Georgia epidemiology report, Vol. 25, no. 1 (Jan. 2009)

January 2009

volume 25 number 01

Gerogia's Newborn Metabolic, Endocrine, and Hemoglobinopathy Screening (NBS) Program

Georgia's Newborn Metabolic, Endocrine, and Hemoglobinopathy Screening (NBS) program is designed to identify and provide early treatment for select inherited disorders that would otherwise cause significant morbidity, including abnormal physical and mental growth and development, or death. The five components of the NBS program are:
Screening: universal testing of newborns though a heel stick blood specimen sent to the Georgia Public Health Laboratory.
Follow-up: rapid identification and referral of all newborns with a positive screen.
Medical Diagnosis: diagnostic evaluation by a private physician or tertiary treatment center after abnormal test results are found, to confirm or rule out abnormal findings.
Management: rapid implementation and long-term planning of therapy after confirmed diagnosis.
Evaluation: validation of testing procedures, efficiency of follow up and intervention. Furthermore, adding other tests to the system is considered, when indicated by research and scientific evidence.
Georgia's newborn screening program began in 1968 with routine screening for phenylketonuria in all newborn infants. Ten years later, legislation passed that expanded screening to 6 metabolic/endocrine conditions with voluntary screening for sickle cell anemia. The 1978 legislation also expanded the program, placing a greater emphasis on follow-up, diagnosis, management, and family counseling. In 1998, screening was mandated for all newborns for hemoglobinopathies including sickle cell anemia, sickle hemoglobin C disease, and sickle beta thalassemia. Since 2007, Georgia law (OCGA 31-12-6 & 3112-7) and Rules and Regulations (Chapter 290-5-24) require that every live born infant have an adequate blood test for 28 disorders (Table 1). The same law also requires that every live born infant be screened for hearing loss. Routine screening for this panel of 29 conditions is recommended by the American College of Medical Genetics.

The screening component of the NBS program begins for most infants at the birth facility before discharge. A few drops of blood are taken from the heel of a one- to seven-day old infant and are transferred to filter paper for transport. This "bloodspot" is sent through the mail or by courier to the Georgia Public Health Laboratory (GPHL) for testing. GPHL received 170,097 of these specimens in 2007. The number of newborn screens was about 20,000 more than the number of births for 2007. This is because infants with abnormal screens may be rescreened several times, with several abnormal results. Additionally, another screen is requested for any child with a newborn screening test performed before 24 hours of life. Before 24 hours, a newborn's developing blood proteins may produce an abnormal result. Screens are considered presumptive abnormal if blood values cross a predetermined cut point. The level of this cut point is determined to use existing resources effectively and minimize the risk of missing a true case. With this strategy, most presumptive abnormal screens are false positives, but the risk of missing a true case is very low. Of the 170,097 specimens received, 23,284 (14%) were presumptive abnormal screens that required further confirmatory testing. Screens with abnormal results for the 28 disorders determined by the blood spot test receive follow-up by GPHL and contractors who contact the family or physician of the infant for further screening or diagnostic testing to confirm or rule out the diagnosis presumptively identified by the initial screen. Hearing screening is also performed before discharge from the birth hospital.
The 23,284 presumptive abnormals included 13,354 (57%) screens that were potentially positive for metabolic or endocrine disease. Of the 13,354, 3,653 screens identified elevated immunoreactive trypsinogen (IRT), indicating increased risk for cystic fibrosis, and 5,202 screens identified abnormal levels of thyroid stimulating hormone (TSH) or thyroxine (T4), indicating increased risk for congenital hypothyroidism. From the 13,354 presumptive abnormal metabolic or endocrine screens, 221 infants were found to have a diagnosed classical disease or disease subtype. The

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other 9,930 (43%) presumptive abnormal screens were for hemoglobin sickle cell carrier or trait; 274 (3%) were found to be carriers, who then received a confirmatory test to assess for sickle cell disease. Sickle cell disease was identified in 248 of the children identified as carriers. Among children who failed the hearing screening, follow up testing identified 159 infants with hearing loss.
The initial abnormal result marks the beginning of the followup component of the NBS program. Depending on the abnormalities identified, infants may be referred for follow up of either metabolic or endocrine conditions, hemoglobin disorders, or hearing loss. Infants with positive metabolic or endocrine screening results are referred immediately by GPHL to the newborn screening follow-up program at Emory University School of Medicine, Division of Medical Genetics. Similarly, follow-up of abnormal results that suggest actual hemoglobin disease is provided through either the Division of Pediatric Hematology/Oncology at the Medical College of Georgia in Augusta, or the Georgia Comprehensive Sickle Cell Center at Grady Heath System in Atlanta, depending on proximity to each facility. If the hemoglobin abnormal results suggest carrier, or "trait" status, the Sickle Cell Foundation of Georgia, Inc. is responsible for follow-up. In each facility, program staff locate the infant, ensure that abnormal results are reported to the infant's health care provider, and make recommendations for follow-up testing. Failed hearing screening results in a referral from the initial screening facility, usually the birth hospital, for diagnostic evaluation to confirm or rule out hearing loss. If an audiologist or physician diagnoses hearing loss, they notify the District Health Department in the district where the child lives so the appropriate public health partners can facilitate intervention.
After screening and diagnosis, the follow-up program provides referral for all diagnosed infants to the appropriate specialist for treatment and long-term management. At Emory, medical geneticists and the Metabolic Nutrition Program are responsible for providing medical and nutritional treatment and management for the infants with metabolic conditions. The Medical College of Georgia in Augusta, Grady Heath System in Atlanta, or the Sickle Cell Foundation of Georgia, Inc., ensure that infants with diagnosed hemoglobin diseases are referred to the appropriate specialist for treatment and long-term management. For hearing loss, an early intervention specialist or educator with the Division of Public Health's Children 1st program will assess the needs of a family and link them to the appropriate services.

