An infant in our practice has an initial CF newborn screen is that is positive.
What do I do and what do I tell the family? What is the likelihood this patient has CF?
What is the strategy for CF newborn screening in Colorado?
Determination of immunoreactive trypsinogen (IRT) concentrations from dried blood spots serves as the basis for cystic fibrosis (CF) newborn screening. Colorado currently uses a two-tier screening program in which IRT is assayed in blood specimens collected at 1-2 days and then again at ~14 days of age (IRT/IRT algorithm). Two elevated IRTs constitute a positive newborn screen for CF and indicate that a sweat test needs to be performed.
By the end of 2007, Colorado will be switching its CF newborn screening program to an IRT/IRT/DNA approach. In this screening protocol, two IRTs will also be collected. If the IRT concentrations are both above a certain threshold, then a DNA mutation analysis (testing for a panel of CF-causing mutations) will be performed in the same dried blood spot.
What is IRT?
Immunoreactive trypsinogen (IRT) is a pancreatic enzyme precursor. IRT concentrations are high in the blood of infants with CF, presumably from leakage of the protein into the circulation due to pancreatic duct blockage. Therefore, IRT is a biomarker of early pancreatic injury in newborns and infants with CF.
A newborn has a positive newborn screen for CF. What does it mean?
Under the current protocol, a positive newborn screen for CF is reported when an infant has 2 elevated IRTs. This means that the newborn needs to undergo a diagnostic sweat test. A positive newborn screen does not mean that the infant has CF. Of those infants with a positive first IRT, only ~10% will have CF. And of those infants with two elevated IRTs (i.e. positive newborn screen), ~35% will have CF. Therefore, most babies with positive newborn screening will NOT have CF. For those infants with two elevated IRTs, sweat testing should be performed within a few days of the second IRT test result.
We recommend that sweat testing be performed at an accredited sweat testing facility. The two best options in Colorado are the laboratories at University Hospital (303-372-0368) or Children's Hospital Colorado (303-861-6287). The cost of sweat tests at University Hospital will be paid by the state newborn screening program.
Bear in mind that the newborn screen is NOT a diagnostic test for CF. A positive newborn screen result means that an infant is at increased risk of having CF.
The mother says she had a negative CF blood test during pregnancy but the baby had a positive newborn screen. Does the newborn still need a sweat test?
YES. Any infant whose newborn screen is positive should have a sweat test. Prenatal CF mutation carrier testing offered to pregnant women does not detect all of the known genetic mutations that cause CF.
What constitutes a definitive diagnosis of CF?
A sweat chloride value >60 mEq/L (or mmol/L) is considered diagnostic for CF. A sweat chloride value <30 mEq/L almost always rules out CF. A sweat chloride value between 30 and 60 mEq/L has been termed ambiguous or "borderline" and is not clearly diagnostic. However, many newborns and young infants with sweat chloride values >40 mEq/L may have CF and require close follow-up.
Does a negative newborn screen completely rule out the possibility that this child has CF?
NO. It is important to remember that screening is NOT 100% certain and a child with negative screening may still turn out to have CF. We miss less than 5% of infants with CF in Colorado through our screening program (i.e. our false negative rate is between 3-5%). Regardless of newborn screen results, we strongly recommend a sweat test be performed in any infant or child with symptoms suggestive of CF including recurrent respiratory tract infections, frequent loose stools, and poor growth.
For any questions regarding CF newborn screening, feel free to contact either Dr. Frank Accurso (CF Center Director) or Dr. Scott Sagel (Associate Center Director).