Newborn Screening in the Philippines
Wilfredo R. Santos, MDNeonatologist
CASE NO. 1
Baby Boy M was born via NSD to a 32 year old G2P1 mother who had regular prenatal check-up and had UTI at 8 months AOG. At birth, he had good cry with an APGAR score of 8,9. Patient was term with a BW = 3.2 kg. He was breastfed and was apparently well until after a week manifested vomiting, jaundice and seizure
CASE NO. 2
Baby Girl C was born via CS to a 34 year old G1P0 mother who had placenta previa totalis. Patient was born preterm at 32 weeks AOG and had an AS of 6,7,8 BW= 1.9 kg . She was ventilated with ET CPAP for a week , The course of the NICU stay was uneventful and she was discharged at 2 wks old. However, poor weight gain and failure to thrive was noted at 1 year old prompting the pediatrician to work up the patient.
Newborn Screening: History
• Started in 1961 in Oregon and Massachussets • Robert Guthrie developed a simple bacterial
inhibition assay for phenylalanine• Test required only a small amount of whole blood
soaked into filter paper• Additional tests for other metabolic disorders
ensued – galactosemia, MSUD and homocystinuria• PKU screening was present throughout the US,
Canada, Europe Australia and Japan by the end of the decade
Approximate Frequencies in the U.S. of Disorders Included in Newborn Screening
Disorders Frequency• Congenital 1:4,000 Hypothyroidism• PKU 1:12,000• Galactosemia 1:60,000• CAH 1:19,000• Homocystinuria 1:200,000• MSUD 1:200,000
Reasons for Newborn Screening
• Babies with metabolic disorders usually appear normal at birth
• Manifestation of metabolic disorders are vague
• The effects of metabolic disorders are progressive and irreversible
• Developmental effects of metabolic disorders are seriously debilitating
• Metabolic disorders are non-infectious; they can affect babies even of the most careful of parents
Goals of Newborn Screening Program
• Total participation of eligible population
• Notification and education of all parents
• Prompt and reliable laboratory testing
• Rapid follow-up of positive tests
• Accurate diagnosis of confirmed positive cases
• Appropriate treatment and counseling
Phil. Newborn Screening Project
• Initiated in June 1996
• Aim: to come up with statistical data to
support the implementation of a screening
program on a nationwide scale
HISTORY OF NEWBORN SCREENING IN THE
PHILIPPINES1996 – PPS/POGS 24 accredited hospitals
Newborn Screening GroupPhilippine Newborn Screening Project
1998 – G6PD was added to the list of disorders. Homocystinuria was deleted
1999 – the DOH included NBSP in the CHILD 2025 Program
2001 – DOH created the National Technical Working Group for the nationwide implementation of NBSP
Who to screen?All newborns
When to screen?- Ideally at third day of life- after at least 24 hours of full feeding
How is newborn screening done?- Heel prick- Filter paper card
What disorders are being screened?
• Congenital Hypothyroidism
• Congenital Adrenal Hyperplasia
• Phenylketonuria
• Galactosemia
• Glucose 6 Phosphate Dehydrogenase Deficiency
CONGENITAL HYPOTHYROIDISM
A disorder affecting infants from birth, is due to the absence or deficiency of the thyroid hormone
Thyroid hormone is responsible for the normal function of certain body organs (bone, muscle, teeth, heart, bowels) and is essential for normal brain development.
Causes of Congenital Hypothyroidism
1). Defective development of the thyroid gland
2). Development of the thyroid gland in an abnormal location
3). Maternal intake of anti-thyroid medication or excess iodine
4). Inherent defect in thyroid hormone production
Diagnosis of Congenital Hypothyroidism
CLINICAL MANIFESTATIONS:
Most of the time, babies with CH appear normal at birth. Clinical diagnosis occurs in less than 5% of newborn because sign and symptoms are often subtle and minimal and non-specific
Laboratory Diagnosis of CH
Newborn ScreeningHigh TSH and T4 levels are confirmatory of
CHThyroid scanBone ageTREATMENT of CH:Thyroid hormone replacement (L-thyroxine
10-15 mg/kg)
Congenital Hypothyroidism
• Results from deficient production of thyroid hormone or a defect in its receptor
• Thyroid hormone is essential to the growth of the brain and body
• Most infants with CH are asymptomatic at birth
• Early diagnosis and treatment of hypothyroidism in the newborn prevents mental retardation
Congenital Hypothyroidism
• Newborn screening programs are designed to
detect elevated serum TSH levels in blood.
• Before the advent of screening, less than 1/3
of affected infants were diagnosed before 3
months of age and only ½ by 6 months of age;
irreversible brain damage developed in most
of these infants
Congenital Adrenal Hyperplasia
• Caused by disorders of adrenal
steroid genesis leading to a deficiency of cortisol
• 75% of affected infants have the salt-losing, virilizing form
• Treatment consists of steroid administration
CONGENITAL ADRENAL HYPERPLASIA
The lack of cortisol is due to deficiency of certain enzymes necessary for its production and this will result to over production or under production of other hormones like aldosterone and androgen
Aldosterone is the hormone responsible for maintaining and controlling the amount of salt such as sodium and potassium in the body
Androgen is the male hormone
Types of CAH
1). 21-hydroxylase (90%)
2). 11-hydroxylase (5%)
3). 3-beta hydroxydehydrogenase and isomerase
4). 20,22 desmolase
5). 17-hydroxylase
Salt-losers ( 80%) Non salt-losers (20%)
Diagnosis of CAH
In girls:
- Abnormal sex organ
- Early appearance of pubic & axillary hairs
- Excessive hairs
- Deep voice
- Failure to menstruate
- Abnormal menstrual period
In boys:
- Enlarged penis
- Early increase in height
- Early appearance of pubic & axillary hairs
- Early development of masculine characteristics
- Small testes upon reaching adolescence
PHENYLKETONURIA
• Inherited enzyme deficiency prevents the baby
from utilizing proteins properly
• Phenylalanine excess disrupts normal
metabolism and causes brain damage
• If not diagnosed and treated early, mental
retardation almost always occur
• Treatment only involves a special diet
• Normal development is possible with early
treatment
What is Phenylketonuria?