In 2006, almost 550 Georgia infants were born outside of a licensed hospital, including births at home, in a doctor's office, or at a clinic. These infants may not have immediate access to newborn screening. According to Georgia Rule and Regulation 290-5-24-.02, when a live birth occurs in a facility other than a licensed hospital, it is the responsibility of the person in charge of the facility or person in attendance to give written notice to the parents, guardian, or other legally responsible person of the legal requirements for the newborn to be tested and to advise where testing can be obtained.
Newborn blood spot screening in Georgia is now routinely done for 28 conditions, many more than just a decade ago. Some of the improvement is due to technological advances, including the increased efficiency of the tandem mass spectrometer (MS/MS). Computers have allowed the automation of MS/MS, which can detect the amount of acylcarnitines and amino acids in the blood and thus evaluate potential amino and organic acidemias and fatty acid oxidation disorders with high precision in a few minutes time.2 Other advances in technology have increased the efficiency of testing for other disorders such as congenital hypothyroidism, cystic fibrosis, and hemoglobinopathies.
Once screening is completed, the results are sent electronically from GPHL to the Division of Public Health to be matched to the birth records. Through this process, birth records that do not have corresponding screening results can be used to identify unscreened infants in need of follow-up. The matching process also provides data for population-based analysis of newborn screening results. This matching is done in a new child health information system called State Electronic Notifiable Disease Surveillance System (SendSS) Newborn. This secure webbased system is designed for hospitals, physicians, state and local public health departments, newborn screening follow-up facilities, and other groups to improve services provided to infants and families in Georgia.
This article was written by Brendan Noggle, M.P.H.
References 1. Centers for Disease Control and Prevention. Impact of Expanded Newborn Screening -- United States, 2006. MMWR 2008;57:1012-1015. 2. Centers for Disease Control and Prevention. Using tandem mass spectrometry for metabolic disease screening among newborns: a report of a work group. MMWR 2001;50(No. RR-3).

Division of Public Health http://health.state.ga.us
S. Elizabeth Ford, M.D., M.B.A., F.A.A.P. Acting Director, State Health Officer
Martha N. Okafor, Ph.D., Deputy Director Health Information, Policy, Strategy, & Accountability

John M. Horan, M.D., M.P.H. State Epidemiologist
Director, Epidemiology Section http://health.state.ga.us/epi
Cherie Drenzek, D.V.M., M.S. Director, Acute Disease Epi Section

Georgia Epidemiology Report Editorial Board
Carol A. Hoban, M.P.H., Ph.D. Editor Kathryn E. Arnold, M.D.
Cherie Drenzek, D.V.M., M.S. John M. Horan, M.D., M.P.H. S. Elizabeth Ford, M.D., M.B.A., F.A.A.P. Angela Alexander - Mailing List Jimmy Clanton, Jr. - Graphic Designer

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Georgia Department of Human Resources
Division of Public Health

Two Peachtree St., N.W. Atlanta, GA 30303-3186 Phone: (404) 657-2588
Fax: (404) 657-7517
Please send comments to: gaepinfo@dhr.state.ga.us

Table 1: Metabolic, Genetic, Hemoglobinopathy, and Hearing Loss Cases Diagnosed in Georgia through Newborn Screening, 2007

Classical conditions included in the blood test for 28 disorders are in bold font, and their variants and subtypes are italicized.

Metabolic and Endocrine Condition
3-Methylcrotonyl-CoA Carboxylase Deficiency Argininosuccinic acidemia Beta-ketothiolase deficiency Biotinidase Deficiency
Biotinidase Deficiency- Partial Carnitine Uptake Defect Citrullinemia Congenital Adrenal Hyperplasia, Classical
Congenital Adrenal Hyperplasia, Variant Cystic Fibrosis Galactosemia, Classical
Galactosemia, Variant Glutaric Acidemia Type I 3-OH 3-CH3 Glutaric Aciduria Homocystinuria Hypothyroidism, Primary
Hypothyroidism, Secondary Isovaleric Acidemia Long-chain L-3-OH Acyl-CoA Dehydrogenase Deficiency Maple Syrup Urine Disease Medium Chain Acyl Co-A Dehydrogenase Deficiency Methylmalonic Acidemia - cbl A Methylmalonic Acidemia - cbl B Multiple Carboxylase Deficiency Phenylketonuria, Classical
Phenylketonuria, Variant (hyperphenylalaninemia) Propionic Acidemia Trifunctional Protein Deficiency Tyrosinemia, Prolonged Neonatal
Tyrosinemia, Type II Very Long-Chain Acyl-CoA Dehydrogenase Deficiency Other Diagnoses not specifically listed in Georgia Rules and Regulations* Metabolic and Endocrine Total

