The Influence of Newborn Screening for Cystic Fibrosis on Pulmonary Outcomes in New South Wales

doi:10.1016/j.jpeds.2005.08.013

The Journal of Pediatrics

Volume 147, Issue 3, Supplement, September 2005, Pages S47-S50

https://doi.org/10.1016/j.jpeds.2005.08.013 Get rights and content

Objectives

To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence.

Study design

Both screening (SG) and non-screening groups (NSG) comprised a cohort of children from Australia previously studied at 1, 5, and 10 years of age. The groups were compared on measures of clinical status obtained during their comprehensive annual review conducted at or near the 15th birthday of the subjects.

Results

Data were collected on 48 of 57 original subjects in the NSG (7 had died; 2 were lost to follow-up) and 52 of 60 original subjects in the SG (4 had died; 2 transferred out of the country; 2 were lost to follow-up). Those dying in the SG were significantly older (by 48 months, P < .05) than those in the NSG. No statistically significant differences were found between the groups in nutritional status. However, subjects in the SG displayed statistically better total Shwachman-Kulczycki scores (7.0, P ≤ .05), chest x-ray scores (2.3, P ≤ .05) and lung function (forced expiratory volume in 1 second by 12.3%, P ≤ .01; forced vital capacity by 12.6%, P ≤ .01; and mean airflow by 23.3%, P ≤ .01).

Conclusions

The previously observed advantage conferred by cystic fibrosis newborn screening on clinical outcomes in infancy and childhood is still apparent in adolescence.

Section snippets

Source of Data

Both the “screening” and “non-screening” groups comprised the cohort of patients previously studied at 5 and 10 years of age.3, 7 This historical cohort comprises 2 groups of children with CF, all of whom received their diagnosis and care from the CF Clinic at The Children's Hospital at Westmead (formerly Royal Alexandra Hospital for Children at Camperdown). The group of subjects with CF born in the 3 years immediately before newborn screening was introduced (July 1978–July 1981, n = 57), were

Differences in Outcome at 15 Years of Age

Of the original 57 subjects in the NSG, 2 subjects were lost to follow-up or had transferred to another CF center before their 15th birthday. An additional 7 had died before their 15th year, leaving a total of 48 from whom data were collected at 15 years. In the SG, data at 15 years were available for a total of 52 of the original 60 subjects. Of the remaining 8 subjects, 4 had died, and 4 had transferred to another center or were lost to follow-up before their 15th birthday.

A total of 11

Discussion

The results presented in this report from a cohort of children in Australia suggest that early treatment after diagnosis of CF via newborn screening improves clinical outcomes over the first 15 years of life. Mortality rates tended to be lower in the SG compared with the NSG, and lung function was significantly better preserved in surviving members of the SG compared with those survivors in the NSG. These findings coupled with the significantly higher chest X-ray and composite

References (15)

B. Wilcken et al.
Reduced morbidity in patients with cystic fibrosis detected by neonatal screening
Lancet
(1985)
B. Wilcken et al.
Neonatal screening for cystic fibrosis: a comparison of two strategies for case detection in 1.2 million babies
J Pediatr
(1995)
M.W. Konstan et al.
Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis
J Pediatr
(2003)
J.E. Dankert-Roelse et al.
Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre
Thorax
(1995)
P.M. Farrell et al.
Nutritional benefits of neonatal screening for cystic fibrosis
N Engl J Med
(1997)
D. Waters et al.
Clinical outcomes of newborn screening for cystic fibrosis
Arch Dis Child Fetal Neonatal Ed
(1999)
P.M. Farrell et al.
Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long term growth
Paediatrics
(2001)

There are more references available in the full text version of this article.

Cited by (62)

