Neonatal Jaundice Dr.masliani

7/27/2019 Neonatal Jaundice Dr.masliani

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IntroductionNeonatal Jaundice is known as

the visible clinical manifestation

of dying skin and sclera yellow

during the neonatal per iod,

resulting from deposition of

bilirubin in the neonatal bodies.


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BILIRUBIN

Non-polar, water insoluble compound requiring

conjugation with glucuronic acid to form a water

soluble product that can be excreted.

It circulates to the liver reversibly bound to

albumin


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BILIRUBIN PHYSIOLOGY

Increased production in neonate due to larger red cell

volume, which produces bilirubin as cells are broken

down and shorter RBC life span, so broken down faster. Heme is catabolized within the reticuloendothelial

system by heme oxygenase to form biliverdin.

Biliverdin is metabolized to bilirubin in the presence of

biliverdin reductase


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Bilirubin Physiology

Final product ofheme degredation

Insoluble in plasma(needs to bebound to albumin)

Has to go to liver

to be conjugatedAfter liver,

excreted in bile


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Bilirubin Physiology

Ligandins responsible for transport from plasma

membrane to endoplasmic reticulum.

Bilirubin conjugated in presence of UDPGT

(uridine diphosphate glucuronyl transferase) to

mono and diglucoronides, which are then

excreted into bile canaliculi.


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Enterohepatic Circulation

Meconium contains 100-200mg of conjugated bilirubinat birth.

Conjugated bilirubin is unstable and easily hydrolyzedto unconjugated bilirubin.

This process occurs non-enzymatically in the duodenumand jejunum and also occurs in the presence of beta-

glucuronidase, an enteric mucosal enzyme, which isfound in high concentration in newborn infants and inhuman milk.


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Conjugation

Since conjugated bilirubin crosses the placenta very

little, conjugation is not active in the fetus with levels of

UDPGT about 1% of adult levels at 30 - 40 weeksgestation

After birth, the levels of UDPGT rise rapidly but do not

reach adult levels until 4-6 weeks of age.

Ligandins, which are necessary for intracellular

transport of bilirubin, are also low at birth and reach

adult levels by 3-5 days.


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Metabolism of Bilirubin Increased bilirubin production

Less effective binding and transportation

Less efficient hepatic conjugation

Enhanced absorption of bilirubin via the

enterohepatic circulation


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Clinical Manifestation Jaundice may be present at birth or at any

time during the neonatal period.

Jaundice usually begins on the face and, as

the serum level increases, progresses to thechest and abdomen and then the feet.

Jaundice resulting from deposition of indirect

bilirubin in the skin tends to appear bright

yellow or orange; jaundice of the obstructive

type (direct bilibrubin), a greenish or muddy

yellow.


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Hyperbilirubinemia Signs

Skin yellowing

Not visible if bili 15 [soles = 20]


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Methods of DiagnosisA complete diagnostic evaluationDetermination of direct and indicrect

bilirubin fractionsDetermination of hemoglobin

Reticulocyte count

Blood typeCoombs test

Examination of the peripheral blood smear


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ClassificationsDirect-reacting hyperbilirubinemia

Hepatitis

Cholestasis

Inborn errors of metabolism

Sepsis


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Classifications

Indirect-reacting hyperbilirubinemiaHemolysis

Reticulocytosis

Evidences of red blood cell destruction

A positive Coombs test

Blood group incompatibility

Positive results of specific examination


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ClassificationsDirect and indirect- reactin

hyperbilirubinemia

Hepatitis

Sepsis

Liver damage complicated by Hemolysis


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Classifications Physiologic jaundice

Clinical jaundice appears at 2-3 days.

Total bilirubin rises by less than 5 mg/dl (86

umol/L) per day.

Peak bilirubin occurs at 3-5 days of age.Peak bilirubin concentration in Full-term infant


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ClassificationsPathologic jaundice

Clinical jaundice appears in 24 hours of age.

Total bilirubin rises by higher than 5 mg/dl(86 umol/L) per day.

Peak concentration of total bilirubin is more

than 12 mg/dL in the term infant and 15 mg/

dL in the preterm infant.


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ClassificationsPathologic jaundiceClinical jaundice is not resolved in 2

weeks in the term infant and in 4 weeks inthe Preterm infant.

Clinical jaundice appears again after it has

been resolved.

Direct bilirubin concentration is more than

1.5 mg/dL (26umol/L).


