4.1.

NEONATAL SCREENING

LEARNING OBJECTIVES

At the end of this module, you should be able to:

1. Explain what neonatal screening is

2. List the common conditions for which the newborn is usually
screened
3. Explain the advantages of neonatal screening
4. Discuss how this is being done in Indian context
5. Explain the role of a Family Physician in neonatal screening

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 MODULE MAP

Introduction
Importance in Primary Care
The Indian Context
Trigger Patient Studies
I. Definitions
II. Importance of neonatal screening
III. The basis of neonatal screening
IV. Neonatal screening in developed countries
V. Neonatal screening in India
Take a Break I
VI. Neonatal Conditions that need screening
A. Congenital hypothyroidism
B. Congenital hearing loss
C. Congenital heart disease
D. Biotinidase deficiency
E. G6PD Deficiency
F. Galactosemia
G. Sickle cell disease and other hemoglobinopathies
Take a Break II
Summary
Answers
Appendices
References & Further Readings

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INTRODUCTION
When we look at the ten areas of care extended by the Family Physician, we know that screening
is a very important part of the care provided by the Family Physician. But neonatal screening
differs from adult screening in many ways, though the basic principle remains the same. With
neonatal screening tests becoming a subject of political controversy in the last decade all over the
world, is there a possibility of this screening tests being useful? Especially in Indian context
where the infectious diseases that can be prevented by a mere availability of clean water and air?
If so, what we, as Family Physicians can do about it?
In this module, we will see what the neonatal screening tests in developed countries are and also
in our country and what can we do in our own health setups.

IMPORTANCE IN PRIMARY CARE

Since neonatal screening is to find shortly after birth, the diseases which are treatable but not
clinically evident in the newborn, it is very important in primary care. In countries where
expanded neonatal screening is very much a practical part of health care, the follow-up testing
after screening is coordinated between geneticists and the infant's Pediatrician or Primary Care
Physician.

THE INDIAN SCENARIO

Neonatal screening started as the basic screening of the heel prick blood
sample of a newborn and it became a public policy the USA first, before
almost 4 decades. In many countries, this has become a public policy now.
Though we have pilot programs in many places in India, we still do not
have neonatal screening as a national program.
In February 2013, National Rural Health Mission of India launched a program Rashtriya Bal
Suraksha Karyakram (RBSK) – Child Health Screening and Early Intervention Services under
NRHM. The program is aimed at screening over 27 crore children from 0 to 18 years for 4 Ds -
Defects at birth, Diseases, Defciencies and Development Delays including Disabilities. As
rightly stated by Mr. Ghulam Nabi Azad, the Union Minister of Health & Family Welfare, “It is
a gigantic task”.

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These 27 crore children are divided into three categories:

Categories Age group Estimated Coverage

Babies born at public health facilities and home Birth to 6 weeks 2 crores
Preschool children in rural areas and urban slums 6 weeks to 6 years 8 crores
Children enrolled in classes 1st to 12th in 6 to 18 years 17 crores
Government and Government aided schools
Table 4.1.1 Categories of Children for Screening under NRHM

According to this, 2 crores of new born are included in this neonatal screening program.
According to NRHM report, about 7.9 million children are born annually with a serious birth
defect of genetic or partially genetic origin which accounts for 6 percent of the total births
globally. With a large birth cohort of almost 26 million per year, India would account for the
largest share of birth defects in the world. An ICMR study from five zonal centers in India
covering 5 lakh newborns has revealed an incidence of congenital hypothyroidism to be 1 in
1000 live births. Also, prevalence of diseases like sickle cell anemia, beta thalassemias etc. are
more in specific areas of our country.
Operational guidelines of this screening program are discussed later in this module.

TRIGGER PATIENT STUDIES

There are some case studies given below.
• Try to answer before studying the module
• Do not look at the answers now
• Study the module and then answer the same questions
• Then look at the answers & be encouraged by the learning accomplished!!!

Patient Study 4.1.1

Mrs. Suganya brings her 3 year old son Dinesh with complaints of constipation. With a single
look, you make your diagnosis- the look is unmistakable – the child has all
the features of hypothyroidism. When you ask the mother about the other
complaints, she hesitatingly tells you, “You know, doctor…. He is not like
my other children… he does not talk or walk… just sits in the place I keep
him... he would just cry when he wants something…”

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1. What is the single most important condition that can cause mental retardation and can
be completely reversed with early diagnosis and medical management?

2. If it is early diagnosis, how early?

3. Now Dinesh is 3 years old. Will treatment help him to achieve full cure?

4. Like so many children in our country who struggle through their life with delayed physical
growth and delayed development, you understand Dinesh is suffering.
What do you think about a screening program for neonates in India? Do you think it is cost
effective?

Patient Study 4.1.2

Mrs. Lakshmi, from a far off

village has brought her one year
old son to your clinic. She says
that her son was delivered at
home and he was born with a tumor in his back. Since the grandmother believed it is the curse of
gods, so far he has been treated by local pujaris. They have spent a lot of money on him and
nobody in the village talks to her properly because she has given birth to an abnormal child.

On examination, he has a meningocele. His lower limbs are neurologically normal.

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1. Why there was a delay in bringing the child to the hospital?

While in developed countries, screening of newborn stands for screening for genetic and some
non genetic disorders’ NRHM has launched a program which will train the ASHAs to look for
congenital anomalies in community deliveries. One of the training tools is a book with pictures
of various congenital anomalies.
2. What is your opinion about this?

I.DEFINITIONS

Newborn screening: Newborn screening is testing performed on

newborn babies to detect a wide variety of disorders though the
manifestations of the disease are absent. Typically, testing is
performed on a blood sample obtained from a heel prick when the
baby is two or three days old.

Most newborn screening tests are done by measuring metabolites and enzyme activity in
whole blood samples collected on specialized filter paper, however many areas are starting to
screen infants for hearing loss using automated auditory brainstem response and congenital
heart defects using pulse oximetry. Most of the areas of screening suggested by NRHM
involve physical examination. Diseases that require blood investigation and common in India
like congenital hypothyroidism, sickle cell anemia and beta thalassemia are classified as
“optional”, depending on the geographical location.

II. IMPORTANCE OF NEONATAL SCREENING

American academy of pediatrics declares neonatal screening as one of the finest achievements of
preventive medicine. One mother of a child who was screened and diagnosed to have a genetic
disease (clinical manifestations can be prevented by simple dietary modifications) has said “how
much difference few drops of blood can make in a life ...”

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 As we go through section 4, which discusses about the common diseases that can be prevented
by neonatal screening, it will become clear how an early diagnosis bring about a dramatic
change. There are controversies about neonatal screening even in countries where it is a public
policy about the usefulness of screening a disease which is very rare and the treatment is not very
definite.