Cases
4 0 0 0 2 0 0 13 0 24 3 35 1 0 0 67 27 0 0 1 12 0 0 0 7 1 0 13 2 0 1 8 221

Hemoglobinopathies#
Sickle Cell Anemia Sickle Hemoglobin C Disease Sickle Beta Thalassemia

248

Diagnosed Hearing Loss

159

Case counts based on reports received by February, 2009. * Glucose-6-phosphate Dehydrogenase Deficiency, Hypermethioninemia, Hyperthyroidism, and Short-chain Acyl-coenzyme A
Dehydrogenase Deficiency # A single summary count is presented for the three hemoglobinopathies because screening test results do not always
definitively distinguish which of these conditions an infant may have. The specific diagnoses are made in subsequent evaluation, and those results are not routinely reported back to the NBS program.
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The Georgia Epidemiology Report Epidemiology Branch Two Peachtree St., NW Atlanta, GA 30303-3186
Providers can contact Public Health IMMEDIATELY 24 hours a day, 7 days a week, by calling: 1-866-PUB-HLTH (1-866-782-4584) to report immediately notifiable diseases and public health emergencies

PRESORTED STANDARD U.S. POSTAGE
PAID ATLANTA, GA PERMIT NO. 4528

January 2009

Volume25Number01

Reported Cases of Selected Notifiable Diseases in Georgia, Profile* for October 2008

Selected Notifiable Diseases
Campylobacteriosis Chlamydia trachomatis Cryptosporidiosis E. coli O157:H7 Giardiasis Gonorrhea Haemophilus influenzae (invasive) Hepatitis A (acute) Hepatitis B (acute) Legionellosis Lyme Disease Meningococcal Disease (invasive) Mumps Pertussis Rubella Salmonellosis Shigellosis Syphilis - Primary Syphilis - Secondary Syphilis - Early Latent Syphilis - Other** Syphilis - Congenital Tuberculosis

Total Reported for October 2008
2008 47 738 28 5 63 390 11 4 17 3 1 0 0 3 0 246 85 7 51 43 91 0 42

Previous 3 Months Total Ending in October

2006 2007 2008

166

172

186

10132

11453

7193

133

105

85

16

28

18

252

251

190

5563

4857

3018

19

29

24

16

14

20

55

48

46

13

10

15

1

1

9

4

10

2

0

0

0

11

3

7

0

0

0

756

845

887

492

363

219

31

36

30

153

167

186

91

103

135

261

292

283

1

2

1

129

111

127

Previous 12 Months Total Ending in October

2006 2007 2008

574

668

715

39509

43756

38662

275

243

250

42

44

48

720

687

686

20022

18495

15019

114

130

146

59

68

54

190

160

167

36

43

45

7

10

36

19

26

19

5

0

2

31

18

23

0

0

0

1831

1985

2309

1169

1693

1274

123

111

129

479

567

711

388

437

511

1006

1159

1311

8

11

9

516

475

502

* The cumulative numbers in the above table reflect the date the disease was first diagnosed rather than the date the report was received at the state office, and therefore are subject to change over time due to late reporting. The 3 month delay in the disease profile for a given month is designed to minimize any changes that may occur. This method of summarizing data is expected to provide a better overall measure of disease trends and patterns in Georgia.
** Other syphilis includes latent (unknown duration), late latent, late with symptomatic manifestations, and neurosyphilis.
AIDS Profile Update

Report Period
Latest 12 Months

Disease

Total Cases Reported*

Classification <13yrs

>=13yrs Total

HIV, non-AIDS 19

3,084

3,103

Percent Female MSM

28

26

Risk Group Distribution %

IDU

MSM&IDU HS

Unknown Perinatal White

2

1

4

67

1

18

Race Distribution %

Black

Hispanic Other

77

4

1

12/07-11/08 AIDS

2

1,939

1,941

27

29

3

1

7

59

<1

18

74

5

<1

Five Years Ago:**

HIV, non-AIDS 79

1,577

1,656

36

30

8

3

16

37

5

20

76

3

1

12/03-11/04 AIDS

12

1,539

1,551

29

33

7

3

15

41

1

19

75

5

<1

Cumulative: HIV, non-AIDS 222

12,840

13,062

31

28

6

2

10

53

2

21

75

4

1

07/81-11/08 AIDS

239

33,421

33,660

20

43

14

5

14

23

1

30

67

3

1

Yrs - Age at diagnosis in years

MSM - Men having sex with men

IDU - Injection drug users

HS - Heterosexual

* Case totals are accumulated by date of report to the Epidemiology Section ** Due to a change in the surveillance system, case counts may be artificially low during this time period

***HIV, non-AIDS was not collected until 12/31/2003

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