Clinical Aspect of Hyperbilirubinemia

CLINICAL JAUNDICE80% of premature babyVisible jaundice: serum bilirubin > 5 mg/dL

Neonatal Jaundice: WHY WE WORRY ?Acute Bilirubin Encephalopathy

Early phase lethargic, hypotonia, suck poorlyIntermediate phase stupor, irritability, hypertonia (retrocollis and opistotonus) Fever, high-pitched cry

Kernicterus

Chronic form of bilirubin encephalopathyAthetoid CP, auditory dysfunction, paralysis upward gaze

Kernicterus - NeuropathologyYellow staining and neuronal necrosis

Basal ganglia:

globus pallidus subthalamic nucleusCranial 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

Jaundice in preterm neonatesOnset earlierPeaks laterHigher peakTakes longer to resolve up to 3 weeksWhat level is physiologic?

Physiologic vs Non-physiologic hyperbilirubinemia

Criteria that Rule Out the Diagnosis of Physiologic JaundiceClinical 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

BASISCAUSES

Indirect HYPERBILIRUBINEMIAOVERPRODUCTION ( HEMOLYSIS)Extravascular blood- hematomas, bruisesFeto-maternal blood group incompatibility

Rh - mom / baby Rh + O group mom / baby A or BIntrinsic red cell defects

G-6-PD deficiency hereditary spherocytosisPolycythemia

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

Indirect HYPERBILIRUBINEMIAG6PD DEFICIENCY

PrematurityHypothyroidismInherited deficiency of conjugating enzyme uridine diphosphate glucuronyl transferaseOther metabolic disorders

Indirect HYPERBILIRUBINEMIAUNDERSECRETION

ENTEROHEPATIC CIRCULATION

Decreased enteral intakePyloric stenosisIntestinal atresia/ stenosisMeconium ileusMeconium plugHirschsprungs disease

Indirect HYPERBILIRUBINEMIASECRETED but REABSORBED from gut

CholestasisBiliary atresiaCholedochal cyst

Direct bilirubin > 2 mg/dLTime of appearanceColor of stoolsColor of urine

Direct HYPERBILIRUBINEMIAOBSTRUCTIVE DISORDERS

Bacterial sepsisIntrauterine infections: TORCH

HYPERBILIRUBINEMIAMIXED

HistoryPhysical exam:

gestational ageactivity/ feedinglevel of icteruspallorhepatosplenomegalybruising, cephalhematoma

HYPERBILIRUBINEMIADIAGNOSIS

Laboratory tests

Bilirubin levels: total and directMothers blood group and Rh typeBabys blood group and Rh typeDirect Coombs test on babyHemoglobinBlood smear Reticulocyte count

HYPERBILIRUBINEMIADIAGNOSIS

LikelyRhesus, ABO, or other hemolytic diseaseSpherocytosis

Less likelyCongenital infectionG-6-P-D deficiency

Rapidly developing jaundice on Day 1

Rapidly onset jaundice after 48 hours of ageLikelyInfectionG-6-P-D deficiency

Less likelyCongenital Rh, ABO, spherocytosis

HYDRATION - FEEDING PHOTOTHERAPYEXCHANGE TRANSFUSION

PhenobarbitalTin protoporphyrin

HYPERBILIRUBINEMIAMANAGEMENT

Management of Hyperbilirubinemia in the Newborn Infant 35 or more weeks of gestationPromote and support successful breast-feedingPerform a systematic assessment before discharge for the risk of severe hyperbilirubinemiaProvide early and focussed follow-up based on risk assessmentWhen indicated, treat newborns with phototherapy or exchange transfusion to prevent the development of severe jaundice and possibly, kernicterus.

Feeding to Prevent and Treat Neonatal JaundiceMothers 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 assessmentof severity of jaundiceCephalocaudal progressionface 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 BilirubinometersUseful as screening device TcB measurement fairly accurate

in most infants with TSB < 15 mg/dLIndependent of age, race and weightNot accurate after phototherapy

Complications of phototherapySignificant complications very rareseparation of mother and babyincreased insensible water loss and dehydration in premature babyPDAROP

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

wasteRed Blood CellsDouble volume Exchange Transfusion2 X 85 mL/kg

EXCHANGE TRANSFUSION COMPLICATIONS cardiac failuremetabolic- hypoglycemia, hyperkalemia, hypocalcemiaair embolismbacterial sepsistransfusion transmitted viral diseasenecrotizing enterocolitisportal 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)

Total Bilirubin Level (mg/dL)*

Phototherapy

Exchange Transfusion

< 1.500

5-8

13-16

1.500-1.999

8-12

16-18

2.000-2.499

11-14

18-20

Guidelines for use of phototherapy and exchange transfusion in preterm infants based on gestational age

Gestational age (weeks)

Total bilirubin level (mg/dL)

Phototherapy

Exchange transfusion

Sick*

Well

36

14.6

17.5

20.5

32

8.8

14.6

17.5

28

5.8

11.7

14.6

24

4.7

8.8

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

1.250-1.499 g

1.500-1.999 g

2.000-2.499 g

Standard risk

Total bilirubin

13

15

17

18

B/A ratio

5.2

6.0

6.8

7.2

High risk*

Total bilirubin

10

13

15

17

B/A ratio

4.0

5.2

6.0

6.8

Guidelines for the Management of Hyperbilirubinemia Based on Birth Weight and Relative Health of the Newborn

Serum Total Bilirubin Level (mg/dL)

Birth Weight

Healthy

Sick

Phototherapy

Exchange Transfusion

Phototherapy

Exchange Transfusion

Premature

< 1000 g

1001 1500 g

1501 2000 g

2001 2500 g

Term

> 2500 g

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 IkterusPocket Book WHO, 2005

USIA

Bilirubin Serum Total (mg/dL)

Terapi sinar

Transfusi tukar

Tanpa

Faktor Risiko

Prematur atau

Dengan Faktor Risiko

Tanpa

Faktor Risiko

Prematur atau

Dengan Faktor Risiko

Hari 1

Setiap ikterus yang terlihat

15

13

Hari 2

15

13

25

15

Hari 3

18

16

30

20

Hari 4 dst

20

17

30

20