III. THE BASIS OF NEONATAL SCREENING

Neonatal screening differs in many ways from other areas of screening which follow Wilson and
Jungner classic criteria. The basic accepted rules of neonatal screening are:
 Having an acceptable treatment protocol in place that changes the outcome for patients
diagnosed early with the disease
 An understanding of the condition's natural history
 An understanding about who will be treated as a patient
 A screening test that is reliable for both affected and unaffected patients and is acceptable to
the public

VI. NEONATAL SCREENING IN DEVELOPED COUNTRIES

Neonatal screening became a public health program first in United States of America; but now,
in many countries around the world, it is an important public health policy. The list of diseases
screened in US makes a big list; it is given in the appendix 4.1.1.
This list differs from country to country. For most developed countries, initial targets for
screening were phenylketonuria and congenital hypothyroidism, but now include other genetic
disorders like congenital adrenal hyperplasia,(CAH), cystic fibrosis, galactosemia, G6PD
deficiency, biotinidase deficiency, hemoglobinopathies e.g. Sickle Cell Disease (SCD), and
conditions such as hearing and intrauterine infections, especially toxoplasmosis.

As we saw before, 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.

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Optimal Timing and Method of Sampling
The American Academy of Pediatrics has advocated the ideal time of sampling after 72 hours
and within 7 days of life. However, this policy would be very difficult in India to adopt due to
high birth rate, limited space in most hospitals and definite resistance. A recent document
suggests that the screening be done at 24-48 hours of life when, enteral feeding has been
established, renal function is improving and the hepatic metabolism is in the process of
becoming mature. Thus it may be ideal for our setup, to take the sample after first 24 hours of
life.
Since dried blood spot remains stable for years, the mode of collection should be capillary blood
from the heel, impregnation of drops of blood into filter paper, drying of these blood spots and
transport of the specimens to a central screening laboratory.

V. NEONATAL SCREENING PROGRAM IN INDIA

If we see the list of conditions in the appendix, we will know it is not possible in our country
because of various reasons. Though there are recommendations, there is no organized neonatal
screening program in India.
 Screening all the children is not practical and not financially feasible; because of the high
prevalence of infectious disease that are claiming the children, health policies have
typically targeted infectious morbidities and mortalities.
 One of the important needs for a screening program is the availability of the data
regarding disease burden.
 The collection of blood in filter paper, which is the standard method of collecting blood
for screening, is difficult in pour country because of high home delivery rate, early
discharge from hospitals and cultural taboos related to newborns.
 Certain countries are using tandem mass spectrometry to screen for a wide range of
disorders. The technique is expensive and available only at a handful of centers in India
Because the above sited problems, neonatal screening in India is totally different from what is
practiced in the developed countries. The below mentioned conditions and how this can be done
are proposed by the NRHM through the Rashtriya Bal Suraksha Karyakram (RBSK) scheme:

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Conditions identified for screening:

Identified Health Conditions for Child Health Screening and Early Intervention Services
1. Neural Tube Defect
2. Down’s Syndrome
3. Cleft Lip & Palate / Cleft Palate alone
4. Talipes (club foot)
5. Developmental Dysplasia of the Hip
6. Congenital Cataract
7. Congenital Deafness
8. Congenital Heart Diseases
9. Retinopathy of Prematurity
Optional conditions: Congenital Hypothyroidism, Sickle Cell Anemia, Beta Thalassemia

How is this being done under RBSK?

a. Facility-based newborn screening
This includes screening of birth defects in institutional deliveries at public health facilities,
especially at the designated delivery points by ANMs, Medical Officers/ Gynaecologists.
Existing health service providers at all designated delivery points will be trained to detect,
register report and refer birth defects to the District Early Intervention Centers in District
Hospitals.
b. Community-based newborn screening (age 0-6 weeks) for birth defects
Accredited Social Health Activists (ASHAs) during home visits for newborn care will use the
opportunity to screen the babies born at home and the institutions till 6 weeks of age. ASHAs
will be trained with simple tools for detecting gross birth defects. Further ASHAs will mobilize
caregivers of children to attend the local Anganwadi Centers for screening by the
dedicated Mobile Health Team.
For performing the above additional tasks, she would be equipped with a tool kit consisting of a
pictorial reference book having self-explanatory pictures for identification of birth defects.
Suitable performance based incentive may also be provided to ASHAs.
The following table gives an overview of the primary screening levels and the conditions
screened at each level.

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 Primary screening level Action
1
Condition selected By In health Block DEIC
ASHA facilities Health
where baby Team
is delivered (6 weeks
and
above)
Neural Tube Defect Yes Yes Surgery, tie up with Tertiary Public
Hospital
Down’s Syndrome2 Yes Yes Management at DEIC
Cleft Lip & Palate Yes Yes Surgery, tie up with Tertiary Public
Hospital including ‘Smile Train’3
Club Foot Yes Yes Surgery, tie up with Tertiary Public
Hospital including ‘Smile Train’
Developmental Yes Yes Yes Management at DH
Dysplasia of the Hip
Congenital Cataract Yes Yes Yes Management at DH
Congenital Deafness Yes Yes Yes Tie up with Tertiary Public
Hospital
Congenital Heart Yes Yes Yes Surgery, tie up with Tertiary Public
Diseases Hospital including ‘Smile Train’
Retinopathy of Yes Tie up with Tertiary Public
Prematurity only for Hospital
preterm babies
1
DEIC - District Early Intervention Center
2
1/140 Children with Downs can have hypothyroidism
3
Smile Train India provides free cleft and palate treatment across India through our nationwide network of
accredited treatment centers

Pilot studies for neonatal screening in India

There aren’t many studies in the prevalence of inherited disorders and neonatal screening.
 As of march 1st, 2014, in the state of Kerala, based on the study of frequency of congenital
disorders1 conducted by the Christian Medical College, Vellore, neonatal screening for
congenital hypothyroidism, congenital adrenal hyperplasia (CAH) and G6 PD deficiency is
available in select 45 government hospitals that have more than 100 deliveries a month. To
1
The approximate prevalence in India of congenital hypothyroidism is 6 per 10,000 newborns; CAH has a
prevalence rate of 4.5 in 10,000 live births while G6 PD is 5 in 10,000 live births.

