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.
Highlights
Characteristics and pregnancy outcomes Maternal age Employed outside the home Yes No Body mass index Primigravida Smoking during pregnancy IVF-ET/natural conception IVF-ETe Natural conception Gestational age at delivery Delivery Cesarean Vaginal Neonatal sex Male/male Female/female
Our results demonstrated that phenotypic discordance in selective intrauterine growth restriction (sIUGR) twins was related to altered essential amino acid composition, disrupted amino acid biochemical pathways and fatty acid metabolism
The amniotic fluid volume and Apgar score (1, 5, and 10 min) were similar between co-twins in both groups, while the birth weight was significantly different within sIUGR co-twins (p < 0.002)
Summary
Characteristics and pregnancy outcomes Maternal age (years) Employed outside the home Yes No Body mass index (kg/m2) Primigravida Smoking during pregnancy IVF-ET/natural conception IVF-ETe Natural conception Gestational age at delivery (wks) Delivery Cesarean Vaginal Neonatal sex Male/male Female/female. Both the mother and offspring[5,6]. SIUGR twins are the best model to investigate the pathophysiology underpinning fetal growth impairment of humans, as monochorionic twins have identical genotypes; the discordance in their intrauterine growth can be attributed to differences in non-shared environments[18]. Comparing sIUGR twins with IUGR singletons may reveal common mechanisms of suboptimal intrauterine growth
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