by DR.AWS NIDHAM KREADY M.B.Ch.B

1. Neonatal Jaundice
Presentated by
Aws Nitham Kready

2. • Hyperbilirubinemia : it is condition in
which there is elevated bilirubin level above
the normal value
• Jaundice :- yellowish discoloration of skin
and sclera results from the accumulation
of unconjugated, nonpolar, lipid-soluble bilirubin
pigment in the skin.

4. Normal metabolism of bilirubin
• Bilirubin is produced by catabolism of
hemoglobin in the reticuloendothelial system
• The normal newborn produces 6 to 10 mg
of bilirubin/kg/day, as opposed to the
production of 3 to 4 mg/kg/day in the adult.

5. Sources of bilirubin
• Hemoglobin released from senescent RBCs in the
reticuloendothelial system
is the source of 80% of all bilirubin production. One gram
of hemoglobin produces
34 mg of bilirubin.
• The other 20% of bilirubin is called early-labeled
bilirubin. It is derived from hemoglobin released by
ineffective erythropoiesis in the bone marrow,
from other heme-containing proteins in tissues (e.g.,
myoglobin, cytochromes,
catalase, and peroxidase), and from free heme

8. • 1 gm of hemoglobin produce 35mg of bilirubin
• Newborn have twofold to threefold greater
rate of bilirubin production (6-10mg/kg/24hr)
vs (3mg /kg/ 24 ) in adult

9. Jaundice

10. Epidemiology
• An estimated 50% of term and 80% of
preterm infants develop jaundice, typically 2-4
days afer birth.Neonatal hyperbilirubinemia is
extremely common because almost every
newborn develops an unconjugated serum
bilirubin level of more than 30 µmol/L (1.8
mg/dL) during the first week of life.

11. • Unconjugated hyperbilirubinemia may be caused or increased by any
factor that
• (1) increases the load of bilirubin to be metabolized by the liver (hemolytic
anemias, polycythemia, bruising or internal hemorrhage, shortened red
blood cell life as a result of immaturity or transfusion of cells, increased
enterohepatic circulation, infection)
(2) damages or reduces the activity of the transferase enzyme or other
related enzymes (genetic deficiency, hypoxia, infection,thyroid deficiency);
(3) competes for or blocks the transferase enzyme (drugs and other
substances requiring glucuronic acid conjugation); or
(4) leads to an absence or decreased amounts of the enzyme or to reduction
of bilirubin uptake by liver cells (genetic defect, and prematurity).

14. Etiology of increase conjucated
bilirubin
• Direct-reacting hyperbilirubinemia (defined as a direct
bilirubin level >2 mg/dL or > 20% of the total bilirubin) Is
never physiologic and should always be evaluated thoroughly
according to the diagnostic categories.
Direct- reacting bilirubin (composed mostly of conjugated
bilirubin) is not neurotoxic to the infant but signifies
a serious underlying disorder involving cholestasis or
hepatocellular injury.

15. • The diagnostic evaluation of patients with direct-
reacting hyperbilirubinemia involves the determination
of the levels of liver enzymes (aspartate
aminotransferase, alkaline phosphatase, alanine
aminotransferase, and γ-glutamyl transpeptidase),
bacterial and viral cultures, Metabolic screening tests,
hepaticul trasound, sweat chloride test, and occasionally
liver biopsy. In addition, the presence of dark urine and
gray-white (acholic) stools with jaundice after the second
week of life strongly suggests biliary atresia

17. Risk factors of jaundice

20. CLINICAL MANIFESTATIONS
• Jaundice may be present at birth or may appear at any time
during the neonatal period, depending on etiology. Jaundice
usually becomes apparent in a cephalocaudal progression,
starting on the face and progressing to the abdomen and then
the feet, as serum levels increase. Dermal pressure may reveal
the anatomic progression of jaundice (face, ≈ 5 mg/dL; mid-
abdomen, ≈ 15 mg/dL; soles, ≈ 20 mg/dL), but clinical
examination cannot be depended on to estimate serum
levels. Jaundice to the midabdomen, signs or symptoms, high-
risk factors that suggest nonphysiologic jaundice, or hemolysis
must be evaluated further

