Prof. Dr J P Soni

Dr S N Medical college; JODHPUR

INDIA50th2

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NEW BORN

SCREENING

Newborn Screening

Every couple & family wants after birth

Baby should remain Healthy

Four millions are born with congenital problems

140 MILLION CHILDERN ARE BORN

EVERY YEAR

25-30% are expected to have Inborn Error of Metabolism

1: 1350

5-15% of all sick newborn In NICU expected to have

Transient or permanent IEM

Inborn errors of

metabolismDefinition:

Inborn errors of

metabolism is a rare group of

recessive genetic disorders in

which the body cannot

metabolize food components

normally. These disorders are

usually caused by defects in the

enzymes involved in the

biochemical pathways that break

down food components.

Prior to delivery, “A Fetus” is

usually "protected" from any

ill-effects of a

metabolic disease

either by the

Maternal circulation which

provide missing product

or

Placenta which remove toxic

substances.

Inborn Errors of Small molecule Metabolism

Example: Galactosemia

I E M - Large molecule : Lysosomal storage diseases

Example: Gaucher's Disease

Disorders of Energy Metabolism

Example Glycogen Storage Disease

Other more rare classes of metabolism error Peroxisomal disorders

Transport disorders

Defects in purine and pyrimidine metabolism & Receptor Defects

IEM Classification:

Population : 1220 million

Birth rate 20.6/1000

Every day 30,000 babies are born

Incidence of neonatal disorder is approximately 1:1000

Thus every day 30 newborns are born with

Different Neonatal disorders

Population ; 1220 million

Birth rate 20.6/1000

Congenital Hypothyroidism (1965) - 1: 1700

Every year 15000 neonates are born with it

Every day 30.000 babies are born

Every day 1 new born / 1000 is born with neonatal disorder

Every day 30 newborns are born with neonatal disorders

Population ; 1220 million

Birth rate 20.6/1000

G-6PD(Glucose 6 phosphate deficiency ) : 1: 2200,

3.5 lacs; Male 28.3%; Female : 1.05%

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Congenital Adrenal Hyperplasia(1990) : 1: 2575

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Cystic Fibrosis(1995) :1:10000 – 1: 40000

INDIA

Population ; 1220 million

Birth rate 20.6/1000

PKU (Phenylketonuria) : 1: 18300

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Biotinidase deficiency(1990) :

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Galactosemia: 1: 10300

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Mapple syp urine disease : 1: 10215

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Tyrosinemia : 1: 6234

INDIA

Population ; 1220 million

Birth rate 20.6/1000

down syndrome: 20,000

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Thalassemia : 14,000

INDIA

Population ; 1220 million

Birth rate 20.6/1000

Sickle cell anemia: 5,000

INDIA

Individually these diseases are very rare, but when all are

clubbed together they are not very uncommon.

Incidence is approximately 1: 1000 newborn

Even then our country do not have national wide any

new born preventive program

INDIA50th2

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NEW BORN

SCREENING

Q. What types of

screening do we have

for such patients ?

1. Prenatal Diagnostic screening – is type of

primary prevention for At risk fetus.

2. New born screening – is type of secondary

Prevention for Pre-symptomatic newborns

3. High risk screening – symptomatic new borns

4. Postmortem screening – Metabolic Autopsy

is type of secondary

Prevention for Pre-symptomatic newborns

Q.When newborn screening program

was started?

Ans:

Newborn screening program was started in the

United States in the early 1960s, and since than

it has been expanded to countries around the

world.

On April 24, 2008, President George W. Bush

signed into law the Newborn Screening Saves

Lives Act of 2007

What are the

component of

Newborn Screening ?

Components of NBS

1. Education: Professionals, parents and policy makers

2. Screening:

Collection activities, Specimen delivery, Laboratory testing and Result reporting

3. Early Follow-up:

4. Diagnosis:

5. Management:

Medical mgt, Long term follow-up, Specimen mgt

6. Evaluation:

What is Newborn

Screening ?

Most newborn screening tests are done by measuring

metabolites and enzyme activity in whole blood samples

collected on specialized filter paper

Hearing loss using automated auditory brainstem response.

Congenital heart defects using pulse oximetry

Congenital hypothyroidism and congenital adrenal hyperplasia

Immunoassays measure .

Cystic fibrosis and severe combined immunodeficiency -

Molecular techniques -.

Infants who are screen positive undergo further testing to

determine if they are truly affected with a disease or if the test

result is falsly positive.

Ans:

NBS is an essential public health program

To

Screen New Born Babies for

Metabolic disorders

Genetic diseases

Blood diseases

Nongenetic – Toxoplasmosis etc.

Q. What is the Goal of NBS ?

Ans:

The Goal of NBS is –

Timely detection of disorders - that is during

neonatal period

To Prevent morbidity, mortility & disability

(mental retardation or a lifelong impairment).

