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Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

ABSTRACT: BACKGROUND:Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins. METHODS:Hair samples were collected at delivery from 10 pairs of type 1 sIUGR twins, 8 pairs of types 2&3 sIUGR twins, and 11 pairs of twins without sIUGR. The hair metabolome was characterized using gas chromatography-mass spectrometry. RESULTS:Our results demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28?weeks of gestation but not with birthweight. The hair profiles were capable of discriminating type2&3 sIUGR twins from twins without sIUGR. In particular, the metabolites 2-aminobutyric acid, cysteine, alanine, and tyrosine all displayed areas under the receiver operating characteristic curve were above 0.9. The metabolic pathway analysis highlighted the associations of sIUGR twins with abnormal umbilical artery flow with increased metabolites from a nutrient depletion pathway, glutathione metabolism, and nerve development. CONCLUSION:This study offers novel insight into the severity of intrauterine ischemia and hypoxia for T2&3 sIUGR twins, through evaluation of the neonatal hair metabolome.

SUBMITTER: Yang J

PROVIDER: S-EPMC7193362 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

Yang Jing J Wei Yuan Y Qi Hongbo H Yin Nanlin N Yang Yang Y Li Zailing Z Xu Lili L Wang Xueju X Yuan Pengbo P Li Luyao L Han Ting-Li TL Zhao Yangyu Y

Molecular medicine (Cambridge, Mass.) 20200501 1

<h4>Background</h4>Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins.<h4>Methods</h4>Hair samples were collected at delivery from 10 pairs of t ...[more]

PMID: 32357834

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Project description:IntroductionEarly-onset fetal growth restriction is a pregnancy complication often coinciding with abnormal Doppler flow in the umbilical artery. Absent or reversed end-diastolic flow in the umbilical artery is associated with adverse perinatal outcome. As the optimal management of this condition is unclear, the objective of this study was to analyze the time interval from admission to delivery of pregnancies with early-onset fetal growth restriction, while pursuing a policy of postponing delivery unless active management of labor would be required because of fetal distress or maternal condition. We also assessed short- and long-term perinatal outcome.Material and methodsIn this historical cohort study, all pregnant women with singleton pregnancies, admitted during 2004-2015 with early-onset fetal growth restriction were included. Pregnancies with absent or reversed end-diastolic flow (AREDF) were compared with pregnancies with a positive end-diastolic Doppler flow (PEDF). Time until delivery was determined and perinatal outcome was assessed for both groups.ResultsIn our study, 111 women were allocated to the PEDF group and 109 to the AREDF group. In the AREDF group, fetal distress was more often an indication for delivery, in comparison with the PEDF group (p = .004). Median time until delivery in patients admitted between 26 and 28 weeks' gestation was 6+5 weeks in the PEDF group and 1+4 weeks in the AREDF group (p = .001). No statistically significant difference was found between the Doppler groups in the composite adverse neonatal outcome, which includes at least one of the following outcomes: infant respiratory distress syndrome, sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage >grade 2, periventricular leukomalacia and perinatal death (p = .63).ConclusionsIn this study, comprising pregnancies with early-onset fetal growth restriction, fetal distress was observed more frequently in the AREDF group with the consequence of delivery at an earlier stage of gestation, compared with the PEDF group. AREDF was not associated with increased perinatal morbidity and mortality compared with PEDF.

Project description:BackgroundIntrauterine growth restriction (IUGR), which refers to reduced fetal growth in the context of placental insufficiency, is etiologically heterogeneous. IUGR is associated not only with perinatal morbidity and mortality but also with adult-onset disorders, such as cardiovascular disease and diabetes, posing a major health burden. Placental epigenetic dysregulation has been proposed as one mechanism that causes IUGR; however, the spectrum of epigenetic pathophysiological mechanisms leading to IUGR remains to be elucidated. Monozygotic monochorionic twins are particularly affected by IUGR, in the setting of severe discordant growth. Because monozygotic twins have the same genotype at conception and a shared maternal environment, they provide an ideal model system for studying epigenetic dysregulation of the placenta.ResultsWe compared genome-wide placental DNA methylation patterns of severely growth-discordant twins to identify novel candidate genes for IUGR. Snap-frozen placental samples for eight severely growth-discordant monozygotic monochorionic twin pairs were obtained at delivery from each twin. A high-resolution DNA methylation array platform was used to identify methylation differences between IUGR and normal twins. Our analysis revealed differentially methylated regions in the promoters of eight genes: DECR1, ZNF300, DNAJA4, CCL28, LEPR, HSPA1A/L, GSTO1, and GNE. The largest methylation differences between the two groups were in the promoters of DECR1 and ZNF300. The significance of these group differences was independently validated by bisulfite pyrosequencing, implicating aberrations in fatty acid beta oxidation and transcriptional regulation, respectively. Further analysis of the array data identified methylation changes most prominently affecting the Wnt and cadherin pathways in the IUGR cohort.ConclusionsOur results suggest that IUGR in monozygotic twins is associated with impairments in lipid metabolism and transcriptional regulation as well as cadherin and Wnt signaling. We show that monozygotic monochorionic twins discordant for growth provide a useful model to study one type of the epigenetic placental dysregulation that drives IUGR.

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Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

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Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

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