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.