State Newborn Screening in the Tandem Mass Spectrometry Era: More Tests, More False-Positive Results

Abstract

State newborn screening programs have expanded dramatically in the past decade. Because the benefit of such testing may be unclear in some cases and because the number of infants who may receive false-positive results and may be labeled falsely as having disease is potentially sizeable, a more cautious approach is needed.

Reduction in newborn screening metabolic false-positive results following a new collection protocol

“…The FPR of 5.8% found in all patients in the study Level IIIC NICU was higher than what has been reported for the overall newborn population, where rates range from 0.11 to 0.3%. 5,6,12,19 Our results do, however, agree with others who have demonstrated a higher FPR in premature infants or in those admitted to a NICU. [6][7][8][9]20 The results also indicate that an increased FPR can be expected with a lower birth weight as has been shown by others.…”

“…4 The collection technique and sample requirements remain the same as those originally established; therefore, the use of tandem mass spectrometry is an efficient method to screen for many conditions without increasing the amount of blood required. 5 In 2005, the American Academy of Pediatrics endorsed the recommendations by the American College of Medical Genetics and Genomics to increase the number of disorders included in the newborn screen core panel to 29 identified conditions and 25 additional conditions that are part of the differential diagnosis in the core panel. 1,2 Most infants are born healthy and discharged within 1-2 days after birth.…”

Precision newborn screening for lysosomal disorders

“…32,36 Newborn screening is based on laboratory tests performed on a growing proportion of~130 millions of newborns worldwide every year. Poor performance on a mass scale distresses a multitude of patients 37 and exposes their families and providers to high risk of psychosocial harm. 38 In the case of lysosomal disorders, genomic medicine has struggled to bring closure to the evaluation of presumptive positive cases with an abundance of inconclusive molecular results.…”

The impact of false-positive newborn screening results on families: a qualitative study

“…1 One study 2 estimates a minimum FP rate of 0.33% or 1/300 infants. If correct, then, with the US birth rate of four million a year, 3 more than 13,000 families each year may experience FP NBS, and this may be a low estimate.…”