Research Uncovers Inequities in Diagnosis of Infants with Cystic Fibrosis

Research by Susanna McColley, MD, from Lurie Children’s, and colleagues found that too many infants receive a delayed diagnosis of cystic fibrosis (CF), which leads to worse outcomes. This is particularly the case for infants who are Black, Hispanic, Asian, or multiracial. In 2023, these groups made up 22 percent percent of newly diagnosed people with CF, according to the Cystic Fibrosis Foundation Registry.

CF is a genetic disorder that causes problems with digestion and breathing. It is included in newborn screening. If newborn screening results are out of normal range, parents need to follow up with their baby’s pediatrician right away. Further evaluation is necessary to diagnose CF, and this should occur within the first month of life so that treatment can begin as soon as possible.

“Our research found that CF diagnosis in babies within 10 days of age produces better height and weight outcomes compared to diagnosis at 6 weeks of age, so time is of the essence,” said Dr. McColley, an internationally recognized expert in cystic fibrosis newborn screening, pediatric pulmonologist at Lurie Children’s and Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “With CF, our big focus in infancy is on nutrition. We know that good nutrition improves lung function, and better height and weight measures are associated with longer lifespan in people with CF.”

When CF was first described in 1938, it was usually fatal in early life. Thanks to improvements in diagnosis and treatment, the median predicted survival is 61 years of age among people with CF born between 2019 and 2023.

So why is CF diagnosis more often delayed in infants of color? Dr. McColley explained that one of the reasons is diagnostic bias, which stems from lack of awareness among physicians that CF can occur in babies of all racial and ethnic backgrounds.

“CF was originally described as occurring in children from broad geographies and ancestries. Unfortunately, in textbooks and research reports, it is often described as the most common genetic fatal disease in people of European ancestry. Medical schools and residency programs have therefore perpetuated the misconception that CF is a concern only in White babies,” she said.

Also, people with CF from minoritized groups are more likely to have zero or only one variant of the gene that causes CF detected on newborn screening tests, she added. This is because newborn screening panels tend to not include genetic variants that are rarer.

An infant has CF when two CF-causing gene variants are inherited, one from each parent. 

“While over 1,000 gene variants have been shown to cause CF, many states use limited gene variant panels, which miss variants that are not predominant in European populations and/or are rarer,” said Dr. McColley. “Newborn screening panels need to become more representative of the entire population and include less common genetic variants to identify more Black, Hispanic and Asian babies with CF.”

When zero variants are detected, the screening test is falsely called negative (or normal). When only one variant is detected on newborn screening, physicians may assume that the infant carries the gene defect but is not affected and can delay referral.  

However, one in 10 of infants who are diagnosed with CF have only one gene variant detected. They are generally diagnosed later, which raises the risk of complications and is associated with worse growth in preschool years, which then increases the risk of lower lung function and early mortality.

Dr. McColley emphasized that since newborn screening results can be falsely normal, if a baby develops symptoms of CF in the first months of life, including bowel obstruction and poor weight gain, an immediate referral for diagnostic evaluation is necessary. Onset of symptoms can also be delayed, she added.

“We need immediate action to raise awareness and dispel long-held misconceptions about this disease, and ongoing research on methods to assure that every baby with CF has an early diagnosis,” said Dr. McColley.

To learn more about CF and newborn screening, view a recent report that Dr. McColley co-authored, in partnership with the Cystic Fibrosis Foundation and funded by the Centers for Disease Control and Prevention (CDC).

Dr. McColley also discusses newborn screening and her work promoting equity in early diagnosis and care for CF on the In Pursuit podcast from Stanley Manne Children’s Research Institute at Lurie Children’s.

Dr. McColley’s research on newborn screening was supported by the Rosenau Family Research Foundation.