By

Early detection

Complex system of Diagnosis

Complexity of Treatment

Q. Who should be offer NBS ?

Ans: All New Born Babies should be given

Opportunity for New Born Screening .

As all babies looks Normal at birth.

There is variable window period before baby

Develops overt clinical picture of disease after

birth.

Thus one can diagnosing & treat the

disease before obvious clinical manifestation by NBS.

Thus baby with IEM will not develop

catastrophic consequences and complications.

Q. How to select diseases under

NBS program?

Ans:

The condition sought should be an important health problem

There should be an accepted treatment for patients with recognized

disease.

Facilities for diagnosis and treatment should be available

There should be a recognizable latent or early symptomatic stage

There should be a suitable test or examination

Newborn screening programs initially used

screening criteria based largely on criteria

established by JMG Wilson and F. Jungner in 1968

Ans :

The test should be acceptable to the population

The natural history of the condition, including development from

latent to declared disease, should be adequately understood

There should be an agreed policy on whom to treat as patients

The cost of case-finding (including diagnosis and treatment of patients

diagnosed) should be economically balanced in relation to possible

expenditure on medical care as a whole

Case-finding should be a continuing process and not a “once and for

all” project.

INDIA

Q. What is basic NBS program?

Ans . Basics of Newborn Screening program

vary from country to country -

India core screening should include test for

diagnosis of

Congenital Hypothyroidism Cong.

Adrenal Hyperplasia

G6PD. Cystic fibrosis, Sickle cell anemia

Biotinidase

INDIA

Q. What is expanded NBS program ?

Ans : Disease under expanded NBS are

diagnosed either by

MS/MS

Tandem mass spectrometry

Like : aminoacidopaties, organic acidemia &

disorder of fatty acid oxidation.

Q. When to collect blood for NBS?

Ans :

For congenital Hypothyroidism Cord blood can

be collected

For NBS blood should be collected before discharge

Between 72 hours to 7 days, When baby had at least

6-8 times adequate breast feeding.

Metabolism of neonate needs 4-5 days for liver to

function independently, to give true picture of

neonatal marker.

Q. How to collect blood for NBS?

Specimen Collection: Dried Blood Spots

•Do not touch any of the filter paper circle before or after collection.

•Select puncture site and cleanse with 70% isopropanol.

•Use a sterile, disposable lancet with 2.0 mm, or less, point

•Wipe away first blood drop.

•Use second LARGE blood drop to apply to surface of FDA-approved filter

paper circle.

•If not completely filled, add a second LARGE drop immediately.

•FILL all required circles completely. FILL from only one side of the filter

paper.

•Dry specimen at room temperature 3-4 hours in HORIZONTAL position.

•See NCCLS LA4-A3, 1997. Blood collection on filter paper for neonatal

screening programs; Approved standard.

Ans : Blood should be collected from Heel prick

on filter paper with following properties-

Filter paper should be Homogenous

Filter paper should absorb 100ul blood in 12 sec &

Produce circle of 12 mm diameter.

What Variables Affects

Measurements for

Specimens Collected on Filter Paper ?

Variables Affecting Measurements for

Specimens Collected on Filter Paper

Handling and storage of paper

Humidity condition of paper

Volume of blood collected

Haematocrit level of blood donor

Absorption time for blood

Q. What precaution should be taken

While collecting blood for NBS ?

Ans : Blood should be collected from Heel prick

on one side of filter paper.

Blood should be dried at room temperature.

Blood should not be collected in layers on paper.

Venous blood & syringe should be avoided.

Discard first drop of blood.

Cord blood should be avoided as it is contaminated

with maternal blood

When to say specimens is

Unsatisfactory ?

Unsatisfactory Specimens

Clotted or Layered

Serum Rings

Specimen Not Dried Before Mailing

Supersaturated

No Blood

Diluted, Discolored, or Contaminated

Scratched or Abraded

Quantity Insufficient for Testing

Q. Which new born disorders should

be screened in India ?

Ans : for Our country new born screening is

divided into three groups

Group A : All new borns should be screen for

Cong. Hypo-thyrodism

Cong. Adrenal Hyperplasia

G 6-PD

Group B: Screening in the high risk population-

If history of MR, Seizure disorders, Critically ill

new born or SIDS – IEM and consanguinity

Phenylketonuria, Homocystinuria, Alkaptonuria,

Galactosemia, Sickle cell anemia, Cystic fibrosis,

Biotinidase def, MSUD, Tyrosinemia, FAOD, MCAD

Group C : Expanded New Born Screening

By TMS screening 30-40 IEM

resource Rich Setting

Q. Which new born disorders can be treated ?

Ans :

PKU

Congenital Hypothyroidism

Galactosemia

Sickle Cell Disease

Biotinidase Deficiency

Congenital Adrenal Hyperplasia

Maple Syrup Urine Disease (MSUD)

Homocystinuria

Tyrosinemia

Cystic Fibrosis

Toxoplasmosis

Gaucher, MPS, Fabry disease, Pompe disease