Neonatal Hyperbilirubinemia.. updates

1. Neonatal
Hyperbilirubinemia
MODERATOR :- DR. ASRAT ( CONSULTANT NEONATOLOGIST)
PRESENTER :- DR. TAJUDIN ADEM( PEDIATRIC RESIDENT)
AAU CHS 2019.G.C

2. Outlines
 Introduction
 Definitions
 Bilirubin metabolism
 Classification
 Causes of hperbilirubinemia
 Clinical features
 Management

3. Introduction
 Almost all newborn infants develops a total serum bil(TB) of >=2mgdl
 As TB increases it produces neonatal jaundice(yellowish
discoloration)
 Neonates with severe hyperbilirubinemia (TB >= 25mgdl) are at
increased risk of bilirubin induced neurologic dysfunction(BIND)

4. Definition
 Neonatal hyperbilirubinemia in infants>= 35wks GA is defined as
TB > 95th centiles on hour-specific Bhutani nomogram
 Severe neonatal hyperbilirubinemia is TB> 25mg/dl
 Acute bilirubin encephalopathy(ABE) is used to describe the
acute manifestation of BIND
 Kernicterus is term to describe the chronic and permanent sequel
of BIND

5. Definition…..
 Neonatal Jaundice :- is the term used to describe Non pathologic
yellowish discoloration visible in skin and sclarae
and is caused by normal neonatal neonatal changes of bilirubin
metabolism that results in ( increased production, Decreased clearance
and increased enterohepatic circulation)
 Incidence of Jaundice.
Approximately 60-70% of Term neonates develop jaundice.
In preterm neonates the incidence is about 80%.

6. Defn………
 Neonatal hyperbilirubinemia :- is TB > 95th
centiles on hour specific bhutani nomogram
which is caused by pathologic conditions or
exaggerated physiologic processes.

8. Bilirubin Metabolism
 Bilirubin Production
Sources of heme:
 Hemoglobin, myoglobin, enzymes such as catalase,
peroxidase, synthase and cytochromes
 80--90% of the bilirubin is derived from breakdown of
hemoglobin or from ineffective erythropoiesis and 10--20% from
others heme containing proteins(like catalase and cytochromes)

9. Bil. Metabolism……
Heme oxygenase Biliverdin reductase
 Heme -----Biliverdin ------ Bilirubin
 Bilirubin is lipophillic and insoluble at normal pH.
 Unbound bilirubin cannot be transported in serum or excreted by the
liver or kidneys because its solubility is very low.
 However, it becomes soluble in aqueous solutions when it is attached
to proteins, such as albumin.

10. Bil. Metabolism…..
 Bilirubin Clearance and exceretion ( Steps )
Bilirubin produced in the peripheral regions of the body is
transported to the liver, bound to albumin
 Hepatic Uptake ( ligandins )
 Conjugation(by the action of UDP-GT enzyme)
 Biliary exceretion

11. Hepaticuptake
Conjugation

12. Bil. Metabolism……
Excretion and Enterohepatic Circulation of Bilirubin
Conjugated bilirubin from the hepatocytes → canaliculi →bile duct → to the
lumen of intestine
 within the bowel by action of ß- glucuronidase:
Conjugated Bil. → (by) → bilirubin + glucuronic acid
Which will be re-absorbed & inter to the blood
again (Entero-hepatic circulation)
The rest of CB is converted by intestinal flora in to
Urobilin or Stercobilin — and excreted with stool or
some by urine

14. Classification of jaundice
 physiologic
 pathologic( Indirect(UCB) or Direct
hyperbilirubinemia)

15. Physiologic Jaundice
 To define physiologic ranges of serum bilirubin
concentration in newborns is debatable because it is
influenced by:
 Length of gestation
 Birth weight
 Nutritional status
 Mode of feeding
 Race

16. Physiologic...
 What determines the normal range ?
◦ Rate of increase of bilirubin concentration,
◦A level for a specific post-partum age, or
◦The maximum level attained.
◦Type of bilirubin

17. Physiologic versus Pathologic Jaundice
 Criteria that rule-out diagnosis of physiologic jaundice
 Clinical jaundice in the first 24 hours.
 TSB concentrations increasing by more than 5 mg/dl/day
 TSB concentrations increasing by more than 0.5 mg/dl/hr
 TSB concentrations exceeding 12.9 mg/dl in a full-term infant
or 15 mg/dl in premature infant at any postnatal age.
 Direct serum bilirubin concentration exceeding 1.2 to 2 mg/dl.
 Clinical jaundice persisting for more than one week in full-term
neonate or 2 weeks in premature infant.

