Transcript Neonatal Jaundice.ppt

Neonatal Jaundice
Dr. AbdulRahman Al Nemri, MD
Chairman of Pediatric Department
Associate Professor
Senior Consultant Neonatologist
Introduction
Yellow-orange pigment Icterus –
ikteros - bilirubin in the skin and
sclerae. It affects 60% of neonates.
Jaundice = galbus (it appears when TSB is
more than 34umol/l in adults Vs >86 in neonates)
It is one of the most common clinical
phenomena encountered in
newborns.
Bilirubin Production
 Bilirubin is obtained by degrading heme from
hemoglobin-containing RBCs (80% of bilirubin is
from Hb).
 RBC life in adults is 120 days. In children, it is
shorter (90 days) giving them higher turnover rates
specially in premature infants.
 It functions as an antioxidant against free radicals,
and an emulsion to lipids.
 20% from ineffective erythropoiesis and turnover of
non-hemoglobin hemoproteins (eg, myoglobin,
catalase, nitric oxide synthase, peroxidases, and
cytochromes).
A scheme for the origin of bilirubin
03/11/1437
Wong, R. J. et al. Neoreviews 2007;8:e58-e67
Heme catabolic pathway
Heme oxygenase breaks
down the heme to CO and
bilirubin. Therefore CO
measurement can estimate
the amount of bilirubin.
Wong, R. J. et al. Neoreviews 2007;8:e58-e67
Copyright ©2007 American Academy of Pediatrics
Bilirubin Transport
• Free Bilirubin is lipid soluble (hydrophobic), crosses the
BBB and is toxic to the brain, therefore it binds to
albumin.
• It binds reversibly to albumin (bilirubin:albumin)
• (about 0.8 - 7 mg of bilirubin per gram of albumin- )
• Low Albumin level and affinity binding sites
• Aqueous diffusion
• The movement of bilirubin from the circulation into tissue
cross BBB.
• Albumin-bilirubin conjugate is transports to hepatocytes.
Conjugation
• Conjugation of bilirubin (in the hepatocytes)
with glucuronic acid (water-soluble,
nonneurotoxic bilirubin) by the enzyme UGT.
• uridine diphospho- glucuronosyltransferase
(UGT), lack of this enzyme in neonates will
increase its toxicity.
• Decrease conjugation by:
1.Slower rate of hepatic uptake of free bilirubin
from the blood
2. Decreased concentrations of (UGT) +
Bilirubin Excretion
• Conjugated bilirubin enter the bile ducts and
are excreted with the bile into the intestinal
tract.
• Mono Or Diglucuronide > unconjugated Bili
• In the colon, bacterial flora in older
neonates hydrogenate bilirubin to
urobilinogen, urobilins, and stercobilins.
• Part of the urobilinogen is absorbed into the
portal circulation and excreted by the kidney.
biliverdin reductase
beta-glucuronidase
Bilirubin oxidase
uridine diphospho- glucuronosyltransferase (UGT)
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RISK FACTORS FOR SIGNIFICANT
JAUNDICE
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Gestational Age more in premature
Race (Genetic @ environmental
Maternal illness DM & Blood group (ABO or Rhs)
Family history of jaundice requiring
phototherapy
• Hemolysis (G6PD, Spherocytosis)
• Severe bruising
• Breastfeeding
History
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Origin of the infant
Blood group
Autoimmune diseases.
Hemoglobinopathies.
Onset and associated symptoms (lethargy, poor
suckling and crying).
• Color of the stool and urine.
• Color of the skin: if pale then hemolytic anemia.
Jaundiced.
• Check for hepato-spleenomegaly.
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Etiological Classification
1.
Increased bilirubin load
•
I.
Hemolytic causes
Coombs' test positive: Rh factor incompatibility, ABO
II.
incompatibility, minor antigens, autoimmune as lupus and RA
because antibodies are already there. Which one is common ?
Coombs' test negative: red blood cell membrane defects
(spherocytosis, elliptocytosis), red blood cell enzyme defects (G6PD
deficiency, pyruvate kinase deficiency)

Why not thalasemia or SCD?
SCA and thalasemia beta are never a DDx because they are a beta chain
abnormality while the neonate HbF which consists of alfa and
gamma chains, while thalasemia alfa (there will be in utero
hemolysis) and G6PD are imp DDx.
Physsiologic Mechanism
Binding
Bilirubin
production
Transportation
Entero-hepatic
conjugation
Hepatitis.
Sepsis can cause
hemolysis and affects the
hepatocytes impairing
conjugation.