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 all hospitals in the city not covered by the government, the Indian Academy of Pediatrics
proposes to launch this programme in phases.
 A pilot newborn screening project in Karnataka was carried out on 125 thousand newborns;
homocysteneimia, hyperglycinemia, MSUD, PKU, hypothyroidism and G6PDdeficiency
were found to be the common errors.
 Another pilot program Expanded Newborn Screening was started in 2000 at Hyderabad to
screen amino acid disorders, CH, congenital adrenal hyperplasia (CAH), G6PD deficiency,
biotinidase deficiency, galactosemia and cystic fibrosis. Testing a total of eighteen thousand
three hundred babies, the results revealed a high prevalence of CH (1 in 1700). The next
common disorder was congenital adrenal hyperplasia followed by G6PD deficiency.
Aminoacidopathies as a group constituted the next most common disorder.
 Including 5 nearly completely reversible and treatable disorders like congenital
hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase
deficiency, biotinidase deficiency and galactosemia in screening is suggested by some.
 Studies done in India using different hearing screening protocols have estimated the
prevalence of neonatal hearing loss to vary between 1 and 8 per 1000 babies screened.
Early identification and intervention for hearing loss by 6 months of age provides better
prognosis in language development, academic success, social integration and successful
participation in the society.

TAKE A BREAK 1

Patient Study .4 .1.2

1. If you are teaching your health worker to identify a child with Down syndrome, what features
would you teach her to look for?

2. Down syndrome, being a chromosomal anomaly, are there any advantages of diagnosing it
early? Explain

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VII. CONDITIONS THAT NEED SCREENING
As we discussed earlier, the list of conditions that are screened in developed countries is long. In
the following section, we will discuss the conditions for which the pilot screening has started or
screening is done by some state governments, apart from the conditions suggested by NRHM.
A. Congenital hypothyroidism
Thyroid hormone deficiency at birth is one of the most common treatable causes of mental
retardation. There are multiple etiologies of this disorder, heritable and sporadic, varying in
severity. There is an inverse relationship between age at diagnosis and neurodevelopmental
outcome; the later treatment is started, the lower the IQ will be.
Incidence
The incidence of hypothyroidism in India is . Newborn infants
with Down syndrome are at increased risk of having CH
(approximately 1 in 140 newborns).
Clinical Manifestations
1. Most affected infants appear normal at birth, without
obvious manifestations. This is likely the result of trans
placental passage of some maternal thyroid hormone
2. Head circumference may be at a slightly higher
percentile because of brain myxedema.
3. Approximately 5% of these infants, generally those who
are more severely affected, have recognizable features at
birth, including large fontanels and wide sutures,
macroglossia, distended abdomen with umbilical hernia,
and skin mottling.
4. As maternal thyroid hormone is excreted and disappears in the first few weeks, clinical
features gradually become apparent. These infants are slow to feed, constipated, lethargic,
and sleep more (“sleep through the night” early), often needing to be awakened to feed.
They may have a hoarse cry, may feel cool to touch, may be hypotonic with slow reflexes,
and may have prolonged jaundice. A goiter is seen in 5% to 10% of these infants.
5. If hypothyroidism goes undiagnosed beyond 2 to 3 months of age, infants will begin to
manifest slow linear growth. If this disorder is untreated, studies show a loss of IQ
proportionate to the age at which treatment is started: if treatment is started at 0 to 3 months
of age, mean IQ is 89 (range: 64–107); if treatment is started at 3 to 6 months of age, mean
IQ is 71 (range: 35–96); if treatment is started at older than 6 months, mean IQ is 54 (range:
25–80).

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6. Other long-term neurologic sequelae include ataxia, gross and fine motor incoordination,
hypotonia and spasticity, speech disorders, problems with attention span, and strabismus.
Approximately 10% of these infants will have an associated sensorineural deafness, and
approximately 10% will have other congenital anomalies, most commonly cardiac defects.
Inheritance
Approximately 85% of cases are sporadic, and 15% are hereditary.
Benefits of Newborn Screening
As we know, the screening for neonatal hypothyroidism is positive and if it is confirmed, it
almost gives a second chance for the baby for the whole life.
Screening
These are based on measurement of TSH or thyroxine (T4) on the second or third day of life by
heel prick. In India, it is done by TSH estimation in the cord blood or by heel prick on the second
or third day.
There are three ways of doing it:
1. Primary TSH, back upT4 – TSH is checked first, if high, then T4 is checked.
2. Primary T4, back up TSH - T4 is checked first, if low, then TSH is checked.
3. Concomitant T4 and TSH – This is more accurate, but increases the cost.
Screening programs usually use a cut off of T4 < 6.5 ug/dL and TSH > 20mu/L. But, we have
to be aware that the levels vary according to the day the blood was taken.
Follow-up and Diagnostic Testing
Infants with abnormal Infants with abnormal screening results must have confirmatory thyroid
function tests in venous blood. Once hypothyroid status is confirmed, patient evaluated for the
causes and started on treatment. earlier you start the treatment, better the prognosis would be.
Brief Overview of Disease Management
1. Levothyroxine is the treatment of choice; only tablets should be used, because liquid
preparations are not stable.
2. The recommended starting dose is 10 to 15μg/kg per day; it is important that the initial dose
correct hypothyroxinemia as rapidly as possible. Tailor the dose according to the severity of
the disease
3. Up to 30 percent of children with congenital hypothyroidism have a transient form and will
regain normal endogenous thyroid function during early life. Therefore, thyroid function
should be retested around three years of age to determine whether the hypothyroidism is
permanent or transient. In most cases, this is done by discontinuing therapy for 30 days and
monitoring thyroid hormones.

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B. Congenital hearing loss
Congenital hearing loss is defined as permanent and is bilateral or unilateral, is sensory or
conductive, and averages 30 dB or more in the frequency region important for speech
recognition. Congenital hearing loss has many etiologies, with at least half associated with
genetic risk factors.
Prevalence
As we saw before, the incidence of hearing loss in India is around 1-8/ 1000 children
Clinical Manifestations
The spectrum of congenital hearing loss ranges from mild to profound hearing loss. In syndromic
hearing loss, the auditory pathology may be conductive and/or sensorineural, unilateral or
bilateral, symmetrical or asymmetrical, and progressive or stable. The auditory pathology of
nonsyndromic hearing impairment is usually sensorineural.
Benefits of Newborn Screening
The goals of newborn screening are to identify those infants with hearing loss early for prompt
intervention to diminish the morbidity associated with congenital hearing loss. Left undetected
and untreated, hearing impairment can affect speech and many other cognitive abilities. For
children without risk factors, hearing loss frequently escapes detection until the age when
hearing children normally begin to talk (9 months or older). Current theory views auditory
stimulation during the first 6 months of life as critical to development of speech and language
skills.
Screening
Tests used for screening newborns for hearing loss include Otoacoustic emissions (OAE) and
automated Auditory Brainstem Response audiometry (aABR). While OAE is cheap, quick,
simple and reliable with a sensitivity of 100% and specificity of 99.02%, aABR has the
additional advantage of identifying neonates with auditory neuropathy unlike testing for OAE.
The other advantages of aABR include rapidity, easy-to-use and high sensitivity (0.99) and
specificity.

