Babies with CF Not Diagnosed in Newborn Screenings Do More Poorly, Study Finds

Children diagnosed with cystic fibrosis (CF) months after their birth have worse clinical outcomes than those diagnosed as newborns, a study reports. Its authors argue for improvements in CF diagnostic programs to detect these cases in infants as early as possible.

The study, “Differences In Outcomes Between Early And Late Diagnosis Of Cystic Fibrosis In The Newborn Screening Era,” was published in the Journal of Pediatrics.

Newborns are screened for CF in many countries, through a process that looks for whether the child has increased levels of immunoreactive trypsinogen (IRT) and/or one or two copies of the F508del mutation within the CFTR gene, which leads to CF. But not all CF cases are identified through newborn screenings, and the condition is only caught when symptoms begin to appear. “Accounting for differences in IRT cutoffs and the number of mutations in DNA panels worldwide, the sensitivity of NBS [newborn screenings] varies between 86.6% and 97.5%,” the study noted.

These screening programs are also a matter of intense debate, primarily because of a lack of clinical trial data. The longer term health of CF children missed in these screening is also largely unknown.

This study aimed to determine if children with a late CF diagnosis, despite being screened as newborns, had different clinical outcomes than newborns diagnosed with CF through a screening.

Researchers retrospectively analyzed data from CF patients in New South Wales, Australia, from 1988 to 2010. A late diagnosis was considered for the cases in which screenings returned with negative results (negative IRT or no F508del), or returned with a positive result — but a follow-up sweat chloride test was below 60 mmol/L and CF was not diagnosed. Patients were matched according to age, gender, hospital, and exocrine pancreatic status.

The team identified 45 cases of CF late diagnosis (39 NBS-negative and 6 NBS-positive), and compared them to 90 CF children identified as newborns. The median age in the late diagnosis group was 1.35 years, and 0.12 years (nearly two months of age) in the early diagnose group.

Results showed that those babies diagnosed months later had more respiratory symptoms at the time of diagnosis, a higher rate of hospital admissions per year due to respiratory illnesses, worse lung function, and higher rates of chronic infection with Pseudomonas aeruginosa. Not surprisingly, these children also showed a failure to thrive, the study noted.

“[T]his study serves to highlight the outcomes of those patients with CF who have a missed or late diagnosis despite NBS,” the researchers wrote. “A late diagnosis seems to be associated with worse health at diagnosis and worse outcomes with regard to growth and respiratory outcomes.”

For this reason, newborn screening programs for CF are important and worth supporting, they concluded. But, they added,  screening failures also highlight that these programs still require attention and improvement.