NEONATAL JAUNDICE

Babelyn T. Dimabayao

Jaundice
Hyperbilirubinemia
to an excessive level of accumulated bilirubin in the blood Characterized by jaundice, a yellowish discoloration of the skin, sclerae, mucous membranes and nails Total serum bilirubin (TSB) of >5 mg/dL
Refers

Significance
in up to 60% of term and 80% of preterm Severe complications possible
Present


kernicterus

Neonatal Jaundice
Increased rbcs Shortened rbc lifespan Immature hepatic uptake & conjugation

Increased enterohepatic circulation

Hb globin + heme 1g Hb = 34mg bilirubin

Non heme source 1 mg / kg

Bilirubin
Ligandin (Y - acceptor) Bilirubin glucuronidase

Intestine

Bil glucuronide

Bil glucuronide glucuronidase bacteria

Bilirubin

Stercobilin

Area of body Face Upper trunk Lower trunk & thighs Arms and lower legs Palms & soles

Bilirubin levels
mg/dl (*17=umol)

4-8 5-12 8-16 11-18 > 15

Neonatal Jaundice

Differential Diagnosis
1st 24 hours
Erythroblastosis fetalis Concealed hemorrhage Sepsis or congenital infections (syphilis, cytomegalovirus, rubella, and toxoplasmosis) Extensive ecchymosis or blood extravasation (premature infants)

2nd to 3rd day of life

Physiologic jaundice Familial non-hemolytic icterus (Crigler-Najjar syndrome) Breast-feeding jaundice (early onset)

Differential Diagnosis
3rd day and within the 1st wk
Bacterial sepsis or urinary tract infection Other infections (syphilis, toxoplasmosis, cytomegalovirus, or enterovirus)

After 1st week

Breast-milk jaundice Septicemia Congenital atresia or paucity of the bile ducts Hepatitis Galactosemia, hypothyroidism, cystic fibrosis, Congenital hemolytic anemia crises related to red cell morphology and enzyme deficiencies

Differential Diagnosis
1st month of life
Hyperalimentation-associated cholestasis Hepatitis Cytomegalic inclusion disease Syphilis Toxoplasmosis Familial non-hemolytic icterus Congenital atresia of the bile ducts Galactosemia Inspissated bile syndrome following hemolytic disease of the newborn

Physiologic Jaundice
Appears after 24 hours Maximum intensity by 4th-5th day in term & 7th day in preterm Serum level less than 15 mg/dl Disappears without any treatment Increased bilirubin production from the breakdown of fetal RBCs combined with transient limitation in the conjugation of bilirubin by the immature liver

Physiologic Jaundice

Breastmilk Jaundice
Elevated unconjugated bilirubin Prolongation of physiologic jaundice
Slower
 66% of breastfed babies jaundiced  May persist up to 3 months

decrease to adult levels of bilirubin

into 3rd week of life

May

have second peak @ day 10

Average max TSB = 10-12 mg/dL TSB may reach 22-24 mg/dL Milk factor (?)
Beta

glucoronidase: increase deconjugation and reabsorption

Breastfeeding Jaundice
Elevated unconjugated bilirubin Benign or pathologic
Elevated

bilirubin in the 1st week of life tends to worsen breast milk jaundice during later weeks

Equivalent to starvation jaundice in adults Mandates improved/increased breastfeeding

No

water or dextrose supplementation

Common Causes of Pathologic Jaundice

Risk Factors

Pathologic Jaundice
Features
in 1st 24 hrs Rapidly rising TSB (> 5 mg/dL per day) TSB > 17 mg/dL Direct bilirubin >2mg/dL
Jaundice

Erythroblastosis Fetalis
Develops in an unborn infant when the mother and baby have different blood types Mother produces antibodies that attack the developing baby's red blood cells

ABO Incompatibility
Occurs when the major blood group antigens of the fetus are different from those of the mother Most common is between a type O mother and type A or B infant May occur in the first pregnancy

Rh Incompatibility
Rh-negative pregnant mother is exposed to Rhpositive fetal red blood cells
y

Fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or normal delivery

Rh-negative female receives an Rh-positive blood transfusion Usually manifests in second/succeeding pregnancies

Infections
Congenital TORCH Infection Hepatitis Sepsis UTI Pneumonia Partly due to inadequate liver functioning but majority is due to plugging and subsequent bile stasis Intracellular accumulation of unconjugated bilirubin and by "toxic" cellular alterations, such as giant-cell transformation

Infections

G6PD Deficiency
A cause of kernicterus in up to 35% of cases Always suspect if severe hyperbilirubinemia or poor response to phototherapy Ethnic origin

