MTLAWS AND BIOETHICS ─ With this goal, the government
RA 9288 or the “PHILIPPINE NEWBORN
SCREENING ACT OF 2004”
HISTORY AND INTRODUCTION
• Philippine Newborn Screening Project
- Iniaited on June 27,1996
• JANUARY 03, 2000
- DOH issued AO No. 1-A, series 2000
stating the “Policies for the Nationwide
Implementation of Newborn Screening”
- During this period NBS panel included
o Congenital Hypothroidism
o Congenial Adrenal Hyperplasia
o Galactosemia
o Phenlyketonuria
• DECEMBER 09, 2003
- DOH issued AO No. 121, series 2003
with subject “Strengthening
Implementation of the National Newborn
Screening System”
- This time NBS covered
o Congenital Hypothroidism
o Congenial Adrenal Hyperplasia
o Galactosemia
o Phenlyketonuria
o Glucose-6-Phosphate
Dehydrogenase Deficiency
(G6PD)
• JANUARY 20, 2004
- President Gloria Macapagal Arroyo
issued Proclamation No. 540
- Which declared the first week of
october of each year as the “National
Newborn Screening Week”
• RA 9288
─ Enacted: April 07, 2004
─ Approved: July 07, 2004
─ IRR issued: October 07, 2004
─ Under this law, it becomes the policy
of the government to protect and
promote the right to health of the
people, including the right of children
to survival, as well as full and healthy
development as normal individuals
institutionalized a comprehensive NBS
system that is comprehensive,
integrative, and sustainable and will
facilitate collaboration among
government + non-government
agencies.
─ The NBS system ensures that every
baby born in the Philippines is offered
the opportunity to undergo NBS and
thus spared from heritable conditions
that can lead to mental retardation
and death if undected
─ By force of RA 9288, NBS became a
part of standard practice of
NEONATAL CARE
• MAY 15, 2012
─ The DOH issued: Department
Memorandum No. 2012-0154
─ Directing the inclusion of MAPLE
SYRUP URINE DISEASE (MSUD) in
the NBS panel making it so that there
are now a total of 6 parameters in NBS
• NOVEMBER 19, 2014
─ The DOH issued: AO 2014-0045 or the
“Guidelines on the Implementation of
the Expanded Newborn Screening
Program” (ENBS)
─ This detects a total of 28 Newborn
disorders falling under various types,
namely
o Hemoglobinopathies
o Amino Acid disorders
o Organic acidurias
o Disorders of fatty oxidation
o Disorders of carbohydrate
metabolism
o Disorders of biotin metabolism
o Cystic fibrosis
o Endocrine disorders
• NOVEMBER 05, 2018
─ DOH promulgated: AO 2018-0025 with
a subject “National Policy and
Strategic Framework on Expanded
Newborn Screening for 2017-2030”
• MARCH 29, 2019
─ DOH released: AO 2014-0045-A
─ Which directed that Option 1 (6-test)
will be offered until April 30,2019
ONLY
• MAY 01, 2019
─ ALL infants born in accredited facilities
shall be tested for Option 2 (ENBS
test) only
RA 9288
Overview
─ Also known as the “Newborn
Screening Act of 2004”
─ A law promulgating a comprehensive
policy and a national system for
ensuring NBS
OBJECTIVES
1. To ensure that every newborn has
access to newborn screening for
certain heratible conditions that can
result in mental retardation, serious
health complications, or death if left
undetected and untreated
2. To establish and integrate a
sustainable newborn screening
system within the public health
delivery system
3. To ensure that ALL health practitioners
are aware of the advantages of
newborn screening and of their
respective responsibilities in offering
newborns the opportunity to undergo
newborn screening; and
4. To ensure that parents recognize their
responsibility in promoting their child’s
right to health and full development,
within the context of responsible
parenthood, by protecting their child
from preventable causes of disability
and death through newborn screening
NEWBORN SCREENING
─ Process of collecting a few drops of
BLOOD from the newborn onto an
appropriate collection card and
performing biochemical testing to
determine if the newborn has a
heritable condition
─ A simple procedure used to find out if
a newborn has a CONGENITAL
DISORDER that may lead to mental
retardation or even death if left
untreated
─ An essential public health strategy that
enables early detection and
management of several congenital
disorder
o Metabolic and endocrine
disorders
o Hemoglobinopathies
o Cystic Fibrosis
EXPANDED NEWBORN SCREENING
─ ENBS is an examination that increases
the coverage of the NBS panel from
six → 28 types of congenital disorders
• AO 2014-0045-A
─ States that effective May 1, 2019, ALL
infants born in accredited NBS
facilities shall be tested for ENBS only
• NEWBORN
─ refers to a child from the time of
complete delivery – 30 days old
PERFORMANCE OF NBS
✓ As a general rule, NBS shall be
performed AFTER 24 HOURS of life
but NOT LATER than 3 days from the
complete delivery of the newborn
EXCEPTION:
a newborn must be placed in INTENSIVE
CARE in order to ensure survival may be
exempted from the 3-day requirement but
must be tested by 7 DAYS OF AGE
HERITABLE / CONGENITAL DISORDERS
TESTED UNDER ENBS
HERITABLE CONDITION
─ Any congenital trait that can result in
mental retardation, physical deformity,
or death if left undeteted and untreated
─ Inherited from the GENES of either or
both biological parents