18. Causes of hyperbilirubinemia
 Increased production (most common cause of pathologic UCB)
 isoimmune hemolysis( Rh or ABO incompatibility)
 RBC membrane and enzyme defects( PK def. , G6PD def. spherocytosis,
elliptocytosis)—nonimmune
 sepsis
 Decreased clearance (inherited defects in genes that codes UGTA1)
 Crigler-Najjar synd. And Gilbert synd
 Congenital hypothyroidism and galactosemia
 Increased EHC
 Breast feeding and Breast milk jaundice
 Impaired intestinal motility( functional or anatomic obstruction)

19. Breast-Feeding Jaundice & Breast-Milk
Jaundice

20. Clinical features
 History
 Family history
Famiy hx of jaundice, anemia, spleenectomy or early GB disease
suggest hereditary hemolytic anemia( spherocytosis, G6PD etc
Family Hx of liver Dx(galactosemia, A1 antitrypsin, gilbert dxs,
crigller Najjar synd or cystic fibrosis)
Ethnic or geographic origin associated with
hyperbilirubinemia (East Asian, Greek, and American Indian)

21. Clinical features…..
 History……..
 Pregnancy history
Illness during pregnancy(congenital viral , bacterial, protozoa Infants of diabetic
mothers
Maternal drugs may interfere with bilirubin binding to albumin, making
bilirubin toxic at relatively low levels( sulfonamides, nitrofurantoin and
antimalarials)
 Labor and delivery history
Birth trauma may be associated with extravascular bleeding and hemolysis
Infants with hypoxic-ischemic injury
delayed cord clamping

22. Clinical feature…..
 History
 Infant hx
Delayed or infrequent stooling( poor intake, intestinal obstruction, ed EHC
Sepsis
Vomiting
 Physical Exam
Preterm
SGA
Microcephally( congenital infections)
Extravascular blood, pallor, petechie
Hepatospleenomegally

23. Clinical features…..
 Laboratory tests
 CBC, BG and RH
 BIL(D & T) and TcB
 Others :- Mothers blood type, Rh antibody screen
 Coombs test, ETCO (end tidal carbon monoxide)
 G6PD activity screening
 Bilirubin to Albumin Molar Ratio >= 0.5

25. Complications…..(CF)
 Neurologic manifestations:-Term and late preterm infants are at risk for
BIND when TB concentrations ≥25 mg/dL
 BIND (reversible or irreversible)
 Acute bilirubin encephalopathy (ABE) :- reversible, typically
progresses through 3 phases
 Phase 1:-Early phase(clinical signs may be subtle. The infant is sleepy but
arousable has mild to moderate hypotonia and a high-pitched cry.
 Phase 2:-Intermidiate phase:- The infant can be febrile, lethargic with a
poor suck, or irritable and jittery with a strong suck. The cry can be shrill and the
infant is difficult to console, ( Retrocollis and opisthotonos) with stimulation

26.  Phase 3(Advanced phase):-characterized by apnea, inability to feed,
fever, seizures, and a semicomatose state that progresses to coma
 Kernicterus :-the chronic and permanent sequelae of BIND
develops during the first year after birth, Cognitive function usually is
relatively spared.
Major features are
 Choreoathetoid cerebral palsy (CP) (chorea, ballismus, tremor, and
dystonia)
 SNHL
 Gaze abnormalities, especially limitation of upward gaze.
 Dental enamel dysplasia

27. Management……
 Phototherapy
 Exchange transfusion
 Medications (Phenobarbital and Metalloporphyrins)

28. Assess all infants for Jaundice based on gestational age and
risk factors on admission
 High Risk:
Preterm infants < 35 weeks
Preterm infants 35-37 weeks with ≥ 1 Risk Factor
 Medium Risk:
Preterm infants 35-37 weeks, without any Risk Factors
Term infants ≥ 38 weeks with ≥ 1 Risk Factor
Low Risk:
Term infants ≥ 38 weeks without Risk Factors
Risk Factors
 isoimmune HD
 HIE/ Birth asyphxia
 Sepsis
 polycythemia
 Acidosis(PH< 7)
 Alb < 3
 Preious sibling with exchange/
kernicterus
 Jaundice in the frist 24 hrs
 EBF
 Excessive Wt loss (> 10%)

29. Phototherapy...
 The formal complete designation of the native
bilirubin molecule is 4Z,15Z-bilirubin IXα.
 Native bilirubin is nearly insoluble in water at physiologic pH.
 Phototherapy works by using light energy to change bilirubin into
more water-soluble forms, thus by passing conjugation step in the liver.

