NEWBORN SCREENING

Newborn Screening is a simple procedure to find out if a baby has a congenital metabolic disorder that may lead to mental retardation or even death if left untreated.

Why is newborn screening important? Most babies with metabolic disorders look normal at birth. By doing newborn screening, metabolic disorders may be detected even before clinical signs and symptoms are present. And as a result of this, treatment can be given to prevent consequences of untreated conditions.

R.A. 9288 Newborn Screening Act of 2004 An act promulgating a comprehensive policy and a national system for ensuring newborn screening Is a public health program for the EARLY DETECTION of disorders that can lead to mental retardation and death. Save babies from mental retardation and death. It is an integral part of ROUTINE NEWBORN CARE in developed countries.

Highlights of RA 9288 and Its Implementing Rules and Regulations

Sec. 2. Declaration of Policy The state shall institutionalize a Newborn Screening System that is comprehensive, integrative, sustainable and collaborative. - To ensure that every baby born in the Philippines is offered the opportunity to undergo NBS and be spared from heritable conditions that can lead to mental retardation and death.

 Sec. 5. Obligation of health workers to inform about newborn screening among its clients. Sec. 9. DOH and PHIC shall require health institutions to provide newborn screening services as condition for licensure and accreditation. Sec. 10. Defining DOH as lead agency. Sec. 11. Creation of advisory Committee on NBS. Sec. 12. Establishment and accreditation of the Newborn Screening Centers (NSC). Sec. 13. Establishment of NBS Reference Center (NSRC) by the NHI. Sec. 16. PHIC inclusion of NBS and its benefits

Objectives: To establish the incidence of commonly encountered metabolic conditions To make recommendations to appropriate authorities on results of national importance Mission: To gather data to support nationwide implementation of the newborn screening program. Vision: To make newborn screening available to all Filipino babies. *APRIL 6, 2008 Enactment of the Newborn Screening Act of 2004 *Oct. 5, 2004 Signing of the implementing Rules and Regulations of RA 9288

Role of health facilities in the Implementation of RA 9288 Sec. 14. Health facilities as a major stakeholder shall ensure the implementation of NBS. Sec. 19B of IRR The government and private health facilities are highly encouraged to develop a scheme providing partial and full subsidy depending on the financial capabilities of parents. Sec. 19 D of IRR A health facility may collect a reasonable fee for the collection of samples which shall not be greater than the maximum allowable fee by the DOH. Sec. 21 A of IRR All hospitals, birthing facilities, RHUs, Health Centers and other collecting health facilities throughout the country shall have NBS collection kits at all times.

What if the parents refuse NBS testing?

A copy of refusal documentation shall be made part of the newborns medical record and shall be indicated in the national newborn screening data base.

NBS Flow of Operations Motivating parents Collecting samples Sending samples to the laboratory Performing the tests Relaying results Recalling patients

When is newborn screening done? Newborn Screening is ideally done on the 48th (day 2) 72nd (day 3) hour of life. However, it may also be done 24 hours from birth. Some disorders are not detected if the test is done earlier than 24 hours. Shall be performed after 24 hours of life but not later than 3 days from complete delivery of the newborn. A newborn under intensive care for survival may be exempted from 3-day requirement but must be tested by 7 days of age.

How is newborn screening done? Newborn Screening is a simple procedure. Using the heel prick method, a few drops of blood are taken from the babys heel and blotted on a special absorbent filter card. The blood is dried for 4 hours and sent to the Newborn Screening Center (NSC).

Who will collect the sample for newborn screening? The blood sample for Newborn Screening may be collected by a trained physician, nurse, midwife or medical technologist.

Where is newborn screening available? Newborn Screening is available in participating Newborn Screening Facilities (hospitals, lying-ins, rural health units and health centers). If babies are delivered at home, they may be brought to the nearest Newborn Screening Facility.

When are newborn screening results available? Normal Newborn Screening results are available 7 14 working days from the time newborn screening samples are received at the Newborn Screening Centers. Positive NBS results are relayed from the NBC to the NSF immediately. Parents should claim the results from their physician or health practitioner.

What is the meaning of the newborn screening result? A negative screen means that the Newborn screening result is normal. A positive screen means that the newborn must be brought back to his/her health practitioner for further testing.

What should be done when a baby has a positive Newborn Screening result? Babies with positive results should be referred at once to a specialist for confirmatory testing and further management. Consult http://www.nrsc-nih.org.ph for the list of specialists.

What is the cost of newborn screening? Newborn Screening Fee is 550.00

What are the disorders included in the Philippine newborn screening program?