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Causes of

Pathologic JaundiceInfectivejaundice

Neonatal hepatitis

TORCH infection

Neonatal sepsis


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Causes of

Pathologic Jaundice Jaundice associated without infection

Hemolytic disease of the newborn

ABO incompatibility

Rh incompatibility

Biliary atresia

Jaundice associated with breast- feeding


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Causes of

Pathologic JaundiceBreast milk jaundice

It is caused by prolonged increased enterohepatic

circulation of bilirubin. (-GD)

The hyperbilirubinemia peaks at 10-15 days of age.

The level of unconjugated hyperbilirubinemia is at

10-30 mg/dL (172-516 umol/L).If nursing is interrupted for 72 hours, the bilirubin

level falls quickly.


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Causes of

Pathologic JaundiceGenetic disease

Congenital deficiencies of the enzymes

glucose-6-phosphate dehydrogenase (G-6-PD)

Thalassemia

Cystic fibrosis

Drug

Vitamin k

Novobiocin


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Hemolytic

Disease of

the Newborndr. Masliani


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Introduction

Hemolytic disease of the newborn

It is an isoimmunity hemolysis associated

with ABO or Rh incompatibility.It results from transplacental passage of

maternal antiboddy active against RBC

antigens of the infant, leading to an

increased rate of RBC destruction.

It is an important cause of anemia and

jaundice in newborn infant.


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Etiology and Pathogenesis

ABO hemolytic disease

ABO incompatibility

Type O mothers

Type A or B fetuses

Presence of IgG anti-A or Anti-B antibodies in

type O mother

Frequently occurring during the first pregnancy

without prior sensitization


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Etiology and PathogenesisRh hemolytic disease

Rh blood group antigens (C, c, D, d, E, e)

D>E>C>c>e

Pathophysiology of alloimmune hemolysis

resulting from Rh incompatibilityAn Rh-negative mother

An Rh-positive fetus

Leakage of fetal RBC into maternal circulationMaternal sensitization to D antigen on fetal RBC


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Etiology and Pathogenesis

Production and transplacental passage

of maternal anti-D antibodies into fetal

circulation

Attachment of maternal antibodies to

Rh-positive fetal RBC

Destruction of antibody-coated fetal

RBC


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Etiology and PathogenesisRh hemolytic disease was rare during the first

pregnancy involving an Rh-positive fetus.

Once sensitization has occurred, re-exposure

to Rh D RBC in subsequent pregnancies leads

to an anamnestic response, with an increase

in the maternal anti-Rh D antibody titer.

The likelihood of an infant being affected

increased significantly with each subsequent

pregnancy.


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Etiology and PathogenesisSignificant hemolysis occurring in the

first pregnancy indicates prior maternal

exposure to Rh-positive RBC.

Fetal bleeding associated with a previous

spontaneous or therapeutic abortion

Ectopic pregnancy

A variety of different prenatal proceduresTransfusion of some other blood product

containing Rh D RBC in an Rh-negative

mother


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Clinical Manifestations

Jaundice

Anemia

Hydrops

Massive enlargement of the liver and

spleen

Bilirubin encephalopathy (Kernicterus)


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Clinical ManifestationsClinical Features Of Hemolytic Disease

Clinical Features Rh ABO

Frequency Unusual Common

Anemia Marked Minimal

Jaundice Marked Minimal to moderate

Hydrops Common Rare

Hepatosplenomegaly Marked Minimal

Kernicterus Common Rare


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Laboratory Diagnosis

Laboratory Features Of Hemolytic Disease

Laboratory Features Rh ABO

blood type of Mother Rh negative O

blood type of Infant Rh positive A or B

Anemia Marked MinimalDirect Commbs test Positive Negative

Indirect Commbs test Positive Usually positive

Hyperbilirubinemia marked Variable

RBC morphology Nucleated RBC Spherocytes


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Diagnosis

The definitive diagnosis requires

demonstration of blood group

incompatibility and of corresponding

antibody bound to the infants RBC.


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DiagnosisAntenatal Diagnosis

History

Expectant parents blood types

Maternal titer of IgG antibodies to D or E(>1:32)

At 1216 wkAt 2832 wkAt 36 wk

Fetal Rh and ABO status

Fetal jaundice level


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Diagnosis Postnatal diagnosis

Jaundice at < 24 hr

Anemia (Hematocrit and hemoglobinexamination)

Rh or ABO incompatibility

Coombs test positive

Examination for RBC antibodies in the

mothers serum


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Differential Diagnosis

Congenital nephrosis

Neonatal anemia

Physiological jaundice


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Treatment

Main goals

To prevent intrauterine or extrauterine

death of fetal or infant form severe anemia

and hypoxic

To avoid neurotoxicity fromhyperbilirubinemia


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TreatmentTreatment of the unborn infant

