Neonatal

Screening
Hasanuddin
Jot Jin Yin
Megat Mohd Azman

Why Do Newborn
Screening?
Early detection & early treatment of newborn
screening disorders:
Lessens severity of complications
Improves quality of life
Lack of early detection & treatment can lead to:
Severe mental retardation
Inadequate growth & development
Death

Neonatal Screening in
Malaysia
Screening tests done at birth, for all babies:
Glucose-6-phospate dehydrogenase (G6PD)
deficiency
Congenital hypothyroidism

Screening test done in high risk neonates:

Hearing impairment screening
Eye screening

Glucose-6phosphate
dehydrogenase
(G6PD) deficiency

Introduction
Commonest red cell enzymopathy
Affecting over 100 million people worldwide.
It has a high prevalence (1020%) in individuals
originating from central Africa, the Mediterranean,
the Middle East and the Far East.

Function
G6PD is the rate-limiting enzyme in the pentose
phosphate pathway and is essential for preventing
oxidative damage to red cells.
Red cells lacking G6PD are susceptible to oxidantinduced haemolysis
G6PD deficiency is X-linked and therefore
predominantly affects males.

Causes

Clinical feature

Diagnosis
Diagnosis/Screening:
Cord blood collection for quantitative enzyme assay
Enzymatic colorimetric assay for the quantitative determination of
G6PD deficiency
6.4 U/gHb- Any neonate with an activity below this value was
diagnosed as G6PD deficient
Not 100% sensitive, may miss some cases
Laboratory findings:
1. Peripheral blood smear shows fragmented bite cells and
polychromasia, spherocytosis, Heinz bodies
2. A "direct antiglobulin test" (Coombs' test) this should be negative,
as hemolysis in G6PD is not immune-mediated

Heinz bodies and bite cells

Management
The most important measure is prevention avoidance of
the drugs and foods that cause hemolysis.
Vaccination against some common pathogens (e.g. hepatitis
A and hepatitis B) may prevent infection-induced attacks.
In the acute phase of hemolysis, blood transfusions might be
necessary, or even dialysis in acute kidney failure.
Some patients may benefit from removal of the spleen
(splenectomy),as this is an important site of red cell
destruction.
Folic acid should be used in any disorder featuring a high
red cell turnover

Congenital
hypothyroidism

Congenital hypothyroidism
Congenital hypothyroidism is a deficiency of the circulating
thyroid hormone at birth
It can occur because of an anatomic defect in the gland, an
inborn error of thyroid metabolism, or iodine deficiency.
The incidence of congenital hypothyroidism, as detected
through newborn screening, is approximately 1 per 4000
births
Twins
twins are approximately 12 times as likely to have
congenital hypothyroidism as singletons.
female-to-male ratio of a 2:1.

Signs and symptoms

Symptoms
Decreased activity
Large anterior fontanelle
Poor feeding and weight gain
Small stature or poor growth
Jaundice
Decreased stooling or constipation
Hypotonia
Hoarse cry
Signs
Coarse facial features
Macroglossia
Large fontanelles
Umbilical hernia
Mottled, cool, and dry skin
Developmental delay
Pallor
Myxedema
Goiter

DIAGNOSIS

Cord blood sample test for TSH.

If high TSH check T4, if low TSH check for other pituitary
defects.
Combination of low or low-normal serum total T4 levels and
a serum TSH within the reference range suggests thyroidbinding globulin (TBG) deficiency
Other investigations: radioactive iodine uptake study,
ultrasound, antithyroid antibodies
Thyroid scanning- (using technetium-99m or iodine-123),
the absence of radionuclide uptake suggests thyroid
receptor blocking antibodies, - can also demonstrate the
presence of an ectopic thyroid, such as a lingual or
sublingual gland

MANAGEMENT
Thyroid replacement: thyroxine 10-15g/kg/day
Infants with very low or undetectable T4, give 50
g daily.
Free T4 levels should be maintained at all times in
the upper normal range during the first 3 years of
life.
Follow up: TSH and Free T4, every month during
infancy, every 3 months from age 1-3, and 6
monthly thereafter.

MANAGEMENT
TIMING- should begin after diagnosis
DURATION- life long except in children suspected of having
transient hypothyroidism where re- evaluation is done at 3 years of
age
PREPARATION
1. No approved liquid preparation
2. Only L- thyroxin in tablet should be use crushed and mixed with
breast milk, formula, water and fed the infant but to not soy
contain or iron contain in which iron will reduce absorption of T4.
.Follow-up
. Monitor growth parameters and developmental assessment.

High Risk
Screening

Hearing impairment
screening
Neonates with risk factors for hearing loss are screened at
week 4-5 of life.
Hearing test for neonates:
Auditory brainstem response (ABR)- assessment of hearing
thresholds and the functional status of the auditory neural
pathway
Otoacoustic emissions (OAE) test - to determine cochlear
status, specifically hair cell function.
Good prognosis (better language and social development) if
treatment initiated <6 months.
Early treatment is essential for hearing pathway development.

