The Urinary Metabolome of Newborns with Perinatal Complications

Abstract

Maternal pathological conditions such as infections and chronic diseases, along with unexpected events during labor, can lead to life-threatening perinatal outcomes. These outcomes can have irreversible consequences throughout an individual’s entire life. Urinary metabolomics can provide valuable insights into early physiological adaptations in healthy newborns, as well as metabolic disturbances in premature infants or infants with birth complications. In the present study, we measured 180 metabolites and metabolite ratios in the urine of 13 healthy (hospital-discharged) and 38 critically ill newborns (admitted to the neonatal intensive care unit (NICU)). We used an in-house-developed targeted tandem mass spectrometry (MS/MS)-based metabolomic assay (TMIC Mega) combining liquid chromatography (LC-MS/MS) and flow injection analysis (FIA-MS/MS) to quantitatively analyze up to 26 classes of compounds. Average urinary concentrations (and ranges) for 167 different metabolites from 38 critically ill NICU newborns during their first 24 h of life were determined. Similar sets of urinary values were determined for the 13 healthy newborns. These reference data have been uploaded to the Human Metabolome Database. Urinary concentrations and ranges of 37 metabolites are reported for the first time for newborns. Significant differences were found in the urinary levels of 44 metabolites between healthy newborns and those admitted at the NICU. Metabolites such as acylcarnitines, amino acids and derivatives, biogenic amines, sugars, and organic acids are dysregulated in newborns with bronchopulmonary dysplasia (BPD), asphyxia, or newborns exposed to SARS-CoV-2 during the intrauterine period. Urine can serve as a valuable source of information for understanding metabolic alterations associated with life-threatening perinatal outcomes.

Challenges and recent advances in quantitative mass spectrometry‐based metabolomics

“…In certain cases, the broad range of metabolites covered enables a more exploratory approach, while maintaining a quantitative dimension. Many recent studies have used such kits to investigate metabolic variations in complex samples, such as urine 79 and faeces. 80 Using a commercial kit‐based assay, Franco et al.…”

Olaris Global Panel (OGP): A Highly Accurate and Reproducible Triple Quadrupole Mass Spectrometry-Based Metabolomics Method for Clinical Biomarker Discovery

“…Finally, the cost-effectiveness and ruggedness of the QqQ instruments, along with the simplified data processing pipeline, make it feasible to process very large datasets and implement the method in clinical laboratories without expert metabolomics experience. Recent examples of QqQ-based metabolomics include a seminal work by López-Hernández et al, in which 180 urinary metabolites in a set of samples from both healthy and ill newborns admitted to the NICU were measured to investigate metabolic signatures related to life-threatening perinatal complication [26]. In another study, QqQ-based metabolomics was used to analyze a total of 184 metabolites in a large European population in order to identify potential biomarkers for cardiovascular risk assessment [27].…”