Utero transfusion

IndicationHydrops

Anemia (Hematocrit


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Treatment

Delivery in advance

IndicationPulmonary maturity

Fetal distress

Maternal titer of Rh antibodies > 1:32

3537 wk of gestation


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Treatment Treatment of the liveborn infant

Immediate resuscitation and supportive

therapy

Temperature stabilization

Correction of acidosis: 1-2mEq/kg of sodium

bicarbonate

A small transfusion compatible packed RBCVolume expansion for hypotension

Provision of assisted ventilation for respiratory

failure


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TreatmentPhototherapy

Blue spectrum of 427-475 nm (or White

or Green)

Irradiance:10-12W/cm2

Protection of eyes and genital

Indication

Bilirubin10mg/dl at12 hrBilirubin12-14mg/dl at18 hrBilirubin15mg/dl at 24 hr


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Phototherapy

Use blue wavelengths of light to alter

unconjugated bilirubin in the skin.

Bilirubin converted to less toxic water-soluble photoisomers

Excreted in the bile and urine without

conjugation
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75th Percentile

40th Percentile
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When To Start Phototherapy?

TSB at 95th percentile

Although, may be facility dependent


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Phototherapy Optimization Ideal configuration: 4 special blue bulbs

(F20T12/BB) placed centrally, with two daylightfluorescent tubes on either side

Power output of the lights (irradiance) is directlyrelated to the distance between the lights andthe newborn

Ideal light distance: 15 to 20 cm from the infant

Naked

Eye shields For double phototherapy: a fiber-optic pad can

be placed under the newborn (twice as effectiveas standard phototherapy)


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Phototherapy Tid-Bits

If TSB levels approach or exceed theexchange transfusion line the sides of thebassinet, incubator, or warmer should belined with aluminum foil or white material

If the total serum bilirubin does not decrease

or continues to rise in an infant who isreceiving intensive phototherapy, stronglysuggests hemolysis

Infants who receive phototherapy and have

an elevated conjugated bilirubin level(cholestatic jaundice) may develop thebronze-baby syndrome (browndiscoloration)


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Phototherapy Cessation

Decline avg at 1-2 points within 4-6 hours

Decline may be slow in breastfed than in formulafed

Can be stopped if


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Phototherapy Complication

Burns

Dehydration

Retinal Damage

Thermoregulatory

instability

Riboflavin destruction

Loose stools/diarrhea

Tanning of the skin

Hypocalcemia

Bronze-baby

syndrome


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Hydration Assessment

Percentage of birth weight lost

Mucous membranes

Fontanelle

Skin turgor


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Babies under phototherapy


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Treatment

Exchange transfusionIndication

Hemoglobin120g/LHydrops, hepatosplenomegaly and heart failure

Bilirubin in the 1st12 of life>0.75mg/dl/hr

Bilirubin concentration>20mg/dl

Factors supporting early exchange transfusion:

Previous kernicterus in a sibling, reticulocytecounts greater than 15%, asphyxia of neonate

and premature infant


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TreatmentBlood volume of exchange transfusion

Double-volume exchange transfusion :150-

180ml/kg

Blood choose of Rh incompatibility

Rh in accordance with mother

ABO in accordance with neonate

Blood choose of ABO incompatibility

Plasm of AB type

RBC of O type


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Treatment

Drug treatment

Intravenous immuneglobulin (IVIG)

Human albumin

Protoporphyrins : Sn-PP; Zn-PP

Glucocorticoids: Dexamethasone

Inducerof liver enzyme: Luminal


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Prevention Intramuscular injection of 300ug of human

anti-D globulin to an Rh-negative mother

Within 72 hr of delivery of an ectopic pregnancy

Abdominal trauma in pregnancy

AmniocentesisChorionic villus biopsy

Abortion


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KERNICTERUS

Staining of the brain by bilirubin

Early symptoms-acute bilirubin encephalopathy-poor

feeding, abnormal cry, hypotonia, Intermediate phase-stupor, irritability, hypertonia

Lateshrill cry, no feeding, opisthotonus, apnea,

seizures, coma, death


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KERNICTERUS

Late sequelae can include

gaze abnormalities

feeding difficulties

Dystonia

Incoordination

Choreoathetosis

sensorineural hearing loss

painful muscle spasms


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KERNICTERUS

Incidence of bilirubin levels>30 1/10,000

Over 120 cases kernicterus documented since 1990

Overwhelming majority term, breastfed Majority of those had levels in high 30s to 40s.

Lowest level recorded in case series of 111 from 1991-2002 was 20.7, but the mean was 38.

Many cases had no planned follow up and had beendischarged early (

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Neonatal Jaundice Dr.masliani