• Is a public health program designed to screen infants
shortly after birth for a list of conditions that are
treatable, but not clinically evident in the newborn
• Some of the conditions are only detectable after
irreversible damage has been done
• In some cases sudden death is the first manifestation of
Second screen strongly recommended
between 7 and 14 days of age
Third screen recommended for
sick and premature infants
Washington State law requires that every newborn be
tested within five days of age1
Who is screened?
• Most babies with metabolic disorder look normal at birth.
• By the appearance of signs and symptoms, irreversible
consequences are already present.
• So screening is essential as it allows
early intervention and prevention
of irreversible damage.
Why do newborn screening?
Criteria for Newborn Screening
Cost-effective to diagnose and treat
Wilson & Jungner, 1968
• Using the heel prick method, a
few drops of blood are taken from
the baby’s heel
• Blotted on a special absorbent
• Blood is dried for 4 hours and
sent to the Newborn Screening
The filter paper is often attached to a form containing required information about
the infant and parents. This includes:
• Date and time of birth.
• Date and time of sample collection.
• The infant's weight and gestational age.
• Information about whether the baby has had a blood transfusion
• Any additional nutrition the baby may have received (TPN).
3. Enzyme assays are used to screen for
galactosemia and biotinidase deficiency
4.Immunoassays measure thyroid
hormones for the diagnosis of congenital
hypothyroidism and 17-
hydroxyprogesterone for the diagnosis of
congenital adrenal hyperplasia.
5. Molecular techniques are used for the
diagnosis of cystic fibrosis and severe
B. bedside testing for hearing loss using evoked auditory
potentials and congenital heart defects using pulse oximetry.
• Immediately reported by phone and fax to baby’s
• Phone calls made by genetic counselors and/or
clinicians who are familiar with the disorders
together with the pediatrician and the primary heath
care provider for immediate assessment and early
The conditions included in newborn screening programs
around the world vary greatly, based on
Prevalence of certain diseases within a population
political pressure and availability of resources for both testing
and follow-up of identified patients.
Which disorders should be identified?
2002 Maternal and Child Health Bureau commissioned ACMG
Recommend a core panel to create uniform NBS across all
states through scoring system.
Which disorders should be identified?
Incidence of condition
Sign & Symptoms clinically
identifiable in the first 48 hours
Burden of disease
(natural Hx if untreated)
Does a sensitive AND specific screening test currently exist
Test characteristics ( Yes= apply
score; no = zero)
Availability of treatment
Cost of treatment
Potential efficacy of existing
Benefits of early intervention
Benefits of early identification
(family & society)
Benefits diagnosis and treatment prevent mortality
Availability of diagnostic confirmation
Simplicity of therapy
Phenylalanine -------------------//----------------------- Tyrosine
(substrate) phenylalanine hydroxylase (product)
Disorder of phenylalanine hydroxylation leading to
accumulation of this amino acid.
Patients have progressive developmental delay up to
severe mental retardation, seizures and autistic-like
• The most commonly included disorders of the endocrine system
are congenital hypothyroidism (CH) and congenital
adrenal hyperplasia (CAH).
• Congenital hypothyroidism
• Breathing problems, anemia, slow heart rate, delayed milestones,
poor weight gain and growth, hearing loss, jaundice
• Screening for CH is done by measuring thyroxin (T4),
thyrotropin (TSH) or a combination of both analytes
• CH was added to many newborn screening programs in the
1970s, often as the second condition included after PKU.
• The most common cause of CH is dysgenesis of the thyroid
• Early hormonal substitution can control the condition.
Congenital adrenal hyperplasia
• Elevated 17-hydroxyprogesterone
(17OHP) is the primary marker used
when screening for CAH, most
commonly done using enzyme-linked
immunosorbant assays, tandem
mass spectrometry test to reduce the
number of false positive results.
• Classic CAH is caused by a deficiency
of the enzyme steroid 21-hydroxylase,
and comes in two forms - simple
virilizing and a salt-wasting form.
• Treatement is steroids.