At present, the NBS program of the DOH

offers an ENBS test consisting of 28+ panels
falling under various types of heritable
conditions. The few drops of blood are
collected using ENBS FILTER PAPER
CARDS

Specimen of choice: WHOLE BLOOD

extracted through the following
✓ Skin puncture
✓ Capillary puncture or.
✓ Heelstick
ENDOCRINE DISORDER [CC]

ENDOCRINE Disorder Abbreviation Metabolite tested Description

Congenital Hypothyroidism CH Thyroid-Stimulating Hormone (TSH) Condition resulting from

Thyroid Dysgenesis (TD)
that represents an absent,
ectopic or hypoplastic thyroid
which affects thyroid hormone
production

Commonly results in: mental

retardation

Congenital Adrenal CAH 17-Hydroxy-progesterone A group of disorders resulting

Hyperplasia (17 a-OHP) from enzymatic defects of
biosynthesis of steroids
such as 21-Hydroxylase
deficiency

Others are due to

o Cholesterol desmolase
11B-hydroxylase
deficiency
o 17B-hydroxylase
deficiency
o 3B-hydroxysteroid
dehydrogenase
AMINO ACID DISORDER

AMINO ACID Disorder Abbreviation Metabolite tested Description

Homocystinuria HCY Methionine Caused by cystathionin β-

synthase deficiency
Inborn error of the
transsulfation pathway causes

Increase levels of
HOMOCYSTEINE and
METHIONINE in blood

Hypermethioninemia / MAT Methionine Abnormal elevation of plasma

Methionine adenosine methionine that persists
transferase deficiency beyond infancy and is not
caused by homocystinuria

Maple Syrup urine disease MSUD Leucine Defect or deficiency of the

branched-chain ketoacid
dehydrogenase complex

Elevated quantities of
• Leucine
• Isoleucine
• Valine
• Oxoacids

Phenylketonuria PKU Phenylalanine Disorder of AROMATIC

AMINO ACID METABOLISM

Phenylalanine cannot be
converted to ➝ TYROSINE

Deficiency Enzye:
PHENYLALANINE
HYDROXYLASE

Tyrosinemia type I TYR Succinylacetone (SA) Also known as

“Hepatorenal tyrosinemia”,
“tyrosinosis” or “Hereditary
Tyrosinemia”

Deficient Enzyme:
FUMARYLACETOACETASE

Tyrosinemia Type (II), III Tyrosine (also known as

“Oculocutaneous
tyrosinemia” or
“RICHNER-HANHART
syndrome”

Deficiency Enzyme:
TYROSINE
AMINOTRANSFERASE
FATTY ACID DISORDERS

─ A group of AUTOSOMAL RECESSIVE disorders caused by deficiency or absence of any

of the enzymes needed by BETA-OXIDATION

FATTY ACID Disorder Abbreviation Metabolite tested Description

Carnitine CPT1 Hexadecanoylcarnitine + CPT Rare disorder characterized by the lack

Palmioyltransferase I ration of CPT1
deficiency (CPT1D)
Carnitine Palmioyltransferase I
─ converts long chain fatty acyl
molecules to their corresponding
acylcarnitines
─ catalyzes the rate limiting step of
long-chain fatty acid import into the
mitochondria and is the main
regulatory enzyme of the system

Carnitine CPT2 Hexadecanoylcarnitine + CPT disorder characterized by the lack of

Palmioyltransferase II
deficiency (CPT2D)
ration CPT2
Carnitine Palmioyltransferase II
─ responsible for the LAST STEP of
the carnine-dependent transport
system
─ In this disorder, long chain-
acylcarnites are translocated but
are NOT EFFICIENTLY converted
to Acyl-CoAs