CONGENITAL HYPOTHYROIDISM (CH) - CRETINISM CH results from lack or absence of thyroid hormone which is essential for the growth of the brain and the body. If the disorder is not detected and hormone replacement is not initiated within four weeks, the babys physical growth will be affected. He/she may suffer from mental retardation. A deficiency of thyroid hormone, usually characterized by low serum thyroxine (T4) and elevated serum thyroid stimulating hormone (TSH)

 Who is at risk? 1. Infants whose mothers have thyroiditis or have been on anti-thyroid drugs 2. Infants with family history of hypothyroidism or goiter or enzymatic defect of the thyroid 3. Sick premature infants are at risk for transient hypothyroidism 4. Infants who have midline defects 5. Infants whose mothers have deficiency or excess of iodine 6. Infants with Pendreds syndrome: congenital deafness, goiter, * iodine organification defect.

Clinical manifestations: growth (short stature) and mental retardation, feeding difficulties, abdominal distention, prolonged neonatal jaundice, lethargy, hypothermia, coarse and dry skin & hair, hoarse cry & constipation. Specific therapy: premature infants with transient hypothyroidism do not require therapy; all hypothyroidism infants should be started with substitution therapy: - Thyroid replacement should be given immediately - Monitor T4 closely and keep T4 within normal limits.

 Maintain 1-thyroxine levels in upper half of normal range; periodic bone age to monitor growth. Prognosis: congenital hypothyroidism often results in irreversible mental retardation if thyroid replacement therapy is not begun during the first few months of life.

CONGENITAL ADRENAL HYPERPLASIA (CAH) (CAH)

CAH is an endocrine disorder that causes severe salt loss, dehydration and abnormally high levels of male sex hormones in both boys and girls. If not detected and treated early, babies may die within 7 14 days. Group of autosomal recessive disorder affecting one or more of those enzymes necessary for the biosynthesis of cortisol.

 Enzymes affected: - Cholesterol side chain cleavage enzyme complex - 3 beta hydroxysteroid dehydrogenase - 17 alpha hydroxylase - 21-hydroxylase - 11 beta hydroxylase * 21-hydroxylase deficiency most common cause of CAH; 90% of all cases. Elevated enzyme: 17-hydroxyprogesterone and abnormal electrolytes

 Clinical manifestations: hyponatremia, hypokalemia, hypoglycemia, dehydration, and early death; ambiguous genitalia is females, progressive virilization in both sexes. *Virilization appearance of secondary male characteristics especially in females.

 Forms: 1. Simple Virilizing Form affected fetuses produce increased amounts of androgens in the 1st trimester. - In female fetus, this may lead to varying degrees of male differentiation of external genitalia and urogenital sinus, but the internal genital ducts develop normally along the female lines. - At birth: masculinization of females mild clitomegaly with some labial fusion and perineal or penile hypospadia.

- In males external genitalia are usually normal at birth, slight enlargement of the penis may occur. - Female and male neonate may have increased pigmentation of the genitalia and areola. 2. Salt Losing Form severe deficiency of 21hydroxylase enzyme results in significant impairment of cortisol and aldosterone synthesis. - During the first weeks of life there is acute adrenal crisis and sodium wasting. - Nonspecific symptoms: lethargy, poor appetite, regurgitation on feedings, failure to thrive,

weightloss, hyperkalemia, and metabolic acidosis may be seen early Severe signs and symptoms (occur within 1 2 days) : dehydration, hypotension, muscle weakness, obfundation, gray or cyanotic appearance, cold and clammy skin, hyperkalemia, cardiac conduction abnormalities and hyponatremic or hypoglycemic seizures. 3. Late onset 21-hydroxylae deficiency does not have clinical manifestations in the fetus, neonate or infants; both forms are characterized by abnormal virilization of the female fetus.

 Treatment: cortisol replacement, sodium supplementation - acute salt-losing adrenal crisis: fluid replacement, sodium replacement, continuous glucose infusion, glucocorticoid therapy, and mineraloid replacement. - Plastic surgery for ambiguous genitalia.

GALACTOSEMIA (GAL) GAL is a condition in which babies are unable to process galactose, the sugar present in milk. Results: galactose and galactitol accumulation in nerve tissue, liver, kidney & ocular lens. Accumulation of excessive galactose in the body can cause many problems, including liver damage, brain damage and cataracts. Disorder of carbohydrate metabolism. Deficient enzyme: galactose-1-PO4 uridyltransferase.

 Clinical Manifestations: hepatomegaly, neonatal jaundice, mental retardation, renal fanconi syndrome, severe dehydration, sepsis, cataracts/blindness, and death if not treated. Treatment: Galactose-free diet; soy formulas in infancy; lactose-free solid foods. Prognosis: Reversal of cataracts if treated before 3 months of age. Early detection by NBS can prevent the clinical manifestations of the condition.

PHENYLKETONURIA (PKU) PKU is a rare condition in which the baby cannot properly use one of the building blocks of protein called phenylalanine. Excessive accumulation of phenylalanine in the blood causes damage of nerve cells resulting to brain damage. Disorder of amino acid metabolism; the amino acid is found in all proteins & some artificial sweeteners. An inherited disorder that increases the amount of amino acid phenylalanine to harmful levels in the blood

 Types of PKU: 1. Classic PKU severe form Infant appears normal until they are a few months old. Without treatment: permanent mental retardation, behavioral problems, seizures, delayed development, movement disorders, with musty or mouselike odor, lighter skin & hair, & eczema. 2. Moderate & Mild PKU causes smaller risk of brain damage.

