neonatal jaundice dr. abdulrahman al nemri, md chairman of pediatric department associate professor...
TRANSCRIPT
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Neonatal Jaundice
Dr. AbdulRahman Al Nemri, MDChairman of Pediatric Department
Associate ProfessorSenior Consultant Neonatologist
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Introduction
Yellow-orange pigment Icterus –ikteros - bilirubin in the skin and sclerae
Jaundice = galbus ( TSB 34umol/l Vs 86 -119)
It is one of the most common clinical phenomena encountered in newborns
(How common is it?)
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Bilirubin Production
Degrading heme from hemoglobin-containing RBCs ( 80% )
20% from ineffective erythropoiesis + Turnover of non-hemoglobin
hemoproteins (eg, myoglobin, catalase, nitric oxide synthase, peroxidases, and cytochromes).
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/ /١٤٤٤ ٠٩ ٢٩ Wong, R. J. et al. Neoreviews 2007;8:e58-e67
A scheme for the origin of bilirubin
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Copyright ©2007 American Academy of PediatricsWong, R. J. et al. Neoreviews 2007;8:e58-e67
Heme catabolic pathway
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Bilirubin oxidase
beta-glucuronidase
biliverdin reductase
uridine diphospho- glucuronosyltransferase (UGT)
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RISK FACTORS FOR SIGNIFICANT JAUNDICE
• 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
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Etiological Classification
1. Increased bilirubin load • Hemolytic causesI. Coombs' test positive: Rh factor
incompatibility, ABO incompatibility, minor antigens Which one is common ?
II. 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?
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Bilirubin production
Entero-hepatic conjugation
Bilirubin Elimination
Physsiologic Mechanism
Binding
Transportation
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Nonhemolytic causes
• Increased unconjugated bilirubin level, normal percentage of reticulocytes
Physiologic jaundiceExtravascular sourcesPolycythemiaExaggerated enterohepatic circulation
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2- Decreased bilirubin conjugation
Physiologic jaundiceCrigler-Najjar syndromeGilbert syndromeHypothyroidismBreast milk jaundice
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3- Impaired bilirubin excretion
• Conjugated bilirubin level of >2 mg per dL (34 μmol per L) or >20% of total serum bilirubin level
Biliary obstructionInfectionMetabolic disorderChromosomal abnormality
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Physiologic jaundice
• increased breakdown of fetal erythrocytes. shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates
• Hepatic excretory capacity is slow
• low activity of glucuronyl transferas
• 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 nonphysiologic
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What is the commonest cause of non hemolytic
hyperbilirubineamia?
What are the other D/D?
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What are the criteria of physiological Jaundice ?
1. Onset
2. Rate of TSB increment
3. Level of TSB
4. Type of Bili
5. Duration
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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)
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JAUNDICE AND BREAST FEEDING
• Early-Onset Breast feedingBreast 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 milkBreast 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)
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PATHOLOGIC JAUNDICE
All etiologies of jaundice beyond
1) Physiologic
2) breastfeeding or 3) breast milk jaundice
are considered pathologic.
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Un-Conugated Hyperbilirubinemia
1. Excessive Bilirubin Production
2. Impaired Conjugation
3. Excretion
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Hemolytic Disease
Blood group incompatibility
Red cell enzyme deficiency
Red blood cell membrane defect
Extravascular Blood
Polycythemia
Sepsis
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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.
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Diagnosis
• HISTORY
• PHYSICAL EXAMINATION
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Laboratory Evaluation of Term Newborn with Jaundice
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Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Algorithm for the management of jaundice in the newborn nursery
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Management
• An increased incidence of kernicterus was found to be associated with total serum bilirubin levels above 20 mg per dL in the presence of hemolysis
1. Hydration And Supportive measures
2. Management guidelines now focus primarily on phototherapy as initial treatment.
3. Aggressive guidelines recommending the use of exchange transfusion in all infants with significant hyperbilirubinemia
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ELEVATED CONJUGATED BILIRUBIN LEVELS ARE NOT DIRECTLY TOXIC TO BRAIN CELLS IN THE NEONATE.
Conjugated hyperbilirubinemia is never physiologic, and it may indicate the presence of a potentially serious underlying disorder HOWEVER
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Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation
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Guidelines for managment
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PHOTOTHERAPY
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PHOTOTHERAPY
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)
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EXCHANGE TRANSFUSION
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EXCHANGE TRANSFUSION
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OTHER
• Mesoporphyrin Still under investigation
• Albumin trnsafusion
• Antibiotics
• Fluid and Electrolytes
• D5% water NO
• Phenobarbiton ?
