Metabolic characterization of amniotic fluids of fetuses with enlarged nuchal translucency

In prenatal diagnosis, a thickened nuchal translucency (NT) is one of the most sensitive and specific markers for several defects but it may also be found in 5% of healthy fetuses. The pathophysiological causes that lead to an increase in NT are not yet fully understood. Metabolomics represents a new promising approach, useful for studying different metabolites in biological organisms in response to environmental stressors. The aim of our study was to investigate the metabolomic profile of the amniotic fluid samples (AFS) of euploid fetuses with enlarged nuchal translucency (ENT) compared to a control group (C group). This study was carried out on a group of women who underwent second-trimester amniocentesis for advanced maternal age (C group) or for NT ≥95 th percentile (ENT group) found during first-trimester aneuploidy screening. AFS were analyzed with proton nuclear magnetic resonance ( 1 H-NMR) and high-performance liquid chromatography (HPLC), and subsequent multivariate and univariate statistical analyses were conducted, followed by pathway analysis. In total, 67 AFS from the C group and 23 from the ENT group were analyzed. Partial least square discriminate analysis was carried out (R 2 X=0.784, R 2 Y=0.658, Q 2 =0.622, P<0.0001). A different metabolic profile was observed in the ENT group compared with the C group, suggesting an energetic shift to a glycolytic phenotype in an oxidative environment in the ENT group compared to the C group. Metabolomic studies enable the identification of metabolic alterations occurring in fetuses with ENT. These findings may provide a new basis for better understanding the pathophysiological mechanisms in this prenatal phenomenon.