Outcomes of early repeat sweat testing in infants with cystic fibrosis
transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF
screen-positive, inconclusive diagnosis (CFSPID)
Background: Reaching early and definitive diagnosis in infants with
cystic fibrosis (CF) transmembrane conductance regulator-related
metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis
(CFSPID) is a priority of all CF newborn screening programs. Currently,
sweat testing is the gold standard for CF diagnosis or exclusion. We
assessed outcomes in a cohort of Italian CRMS/CFSPID infants who
underwent repeat sweat testing in the first year of life. Methods: This
multicentre, prospective study analysed clinical data and outcomes in
CRMS/CFSPID infants born between September 1, 2018 and December 31,
2019, and followed until June 30, 2020. All subjects underwent CF
transmembrane conductance regulator (CFTR) gene sequencing and the
search for CFTR macrodeletions/macroduplications, and repeat sweat
testing in the first year of life. Results: Fifty subjects (median age
at end of follow-up, 16 months [range, 7–21 months]) were enrolled.
Forty-one (82%) had the first sweat chloride in the intermediate range.
During follow up, 150 sweat tests were performed (range, 1–7/infant).
After a median follow-up of 8.5 months (range 1–16.2 months), 11 (22%)
subjects were definitively diagnosed as follows: CF (n=2 [4%]) at 2
and 5 months, respectively; healthy carrier (n=8 [16%]), at a
median age of 4 months (range 2–8 months); and healthy (n=1 [2%])
at 2 months of age. Inconclusive diagnosis remained in 39 (78%)
infants. Conclusions: Early repeat sweat testing in the first year of
life can shorten the time to definitive diagnosis in screening positive
subjects with initial sweat chloride levels in the intermediate range.