Newborn screening (NBS) algorithms for cystic fibrosis (CF) vary in the United States, especially among racial and ethnic groups, according to a cross-sectional analysis published in the journal Pediatric Pulmonology.

In fact, the NBS algorithms include different CF transmembrane conductance regulator (CFTR) variants.

The researchers sought to identify differences in detection rates by race and ethnicity among CFTR variant panels, to define each US state detection rate for CFTR variant panels and to describe the rate of false-negative NBS and delayed diagnoses based on race and ethnicity.

Since 2009, all of the 50 US states and the District of Columbia screen newborns for CF. It is well known that early diagnosis and treatment of CF via NBS programs reduce such severe symptoms as failure to thrive and salt depletion, and are linked to improved pulmonary outcomes, nutrition, and survival.

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With most NBS algorithms usually requiring the detection of 1 or more CFTR variant for a test to be considered positive, a test could erroneously be reported as negative if an infant had CF, but no variants were detected. Because CFTR variant frequency differs among racial and ethnic groups, the concern exists that CF NBS genetic panels can be associated with a disparity in diagnosis.

The current study evaluated CFTR variants in a total of 46,729 genotyped persons in the CF Foundation Patient Registry in 2020, which is intended to estimate the detection of 1 or more CFTR variant through 7 genetic panels by race and ethnicity among genotyped people with CF, or people with CFTR-related metabolic syndrome (CRMS) or with CF screen-positive inconclusive diagnosis.

Results of the study showed that for all panels, detection of 1 or more CFTR variant was highest among non-Hispanic White people with CF (ie, 87.5%-97.0%) and lowest among Black, Asian, and Hispanic people with CF (ie, 41.9%-93.1%). In addition, detection of 1 or more CFTR variant was lowest among Black, Asian, and Hispanic people with CRMS/CFTR-related disorders (ie, 48.4%-64.8%).

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States with increased racial and ethnic diversity were shown to have lower detection rates for all of the panels evaluated. In all, 3.8% of people with CF had a false-negative NBS and 11.8% experienced a delayed diagnosis. People with CF who were Black, Hispanic, or of mixed race were overrepresented.

The authors concluded that “These results indicate that nationwide quality improvement in detection of disease-causing CFTR variants is needed.”


McGarry ME, Ren CL, W R, Farrell PM, McColley SA. Detection of disease-causing CFTR variants in state newborn screening programs. Pediatr Pulmonol. Published online October 13, 2022. doi:10.1002/ppul.26209