). Fetal blood samples were obtained from the umbilical vein immediately after fetal extraction. A non-targeted metabolomic profiling investigated fetal metabolism alterations by using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Median fetal aIT was significantly larger in Group 1 (median value = 0.9 mm; range = 0.8-1.0 mm; p < .002) and Group 2 (median value = 0.8 mm; range = 0.7-0.8 mm; p < .002) than in AGA Group 3 (median value = 0.5 mm; range = 0.4-0.6 mm; p < .002). Metabolomic analyses, performed on four sIUGR cases (Group 1) compared with four AGA co-twins, showed an upregulation of phenylalanine, sphingosine, glycerophosphocholine, and choline, and a downregulation of valine, tryptophan, isoleucine, and proline sIUGR Group 1 compared with AGA. Although for metabolomics data only a statistical tendency (and not a statistical significance) was reached due to the small sample size, we believe that our results represent a valid starting point for further in-depth metabolomic and proteomic investigations of sIUGR in MCDA fetuses.