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Conjugated Hyperbili
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kernicterus
basal ganglia hippocampus
cranial nerve nuclei geniculate bodies
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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
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KERNICTERUS
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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
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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
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High pitched cry Arching of the baby's body into a bowWeakness, limpness, floppiness Difficulty nursing and/or sucking
WHAT IS THE TREATMENT ?
Term Infant with Jaundice and
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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
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Clinical Spectrum: Adverse Effects of Newborn Jaundice
Bilirubin Induced Neurologic Dysfunction (BIND)
Acute Bilirubin Encephalopathy
Chronic Post-icteric Sequelae (Kernicterus)
Auditory Neuropathy (isolated)
Subtle manifestations (extra-pyramidal and central posturing disorders) suspected but not
yet proven
Death: respiratory failure
Outcome influenced by timely intervention
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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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Risk Factors
1. ASPHYXIA
2. ACIDOSIS
3. SEPSIS
4. HYPOALBUMINEMIA
5. YOUNG GESTATIONAL AGE
6. LOW BIRTH WT
7. HYPERTHERMIA
8. RESPIRATORY DISTRESS
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Magnetic resonance imaging of the head. Hyperintense basal ganglia lesions on T2-weighted images
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Management of HyperbilirubinemiaManagement of HyperbilirubinemiaAAP Alerts:AAP Alerts:
Clinical Overview:Usually benign; but potential of bilirubin toxicity
Focus:Reduce incidence of severe hyperbilirubinemia
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Prevention
Recommend: 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.
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AAP 2004: Recommendations
I. Primary Prevention: lactation supportII. Risk assessment for severe
hyperbilirubinemia:III. Interpretation of TSB valuesIV. Cause of jaundice/hyperbilirubinemia.V. Pre-discharge risk assessment VI. Hospital policies and proceduresVII. Treatment
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Summary
• Bilirubin physiology
• Prevent neurotoxicity
• Identify and treat illness associated with excess production, impaired conjugation or inadequate elimination
• Combination of therapy
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MCQs
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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. Another Coomb’s test
B. Brainstem auditory evoked response
C. Computed tomography of the head
D. Hemoglobin electrophoresis
E. Indirect retinoscopy
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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. Another Coomb’s test
B. Brainstem auditory evoked response
C. Computed tomography of the head
D. Hemoglobin electrophoresis
E. Indirect retinoscopy
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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. Bacterial sepsis
B. Blood group incompatibility
C. Breast milk jaundice
D. Hypothyroidism
E. Intrauterine infection
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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. Bacterial sepsis
B. Blood group incompatibility
C. Breast milk jaundice
D. Hypothyroidism
E. Intrauterine infection
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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.
![Page 62: Neonatal Jaundice Dr. AbdulRahman Al Nemri, MD Chairman of Pediatric Department Associate Professor Senior Consultant Neonatologist](https://reader036.vdocuments.us/reader036/viewer/2022062422/56649e855503460f94b87efb/html5/thumbnails/62.jpg)
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.
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Of the following conditions, which is the MOST consistent with findings of mild cholestasis without evidence of billiary atresia?
A. Lead intoxication
B. Chronic hemolytic disease
C. Alpha – antitrypsin deficiency
D. Breast milk jaundice
E. Crigler-Najjar Syndrome
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Of the following conditions, which is the MOST consistent with findings of mild cholestasis without evidence of billiary atresia?
A. Lead intoxication
B. Chronic hemolytic disease
C. Alpha – antitrypsin deficiency
D. Breast milk jaundice
E. Crigler-Najjar Syndrome
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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
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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 cholecystogramD. Obtain a total and direct serum bilirubin levels
and studies of liver function
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The following statement is correct regarding bilirubine
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
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The following statement is correct regarding bilirubine
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
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74
-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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75
-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
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77
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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78
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
![Page 74: Neonatal Jaundice Dr. AbdulRahman Al Nemri, MD Chairman of Pediatric Department Associate Professor Senior Consultant Neonatologist](https://reader036.vdocuments.us/reader036/viewer/2022062422/56649e855503460f94b87efb/html5/thumbnails/74.jpg)
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 syndromeB) Crigler-Najjar Syndrome C) GalactosemD) Gilbert SyndromeE) Dubin-Johnson 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 syndromeB) Crigler-Najjar Syndrome C) GalactosemD) Gilbert SyndromeE) Dubin-Johnson Syndrome
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