Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era

• Published in: The Journal of pediatrics Vol. 181; pp. 137 - 145.e1
• Main Authors: Coffey, Michael J., BMed, MD, Whitaker, Viola, Gentin, Natalie, MBBCh, FRACP, Junek, Rosie, DCH, Shalhoub, Carolyn, BSc(Hons), GradDip(Counselling), Nightingale, Scott, BMed(Hons), MClinEpid, FRACP, Hilton, Jodi, BMed, FRACP, Wiley, Veronica, PhD, Wilcken, Bridget, MD, FRACP, Gaskin, Kevin J., MD, FRACP, Ooi, Chee Y., MBBS, FRACP, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2017
• Subjects: Age Factors; Australia; Cystic Fibrosis - diagnosis; Cystic Fibrosis - mortality; Cystic Fibrosis - therapy; cystic fibrosis transmembrane conductance regulator; Databases, Factual; Delayed Diagnosis - adverse effects; Disease Progression; Female; growth; Hospitalization - statistics & numerical data; Humans; Infant, Newborn; lung function; Male; Neonatal Screening - methods; New South Wales; Outcome Assessment (Health Care); Pediatrics; Prognosis; Respiratory Function Tests; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Survival Rate; Forced expiratory volume in 1 second percentage of predicted; New South Wales; PS; CF transmembrane conductance regulator; Immunoreactive trypsinogen; IRT; CFSPID; SC; Body mass index; lung function; LD-CF; Newborn screening; Pancreatic sufficient; MI; NBS; BMI; CF; CF screen positive inconclusive diagnosis; Cystic fibrosis; LD-NBS-pos; Late diagnosis newborn screen positive; LD-NBS-neg; Pancreatic insufficient; Sweat chloride; Late diagnosis newborn screen negative; NBS-CF; NSW; Late diagnosis of cystic fibrosis; cystic fibrosis transmembrane conductance regulator; Newborn screen diagnosed CF; PI; growth; FEV1; Australia; CFTR; Meconium ileus
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2016.10.045

Objectives To evaluate children with cystic fibrosis (CF) who had a late diagnosis of CF (LD-CF) despite newborn screening (NBS) and compare their clinical outcomes with children diagnosed after a positive NBS (NBS-CF). Study design A retrospective review of patients with LD-CF in New South Wales, Australia, from 1988 to 2010 was performed. LD-CF was defined as NBS-negative (negative immunoreactive trypsinogen or no F508del ) or NBS-positive but discharged following sweat chloride < 60 mmol/L. Cases of LD-CF were each matched 1:2 with patients with NBS-CF for age, sex, hospital, and exocrine pancreatic status. Results A total of 45 LD-CF cases were identified (39 NBS-negative and 6 NBS-positive) with 90 NBS-CF matched controls. Median age (IQR) of diagnosis for LD-CF and NBS-CF was 1.35 (0.4-2.8) and 0.12 (0.03-0.2) years, respectively ( P  <   .0001). Estimated incidence of LD-CF was 1 in 45 000 live births. Compared with NBS-CF, LD-CF had more respiratory manifestations at time of diagnosis (66% vs 4%; P  <   .0001), a higher rate of hospital admission per year for respiratory illness (0.49 vs 0.2; P  = .0004), worse lung function (forced expiratory volume in 1 second percentage of predicted, 0.88 vs 0.97; P  = .007), and higher rates of chronic colonization with Pseudomonas aeruginosa (47% vs 24%; P  = .01). The LD-CF cohort also appeared to be shorter than NBS-CF controls (mean height z -score −0.65 vs −0.03; P  = .02). Conclusions LD-CF, despite NBS, seems to be associated with worse health before diagnosis and worse later growth and respiratory outcomes, thus providing further support for NBS programs for CF.