Download The Philippine Newborn Screening Project

Good
Afternoon!
Screening Newborns
too?
Lorna Ramos-Abad,MD
Dept. of Pediatrics
UP College of Med-Phil Gen Hospital
OBJECTIVES

To increase awareness among practitioners
about the availability of newborn screening
in the Philippines
 To discuss briefly the conditions included in
the newborn screening panel
 To highlight important provisions in the
NBS act
What is Newborn Screening?

In most developed countries:
– An integral part of routine newborn care
 As routine as Vitamin K injection or Cord Care

In the Philippines:
– It is now recognized as part of the standard
newborn care
Newborn Screening:Rationale

early identification of congenital
metabolic disorders that can lead to
mental retardation or death if not
treated

involves collection of a few drops of
blood by heel prick after the first 48
hours of life
How is Newborn Screening
Performed?
Blood sample collection
(>24 hours of life in term
newborns)
Analysis for the presence of
the disorders screened (NIH
laboratory)
Positive
Negative
Confirmatory Test
No further
testing
Positive
Appropriate treatment and referrals
Which disorders are screened?
In the Philippines:
 Congenital Adrenal Hyperplasia (CAH)
– 21 hydroxylase deficiency

Congenital Hypothyroidism (CH)
– Primary Congenital Hypothyroidism

Glucose 6-Phosphate Dehydrogenase (G6PD)
deficiency
 Galactosemia
 Phenylketonuria (PKU)
MAGNITUDE OF THE
PROBLEM
Local prevalence of these disorders
*
Condition
No. of
Confirmed
Cases
Incidence
rates
Estimated no. of
Babies Affected
Annually (Assuming a
cohort of 2.0M
newborns)
CH
130
1:3,065
594
CAH
68
1:5,860
337
GAL
4
1:99,618
22
PKU
4
1: 9,618
29
G6PD Deficiency
5,666
1:57
33,334
TOTAL
5,872
34,316
CLINICAL MANIFESTATIONS AT BIRTH
DISORDER
CAH
APPEARANCE AT BIRTH
Hyperpigmentation
Ambiguous Genitalia in female
infants
CH
Normal
GAL
Normal
PKU
Normal
G6PD Deficiency
Normal
When do typical signs and
symptoms appear?
DISORDER
CAH
CH
GOLDEN PERIOD
7-14 days
4 weeks
Gal
2 weeks
PKU
3 weeks
G6PD deficiency
On exposure to specific agents
causing hemolysis
What happens to unscreened and
untreated babies?
Disorder
Screened
CAH
UNSCREENED, UNTREATED
CH
Severe Growth and Mental
Retardation
GAL
Death or Cataracts
PKU
Severe Mental Retardation
G6PD Deficiency
Severe Anemia, Jaundice,
Kernicterus
Death
What is CONGENITAL
ADRENAL
HYPERPLASIA?
Steroidogenesis
Cholesterol
17 OH Pregnenolone
3HSD
Progesterone
17OHP
11 Deoxycortisol
11 hydroxylase
Corticosterone
P450c11AS
ALDOSTERONE
DHEAS
Androstenedione
17 HSD
P450c21
11 DOC
P450c17
Pregnenolone
P450c17
P450scc
CORTISOL
TESTOSTERONE
CAH, Salt Losing
 Clinical Manifestations
– Increased pigmentation
– Ambiguous genitalia in
female infants
– Poor suck, weak cry
– Vomiting, excessive
urination, dehydration
– Irritability and seizures
– Failure to thrive
– Hypotension, shock
– Coma
Congenital Adrenal Hyperplasia
 Late Manifestations
– Precocious puberty
– “Skin Puberty”:
pubic hair growth,
oily skin, “body
odor"
– Dark skin color
– Short adult stature
Congenital Hypothyroidism
 A deficiency
in serum concentration of free
thyroid hormone (fT4)
 Transient (10%) or
permanent (90%)
 Forms: Primary (most common) or
Secondary or Tertiary
Congenital Hypothyroidism
 Clinical Manifestations
– Prolonged jaundice
– Inactive defecation
– Umbilical Hernia
– Hypotonia
– Skin: rough and dry
 Pallor, coldness,
hypothermia, edema
– “Rough” facial features
 Edema, flat nasal bridge,
enlarged tongue
– Open fontanelles
– Delayed overall development
Congenital Hypothyroidism
 Late Manifestations
– Mental retardation
– Growth retardation
– Delayed skeletal
maturation
– Delayed dental
development and tooth
eruption
– Delayed puberty
Galactosemia

Galactose
– Component of dietary sugars
– Converted to GLUCOSE for energy storage
(glycogen) and energy production

