The State of California Newborn Screening Program
Risk of Having a Child With an Abnormality Child with abnormality 3-5%
Normal child 95 - 97 %
Causes of Birth Defects Genetics 20% 60%
20% Environment
Combination
Goal of the Newborn Screening Program To prevent long-term effects of genetic disease through early screening and intervention
Criteria for a Screening Program 1. Important health problems 2. Associated with disease / known symptoms 3. Amenable to treatment
Criteria for a Screening Program 4. Easy to detect, reliably and economically 5. Adequate methods of confirmation and follow-up available.
Autosomal Recessive Inheritance
Not a carrier
25 %
Carrier
Carrier
50 %
Disorde r
25 %
1. Education 2. Testing 3. Retrieval of identified cases 4. Diagnosis 5. Treatment 6. Evaluation
History of Newborn Screening 1966 – PKU *1980 - Hypothyroidism and Galactosemia 1990 - Sickle cell and other Hgb 1999 - Hgb H and Hgb H/Constant Spring
History of Newborn Screening
2005 - CAH and Metabolic Disorders 2007 - CF and Biotinidase Deficiency 2010 - Severe Combined Immune Deficiency (SCID)
TOTAL: 78 Disorders *Over 13,000,000 specimens are stored at the State Lab
BARCLAYS OFFICIAL CALIFORNIA CODE OF REGULATIONS TITLE 17 PUBLIC HEALTH DIVISION
Title 17 6505 (Registrar 86, No. 47-11-22-86) 6805 Collection of Specimen • All infants born in a licensed perinatal health facility must have a NBS specimen collected as close to discharge as is practical with the following exceptions. • Infants remaining in the hospital for more than five days must have the NBS specimen collected on or before the sixth day of age. • Infants who are transfused with red blood cells (RBC), must have a specimen collected prior to the transfusion.
Title 17 6506 (Registrar 86, No. 47-11-22-86) 6506. Reporting and follow-up of tests. (1) Perinatal licensed health facilities shall review each newborn’s medical record within 14 days from the date of discharge to determine that the results of required tests are filled in the newborn’s medical record, or that a parent’s or legal guardian’s signed refusal has been filled in the newborn’s medical record.
Newborn Screening Program Area Service Centers (NBS-ASCs)
Stanford University Medical Center, Palo Alto Children’s Hospital Central Calif., Madera UCLA Medical Center Harbor/UCLA Medical Center Rady Children’s Hospital, San Diego
Kaiser Permanente North
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Kaiser Permanente, Northern CA Kaiser Permanente, Southern CA
Kaiser Permanente South
Western Clinical LabRoseville Kaiser Regional (North) Allied Medical Lab – Mountai n View
Laboratory Service Areas Fresno Community Hospital Lab
Quest Diagnostics – West Hills Memorial Medical Center of Long Beach
Kaiser Regional (South)
Genetic Disease Laboratory State of California, Richmond Stanford ARUP Quest Hemoglobin Reference Laboratory Children’s Hospital, Oakland
Follow-up Education Consultation Referral Evaluation Quality improvement
“Important Information for Parents” about the Newborn Screening Test
California Newborn Screening Test Request Form (TRF) State form Health Connect “Newborn Screening Panel CA” Order # 213115
New Test Request Forms Has an expiration date Now has 6 blood spots on filter paper
All Information on the NBS-TRF MUST BE CORRECT ACCURATE & LEGIBLE
Give the PINK/BLUE Parent’s Copy to the parent
Newborn Screening Nurse Coordinators
Follow-up Referral Education Consultation
Notified of presumptive positive cases, true earlies, inadequates, data entry errors, and special forms
Presumptive Positive Case Inadequate True Early
Contact Specialist, Neonatologist, and/or PCP Monitor patient status
Newborn Screening Specialists Metabolic Specialist Dr. Rebecca Mardach Newborn Screening Medical Director (LAMC) Pediatric Endocrinologists Pulmonary & Cystic Fibrosis Specialist Dr. Muhammad Saeed Cystic Fibrosis Center Director (LAMC) Pediatric Hematologist Dr. Richard Shearer Sickle Cell and Hematology Center Director (WLA)
Newborn Screening Process Hospital Births Blood Spot Collected Before Discharge
Mail Test Results
Mail Courier
Notification of Discharge without Collection
Contract Laboratory Unable PKU Demographic to Test Galactosemia Data Positive Hypothyroid Entry Genetic Test
Sickle Cell
Disease Branch
GDL DATABASE
NBS Follow-up Contractor Information Mail Test Entered Results
Follow-up Notification Not Collected Missing Data Contacts
