Cord blood metabolomic profiling in intrauterine growth restriction |
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Authors: | Email author" target="_blank">Donata?FavrettoEmail author Erich?Cosmi Eugenio?Ragazzi Silvia?Visentin Marianna?Tucci Paolo?Fais Giovanni?Cecchetto Vincenzo?Zanardo Guido?Viel Santo?Davide?Ferrara |
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Institution: | (1) Department of Public Health and Environmental Medicine, Forensic Toxicology and Antidoping Unit, University of Padova, 35122 Padova, Italy;(2) Department of Gynecological Science and Human Reproduction, University of Padova, 35122 Padova, Italy;(3) Department of Pharmacology and Anesthesiology, University of Padova, 35122 Padova, Italy;(4) Department of Pediatrics, University of Padova, 35122 Padova, Italy |
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Abstract: | A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR).
Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes
beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was
employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass
spectrometry (LC-HRMS) analysis of cord blood collected soon after birth. Samples were collected from 22 IUGR and 21 appropriate
for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001). Serum samples were immediately obtained and deproteinized by mixing with methanol at room temperature and centrifugation;
supernatants were lyophilized and reconstituted in water for analysis. LC-HRMS analyses were performed on an Orbitrap mass
spectrometer linked to a Surveyor Plus LC. Samples were injected into a 1.0 × 150-mm Luna C18 column. Spectra were collected
in full-scan mode at a resolution of approximately 30,000. Data were acquired over the m/z range of 50–1,000, with measurements performed in duplicate. To observe metabolic variations between the two sets of samples,
LC-HRMS data were analyzed by a principal component analysis model. Many features (e.g., ionic species with specific retention
times) differed between the two classes of samples: among these, the essential amino acids phenylalanine, tryptophan, and
methionine were identified by comparison with available databases. Logistic regression coupled to a receiver-operating characteristic
curve identified a cut-off value for phenylalanine and tryptophan, which gave excellent discrimination between IUGR and AGA
fetuses. Non-targeted LC-HRMS analysis of cord blood collected at birth allowed the identification of significant differences
in relative abundances of essential amino acids between IUGR and AGA fetuses, emerging as a promising tool for studying metabolic
alterations. |
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