 Mothers with high level of phenylalanine risks babies to mental retardation, slow growth, heart defects or other problems of the heart, microcephaly and behavioral problems. Women with uncontrolled phenylalanine levels is at risk of pregnancy loss. Treatment: dietary phenylalanine restriction lifelong; possible tyresine supplementation Early detection by NBS prevents mental deficiency provided phenylalanine restriction is initiated before 1 month of age.

GLUCOSE-6 PHOSPHATE GLUCOSEDEHYDROGENASE DEFICIENCY (G6PD Def)

G6PD deficiency is a condition where the body lacks the enzyme called G6PD. Disorder of carbohydrate metabolism Results: inability of the cell to detoxify oxidizing agents. Babies with this deficiency may have hemolytic anemia resulting from exposure to oxidative substances found in drugs, foods and chemicals. An enzyme deficiency of the RBCs that leads to abnormal rupture of the RBCs called hemolytic anemia (abnormally decreased RBC count).

 Hemolytic anemia occurs after exposure to compounds with oxidants and drugs, i.e., malaria drugs, sulfonamides, anti-itching drugs, dapsone & others; also fava beans (favism) which occurs with in a day of ingestion characterized by: fever, back pain, headache, nausea, chills and pneumonia. Clinical Manifestations: hemolytic anemia, neonatal jaundice and signs of kernicterus.

 Who are at risk? 1.Infants who develop neonatal jaundice without evidence of isoimmunization, esp. with histories of exposure to certain drugs &/or evidence of infection, hypoxia or acidosis. 2.Male infants because they have only 1 x chromosome; deficiency is located in x chromosomes. 3.Infants with family history of neonatal jaundice 4.Premature infants who have transient non-genetically determined G6PD deficiency that lasts 3-5 days. Treatment: preventive/supportive

Why screen your baby?

Disorders Screened Effect if NOT SCREENED Effect if SCREENED & treated

Congenital Hypothyroidism Congenital Adrenal Hyperplasia Galactosemia Phenylketonuria G6PD Deficiency

Severe Mental Retardation Death Death or Cataracts Severe Mental Retardation Severe Anemia, Kernicterus

Normal Alive and normal Alive and normal Normal Normal

Inborn Error of Metabolism (IEM) Congenital Hypothyroidism Congenital Adrenal Hyperplasia Galactosemia Phenylketonuria Glucose-6 Phosphate Dehydrogenase Deficiency Maple Syrup Urine Disease (MSUD) Homocystinuria

Clues to IEM in Neonates

Overwhelming illness Sepsis; apnea Lethargy or deep coma Unusual vomiting Intractable seizures Prolonged jaundice Hypotonia Unusual odor Extensive dematoses Family history of siblings Dying young

Clues to IEM in Children Failure to thrive Mental retardation Microcephaly/macrocephaly Recurrent hypoglycemia Gait abnormalities Osteoporosis Hypopigmentation Minor malformation Unusual odor

MAPLE SYRUP URINE DISEASE (MSUD) (MSUD) Disorder of amino acid metabolism. Deficient enzyme: Branched chain ketoacid decarboxylase (BCKAD) Elevated enzymes: Leucine, valine and isoleucine. Clinical manifestations: overwhelming illness in the first week of life, lethargy progressing to coma, Opisthotonus, hypertonicity seizures, vomiting/feeding problems, maple syrup smells, acidosis, infant death or severe mental retardation and neurologic impairment, behavioral disorders, drowsiness, & apnea

 Prevention: Dietary restriction of leucine, valine & isoleucine; MSUD milk; thiamine supplement if responsive. Intervention during acute crisis: hemo or peritoneal dialysis, anticonvulsants, adequate calories and hydration. Prognosis: guarded NBS detects and prevents metabolic crisis and reduces mental deficiency.

HOMOCYSTINURIA Disorder of amino acid metabolism Deficient enzyme: Cystathione synthase Elevated enzyme: Methionine Result: accumulation of homocysteine and methionine Clinical manifestations: arterial/venous thromboembolic phenomena (early onset thromboses), subluxation of lens, mental retardation, failure to thrive, osteoporosis, genu valgum/pes cavus, malar rash, seizures, behavioral disorders, dislocated lenses, tall lanky body habitus

 Therapy: dietary methionine restriction; 100 -500mg pyridoxine; 1 15 mg/day folate; betaine (methyl donor); aspirin/dipyridamole; cystine supplement; vitamin B6 supplement if responsive. Prognosis: early detection by NBS prevents mental retardation, seizures, and delays the onset of lens subluxation if methionine restriction is begun in the neonatal period.