Bilirubin
Elimination
Nonhemolytic causes
• Increased unconjugated bilirubin level,
normal percentage of reticulocytes
Physiologic jaundice
Extravascular sources
Polycythemia
Exaggerated enterohepatic circulation
2- Decreased bilirubin conjugation
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Physiologic jaundice
Crigler-Najjar syndrome: deficiency of UGT enzyme.
Gilbert syndrome.
Hypothyroidism.
Cystic fibrosis.
Metabolic in-born illness.
Alfa one antitrypsin deficiency.
Breast milk jaundice
Hep B or C TORCH or any bacterial infection to the liver.
affects the liver and impairs the conjugation.
 Hepatomegaly and hepatits.
3- Impaired bilirubin excretion
• Conjugated bilirubin level of >2 mg per dL (34 μmol per
L) or >20% of total serum bilirubin level
 Biliary obstruction e.g. biliary atresia can be extrahepatic (they come with distinctive features) or intrahepatic. Or obstruction outside the biliary system e.g.
hematoma, hemangioma, choledecal cyst, pancreatic or
duodenal mass.
 Infection
 Metabolic disorder
 Chromosomal abnormality e.g. dobbin Johnson and
Rotters syndrome.
Physiologic jaundice
• increased breakdown of fetal erythrocytes.
shortened lifespan of fetal erythrocytes and the
higher erythrocyte mass in neonates
• The commonest cause of jaundice in term babies.
• Hepatic excretory capacity is slow because
hepatocytes are still not mature.
• low activity of glucuronyl transferase
• Typically, presentation is on the second or third
day of life.
• Jaundice that is visible during the first 24 hours
of life is likely to be non-physiologic
What is the commonest cause of non
hemolytic hyperbilirubineamia?
Physiological jaundice.
What are the other D/D?
What are the criteria of physiological Jaundice
?
1. Onset more than 24 hours but less than 2
weeks.
2. Rate of TSB increment not more than 5
mg.
3. Level of TSB less than 25 mmol/l.
4. Type of Bili: un-conjugated, if conjugated
its pathological.
5. Duration
03/11/1437
Infants with multiple risk factors
may develop an exaggerated
form of physiologic jaundice in
which the total serum bilirubin
level may rise as high as 17 mg
per dL (291 μ mol per L)
JAUNDICE AND BREAST FEEDING
• Early-Onset Breast feeding associated
Jaundice or B Feeding failure J.
• Decreased volume and frequency of
feedings may result in mild dehydration and
the delayed passage of meconium
• Breast milk jaundice occurs later in the
newborn period usually peaking in the sixth
to 14th days of life.
• B Milk Metabolites ( progestrin, pregnane 3α,20β)
PATHOLOGIC JAUNDICE
All etiologies of jaundice beyond
1) Physiologic
2) Breastfeeding (the baby does not feed
and becomes dehydrated) or
3) breast milk jaundice (milk content
causing jaundice)
are considered pathologic.
Un-Conugated
Hyperbilirubinemia
1. Excessive Bilirubin
Production
2. Impaired Conjugation
3. Excretion
Hemolytic Disease
Blood group incompatibility
Red cell enzyme deficiency
Red blood cell membrane defect
Extravascular Blood
Polycythemia
Sepsis
ABO Incompatibility
• ABO Incompatibility is the most common
cause of hemolytic jaundice
• Only 10-20% of infants with ABO mismatch
develop significant jaundice
• Coombs positive ABO is more likely to cause
hemolysis
• Conversely, Coombs negative ABO
mismatch does occasionally cause significant
hemolysis, but this is rather rare.
Diagnosis
• HISTORY
• PHYSICAL EXAMINATION
Laboratory Evaluation of Term Newborn with
Jaundice
<24 hours
24-48 hours
>2 weeks
Management
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2.
3.
4.
An increased incidence of kernicterus (mostly in
the basal ganglia, cranial nerves mainly auditory)
was found to be associated with total serum
bilirubin levels above 20 mg per dL in the presence
of hemolysis
Hydration And Supportive measures
Management guidelines now focus primarily on
phototherapy (anti-oxidant) as initial treatment.
Aggressive guidelines recommending the use of
exchange transfusion in all infants with significant
hyperbilirubinemia.
Albumin can be given when there is an increase in
the level of free bilirubin (>25 mg/dl).
Conjugated hyperbilirubinemia is never
physiologic, and it may indicate the
presence of a potentially serious
underlying disorder HOWEVER
ELEVATED CONJUGATED BILIRUBIN
LEVELS ARE NOT DIRECTLY TOXIC TO
BRAIN CELLS IN THE NEONATE.
