Metabolic Biomarkers of Monochorionic Twins Complicated With Selective Intrauterine Growth Restriction in Cord Plasma and Placental Tissue

Abstract

The selective intrauterine growth restriction (sIUGR) of monochorionic diamniotic (MCDC) twins causes phenotypic growth discordance, which is correlated with metabolomic pertubations. A global, untargeted identification of the metabolic fingerprint may help elucidate the etiology of sIUGR. Umbilical cord blood and placentas collected from 15 pairs of sIUGR monochorionic twins, 24 pairs of uncomplicated twins, and 14 singletons diagnosed with intrauterine growth restriction (IUGR) were subjected to gas chromatography-mass spectrometry based metabolomic analyses. Supervised multivariate regression analysis and pathway analysis were performed to compare control twins with sIUGR twins. A generalized estimating equation (GEE) model was utilized to explore metabolic differences within sIUGR co-twins. Linear logistic regression was applied to screen metabolites that significantly differed in concentration between control twins and sIUGR twins or IUGR singletons. Umbilical cord blood demonstrated better global metabolomic separation of sIUGR and control twins compared to the placenta. Disrupted amino acid and fatty acid metabolism as well as high levels of exposure to environmental xenobiotics were associated with sIUGR. The metabolic abnormalities in MCDA twins suggested that in utero growth discordance is caused by intrauterine and extrauterine environmental factors, rather than genetics. Thus, this study provides new therapeutic targets and strategies for sIUGR management and prevention.