10. Cystic Fibrosis (CF)

10. Cystic Fibrosis (CF) 10.0 Introduction testing protocol may be evaluated. Additionally, programs were asked to report the number of positive patie...
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10. Cystic Fibrosis (CF) 10.0 Introduction testing protocol may be evaluated. Additionally, programs were asked to report the number of positive patients ‘lost to follow-up’ as a means of evaluating the follow-up procedures. These data are reported in Table 10.02. Programs wishing to explain some of their responses included information as footnotes to the table. Because some requested data were not submitted, some care should be exercised in their use.

Screening for cystic fibrosis is included in only a few screening programs. The debate continues as to the benefits of newborn screening for CF given the lack of a curative treatment regimen. It is now generally accepted that a stepwise screening procedure, including screening for immunoreactive trypsin, secondary screening with DNA for ∆F508 (the most frequent and most severe mutation in the U.S. population), and confirmatory sweat testing, provide the most effective screening protocol.

10.3 Second Screen Results

All data reported here were collected from questionnaires submitted to programs as noted in Chapter 3. Only programs with CF screening included in their testing scheme are listed in the Tables. Connecticut is included because the screening program in place at the University of Connecticut Medical School accounts for a significant number of screened newborns even though it is not ‘officially’ a part of the state screening program.

Please see Section 3.6 for a more complete discussion of the data on second screening tests. Second screen data are reported in Table 10.03 and are divided on the basis of whether the second screens are required on all newborns (‘required’) or are obtained on some other basis (‘discretionary’) when a second test is performed without regard for the initial screening result. Programs that requested a second screen because of either a certain result on the first screen that acted as impetus for a second screen or because of an unsatisfactory first screen (usually due to sample condition or early collection) were asked to report these data as ‘repeat screens’ and these are also included.

10.1 Laboratory Procedures In order to identify laboratory procedures in use, programs were asked to report their laboratory protocols and definitions for samples considered ‘not normal.’ These data are reported in Table 10.01. Although only a few programs are screening, several different approaches to laboratory testing exist along with varying definitions of ‘not normal.’ Research continues as to the best approach to screening.

For each case, the data requested included the total infants tested, the total with findings considered not normal, and the number of confirmed cases divided by type of clinical finding. It should be recognized that this is a different way of reporting these data than previously and may, therefore, be somewhat confusing. It is hoped that these data better represent the findings from additional screens. Once again, the reader is cautioned about using the data without regard to notes of explanation.

10.2 Initial Screening Results In order to ascertain the effectiveness of screening for CF, programs were asked to report their findings on initial screening. Initial screening was defined as the first reportable test, and programs were asked not to include duplicate screenings. By reviewing the number of infants screened and confirmed, versus the number of positive tests reported, the efficiency of the

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10.4 Cases of CF Divided by Sex and Race/Ethnicity Programs were asked to report the total of all confirmed cases of CF, whether detected on first

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or second screen, divided by sex and race/ethnicity. The term race/ethnicity was used because some states with high Hispanic populations maintain Hispanic data in much the same way that other states maintain racial data. These data are reported in Table 10.04. For comparative data about the breakdown of births in all states and territories, the reader is referred to the tables in Chapter 1.

10.8 Summation of Results Table 10.08 sums the significant testing data from this Chapter. It includes the total births from Table 1.01, the total infants reported as being screened, and the testing data reported in Tables 10.02 and 10.03. Comparative percentages have been provided at the request of a number of readers, but in at least one case these data appear to be based on estimates or on data that contain duplicate information causing the total compliance percentage to exceed 100%. Hopefully, future data reports will be able to correct these data.

10.5 Time Until Treatment for Cystic Fibrosis In order to look at overall program efficiency with respect to treating newborns identified with cystic fibrosis, programs were asked to report the number of days from birth until treatment. The general definition of treatment used in the questionnaire was, “positive sweat chloride test” and programs using a different definition were asked to report their definition for inclusion as a footnote to the tabulation. Similarly programs were asked to provide footnote information for any cases not treated within the first 21 days of life. These data are reported in Table 10.05.

