Beyond Targeted Newborn Screening: A Nontargeted Metabolomics Workflow to Investigate Birthweight-Metabolome...

Area of Science:

• Biochemistry
• Metabolomics
• Public Health

Background:

• Newborn screening (NBS) uses mass spectrometry but has limited biomarker scope.
• Current methods struggle with overlapping biomarkers between healthy and diseased infants.

Purpose of the Study:

• Develop a robust, nontargeted liquid chromatography-mass spectrometry (LC-MS) workflow for dried bloodspot (DBS) analysis.
• Expand metabolite profiling for improved newborn screening and biomarker discovery.

Main Methods:

• Nontargeted LC-MS analysis of 810 newborn DBS samples.
• Utilized HILIC chromatography for broad metabolite coverage, including amino acids, acylcarnitines, and lipids.
• Correlated metabolite levels with birthweight and identified novel biomarkers.

Main Results:

• Identified correlations to improve accuracy of existing NBS markers like isovalerylcarnitine.
• Discovered new metabolic phenotypes related to parenteral nutrition and maternal nicotine exposure.
• Found N-acetyltyrosine and N-acetylputrescine as valuable biomarkers for specific newborn conditions.

Conclusions:

• The developed LC-MS workflow enhances NBS capabilities by profiling thousands of metabolites.
• Identified novel biomarkers that can improve diagnostic accuracy and account for variability in newborn populations.
• This approach supports the discovery of new biomarkers for improved preventative public health initiatives.