Gestational Age-Related Urinary Peptidome Changes in Preterm and Term Born Infants

Abstract

<b><i>Introduction:</i></b> Preterm infants are at risk for a variety of somatic and neurological disorders. In recent years, biofluid proteomics has emerged as a potential diagnostic tool for biomarker analysis. The aim of this study was to determine gestational age (GA)-related patterns of the urinary peptidome in preterm infants for researching potential novel prognostic biomarkers. <b><i>Methods:</i></b> We performed urinary peptidomics in longitudinal samples of 24 preterm (mean GA weeks 28 + 1 [24+1–31 + 6]) and 27 term born controls (mean GA weeks 39 + 2 [37+0–41 + 1]) using capillary electrophoresis combined with mass spectrometry (CE-MS). Peptides were sequenced using CE-MS/MS or LC-MS/MS analysis and were deposited, matched, and annotated in a Microsoft SQL database for statistical analysis. We compared their abundance in urine of preterm and term born infants and performed a validation analysis as well as correlations to GA and clinical risk scores. <b><i>Results:</i></b> Our results confirmed significant differences in the abundance of peptides and the hypothesis of age-dependent urinary peptidome changes in preterm and term infants. In preterm infants, <i>SLC38A10 (solute carrier family 38 member 10)</i> is one of the most abundant peptides. Combined urinary peptides correlated with clinical risk scores (<i>p</i> &lt; 0.05). <b><i>Conclusion:</i></b> This is the first study reporting GA-related urinary peptidome changes of preterm infants detected by CE-MS and a modulation of the peptidome with GA. Further research is required to locate peptidome clusters correlated with specific clinical complications and long-term outcome. This may identify preterm infants at higher risk for adverse outcome who would benefit from early intervention.