Preprint Article Version 1 This version is not peer-reviewed

N-Acetyltyrosine as a Biomarker of Parenteral Nutrition Administration in First-Tier Newborn Born Screening Assays

Version 1 : Received: 31 October 2024 / Approved: 1 November 2024 / Online: 1 November 2024 (13:51:46 CET)

How to cite: Pickens, C. A.; Sah, S.; Chandrappa, R.; Isenberg, S. L.; Courtney, E. R.; Lim, T.; Chace, D.; Lee, R.; Cuthbert, C. D.; Petritis, K. N-Acetyltyrosine as a Biomarker of Parenteral Nutrition Administration in First-Tier Newborn Born Screening Assays. Preprints 2024, 2024110057. https://doi.org/10.20944/preprints202411.0057.v1 Pickens, C. A.; Sah, S.; Chandrappa, R.; Isenberg, S. L.; Courtney, E. R.; Lim, T.; Chace, D.; Lee, R.; Cuthbert, C. D.; Petritis, K. N-Acetyltyrosine as a Biomarker of Parenteral Nutrition Administration in First-Tier Newborn Born Screening Assays. Preprints 2024, 2024110057. https://doi.org/10.20944/preprints202411.0057.v1

Abstract

Background: Parenteral nutrition (PN) is a nutrient solution administered intravenously (IV) to premature babies. PN causes elevations of some amino acids in blood samples that are also biomarkers used in newborn screening (NBS). Therefore, PN status must be annotated on dried blood spot (DBS) cards by clinicians to reduce NBS laboratory burdens associated with potential false results, however, NBS laboratories continue to receive DBS with misannotated PN status. N-acetyltyrosine (NAT), a water-soluble tyrosine analog used to increase tyrosine bioavailability in PN solutions, can be used as a blood-based biomarker of PN administration in NBS assays. Methods: Residual DBS specimens and manufactured DBS were used in analyses. The assay was developed and validated using flow injection analysis tandem mass spectrometry (FIA-MS/MS) for detection of NAT. Results: NAT was only present in neonate DBS with annotated PN administration, and was multiplexed into first-tier newborn screening assays. NAT was highly correlated with amino acids present in PN solutions such as arginine, leucine, methionine, phenylalanine, and valine. In our sample cohort, we determined an NAT cutoff could aid identification of misannotated neonates administered PN. We also report the Amadori rearrangement product valine-hexose (Val-Hex) was quantifiable in neonates administered PN, which we suspect forms in the PN solution and/or IV lines. Conclusions: Here we present the first known use of NAT as a biomarker for PN administration, which is currently being piloted by two U.S. NBS laboratories. NAT and Val-Hex can aid identification of misannotated DBS from neonates administered PN, thus, decreasing false positive rates.

Keywords

Newborn Screening; Parenteral nutrition; Metabolic disorders; multiplexing; biomarker

Subject

Medicine and Pharmacology, Pediatrics, Perinatology and Child Health

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.