Cystic fibrosis screening soars; Still Below Target Levels.

[Guest guest]

HEADLINE: Cystic fibrosis screening soars; Still Below Target Levels.

BYLINE: Zoler, Mitchel L.

Screening of pregnant women and their partners for cystic fibrosis mutations

has skyrocketed since September 2001, when the American College of

Obstetricians

and Gynecologists and the American College of Medical Genetics recommended

that

physicians make screening available to all couples seeking preconception or

prenatal care.

But despite the soaring numbers, by early this year cystic fibrosis (CF)

screening was still way below target goals. Best estimates of screening

volume

in the United States in early 2003 placed the number at an annualized rate

of

perhaps 300,000500,000 tests, a level far above the rate through the end of

2001, but a figure that's dwarfed by the approximately 4 million live births

a

year in the United States.

Because a large percentage of pregnant women and their partners are supposed

to be offered screening, and most prospective parents don't know their CF

carrier status, a few million tests would need to be done each year if

screening

were offered by most obstetricians.

" ACOG is focused on getting the word out to obstetricians, " said Dr. Deborah

A. Driscoll, an ob.gyn. at the University of Pennsylvania, Philadelphia, and

chair of ACOG's committee on genetics. " We're a little concerned about the

potential liability if physicians don't offer screening, so we feel that

it's

really important to keep educating our fellows, " she said in an interview.

" I talk to a lot of obstetricians at grand rounds, and I often ask whether

any of them are offering CF screening to their patients, and it's not

unusual

for no one in the room to raise their hand, " said Dr. Wayne W. Grody, a

member

of the CF screening task force that the American College of Medical Genetics

(ACMG) runs with ACOG.

" It's not that obstetricians are not aware of this; they've seen the

mailings. But they say that they don't have the time to talk with patients

about

it, that their patients come from ethnic groups where the prevalence of

mutations is low, and that they are not sure who will pay for the test, " Dr.

Grody told this newspaper.

Laboratories generally charge about $ 150-$ 200 for the current, standard CF

carrier test, and insurance coverage is currently spotty, even though

" insurers

should pay for it because screening is now the standard of care, " according

to

Dr. Grody, who is professor of medical genetics at the University of

California,

Los Angeles.

S. , Ph.D., executive director of the ACMG and another task

force member, guessed that by early 2003 about 20%-25% of U.S. obstetricians

were offering CF screening to couples planning a pregnancy or to pregnant

women

and their partners.

To get a better handle on exactly how widely obstetricians are offering

screening, ACOG is now devising a survey that will be sent to all of its

fellows

in the fall, Dr. Driscoll said.

ACOG's committee on genetics is also drafting a new mailing to fellows that

will " remind them to offer screening and review who to offer it to and what

to

do if a patient is found to carry a mutation, " she said.

In a typical screening scenario, an obstetrician will introduce the option

of carrier screening for CF, usually by giving the patient a brochure on the

subject that's published by ACOG, having the patient watch a video that the

physician has prepared, or discussing the option with the patient.

Providing ACOG's brochure is the minimum step that physicians can do to

adequately fulfill their responsibility, Dr. Driscoll said.

If a woman opts to be screened, her specimen will be sent to a laboratory

that runs the standard test specified by the ACOG and ACMG task force. If

she

harbors a CF mutation that is associated with causing severe disease, her

partner will then be screened.

If both parents carry a disease-linked mutation, then they'll receive

additional counseling about the risk that their children will face for

inheriting CF. The couple may then opt for genetic testing of the fetus and

may

consider terminating the pregnancy if the fetus has two CF-causing

mutations.

Although many obstetricians have yet to adopt the standard that ACOG set for

the specialty, 2002 saw a huge leap in CF testing.

About 50 laboratories across the United States participate in a proficiency

program for CF-mutation testing that's jointly run by the ACMG and the

College

of American Pathology, said Dr. Grody, chair of the committee that

administers

the proficiency-testing program.

Among these labs, the vast majority perform relatively small numbers of

tests at medical centers; the bulk of testing in the United States is done

by a

handful of large, commercial laboratories, most notably Quest Diagnostics

Inc.,

Genzyme Corp., and the Laboratory Corporation of America (Lab Corp).

A survey by this newspaper of these three laboratories found that two

insisted on keeping the exact volume of their CF testing program

confidential.

A spokesman for Genzyme said that their testing volume rose about threefold

from before September 2001 to January 2003. The number of tests ordered

doubled

last year and then showed a second, marked rise early this year.

A spokesman for Quest said that it was running nearly four times as many

tests by the end of last year as it had a year before, and as of early 2003

it

was performing " hundreds of thousands of tests " on an annualized basis.

A spokesman for LabCorp said that its testing volume had jumped by more than

11-fold from before October 2001 to December 2002.

