Updated guidelines aim to boost equity in CF newborn screening
New recommendations from CFF call for follow-up genetic testing if positive
The Cystic Fibrosis Foundation (CFF) has published updated newborn screening (NBS) guidelines to help ensure better equity in the diagnosis and treatment of cystic fibrosis (CF) in the U.S.
A key recommendation is that, should an initial NBS result be positive, follow-up genetic testing should involve all possible CF-causing mutations — including rare ones more likely to affect racial and ethnic minorities that are currently excluded in some states.
“Newborn screening should be updated and standardized so that it benefits all families equally,” Meghan McGarry, MD, one of the study’s lead authors, a pediatric lung specialist and associate professor at the University of Washington School of Medicine, said in a university news story. McGarry stressed the importance of CF newborn screening in babies with Black, Hispanic, Asian, and American Indian ancestry, as well as multiracial heritage.
“All babies deserve early diagnosis and early treatment so they can have the best outcomes,” McGarry added.
The guidelines were described in “Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation,” a study published in the International Journal of Neonatal Screening.
CF newborn screening required in all US states since 2010
CF is caused by mutations in the CFTR gene, leading to a dysfunctional or missing protein of the same name, which is involved in regulating the flow of salt and water in and out of cells. Consequently, thick and sticky mucus accumulates throughout the body, leading to breathing problems and nutritional deficiencies, among other symptoms.
The earlier CF is diagnosed, the sooner critical treatments can be started to avoid more serious complications.
“Because the disease impairs the newborn’s ability to absorb nutrients, a delay in diagnosis of a week or so can lead to damaging weight loss and other complications,” McGarry said. “If the diagnosis is missed, you will often see serious growth problems and permanent lung damage as the child grows older.”
Since 2010, all babies in the U.S. are screened for CF via NBS, which has contributed to improved outcomes for people with the genetic disease in recent years.
NBS for CF involves collecting a small blood sample from the newborn via a heel prick and testing it for immunoreactive trypsinogen, or IRT, a protein that’s usually elevated in newborns with the disease. If IRT levels are high, additional tests aim to identify a CFTR mutation and confirm the diagnosis.
However, while all states include CF in their NBS programs, protocols vary.
Per the research team, “variations among states in the U.S. regarding CF NBS algorithms and follow-up practices can lead to differences in equity, sensitivity, and timeliness of intervention.”
A key variable is that states differ in the CFTR mutations for which they’ll test. More than 1,000 mutations are known to cause CF, but some states only test for one common one, and others look at a small group of a couple dozen.
Cases most likely to be missed are those associated with rarer mutations, which occur more commonly in racial and ethnic minorities, including Asian, Hispanic, Black, American Indian, and multiracial infants. This can put these children at a greater risk of serious complications arising from delayed treatment, per the researchers.
Negative results should not rule out CF if baby shows symptoms
The goal of the guidelines is to develop recommendations on best practices for newborn screening that will reduce disparities in diagnosis and care. These recommendations were developed by a multidisciplinary committee that included clinicians, researchers, parents, and NBS program experts.
The committee suggested that, rather than having a single fixed cutoff value for IRT, the metrics should use floating cutoffs that better account for factors such as seasonal changes in temperature that can affect the results.
Should IRT levels be elevated, it’s recommended that labs should screen for all mutations associated with CF — not just a small group of the most common ones. Labs should run these tests at least twice a week, or as often as resources allow, to ensure no delays in results, the committee urged.
If genetic testing for CFTR variants is not comprehensive, the committee also recommended other pathways for diagnostic testing depending on the types of molecular analyses that are performed.
Finally, the authors suggested that a child’s primary care provider and a CF specialist should be notified of abnormal screening results.
Importantly, however, the committee emphasized that NBS results are not enough to definitively establish CF: A positive result doesn’t mean a newborn certainly has the disease, and a negative finding does not mean they certainly don’t, the member stressed.
Families have faced difficulties getting further testing, despite the baby showing classic signs of cystic fibrosis, based on a normal initial screen. … If a baby presents with signs and symptoms of [CF], pediatricians should not rule out cystic fibrosis solely on the basis of their normal newborn screening.
“If a baby presents with signs and symptoms of cystic fibrosis, pediatricians should not rule out cystic fibrosis solely on the basis of their normal newborn screening,” McGarry said, noting that “families have faced difficulties getting further testing, despite the baby showing classic signs of cystic fibrosis, based on a normal initial screen.”
Additional evaluations, especially the gold-standard sweat chloride test, are needed to definitively establish CF after a positive NBS result, per the committee.
The members acknowledged that resources could limit the feasibility of adopting these practices in some states.
“States are encouraged to make incremental changes to improve their CF NBS protocols as they work toward full guideline implementation,” the committee concluded.
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