Newborn Screening for Isovaleric Acidemia: Treatment With Pivalate‐Generating Antibiotics Contributed to False C5‐Carnitine Positivity in a Chinese Population

Abstract

ABSTRACT Background Newborn screening (NBS) for isovaleric acidemia (IVA) is implemented via tandem mass spectrometry (MS/MS), but false‐positive results are still common. In addition, NBS for IVA is limited by a lack of suitable biomarkers, especially after the use of pivaloylester‐containing antibiotics. Methods We conducted a retrospective cohort study to explore the clinical correlation between antibiotic administration and false‐positive results for isovalerylcarnitine (C5). Results A total of 509,313 newborns were recruited from the initial NBS study, only one of whom underwent genetic confirmation, conducted between 2015 and 2020. Significant associations between false‐positive C5‐carnitine screening results and treatment with pivalate‐generating antibiotics were identified with retrospective analysis. Conclusions The current results highlight the detrimental effects of false‐positive C5‐carnitine screening results. Unless the licensing of pivalate‐generating antibiotics for use during the neonatal period is reconsidered, a second‐tier test for C5 determination will be necessary.

Keywords

• isovaleric acidemia
• pivalate‐generating antibiotics
• second‐tier screening