Abstract
Newborn screening for Cystic Fibrosis has been implemented in most programs worldwide, but the approach used varies, including combinations of immunoreactive trypsinogen (IRT) and CFTR mutation analysis on one or more specimens. The British Columbia (BC) newborn screening program tests ~45,000 infants per year in BC and the Yukon Territory, covering almost 1.5 million km2 in western Canada. CF screening was initiated using an IRT-DNA-IRT approach with a second bloodspot card at 21 days of age for all CFTR mutation heterozygotes and any non-carriers in the top 0.1% for IRT. This second IRT was implemented to avoid sweat testing of infants without persistent hypertrypsinemia, reducing the burden of travel for families. Over nine years (2010–2018), 401,977 infants were screened and CF was confirmed in 76, and a further 28 were deemed CF screen positive inconclusive diagnosis (CFSPID). Day 21 IRT was normal in 880 CFTR mutation carriers who were quoted a very low CF risk and offered optional sweat testing. Only 13% of families opted for sweat testing and a total of 1036 sweat tests were avoided. There were six false negative CF cases (and three CFSPID) due to a low initial IRT or no CFTR mutations. Although one CFSPID case had a normal repeat IRT result, the addition of the day 21 IRT did not contribute to any CF false negatives.
Highlights
Cystic fibrosis (CF) is one of the few disorders for which randomized controlled trials have been conducted to provide support for population-wide newborn screening
While the vast majority of programs start with the measurement of immunoreactive trypsinogen (IRT) using dried bloodspots and finish with sweat chloride levels as a confirmatory diagnostic test, a number of secondary biochemical or molecular tests may be employed in variable sequence between these end points
Over a nine-year period in British Columbia, 401,977 infants were screened with 76 cases of Cystic Fibrosis detected and an additional 28 infants defined as CF screen positive inconclusive diagnosis (CFSPID) following standard diagnostic guidelines [7]
Summary
Cystic fibrosis (CF) is one of the few disorders for which randomized controlled trials have been conducted to provide support for population-wide newborn screening. While the vast majority of programs start with the measurement of immunoreactive trypsinogen (IRT) using dried bloodspots and finish with sweat chloride levels (sweat test) as a confirmatory diagnostic test, a number of secondary biochemical or molecular tests may be employed in variable sequence between these end points Much of this diversity stems from the fact that no one test is sufficiently sensitive nor specific enough to differentiate newborns who are likely to develop clinically significant disease from the general population. The primary IRT marker by itself has a positive predictive value (PPV) for CF of less than 1% and will miss ~2–5% of cases regardless of the subsequent screening algorithm [1,2] Despite these constraints, a number of well-designed screening algorithms have been shown to provide acceptable performance for the detection of CF in the newborn period. Neonatal Screen. 2020, 6, 46; doi:10.3390/ijns6020046 www.mdpi.com/journal/ijns
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