Hearing Impairment
Screening
Indications:
Family history of hereditary childhood sensorineural hearing loss
In-utero infection, such as TORCH
Craniofacial anomalies including those with morphological
abnormalities of the pinna and ear canal
Birth weight less than 1,500 grams (1.5 kg)
Hyperbilirubinemia at a serum level requiring exchange transfusion
Ototoxic medications
Bacterial meningitis
APGAR scores of 0 4 at 1 minute or 0 6 at 5 minutes
Mechanical ventilation lasting 5 days or longer
Stigmata or other findings associated with a syndrome known to
include a sensorineural and/or conductive hearing loss

Eye Screening
Eye screening is done in:
Premature baby (birth weight<1.5kg or GA<30weeks)
Intrauterine growth restriction baby
Perinatal complications
Eye disorder screened at birth or during infancy:
Congenital cataract/glaucoma/corneal opacity red
reflex
Retinopathy of
prematurity

Eye Screening
Management:
Medical or surgical intervention
Counselling of parents and follow up
Referral to opthalmologist, geneticist if indicated

Extended
neonatal
screening

Heel Prick Test

Newborn blood spot

screening
Also known as Guthrie test or Heel prick test
Mothers of all newborn babies are offered testing
for some conditions by testing a blood spot taken
from the baby at 5-8 days of life (ideally on day 5).

Screen for disorders such

as:
Phenylketonuria

Sickle cell disease

Cystic fibrosis
Congenital hypothyrodism
Homocystinuria

Procedure
The baby's heel is cleaned with alcohol, and then
the heel is poked with a small needle.
Several drops of blood are collected inside circles
on a special piece of paper.
When enough blood has been collected, a small
bandage is put on the site.

Phenylketonuria (PKU)
Incidence 1:12,000
Inherited autosomal recessive condition, caused
by phenylalanine hydroxylase deficiency, which
results in the inability to convert phenylalanine to
tyrosine.
Normal levels of phenylalanine: <3mg/dL

Phenylketonuria (PKU)
Clinical features:
Brain damage (caused by high levels of
phenylalanine), leading to severe, progressive
intellectual impairment and epilepsy.
Blond hair, blue iris, fair skin (due to competitive
inhibition of tyrosinase which converts tyrosine to
melanin).

Phenylketonuria (PKU)
Management:

Diet low in phenylalanine which reduces the levels

of phenylalanine in the body and prevents brain
damage promotes normal growth and development.
Diet restriction for 8-10 years.
If dietary treatment initiated within few weeks of
birth and blood phenylalanine levels are carefully
monitored, mental retardation may be preventable

Sickle Cell Disease

A group of disorders that affects hemoglobin, the
molecule in red blood cells that delivers oxygen to cells
throughout the body.
Have atypical hemoglobin molecules called
hemoglobin S, which can distort red blood cells into a
sickle, or crescent shape.
Mutations in theHBBgene cause sickle cell disease, it
is inherited in an autosomal recessive pattern.
If a child tests positive on the screening test, a second
blood test (called a hemoglobin electrophoresis) should
be performed to confirm the diagnosis.

Normal Vs. Sickle Red

Cells
Normal

Disc-Shaped

Sickle

Deformable

Sickle-Shaped

Life span of 120

days

Rigid
Lives for 20 days or
less

Hemolysis and Vasoocclusion

Hemolysis:
The anemia in SCD is caused
by red cell destruction, or
hemolysis, and the degree of
anemia varies widely
between patients. The
production of red cells by
the bone marrow increases
dramatically, but is unable
to keep pace with the
destruction.

Vaso-occlusion:
Occurs when the rigid sickle
shaped cells fail to move
through the small blood
vessels, blocking local blood
flow to a microscopic region
of tissue. Amplified many
times, these episodes
produce tissue hypoxia. The
result is pain, and often
damage to organs.

Hemolysis and Vasoocclusion

Chronic Manifestations:

Acute Manifestations:

Anemia

Bacterial Sepsis or meningitis*

Jaundice
Splenomegaly

Recurrent vaso-occlusive pain

(dactylitis, muscoskeletal or
abdominal pain)

Functional asplenia

Splenic Sequestration*

Cardiomegaly and functional

murmurs

Aplastic Crisis*

Delayed growth and sexual

maturation

Stroke*

Acute Chest Syndrome*

Restrictive lung disease*

Priapism

Pulmonary Hypertension*

Hematuria, including papillary

necrosis

Avascular necrosis
Leg ulcers
Transfusional hemosiderosis*

*Potential cause of mortality

Sickle Cell Disease

Clinical features
SCD causes minimal effects in some people and
more serious problems in others.
Symptoms can be chronic (on-going or long-term)
or acute (immediate or short-term).
The symptoms of SCD are related to anemia, pain
or the effects of SCD on specific body parts.
Most infants do not show signs of SCD until they
are a few months old. Often, the first sign of SCD
is pain or swelling in the childs hands or feet
when small blood vessels become blocked. This
causes some children to develop a fever.

