(22) Characteristics of Late Diagnosis Through Newborn Screening and Effects on Growth and Pulmonary Health Outcomes in Infants with CF

Background: Newborn screening (NBS) for CF was fully implemented in the US in 2010, but delays in timeliness of evaluation for infants with positive NBS tests persist. We aimed to determine characteristics and impact of late CF care and on health outcomes in infants with CF.

Methods: We studied infants enrolled in the CFFPR born 2010-2018 and diagnosed between 0-365 days of age. Exclusions were meconium ileus, prematurity, sweat chloride < 30 mEq/L, CFTR modulator use before age 1, missing gestational age, and missing zip code. Age at first evaluation (AFE) was defined as the earliest age of one (or more) of the following CF events: sweat test, a CF Center clinical encounter, or a care episode lasting >24 hours (i.e., hospitalization). We compared initial CF event characteristics and nutritional and pulmonary health outcomes of infants from the youngest AFE quartile (early) to the oldest AFE quartile (late), matching for covariates chosen a priori of gender, median income by zip code, race, ethnicity, genotype (McKone class) and pancreatic status.

Results: Among 6879 infants, 3607 met inclusion criteria. After quartile assignment and matching, 551 infants were in each cohort. Median AFE was 10d (IQR 8, 12) in the early cohort and 47d (IQR 37, 72) in the late cohort (p< .001). Late infants were more likely to have only 1 CFTR variant detected on commercial 23 variant panels (28% vs. 22% for early, p=0.01) and on and 39 variant panels (26% vs. 17% for early, p< 0.001). Late infants were also more likely to have a first CF event as a sweat test (70% vs. 50% for early, p< 0.001) and less likely to have a first CF event as a clinical encounter (49% vs. 61% for early, p< 0.001). Breastfeeding rates were significantly lower at 2 months and 6 months of age among the late infants. Lastly, late infants less commonly had parents with reported college or graduate school education. Despite no differences in birth weight or length, late infants had lower median weight-for-age Z-score and height-for-age Z-score at first encounter and at 1 year. At 3 and 5 years, weight-for-age Z-scores were similar, but late infants had persistently lower height-for-age. There were no differences in Pseudomonas aeruginosa infection, pulmonary function at age 7y, or hospitalization rates between cohorts.

Conclusions: Use of limited CFTR variant panels may result in later evaluation at a CF Center. Though groups were matched for income, parent education may also contribute to later diagnosis, potentially through difficulties navigating the health care system and confirmatory testing. Late diagnosis was associated with reduced breastfeeding rates, weight and height at presentation and age 1 year, and height through 5 years of age. This study highlights ongoing delays in timely newborn screen exist in the United States with resultant long-term consequences. Qualitative studies and improvement work that evaluate more specific systems-factors within individual NBS follow-up programs are essential to ensure equitable and timely evaluation at a CF Care Center for all infants (MCCOLL19QI10).

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