Application of a second-tier newborn screening assay for c5 isoforms

Area of Science:

• Biochemistry
• Neonatal Screening
• Metabolic Disorders

Background:

• Neonatal screening programs aim to detect metabolic disorders early.
• False-positive results can lead to unnecessary investigations and parental anxiety.
• Maternal antibiotic use during pregnancy can interfere with newborn metabolic screening.

Purpose of the Study:

• To report a case of false-positive newborn screening for isovaleric acidemia.
• To highlight the impact of maternal pivalic acid antibiotic exposure.
• To emphasize the utility of second-tier tandem mass spectrometry (MS) testing.

Main Methods:

• Analysis of a dried blood spot sample from a newborn.
• Utilized a second-tier tandem MS technique for metabolic screening.
• Investigated the presence of pivalic acid and its metabolites.

Main Results:

• Identified pivalic acid in the newborn's blood sample, mimicking isovaleric acidemia.
• Confirmed the source of pivalic acid as maternal antibiotic treatment before delivery.
• Demonstrated that the second-tier test accurately identified the cause of the false-positive result.

Conclusions:

• Maternal pivalic acid exposure can cause false-positive newborn screening for isovaleric acidemia.
• Early implementation of second-tier tandem MS testing can prevent unnecessary diagnostic procedures.
• Timely and accurate diagnosis reduces parental stress and healthcare costs associated with false-positive newborn screening.