As of last December, LabCorp was running more than 11,000 CF tests a month,

an annualized rate of more than 130,000 tests.

On the basis of these and other industry numbers, it's safe to say that by

the start of this year, the overall volume of CF testing in the United

States

was more than 300,000 tests a year and growing, said Dr. .

CF Mutations by Race and Ethnicity

Mutation Detection

Chance Both Chance of Rate using

Race or Partners Are Having Child 25-Mutation

Ethnicity CF rs With CF Panel Screen

White

(European ancestry) 1 in 625 1 in 2,500 90%

Hispanic American 1 in 2,100 1 in 8,500 57%

African American 1 in 4,200 1 in 17,000 69%

Asian American 1 in 8,100 1 in 32,400 insufficient data

RELATED ARTICLE: Changes Planned for CF Screening Panel

The panel of cystic fibrosis mutations that laboratories look for when

running a carrier screening test will change by next fall.

The standard screening panel tests for 25 different mutations in the cystic

fibrosis (CF) gene, called CFTR. The panel was established by the joint task

force of the American College of Obstetricians and Gynecologists and the

American College of Medical Genetics (ACMG) in 2001. But hands-on experience

with this panel has led to a few problems, and so some fine-tuning will

occur

later this year, said S. , Ph.D., executive director of the

ACMG

and a member of the CF carrier screening task force.

Although details of the changes are still to come, two refinements are

already clear. One involves reemphasizing that the test for a mutation known

as

5T should not be part of the primary screening panel because the results of

the

test lack clinical significance. Some laboratories have included 5T in their

primary screen, and this has led to some people being erroneously flagged as

mutation carriers and undergoing unnecessary genetic counseling, Dr.

said.

The 5T variant appears in about 5% of the population.

The second change will involve reassessing the significance of another

mutation, I148T, which is about 100 times more prevalent than originally

thought. This high prevalence suggests that the mutation may not really

cause

CF.

What's unlikely to change much is the modest number of mutations called for

in the screening panel. The 2001 recommendations set this at 25 (Out of more

than 800 identified), but some laboratories have offered broader screens,

involving as many as 70 mutations and have promoted these tests as better.

This is not the case, said Dr. Wayne W. Grody, professor of medical genetics

at the University of California, Los Angeles, and a member of the CF

screening

task force. " Larger panels are more confusing and more expensive. They're

not

worth it, " he said.

[Guest guest]

HEADLINE: Cystic fibrosis screening soars; Still Below Target Levels.

BYLINE: Zoler, Mitchel L.

Screening of pregnant women and their partners for cystic fibrosis mutations

has skyrocketed since September 2001, when the American College of

Obstetricians

and Gynecologists and the American College of Medical Genetics recommended

that

physicians make screening available to all couples seeking preconception or

prenatal care.

But despite the soaring numbers, by early this year cystic fibrosis (CF)

screening was still way below target goals. Best estimates of screening

volume

in the United States in early 2003 placed the number at an annualized rate

of

perhaps 300,000500,000 tests, a level far above the rate through the end of

2001, but a figure that's dwarfed by the approximately 4 million live births

a

year in the United States.

Because a large percentage of pregnant women and their partners are supposed

to be offered screening, and most prospective parents don't know their CF

carrier status, a few million tests would need to be done each year if

screening

were offered by most obstetricians.

" ACOG is focused on getting the word out to obstetricians, " said Dr. Deborah

A. Driscoll, an ob.gyn. at the University of Pennsylvania, Philadelphia, and

chair of ACOG's committee on genetics. " We're a little concerned about the

potential liability if physicians don't offer screening, so we feel that

it's

really important to keep educating our fellows, " she said in an interview.

" I talk to a lot of obstetricians at grand rounds, and I often ask whether

any of them are offering CF screening to their patients, and it's not

unusual

for no one in the room to raise their hand, " said Dr. Wayne W. Grody, a

member

of the CF screening task force that the American College of Medical Genetics

(ACMG) runs with ACOG.

" It's not that obstetricians are not aware of this; they've seen the

mailings. But they say that they don't have the time to talk with patients

about

it, that their patients come from ethnic groups where the prevalence of

mutations is low, and that they are not sure who will pay for the test, " Dr.

Grody told this newspaper.

Laboratories generally charge about $ 150-$ 200 for the current, standard CF

carrier test, and insurance coverage is currently spotty, even though

" insurers

should pay for it because screening is now the standard of care, " according

to

Dr. Grody, who is professor of medical genetics at the University of

California,

Los Angeles.

S. , Ph.D., executive director of the ACMG and another task

force member, guessed that by early 2003 about 20%-25% of U.S. obstetricians

were offering CF screening to couples planning a pregnancy or to pregnant

women

and their partners.

