Newborn screenings are more likely to miss a diagnosis of cystic fibrosis in non-white babies

Newborn screenings are more likely to miss a diagnosis of cystic fibrosis in non-white babies

Researchers are calling for better newborn screening in the US

Cystic fibrosis is more often missed in newborn screenings for non-white babies than for white babies, putting black, Hispanic, Asian, American Indian and Alaskan newborns at higher risk of irreversible lung damage and other serious consequences, a new study finds.

The genetic panels used in newborn screening programs vary by state, but most tend to test for cystic fibrosis gene mutations that are common in white populations while excluding mutations that are more common in nonwhite populations, said Meghan McGarry, MD, associate professor of pediatrics at UC San Francisco (UCSF) Benioff Children’s Hospitals and lead author of the study published today in Pediatric Pulmonology.

Newborn screenings are intended to be a public health measure that is consistent across all populations, but in practice we are actually creating disparities because children of color go undiagnosed with cystic fibrosis until old age. This means they receive treatment later when symptoms appear, and their outcomes are often worse.”

Meghan McGarry, MD, associate professor of pediatrics at UC San Francisco (UCSF) Benioff Children's Hospitals.

Cystic fibrosis is one of the most common genetic diseases, with approximately 1,000 new cases diagnosed each year. The disease causes a protein that helps regulate mucus to malfunction, which can lead to blockages and trapped germs and ultimately infections such as bronchitis and pneumonia. Early diagnosis and treatment can reduce serious symptoms such as failure to thrive and is associated with improved nutrition, better pulmonary outcomes and survival.

Better screenings needed

To determine case detection rates, researchers analyzed the genetic mutations of 46,729 people in the 2020 Cystic Fibrosis Foundation Patient Registry and then calculated the rate of delayed diagnoses or false-negative tests by race and ethnicity. They also compared data between states.

In most states, newborn screening is positive only if at least one disease-causing variant of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is detected. This study found that the detection rate of at least one CFTR variant in patients with known cystic fibrosis was 56-77% in Asian patients, 73-86% in black patients, 84-91% in American Indian and Alaska Native patients, and 81-94% in Hispanic patients, compared to 95-97% in white patients. The differences between races and ethnicities were even greater when testing aimed to detect two CTFR variants instead of just one.

The states with greater racial and ethnic diversity had lower detection rates for each variant panel. Likewise, overall detection rates were higher for genetic panels containing more variants compared to fewer variants, although this was not the case for all races/ethnicities.

Genetics & Genomics eBook

Compilation of the top interviews, articles and news from the last year. Download a copy today

“For newborn screenings to be equitable, they must include CTFR variant panels that reflect the racial and ethnic diversity of the population,” McGarry said. “Three states – Wisconsin, New York and California – are doing this well, using full sequencing and systematic surveillance and review of who is missing, what variants they had and whether they should add variants to the panels.”

While race and ethnicity are social constructs, the genes that cause cystic fibrosis vary by race, ethnicity and region, Dr. Susanna McColley, professor of pediatrics at Northwestern University Feinberg School of Medicine and physician at Ann & Robert H. Lurie Children's Hospital of Chicago, and senior author of the study.

“Bias in newborn screening testing is coupled with clinician bias against diagnosing cystic fibrosis in Black, Hispanic, Asian and Alaska Native/Alaska Native babies, which can have fatal consequences,” McColley said. “We hope this work will lead to more equitable screening across all states.”

“Two diseases” based on race

About 20% of cystic fibrosis cases come from racial and ethnic minorities, and the disease occurs in people of all ethnicities and races in the United States. The delays in identifying and treating nonwhite patients have essentially created two diseases, McGarry noted.

"Most white children with cystic fibrosis today are never hospitalized; for them, it's an outpatient illness and they're likely to live full lives. However, if you're not white, you're more likely to be the one in the hospital all the time with a serious illness," McGarry said. “We now have a young patient who had a normal newborn screening and was not diagnosed with cystic fibrosis until he was placed on the ventilator and intubated with multiple pneumonias and permanent lung damage.”

The goal is to diagnose children before they are a month old to avoid irreversible damage, she added.

"As early as four weeks, you can already see permanent lung damage. Some even have symptoms in utero, although most undiagnosed babies have respiratory symptoms around 4-8 weeks," McGarry said. “There is good research that shows that if you can be diagnosed through newborn screening before you have a lot of illnesses – rather than being diagnosed with symptoms – you will have much better long-term outcomes.”

Source:

University of California – San Francisco

Reference:

McGarry, ME, et al. (2022) Detection of disease-causing CFTR variants in state newborn screening programs. Pediatric Pulmonology. doi.org/10.1002/ppul.26209.

.