Clinical Aspect of Hyperbilirubinemia

CLINICAL JAUNDICE
80% of premature baby Visible jaundice: serum bilirubin > 5 mg/dL

Neonatal Jaundice: WHY WE WORRY ?

Acute Bilirubin Encephalopathy

Early phase

Intermediate phase

lethargic, hypotonia, suck poorly

stupor, irritability, hypertonia (retrocollis and opistotonus)

Fever, high-pitched cry

Kernicterus

Chronic form of bilirubin encephalopathy

Athetoid CP, auditory dysfunction, paralysis upward gaze

Kernicterus

Neuropathology

Yellow staining and neuronal necrosis

Basal ganglia:
globus pallidus subthalamic nucleus

Cranial nerve nuclei:

vestibulocochlear oculomotor facial

Cerebellar nuclei

1990 - .. 125 CASES OF KERNICTERUS in the United States Cases of Kernicterus in Indonesia ?

A preventable tragedy

BILIRUBIN SYNTHESIS, TRANSPORT, AND METABOLISM

BASIS FOR INCREASED BILIRUBIN LEVELS IN THE NEWBORN

Serum Bilirubin levels in term and preterm infants

16 14 12 10 8 6 4 2 0 day 1 day 2 day 3 day 4 day 5 day 6 day 7 Normal term Preterm

Jaundice in preterm neonates

Onset earlier Peaks later Higher peak Takes longer to resolve up to 3 weeks

What

level is physiologic?

Physiologic vs Non-physiologic hyperbilirubinemia

20 18 16 14 12 10 8 6 4 2 0 day 1 day 2 day 3 day 4 day 5 day 6 day 7

physiologic non- physiologic

Criteria that Rule Out the Diagnosis of Physiologic Jaundice

Clinical jaundice in the first 24 hours of live Jaundice lasting longer than 21 days in preterm infants STB concentration increasing by more 0.2 mg/dL

per hour or 5 mg/dL per day

Direct serum bilirubin concentration exceeding 1.5-2 mg/dL

Jaundice who need phototherapy
Sign of underlying disease

CAUSES OF NEONATAL INDIRECT HYPERBILIRUBINEMIA

BASIS CAUSES

Indirect HYPERBILIRUBINEMIA
OVERPRODUCTION ( HEMOLYSIS)

Extravascular blood- hematomas, bruises Feto-maternal blood group incompatibility Rh - mom / baby Rh + O group mom / baby A or B Intrinsic red cell defects G-6-PD deficiency hereditary spherocytosis Polycythemia

Indirect HYPERBILIRUBINEMIA
G6PD DEFICIENCY

X- Linked disorder (2-6% carrier rate in Indonesia) enzyme protects red cell from oxidative damage >150 mutations Onset of jaundice usually day 2 - 3, peaks day 4 - 5 Hyperbilirubinemia may be out of proportion to anemia Diagnosis- enzyme assay baby and mother DNA analysis

Indirect HYPERBILIRUBINEMIA
UNDERSECRETION

Prematurity Hypothyroidism Inherited deficiency of conjugating enzyme uridine diphosphate glucuronyl transferase Other metabolic disorders

Indirect HYPERBILIRUBINEMIA
SECRETED but REABSORBED from gut

ENTEROHEPATIC CIRCULATION Decreased enteral intake Pyloric stenosis Intestinal atresia/ stenosis Meconium ileus Meconium plug Hirschsprungs disease

Direct HYPERBILIRUBINEMIA
OBSTRUCTIVE DISORDERS

# # # #

Cholestasis Biliary atresia Choledochal cyst

Direct bilirubin > 2 mg/dL Time of appearance Color of stools Color of urine

HYPERBILIRUBINEMIA
MIXED

Bacterial sepsis Intrauterine infections: TORCH

HYPERBILIRUBINEMIA
DIAGNOSIS

History Physical exam: gestational age activity/ feeding level of icterus pallor hepatosplenomegaly bruising, cephalhematoma

HYPERBILIRUBINEMIA
DIAGNOSIS

Laboratory tests

Bilirubin levels: total and direct Mothers blood group and Rh type Babys blood group and Rh type Direct Coombs test on baby Hemoglobin Blood smear Reticulocyte count

Rapidly developing jaundice

on Day 1
Likely Rhesus, ABO, or other hemolytic disease Spherocytosis

Less likely Congenital infection G-6-P-D deficiency

Rapidly onset jaundice

after 48 hours of age
Likely Infection G-6-P-D deficiency
Less likely Congenital Rh, ABO, spherocytosis

HYPERBILIRUBINEMIA
MANAGEMENT

HYDRATION - FEEDING PHOTOTHERAPY EXCHANGE TRANSFUSION

Phenobarbital Tin protoporphyrin

Management of Hyperbilirubinemia in the Newborn Infant 35 or more weeks of gestation

Promote and support successful breast-feeding Perform a systematic assessment before discharge for the risk of severe hyperbilirubinemia Provide early and focussed follow-up based on risk assessment When indicated, treat newborns with phototherapy or exchange transfusion to prevent the development of severe jaundice and possibly, kernicterus.

