39: Five Years of Cystic Fibrosis Newborn Screening: Our Experience

In the spring of 2008, Newborn Screening Ontario (NSO) expanded their panel to include cystic fibrosis (CF), using an immunoreactive trypsinogen (IRT)/DNA protocol. Those that are positive are referred for a sweat test, which is still considered the gold standard for diagnosis. The goal is to detect a population at risk for CF and upon diagnosis, initiate therapy, minimizing adverse outcomes. We have chosen to perform confirmatory molecular testing on each screen-positive individual, differing from some other centres in Ontario, because our hospital laboratory uses a larger mutation panel (70+6 polymorphisms) compared to that used by NSO (39 +3 polymorphisms). This aligns with the provincial recommendations set out by NSO as part of the diagnostic work up. To examine whether confirmatory molecular testing using our expanded panel on all screen-positive newborns is justified. We performed a retrospective descriptive analysis of the results of our program recorded from April 2008 to 2013 using an internal database. Particular note was made of individuals found to have a second mutation with our confirmatory panel, and of the sweat chloride obtained. 337 patients have screened positive and been referred to our centre for sweat chloride testing. Of these, 25 (7.4%) have been referred with two mutations identified and 258 (76.5%) have one known mutation found. In addition, 47 (13.9%) have no known mutations, but are offered a sweat chloride as their IRT level exceeds the 99th percentile. Using our expanded panel, we uncovered a second mutation in 14 children, eight of whom would have been discharged as unaffected as they had normal initial sweat tests. Thirteen infants had a sweat chloride that fell within the ‘borderline’ range of 30 mmol/L to 60 mmol/L, of whom seven infants had two known mutations already identified by NSO, four infants had an additional mutation identified on our panel, and two infants required sequencing to identify a second mutation. To our knowledge, since the inception of this program, there have been no children with classical CF that were not identified on newborn screen. Though our approach may identify otherwise ‘healthy’ infants with a second mutation of unknown clinical relevance, given the uncertainty of the long-term prognosis associated with some mutations, we feel it continues to be warranted until more information is known.

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