HYPERBILIRUBINEMIA IN TERM NEONATES

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HYPERBILIRUBINEMIA IN TERM NEONATES

• Tanya Oberoi Pandya D.O., M.B.A.
• Vishaan Pandya (Masters In Colic, PhD in
  Poopology)

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Definition

• Infants gt/ 35wks GA Total Serum Bilirubin gt95th
  percentile for hours-of-age
• Up to 60 of term newborns have clinical jaundice
  in the first week of life

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Bilirubin

• 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

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Risk Factors
Maternal Factors Neonatal Factors
ABO incompatability Rh incompatability Breastfeeding Ethnicity Asian, Native American Maternal Illness Gestational Diabetes Drugs Diazepam, oxytocin Prematurity Previously affected sibling Cephalohematomas Bruising Trauma from instrument delivery Delayed meconium passage Male gender Polycythemia Prematurity Excessive wt loss after birth Infections TORCH Infrequent feedings Drugs chloramphenicol, sufisoxazole acetyl with erythromycin (pediazole)
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Why Neonates? (

• Newborn Bilirubin Production 6 to 8 mg/kg/day
• Adult Bilirubin Production HALF that!
• Newborn
• Relative polycythemia
• Increased RBC turnover

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So Whats The Big Deal?

• KERNICTERUS!!!

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Kernicterus

• Neurologic consequences of unconjugated bilirubin
  deposition in brain
• Damage scarring of basal ganglia brain stem

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Kernicterus (Contd)

• Unconjugated bilirubin gt albumin binding capacity
• Unconjugated bilirubin Fat Soluble
• Enters BBB
• No specific level definitive for kernicturus
• Be worried if Bilirubin level
• gt25 in term baby WITHOUT hemolysis
• gt20 in term baby WITH hemolysis

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Kernicterus Signs
Early (3-4d) Late (gt1 wk) Chronic (by 3 yrs of age)
Lethargy Poor feeding High-pitched cry Hypotonia Irritability Opisthotonos Seizures Apnea Oculogyric crisis Hypertonia Fever Athetoid cerebral palsy High-frequency hearing loss Paralysis of upward gaze Dental dysplasia Mild mental retardation
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Consequences of Kernicterus

• Developmental delay
• Motor delay
• Sensorineural deafness
• Mild mental retardation

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Classification
Increased Bilirubin Load Decreased Bilirubin Conjugation Impaired Bilirubin Excretion
Hemolytic causes Characteristics increased unconjugated bilirubin level, gt6 retic, Hb lt13 Coombs' test positive Rh factor incompatibility, ABO incompatibility, minor antigens Coombs' test negative RBC membrane defects (spherocytosis, elliptocytosis), RBC enzyme defects (G6PD deficiency, pyruvate kinase deficiency), drugs (e.g., sulfisoxazole acetyl with erythromycin ethylsuccinate (Pediazole), streptomycin, Vit K), abnl RBC (hemoglobinopathies), sepsis Nonhemolytic causes Characteristics increased unconjugated bilirubin level, normal retic level Extravascular sources Cephalohematoma, bruising, CNS hemorrhage, swallowed blood Polycythemia fetal-maternal transfusion, delayed cord clamping, twin-twin transfusion Exaggerated enterohepatic circulation cystic fibrosis, ileal atresia, pyloric stenosis, Hirschsprung's dz, breast milk jaundice Characteristics increased unconjugated bilirubin level, normal percentage of reticulocytes Physiologic jaundice Crigler-Najjar syndrome types 1 and 2 Gilbert syndrome Hypothyroidism Breast milk jaundice Characteristics increased unconjugated and conjugated bilirubin level, neg Coombs' test, conjugated bilirubin level of gt2 or gt20 of total serum bilirubin level, conjugated bilirubin in urine Biliary obstruction biliary atresia, choledochal cyst, primary sclerosing cholangitis, gallstones, neoplasm, Dubin-Johnson syndrome, Rotor's syndrome Infection sepsis, UTI, syphilis, toxoplasmosis, tuberculosis, hepatitis, rubella, herpes Metabolic disorder alpha1 antitrypsin deficiency, cystic fibrosis, galactosemia, glycogen storage disease, Gaucher's disease, hypothyroidism, Wilson's dz, Niemann-Pick dz Chromosomal abnormality Turner's syndrome, trisomy 18 and 21 syndromes Drugs aspirin, APAP, sulfa, alcohol, rifampin, erythromycin, corticosteroids, tetracycline
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3
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Common Causes

• Physiologic Jaundice
• Breastfeeding Jaundice
• Breastmilk Jaundice

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Physiologic Jaundice

• Occurs gt24hours of life, drop by week 1 of life
• Increased bilirubin load d/t relative
  polycythemia
• Shortened erythrocyte life span (80 days compared
  with the adult 120 days)
• Immature hepatic uptake and conjugation processes
• Increased enterohepatic circulation

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Breastfeeding Jaundice

• Occurs 3-4 days of life
• Due to insufficient milk production by mom or
  intake by baby relative caloric deprivation in
  the first few days of life.
• Decreased volume and frequency of feedings
  --gtpassive dehydration and the delayed passage of
  meconium

