Without newborn screening, cystic fibrosis (CF) is not diagnosed until symptoms begin to appear and are advanced enough to cause delayed growth and respiratory problems. Usually, this occurs in the first two years of life -- but by the time the diagnosis is made, damage has already been done.
With newborn screening, however, CF is diagnosed in the first few weeks of life and babies can begin treatment immediately, thus avoiding the malnutrition and respiratory distress that would otherwise be inevitable. Early diagnosis and treatment also has the potential to increase the life expectancy of people with CF. People currently living with cystic fibrosis can realistically expect to live into their mid-thirties, but some studies predict that babies born today with CF will live into their fifties because of early diagnosis and better treatment.
Newborn screening for cystic fibrosis is a test to detect the possibility of having cystic fibrosis. It is the first step in a process that ultimately leads to diagnosis of cystic fibrosis, identification of CF carriers, or eliminates both possibilities. If results of the initial screening are positive, that does not mean a baby has cystic fibrosis. A positive screening simply means that further testing must be done to determine the significance of the positive result.
First Step - Raising the Red Flag
The first step of newborn screening is a blood test that is done a couple of days after birth. Blood is drawn from the baby and sent to a state lab to screen for several disorders. The screening test for CF looks for elevated levels of a substance called immunoreactive trypsinogen (IRT), which is an enzyme created by the pancreas. Babies born with cystic fibrosis often have high levels of IRT in their blood, but other conditions can also cause the enzyme to be elevated.
If a newborn screening for CF is positive, that means that high levels of IRT were detected. Each state determines its own guidelines for normal and abnormal levels of IRT. Some states have a fixed value that constitutes a positive level and some states select a percentage of the highest IRT levels reported each day.
Second Step – Genetic Testing
If the initial newborn screening for IRT is positive, most states do another test on the blood to find out if the baby has a mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). There are more than 1,200 known mutations of the CFTR gene that cause cystic fibrosis. It is not practical or financially feasible to test for all of them, but most states test for several of the most common mutations. Again, each state decides which mutations to include in the testing panel.
If a mutation of the CFTR gene is detected, the baby is either a CF carrier or has cystic fibrosis disease. The state lab will notify the baby’s primary physician and in some states they will also notify the county health department or other agency that is approved and trained to provide follow-up with families.
If IRT levels are elevated but no mutation of the CFTR gene is detected, the results of both tests are sent to the baby’s primary care physician who will determine if further testing is needed.
Third Step – Sweat Test
The sweat chloride test, or sweat test, has been the gold standard test used to diagnose cystic fibrosis for many years. The test measures the amount of salt in a person’s sweat, which is higher than normal in people with CF. A chloride content greater than 60 mmol/liter is considered a positive result.
When the primary care physician receives the results of the newborn screening from the state laboratory, he or she will decide whether further testing should be done. If IRT levels were elevated but no CFTR mutation was detected, the primary physician may order a sweat test anyway just in case the baby has one of the less common mutations that was not included in the genetic testing panel.
If the newborn screening detected a CFTR mutation, the primary care physician will order a sweat test to determine if the baby has CF disease. If the sweat chloride test is positive, the baby has cystic fibrosis and will usually be referred to an accredited CF center to begin treatment. If genetic testing revealed a mutation in the CFTR gene but the sweat chloride test is negative, the baby is a CF carrier but does not have the disease and does not require treatment. In either case, genetic counseling is usually done with the family to explain the long-term implications of the results.
Comeau, A.M., PhD, Accurso, F.J., MD, White, T.B., PhD, Campbell, III, P.W., MD, Hoffman, G., BS, Parad, R.B., MD, MPH, Wilfond, B.S., MD, Rosenfeld, M., MD, MPH, Sontag, M.K., PhD, Massie,J., MBBS, FRACP, PhD, Farrell, P.M., MD, PhD, and O'Sullivan, B.P., MD. “Guidelines for Implementation of Cystic Fibrosis Newborn Screening Programs: Cystic Fibrosis Foundation Workshop Report”. Pediatrics. 2007. 119:2 e495-e518. 6 July 2008.