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 The aABR phone consists of a handheld headphone unit which is positioned on the baby’s head
after application of electrode gel at the points of contact with the electrodes (vertex and mastoid).

An optimized chirp stimulus is used at 35dB and the system

automatically detects the presence of an auditory brainstem response

If response is detected, the Failure to detect a response

test produces a “PASS” within 180 seconds produces
result a “REFER” result

Follow-up and Diagnostic Testing

Infants who do not “pass” the screening are either rescreened before discharge or given an
appointment for rescreening as outpatients. Results of the screening are generally transmitted to
the primary care physician of record, to the parents, and to the state health department. Failure to
pass the screening results in a recommendation for referral to a qualified audiologist for
confirmatory testing for congenital hearing loss.
Brief Overview of Disease Management
1. Appropriate management of all persons identified with congenital hearing loss requires a
comprehensive pediatric and genetic evaluation.
2. On the basis of the outcome of the evaluation, other types of professional expertise also
may be needed, including professionals with experience with syndromic hearing loss
(e.g., ophthalmology, cardiology, nephrology, neurology).
In approximately 30% of patients, there will be no obvious etiology. An important goal of the
genetic evaluation is to attempt to distinguish isolated or simplex cases, in which the risk of
deafness in subsequent offspring may be 25%, from sporadic cases, which have a low risk of
recurrence.
After diagnosis of hearing loss, continuity of care for the affected infant is important to reduce
morbidity.
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C. Congenital heart disease
American academy of pediatrics has recommended that all the babies should be screened for
congenital heart disease with pulse oximetry. According to a meta-analysis of 13 studies and
229,421 children, pulse oximetry is highly specific and moderately sensitive for detection of
critical CHD and it meets the criteria for universal screening.
Incidence
Overall, nearly one percent of all newborns have a congenital heart defect (CHD). CHDs are the
leading cause of birth defect-associated infant illness and death.
Benefits of Newborn Screening
The meta-analysis which was mentioned earlier also concluded that pulse oximetry screening2
can lead to the early detection of lesions such as coarctation of the aorta, interrupted aortic arch,
transposition of the aorta, aortic and pulmonary stenosis, tetralogy of Fallot, pulmonary atresia
and total anomalous pulmonary venous connection. Data have shown that universal neonatal
screening with pulse oximetry improves the identification of patients with critical CHD
compared with physical examination alone.
Screening
Babies who do not need to be screened are those who are already known to have CCHD, such as
those identified by prenatal ultrasound or who have already had an echocardiogram. The
following algorithm is suggested by American Academy of Pediatrics:

2
1.Measurements should not be performed when the infant is crying or moving because it reduces the
quality of the signal and the accuracy of the Oximetry testing also may miss hypoxia because of
interference from ambient light, partial probe detachment, electromagnetic interference, poor perfusion at
the site of measurement, and the presence of dyshemoglobinemia.
2. The partial pressure of oxygen decreases with increasing elevation. As a result, children born at high
altitude (e.g., >800 meters) may have lower pulse-oximetry levels than those born at sea level. The
CCHD screening algorithm was based on studies done near sea level. Therefore, there may be more false-
positives among babies screened at high altitude.

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 Screening should begin after 24 hours of age or shortly before discharge if the baby is less than 24 hours of
age. Waiting until 24 hours of life will decrease the false-positive results.

Screening is recommended in the right hand and either foot. Screening at both places can occur
simultaneously or in direct sequence.

Oxygen saturation is less Oxygen saturation is greater

Oxygen saturation is greater than 90% and
than 90% in right hand or than 95% there is less than
less than 95% in the right hand and foot,
foot 3% difference between the
or there is more than 3% difference
right hand and foot
between the right hand and foot

Positive screen Inconclusive. Repeat screen Negative screen

after one hour

Oxygen saturation is less Oxygen saturation is greater

Oxygen saturation is greater than 90% and
than 90% in right hand or than 95% there is less than
less than 95% in the right hand and foot,
foot 3% difference between the
or there is more than 3% difference
right hand and foot
between the right hand and foot

Positive screen Inconclusive. Repeat screen Negative screen

after one hour

Oxygen saturation is less Oxygen saturation is greater than 90% and Oxygen saturation is greater
than 90% in right hand or less than 95% in the right hand and foot, than 95% there is less than
foot or there is more than 3% difference 3% difference between the
between the right hand and foot right hand and foot

Positive screen Negative screen

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Follow-up and Diagnostic Testing

Failed screen

Step 1: Make sure the baby is hemodynamically stable

Step 2: Evaluate: Does the baby have sepsis or pneumonia?

Treat or refer Yes No Needs ECHO

Pulse oximetry fails to identify all patients with left-

sided obstructive lesions with a patent ductus arteriosus,
and will not detect non cyanotic congenital heart
lesions, such as ventricular septal defect.

D. Biotinidase deficiency
What is biotinidase deficiency?
Biotinidase deficiency is a disorder of biotin recycling. Biotin is a water-soluble vitamin of the B
complex that acts as a coenzyme in each of 4 carboxylases in humans. Missing a diagnosis of
biotinidase deficiency, a condition that is easily treated with vitamin supplementation, can have
severe consequences, including seizures, developmental delay, and sensorineural deafness.
Incidence
Most affected individuals who have been identified are of European descent.
Clinical Manifestations
1. Clinical symptoms can start as early as the first week of life up to 10 years of age. Most
infants first exhibit clinical symptoms between 3 and 6 months of age.
2. The commonly affected systems are the central nervous system and skin. Affected
children usually have myoclonic seizures, hypotonia, seborrhoeic or atopic dermatitis,
partial or complete alopecia, and conjunctivitis.

