Early diagnosis article

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Pediatrics, February 2003 Journal Scan

From

The Journal of Pediatrics

December 2002 (Volume 141, Number 6)

The Impact of Early Cystic Fibrosis Diagnosis on Pulmonary Function in

ChildrenWang SS, O'Leary LA, Fitzsimmons SC, Khoury MJ

The Journal of Pediatrics. 2002;141(6):804-810

One of the reasons that testing for cystic fibrosis (CF) has not been added

to the battery of routine newborn screening tests in most states is the lack

of randomized data demonstrating that diagnosing a newborn with CF improves

either lung function or nutritional outcome when compared with children who

are diagnosed when their symptoms become apparent later in life. This study

evaluated differences in lung function between children diagnosed with CF at

younger than 6 weeks of age and those diagnosed at older ages.

The authors reviewed data from the national registry of patients with CF who

were diagnosed between 1982 and 1990 and followed until 1996. The patients

were aged 6 to 10 years at the time of pulmonary evaluation. There were 3625

children entered into the registry during that period who were still

followed

as of 1996. The authors reported that approximately 75% of CF patients in

the

United States are entered into the registry.

The " case " group comprised infants identified at < 6 weeks of age, with the

comparison group being diagnosed between 6 weeks and 36 months of age.

Children diagnosed with CF after 36 months and children who suffered

meconium

ileus were excluded. The diagnosis of CF was made by either sweat chloride

or

DNA testing. The outcome variables included forced expiratory volume in 1

second (FEV1) and forced vital capacity (FVC), but the authors reported only

results related to FEV1 because the findings were similar regardless of

measure employed. Subjects were first classified as having moderate (FEV1 <

70% of predicted) or severe (< 40% of predicted) impairment of pulmonary

function, but the authors combined these groups for analyses owing to the

small numbers obtained.

The results revealed no significant differences in pulmonary function

between

the children diagnosed late or early if they were born before 1987. However,

for children born after 1987, early diagnosis of CF and being asymptomatic

was associated with higher FEV1 measurements on average. In the post-1987

birth group, early diagnosis of CF in symptomatic patients was not

associated

with improved pulmonary function. In a similar manner, smaller proportions

of

early-diagnosed and asymptomatic patients had moderate-to-severe impairment

of lung function (approximately 4% to 12%) compared with patients diagnosed

later or patients diagnosed early who were symptomatic (approximately 8% to

22%).

In multivariate analysis using the entire group (pre- and post-1987 entry),

there were no differences in impaired lung function based on time diagnosed

or symptomatology of diagnosis. In the group born after 1987, children with

symptoms who were diagnosed early or symptomatic children diagnosed later

were approximately twice as likely to have moderate-to-severe lung

impairment

compared with children diagnosed early who were asymptomatic, but the

differences were not statistically significant. The authors concluded that

the data supported early diagnosis of CF for improved pulmonary functioning

later on.

Reviewer CommentThis is a very valuable study, and it may well be the best

data currently available to help answer the research question. However, the

fact that early diagnosis did not show a statistically significant

association with lung function cannot be ignored. The only benefit appeared

to be in asymptomatic and early-diagnosed individuals, but the original

question was whether early diagnosis (regardless of symptoms) was helpful.

The lack of statistical significance in this study may be related to power

issues due to the number of participants. The observational nature of the

study is also a notable limitation: in a clinical trial, all children within

certain groups should receive the same interventions. The interventions

experienced by these participants, while undoubtedly following generally

accepted practices, certainly varied a great deal.

This study does offer the suggestion that early diagnosis can be beneficial,

but it does not provide definitive evidence. In an accompanying editorial,

Farrel and Fost review the many ethical issues involved in screening adults

considering pregnancy and newborns.[1]

Reference

Farrell PM, Fost N. Prenatal screening for cystic fibrosis: where are we

now?

J Pediatr. 2002;141:758-763.