Phenylketonuria or PKU is a condition characterized by high serum levels of phenylalanine and phenylketones in the urine due to absence of the enzyme phenylalanine hydroxylase.
PKU is an autosomal recessive disorder due to defective gene locus on the q22-q24.1 band region of chromosome 12
Diagnosis of PKU
CLINICAL MANIFESTATIONS:
- impaired brain development
- musty body odor, eczema
- lighter skin and hair color (decreased tyrosine levels)
- exaggerated DTR’s, paraplegia, hemiplegia
Treatment of PKU
Diet consisting of low phenylalanine and controlled amounts of tyrosine and other amino acids
Special milk formula
Galactosemia
• Babies with this disorder cannot metabolize
galactose
• Accumulation of galactose in the body can
cause multiple problems – brain damage,
cataracts, liver cirrhosis
• Babies are treated by putting them on a
special galactose – free diet
What is Galactosemia?It is an autosomal recessive disorder
characterized by the body’s inability to use galactose as a source of energy.
3 Enzyme deficiencies:
1). Galactokinase, which converts galactose to galactose-1-phosphate
2). Uridine diphosphate (UDP) galactose-4-epimerase
3). Galactose-1-phosphate uridyltransferase (GALT)
- responsible for hereditary or classical galactosemia
Signs & Symptoms of Galactosemia
- Hypoglycemia- Irritability- Vomiting - Jaundice- Diarrhea- Liver enlargement- Sepsis (E. Coli)
• COMPLICATIONS:- Cataract- Learning disabilities- Neurologic disorders- Speech disorder
WHAT IS G6PD?What is G6PD ?
G6PD is a cytoplasmic enzyme important in the production of NADPH in cells which is required in various biosynthetic pathways .
G6PD plays a key role in protecting RBC’s from oxidative stress, without it they will be prone to hemolysis leading to anemia and jaundice
What Triggers the Symptoms of G6PD Deficiency?
1. Ingestion of fava beans oand other type of foods (tokwa, taho and soya-containing food)
2. Infection – hepatitis, pneumonia, typhoid fever)
3. Intake of drugs - Primaquine
Diagnosis of G6PD Deficiency
In babies: early appearance and persistence of jaundice
In older children and adults: symptoms of pallor, dizziness, headache, jaundice, tea-colored urine
Confirmatory Test: Assay Test for quantitative determination of G6PD using patient’s erythrocytes. A positive assay is a value of <118 mU/10 9 RBC’s
Flow ChartOB explains Newborn Screening to mothers
Consents obtained by OB
NBS explained by the pediatrician if consent not yet secured
Newborn Screening done If discharged < 48 hours on the 3rd day of Newborn Screening done
at 1st check up
Filter card samples sent to NIH via FedEx
Samples are sorted
Rejected samples Accepted samples
NIH requests for repeat Laboratory runs in the samples sample collection
Positive screen Negative screen
NIH informs Hospital Results released to
Coordinator coordinators
AMD is informed Results are relayed to
Pediatricians
Patients recalled for confirmation tests
Newborn Screening: Cost - Effective
• Prevents mental retardation and even death
• Saves on hospitalization costs incurred from complications of metabolic disorders
• Saves on costs for special education and therapy if early treatment is missed
• Saves children from a life of complete dependence
• Saves families from the frustrating and heartbreaking task of caring for an affected child
Causes of Unsatisfactory Samples
1. Blood clots on surface
2. Incomplete saturation
3. Filter paper damaged
4. Blood layered on surface
5. Blood applied on both sides
6. Contamination
7. QNS to complete testing
When to Collect Samples
Full – term Infants
Collect sample before discharge from hospital of birth. If initial sample was collected before 24 hours of age obtain repeat sample in about 14 days.
Home/out of hospital births
The birth attendant (physician, midwife, or certified nurse) is responsible for collecting a sample before one week of life for out of hospital births.
When to Collect Samples
Extended Hospital stays (Premature/Sick infants)
Collect sample by the seventh day of life unless a
transfusion is imminent. Hospital stays longer
than 14 days require a repeat screening at time
of discharge or at one month of age if hospital
stay is longer than one month
When to Collect Samples
Transfused Infants
Collect initial sample before transfusion, if possible.
If sample is collected before transfusion and less than 24 hours of age, repeat testing at 30 and 60 days of life.
If initial sample was collected post-transfusion, testing should be done at 6,30 and 60 days of life.
When to Collect Samples
Transferred Infants
If transfer to another hospital is imminent,
collect sample before transfer, if at all
possible. Be sure to inform the transferring
hospital of collection status, including
whether or not the sample was collected,
age at time of collection, transfusion status,
etc.
When to Collect Samples
Parent Refusal of Newborn Screening Testing
Parents may refuse newborn screening testing
of their baby ONLY “on the grounds that it
conflicts with their religious tenets and
practices”. Parents refusing under this
condition should sign a statement that is
placed in the infant’s medical record.
Cost of Newborn Screening
Two Screening Packages:
1). Screening for 5 Disorders : P550.00
CH, CAH, GAL, PKU, G6PD
2). Screening for 2 Disorders only : P310.00
CH and CAH
THANK
YOU !