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
No further testing

Confirmatory Test
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) 594

CH

130

1:3,065

CAH GAL PKU G6PD Deficiency

TOTAL

68 4 4 5,666
5,872

1:5,860 1:99,618 1: 9,618 1:57

337 22 29 33,334
34,316

CLINICAL MANIFESTATIONS AT BIRTH

DISORDER CAH APPEARANCE AT BIRTH Hyperpigmentation Ambiguous Genitalia in female infants

CH GAL PKU G6PD Deficiency

Normal Normal Normal Normal

When do typical signs and symptoms appear?

DISORDER CAH CH Gal PKU G6PD deficiency GOLDEN PERIOD 7-14 days 4 weeks 2 weeks 3 weeks On exposure to specific agents causing hemolysis

What happens to unscreened and untreated babies?

Disorder Screened CAH UNSCREENED, UNTREATED Death

CH
GAL PKU G6PD Deficiency

Severe Growth and Mental Retardation Death or Cataracts

Severe Mental Retardation Severe Anemia, Jaundice, Kernicterus

What is CONGENITAL ADRENAL HYPERPLASIA?

Steroidogenesis
Cholesterol P450scc Pregnenolone

P450c17

17 OH Pregnenolone 3HSD 17OHP

P450c17

DHEAS

Progesterone P450c21 11 DOC

Androstenedione 17 HSD

11 Deoxycortisol 11 hydroxylase

TESTOSTERONE

Corticosterone P450c11AS ALDOSTERONE

CORTISOL

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, RBCs 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

Congenital Adrenal Hyperplasia (CAH)

17 OHP

Congenital Hypothyroidism (CH)

Galactosemia (GAL) Phenylketonuria (PKU) Glucose 6-Phosphate Dehydrogenase (G6PD) Deficiency

TSH

T4 TSH
GALT activity PAH activity G6PD activity

Galactose Phenylalanine G6PD activity

Treatment
Disorder CAH CH GAL PKU G6PD Deficiency
Treatment
Supplementation Glucocorticoid, mineralocorticoid, NaCl

Supplementation
Avoidance

Thyroid Hormone
Galactose, Lactose

Avoidance
Avoidance

Protein diet
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, LyingIn 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 CH CAH GAL PKU IF SCREENED AND TREATED P10 a day (thyroid hormone) P 1.34 134 a day (steroids) P 35 (soy formula) P 44 (low protein formula) IF NOT SCREENED P 195 a day P 1073 a day P 410 a day P 6,492 a day

G6PD Deficiency
*UP-PGH Service Ward 2002

None

P 84 a day

SAVING 34,000 BABIES A YEAR FROM MENTAL RETARDATION AND DEATH!!! IS MORE THAN ENOUGH REASON TO SCREEN BABIES

Thank you for listening!