Sickle Cell Disease

Clinical features
Signs of anemia include:
Fatigue(feeling tired or weak)
Shortness of breath
Dizziness
Headaches
Cold hands or feet
Pale skin
Chest pain

Sickle Cell Disease

Management
Health maintenance
Infection prevention
Pain management
Sickle emergencies
Chronic disease management

Cystic Fibrosis
1 in 2,500 babies born in the UK have CF
The carrier rate is 1 in 25.
It is an inherited autosomal recessive condition.
The mucous in the lungs and digestive system is
thick and sticky resulting in respiratory infections
and difficulties in digesting food properly.
Neonatal screening has significantly reduced the
age of diagnosis of CF.

Cystic Fibrosis
Clinical features
CF is variable and causes minimal effects in some
people and more serious health problems in others.
Symptoms usually start in early childhood. In fact, most
children with CF show effects before one year of age.
About 15-20% of newborns with CF have a blockage of
their intestines calledmeconium ileus. This is caused by
thick stool that gets stuck in the intestines.
About 15% of children with CF have lung effects but do
not have problems with digestion. About 85% of
children have problems with both lungs and digestion.

Cystic Fibrosis
Clinical features
The first things parents often notice when a child has CF are:
Salty sweat; many parents notice a salty taste when kissing their
child
Poor weight gain and growth, even when a baby or child eats a lot.
This is called failure to thrive (FTT)
Constant coughing or wheezing
Thick mucus and phlegm
Many lung and sinus infections (pneumoniasandbronchitis)
Greasy, smelly stools that are bulky and pale colored
Intestinal problems (diarrhea or constipation, pain, gas)

Cystic Fibrosis
Treatment
Pancreatic enzymes
People with CF who have blockage of the pancreas
(also called ''pancreatic insufficiency') need to
take digestive enzymes in capsule form.
Pancreatic enzymes, along with a carefully
planned diet, will help treat failure to thrive and
will help your baby to grow at a healthier rate.

Cystic Fibrosis
Diet and Vitamins:
Vitamin supplements: People with CF have trouble absorbing
some vitamins, especially fat-soluble vitamins such as vitamin A, D,
E and K. Specific supplements may be suggested for your child.
A higher-calorie diet: Many babies and children with CF need
more food than typical in order to stay healthy. Some children with
CF need up to twice the normal number of calories to grow
appropriately. Adieticianwho has experience with CF can help you
come up with a good nutrition plan for your child.
Extra fluid: Your child may need to drink more water and liquids
than other children in order to help loosen the thick mucus and to
prevent dehydration. Children with CF lose more salt than others,
especially during exercise or in hot weather

Cystic Fibrosis
Medications:
Bronchodilators: These are inhaled drugs that open the
airways to the lungs
Mucus thinners: These are inhaled drugs that make mucus
thinner and easier to cough up. One type commonly used by
people with CF is called Pulmozyme.
Antibiotics: These may be used to fight off infections that
sometimes occur in the lungs of people with CF. There are
many types of antibiotics that may be used for people with
CF. One type of inhaled antibiotic that is often used for CF
treatment is called Tobramycin (TOBI).
Other medications may be suggested for children or adults
with liver disease, high blood sugar levels, or bone thinning.

Cystic Fibrosis
Surgical therapy may be required for the treatment of the following
respiratory complications:
Pneumothorax
Massive recurrent or persistent hemoptysis
Nasal polyps
Persistent and chronic sinusitis

GI tract complications requiring surgical therapy are as follows:

Meconium ileus
Intussusception
Gastrostomy tube placement for supplemental feeding
Rectal prolapse

Homocystinuria
Homocystinuria is a rare inherited metabolic disorder
characterised by an increased blood and urine
concentration of homocysteine - a sulfur-containing amino
acid.
The incidence is 1 in 344,000 worldwide but it is much
higher in Ireland (1 in 65,000). All cases are inherited as
autosomal recessive.
Affected individuals appear normal at birth but develop
serious complications in childhood.
Symptoms may occur as mildly delayed development
orfailure to thrive. Increasingvisual problemsmay lead to
diagnosis of this condition.

Homocystinuria
Management
Patients may be divided into pyridoxine-sensitive and
pyridoxine-insensitive groups.
In the first group, pyridoxine,folic acid, andvitamin B-12are
prescribed. These 3 vitamins, in combination, reduce the
homocysteine levels as well as provide clinical benefit
Pyridoxine, at a dose of 100-500 mg/d, is the drug of choice.
If patients are pyridoxine insensitive, a low-methionine diet
initiated at diagnosis, along withbetainesupplementation,
may help reduce homocysteine levels

THANK YOU