Scikle cell disease
• A sickle cell test is a blood test done to screen for sickle cell
trait or sickle cell disease.
• The red blood cells deform because they
contain an abnormal type of hemoglobin,
called hemoglobin S, instead of the normal hemoglobin.
Penicillin has been used in children with sickle
cell disease, blood transfusions for patients
identified with severe thalassemia.
Also known as mucoviscidosis, is an
autosomal recessive genetic disorder. It
affects most critically the lungs, and also the
pancreas, liver, and intestine. It is
characterized by abnormal transport of
chloride and sodium across an epithelium,
leading to thick, viscous secretions.
• CF is caused by a mutation in the gene for
the protein cystic fibrosis transmembrane
conductance regulator (CFTR)
• The newborn screen initially measures for raised
blood concentration of immunoreactive
trypsinogen. Infants with an abnormal newborn
screen need a sweat test .
• People with CF have increased amounts of sodium
and chloride in their sweat. In contrast, they have
less thiocyanate and hypothiocyanite in their
saliva and mucus. CF can also be diagnosed by
identification of mutations in the CFTR gene.
• No cure for cystic fibrosis but early
diagnosis can improve the codition
• The cornerstones of management are
proactive treatment of airway
infection, and encouragement of good
nutrition and an active lifestyle.
• Recently therapies such as
transplantation and gene therapy
aim to cure some of the effects of
Urea cycle disorders
Disorders of the distal urea cycle, such as citrullinemia,
argininosuccinic aciduria and argininemia are included in
newborn screening programs in many jurisdictions that using
tandem mass spectrometry to identify key amino acids.
Proximal urea cycle defects, such as ornithine transcarbamylase
deficiency and carbamoyl phosphate synthetase deficiency are
not included in newborn screening panels because
A. They are not reliably detected using current technology
B. Severely affected infants will present with clinical symptoms
before newborn screening results are available.
Some regions claim to screen for
HHH syndrome (hyperammonemia,
based on the detection of elevated
ornithine levels in the newborn
screening dried blood spot
SCID has not
been added to
It requires PCR is
affected infants also
SCID is a stem
Severe combined immunodeficiency
Others recently added disorders
Duchenne muscular dystrophy
• X-linked disorder caused by
defective production of dystrophin.
• Many jurisdictions around the world
have screened for DMD using
elevated levels of creatine kinase
measured in dried blood spots
• Galactosemia occurs when an enzyme
galactose-1-phosphate uridyl transferase
deficient or not woking properly.
• (Coagulopathy, sepsis, severe jaundice,
• Treatment Restrict milk products
Caused by a lack of the enzyme biotinidase
Progressive hearing loss
Skin problems – eczema
Treated with biotin
• Screening for G6PD: by measuring the level of the
enzyme can prevent haemolytic crisis especially if family
history is present.
• Screening for diabetes: by measuring the level of IGF-1.
• Screening for hyperbilirubinaemia: by measuring total
and direct serum bilirubin.
Be informed about
Parents, on behalf of their children, have the right to
Parents and consumers must be involved in all parts of the
policy-making and implementation process
Pitfalls of Newborn Screening
• Not collecting newborn screening sample prior to transfusion
because the baby is “too young” or has not yet been fed
– Transfusions and feeding history alter results of some, but not
all of the newborn screening tests.
– Card has place to list transfusions, time of first feeding,
antibiotics, overall health and birthweight.
• Meaningful interpretation of test results takes all those bits
of information into account.
• Not collecting an adequate newborn screening sample
– Most newborn screening tests are quantitative.
• More or less blood means higher or lower values and may
lead to false positives or negatives.
• Diagrams of correct circle filling are meant to ensure that the
appropriate amount of blood is on the filter paper, and that
there is no evidence of dilution (with alcohol, for example)
• Assuming that an abnormal newborn screen is a false positive
because the baby is well and/or because factors known to be
associated with a false positive are present.
– This runs counter to the whole purpose of newborn screening,
which is to pick up kids BEFORE they are symptomatic