Guidelines for phototherapy in hospitalized infants of 35 or
more weeks' gestation
Guidelines for managment
Management
• Depending on the chart: Either assure or
conservatively hydrate if still not responding or in
the phototherapy zone do phototherapy, and
finally exchange transfusion.
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AAP recommendations
PHOTOTHERAPY
Any baby with jaundice must be investigated.
We do CBC to check the levels of bilirubin,
whether its in the phototherapy zone or not.
(if less than 8 and its in an unconjugated
type then just reassure.)
light at blue or blue-green wavelengths converts the
bilirubin molecule into a form that is either easier to
excrete or is less toxic to the neonate
The effective spectrum for this process has been
identified in vitro to peak at around 450nm (blue light)
EXCHANGE TRANSFUSION
OTHER
• Mesoporphyrin Still under investigation
• Albumin trnsafusion
• Antibiotics
• Fluid and Electrolytes
• D5% water NO it’s a wrong practice just
give the baby milk.
• Phenobarbiton ?
basal ganglia
hippocampus
kernicterus
geniculate bodies
cranial nerve nuclei
Especially the
vestibulocochlear nerve.
Pathophysiology
• Bilirubin staining in the regions of the
basal ganglia, hippocampus,
substantia nigra, and brainstem nuclei
• Staining can occur in the absence of
severe hyperbilirubinemia
• Characteristic patterns of neuronal
necrosis
KERNICTERUS
Causes
• Severe hemolytic processes were identified in
19 out of 80 babies (24%)
• glucose-6-phosphate dehydrogenase (G6PD)
deficiency was diagnosed in 18 out of 80.
• galactosemia occurred in 2 out of 80
• Crigler-Najjar syndrome type I occurred in 1
• NO etiology for the severe hyperbilirubinemia
was discovered in 73% of cases
• In SA its more commonly due to G6PD and
crigler Najjar.
Incidence
• Do we have any registry in Saudi Arabia??
• All reported cases from Saudi literatures
were secondary to Crigler Najjarr syndrome
Am J MedGenet. 1998 Aug 27;79(1):12-5
Term Infant with Jaundice and
High pitched cry
Arching of the baby's body into a bow
Weakness, limpness, floppiness
 Difficulty nursing and/or sucking
WHAT IS THE TREATMENT ?
KERNICTERUS DIAGNOSIS
• Early symptoms-acute bilirubin
encephalopathy-poor feeding, abnormal cry,
hypotonia,
• Intermediate phase- stupor, irritability,
hypertonia
• Late phase shrill cry, no feeding,
opisthotonus, apnea, seizures, coma, death
Clinical Spectrum: Adverse Effects of Newborn Jaundice
Acute Bilirubin
Encephalopathy
Death: respiratory
failure
Chronic Post-icteric
Sequelae (Kernicterus)
Outcome influenced
by timely intervention
Auditory Neuropathy (isolated)
Subtle manifestations (extra-pyramidal and
central posturing disorders) suspected but not
yet proven
Bilirubin Induced Neurologic Dysfunction (BIND)
KERNICTERUS
• Late sequelae can include
 gaze abnormalities
 feeding difficulties
 dystonia
 incoordination
 choreoathetosis
 sensorineural hearing loss
 painful muscle spasms
KERNICTERUS
• Incidence of bilirubin levels >30 1/10,000
• Over 120 cases kernicterus documented since
1990
• 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
been discharged early (<48 hours).
Risk Factors
1.
2.
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ASPHYXIA
ACIDOSIS
SEPSIS
HYPOALBUMINEMIA
YOUNG GESTATIONAL AGE
LOW BIRTH WT
HYPERTHERMIA
RESPIRATORY DISTRESS
Magnetic resonance imaging of the head. Hyperintense basal
ganglia lesions on T2-weighted images
Management of Hyperbilirubinemia
AAP Alerts:
 Clinical
Overview:
 Usually benign; but potential of
bilirubin toxicity
 Focus:
 Reduce incidence of severe
hyperbilirubinemia
Prevention
Recommend:
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Promote and support successful
breastfeeding.
Universal systematic pre-discharge
assessment.
Provide targeted follow-up based on the
risk.
Track outcome for timely treatment to
prevent excessive hyperbilirubinemia
and possibly, kernicterus.
AAP 2004: Recommendations
I.
II.
III.
IV.
V.
VI.
VII.
Primary Prevention: lactation support
Risk assessment for severe
hyperbilirubinemia:
Interpretation of TSB values
Cause of jaundice/hyperbilirubinemia.