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 3. Other features may include developmental delay, sensorineural hearing loss, lethargy,
ataxia, breathing problems, hepatosplenomegaly, and coma.
4. Laboratory findings vary and can include ketolactic acidosis, organic aciduria, and mild
hyperammonemia.
5. Individuals with partial biotinidase deficiency can present with skin manifestations and
no neurologic symptoms. Several children with profound deficiency have presented later
in childhood or during adolescence with hemiparesis and eye findings (scotoma).
Benefits of Newborn Screening
Biotinidase deficiency has been identified as an appropriate disorder for newborn screening by
numerous countries and states because of
 The potentially tragic outcome if not diagnosed
 Availability of effective, low-cost treatment.
 Once symptoms have occurred, some of the findings are not reversible with therapy. This is
particularly true in the case of the neurologic findings. For example, sensorineural hearing
loss is common (detected in approximately 75% of symptomatic children with profound
deficiency) and is usually irreversible.
Screening
The best method of screening is a semiquantitative colorimetric assessment of biotinidase
activity that can be performed on whole blood spotted on filter paper.
Follow-up and Diagnostic Testing
A positive screening result for biotinidase deficiency should be followed up with definitive
testing for diagnosis. Quantitative measurement of enzyme activity should be performed on a
fresh serum sample.
Brief Overview of Disease Management
 Children with profound biotinidase deficiency have been treated successfully with biotin.
Pharmacologic doses of biotin (5–20 mg/day) were determined empirically
 Once therapy is instituted, cutaneous symptoms resolve quickly, as do seizures and ataxia.
Some of the symptoms are less reversible, including hearing loss and optic atrophy.
Children who have developmental delay have been noted in some cases to achieve new
milestones and regain lost milestones after beginning therapy..
 Partial biotinidase deficiency can probably be treated with lower doses of biotin (1–5
mg/day) and/or only during times of metabolic stress. In others with partial deficiency, it has
been noted that mild intercurrent illnesses such as gastroenteritis can lead to development of
typical clinical symptoms that resolve with biotin therapy.

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E. Glucose 6 Phosphate Dehydrogenase deficiency

Glucose 6 Phosphate Dehydrogenase deficiency is an inheritable X linked recessive disorder

which results in hemolysis in affected individuals under the influence of oxidants.
Prevalence
Prevalence of G6PD deficiency is high in South East Asia; in South Asia, that is the region
occupied by India, the incidence is slightly lower, ranged from 0-27% depending on the place,
ethnic and linguistic groups.
Clinical Manifestations
 Neonatal jaundice – common manifestation of G6PD deficiency in Asia
 Acute hemolytic anemia – triggered by infection and by the ingestion of certain drugs;
common problematic drugs are primaquine and dapsone and common problematic
infection is hepatitis.
 Chronic non spherocytic hemolytic anemia
Benefits of Newborn Screening
Because of the prevalence of the deficiency in the country, neonatal screening helps to identify
the cause for neonatal hyperbilirubinemia and also, if identified, helps the avoidance of the
agents that can precipitate the hemolysis. In the non pediatric population, there is no
recommendation for screening.
Screening
Semiquantiative fluorescent screening AND methemoglobin reduction test are used.
Follow-up and Diagnostic Testing
Once identified, quantitative assessment test of G6PD activity is necessary.
Brief Overview of Disease Management
In neonatal jaundice due to G6PD deficiency, phototherapy, and if needed exchange
phototherapy is needed to prevent kernicterus
Episodes of hemolysis in patients with G6PD deficiency are usually self-limited. Transfusion
with packed red cells may be necessary in cases of severe hemolysis and symptomatic anemia.
In patients with chronic hemolytic anemia, avoidance of oxidant agents is the most prudent.
Administration of folic acid in a dose of 1 mg/day may prevent worsening of anemia.

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F. Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a family of inherited disorders of the adrenal cortex that
impair steroidogenic enzyme activity essential for cortisol biosynthesis.
21-OH deficiency results in cortisol deficiency with or without aldosterone deficiency. Cortisol
deficiency from early fetal life leads to increased adrenocorticotropic hormone (ACTH)
secretion, which then stimulates excess secretion of the precursor steroids including 17-OH-
progesterone (17-OHP) and causes hyperplastic changes of the adrenal cortex. The precursor
steroids can only be metabolized by way of the androgen biosynthetic pathway, resulting in
excess androgen production that virilizes the genitalia. Aldosterone deficiency contributes to
SW. The increased circulating 17-OHP concentration is diagnostic for 21-OH deficiency.
Incidence
An exceedingly high CAH incidence (1 in 282 live births) exists among Yupik Eskimos in
western Alaska. As we saw, the incidence in Indian children is
Clinical Manifestation and Variability
The spectrum of disease in CAH
1. Classic, severe salt-wasting (SW) form
2. Classic, less severe” simple-virilizing (SV) form
3. Mild, non classic form

Forms of the disease Clinical manifestations

Classic, severe salt-  Poor feeding, vomiting, loose stools or diarrhea, weak cry, failure to
wasting (SW) form thrive, dehydration, and lethargy.
 These symptoms may not be evident until serum sodium concentrations
are below 125 mEq/L
 If untreated, circulatory collapse, shock, and death are inevitable.
 Permanent brain injury attributable to shock, lower cognitive scores,
and learning disabilities are observed in some with the SW form.
 Affected females have ambiguous genitalia (AG) (but normal internal
reproductive anatomy), prompting a clinical diagnosis in many.
Affected males have no obvious physical signs of CAH. So, male
children may go undiagnosed until adrenal crisis.
 If inadequately treated, postnatal virilization (girls), pseudo- or true-
precocious puberty (boys), and premature growth acceleration (boys
and girls) occur, leading to early growth cessation.

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Classic, less severe”  These do not manifest adrenal-insufficiency symptoms unless subjected
simple-virilizing (SV) to severe stress but exhibit virilization as in patients with SW.
 Males and some females with the SV form are not diagnosed until much
later when symptoms of virilization, precocious pseudo puberty, or
growth acceleration occur.
 The markedly advanced skeletal age of patients with the SV form
diagnosed late contributes to their short adult stature.
 Late discovery of incorrect male sex assignment in females with the SW
and SV forms causes extreme distress to the family and matured
patients.
Mild 21-OH Produces no symptoms at birth and manifests as premature sexual hair, acne,
deficiency and mild growth acceleration in childhood and hirsuitism, excessive acne,
menstrual disorder, and infertility later in life.
Mortality
The mortality rate for infants with the SW form not detected through newborn screening was
11.9%, which was fivefold higher than that of the general population (2.29%).
Rationale for and Benefits of Newborn Screening
The goals of newborn screening are to (1) prevent life-threatening adrenal crisis, thereby averting
shock, brain damage, and death, (2) prevent male sex assignment for life in virilized female
newborns, and (3) prevent progressive effects of excess adrenal androgens, which cause short
stature and psychosexual disturbances in boys and girls.
Screening
Screening for 21-OH deficiency is accomplished by measurement of 17-OHP concentration in
the dried blood spot. Sampling at less than 1 day is associated with a high rate of false-positive
results, and sampling beyond 5 to 7 days of age reduces the benefit of screening. Normal preterm
infants have higher concentrations of 17-OHP than do term infants.
Follow-up
Urgent evaluation of electrolytes and 17-OHP is needed in
1. Newborn with ambiguous genitalia with exceptionally high or moderately high 17-OHP
2. Sick or asymptomatic male newborn infants with exceptionally high or moderately high 17-
OHP
3. Sick female newborn infants with exceptionally high 17-OHP
4. The evaluation is necessary in asymptomatic normal female infants with moderately high 17-
OHP concentrations and in sick female infants with normal genitalia and moderately high 17-
OHP concentrations, but these newborns are at low risk of having SW CAH.

