Background and Objectives: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). Methods: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010-2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. Results: From 2010-2020, there were 8,765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7,591 children had a clinical diagnosis of CF and 1,174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1-9.1% after the first year of life. Conclusions: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

Rationale: Cystic Fibrosis (CF) newborn screening (NBS) algorithms in the USA vary by state. Differences in CF NBS algorithms could potentially affect the detection rate of CF newborns and lead to disparities in CF diagnosis amongst different racial and ethnic groups. Objectives: Generate a database of CF NBS algorithms in the USA and identify processes that may potentially lead to missed diagnoses or lead to health care disparities. Methods: We sent an online survey to state and regional CF and NBS leaders about the type and threshold of immunoreactive trypsinogen (IRT) cutoff used and methods used for CFTR gene variant analysis. Follow-up by email and phone was done to ensure a response from every state, clarify responses, and resolve discordances . Results: There was wide variation in the NBS algorithms employed by different states. Approximately half the states use a floating IRT cutoff and half use a fixed IRT cutoff. CFTR variant analysis also varied widely, with 2 states analyzing only for the F508del variant and 4 states incorporating CFTR gene sequencing. The other states used CFTR variant panels ranging from 23 to 365 CFTR variants. Conclusions: CF NBS algorithms vary widely amongst the different states in the USA, which affects the ability of CF NBS to diagnose newborn infants with CF consistently and uniformly across the country and potentially may miss more infants with CF from minority populations. Our results identify an important area for quality improvement in CF NBS.

Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO)) were performed at 6 months corrected age. Results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into non-severe (N=41) and severe (N=105) groups. There was no significant difference in DCLO and DLCO/aveolar volume amongst the three groups. Forced vital capacity was similar amongst the three groups, but the non-severe Pre-E group had significantly higher forced expiratory flows that the other two. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.