A Scoping Review: Urinary Markers of Metabolic Maturation in Preterm Infants and Future Interventions to Improve Growth

Abstract

Background: Growth failure in infants born preterm is a significant issue, increasing the risk of poorer neurodevelopmental outcomes and metabolic syndrome later in life. During the first 1000 days of life biological systems mature rapidly involving developmental programming, cellular senescence, and metabolic maturation, regulating normal growth and development. However, little is known about metabolic maturation in infants born preterm and the relationship with growth. Objective: To examine the available evidence on urinary markers of metabolic maturation and their relationship with growth in infants born preterm. Eligibility criteria: Studies including in this scoping review using qualitative or quantitative methods to describe urinary markers of metabolic maturation and the relationship with growth in infants born preterm. Results: After a screening process 15 titles were included in this review, from 1998–2021 drawing from China (n = 1), Italy (n = 3), Germany (n = 3), Greece (n = 1), Japan (n = 2), Norway (n = 1), Portugal (n = 1), Spain (n = 2) and USA (n = 1). The included studies examined urinary metabolites in 1131 infants. A content analysis identified 4 overarching themes relating to; (i) metabolic maturation relative to gestational age, (ii) metabolic signature and changes in urinary metabolites over time, (iii) nutrition and (iv) growth. Conclusion: The results of this scoping review suggest there are considerable gaps in our knowledge relating to factors associated with metabolic instability, what constitutes normal maturation of preterm infants, and how the development of reference phenome age z scores for metabolites of interest could improve nutritional and growth outcomes.

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“…Betaine and dimethylglycine are related compounds that have been investigated for health benefits, including their roles in cellular processes and their function as methyl donors in several metabolic pathways, such as DNA methylation, for potential antioxidant properties [23][24][25]. Oxidative stress plays a role in the development and progression of BPD [26].…”

Identification of Novel Biomarkers in Late Preterm Neonates with Respiratory Distress Syndrome (RDS) Using Urinary Metabolomic Analysis

“…Furthermore, prematurity has been associated with impaired amino acid, carbohydrate, and fatty acid metabolism, followed by an increase in tricarboxylic acid (TCA) cycle metabolites and urinary choline metabolites. Oxidative stress markers are also higher in preterm infants and are further impaired by parenteral nutrition and formula feeding [ 49 ]. Exposure to medical treatment may also drive urine metabolomics patterns in hospitalized neonates.…”