30. PhotoTx Mechanism…

32. photoTx……..
 variables influencing the efficacy of phototherapy
 Wave length
 Irradiance(energy output)
 The surface area of exposed newborn

33. 15---20cm
Conventional
PhotoTx
Intensive
PhotoTx
Irradiance 6 —12 µW/cm2/nm >= 30µw/cm2
Distance b/n
Source and Baby
Within 40 cm 15 – 20 cm
Level of Bil.
Decrement on
exposure
6 – 20 % 30 – 40%
 If an incubator is used, there should be a 5 to 8-
cm space between it an the lamp cover to prevent
overheating

34. Complication of phototherapy
* Insensible water loss
* Watery and frequent stool
* Retinal damage,
* Gonadal effect (infertility?)
* Erythema and increased blood flow
* Bronze baby syndrome (with increased CB)
* Low calcium level (in preterm)
* Interferes with maternal infant bonding

36. PhotoTx.
1. Check bilirubin and hematocrit at list once a day and use total serum bilirubin to evaluate.
2. Increase the total amount of fluid by 20 – 30 %, or feed him frequently to replace the
insensible water loss.
3. If bilirubin result becomes below the photo range, check the bilirubin one more time and
continue phototherapy for one day more in high risk babies to avoid rebound elevation.
4. If the baby has early signs of bilirubin encephalopathy like lethargy decreased feeding and
becomes hypotonic (NB- you may not see the classical sign and symptoms in preterm babies),
do exchange transfusion after stabilizing.
5. At discharge tell the mother to expose her baby to sun light starting on the same day.
6. Measure the irradiance capacity of the phototherapy machine at list once in a month.

37. Exchange transfusion
 Keep NPO 2-3 hours before and after exchange transfusion, put him on MF.
 Place NG tube and Remove gastric contents; and leave on open drainage.
 In Rh incompatibility, prepare blood which is Rh compatible to the mother and blood
group compatible to the newborn or O negative blood if prepared prior to delivery.
 In ABO incompatibility, Prepare blood which is blood group compatible to the mother
(O), and Rh compatible to the mother and newborn. If available O negative blood is
preferred to all type of incompatibility.
 In other Isoimmune hemolytic disease the blood should not contain the sensitizing
antigen, and should be cross-matched against the mother.
 In non-immune hyperbilirubinemia blood is typed and cross-matched against the
plasma and red cell of the infant.
 Blood to be exchanged should be less than 5 - 7 days old with Hct of 40-50 % and
cross matched.
 Blood should not be warmed under radiant warmer or put in hot water to avoid
hemolysis.

38.  Do the procedure under strict aseptic condition, scrub as for major procedure.
(gown, mask, hair cover etc)
Prepare a helper, sterile gloves, number 6 NG tube, guide, bled, syringes (5cc,
10cc, and 20cc), procedure set and Calcium gluconate, Three-way stopcocks with
locking connections, Waste receptacle (empty IV bottle or bag)
 Amount of blood needed for exchange should be calculated as
 For term = 2 x weight x 85
 For preterm = 2 x weight x 100

39. Exchange……
 If there was a break in sterile technique, treat with Cloxacillin and
Gentamycine for 2 to 3 days.
blood is removed in aliquots that are tolerated by the infant.
5 mL for infants <1,500 g
10 mll For 1500—2500g
15 ml For 2500– 3500 g
20 ml For > 3500 g
NB - If the baby seams sick draw only 5 ml blood each time, slow the procedure or
stop till becomes stable, this will minimizes the stress on the CVS. The
recommended time for exchange transfusion should not be more than one hour and
do not you the same blood after 4 hours stay in the ward.

40. Exch…….
1. The blood should be gently mixed after every deciliter of exchange to prevent the settling of
RBCs and the transfusion of anemic blood at the end of the exchange.
2. Keep the baby under radiant warmer or inside incubator during the procedure to avoid
hypothermia.
3. Record the vital sign (HR, RR, T) every 15 minutes during the procedure.
After the procedure give Calcium gluconate 2 ml/kg diluted with 5% D/W over 10 minutes
under strict monitoring of the heart beat to avoid bradycardia and cardiac arrest with
subsequent determination of serum Calcium level.

41. 1. monitor vital signs closely for at least 4 to 6 hours.
2. RBS 30 min to 1 hour of time , then every 4-6 hours for the 1st 24 hours.
3. After 6 – 12 hours transfuse the baby with platelet 10ml/kg (if platelet level is <
30,000/mic/L) to replace the lose during the procedure and avoid bleeding disorders.
1. After exchange transfusion, phototherapy is continued and bilirubin levels are measured
after 6 – 12 hours (every 4 hours in the best setup).
2. When the exchange transfusion is finished, a silk purse-string suture should be placed around
the vein and removes the catheters after the next bilirubin result.
3. Bil decreased by 25 - 45 % , then at least once per day with the Hct.

42. Complications of exchange
 Metabolic: Hypocalcemia, hypo- or hyperglycemia, hyperkalemia
 Cardiorespiratory: Apnea, bradycardia, hypotension, hypertension arrhythmia,
infarction, volume overload and cardiac arrest.
 Hematologic: Bleeding, thrombocytopenia, dilutional coagulopathy, neutropenia,
disseminated intravascular coagulation
 Vascular catheter-related: Vasospasm,perforation, thrombosis, embolization
with air or clot.
 Gastrointestinal: Feeding intolerance, ischemic injury, necrotizing enterocolitis
 Infection: Omphalitis, septicemia

46. References
References
Fanaroff and martin 10 th ED
Nelson 21st Edition
Uptodate 2018
AAP
 Guideline AAU CHS

47. Questions
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