Carnitine uptake CUD Free carnitine Also known as “Carnitine Transporter

deficiency Deficiency”

Abnormality in the transport

mechanism that facilitates carnitine’s
entry into certain cells

Neonates who are found positive for this

condition do not actually have it but
reflect the decreased levels of THEIR
MOTHERS

Glutaric acidemia type GA II Butyrylcarnitine + A disorder of fatty acid, amino acid, and
II (GA2) Isovalerylcarnitin choline oxidation caused by defects in
any of one of the two
FLAVOPROTEINS,
• Electron transport
Flavoprotein (ETF)
• ETF: Ubiquinone
Oxidoreducatase (ETFQO) –
which affects 14
dehydrogenases

Long chain LCHAD 3- Mutations in the HADHA gene are

hydroxyacyl-CoA Hydroxyhexadecanoylcarnitine present in the newborn
dehydrogenase
deficiency
Medium chain-Acyl- MCAD Octanoylcarnitine MOST COMMON defect of fatty acid
CoA dehydrogenase oxidation and is associated with
deficiency “Sudden Infant Death Syndrome”
(SIDS)

Very long chain-Acyl- VLCAD Tetradecanoylcarnitine Multiple tissues are affected. Disease
CoA dehydrogenase prevents certain fats from being
deficiency converted into energy

Tri-functional protein TFP Hydroxyhexa- Decreased activity of all three enzymatic

deficiency decanoylcarnitine components:
• LCHAD
• Long-chain 2,3 enoly CoA
Hydratase
• LKAT
ORGANIC ACIDURIAS DISORDERS

─ A group of AUTOSOMAL RECESSIVE disorders caused by deficiency or absence of any

of the enzymes needed to break down SPECIFIC PROTEINS

Disorder Abbreviation Metabolite tested Description

3-Methylcrotnyl CoA 3MCC 3-Hydroxyisovalerylcarnitine Disroder of LEUCINE metabolism.

carboxylase deficiency Was first described by ELDJARN et al.
1970.

Positive neonates do not actually have

the condition but instead reflect the
increased level of metabolites of their
mothers

Beta ketothiolase BKT Hydroxyisovalerylcarnitine Defect of mitochondrial acetoacetyl-

deficiency COA thiolase involving KETONE body
metabolism and ISOLEUCINE
catabolism

Glutaric Acidemia GA I Glutarylcarnitine First descbribed by GOODMAN (1975)

Type I Deficiency in glutaryl-CoA
Dehydrogenase

Causes increase in
• Glutaric
• 3-hydroxyglutaric
• Glutaconic
• Glutarylcarnitine

Isovaleric Acidemia IVA Isovalerylcarnitine FIRST Organic Acidemia to be

described. Deficiency of Isovaleryl-CoA
dehydrogenase.

Methylmalonic MMA Propionylcarnitine Defect in metholmalonyl-CoA mutase

Acidemia or a defect in enzyme’s VITAMIN B12
derived co-factor
5’deoxyadenosylcobalamin

Patients with methylmalonly CoA

mutase: two subgroups exist
• MUTo – no enzyme activity
• MUT’ – have residual activity

Multiple Carboxylase MCD 3-Hydroxyisovalerylcarnitine Caused by holocarboxylase

deficiency + Pronionylcarnitine synthetase enzyme – responsible for
covalent binding of BIOTIN with
inactive apocarboxylases

Propionic Acidemia PA Propionylcarnitine

UREA CYCLE DEFECTS
─ Elicit errors in NITROGEN disposal.

• UREA CYCLE - main pathway that the body uses to eliminate excess NITROGEN. As well as
facilitate the conversion of AMMONIA ➝ UREA

Disorder Abbreviation Metabolite tested Description

Citrullinemia CIT Citrulline Inborn error resulting from the deficiency

of

ARGINOSUCCINATE SYNTHETASE
─ Present in all tissues but
highest in liver where it helps
facilitates UREA cycle
Argininosuccinic ASA Citrulline
Aciduria

HEMOGLOBINOPATHIES
─ Structural abnormalities and are usually due to a SINGLE AMINO ACID SUBSTITUTION

• THALASSEMIAS – decreased production in EITHER a or B globin chains

Note: imbalance of production of globin chain results in hemolytic anemia or precipitation of RBCS
in bone marrow
• INEFFECTIVE ERYTHROPOESIS – precipitation of red cells in the bone marrow

