Expanded Newborn Screening in Italy Using Tandem Mass Spectrometry: Two Years of National Experience

Abstract

Newborn screening (NBS) for inborn errors of metabolism is one of the most advanced tools for secondary prevention in medicine, as it allows early diagnosis and prompt treatment initiation. The expanded newborn screening was introduced in Italy between 2016 and 2017 (Law 167/2016; DM 13 October 2016; DPCM 12-1-2017). A total of 1,586,578 infants born in Italy were screened between January 2017 and December 2020. For this survey, we collected data from 15 Italian screening laboratories, focusing on the metabolic disorders identified by tandem mass spectrometry (MS/MS) based analysis between January 2019 and December 2020. Aminoacidemias were the most common inborn errors in Italy, and an equal percentage was observed in detecting organic acidemias and mitochondrial fatty acids beta-oxidation defects. Second-tier tests are widely used in most laboratories to reduce false positives. For example, second-tier tests for methylmalonic acid and homocysteine considerably improved the screening of CblC without increasing unnecessary recalls. Finally, the newborn screening allowed us to identify conditions that are mainly secondary to a maternal deficiency. We describe the goals reached since the introduction of the screening in Italy by exchanging knowledge and experiences among the laboratories.

Keywords: aminoacidemias; fatty acid oxidation disorders; inborn errors of metabolism; newborn screening; organic acidemias; tandem mass spectrometry; urea cycle defects.

Figure 1

Map of Italian regions. The blue dots represent laboratories performing expanded Newborn Screening in Italy. The red dot marks the only regional laboratory not performing NBS tests by MS/MS in the years 2019–2020. Regions without a dot have established interregional agreements with neighboring region as described in paragraph 2.2 NBS Regional Organization and coverage.

Figure 2

NBS flow chart.

Figure 3

The percentage of different classes of inborn errors of metabolisms in the Italian neonatal population during years 2019–2020, (A). The distribution of the different conditions identified by Expanded Newborn Screening, (B–E).