Pre-discharge risk assessment
Hospital policies and procedures
Treatment
Summary
• Bilirubin physiology
• Prevent neurotoxicity
• Identify and treat illness
associated with excess
production, impaired conjugation
or inadequate elimination
• Combination of therapy
A 3-day old full term infant with hemolytic disease of the newborn
due to Rh incompatibility has a serum indirect bilirubin
concentration of 33 mg/dL. You perform an exchange transfusion
with no further elevations of bilirubin above 19 mg/dL. Among the
following, the MOST appropriate study to use to follow up on this
infant is:
A.
B.
C.
D.
E.
Another Coomb’s test
Brainstem auditory evoked response
Computed tomography of the head
Hemoglobin electrophoresis
Indirect retinoscopy
7-day old breastfeed infant born at term has had decreased
appetite, irritability and vomiting for 24 hours. On Physical
examination, the infant appears listless. Respiratory Rate: 40/min,
Heart Rate : 160/min, and blood pressure: 68/38 mm Hg. The skin
and sclera are icteric but no other abnormalities noted. Laboratory
studies reveal: Hemoglobin: 12 gm/dL. Urinalysis is negative for
reducing substances. Of the following, the MOST likely diagnosis is:
A.
B.
C.
D.
E.
Bacterial sepsis
Blood group incompatibility
Breast milk jaundice
Hypothyroidism
Intrauterine infection
A 3-day old , breast fed infant develops jaundice. The serum bilirubin
level is 12 mg/dL with a direct bilirubin component of 0.5 mg/dL. The
infant’s mother asks whether the jaundice might be associated with
breastfeeding. Which of the following statements regarding
hyperbilirubinaemia associated with breast feeding is TRUE:
A. Indirect hyperbilirubinaemia associated with
breast feeding may occur as early as the first
day of life.
B. Water supplementation in breast-fed infants will
significantly reduce serum concentrations of
indirect bilirubin
C. Hyperbilirubinemia associated with breast
feeding may persist for 8 to 12 weeks
D. Decreased clearance of bilirubin may play a
role in breast feeding jaundice, breast milk
jaundice.
Of the following conditions, which is the MOST
consistent with findings of mild cholestasis
without evidence of billiary atresia?
A.
B.
C.
D.
E.
Lead intoxication
Chronic hemolytic disease
Alpha – antitrypsin deficiency
Breast milk jaundice
Crigler-Najjar Syndrome
A 4-week old, breast-fed boy has had mild jaundice
since birth. Weight gain has been poor. The urine is
light yellow-brown, and the stools are pale yellow-green
in color. At this point, the MOST appropriate next step
in management is to:
A. Observe the child clinically for 2 to 4 weeks
B. Stop breastfeeding and re-examine the child in
7 to 10 days
C. Obtain a cholecystogram
D. Obtain a total and direct serum bilirubin levels
and studies of liver function
The following statement is correct regarding
bilirubin
A. Is normally excreted in the urine following its conjugation to
glucuronic acid
B. May achieve high blood levels due to haemolysis
associated with glucose-6-phosphate dehydrogenase
deficiency
C. Must be prevented from reaching 340 umol/L in well term
babies by use of exchange transfusion if necessary
D. Results from the oxidation of haemoglobin by the enzyme
glucuronyl transferase
E. Is normally about 50% bound to albumin and 50% as the
unbound
-Neonatal jaundice is associated with all of the following
except :
A. prematurity
B. cystic fibrosis
C. Gilbert’s syndrome
D. breast milk feeding
E. neonatal thyrotoxicosis
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A Term Baby Is Found to Have Serum bilirubin of 250 umol/l at 18
Hours of Age.
Which of the Following Is True?
A. Physiological jaundice is the most likely
cause
B. An urgent conjugated bilirubin level is
indicated
C. It is unlikely to be due to haemolysis
D. The infants blood group and Coombs test
are the most important investigations
E. There is no indication to start phototherapy
Un-conjugated (indirect) hyperbilirubinaemia
occurs in the followings Except:A. on transfusion of incompatible ABO/Rh
blood
B. Sepsis neonatorum
C. in glucose-6-phosphate
dehydrogenase (G6PD) deficiency
D. in type I Crigler-Najjar syndrome
E. Rotter,s syndrome
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In an infant who appeared healthy at birth, vomiting and diarrhea
developed at 1 week of age. She gained weight poorly despite a change
from breast milk to infant formula feeding at 2 weeks of age. At 3 weeks
of age, she is brought to the emergency department where she is found
to be lethargic and to have hepatomegaly. Of the following, the most
likely diagnosis is
A) Inspissated bile syndrome
B) Crigler-Najjar Syndrome
C) Galactosemia
D) Gilbert Syndrome
E) Dubin-Johnson Syndrome