First guideline on newborn screening for cystic fibrosis calls for changes in practice to improve outcomes

The United States Cystic Fibrosis Foundation released the first guideline on newborn screening for cystic fibrosis (CF), in order to improve timely detection of CF in infants from all racial and ethnic backgrounds. The new guideline, based on systematic literature reviews and published in the International Journal of Neonatal Screening, reflects rigorous scientific investigation and perspectives from parents, CF specialists, public health representatives, primary care providers and genetic counselors.

CF is a genetic disorder that causes problems with digestion and breathing. Currently, newborns in every state are screened for CF. However, great variation in practice and the genetic panels used contributes to missed and delayed diagnosis, which leads to worse outcomes.

“Delays more often occur in diagnosis of infants who are Black, Hispanic, or Asian, in part because these groups tend to have CF-causing gene variants that are rarer and seldom included in the newborn screening panels. These infants frequently screen negative and get diagnosed much later when they exhibit symptoms. The delay in care causes more severe illness trajectory,” explained co-senior author Susanna McColley, MD, an internationally recognized expert in CF newborn screening, pediatric pulmonologist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine.

“The most common CF-causing gene variant, which is featured in all genetic panels, is predominantly found in people of European descent, whereas it is much less frequent in people of other ancestries,” she said. “It is important to recognize that babies of any race and ethnicity can have CF. Newborn screening panels need to become representative of the entire population.”

The new guideline sets out to make newborn screening for CF more equitable by recommending that states test for all CF-causing gene variants. As of September 2024, 1,085 CF-causing gene variants have been recognized. Current state panels range from including only the single most common CF-causing gene variant to including almost all variants.

“We realize that big changes will take time to implement and intermediate improvement strategies will be needed,” said Dr. McColley. “For example, if a state can’t screen for all gene variants that cause CF, then genetic sequencing could be performed in addition to the limited panel currently used.”

Another key recommendation that aims to prevent missed cases of CF involves a test that measures the levels of a chemical made by the pancreas called immunoreactive trypsinogen (IRT), which is increased in people with CF. This test is part of CF newborn screening in every state and is performed prior to genetic testing. According to the new guideline, if IRT is very high, CF should be suspected even if the genetic test result is normal, unless all known gene variants that cause CF are included in the genetic test.

To improve the timeliness of diagnostic evaluation, the guideline recommends that both the primary care provider and CF specialist get notified when newborn screening results are abnormal (or positive). This is very different from current practice, which varies by state and usually does not include a CF specialist in the communication of positive results.

“Time is of the essence, and we need better coordination between public health departments, primary care and CF specialists to promote timely diagnostic follow-up of positive newborn screening results,” said Dr. McColley. “It is also critical for parents to be proactive and ask their baby’s doctor about newborn screening results, and make sure that follow-up occurs as soon as possible if the results are abnormal.”

To learn more about CF and newborn screening, view a recent report that Dr. McColley co-authored, in partnership with the Cystic Fibrosis Foundation.

The United States Cystic Fibrosis Foundation released the first guideline on newborn screening for cystic fibrosis (CF), in order to improve timely detection of CF in infants from all racial and ethnic backgrounds. The new guideline, based on systematic literature reviews and published in the International Journal of Neonatal Screening, reflects rigorous scientific investigation and perspectives from parents, CF specialists, public health representatives, primary care providers and genetic counselors.

CF is a genetic disorder that causes problems with digestion and breathing. Currently, newborns in every state are screened for CF. However, great variation in practice and the genetic panels used contributes to missed and delayed diagnosis, which leads to worse outcomes.

“Delays more often occur in diagnosis of infants who are Black, Hispanic, or Asian, in part because these groups tend to have CF-causing gene variants that are rarer and seldom included in the newborn screening panels. These infants frequently screen negative and get diagnosed much later when they exhibit symptoms. The delay in care causes more severe illness trajectory,” explained co-senior author Susanna McColley, MD, an internationally recognized expert in CF newborn screening, pediatric pulmonologist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine.

“The most common CF-causing gene variant, which is featured in all genetic panels, is predominantly found in people of European descent, whereas it is much less frequent in people of other ancestries,” she said. “It is important to recognize that babies of any race and ethnicity can have CF. Newborn screening panels need to become representative of the entire population.”

The new guideline sets out to make newborn screening for CF more equitable by recommending that states test for all CF-causing gene variants. As of September 2024, 1,085 CF-causing gene variants have been recognized. Current state panels range from including only the single most common CF-causing gene variant to including almost all variants.

“We realize that big changes will take time to implement and intermediate improvement strategies will be needed,” said Dr. McColley. “For example, if a state can’t screen for all gene variants that cause CF, then genetic sequencing could be performed in addition to the limited panel currently used.”

Another key recommendation that aims to prevent missed cases of CF involves a test that measures the levels of a chemical made by the pancreas called immunoreactive trypsinogen (IRT), which is increased in people with CF. This test is part of CF newborn screening in every state and is performed prior to genetic testing. According to the new guideline, if IRT is very high, CF should be suspected even if the genetic test result is normal, unless all known gene variants that cause CF are included in the genetic test.

To improve the timeliness of diagnostic evaluation, the guideline recommends that both the primary care provider and CF specialist get notified when newborn screening results are abnormal (or positive). This is very different from current practice, which varies by state and usually does not include a CF specialist in the communication of positive results.

“Time is of the essence, and we need better coordination between public health departments, primary care and CF specialists to promote timely diagnostic follow-up of positive newborn screening results,” said Dr. McColley. “It is also critical for parents to be proactive and ask their baby’s doctor about newborn screening results, and make sure that follow-up occurs as soon as possible if the results are abnormal.”

To learn more about CF and newborn screening, view a recent report that Dr. McColley co-authored, in partnership with the Cystic Fibrosis Foundation.