Newborn’s Physician “Unable to Test” New Specimen Collected
Parents
}
Recall Specimen Collected
Disorder Prevalence
GDL– PKU, Hypothyroid Contract-Galactosemia Lab Contract-Biopterin Lab Contract-Hemoglobin Lab
Total Related Disorders
KAISER CA Birth SOUTH Prevalence Prevalence
Endocrine
1 in 1,748
1 in 1,282
Metabolic
1 in 3,231
1 in 3,460
Hemoglobinopathies
1 in 2,553
1 in 1,442
Cystic Fibrosis
1 in 3,004
1 in 1,442
California Newborn Screening Program Birth Prevalence of Genetic Disorders in California, January 1, 2006 – December 31, 2011 (6 years) n= 3,185,874 newborns screened
Disorders Detectable by NBS Program as of January 19, 2011 I. Cystic Fibrosis II. Endocrine Disorders (4) III.Metabolic Disorders (via Tandem Mass Spectrometry (MS/MS) Screening) A. Amino Acid Disorders (19) B. Organic Acid Disorders (17) C. Fatty Acid Oxidation Disorders (11) IV.Other Metabolic Disorders (2) V. Hemoglobin Disorders (24)
Anaheim
2188
2
0
1
2
0
0
0
0
Baldwin Park
2812
2
1SW
2
3
0
0
1PBD
0
Downey
3577
2
0
5
2
0
0
1PBD
0
Fontana
4315
4
1SW
2
4
0
0
Transient tyro
0
Irvine
2454
0
0
1
0
0
0
MCADD&IBDHD
0
Los Angeles
2229
1
2SW
1
CF/CRMS
0
0
0
0
Moreno Valley
352
0
0
0
0
0
0
0
0
Panorama City & BK & AV Riverside
3102
2
0
2
2CF
1
0
1 MCADD
0
3396
6
1NC
1
0
0
0
3 CTD
0
San Diego & Palomar South Bay
5181
1
0
5
2
0
0
0
0
1905
0
1NC
2
1
0
0
0
0
W. Los Angeles
1613
1
0
0
0
0
0
0
0
Woodland Hills
1481
0
0
0
1
0
0
0
0
34,605
21
6
22
24
1
0
9
0
Totals
5 CRMS
TOTAL CASES
Severe Combined Immune Deficiency (SCID)
Metabolic
Galactosemia & variants
Phenyl-ketonuria (PKU) & variants
Cystic Fibrosis & CRMS
Hemoglobin-opathies
Congenital Adrenal Hyperplasia
Primary Congenital Hypothyroidismm
2011
Birth Rate (estimated)
January 2011 – December 2011
5 9 10 12 3 6 0 13 11 8 4 1 1 83
Total Presumptive Positives (290) Approx. 1 in 119 Births is a Presumptive Positive Total Disorders/Cases (83) Approx. 1 in 417 Births is a Disorder/Case Approx. 1 in 4 Presumptive Positives is a Disorder/Case
Overview of Disorders
Phenylketonuria (PKU)
PKU Prevalence in California 1/35,796
Phenylalanine I. Phenylalanine
Tyrosine hydroxylase
Tetrahydrobiopterin (BH4)
Dihydrobiopterin (BH2)
Dihydropteridine reductase
Biopterin
Guanosine triphosphate
Mental Retardation Neurological and behavioral disorders
Classical Galactosemia Prevalence in California 1/93,702
Galactose + ATP Galactokinase Galactose-1-Phosphate + UDP Glucose UDP Galactose UDP Glucose + PP
Galactose
(1) Mg + + (2) Transferase (3) NAD 4-Epimerase (4)
Pyrophosphorylase (5) NADPH Aldose Reductase
Galactose-1-Phosphate + ADP UDP Galactose +Glucose-1-Phosphate UDP Glucose Glucose-1-Phosphate
Galactitol
Effects of Untreated Galactosemia Red blood cells
Optic lens - cataract
Kidneys - albuminuria - glactosuria - aminoaciduria
Brain Liver - mental retardation - jaundice - hepatomegaly - cirrhosis
Sickle Cell Disease and Other Hemoglobinopathies
Birth Prevalence in California of Hemoglobinopathies 1/2,553
Clinically Significant Hemoglobin Results Sickle Cell Disorders FS FSC FSD FSE FS variant
Fsa FCS FDS FES F + variant + S
Thalassemia F only - Beta thalassemia major Hb E Beta thalassemia
Clinical Manifestation of Sickle Cell Disease Infections Vaso-occlusive crisis Anemia Splenic Sequestration
Early Diagnosis
Penicillin
Immunization
Well-child care
Nutrition
Education and counseling
Primary Congenital Hypothyroidism Prevalence in California 1/9,996
Thyroid Dysgenesis Aplasia Hypoplasia Ectopic Gland
90%
Other Inborn errors of hormone synthesis Maternal drug intake Hypothalamic/pituitary abnormality
10%
Symptoms of Hypothyroidism skin mottling puffy eyes lethargy thick tongue hoarse cry coarse facial features
Gestational age > 42 weeks
Birthweight > 4000 grams
Constipation
Slow feeding
Mental retardation Impaired growth
Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia Prevalence in California 1/17,699
congenital – present at birth adrenal – involving the adrenal glands (located on top of the kidneys) hyperplasia – overgrown tissue
Types of CAH u Classical Salt Wasting Simple Virilizing Non-Classical or late-onset
An inherited disorder that results from inadequate production of the hormones cortisol and /or aldosterone, and excessive production of the hormone androgen
Cortisol maintains the body’s energy supply and controls the body’s reaction to stress. Instead of making cortisol, the adrenal glands produce more androgens.
