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

Abstract

Original research article INTRODUCTIONInborn errors of metabolism are a group of rare, inherited disorders that, when left undiagnosed and untreated, can have devastating complications or even result in death. Infants with inborn metabolic diseases can be detected with biochemical testing even though they are often asymptomatic at birth. The goal of newborn screening (NBS) is to test all infants and properly identify those with a disorder early so that prompt therapy may be initiated. The American Academy of Pediatrics and the American College of Medical Genetics and Genomics recommend that all newborn infants undergo NBS shortly after birth.1,2 NBS testing began in the United States in the early 1960s with screening for phenylketonuria, and, over the years, it has evolved into a complex program testing for multiple conditions.3,4 The number of diseases screened for has greatly increased with the availability of new technology like tandem mass spectrometry, which measures amino acids for the diagnosis of aminoacidopathies and acylcarnitines for the detection of fatty acid oxidation defects and organic adicemias using dried blood spots on filter paper. 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. 1,2Most infants are born healthy and discharged within 1-2 days after birth. Infants born ill or prematurely require longer hospitalization and often receive intensive medical care in a neonatal intensive care unit (NICU). Various medical therapies, including total parenteral nutrition (TPN), provided in the NICU and the liver immaturity of the preterm infant's metabolic system contribute to higher rates of presumptive positive NBS results in this group. [6][7][8][9] This population requires special planning and investigation into the best practice for collecting the NBS specimen in a manner to reduce the potential of a false-positive result (FPR), a result that is out of the range established by the NBS laboratory (presumptively positive), and additional testing confirms that no disorder exists. However, despite the importance of this problem, there is limited literature about how to decrease the FPR in the NICU population.In 2009, the Clinical and Laboratory Standards Institute published the document entitled "Newborn Screening for Preterm, Low Birth Weight, and Sick Newborns".10 This document Purpose: Newborn screening includes testing for many metabolic diseases. False-positive results are higher among neonatal intensive care unit infants, resulting in increased confirmatory testing and family...

The dried blood spot sampling method in the laboratory medicine

“…The changes in the concentration of individual molecules might not have such an informative character as the monitoring of several biomarker molecules and their comparison in relation to each other. These metabolic patterns are evaluated in the context of different disease states (7,9,(70)(71)(72)(73).…”

Stopping Parenteral Nutrition for 3 Hours Reduces False Positives in Newborn Screening

“…6,9,[19][20][21][22][23] This study shows a new NBS blood collection, the 3-hour stop-PN protocol, can significantly reduce falsepositive AA results and the associated medical costs. The current study confirms and expands the results of a smaller study of the effect of holding AA containing PN by Morris et al 23 The current study includes a much larger sample size of VLBW infants (87 vs 413 in this study). In addition, our protocol used the same dextrose concentration as in infant's PN running during 3-hour stop-PN infusion to avoid fluctuation in plasma glucose.…”

Undiagnosed Metabolic Dysfunction and Sudden Infant Death Syndrome – A Case‐Control Study

“…Five controls were randomly selected from the NBS database for each case matching on MS/MS testing date and lab code, which ensured that cases and controls were comparable on age and MS/MS testing methods. Individuals with known chromosomal and neural tube defects and other genetic disorders; of twins and multiple births; or with MS/MS analyte patterns implying a total parenteral nutrition (TPN) diet were excluded due to potential impact on the MS/MS analyte values …”