Newborn Screening

1
Newborn Screening

• Baylor College of Medicine
• Anoop Agrawal, M.D.

2
History of Newborn Screening

• Began in the early 1960s
• In 1961, Dr. Robert Guthrie developed an assay
  that could detect elevated levels of
  phenylalanine from a single drop of an infants
  blood.
• By 1965, over half of U.S. states had mandated
  PKU testing.
• In 1995, most states screened for five disorders
  on average.

3
Expansion of Screening

• In the 1990s, a new technology was developed
  known as tandem mass spectromety or MS/MS. This
  tool was able to screen for multiple biochemical
  markers (and hence disorders) using the same drop
  of blood.
• In March 2005, the American College of Medical
  Genetics (ACMG) issued a report advocating for a
  mandated uniform panel of 29 disorders.
• Prior to 2005, there was significant variablity
  amongst states in mandated screening ranging
  from zero to eight
• By 2005, average number of conditions tested for
  by states increased to 24

4
Newborn Screening

• Currently, how many genetic diseases are
  available for newborn screening?
• The ACMG recommends states screen for 48 genetic
  diseases.
• How many genetic diseases are currently screened
  for in the state of Texas?
• As of Dec 09, Texas now screens for 28.

5
Extent of Mandatory Expanded Screening
Fourteen states do not mandate the expanded
testing. Parents are offered the testing through
a voluntary pilot program.
6
Screening in Texas

• In 2005, HB790 was passed requiring expansion of
  the newborn screening program using the ACMG
  (American College of Medical Genetics)
  recommended panel as funds allowed.
• As of Dec 09, the number of diseases screened
  increased to from 27 to 28.
• Prior to that, only five diseases were screened
  PKU, hypothyroidism, galactosemia, sickle cell
  disease, congenital adrenal hyperplasia
• In Texas, the Department of State Health Services
  (DSHS) operates the newborn screening case
  management program.

7
What conditions are screened for in Texas?
8
Newborn Screens for Texas
9
Incidence of inborn errors

• Which of the following inborn errors of
  metabolism has the highest incidence?

A. congenital adrenal hyperplasia
B. congenital hypothyroidism
C. cystic fibrosis
D. galactosemia
E. phenylketonuria
1 in 12,000
1 in 3,500
1 in 4,000
1 in 60,000-80,000
1 in 10,000-25,000
Cystic fibrosis is now tested for in the state
of Texas.
10
Most common congenital defect

• What is the most common congenital defect
  screened for?
• The overall number one most common disease
  screened for is hearing loss.
• It has an incidence of 2-3 in 1,000. Almost 20x
  more common than PKU
• Currently screened for via OAE, ABER
• DNA testing for hearing loss is already possible,
  but not yet employed.
• 50 of newborns with hearing loss is due to
  genetic factors
• 90 of newborns with hearing loss are born to
  hearing parents

11
Estimated Expansion Statistics

• In Texas
• Approximately 400,000 births a year
• Approximately 800,000 specimens a year collected
  and tested
• Follow-up on approximately 15,000 abnormal
  screens a year
• Approximately 600 diagnosed cases per year

12
More is better, right?

• Expanded newborn screen has raised concerns
  amongst some.
• The identification of an abnormality that does
  not become clinically apparent is termed
  pseudodisease.
• Several of the newly added biochemical disorders
  maybe pseudodiseases.
• Currently research suggests 3-MCC (is done in
  Texas) and SCAD (not in Texas) may not lead to
  significant disease.
• Histidenemia is one that has been removed from
  screening due to lack of clinical disease in
  long-term studies

13
More is better, right?

• This raises the question of How many more of the
  conditions added to the expanded list will become
  pseudodiseases?
• Expanded screen for multiple rare disorders
  inevitably leads to more false positive results
  even when specificity is high
• Indirect costs of expanded newborn screening
• Parental anxiety
• Cost of more diagnostic testing
• Potential lack of meaningful intervention

14
Scenario One

• You receive a phone call from the Texas
  Department of State Health Services. A six day
  old patient you saw yesterday has a positive
  newborn screening test for increased methionine
  and may have Homocystinuria. A review of the
  chart shows the child had a normal exam and
  seemed to be doing well.
• What should you do next?
• Where do you go for more information?

15
What do you do next?

• Know what resources are available to assist you.
• FACT sheets created by the AAP to provide
  pediatricians and parents with general
  information on the condition
• Can be found on AAP website or Texas State
  Department of Health website www.dshs.state.tx.us
  /newborn
• These are also available in spanish on the Texas
  site.
• ACT sheets created by the American College of
  Medical Genetics. Provides physicians with the
  action plan diagnostic workup and clinical
  manifestations to watch for.
• Also found on Texas website or on ACMGs website
  www.acmg.net

16
FACT Sheets

• Example of FACT sheet from Texas Department of
  State Health Services
• FACT sheets on AAP website are geared more
  towards physicians.
• This covers causes, symptoms, overview of
  treatment and outcomes.
• This sheet by DSHS is designed for parents and
  physicians.

17
ACT Sheets

• Example from ACMG for increased methionine -
  Texas Dept of State Health Services has adapted
  the same information on their website.
• In this case, obtain quantitative amino acids,
  plasma homocysteine level and urine homocysteine
  level.
• Consult with metabolic specialist.
• Counsel and educate family about homocystinuria.
• Report findings to newborn screening program.

18
Scenario Two

• You are seeing a newborn infant in the Level I
  nursery. The parents tell you they do not want
  their child to have newborn screening testing.
  They feel that such testing is not part of Gods
  plan. What should you do?
• In the state of Texas, a parent has the right to
  object to screening if it conflicts with their
  religious tenets or practices.

19
Scenario Three

• You are examining a two week old female in your
  office. The family has recently moved to Houston
  from Miami. After your exam, you inform the
  parents the infant will need a newborn screen.
  The parents ask you why she needs a second
  screen? In Florida, their older child only had
  newborn screening performed once.
• Texas mandates ALL infants have two newborn
  screens. The first must be collected between
  24-48 hours of life. The second may be performed
  between 7-14 days of life.
• What if the baby is 6 months old and has only one
  newborn screen on file?
• In Texas, every child must have 2 newborn screens
  documented by age of 12 months.

20
Hot off the presses!
21
The Future

• Current screening relies on detecting biochemical
  markers via tandem mass spectrometry (MS/MS).
• This methodology enabled expansion of newborn
  screening in an inexpensive, rapid and easy
  manner.
• The future lies in DNA-based screening.
• This will undoubtedly raise the specter of
  diseases screened for along with requiring more
  of the pediatrician.
• DNA testing also raises a host of privacy,
  societal and medical issues which will need to be
  addressed.

22
Bibiliography

• Tarini, BA, Freed GL. Keeping up with the
  newborn screening revolution. Contemporary
  Pediatrics 2007244, 36-49.
• Texas State Department of Health Services,
  www.dshs.state.tx.us/newborn
• National Newborn Screening and Genetics Resource
  Center, www.genes-r-us.uthscsa.edu