Feeding to Prevent and Treat Neonatal Jaundice

Mothers should breast feed their babies caloric intake / dehydration Jaundice Supplementation with water or dextrose water will not prevent or treat hyperbilirubinemia

Systematic Assessment for Neonatal Jaundice

Pregnant women: Blood group and Rh type If mom is Rh negative or O group: Babys cord blood group/ Rh type/ DAT

Monitor infant for jaundice at least every 8-12 hours

If level of jaundice appears excessive for age, perform transcutaneous bilirubin or total serum bilirubin measurement

Clinical assessment of severity of jaundice

Cephalocaudal progression face 5 mg/dL (approximately) upper chest 10 mg/dL (approximately) abdomen and upper thighs 15 mg/dL (approximately) soles of feet 20 mg/dL (approximately) Visual inspection may be misleading

Transcutaneous Bilirubinometers
Useful as screening device TcB measurement fairly accurate in most infants with TSB < 15 mg/dL Independent of age, race and weight Not accurate after phototherapy

Complications of phototherapy

Significant complications very rare separation of mother and baby increased insensible water loss and dehydration in premature baby PDA ROP

What decline in serum bilirubin can you expect with phototherapy?

Rate of decline depends on effectiveness of phototherapy and underlying cause of jaundice Intensive phototherapy should produce a decline in STB of 1-2 mg/dL within 4-6 hours, and the STB level should continue to decline and remain below the threshold level for exchange transfusion

With standard phototherapy, expect decrease of 6% to 20% of the initial bilirubin level in the first 24 hours

Exchange Transfusion

Exchange Transfusion
Double volume Exchange Transfusion 2 X 85 mL/kg

Red Blood Cells waste

EXCHANGE TRANSFUSION
COMPLICATIONS

cardiac failure metabolic- hypoglycemia, hyperkalemia, hypocalcemia air embolism bacterial sepsis transfusion transmitted viral disease necrotizing enterocolitis portal vein thrombosis

Mortality / permanent sequelae 1-12%

Guidelines for the use of phototherapy and exchange transfusion in low birth weight infants based on birth weight
Birth Weight (g) < 1.500 1.500-1.999 2.000-2.499 Total Bilirubin Level (mg/dL)* Phototherapy 5-8 8-12 11-14 Exchange Transfusion 13-16 16-18 18-20

Guidelines for use of phototherapy and exchange transfusion in preterm infants based on gestational age
Gestational age (weeks) 36 32 28 24 Total bilirubin level (mg/dL) Phototherapy 14.6 8.8 5.8 4.7 Exchange transfusion Sick* 17.5 14.6 11.7 8.8 Well 20.5 17.5 14.6 11.7

Guidelines according to birth weight for exchange transfusion in low birth weight infants based on total serum bilirubin (mg/dL) and bilirubin/albumin ratio (mg/g) (whichever comes first)
< 1.250 g
Standard risk Total bilirubin B/A ratio High risk* Total bilirubin B/A ratio 10 4.0 13 5.2 15 6.0 17 6.8 13 5.2 15 6.0 17 6.8 18 7.2

1.250-1.499 g

1.500-1.999 g

2.000-2.499 g

Guidelines for the Management of Hyperbilirubinemia Based on Birth Weight and Relative Health of the Newborn Serum Total Bilirubin Level (mg/dL) Birth Weight Premature < 1000 g 1001 1500 g 1501 2000 g 2001 2500 g Term > 2500 g Healthy
Phototherapy Exchange Transfusion

Sick
Phototherapy Exchange Transfusion

5 7 7 10 10 12 12 15 15 18

Variable Variable Variable Variable 20 25

4 6 6 8 8 10 10 12 12 15

Variable Variable Variable Variable 18 20

Averys Diseases of the Newborn. 2005

Tatalaksana Ikterus
Bilirubin Serum Total (mg/dL)
USIA

Terapi sinar
Tanpa Faktor Risiko Prematur atau Dengan Faktor Risiko

Transfusi tukar
Tanpa Faktor Risiko 15 25 30 30 Prematur atau Dengan Faktor Risiko 13 15 20 20
Pocket Book WHO, 2005

Hari 1 Hari 2 Hari 3 Hari 4 dst

Setiap ikterus yang terlihat 15 18 20 13 16 17