Increased androgen production results in ambiguous genitalia in newborn girls
Aldosterone (salt-retaining hormone) is used by the kidney to help the body maintain normal levels of the salt minerals, sodium and potassium
If the adrenal gland cannot make aldosterone, too much salt and water is lost in the urine, leading to salt deficiency and dehydration
The treatment for CAH is replacement hormones. Female infants who have virilization of the genitalia may require surgical correction.
First Tier Testing Cut-offs 17-OHP value (nmol/L) Birth Weight Urgent Cut-off (specimens with values equal to or above this above this cut-off, cut-off are called out as positive)
19 gene mutations in 2010 Block T-cell development (little or no immune system) Can occur with no previous family history Prevalence - 1: 50,000 to 1: 100,000 Babies are normal at birth Cause chronic and recurrent infections, death in first years of life if untreated
SCID Methodology •Real-Time PCR TREC Assay (PerkinElmer) •TRECs are stable circular DNA molecules •Generated during T- cell development •TREC copies are measured •Low or absent TRECs indicate genetic defect in newborn to generate T lymphocytes •TRECs below the cutoff value are considered as positive for T-cell lymphopenia including SCID •Positives are followed-up
CALIFORNIA SCID NEWBORN SCREENING TREC Test and Follow Up [Puck and Lorey, 11/2/2011, rev 2/23/12eg] Initial TREC Assay
TRECs >40*
TRECs ≤40
Normal
TRECs ≤5
Actin >5000 Actin ≤5000
Repeat TREC
with Actin
TRECs 6-25
TRECs >25
DNA Amplification Failure, Incomplete
Repeat Heel Stick
Actin >10,000 Actin ≤10,000
Positive DNA Amplification Failure Regular
Positive
NICU Incomplete
Normal DNA Amplification Failure TRECs ≤ 25 TRECs >25
*TREC and Actin copies per uL of blood, assuming each 1/8” punch of dried blood filter represents 3 uL of blood.
Positive
Normal
Normal
CBC & diff Lymphocyte subsets at Quest Lab interpreted by CDPH Immunology Consultant
Abnormal
Refer to Primary Immune Deficiency Center
NBS Results Mailers Two mailers are sent out: one is sent to the hospital medical records and one is sent to the doctor listed on the test request form To view the Results Mailers look in the Media Tab, under Description “KP REFERENCE LAB“ AND under File attached to “Lab Procedure Scanned Report”
Presumptive Positive - in Health Connect Snapshot - Abnormal findings on neonatal screening Encounters – Message Newborn Screening Lab Follow-Up Open message – template of disorder, values, and the name and number of specialist who was notified Episodes – Newborn Screening – Link all visits pertaining to NBS (see if current or resolved)
Preventing Missed Cases •
Never rule out the possibility of a disorder solely on the basis of the NBS result.
•
Any signs or symptoms should be followed up on immediately.
•
Report diagnosis to Nurse Coordinators.
Newborn Screen Test Request Form (NBS-TRF) No NBS?? home birth, adoption, born out of state put order in Health Connect contact us at 8-338-3322
NBS - TEST REFUSAL (NBS-TR) Mother must sign If mother refuses (2) nurses must sign – give PINK COPY to mother Send WHITE COPY to STATE Send GOLDENROD COPY to Scanning Document NBS-TR was completed with date & time in BABY DISCHARGE CHECKLIST
NBS NOT OBTAINED (NBS-NO) Complete when a newborn is to be transferred Complete when parents refuse the newborn screen Complete when a newborn expires SEND GOLDENROD COPY TO scanning Document NBS-NO was completed with date & time in BABY DISCHARGE CHECKLIST
Quality Assurance & Improvement “Escape Baby Report” Outpatient Pediatrics and Lab Department staff
Ongoing… Provide site visits region-wide to assist the FCC, NICU, Medical Records and Lab Departments in identifying and correcting newborn screening problems (process and/or procedures).
oClasses provided on the Test Request Form revision oInvolved in Skills Lab sessions oQuarterly Newsletters
Did you know… Within the 158,693 square mile are of California, the Newborn Screening Program operates in 58 counties.
Did you know……… Each year over half a million newborns are screened in California. One in every 1200 babies has a disorder that is screened for by the Program.
Did you know……… Nearly 300 perinatal facilities (maternity centers, children’s and military hospitals) participate in the California Newborn Screening Program. Another 200 providers that include pediatricians, laboratories, clinics, certified nurse midwives and licensed midwives collect screening specimens.
Did you know……… Since 1980 over 13 million newborns were tested in California and over 8000 children were diagnosed with a disorder through the Newborn Screening Program.
www.cdph.ca.gov/NBS for provider/patient information
Any questions?