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Breastfeeding Jaundice Management

• Increase frequency of feedings to more than 10
  per day
• Formula supplement if infant has decline in
  weight gain, delayed stooling, and continued poor
  caloric intake
• Breastfeeding should be continued to maintain
  breast milk production
• Supplemental water or dextrose-water
  administration should be avoided, as it decreases
  breast milk production and places the newborn at
  risk for iatrogenic hyponatremia

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BreastMILK Jaundice

• Occurs later in life
• Day 6 to 14
• Bili 12 to 20
• May stay high for 1-2 months

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BreastMILK Jaundice Etiology

• Unclear
• Substances in maternal milk, such as alpha
  glucuronidases, and nonesterified fatty acids,
  may inhibit normal bilirubin metabolism
• The bilirubin level usually falls continually
  after infant is 2 weeks old, but it may remain
  persistently elevated for 1 to 3 months.

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BreastMILK Jaundice Management

• Breastfeeding may be temporarily interrupted
• Mother should continue to express breast milk to
  maintain production
• With formula substitution, the total serum
  bilirubin level should decline rapidly over 48
  hours,confirming the diagnosis
• Breastfeeding may then be resumed.

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Pathologic Jaundice

• Anything OTHER THAN physiologic or breastfeeding
  or breastmilk jaundice!!

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Pathologic Jaundice Features

• Jaundice within 24 hours after birth
• Rapidly rising total serum bilirubin
  concentration (increase of more than 5 per day),
  and a total serum bilirubin level higher than 17
  in a full-term newborn
• Other features of concern include prolonged
  jaundice
• Evidence of underlying illness
• Elevation of the serum conjugated bilirubin level
  to gt2 mg per dL or more than 20 of the total
  serum bilirubin

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Pathologic Jaundice Causes

• Sepsis
• Rubella
• Toxoplasmosis
• Occult hemorrhage
• Erythroblastosis fetalis.

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Pathologic Jaundice Workup

• Fractionated serum bili (conjugated bili gt2)
• CBC with diff
• Reticulocyte count
• Blood type
• Rh compatability
• Coombs test
• Peripheral blood smear
• G6PD screen (if applicable)
• Blood culture
• UA, urine culture
• TSH for hypothyroidism (on state screen)
• Galactosemia (on state screen)
• Cholestatic Jaundice (need to r/o biliary atresia
  if light colored stool, dark urine, urine with
  bilirubin, persistent jaundice gt3wks)

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Hyperbilirubinemia Signs

• Skin yellowing
• Not visible if bili lt4
• Estimate level by degree of icterus
• Face 5 upper chest, 10 abdomen, 12 palms and
  soles, gt15 soles 20
• Pallor, petechiae, extravasated blood, excessive
  bruising, hepatosplenomegaly, weight loss, and
  evidence of dehydration.

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Diagnosis

• Jaundice in a term newborn fewer than 24 hours
  old is always pathologic
• Based on rate of bilirubin level rise, risk of
  developing significant hyperbilirubinemia can be
  classified as low, intermediate, or high
• If jaundice persists gt 2 weeks in a formula-fed
  infant and gt3 weeks in a breastfed infant,
  further evaluation is warranted

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Diagnosis (contd)

• Laboratory studies
• Fractionated bilirubin level
• Thyroid studies
• Evaluations for metabolic disorders
• Evaluation for hemolytic disease
• Assessment for intestinal obstruction.

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Treatment

• Phototherapy
• Exchange Transfusion

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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

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75th Percentile
40th Percentile
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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 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)

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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)

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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 lt15
• 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

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Phototherapy Complication

• Burns
• Dehydration
• Retinal Damage
• Thermoregulatory instability
• Loose stools
• Tanning of the skin

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Hydration Assessment

• Percentage of birth weight lost
• Mucous membranes
• Fontanelle
• Skin turgor

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Exchange Transfusion

• Most rapid way of decreasing bilirubin
• Removes partially hemolyzed and antibody-coated
  erythrocytes replacing them with uncoated donor
  RBCs that lack the sensitizing antigen

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Exchange Transfusion Indication

• Hemolytic disease
• Severe anemia
• Rapid rise in TSB level (gt1 mg per dL per hour in
  less than six hours)
• Considered in nonhemolytics where intensive
  phototherapy fails
• If the total serum bilirubin level remains
  elevated after intensive phototherapy
• If the initial bilirubin level is meets defined
  critical levels based on the infant's age (approx
  gt20-25)

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Exchange Therapy Complications

• Air embolism
• Vasospasm
• Infarction
• Infection
• Death

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Monitoring

• Recheck bilirubin level every 12-24 hours
• Consider neonatologist consult if Bilirubin gt20
  or pathologic causes suspected

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Prevention

• RhoGham in Rh negative moms
• GA lt12 weeks 50mcg
• GA gt12 weeks 300mcg
• Universal Screening of ALL infants

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Jaundice In Order
TYPE ONSET
Physiologic Jaundice After 24 hours
Breastfeeding Jaundice 3-4 days
Breastmilk Jaundice After 4-7 days
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Quickie on Phototherapy Number

• gt15 at lt24
• gt18 at 25-48
• gt20 at gt48