Screening Infants Helps, But Care Needs Improvement

The implementation of newborn screening for cystic fibrosis (CF) in the U.S. allowed for early diagnosis and clinical evaluation of affected infants, and reduced rates of serious lung infections and hospitalizations over time, according to data from the first nine years of universal screening.

However, early nutritional deficits and hospitalizations in the first year of life remained high, highlighting there is still room for improvement in CF care following a positive diagnosis from newborn screening (NBS), the researchers noted.

The study, “Outcomes of infants born during the first 9 years of CF newborn screening in the United States: a retrospective Cystic Fibrosis Foundation Patient Registry cohort study,” was published in the journal Pediatric Pulmonology.

Estimated to affect more than 70,000 people worldwide, and 30,000 people in the U.S. alone, CF is a genetic disease characterized by the production of salty sweat and abnormally thick mucus in the lungs, digestive tract, and reproductive system, affecting how they work.

This makes CF patients more susceptible to chronic lung infections — particularly of opportunistic bacteria such as the highly antibiotic-resistant Pseudomonas aeruginosa — and pancreatic insufficiency, a condition in which the pancreas is unable to release enough enzymes to properly digest food.

Pancreatic insufficiency can lead to gastrointestinal problems, malnutrition, and impaired growth, which is particularly problematic in children. CF patients often are advised to take enzyme supplements through pancreatic enzyme replacement therapy (PERT).

Given the proven importance of early diagnosis and treatment of CF to achieve better health outcomes and quality of life, several countries have added CF to the list of conditions screened for in newborns.

CF newborn screening was implemented in all U.S. states and Washington D.C., by 2010. It involves the collection of a few drops of blood through a heel prick and the initial analysis of the levels of immunoreactive trypsinogen (IRT), a protein commonly elevated in CF.

If abnormally high IRT levels are detected the test is repeated, or a genetic analysis for the most common CF-causing mutations is conducted; the nature of the second test varies between states. A positive screening result is typically confirmed with a sweat test.

Notably, a previous study reported a temporal association between implementation of NBS for cystic fibrosis in the U.S. and better nutritional outcomes and fewer P. aeruginosa infections.

However, “the outcomes of infants born after universal screening started throughout the US have not been described,” the researchers wrote.

Now, scientists in the U.S., in collaboration with the Cystic Fibrosis Foundation (CFF), evaluated the age at diagnosis and clinical evaluation, as well as clinical outcomes of infants diagnosed with CF during the first nine years of universal NBS in the U.S.

The study, based on data from the CFF Patient Registry, was designed “to form the basis of additional analyses and to plan quality improvement initiatives,” they wrote.

The researchers analyzed data from 6,354 infants born from 2010 to 2018 across all U.S. states with age of recorded CF diagnosis between birth and 1 year. Patients were divided in three groups according to year of birth: 2010–2012 (2,299 infants), 2013–2015 (2,172 babies), and 2016–2018 (1,883 babies).

Age of center-reported diagnosis, age at first CF event (defined as earliest sweat test, clinic visit, or hospitalization), demographics, and clinical outcomes were compared among the three groups.

Results showed that mean age at diagnosis was 15 days in 2010–2012 and 14 days thereafter. Over time, the proportion of infants diagnosed after 2 months of age dropped from 11% to 7.8%.

Most (77%) infants had their first CF event within the first month of life, with the most common being a sweat test. Age at first event, including sweat test and clinic visit, was reduced over time, suggesting closer attention to newborns diagnosed with CF.

However, age at hospitalization at first CF event remained stable.

At first visit, and across groups, failure to thrive/malnutrition was reported in 5–6% of infants, but 38–40% showed lower weight relative to most babies of the same age and sex, indicating that malnutrition “was likely under-recognized,” in these patients, the researchers wrote.

Across all groups and ages, infants’ median height-for-age was below 0, indicating they were shorter than normal.

Over time, breastfeeding increased and oral supplemental feeding reduced, suggesting less need for nutritional intervention. PERT use also dropped over time, which may be due to closer monitoring of pancreatic function and recovery as infant care guidelines were implemented, the team noted.

Also, there was a significant reduction in hospitalizations for all causes and for pulmonary exacerbations (lung function worsening) over time, with the exception of infants younger than 1 year, whose rates showed a descending trend that failed to reach statistical significance.

Notably, about one-third of infants were hospitalized in the first year of life, most commonly for pulmonary exacerbations, highlighting that further improvements can be made in this area.

The proportion of infants positive for P. aeruginosa infection also was reduced over time and in all age groups, which “is an important observation with implications regarding the risk of lung disease in early childhood,” the team wrote.

These findings highlight that NBS for CF resulted in most infants being diagnosed in the first month of life and in several positive health impacts, “but early life nutritional deficits and a high rate of infant hospitalizations persist,” the researchers wrote.

“We hypothesize that optimizing outcomes will require more efficient diagnosis, starting with improved timeliness of evaluation after a positive CF screening test, more effective infant nutritional management, and further development of preventive lung disease therapies,” the team concluded.