Metabolomics of prematurity: analysis of patterns of amino acids, enzymes, and endocrine markers by categories of gestational age.
BACKGROUND
Prematurity may influence the levels of amino acids, enzymes, and endocrine markers obtained through newborn screening. Identifying which analytes are the most affected by degree of prematurity could provide insight into how prematurity impacts metabolism.


METHODS
Analytes from blood spots assayed by Newborn Screening Ontario between March 2006 and April 2009 were used in this analysis. We examined the associations between the degree of prematurity and the levels of amino acids, enzymes, and endocrine markers in all newborns with and without adjustment for birth weight, feeding status, sample timing, transfusion, and sex.


RESULTS
Our analysis included the following cohorts: 373,819 children born at term (>36 wk gestation), 26,483 near-term children (33-36 wk gestation), 4,354 very premature children (28-32 wk gestation), and 1,146 extremely premature children (<28 wk gestation). Of the amino acids showing consistent trends across categories of prematurity, the levels of three amino acids (arginine, leucine, and valine) were at least 50% different between the cohorts of extremely premature and term children. The levels of 17-hydroxyprogesterone increased with increasing prematurity, while thyrotropin-stimulating hormone values consistently decreased with increasing prematurity. None of the three enzyme markers we examined showed a trend in levels across categories of prematurity.


CONCLUSIONS
This study demonstrates that children at different stages of prematurity are metabolically distinct. Future research should focus on the mechanism by which specific analytes are influenced by prematurity.
1] Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada [2] Institute for Clinical Evaluative Sciences, University of Ottawa, Ottawa, Ontario, Canada [3] Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Kumanan
K
Wilson
1] Institute for Clinical Evaluative Sciences, University of Ottawa, Ottawa, Ontario, Canada [2] Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada [3] Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Steven
S
Hawken
1] Institute for Clinical Evaluative Sciences, University of Ottawa, Ottawa, Ontario, Canada [2] Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada [3] Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Robin
R
Ducharme
1] Institute for Clinical Evaluative Sciences, University of Ottawa, Ottawa, Ontario, Canada [2] Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada [3] Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Beth K
BK
Potter
Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Julian
J
Little
1] Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada [2] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada [3] Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Bernard
B
Thébaud
1] Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada [2] Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Pranesh
P
Chakraborty
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000596:Amino Acids / Q000097:blood*; D001120:Arginine / Q000737:chemistry; D001724:Birth Weight; D015331:Cohort Studies; D004703:Endocrine System; D004798:Enzymes / Q000737:chemistry; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D007930:Leucine / Q000737:chemistry; D008297:Male; D055442:Metabolome; D015997:Neonatal Screening; D009864:Ontario; D047928:Premature Birth; D013973:Thyrotropin-Releasing Hormone / Q000097:blood; D013997:Time Factors; D014633:Valine / Q000737:chemistry
D000596:Amino Acids; D004798:Enzymes; D013973:Thyrotropin-Releasing Hormone; D019326:17-alpha-Hydroxyprogesterone; D001120:Arginine; D007930:Leucine; D014633:Valine