Disorder Abbreviation Metabolite tested Description

Alpha thalassemia HgB Hemoglobin Occurs due to deletion of αglobin gene

Loss of four genes results in
• Hydrops fetalis - fatal in utero

Loss of three genes results in

• HbH disease – manifest later in
childhood as moderately severe
anemia

Loss of two genes (trait) or Loss of one

gene (silent carrier) may result in MILD
anemia

Beta thalassemia Total Absence of B chain production

(Bo) or partial reduction of the chain (B+)

Hemoglobin C Indicates newborn is carrier of

Hemoglobin C, also known as
Hemoglobin C trait or Hb AC

Hemoglobin D Indicates newborn is carrier of

Hemoglobin D, also known as
Hemoglobin D trait or Hb AD

Hemoglobin E BE chain is synthesized at a reduced

rate, leading to IMBALANCE of the
globin chains
Sickle cell disease Occurs in patients with predominant
HbS. Affected infants are usually normal
at birth but develop ANEMIA later when
HbS concentration increases and HbF
decreases

OTHER DEFECTS

Disorder Abbreviation Metabolite tested Description

Galactosemia GAL Total Galactose Inhereted in an AUTOSOMMAL

RECESSIVE manner.

Inborn error of carbohydrate metabolism

Elevated levels of GALACTOSE

Glucose-6-phosphate G6PD def G6PD enzyme activity Inadequate or dereased production of

dehydrogenase (G6PD) G6PD – which renders RBCs
deficiency susceptible to OXIDATIVE AGENTS,

➝ leading to HEMOLYTIC ANEMIA

Cystic Fibrosis CF Immunoreactive Trypsine Progressive genetic disease that causes

(IRT) • Persistent Lung infections
• Limits the ability to breathe

People with CF inherited TWO copies

of CF gene; BOTH PARENTS must
have At least 1 copy for the disease to
occur

Biotinidase deficiency BTND Biotinidase enzyme activity Multiple carboxylase deficiency