11-13% of African Americans Mediterranean, Middle East, Arabian peninsula, SE Asia, Africa

Requires intervention at lower TSB levels Testing

Levels may be normal or elevated early  Especially in presence of hemolysis Repeat level at 3 months

G6PD Deficiency
G6PD:
Oxidation

of glucose-6-phosphate to 6phosphogluconate while concomitantly reducing the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP+) to nicotinamide adenine dinucleotide phosphate (NADPH)


NADPH is a cofactor that maintains glutathione in its reduced form

RBCs

rely on enzyme activity as a source of NADPH that protects the cells against oxidative stresses

G6PD Deficiency

Other Enzyme and Metabolic Defects

Pyruvate Kinase Deficiency

Erythrocytes produce ATP thru glycolysis PK potentiates the last step of glycolysis (phosphoenolpyruvate converted to pyruvate) Hampers Na-K ATPase Echinocytes Crigler-Najjar Type I and II Gilberts Syndrome

UGT Deficiency

Alpha 1 Antitrypsin Deficiency Alagille Syndrome Cystic Fibrosis Galactosemia Hypothyroidism

Drug-Induced Jaundice
Competitive Binders
Aspirin Ceftriaxone Sulfisoxazole

Prevention
Breastfeeding
Should

be encouraged for most women 8-12 times/day for 1st several days Assistance and education Avoid supplements in non-dehydrated infants
 Do

not decrease level & severity of hyperbilirubinemia

Prevention
Ongoing assessments for risk of developing severe hyperbilirubinemia
Monitor

at least every 8-12 hours Blood testing

Prenatal (Mom): ABO & Rh type, antibody  Infant cord blood

 

Mom not tested, Rh (-): Coombs, ABO, Rh Mom O or Rh (+): optional to test cord blood

Laboratory Investigation
Indicated (if bilirubin concentrations reach phototherapy levels)
Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombs test) Hemoglobin and hematocrit determinations

Optional (in specific clinical circumstances)

Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations

Discharge
Assess risk
bilirubin  Use nomogram to determine risk zone And/or Assessment of risk factors
Predischarge

TSB Zone High risk High intermed Low intermed Low

Newborns (%) 6 12.5 19.6 61.8

% with TSB >95th % 39.5 12.9 2.26 0

Discharge
Close follow-up necessary
Individualize based on risk Weight, % change from BW, intake, voiding habits, jaundice

Infant Discharge < 24 hours 24-48 hours 48-72 hours

Should be Seen by 72 hours 96 hours 120 hours

ALGORITHM FOR THE MANAGEMENT OF JAUNDICE IN THE NEWBORN NURSERY

Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316

Copyright 2004 American Academy of Pediatrics

Phototherapy
Mechanism: converts bilirubin to water soluble form that is easily excreted Forms
Fluorescent lighting Fiberoptic blankets

Goal is to decrease TSB by 4-5 mg/dL or < 15 mg/dL total Breastfed infants are slower to recover

Phototherapy
Bilirubin levels > 20 mg/dL, phototherapy should be administered continuously until levels fall below 20 mg/dL, upon which it can be administered intermittently

Exchange Transfusion
Mechanism: removes bilirubin and antibodies from circulation and correct anemia Most beneficial to infants with hemolysis

Generally never used until after intensive

phototherapy attempted

Indications
Jaundiced

infant with clinical signs of BIND (lethargy, hypotonia, poor-sucking, high pitched cry) Infants with a TB level greater than the threshold defined by the AAP

After a successful procedure, TB initially falls to half its pre-transfusion value and eventually equilibrates at two-thirds of this initial level

Pharmacologic Treatment
IVIG: can reduce the need for exchange transfusion in infants with hemolytic disease caused by Rh or ABO incompatibility Phenobarbital: increases the conjugation and excretion of bilirubin Ursodeoxycholic acid: increases bile flow and is useful in the treatment of cholestatic jaundice

Complications
Toxicity to basal ganglia and brainstem nuclei 2 terms
Acute bilirubin encephalopathy Kernicterus

Multiple phases

Risk of Kernicterus
TSB level > 25-30 mg/dl Acidosis Increased free bilirubin Low albumin, drug displacement Blood-brain barrier disruption Prematurity, sepsis, ischemia

Kernicterus cases with potentially correctable causes

Early discharge (<48hrs) without f/u within 48 hrs Failure to check bilirubin level if onset in first 24 hours Failure to note risk factors Visual assessment underestimate of severity Delay in testing jaundiced newborns or treating elevated levels Lack of concern for presence of jaundice or parental concern

THANK YOU!