Original ArticleA New Cystic Fibrosis Newborn Screening Algorithm: IRT/IRT1↑/DNA
Section snippets
IRT/IRT1↑/DNA Method
We have developed a new algorithm to screen newborns for CF (Figure 1). All infants born in Colorado receive a first newborn screen before they are discharged from the hospital (at approximately 48 hours of life) and another screen at 2 weeks. We measure the second IRT solely in specimens from infants with an elevated first IRT level (>60ng/mL, approximately 97th percentile). When the IRT level is not elevated on the first newborn screening (NBS) specimen, the second specimen is not tested, and
Results
The primary goal for a screening algorithm for CF is to identify cases, therefore minimizing the number of false negative results. To meet this goal, we investigated a lower initial IRT cutoff from a fixed value of 105 ng/mL. Examining the IRTs of the 312 infants with CF (non-meconium ileus) diagnosed with CF in Colorado with the IRT/IRT-based newborn screening approach between 1982 and 2007 and 20 additional infants who were initially missed by the newborn screening, we determined that a
Discussion
Our projected results indicate that IRT/IRT1↑/DNA provides a better alternative to IRT/IRT in states with 2 screening tests and has advantages compared with both IRT/IRT and IRT/DNA. The sensitivity of IRT/IRT1↑/DNA with an initial cutoff level of 60 ng/mL (approximately 97 percentile) is projected to be >99.5%, which corresponds to 1 potential missed case of every 700 000 live births. This is an improvement compared with the missed case rate for IRT/IRT in Colorado of at least 5%,12 and other
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Cited by (29)
Why cystic fibrosis newborn screening programs have failed to meet original expectations… thus far
2023, Molecular Genetics and MetabolismImproving outcomes for Colorado's IRT-IRT-DNA cystic fibrosis newborn screening algorithm by implementing floating cutoffs
2021, Molecular Genetics and MetabolismCitation Excerpt :The two-tier model measures IRT on a 1st screen collected at 24 to 48 h of life and if abnormal, a repeat IRT is measured from a 2nd screen collected at 8 to 14 days of life. To improve the sensitivity and positive predictive value of CF NBS, the Colorado Newborn Screening Program (CO-NSP) implemented an IRT/IRT/DNA algorithm in 2008, whereby two elevated IRT results with a fixed cutoff (≥ 60 ng/mL), are coupled with CF transmembrane conductance regulator (CFTR) variant analysis [12,13]. At the time of initiation, the 60 ng/mL cutoff represented the 97th percentile of IRT values.
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2021, International Journal for Parasitology: Parasites and WildlifeDiagnosis of Cystic Fibrosis in Screened Populations
2017, Journal of PediatricsImproving the Sensitivity and Positive Predictive Value in a Cystic Fibrosis Newborn Screening Program Using a Repeat Immunoreactive Trypsinogen and Genetic Analysis
2016, Journal of PediatricsCitation Excerpt :The strong laboratory leadership and established program were a critical foundation for implementing CF NBS in Texas. The Texas laboratory decided to deviate from the initial protocol described by Sontag et al,15 most notably testing all DBS from the second collection rather than limiting to just those with elevated IRTs. Although this decision adds significant costs to the program in assessing IRT on over one million samples in 3 years (97.7% of 1 184 205 first specimens had normal IRT), it also resulted in the identification of 6 newborns that had normal IRT concentrations on the first DBS, missing only 3.5% of cases, whereas 6.5% would have been missed had Texas implemented the same algorithm as the other states.
Newborn screening for cystic fibrosis
2016, The Lancet Respiratory MedicineCitation Excerpt :This strategy is often referred to as safety net, failsafe, or ultra-high IRT. Several different protocols exist, including referral straight to sweat testing or measurement of a second IRT at day 21 of age.21,24,27–29 The advantage of incorporating such a strategy is that it compensates for discrimination against ethnic populations with rarer CFTR mutations not included on a typical screening panel.
Supported by the Cystic Fibrosis Foundation SONTAG07AO, NIDDK RO1 DK61886, NHLBI U01 HL081335. The authors declare no real or perceived conflicts of interest.