To get a better handle on exactly how widely obstetricians are offering

screening, ACOG is now devising a survey that will be sent to all of its

fellows

in the fall, Dr. Driscoll said.

ACOG's committee on genetics is also drafting a new mailing to fellows that

will " remind them to offer screening and review who to offer it to and what

to

do if a patient is found to carry a mutation, " she said.

In a typical screening scenario, an obstetrician will introduce the option

of carrier screening for CF, usually by giving the patient a brochure on the

subject that's published by ACOG, having the patient watch a video that the

physician has prepared, or discussing the option with the patient.

Providing ACOG's brochure is the minimum step that physicians can do to

adequately fulfill their responsibility, Dr. Driscoll said.

If a woman opts to be screened, her specimen will be sent to a laboratory

that runs the standard test specified by the ACOG and ACMG task force. If

she

harbors a CF mutation that is associated with causing severe disease, her

partner will then be screened.

If both parents carry a disease-linked mutation, then they'll receive

additional counseling about the risk that their children will face for

inheriting CF. The couple may then opt for genetic testing of the fetus and

may

consider terminating the pregnancy if the fetus has two CF-causing

mutations.

Although many obstetricians have yet to adopt the standard that ACOG set for

the specialty, 2002 saw a huge leap in CF testing.

About 50 laboratories across the United States participate in a proficiency

program for CF-mutation testing that's jointly run by the ACMG and the

College

of American Pathology, said Dr. Grody, chair of the committee that

administers

the proficiency-testing program.

Among these labs, the vast majority perform relatively small numbers of

tests at medical centers; the bulk of testing in the United States is done

by a

handful of large, commercial laboratories, most notably Quest Diagnostics

Inc.,

Genzyme Corp., and the Laboratory Corporation of America (Lab Corp).

A survey by this newspaper of these three laboratories found that two

insisted on keeping the exact volume of their CF testing program

confidential.

A spokesman for Genzyme said that their testing volume rose about threefold

from before September 2001 to January 2003. The number of tests ordered

doubled

last year and then showed a second, marked rise early this year.

A spokesman for Quest said that it was running nearly four times as many

tests by the end of last year as it had a year before, and as of early 2003

it

was performing " hundreds of thousands of tests " on an annualized basis.

A spokesman for LabCorp said that its testing volume had jumped by more than

11-fold from before October 2001 to December 2002.

As of last December, LabCorp was running more than 11,000 CF tests a month,

an annualized rate of more than 130,000 tests.

On the basis of these and other industry numbers, it's safe to say that by

the start of this year, the overall volume of CF testing in the United

States

was more than 300,000 tests a year and growing, said Dr. .

CF Mutations by Race and Ethnicity

Mutation Detection

Chance Both Chance of Rate using

Race or Partners Are Having Child 25-Mutation

Ethnicity CF rs With CF Panel Screen

White

(European ancestry) 1 in 625 1 in 2,500 90%

Hispanic American 1 in 2,100 1 in 8,500 57%

African American 1 in 4,200 1 in 17,000 69%

Asian American 1 in 8,100 1 in 32,400 insufficient data

RELATED ARTICLE: Changes Planned for CF Screening Panel

The panel of cystic fibrosis mutations that laboratories look for when

running a carrier screening test will change by next fall.

The standard screening panel tests for 25 different mutations in the cystic

fibrosis (CF) gene, called CFTR. The panel was established by the joint task

force of the American College of Obstetricians and Gynecologists and the

American College of Medical Genetics (ACMG) in 2001. But hands-on experience

with this panel has led to a few problems, and so some fine-tuning will

occur

later this year, said S. , Ph.D., executive director of the

ACMG

and a member of the CF carrier screening task force.

Although details of the changes are still to come, two refinements are

already clear. One involves reemphasizing that the test for a mutation known

as

5T should not be part of the primary screening panel because the results of

the

test lack clinical significance. Some laboratories have included 5T in their

primary screen, and this has led to some people being erroneously flagged as

mutation carriers and undergoing unnecessary genetic counseling, Dr.

said.

The 5T variant appears in about 5% of the population.

The second change will involve reassessing the significance of another

mutation, I148T, which is about 100 times more prevalent than originally

thought. This high prevalence suggests that the mutation may not really

cause

CF.

What's unlikely to change much is the modest number of mutations called for

in the screening panel. The 2001 recommendations set this at 25 (Out of more

than 800 identified), but some laboratories have offered broader screens,

involving as many as 70 mutations and have promoted these tests as better.

This is not the case, said Dr. Wayne W. Grody, professor of medical genetics

at the University of California, Los Angeles, and a member of the CF

screening

task force. " Larger panels are more confusing and more expensive. They're

not

worth it, " he said.