Galactosemia results from a deficiency of Galactose-1phosphate uridyltransferase (GALT)
– Enzyme responsible for converting galactose to
glucose
Galactosemia
 Clinical Manifestations develop
a few days to two weeks AFTER
INITIATION OF MILK
FEEDINGS
 Poor suck
 Vomiting, occasionally
diarrhea
 Jaundice
 Lethargy, weakness, coma
 Septicemia (E. coli)
 Later: excess galactose deposits
in tissues
 Liver
 Hepatomegaly
 Edema
 Ascites
 Cirrhosis of the liver
 Lens
 Cataracts
 Brain
 Mental retardation
 Kidney
 Growth failure
Galactosemia
(Baby L)
at 4 months
at 1 year old
Phenylketonuria
 Phenylalanine
 Essential amino acid found in most protein
diets
 Tyrosine
 Produced from phenylalanine
 Component of substances that regulate body
functions (hormones/ pigment)
 Inefficient production of tyrosine from
phenylalanine
 Complete absence or profound deficiency of
phenylalanine hydroxylase (PAH) enzyme
activity
Phenylketonuria
 Very high elevations of blood Phenylalanine
– Excessive amounts of waste products of
phenylalanine (phenylketones) in the urine
Gives the urine a characteristic “mousy”
odor
 Low serum levels of tyrosine
– Disturbance in hormone and pigment
production
Phenylketonuria
 Clinical Manifestations
– Vomiting
– Hyperactivity
– Seizures and
hypertonia
– Musty or mousy urine
odor
– Light hair and skin
color
– Seborrheic or
eczematoid rash
– Mental retardation
Persistent Benign Hyperphenylalanemia
(Baby MD)
at 5 months
at 1 year and 10 mos.
G6PD Deficiency
 Function of G6PD
– Certain food and drug have oxidant properties
that causes cell damage
Produce H2O2 and other reactive oxidizing
products (OH+)
– In the red blood cells (RBC), the only
mechanism to neutralize oxidative substances is
through the G6PD activity
Without G6PD, RBC’s undergo
HEMOLYSIS when exposed to oxidative
stress!
OXIDATIVE AGENTS LEADING TO
HEMOLYSIS IN G6PD Deficiency
Drugs
Sulfonamides, quinolones, chloramphenicol,
Vitamin K
Chemicals
Mothballs
Food
Fava beans
Infection
CLINICAL MANIFESTIONS OF
G6PD Deficiency
Acute Hemolytic crisis
Anemia
Decreased oxygen delivery
Enlarged spleen
Increased bilirubin
Jaundice, tea colored urine
Accumulation in tissues
– Brain
• Kernicterus
– Gall bladder
• Gallstones
Screening and Confirmatory Tests
DISORDER
SCREENING TEST
CONFIRMATORY
TEST
17 OHP
17 OHP
TSH
↓T4 ↑TSH
Galactose
↓GALT activity
Phenylketonuria (PKU)
Phenylalanine
↓PAH activity
Glucose 6-Phosphate
Dehydrogenase (G6PD)
Deficiency
G6PD activity
↓G6PD activity
Congenital Adrenal
Hyperplasia (CAH)
Congenital Hypothyroidism
(CH)
Galactosemia (GAL)
Treatment
Disorder
CAH
CH
GAL
PKU
G6PD
Deficiency
Treatment
Supplementation
Glucocorticoid,
mineralocorticoid, NaCl
Supplementation
Thyroid Hormone
Avoidance
Galactose, Lactose
Avoidance
Protein diet
Avoidance
Oxidative drugs, food
and chemicals
Enactment of the
Newborn Screening Act of
2004
(April 6, 2004)
Signing of the
Implementing Rules and
Regulation of RA 9288
(October 5, 2004)
Highlights of RA 9288
 Institutionalize the National Newborn Screening System
– Section 2
 Ensure that every baby born in the Philippines is offered the
opportunity to undergo NBS
 Defining DOH as the lead agency for the implementation of NBS
– Section 10
 Creation of an Advisory Committee on NBS (ACNBS)
– Section 11
 DOH,DILG, NIH, NSRC, CWC,
 3 reps (Pediatrics, Obstetrics, Midwife, Nurse, Family
physician, Endocrinology)
Highlights of RA 9288
 Establishment and
accreditation of the Newborn
Screening Centers (NSC)
– Section 12
 Establishment of the Newborn
Screening Reference Center
(NSRC)
– Section 13
Highlights of RA 9288
 Obligation to inform
– Section 5
Who will inform?
– Any health practitioner who delivers, or
assists in the delivery of a newborn
 What information?
– Availability, nature and benefits of NBS
 Performance of Newborn Screening
– Section 6
 After 24 hours of life but not later than 3 days
 Sick neonates in ICU must be tested by the 7th day of life
– Regardless of weight and age of gestation
Highlights of RA 9288
 Role of Health Institutions
– Section 9
 DOH and PHIC shall require health institutions to provide
newborn screening services as a condition for licensure and
accreditation
• Hospitals, Health infirmaries, Health Centers, Lying-In
centers or Puericulture centers with obstetrical and
pediatric services
– Section 14- A
Serve as collecting health units for blood samples
Establish a Newborn Screening Team
• Information, education, communication,
screening, recall and management of identified
cases
• Section 21-A
All collecting health facilities throughout the country
shall have NBS Specimen Collection Kits AT ALL
TIMES!!!
What is the cost of newborn
screening?
GIVING UP 1.5 sticks
every day for
1 year
Newborn
Screening Fee
P600
2 bottles
every month
for 9 months
1 bottle of coke
every week for
1 year
2 cell cards in 9
months
Missing 55 days
of
daily lotto bet
Cost of Care : 1st year of life
CONDITION
IF SCREENED AND
TREATED
IF NOT
SCREENED
CH
P10 a day
(thyroid hormone)
P 195 a day
CAH
P 1.34 –134 a day
(steroids)
P 1073 a day
GAL
P 35
(soy formula)
P 410 a day
PKU
P 44
(low protein formula)
P 6,492 a day
None
P 84 a day
G6PD Deficiency
*UP-PGH Service Ward 2002
SAVING 34,000 BABIES A YEAR
FROM
MENTAL RETARDATION AND
DEATH!!! IS MORE THAN ENOUGH
REASON TO SCREEN BABIES
Thank you for
listening!