10.6 Historic Data In order to document the value of screening for CF, programs were asked to supply whatever historic data they could on their screening program. In particular, they were asked to give the date the program began and the number of cases detected over the years. These data are given in Table 10.06. Since the programs involved are young, the data are considered to be accurate and comprehensive but the validity may suffer from the same problems as noted in other chapters.

10.7 Total Newborns Screened Table 10.07 gives a summation of the data contained in Tables 10.02 and 10.03 along with the number of births in each state or territory as reported in Table 1.01. This table was included so that a tabulation of these data could be viewed without having to refer to several tables.

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Table 10.01: Cystic Fibrosis - Laboratory Testing Testing Method

State/Territory 1 2

Colorado Connecticut

3

Montana

4

FIA (DELFIA) Immunoreactive Fluorometric

Pennsylvania

ICN

b

Secondary

Definition of NOT NORMAL

Testing Method

(mg/dL)

Definition of NOT NORMAL (mg/dL)

Requiring Further Filter Paper Testing

Requiring Sweat Chloride Testing

> 90 ng/mL IRT on initial specimen > 90 ng/mL

NA

Sweat chloride/DNA

1st specimen > 100 ng/mL

Second test @ 3-4 wks of age > 80ng/mL.

IRT > 90 ng/mL

IRT > 130 ng/mL and no copies of ∆F508

For 2 copies of ∆F508 (homozygous), a sweat test is

PCR

ªF508 mutation

> 70 ng/mL IRT on recall specimens

perform ∆F508

recommended for confirmation.

analysis.

For 1 copy fo ∆F508 (heterozygous), and an IRT of >90 ng/mL, a sweat test is recommended . When a second sample IRT > 90 ng/mL, a sweat test is recommended to rule out or confirm CF.

5

Wisconsin

DELFIA

6

Wyoming

DELFIA

PCR - ∆F508

a > 90 ng/mL IRT initial

a > 70 ng/mL IRT on recall specimens

a = sweat test to be performed at one month of age if one or two ∆F508 allele(s) are reported on newborn screen report; b = supplemental newborn screening program.

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Table 10.02: Initial Screening Results - Cystic Fibrosis Number

Number

Number

Number

of Newborns

of Newborns

of Newborns

Newborns

of Newborns

with

also having

with final

Confirmed

Screened

NOT NORMAL

NOT NORMAL

NOT NORMAL

with

Classification Lost to follow-up

Cystic Fibrosis

State/Territory

∆F508

Tryspin Results

1

Colorado

83,494

2

Connecticut

20,451

304

3 4

Montana Pennsylvania

2,173 82,541

12 184

0 10

5 6

Wisconsin Wyoming

65,874 6,114

38 57

150

c

TOTAL

a

f

619 d

DA

0 26 NC

f

f

Number of

NR

16

e

0 10

2 0 f

17 3

b

46

g

a = number of screens; an unduplicated count of infants screened is not available; b = one infant with normal IRT and no ∆F508 allele(s) has been confirmed with CF, infant is not included in total; c = supplemental newborn screening program; d = 619 were abnormal on initial screen; 141 were abnormal on second screen when first screen was normal (no cases of CF found in that group of 141); e = physician notification or baby ceased to breathe; f = totals not given - too many states reported inaccurate or inappropriate data; g = total given does not include all states.

Table 10.03: Second Screens for Cystic Fibrosis R = Required Second Screens

State/Territory

1 2 3 4

Colorado Connecticut Montana Pennsylvania

5 6

Wisconsin Wyoming

Total

Newborns Receiving Required Second Screen

Newborns Receiving Discretionary Second Screens

Newborns Receiving Repeat Second Screens

R

D

P

Total 2nd Screens

R

304 148

304 211 148

2,217

986

3,203

2,428

1,438

211 b

DA

0

Number of Newborns with NOT NORMAL Trypsin Results

D

0

N/C

DA

d

P = Repeat Second Screens

Number of Newborns with NOT NORMAL

Number of Newborns with NOT NORMAL Classification Lost to follow-up

∆ F508

P

Total

66

0 66

5

5

0

0

N/C

N/C

c

D = Discretionary Second Screens

R

D DA

P 10

N/C

DA

d

Total

DA

R

D

P

N/C

DA

d

Total

R

D

0

P

Total

0

0

7

0 7

1

1

1

1

NR

10

Number of Newborns Confirmed with Cystic Fibrosis

NR

N/C

NA

DA

d

0

N/C

0

8

8

e

Table 10.04: Cases of Cystic Fibrosis Total detected on initial and second screens

