Introduction
Cystic fibrosis (CF) newborn screening (NBS) for has been offered
nationwide in the USA since 2010. The CFF has recommended nationwide
screening, but it deferred to individual states for planning and
screening protocol (algorithm) selection[1]. All CF NBS algorithms
employ measurement of immunoreactive trypsinogen (IRT) as the first
step[2]. Because IRT can be elevated in infants without CF, one of
two different strategies can be used to improve the specificity of NBS.
In the first strategy (IRT/IRT), a repeat IRT is obtained in
approximately 2 weeks, and if still elevated sweat testing is performed.
The other strategy (IRT/DNA) utilizes CF transmembrane conductance
regulator (CFTR ) gene variant analysis, and infants with 1 or 2CFTR variants are referred for sweat testing. Over time, the
IRT/DNA strategy has been found to be more sensitive and faster than the
IRT/IRT strategy, and as of 2020 all states have employed an IRT/DNA
approach or incorporated DNA testing into their IRT/IRT algorithm
(IRT/IRT/DNA)[3-5].
The methods used to define an elevated IRT and to select CFTRvariants for DNA analysis can affect the ability of CF NBS to identify
infants with CF. States can either use a fixed cutoff value to define an
elevated IRT, but this does not account for variability in IRT
measurement reagents and seasonal variation in IRT due its heat
lability[6, 7]. To account for these factors, other states utilize a
floating cutoff determined by a rolling daily average. The specificCFTR variants selected for DNA analysis as well as the total
number of variants analyzed can affect the sensitivity of CF NBS, and
since infants from minority populations are less likely to have common
CFTR variants they may potentially be missed by NBS depending upon the
variants selected.
The demographics of the CF population in the USA have changed markedly
in the last 20 years[8]. In 2000, 9.2% of patients in the CF
Foundation Patient Registry were African-American or Hispanic; as of
2020, this has increased to 14.3%. Analysis of the last 10 years of NBS
data shows that about 20% of newly diagnosed patients were from racial
or ethnic minority populations[9]. These demographic changes, along
with the issues of IRT cutoffs and CFTR variant selection[10,
11], raise concerns about the ability of different state CF NBS
algorithms to identify newborns with CF, especially those from minority
populations. Somewhat surprisingly, a comprehensive database of CF NBS
algorithms by state in the USA has never been report. With that
background in mind, the objective of our work was to fill this knowledge
gap by using an online survey to acquire detailed data on CF NBS
algorithms in every state in the USA and to identify areas for improving
diagnosis of infants with CF, especially those from minority
populations.