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.