Subdivided by Sex and Race/Ethnicity

7

16

4

7

6

5

11

Total

9 3

Female

Total

Male

7

Hispanic

Female

9

Total...... Male

Female

Unknown Male

Female

Other Male

Female

Native American Male

Female

Asian or P. Islander Male

4

Female

3

Male

Female

Black

Male

White

0

0

0

State/Territory 1

Colorado

2

Connecticut

3

Montana

4

Pennsylvania

0 a

6

5

5

Wisconsin

10

7

10

7

17

6

Wyoming

1

2

1

2

3

TOTAL

14

13

29

25

54

1

0

0

0

0

0

0

0

0

15

12

1

total reported is from Table 10.02 and Table 10.03; therefore total does not equal or may differ from data given in Table 10.04 and denotes a problem in reliabilty.

2

ethnicity data not collected.

a = supplemental newborn screening program.

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Table 10.05: Days from Birth Until Treatment Initiated for Cystic Fibrosis Total detected on initial and second screens (blank spaces mean that no infants fell into these categories)

State/Territory 1

Colorado

2

Connecticut

3 4

Montana Pennsylvania b

5 6

Wisconsin Wyoming

21

Unk.

1

10

4

7

TOTAL 16 7 0 11

17

17 3

1

1

Table 10.06: Summation of Years Covered and Number of Cases Detected by Program Cystic Fibrosis State/Territory

Year Started

Total Years

Total Cases

1

Colorado

Jul-1987

9 1/2

130

2

Connecticut

May-1993

3 1/2

24

3 4

Montana Pennsylvania

1992 1987

4 9

2 82

5 6

Wisconsin Wyoming

1994 Sep-1988

2 8 1/4

41 15

a

a = supplemental newborn screening.

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Table 10.07: Total Newborns Screened for Cystic Fibrosis Total Births

Number of Newborns with NOT NORMAL Trypsin Results

State/Territory

Number of Newborns also having NOT NORMAL

∆F508

Number of Newborns with final NOT NORMAL Classification Lost to follow-up

1

Colorado

56,059

619

2

Connecticut

44,327

370

10

0

3 4

Montana Pennsylvania

10,790 148,985

12 189

0 10

0

5 6

Wisconsin Wyoming

66,120 5,867

38 57

150

TOTAL

332,148

1,285

170

a

DA

N/C

27 DA

Number of Newborns Confirmed with Cystic Fibrosis

7 b

2 0 29

16 0 11 17 3 54

a = supplemental newborn screening; b = 23 physician notification and babies ctb; c = total given does not include all states.

c

Table 10.08: Summation Results of Testing for Cystic Fibrosis Total Births

State/Territory

Total Newborns Receiving Initial Screen

% of Newborns Receiving Initial Screen calculated

* 148.94%

Total Newborns Receiving Required 2nd Screen

% of Newborns Receiving Required 2nd scrn. (calc'd)

Total Newborns Receiving Discretionary 2nd Screen

1

Colorado

56,059

83,494

2

Connecticut

44,327

20,451

46.14%

3 4

Montana Pennsylvania

10,790 148,985

2,173 82,541

20.14% 55.40%

211

5 6

Wisconsin Wyoming

66,120 5,867

65,874 6,114

99.63% 104.21%

2,217

332,148

260,647

TOTAL

c

a

* b

b

2,428

% of Total Newborns Newborns Receiving Receiving Discretionary Repeat 2nd scrn. 2nd (calc'd) Screen

% of Newborns Receiving Repeat 2nd scrn. (calc'd)

304

0.69%

148

0.10%

986

1.49%

1.96% 3.35% b

1,438

* Percentage > 100% denotes inability of program to separate Newborns screened from specimens received; a = totals should be viewed as a rough estimate due to inability of many states, to know actual number of newborns screened. Many programs count samples received but cannot eliminate duplication when multiple samples are received; b = cannot be calculated due to inaccurate data; c = supplemental newborn screening.

b