Metabolomics of prematurity: analysis of patterns of amino acids, enzymes and endocrine markers by categories of gestational age

Background — Prematurity may influence amino acids, enzymes and endocrine markers levels obtained through newborn screening. Identifying which analytes are the most affected by degree of prematurity could provide insight into how prematurity impacts metabolism.

Methods — We examined the associations between degree of prematurity and 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 373,819 children born at term (> 36 weeks gestation), 26,483 near-term children (33-36 weeks gestation), 4354 very premature children (28-32 weeks gestation) and 1146 extremely premature children (<28 weeks gestation). Of the amino acids showing consistent trends across categories of prematurity, the levels of 3 amino acids (arginine, leucine and valine) were at least 50% different between extremely premature and term children. Levels of 17-hydroxyprogesterone (17-OHP) increased with increasing prematurity while thyrotropin stimulating hormone (TSH) values consistently decreased with increasing prematurity. None of the three enzyme markers we examined showed a trend in levels across categories of prematurity.

Conclusion — This study demonstrates that children at different stages of prematurity are metabolically distinct. Future research should focus on the mechanism by which prematurity impacts upon the specific analytes influenced by prematurity.