Post on 02-Apr-2018
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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
http://aappolicy.aappublications.org/sub-journals/pediatrics/html/content/vol114/issue1/images/large/zpe0070469050002.jpeg7/27/2019 Neonatal Jaundice Dr.masliani
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75th Percentile
40th Percentile
http://aappolicy.aappublications.org/sub-journals/pediatrics/html/content/vol114/issue1/images/large/zpe0070469050002.jpeghttp://aappolicy.aappublications.org/sub-journals/pediatrics/html/content/vol114/issue1/images/large/zpe0070469050002.jpeghttp://aappolicy.aappublications.org/sub-journals/pediatrics/html/content/vol114/issue1/images/large/zpe0070469050002.jpeghttp://aappolicy.aappublications.org/sub-journals/pediatrics/html/content/vol114/issue1/images/large/zpe0070469050002.jpeghttp://aappolicy.aappublications.org/sub-journals/pediatrics/html/content/vol114/issue1/images/large/zpe0070469050002.jpeg7/27/2019 Neonatal Jaundice Dr.masliani
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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 (