Does newborn screening improve early lung function in cystic fibrosis?
2022, Paediatric Respiratory Reviews
Despite evidence showing an improvement in nutritional outcomes following diagnosis by newborn screening (NBS) for cystic fibrosis (CF), the impact on pulmonary outcomes has been less clear. In this review the approaches to measurement of early lung function and knowledge gained from NBS CF cohorts will be described. Studies which have compared outcomes in those diagnosed by NBS to those diagnosed following symptomatic presentation will be presented. Compiling the evidence base used to evaluate the impact of NBS on pulmonary outcomes has been complicated by improvements in clinical management, infection control practices, as well as public health interventions (such as tobacco smoking bans in public places) that have evolved substantially over recent decades. Forced expiratory volumes have been used as the main outcome but it is important not to draw conclusions for ‘early lung function’ from tests such as spirometry alone, which lack sensitivity in early lung disease. There is, at present, insufficient evidence to draw firm conclusions about the effect of NBS on early lung function. In an era of highly effective treatments targeting the underlying molecular defect responsible for CF, future opportunities for early initiation of treatment may mean that the impact of NBS on early lung function may yet to be realised.
Newborn screening alone insufficient to improve pulmonary outcomes for cystic fibrosis
2021, Journal of Cystic Fibrosis
The Wisconsin Cystic Fibrosis Neonatal Screening Project was a randomized clinical trial (RCT) revealing that children receiving an early diagnosis of CF via newborn screening (NBS) had improved nutritional outcomes but similar lung disease severity compared to those who presented clinically. Because the evaluations of these subjects by protocol ended in 2012, our objective was to assess long-term pulmonary and mortality outcomes.
Retrospective analysis of the RCT cohort utilized longitudinal outcome measures obtained from the Cystic Fibrosis Foundation Patient Registry (CFFPR). Data included screening assignment, clinical characteristics, percent predicted forced expiratory volume in 1 s (ppFEV₁) and mortality. A random intercept model was used to compare the ppFEV₁ decline of subjects between the two groups up to age 26 years. Mortality was analyzed using the Kaplan-Meier method.
Of the 145 subjects who consented to the original study, 104 subjects met inclusion criteria and had adequate data in the CFFPR. Of 57 subjects in the screened group and 47 in the control group, the rates of ppFEV₁ decline were 1.76%/year (95% CI 1.62 to 1.91%) and 1.43%/year (95% CI 1.26 to 1.60%), respectively (p<0.0002). Pseudomonas aeruginosa acquired before 2 years was partially responsible. There was no difference in mortality between the two groups.
NBS alone does not improve pulmonary outcomes in CF, particularly when other risk factors supervene. In an era prior to strict infection control and current therapies, NBS for CF may be associated with worse pulmonary outcomes.
Cystic fibrosis
2021, Biochemical and Molecular Basis of Pediatric Disease
Cystic fibrosis (CF) is the most common, life-shortening, inherited disease affecting Caucasians, involving the lungs, pancreas, intestines, liver, and skin. Newborn screening programs for cystic fibrosis have been implemented across the United States, and early diagnosis and interventions have led to improved pulmonary and nutritional outcomes. More recently, cystic fibrosis transmembrane conductance regulator (CFTR) modifying drugs with mutation-specific effectshave emerged, and are increasingly used in children and adults with cystic fibrosis. In this chapter, we review newborn screening and diagnostic testing for cystic fibrosis, describe existing and emerging therapies, and how these treatments are changing thetrajectory of disease.
Question 10: Could the Burden of Care with Cystic Fibrosis Impact on Educational Outcomes?
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More specifically, extremely low levels of vitamin E during early childhood have been linked with impaired brain development [20]. With approximately 20% of teenagers developing CF related diabetes, there is the risk of hypoglycaemia, resulting in an imbalance between caloric intake [by mouth or with enteral feeds] and insulin dose [4]. Monitoring blood sugars becomes an important additional burden that they must accommodate in their already time-consuming routine.
Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era
2017, Journal of Pediatrics
Citation Excerpt :
This result was also evident in both the LD-NBS-neg and LD-NBS-pos subset cohorts (when compared with their respective NBS-CF control cohorts). Although the association between NBS and improved long-term lung function has been limited,18,42 this finding has previously been reported in our NSW cohort.18,21 The worse lung function in the LD-CF cohort is probably associated with the significantly higher rate of mucoid P aeruginosa isolation compared with NBS-CF controls (42% vs 20%; P = .008).
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).
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.
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).
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.
Background and Epidemiology
2016, Pediatric Clinics of North America

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Original ResearchThe Influence of Newborn Screening for Cystic Fibrosis on Pulmonary Outcomes in New South Wales

Objectives

Study design

Results

Conclusions

Section snippets

Source of Data

Differences in Outcome at 15 Years of Age

Discussion

Lancet

J Pediatr

J Pediatr

Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre

Thorax

Nutritional benefits of neonatal screening for cystic fibrosis

N Engl J Med

Clinical outcomes of newborn screening for cystic fibrosis

Arch Dis Child Fetal Neonatal Ed

Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long term growth

Paediatrics

Original Research
The Influence of Newborn Screening for Cystic Fibrosis on Pulmonary Outcomes in New South Wales