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Diagnosis
Quantitative serum 17-OHP concentration is used for the diagnosis of CAH. Concentrations are
generally higher in individuals with the SW form. Care must be taken to use the appropriate term
or preterm normal values for comparison. With age, serum 17-OHP concentrations decrease in
unaffected neonates but increase in those with CAH. Concentrations in neonates with SW and
SV CAH are higher than the concentrations in infants with the mild form. In neonates with
mildly elevated 17-OHP concentrations,(4–10 ng/Ml), ACTH-stimulation test helps to rule out
nonclassic CAH.
Disease Management
Treatment for CAH involves replacement of cortisol, which suppresses increased ACTH, 17-
OHP, and androgen secretion. Replacement of aldosterone with an analog of mineralocorticoid
(Florinef) is required for patients with SW CAH.
Adequate medical therapy restores normal energy, glucose and electrolyte concentrations, and
fluid balance and prevents excess adrenal androgen effects. Special medical care is needed in
case of stress.
The rate of mortality is 4.3% for treated patients. In virilized female infants, surgical correction
is generally performed before 1 year of age and, if necessary, again before menarche.

G. Galactosemia
Galactosemia, which is an increased concentration of galactose in the blood, has many causes.
The genetic disorders that cause galactosemia vary in severity from a benign condition to a life-
threatening disorder of early infancy. Early diagnosis and treatment of the latter condition can be
lifesaving; hence, newborn screening for this disease has been instituted in many states.
Incidence
Data base on the prevalence of galactosemia in India is not adequate.
Clinical Manifestations
There are 3 types of common enzyme deficiencies:
 Galactose 1-phosphate uridyl transferase (GALT) deficiency : Classic galactosemia
 Galactokinase (GALK) deficiency: Rare
 Galactose-4′-epimerase (GALE) deficiency: Occurs in 2 forms; one form is confined to
red blood cells and has no symptoms, and the second form, which is exceedingly rare.

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 Diseases Clinical manifestations
Classic  Present within the first weeks after birth with a life-threatening
galactosemia illness.
 Feeding intolerance, vomiting and diarrhea, jaundice,
hepatomegaly, lethargy, hypotonia, and excessive bleeding after
venipuncture are characteristic findings. Cataracts are generally
seen at presentation, but they may be mild in the first few weeks of
life and only detectable with slit-lamp examination. Septicemia,
particularly with Escherichia coli, is not uncommon
 Less frequently, patients with classic galactosemia may have a
more chronic presentation, with failure to thrive, poor feeding, and
developmental delay. Black individuals with classic galactosemia,
in particular, frequently have a mild presentation.
Galactokinase  Failure to develop a social smile or to follow objects may represent
(GALK) initial signs of a visual deficit due to cataracts.
deficiency  GI symptoms associated with the ingestion of galactose are
conspicuously absent.
 Growth parameters are unaffected.
Galactose-4′- Usually has enzyme deficiency that is confined to the red blood cells
epimerase and causes no symptoms; the second form of GALE deficiency is rare
(GALE) and may present with developmental delay, hypotonia poor growth and
deficiency sensorineural hearing loss.

Pathophysiology
Because these three enzymes are responsible for the conversion of galactose to galactose 1
phosphate, if they are absent, galactose is converted to galactitol , deposition of which is
responsible for the o clinical findings in galactosemia.
Benefits of Newborn Screening
Exclusion of galactose from the diet results in marked improvement of the life-threatening
complications of classic galactosemia. However, this treatment has only limited efficacy in the
prevention of long-term complications.
Screening
Newborn screening for galactosemia may test for galactose, galactose 1-phosphate plus
galactose, or GALT enzyme deficiency. GALT analysis is performed using red blood cells; there
may be a false-negative result for up to 3 months if the infant has received a blood transfusion.
Tests for galactose and galactose 1-phosphate depend on the infant's diet; therefore, it is

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important to be sure that the infant is receiving galactose-containing formula or breast milk
before testing.
Galactose is a reducing substance, and the presence of reducing substances in the urine is
sometimes suggested as a test for galactosemia. However, this test is neither sensitive nor
specific, and it should not be used as a screening or diagnostic test for galactosemia.
Follow-up and Diagnostic Testing
All newborn infants with positive screening results should be evaluated rapidly for feeding
difficulty, signs of sepsis, jaundice, and hepatomegaly. Untreated classic galactosemia may
progress very rapidly to hepatic toxicity, with death resulting from sepsis or bleeding. Immediate
restriction of dietary galactose is critical and should not await diagnostic testing. Galactose
restriction should be instituted immediately even in the asymptomatic child and should be
continued until the extent of enzyme deficiency.
Brief Overview of Disease Management
 Infants suspected of having galactosemia should be fed with a galactose-free formula until
diagnostic testing confirms a specific diagnosis. Once diagnosed, Milk and milk products are
excluded from the diet indefinitely, because significant ingestion of galactose at any age can
be toxic. Because medications may contain galactose, the pediatrician should instruct parents
to ask the pharmacist if a medication is galactose free before administering it to the child.
 Children who are seriously ill at the time of diagnosis of classic galactosemia require
supportive care, which may include vitamin K supplementation and fresh-frozen plasma
transfusions, antibiotics for presumed Gram-negative sepsis, and phototherapy for
hyperbilirubinemia. After dietary galactose has been eliminated, most infants improve
rapidly.
 Regular nutritional evaluation is necessary to ensure adequate calcium intake.
 Regular developmental evaluation and early speech assessment are also required. Girls
should be monitored frequently in late childhood and adolescence for pubertal development.
Regular measurement of galactose 1-phosphate in red cells is the most common method used
to assess dietary compliance.
Lifelong galactose restriction is also indicated for individuals with GALK and generalized
GALE deficiencies. No treatment seems to be necessary for red blood cell GALE deficiency.
G .Sickle cell disease and other hemoglobinopathies
The term sickle cell disease encompasses a group of genetic disorders characterized by chronic
hemolysis and intermittent episodes of vascular occlusion that cause recurrent episodes of severe
pain and a wide variety of other disease manifestations. Specialized comprehensive medical care
markedly reduces mortality in infancy and early childhood by preventing some disease-related
complications and limiting the severity and sequelae of others.
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Incidence
Clinical Manifestations
 Most infants with SCD are healthy at birth and become symptomatic later during infancy
or childhood.
 The most common clinical manifestation is musculoskeletal or abdominal pain, which
occurs unpredictably and is often excruciating.
 Acute manifestations that may rapidly become life-threatening include bacterial sepsis or
meningitis, splenic sequestration, acute chest syndrome, and stroke.
 Other acute complications include aplastic crises, priapism, and renal papillary necrosis.
 Chronic manifestations include anemia, jaundice, splenomegaly, hyposthenuria,
hematuria, proteinuria, cholelithiasis, and delayed growth and sexual maturation.
 Avascular necrosis of the hip and shoulder, restrictive lung disease, and leg ulcers may
cause chronic disability.
 Pulmonary hypertension is a risk factor for early death. It is important to note that the
severity of SCD varies widely, even among individuals with the same genotype.
Pathophysiology
Sickle hemoglobin is caused by a point mutation in the β-globin gene, which leads to an amino
acid change that causes hemoglobin to polymerize when deoxygenated. Sickle red blood cells are
dehydrated and show oxidative damage and increased adhesion to endothelial cells. The
cumulative effects of these cellular abnormalities are shortened red cell survival and intermittent
episodes of vascular occlusion, which cause tissue ischemia and organ damage.
Inheritance
SCD is an autosomal recessive disorder. Four SCD genotypes (sickle cell anemia, sickle-
hemoglobin C disease, and 2 types of sickle β-thalassemia [sickle β+-thalassemia and sickle β0-
thalassemia]) account for most SCD cases/
Benefits of Newborn Screening
 The primary rationale for newborn screening and presymptomatic diagnosis is prevention
of mortality from pneumococcal sepsis and splenic sequestration during infancy and
childhood.
 Prophylactic penicillin has been shown to reduce the incidence of pneumococcal sepsis
by 84% and is used in conjunction with pneumococcal conjugate and polysaccharide
vaccines and urgent evaluation and treatment of febrile illness with parenteral antibiotics.
 Family education about signs and symptoms of splenic sequestration results in earlier
detection and reduced mortality from that complication.

