Collaborative evaluation study on 18 candidate diseases for newborn screening in 1.77 million samples

Abstract

Analytical and therapeutic innovations led to a continuous but variable extension of newborn screening (NBS) programmes worldwide. Every extension requires a careful evaluation of feasibility, diagnostic (process) quality and possible health benefits to balance benefits and limitations. The aim of this study was to evaluate the suitability of 18 candidate diseases for inclusion in NBS programmes. Utilising tandem mass spectrometry as well as establishing specific diagnostic pathways with second‐tier analyses, three German NBS centres designed and conducted an evaluation study for 18 candidate diseases, all of them inherited metabolic diseases. In total, 1 777 264 NBS samples were analysed. Overall, 441 positive NBS results were reported resulting in 68 confirmed diagnoses, 373 false‐positive cases and an estimated cumulative prevalence of approximately 1 in 26 000 newborns. The positive predictive value ranged from 0.07 (carnitine transporter defect) to 0.67 (HMG‐CoA lyase deficiency). Three individuals were missed and 14 individuals (21%) developed symptoms before the positive NBS results were reported. The majority of tested candidate diseases were found to be suitable for inclusion in NBS programmes, while multiple acyl‐CoA dehydrogenase deficiency, isolated methylmalonic acidurias, propionic acidemia and malonyl‐CoA decarboxylase deficiency showed some and carnitine transporter defect significant limitations. Evaluation studies are an important tool to assess the potential benefits and limitations of expanding NBS programmes to new diseases.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…The possibility of NBS for vitamin B 12 deficiency has also been reported including strategies, results, and public health implications [ 819 ], outcomes of early treatment resulting from NBS [ 820 ], and the results of screening 1.2 million newborns for MMA (and vitamin B 12 deficiency) using a two-tier screening strategy [ 821 ]. A collaborative pilot study conducted at three NBS sites in Germany evaluated 18 candidate disorders for German NBS, many using second-tier strategies, with the majority found suitable for inclusion on the screening panel [ 822 ]. Several reports have targeted IVA NBS (added in 2005).…”

Newborn screening in metachromatic leukodystrophy – European consensus-based recommendations on clinical management

“…Monitoring of screening programs is considered important as regular evaluations and adjustments based on emerging data are necessary. From other disease fields it is known that the disease spectrum changes after introduction of neonatal screening [69,70]. With neonatal identification of patients, the known phenotypic variation of the disease becomes larger and typically milder phenotypes become more prevalent.…”

A Review of Disparities and Unmet Newborn Screening Needs over 33 Years in a Cohort of Mexican Patients with Inborn Errors of Intermediary Metabolism

“…NBS panel selection is a complex public health issue, and the addition of diseases must be performed carefully, considering many factors, such as the benefits, the possible harms, and the economic factors, among others [ 60 , 61 , 62 ]. In addition, controversies still exist for conditions like 3MCC, which are generally asymptomatic [ 63 ], and have even been removed from some NBS programs [ 64 ].…”