New Biomarkers More Accurately Identify CF When Screening Newborns, Study Reports

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by Santiago Gisler |

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Newborn screening

Researchers in Canada found new blood biomarkers that can more accurately detect cystic fibrosis (CF) in newborns than standard screening methods — a discovery that could lead to improvements in early identification of this disease.

The study, “Metabolic Signatures of Cystic Fibrosis Identified in Dried Blood Spots for Newborn Screening Without Carrier Identification,” was published in the Journal of Proteome Research.

In widely used newborn screenings, a drop of blood is extracted from an infant’s heel and analyzed so clinicians might diagnose diseases before symptoms occur. In CF, these screenings can also help prevent or delay complications, and increase life expectancy.

Typical CF screens have relied on assessing immunoreactive trypsinogen (IRT) levels, a pancreatic enzyme that is elevated in CF patients, and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the main cause of CF. However, these tests can often diagnose CF in “healthy carriers,” resulting in “false positives.”

To find more reliable biomarkers, researchers at McMaster University analyzed dried blood spots taken from newborns to assess chemical signatures that differed between infants with and without CF. The samples were stored at Newborn Screening Ontario (NSO) at CHEO, a pediatric health and research center in Ottawa.

“The earlier CF is detected, the earlier it can be managed and treated, which means better health outcomes for affected infants, including their future growth and development,” the study’s lead author, Philip Britz-McKibbin, PhD, a professor in the department of chemistry & chemical biology at McMaster, said in a news release written by Michelle Donovan.

Blood samples from infants with confirmed CF (true CF cases) and healthy infants (screen positives or negatives) were analyzed and compared using mass spectrometry, a method that identifies compounds by measuring their mass and charge.

Researchers found 32 metabolites (including amino acids, like glutamine and tyrosine) that were differentially expressed between true CF cases and screen-negative controls. Also, when comparing true CF cases with screen-positive controls (with one identified CFTR mutation), they found 16 differentially expressed metabolites (including, for example, ophthalmic acid).

“These biomarkers provide new insights into the disease process early in life before symptoms are fully apparent,” Britz-McKibbin said. “Moreover, these compounds can be analyzed by mass spectrometry at incremental costs since it is already used for testing many other genetic diseases at newborn screening facilities around the world.”

Improved treatment, better nutrition, and lung transplants have resulted in an increased median age of survival among CF patients, which is now over 50 in Canada and around 40 in the U.S.

“Ontario started screening for cystic fibrosis in April 2007, and since that time over 400 children have already benefited from early recognition and early treatment. But for every one of these children, about 10 have had a false-positive result,” said Pranesh Chakraborty, medical director of NSO at CHEO. “We want to get this number down and are very hopeful that the new biomarkers discovered by this research project will help us do exactly that.”

According to John Wallenburg, PhD, chief scientific officer at Cystic Fibrosis Canada, normal screenings often require several tests to identify true CF cases, a process that can cause anxiety and distress in the affected families.

These new “data provide insights for more specific newborn screening, as well as early manifestations of the disease,” Wallenburg said.