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Screening
Most newborn screening programs use isoelectric focusing to separate hemoglobins eluted from
dried blood spots.
Follow-up and Diagnostic Testing
Infants with screening results indicative of possible SCD (FS, FSC, FSA) should have
confirmatory testing of a second blood sample accomplished before 2 months of age.
Brief overview of disease management
 SCD is a complex disorder with multisystem manifestations that require specialized
comprehensive care to achieve an optimal outcome.
 Family and patient education about the genetics, clinical manifestations, and treatment of
SCD and its complications are important, particularly because prompt recognition of
potentially life-threatening complications reduces morbidity and mortality.
 Important health maintenance issues include prophylactic medications, particularly
prophylactic penicillin (should be started no later than 2 months of age), and timely
immunizations, especially with the pneumococcal conjugate and polysaccharide vaccines.
 Periodic comprehensive medical evaluations facilitate documentation of important
baseline physical findings and laboratory values, detection of signs of chronic organ
damage, and development of individualized patient care plans.
 Timely and appropriate treatment of acute illness is critical, because life-threatening
complications can develop rapidly.

FAMILY PHYSICIAN AND HIS/HER ROLE IN NEONATAL SCREENING

At the one side of the spectrum, we can see the highly advanced screening in developed
countries with a suggestion to screen the neonate for even the rarest genetic problem, irrespective
of the cost. At the other end of the spectrum, is a scenario where there are no clear public health
guidelines for screening. As Family Physicians in India, how can we make use of the available
limited resources to give the best to our neonates?
We can discuss this in 4 different levels:
In the clinic
1. If you are a Family Physician who is involved in obstetric care, make sure that you do
thorough examination of the baby before discharge.
2. When a newborn is brought to you for immunization, make the first physical examination
as a thorough examination, irrespective of whether the baby was delivered at home or a
hospital.
3. Make use of the neonatal startle reflex to screen for congenital deafness.
4. Identify the high risk newborn and refer them for aABR screening.
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 5. Consider making an investment for a pulse-oximeter, which is an effective tool for
screening neonates for congenital heart disease.
6. If you are working in a set up like corporate hospitals, discuss with the family about
neonatal screening.
With the team
1. Teach your team members to identify the common congenital anomalies; to identify the
high risk newborn.
2. Make an atlas of common congenital anomalies and teach your health workers to use it.
With the Government
If you are working in an area where the screening programs are being run, inform your patients
about them.
In the community
Making the community aware of the inherited disorders, screening and the benefit of early
diagnosis
Be aware of medical geography and look for the diseases peculiar to the location, community
and give high priority to screening for specific diseases prevalent in that particular geographic
area.

TAKE A BREAK 2

Patient Study 4 .1.3

1. You have done a screening test for Mrs. Mala’s baby aged 3 day old. The SPO2 in the right
hand is 94% and the right leg is 90 %. How will you comment on this screening test?

2. How will you proceed now?

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Patient Study 4 .1.4
1. In the routine screening for Mrs. Sinha’s baby, the cord blood T4 has come as 5 micrograms/dl
and the TSH has come as 23 mIu/L. Comment on the report:

2. How will you proceed now?

APPENDIX 4.1.1
APPENDICES

Appendix 1 Neonatal Screening Recommendations of the of the ACMG (American College

of Medical Genetics
‘Core panel’ Recommendations
The following conditions and disorders were recommended as a "core panel" by the 2005 report
of the American College of Medical Genetics (ACMG). The incidences reported below are from
the full report, though the rates may vary in different populations.
Blood cell disorders
 Sickle cell anemia (Hb SS) > 1 in 5,000; among African-Americans 1 in 400
 Sickle-cell disease (Hb S/C) > 1 in 25,000
 Hb S/Beta-Thalassemia (Hb S/Th) > 1 in 50,000
Inborn errors of amino acid metabolism
 Tyrosinemia I (TYR I) < 1 in 100,000
 Argininosuccinic aciduria (ASA) < 1 in 100,000
 Citrullinemia (CIT) < 1 in 100,000
 Phenylketonuria (PKU) > 1 in 25,000
 Maple syrup urine disease (MSUD) < 1 in 100,000
 Homocystinuria (HCY) < 1 in 100,000
Inborn errors of organic acid metabolism
 Glutaric acidemia type I (GA I) > 1 in 75,000
 Hydroxymethylglutaryl lyase deficiency (HMG) < 1 in 100,000
 Isovaleric acidemia (IVA) < 1 in 100,000

