Researchers call for better screening of newborns at United States.
New study finds that cystic fibrosis goes undetected more often during newborn screening in non-white babies than in white babies, leading to a higher risk of irreversible lung damage and other serious outcomes in black newborns, Hispanic, Asian, Native American and Alaskan Native people.
Genetic panels used in newborn screening programs vary by state, but most tend to test for CF gene mutations that are common in white populations, while excluding mutations more common in non-white populations. white women, said Meghan McGarry, MD, associate professor of pediatrics at UC San Francisco (UCSF) Benioff Children’s Hospitals and first author of the study, published today in Pediatric Pulmonology.
Newborn screenings are supposed to be an equal public health measure for all populations, but in practice, we are actually… create disparities because children of color are not diagnosed with cystic fibrosis until later in life. This means that they are treated later when symptoms appear, and their results 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 severe symptoms, like stunting, and is associated with better nutrition, better lung outcomes, and survival.
Better screenings are needed
To determine case detection rates, the researchers analyzed the genetic mutations of 46,729 people in the Cystic Fibrosis Foundation’s 2020 patient registry, then calculated the rate of delayed diagnosis or false-negative tests by race and by ethnicity. They also compared data across states.
In most states, a newborn screen is only positive if at least one variant of the disease-causing cystic fibrosis transmembrane conductance regulator (CFTR) gene is detected. This study found that the detection rate of at least one CFTR gene variant in known CF patients was 56-77% in Asians, 73-86% in Blacks, 84-91% in American Indians and Alaska Natives and 81-94% among Hispanics, compared to 95-97% among whites. The differences between races and ethnicities were even greater when the tests aimed to detect two variants of CTFR instead of just one.
States with greater racial and ethnic diversity had lower detection rates for each panel of variants. Similarly, detection rates were higher overall with genetic panels with more variants than those with fewer variants, although this was not the case for all races/ethnicities.
“For newborn screenings to be fair, they must include panels of CTFR variants that reflect the racial and ethnic diversity of the population,” McGarry said. “Three states – Wisconsin, New York and California – do it well and use full sequencing, while systematically monitoring and reviewing who is unscreened, what variants they had, and whether to add variants to panels. »
Although race and ethnicity are social constructs, the genes that cause cystic fibrosis vary by race, ethnicity and region, said Susanna McColley, MD, professor of pediatrics at Northwestern University Feinberg School of Medicine and physician at the Ann & Robert H. Lurie Children’s Hospital in Chicago, as well as lead author of the study.
“Bias in newborn screening tests is coupled with clinician bias once morest diagnosing CF in Black, Hispanic, Asian, and Native American/Alaskan babies that can have fatal consequences,” McColley said. . “We hope this work will lead to more equitable testing in all states. »
Two diseases depending on the breed
About 20% of cystic fibrosis cases are from racial and ethnic minority groups, and the disease affects people of all ethnicities and races in the United States. Delays in detecting and treating non-white patients have essentially created two diseases, McGarry noted.
“These days, most white children with cystic fibrosis are never hospitalized; for them, it is an ambulatory disease and they will probably have a full life. However, if you’re not white, you’re more likely to be the one who’s in the hospital all the time with a serious illness,” McGarry said. “We currently have a young patient who underwent normal newborn screening, and was only diagnosed with cystic fibrosis when he was on a ventilator and intubated with multiple pneumonias and permanent lung damage. »
The aim is to diagnose children before they are one month old to avoid irreversible damage, she added.
“As early as four weeks, you can already see permanent damage to the lungs. Some even have symptoms in utero, although most undiagnosed babies start having respiratory symptoms around 4-8 weeks,” McGarry said. “Good research shows that if you can be diagnosed by newborn screening before you have a lot of illnesses – rather than being diagnosed with symptoms – you have much better long-term outcomes. »
Source :
University of California–San Francisco
Journal reference:
McGarry, M.E., et al. (2022) Detection of disease-causing CFTR protein variants in state newborn screening programs. Pediatric Pulmonology. doi.org/10.1002/ppul.26209.