INTRODUCTION
Cystic fibrosis (CF) is an autosomal recessive condition caused by
variants in the CF transmembrane conductance regulator (CFTR)gene [1]. Early diagnosis of CF through newborn screening (NBS)
results in improved nutritional and pulmonary outcomes, and since late
2009 CF NBS has been offered in every state in the United States (US)
[2-4]. An unintended consequence of CF NBS is the detection of
infants with an abnormal NBS, but inconclusive diagnostic testing. In
the US, this condition is termed CFTR-related metabolic syndrome (CRMS)
[5]. The analogous term in Europe and Australia is CF screen
positive, inconclusive diagnosis (CFSPID) [6].
There have been numerous studies of the clinical features and outcomes
of CRMS/CFSPID over the last several years [7-9]. Although there are
variations in study design and cohorts, some common themes are present.
The vast majority (~90%) of infants with CRMS/CFSPID do
not convert to CF. However, a small percentage convert to CF, either
because the variants identified through NBS or further testing are
subsequently determined to be CF-causing or because the child’s sweat Cl
rises above the diagnostic threshold of 60 mmol/L. In some cases
children develop clinical features concerning for CF, such as a positive
respiratory culture for Pseudomonas aeruginosa (Pa).
The majority of studies of CRMS have been limited to outcomes in the
first three years of life, and there are limited data on outcomes in
older children. The US CF Foundation Patient Registry (CFFPR) began
collecting data on infants with CRMS in 2010, and contains one of the
largest cohorts of infants with CRMS available. We previously reported
on clinical outcomes in infants with CRMS in the CFFPR in the first 2
years of life, and found that nutritional status was normal in the
majority of infants with CRMS [10]. However, a small percentage
developed clinical features concerning for CF, such as a respiratory
culture positive for Pa. We also found that a substantial proportion
(41%) of infants who meet CFF guideline definition of CRMS were
classified as CF by their CF Care Center.
The objective of this study was to describe the characteristics of
children with CF and CRMS born 2010-2020, with a focus on nutritional,
microbiologic, and pulmonary outcomes through age 10 years. Because our
earlier analysis showed a high proportion of infants with CRMS were
classified clinically as CF, we also aimed to quantify the extent to
which diagnoses of CF or CRMS reported by CF care teams were consistent
with CFF guidelines and characterize any differences in clinical
characteristics among children reported as having CF but meet CFF
guideline criteria for CRMS.