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  3-Methylcrotonyl-CoA carboxylase deficiency (3MCC) > 1 in 75,000
 Methylmalonyl-CoA mutase deficiency (MUT) > 1 in 75,000
 Methylmalonic aciduria, cblA and cblB forms (MMA, Cbl A,B) < 1 in 100,000
 Beta-ketothiolase deficiency (BKT) < 1 in 100,000
 Propionic acidemia (PROP) > 1 in 75,000
 Multiple-CoA carboxylase deficiency (MCD) < 1 in 100,000
Inborn errors of fatty acid metabolism
 Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) > 1 in 75,000
 Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) > 1 in 25,000
 Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) > 1 in 75,000
 Trifunctional protein deficiency (TFP) < 1 in 100,000
 Carnitine uptake defect (CUD) < 1 in 100,000
Miscellaneous multisystem diseases
 Cystic fibrosis (CF) > 1 in 5,000
 Congenital hypothyroidism (CH) > 1 in 5,000
 Biotinidase deficiency (BIOT) > 1 in 75,000
 Congenital adrenal hyperplasia (CAH) > 1 in 25,000
 Classical galactosemia (GALT) > 1 in 50,000
 Severe combined immune deficiency (SCID)
Newborn screening by other methods than blood testing
 Congenital deafness (HEAR) > 1 in 5,000
 Critical congenital heart defects (Screened using pulse oximetry)
Secondary targets
The following disorders are additional conditions that may be detected by screening. Many are
listed as "secondary targets" by the 2005 ACMG report. Some states are now screening for more
than 50 congenital conditions. Many of these are rare and unfamiliar to pediatricians and other
primary health care professionals.
Blood cell disorders
 Variant hemoglobinopathies (including Hb E)
 Glucose-6-phosphate dehydrogenase deficiency (G6PD)

Inborn errors of amino acid metabolism

 Tyrosinemia II
 Argininemia

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  Benign hyperphenylalaninemia
 Defects of biopterin cofactor biosynthesis
 Defects of biopterin cofactor regeneration
 Tyrosinemia III
 Hypermethioninemia
 Citrullinemia type II
Inborn errors of organic acid metabolism
 Methylmalonic acidemia (Cbl C,D)
 Malonic acidemia
 2-Methyl 3-hydroxy butyric aciduria
 Isobutyryl-CoA dehydrogenase deficiency
 2-Methylbutyryl-CoA dehydrogenase deficiency
 3-Methylglutaconyl-CoA hydratase deficiency
 Glutaric acidemia type II
 HHH syndrome (Hyperammonemia, hyperornithinemia, homocitrullinuria syndrome)
 Beta-methyl crotonyl carboxylase deficiency
 Adenosylcobalamin synthesis defects
Inborn errors of fatty acid metabolism
 Medium/short-chain L-3-hydroxy acyl-CoA dehydrogenase deficiency
 Medium-chain ketoacyl-CoA thiolase deficiency
 Dienoyl-CoA reductase deficiency
 Glutaric acidemia type II
 Carnitine palmityl transferase deficiency type 1
 Carnitine palmityl transferase deficiency type 2
 Short-chain acyl-CoA dehydrogenase deficiency (SCAD)
 Carnitine/acylcarnitine Translocase Deficiency (Translocase)
 Short-chain hydroxy Acyl-CoA dehydrogenase deficiency (SCHAD)
 Long-chain acyl-CoA dehydrogenase deficiency (LCAD)
 Glutaric acidemia type II|Multiple acyl-CoA dehydrogenase deficiency (MADD)
Miscellaneous multisystem diseases
 Galactokinase deficiency
 Galactose epimerase deficiency
 Maternal vitamin B12 deficiency

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REFERENCES & FURTHER READINGS
1. Newborn Screening – American academy of pediatrics – fact sheets for providers :
http://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/pehdic/pages/newborn-
screening.aspx
2. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a
systematic review and meta-analysis Indian Heart J. Nov 2012; 64(6): 616. S. Thangaratinam et al
Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a
systematic review and meta-analysis Lancet Vol. 379; 9835 2012 Jun 30 2459 2464doi:
10.1016/j.ihj.2012.10.013
3. Screening for Critical Congenital Heart Defects - Pediatric Genetics; Centers for Disease Control and
Prevention
4. Newborn Screening for CCHD; answers and resources for primary care pediatricians; American
Academy of Pediatrics; http://www.aap.org/en-us/advocacy-and-policy/aap-health-
initiatives/PEHDIC/Pages/Newborn-Screening-for-CCHD.aspx
5. Clinical Screening for Congenital Heart Disease at Birth: A Prospective Study in a Community
Hospital in Kerala; http://www.indianpediatrics.net/jan2011/jan-25-30.htm
6. Taksande AM, Lakhkar B, Gadekar A, Suwarnakar K, Japzape T. Accuracy of pulse oximetry
screening for detecting critical congenital heart disease in the newborns in rural hospital of Central
India. Images Paediatr Cardiol 2013;15(4):5-10; http://www.impaedcard.com/issue/2013/15.4.2.pdf
7. Screening of neonates with critical CHD : http://www.uptodate.com/contents/congenital-heart-
disease-chd-in-the-newborn-presentation-and-screening-for-critical-chd
8. Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: WHO; 1968.
Available from: http://www.who.int/bulletin/volumes/86/4/07-050112BP.pdf
9. Using the fluorescent spot test for neonatal screening of g6pd deficiency; text book on Tropical
Anemia by By Viroj Wiwanitkit Viroj Wiwanitkit. Publisher: New York : Nova Science Publishers,
2007
10. National Newborn Screening Program – Still a Hype or a Hope Now? Indian Pediatr 2013;50: 639-
643 ; Seema Kapoor, *Neerja Gupta and *Madhulika Kabra From Department of Genetics and
Metabolism, MAMC, Associated Lok Nayak Hospital, New Delhi and * Division of Genetics,
Department of Pediatrics, AIIMS, New Delhi, India.
11. Newborn Screening in India: Current Perspectives - Seema Kapoor and Madhulika Kabra* Indian
Pediatr 2010;47: 219-224 From the Department of Pediatrics, Maulana Azad Medical College and
*Department of Pediatrics, AIIMS, New Delhi, India.
12. Universal Neonatal Hearing Screening - Experience in a Tertiary Care Hospital in Southern India ;
Indian Pediatrics 1 October 5,2013 Ann Mary Augustine*Atanu Kumar Jana*Kurien Anil Kuruvilla
,*Sumita Danda, Anjali Lepcha, Jareen Ebenezer,R Oshna Rose Paul, Amit Tyagi And Achamma
Balraj, Department of ENT, Christian Medical College, Vellore; *Department of Neonatology,
Christian Medical College, Vellore and **Department of Medical Genetics, Christian Medical
College,Vellore, Tamil Nadu.
13. Costs and health effects of screening and delivery of hearing aids in Tamil Nadu, India: an
observational study ; Baltussen Rob, Abraham Vinod J, Priya Monica, Achamma Balraj, et al; BMC
Public Health. 2009; 9: 135. Published online May 12, 2009.

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