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(Neonatal Hyperbilirubinemia)
dr. Masliani
Introduction
Neonatal
Jaundice is known as the visible clinical manifestation of dying skin and sclera yellow during the neonatal period, resulting from deposition of bilirubin in the neonatal bodies.
Introduction
as kern-icterus.
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
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
Bilirubin Physiology
Final product of heme degredation Insoluble in plasma (needs to be bound to albumin) Has to go to liver to be conjugated After liver, excreted in bile
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.
Enterohepatic Circulation
Meconium contains 100-200mg of conjugated bilirubin at birth. Conjugated bilirubin is unstable and easily hydrolyzed to unconjugated bilirubin. This process occurs non-enzymatically in the duodenum and jejunum and also occurs in the presence of betaglucuronidase, an enteric mucosal enzyme, which is found in high concentration in newborn infants and in human milk.
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 weeks gestation 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.
Metabolism of Bilirubin
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 the chest 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.
Hyperbilirubinemia Signs
Skin yellowing
Not visible if bili <4
Methods of Diagnosis
bilirubin fractions
Determination of hemoglobin
Reticulocyte count Blood type Coombs test Examination of the peripheral blood smear
Classifications
Direct-reacting
hyperbilirubinemia
Classifications
Indirect-reacting
hyperbilirubinemia
Hemolysis
Reticulocytosis
Evidences
Blood
Positive
Classifications
Direct
Classifications
Physiologic jaundice
Clinical jaundice appears at 2-3 days. Total bilirubin rises by less than 5 mg/dl (86
bilirubin concentration in Full-term infant <12mg/dl (205.2 umol/L) bilirubin concentration in Premature infant <15mg/dl (257umol/L)
Classifications
Pathologic
jaundice
than 12 mg/dL in the term infant and 15 mg/ dL in the preterm infant.
Classifications
Pathologic
jaundice
been resolved.
Direct bilirubin concentration is more than
jaundice
Neonatal hepatitis
TORCH infection
Neonatal sepsis
incompatibility
incompatibility
Biliary atresia
Jaundice associated with breast- feeding
milk jaundice
Thalassemia Cystic
fibrosis k
Drug
Vitamin Novobiocin
Introduction
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
O mothers A or B fetuses of IgG anti-A or Anti-B antibodies in occurring during the first pregnancy
Presence
type O mother
Frequently
Rh hemolytic disease
Rh blood group antigens (C, c, D, d, E, e)
D>E>C>c>e
Rh-negative mother Rh-positive fetus of fetal RBC into maternal circulation sensitization to D antigen on fetal RBC
Leakage Maternal
of maternal antibodies to
of antibody-coated fetal
RBC
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
bleeding associated with a previous spontaneous or therapeutic abortion pregnancy variety of different prenatal procedures
Ectopic A
Transfusion
Clinical Manifestations
Jaundice
Anemia
Hydrops
Massive enlargement of the liver and
spleen
Clinical Manifestations
Clinical Features Of Hemolytic Disease Clinical Features
Frequency
Rh
Unusual
ABO
Common
Anemia
Jaundice Hydrops
Marked
Marked Common
Minimal
Minimal to moderate Rare
Hepatosplenomegaly Marked
Kernicterus Common
Minimal
Rare
Laboratory Diagnosis
Laboratory Features Of Hemolytic Disease Laboratory Features
blood type of Mother blood type of Infant
Rh
Rh negative Rh positive
ABO
O A or B
Anemia
Direct Commbs test Indirect Commbs test
Marked
Positive Positive
Minimal
Negative Usually positive
Hyperbilirubinemia
RBC morphology
marked
Nucleated RBC
Variable
Spherocytes
Diagnosis
The
Diagnosis
Antenatal Diagnosis
History Expectant parents blood types Maternal titer of IgG antibodies to D or E
(>1:32)
1216 wk At 2832 wk At 36 wk
At
Diagnosis
Postnatal diagnosis
Jaundice at < 24 hr Anemia (Hematocrit and hemoglobin
examination)
Rh or ABO incompatibility
Coombs test positive Examination for RBC antibodies in the
mothers serum
Differential Diagnosis
Congenital Neonatal
nephrosis
anemia jaundice
Physiological
Treatment
Main goals
To prevent intrauterine or extrauterine
and hypoxic
To avoid neurotoxicity from
hyperbilirubinemia
Treatment
Treatment
Utero transfusion
Indication
Hydrops
Anemia (Hematocrit<30%)
Method
Packed RBC matching with the mothers
serum
Umbilical vein transfusion
Treatment
Delivery in advance
Indication
Pulmonary maturity
Fetal distress
Treatment
therapy
Temperature
stabilization Correction of acidosis: 1-2mEq/kg of sodium bicarbonate A small transfusion compatible packed RBC Volume expansion for hypotension Provision of assisted ventilation for respiratory failure
Treatment
Phototherapy
Blue
spectrum of 427-475 nm (or White or Green) Irradiance:10-12W/cm2 Protection of eyes and genital Indication
Bilirubin10mg/dl at 12 hr Bilirubin12-14mg/dl at 18 hr Bilirubin15mg/dl at 24 hr
Phototherapy
Use blue wavelengths of light to alter unconjugated bilirubin in the skin. Bilirubin converted to less toxic watersoluble photoisomers Excreted in the bile and urine without conjugation
Phototherapy Optimization
Ideal configuration: 4 special blue bulbs (F20T12/BB) placed centrally, with two daylight fluorescent tubes on either side Power output of the lights (irradiance) is directly related to the distance between the lights and the 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 effective as standard phototherapy)
Phototherapy Tid-Bits
If TSB levels approach or exceed the exchange transfusion line the sides of the bassinet, incubator, or warmer should be lined with aluminum foil or white material If the total serum bilirubin does not decrease or continues to rise in an infant who is receiving intensive phototherapy, strongly suggests hemolysis Infants who receive phototherapy and have an elevated conjugated bilirubin level (cholestatic jaundice) may develop the bronze-baby syndrome (brown discoloration)
Phototherapy Cessation
Decline avg at 1-2 points within 4-6 hours Decline may be slow in breastfed than in formula fed Can be stopped if <15 Turn off lights and check for rebound in ~12 hours Avg rebound ~1 point Hospital discharge does not have to be held for rebound elevation
Phototherapy Complication
Riboflavin destruction Loose stools/diarrhea Tanning of the skin Hypocalcemia Bronze-baby syndrome
Hydration Assessment
Percentage of birth weight lost Mucous membranes Fontanelle Skin turgor
Previous kernicterus in a sibling, reticulocyte counts greater than 15%, asphyxia of neonate and premature infant
180ml/kg
Blood
choose of Rh incompatibility
Blood
Treatment
Drug treatment
Intravenous
Human
albumin Dexamethasone
Protoporphyrins Glucocorticoids:
Prevention
KERNICTERUS
Staining of the brain by bilirubin Early symptoms-acute bilirubin encephalopathy-poor feeding, abnormal cry, hypotonia, Intermediate phase-stupor, irritability, hypertonia Late shrill cry, no feeding, opisthotonus, apnea, seizures, coma, death
KERNICTERUS
Dystonia
Incoordination Choreoathetosis
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 19912002 was 20.7, but the mean was 38. Many cases had no planned follow up and had been discharged early (<48 hours).