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

Michael J Coffey; Viola Whitaker; Natalie Gentin; Rosie Junek; Carolyn Shalhoub; Scott Nightingale; Jodi Hilton; Veronica Wiley; Bridget Wilcken; Kevin J Gaskin; Chee Y Ooi

doi:10.1016/j.jpeds.2016.10.045

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

J Pediatr. 2017 Feb:181:137-145.e1. doi: 10.1016/j.jpeds.2016.10.045. Epub 2016 Nov 10.

Authors

Affiliations

¹ School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
² School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of General Pediatrics, Sydney Children's Hospital Randwick, Sydney, Australia.
³ The Children's Hospital at Westmead, Sydney, Australia.
⁴ Department of Medical Genetics, Sydney Children's Hospital Randwick, Sydney, Australia.
⁵ GrowUpWell Priority Research Centre, University of Newcastle, Newcastle, Australia; Department of Gastroenterology, John Hunter Children's Hospital, Newcastle, Australia.
⁶ University of Newcastle, Newcastle, Australia; Department of Respiratory Medicine, John Hunter Children's Hospital, Newcastle, Australia.
⁷ The Children's Hospital at Westmead, Sydney, Australia; The University of Sydney, Sydney, Australia.
⁸ School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia. Electronic address: keith.ooi@unsw.edu.au.

PMID: 27837951
DOI: 10.1016/j.jpeds.2016.10.045

Abstract

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.

Keywords: Australia; cystic fibrosis transmembrane conductance regulator; growth; lung function.

Publication types

Comparative Study

MeSH terms

Age Factors
Cystic Fibrosis / diagnosis*
Cystic Fibrosis / mortality
Cystic Fibrosis / therapy
Databases, Factual
Delayed Diagnosis / adverse effects*
Disease Progression
Female
Hospitalization / statistics & numerical data*
Humans
Infant, Newborn
Male
Neonatal Screening / methods*
New South Wales
Outcome Assessment, Health Care*
Prognosis
Respiratory Function Tests
Retrospective Studies
Risk Assessment
Severity of Illness Index
Sex Factors
Survival Rate