newborn screening summary 2010

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 !