Metabolomics analysis of umbilical cord blood clarifies changes in saccharides associated with delivery method

Hashimoto, Fusako; Nishiumi, Shin; Miyake, Osamu; Takeichi, Hitomi; Chitose, Mari; Ohtsubo, Hiromi; Ishimori, Shingo; Ninchoji, Takeshi; Hashimura, Yuya; Kono, Hiroshi; Morisada, Naoya; Morioka, Ichiro; Fukuoka, Hiroshi; Yoshida, Masaru; Iijima, Kazumoto

doi:10.1016/j.earlhumdev.2012.10.010

Cited by 18 publications

(17 citation statements)

References 20 publications

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“…Regardless, given that sorbitol dehydrogenase is known to be present in human fetal liver and brain [ 33 ], our findings raise the intriguing possibility that the sorbitol generated by the placenta could still be a substrate for fetal fructose production, which may have important ramifications for the developing fetal brain. Furthermore, because our samples were collected in the absence of labor, they may be a more accurate reflection of fetal exposure as it has been shown that stress from labor induces higher cord blood levels of glucose and fructose compared to levels obtained in the absence of labor [ 34 ]. This may explain why the levels of glucose and fructose we obtained in cord venous blood were lower than those obtained previously from cord blood in women after the onset of labor [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

et al. 2015

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BackgroundFructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose.MethodsIn this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section.ResultsAs expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.ConclusionsThese data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.

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Section: Discussionmentioning

confidence: 99%

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

et al. 2015

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“…In any case, some evidence of metabolic disturbances has already been identified, namely for newborns affected by prematurity (impact on renal and liver function, neuronal development, and amino acids metabolism); 17−20 GDM (disruption of lipid, amino acid, and nucleotide metabolisms 3 ); asphyxia, RDS and MAS (changes in glucose, lactate, tricarboxylic acid (TCA) cycle metabolites and organic acids 11,24,25 ); and IUGR (changes in insulin secretion, protein synthesis and catabolism, lipid synthesis, and cell proliferation 31 ). In this paper, we report, for the first time to our knowledge, the effects of important possible confounders on the urine metabolome of healthy newborns, namely, gender, delivery mode (previously studied through umbilical cord blood only 13 ), gestational age at birth and day-of-life at collection. Taking these effects into account, the impact of prematurity on newborn urine composition is then assessed, building up on previous studies, 17−20 and compared to several other disorders (namely respiratory depression: newborns requiring reanimation after birth; LGA: birth weight above 90th percentile; malformations; jaundice: hyperbilirrubinemia requiring phototherapy; and premature rupture of membranes (PROM): labor after 37th g.w.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Analysis of umbilical cord blood provides a snapshot of maternal-fetal symbiosis, and compositional changes have been detected in relation to (1) perturbations in fetal growth, namely small for gestational age (SGA), 4 intrauterine growth restriction (IUGR), 5,6 low birth weight (LBW), 7 and very low birth weight (VLBW); 8 (2) hypoxic ischemic encephalopathy (HIE) and asphyxia; 9−11 (3) gestational diabetes mellitus (GDM) pregnancies 3,12 ) delivery mode (vaginal delivery vs cesarean section). 13 In addition, newborn blood spots collected during the first week of life and analyzed by 1 H NMR and nanospray ionization with high resolution mass spectrometry (nS-HR-MS) have been studied for the screening of inborn errors of metabolism (IEM). 14−16 The noninvasive collection of newborn urine and subsequent ease to address large cohorts, compared to newborn blood, makes it a particularly interesting biofluid in the present context.…”

Section: ■ Introductionmentioning

confidence: 99%

Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study

et al. 2015

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This work assesses the urinary metabolite signature of prematurity in newborns by nuclear magnetic resonance (NMR) spectroscopy, while establishing the role of possible confounders and signature specificity, through comparison to other disorders. Gender and delivery mode are shown to impact importantly on newborn urine composition, their analysis pointing out at specific metabolite variations requiring consideration in unmatched subject groups. Premature newborns are, however, characterized by a stronger signature of varying metabolites, suggestive of disturbances in nucleotide metabolism, lung surfactants biosynthesis and renal function, along with enhancement of tricarboxylic acid (TCA) cycle activity, fatty acids oxidation, and oxidative stress. Comparison with other abnormal conditions (respiratory depression episode, large for gestational age, malformations, jaundice and premature rupture of membranes) reveals that such signature seems to be largely specific of preterm newborns, showing that NMR metabolomics can retrieve particular disorder effects, as well as general stress effects. These results provide valuable novel information on the metabolic impact of prematurity, contributing to the better understanding of its effects on the newborn's state of health.

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“…The demographic variability of the HIE population will itself account for metabolomic differences; for example, gestational age creates a distinct metabolomic profile [ 52 ], as do mode of delivery [ 53 ] and intrauterine growth [ 54 ]. Other possible confounding factors include gender, ethnicity, maternal BMI, and the length of time the blood sample has spent in the freezer.…”

Section: Translation Of Animal Research To Human Neonatal Studiesmentioning

confidence: 99%

Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field

Denihan

Boylan

Murray

2015

BioMed Research International

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Metabolomics, the latest “omic” technology, is defined as the comprehensive study of all low molecular weight biochemicals, “metabolites” present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field.

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Metabolomics analysis of umbilical cord blood clarifies changes in saccharides associated with delivery method

Cited by 18 publications

References 20 publications

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study

Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field

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