Defect: Inability to cleave BIOCYTIN for

Biotin recycling
REFUSING ENBS
- One of the objectives of RA 9288 is to
ensure that NBS is accessible to all
newborns. However,
- A parent or Legal guardian MAY refuse
testing on the ground of religious beliefs
- Refusal shall be made in writing and
must be included in the newborn’s
medical record as well as be indicated in
the national NBS database
NEWBORN SCREENING FACILITY AND
OTHER FACILITIES
NEWBORN SCREENING FACILITY (NSF)
─ a health facility that does the ff.
o educates parents about NBS
during the PRENATAL period
o Sends the specimens to the NSC
(newborn screening center)
o Recalls patients found positive in
NBS and
o Assists in the management of
patients
ROLES AND FUNCTIONS OF NSFs
1. Integrate NBS in its delivery of health
specifically maternal and newborn
services
2. Serve as a collecting health facility for
NBS
3. Coordinate with duly accredited NSC
covering their area
4. Ensure the adequate and sustained
NBS services such as information,
education, communication, screening,
recall, and management of identified
cases are being provided in the
hospital
5. Establish an NBS team that will be
responsible for
a. Collecting samples
b. Sending samples to accredited
NSC
c. Prompt recall of positive
patients
d. Referral and management of
patients
6. Initiate an appropriate financial system
that will ensure effective and efficient
collection of fees and payment of NBS
services to the NSC
7. Conduct orientation and/or training of
hospital staff on NBS
8. Monitor and evaluate the
implementation of NBS within the
institution
9. Define creative financial packages to
make NBS accessible, particularly
among the economically deprived
populace
NEWBORN SCREENING CENTER (NSC)
─ Facility equipped with an NBS
laboratory that complies with the
standards established by the National
Institutes of Health (NIH) and
provides all required laboratory tests
and recall/follow-up programs for
newborns with heritable conditions
─ NO NSC shall be allowed to operate
unless it has been duly accredited by
the DOH based on the standards set
forth by the
o Advisory Committee on
Newborn Screening
At minimum, Every NSC shall
1. Have a certified laboratory performing
all tests included in the NBS program
2. Have a recall and follow-up programs
for infants found positive for any and
all of the heritable conditions
• RECALL – refers to a procedure for
locating a newborn with possible
heritable condition to provide the
newborn with appropriate lab test to
CONFIRM the diagnosis and
administer treatment
• FOLLOW-UP – requires monitoring of
newborn with heritable condition to
ensure that the NB patient fully
complies with the prescribe diet and
medication
 3. Be supervised and staffed by trained
personnel who have been duly
accredited by the NIH
4. Submit to a PERIODIC announced or
unannounced inspection by the
reference center in order to evaluate
and ensure quality NSC performance
NEWBORN CONFIRMATORY CENTER
─ NBCC, refers to a facility identified by
the DOH to be part of the National
Comprehensive Newborn Screening
System Treatment Netowrk
─ It is equipped to perform
CONFIRMATORY testing to ensure
the accuracy of screening results
NEWBORN SCREENING
REFERENCE CENTER (NSFC)
─ Central facility at the National Institutes
of Health (NIH) that
o defines testing and follow-up
protocols,
o maintains an external laboratory
proficiency testing program
o oversees the national testing
database and case registries
o assists in training activities on
various aspects of the program
o oversees content of educational
materials
o Acts as the SECRETARIAT of
the Advisory Committee on
Newborn Screening
Roles of the NSFC include
1. Providing technical assistance in
setting up NSCs including training and
capability building
2. Defining teting and follow-up protocols
3. Maintaining an external laboratory
proficiency testing program
4. Advocating and desseminating the
importance of taking confirmatory tests
through creation and distribution of
IEC materials
5. Allocating funds for fellowships to
ensure the availability of qualified
health personnel who could be tapped
by the NCNBSS in the followup
treatment and monitoring for prompt
and proper management of newborn
babies who screened positive
6. Developing IEC materials and training
modules, among others, for
dissemination to partners and facilities,
for ENBS promotions
7. Overseeing national testing, database,
case registries, and contents of
registries
8. Conducting regular monitoring and
evaluation of the program
9. Assisting in the national training
activities of the porgram
10. Processing the transfer of funds to the
regional office
NEWBORN SCREENING
CONTINUITY CLINIC
─ Refers to an AMBULATORY CLINIC
based in a tertiary hospital and
identified by the DOH to be part of the
National Comprehensive Newborn
Screening System Treatment
Network
─ Equipped to facilitate continuity of care
for confirmed patients in its area of
coverage
 LICENSING AND ACCREDITAITON
ACCREDITATION
─ Formal authorization issued by the
DOH to an individual, partnership,
corporation, or association and to the
NSC
CERTIFICATE OF ACCREDITATION (COA)
─ Usually issued to NSCs
─ Valid for 3 years
─ To secure, an application is filed to the
HFSRB accomplanied with a
o Certification from the NIH that
the facility was already visited,
inspected, and had passed the
criteria of the NIH
─ If application substantially complied
with the requirements, HFSRB will visit
and inspect the facility of the applicant
─ If applicant meets all the requirements
of the HFSRB, a COA will be issued
Application for RENEWAL OF COA
─ Appication for renewal of COA not filed
within 30 DAYS after expiration shall
be treated as a new application
LICENSE TO OPERATE
─ Given to NBCCs
─ Valid for 1 year
─ The applicant or NBCC should be a
“DOH licensed hospital-based
TERTIARY clinical laboratory”
─ It should be filed to the HFSRB
accompanied with a
o Certification from the
Newborn Screening
Reference Center (NSRC) –
that the facility is compliant with
the technical standards of the
NSRC
─ The LTO of the confirmatory clinical
laboratory shall be incorporated in the
LTO of the clinical laboratory which
explains its validity period of 1 year.
PERFORMANCE OF NEWBORN
SCREENING
HEEL PRICK METHOD
─ The preferred mode of collection of
samples for NBS
Information that must be provided for NBS
1. Age of gestation in WEEKS
2. Type of specimen
3. Date and Time of collection
4. Feeding information
5. Hospital and Place of collection
6. Name of attending Physician
NBS SPECIMEN COLLECTING KIT
• Alcohol
• Dry and Wet Cotton swabs
• Lacets with 3 mm tip
• Gloves
• Tape
• Completely filled-out filter card
STEPS IN PERFORMING NBS
1. Gently massage the baby’s heel to
warm it to increase blood flow
2. Clean the heel by wiping the area with
a cotton swab with alcohol
3. Dry with a cotton swab
4. Prick the
o LATERAL portions of the
PLANTAR surface of the heel
5. Apply intermitted pressure on the
area surrounding the heal, but do not
SQUEEZE
6. Wipe the first blood droplet because
of the potential contamination with
tissue juices
7. Wait for sufficient blood to form
8. Drop the blood on the filter card, filling
each circle so that it is uniformly
absorbed when viewed from the
backside of the card
9. Do not superimpose the blood on top
of another spot
10. Dry the filter card at least FOUR
HOURS or until completely dried by
placing it in a DRYING RACK
11. After drying it can be now sent to the
NSC through a preferred courier