Improved Algorithm for Screening Newborns for Cystic Fibrosis

A comparison of 3 algorithms designed to detect cases of “classic” cystic fibrosis in newborns with negative or inconclusive sweat test results supports the use of a fecal elastase test to identify pancreatic insufficiency requiring immediate treatment.

Investigators looked at experiences in Switzerland, which began testing newborns for cystic fibrosis in 2011. Hospitals there used an IRT-DNA-IRT (immunoreactive trypsinogent) algorithm followed by a sweat test and then tried 3 different protocols when sweat tests were not possible because of no sweat or insufficient sweat.

In 2011, sweat tests were repeated until enough sweat was collected for a successful test (protocol A). In 2012, healthcare facilities proceeded directly to DNA testing (protocol B). In 2013 and 2014, they measured fecal elastase to look for signs of pancreatic insufficiency (protocol C).

The ratio of correct cystic fibrosis diagnoses to inconclusive results immediately after birth was 7:1 (27/4) with protocol A, 2:1 (22/10) with protocol B and 14:1 (54/4) with protocol C. The mean time to definitive diagnosis was significantly shorter with protocol C than protocol A (33 days vs. 42 days; p = 0.014) or protocol B (33 days vs. 40 days; p = 0.036).

“The algorithm for the diagnostic part of the newborn screening used in the cystic fibrosis centers is important and affects the performance of a newborn screening for cystic fibrosis program with regard to the ratio correct cystic fibrosis diagnoses to inconclusive results and the time until definite diagnosis,” the study authors wrote in the Journal of Cystic Fibrosis. “Our results suggest to include fecal elastase after initial sweat test failure in the newborn screening for cystic fibrosis guidelines to keep the proportion of inconclusive diagnoses low and the time until definite diagnosis short.”

In the US, all states currently screen newborns for cystic fibrosis using either a genetic test, which shows whether the baby has faulty CFTR genes, or a blood test designed to show whether the pancreas is working properly. Neither test is definitive, so positive results on either will trigger a sweat test, which measures sweat salinity.

Sweat that’s saltier than normal indicates cystic fibrosis, but tests performed on newborns are often inconclusive due to insufficient sweat. Indeed, many healthcare providers wait until children are a month old to perform such tests in order to ensure enough sweat collection.

Unfortunately, delayed diagnosis means delayed treatment, which can harm children.

“The aim of newborn screening for cystic fibrosis is to detect children with ‘classic’ cystic fibrosis, where early treatment is possible and improves prognosis. Children with inconclusive cystic fibrosis diagnosis should not be detected, as there is no evidence for improvement through early treatment,” the authors of the new study wrote before noting the major problem with current screening recommendations. “No algorithm in current newborn screening guidelines explains what to do when sweat tests fail.”

Of course, parents who want to avoid any delay in diagnosing cystic fibrosis (along with other genetic conditions) do not have to wait for birth. Parents can screen themselves to see if they carry genes that could lead their children to have cystic fibrosis, and they can use prenatal tests like amniocentesis to diagnose such conditions long before children are actually born.