Gestational age-dependent development of the neonatal metabolome
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Gestational age-dependent development of the neonatal metabolome. / Ernst, Madeleine; Rogers, Simon; Lausten-Thomsen, Ulrik; Björkbom, Anders; Laursen, Susan Svane; Courraud, Julie; Borglum, Anders; Nordentoft, Merete; Werge, Thomas; Mortensen, Preben Bo; Hougaard, David M.; Cohen, Arieh S.
In: Pediatric Research, Vol. 89, 2021, p. 1396–1404.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Gestational age-dependent development of the neonatal metabolome
AU - Ernst, Madeleine
AU - Rogers, Simon
AU - Lausten-Thomsen, Ulrik
AU - Björkbom, Anders
AU - Laursen, Susan Svane
AU - Courraud, Julie
AU - Borglum, Anders
AU - Nordentoft, Merete
AU - Werge, Thomas
AU - Mortensen, Preben Bo
AU - Hougaard, David M.
AU - Cohen, Arieh S.
PY - 2021
Y1 - 2021
N2 - BACKGROUND: Prematurity is a severe pathophysiological condition, however, little is known about the gestational age-dependent development of the neonatal metabolome.METHODS: Using an untargeted liquid chromatography-tandem mass spectrometry metabolomics protocol, we measured over 9000 metabolites in 298 neonatal residual heel prick dried blood spots retrieved from the Danish Neonatal Screening Biobank. By combining multiple state-of-the-art metabolome mining tools, we retrieved chemical structural information at a broad level for over 5000 (60%) metabolites and assessed their relation to gestational age.RESULTS: A total of 1459 (similar to 16%) metabolites were significantly correlated with gestational age (false discovery rate-adjusted P <0.05), whereas 83 metabolites explained on average 48% of the variance in gestational age. Using a custom algorithm based on hypergeometric testing, we identified compound classes (617 metabolites) overrepresented with metabolites correlating with gestational age (P <0.05). Metabolites significantly related to gestational age included bile acids, carnitines, polyamines, amino acid-derived compounds, nucleotides, phosphatidylcholines and dipeptides, as well as treatment-related metabolites, such as antibiotics and caffeine.CONCLUSIONS: Our findings elucidate the gestational age-dependent development of the neonatal blood metabolome and suggest that the application of metabolomics tools has great potential to reveal novel biochemical underpinnings of disease and improve our understanding of complex pathophysiological mechanisms underlying prematurity-associated disorders.
AB - BACKGROUND: Prematurity is a severe pathophysiological condition, however, little is known about the gestational age-dependent development of the neonatal metabolome.METHODS: Using an untargeted liquid chromatography-tandem mass spectrometry metabolomics protocol, we measured over 9000 metabolites in 298 neonatal residual heel prick dried blood spots retrieved from the Danish Neonatal Screening Biobank. By combining multiple state-of-the-art metabolome mining tools, we retrieved chemical structural information at a broad level for over 5000 (60%) metabolites and assessed their relation to gestational age.RESULTS: A total of 1459 (similar to 16%) metabolites were significantly correlated with gestational age (false discovery rate-adjusted P <0.05), whereas 83 metabolites explained on average 48% of the variance in gestational age. Using a custom algorithm based on hypergeometric testing, we identified compound classes (617 metabolites) overrepresented with metabolites correlating with gestational age (P <0.05). Metabolites significantly related to gestational age included bile acids, carnitines, polyamines, amino acid-derived compounds, nucleotides, phosphatidylcholines and dipeptides, as well as treatment-related metabolites, such as antibiotics and caffeine.CONCLUSIONS: Our findings elucidate the gestational age-dependent development of the neonatal blood metabolome and suggest that the application of metabolomics tools has great potential to reveal novel biochemical underpinnings of disease and improve our understanding of complex pathophysiological mechanisms underlying prematurity-associated disorders.
KW - PRETERM BIRTH
KW - MOLECULAR NETWORKING
KW - NATURAL-PRODUCTS
KW - MICROBIOTA
KW - MORTALITY
KW - DISCOVERY
KW - AUTISM
U2 - 10.1038/s41390-020-01149-z
DO - 10.1038/s41390-020-01149-z
M3 - Journal article
C2 - 32942288
VL - 89
SP - 1396
EP - 1404
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
ER -
ID: 250540157