21. • jaundice from deposition of indirect bilirubin
in the skin tends to appear bright yellow or
orange, jaundice of the obstructive type
(direct bilirubin) has a greenish or muddy
yellow cast. Infants with severe
hyperbilirubinemia may present with lethargy
and poor feeding and, without treatment, can
progress to acute bilirubin encephalopathy
(kernicterus)

22. Differential diagnosis of jaundice in
neonate
• The differential diagnosis and evalation of
patient with jaundice usually depend on age
of presentation
• The age of presentation is useful guide to
diagnosis the underling cause of jaundice.

25. Neonatal jaundice
Physiological
pathological

26. Physiological jaundice
• Physiologic jaundice is a common cause of
hyperbilirubinemia Among newborns. It is a diagnosis of
exclusion, made after careful evaluation has ruled out more
serious Causes of jaundice, such as hemolysis, infection, and
metabolic diseases. Physiologic jaundice is the result of Many
factors that are normal physiologic characteristics of
newborns: increased bilirubin production resulting From an
increased RBC mass, shortened RBC life span, andhepatic
immaturity of ligandin and glucuronosyltransferase.
Physiologic jaundice may be exaggerated among infants of
Greek and Asian ancestry.

27. • the level of indirect bilirubin in umbilical cord
serum is 1-3 mg/dL and rises at a rate of < 5
mg/ dL/24 hr; thus, jaundice becomes visible
on the 2nd or 3rd day, usually peaking
between the 2nd and 4th days at 5-6 mg/dL
and decreasing to < 2 mg/dL between the
5th and 7th days of life.

28. • The clinical pattern of physiologic jaundice in
term infants includes a peak indirect-reacting
bilirubin level of no more than 12 mg/dL on
day 3 of life.
• In premature infants, the peak is higher
(15 mg/dL) and occurs later (fifth day)

30. • The peak level of indirect bilirubin during
physiologic jaundice may be higher in breast
milk–fed infants than in formula-fed infants
(15 to 17 mg/dL versus 12 mg/dL). This higher
level may be partly a result of the decreased
fluid intake of infants fed breast milk.

31. • Jaundice is unphysiologic or pathologic if it is
clinically evident on the first day of life, if the
bilirubin level increases more than 0.5
mg/dL/hr, if the peak bilirubin is greater than
13 mg/dL in term infants, if the direct bilirubin
fraction is greater than 1.5 mg/dL, or if
hepatosplenomegaly and anemia are present.

32. Jaundice <24 h of age
• It is always pathological
• Jaundice starting within 24 h of birth usually
results from haemolysis. This is particularly
important to identify as the bilirubin is
unconjugated and can rise very rapidly and
reach extremely high levels.

33. Haemolytic disorders
• Rhesus haemolytic disease –(Rh incompatibility):-
• the most common cause of Rh incompatibility is exposure
from an Rh-negative mother by Rh-positive fetal blood during
pregnancy or delivery. As a consequence, blood from the fetal
circulation may leak into the maternal circulation, and, after a
significant exposure, sensitization occurs leading to maternal
antibody production against the foreign Rh antigen.
• Once produced, maternal Rh immunoglobulin G (IgG)
antibodies may cross freely from the placenta to the fetal
circulation, where they form antigen-antibody complexes with
Rh-positive fetal erythrocytes and eventually are destroyed,
resulting in a fetal alloimmune-induced hemolytic anemia
(and jaundice )

34. • ABO incompatibility – This is now more
common than rhesus haemolytic disease.
Most ABO antibodies are IgM and do not cross
the placenta, but some group O women have
an IgG anti-A-haemolysin in the blood which
can cross the placenta and haemolyse the red
cells of a group A infant. Occasionally, group B
infants are affected by anti-B haemolysins.
Haemolysis can cause severe jaundice but it is
usually less severe than in rhesus disease

35. • The infant’s haemoglobin level is usually
normal or only slightly reduced and, in
contrast to rhesus disease,
hepatosplenomegaly is absent. The direct
antibody test (Coombs’ test), which
demonstrates antibody on the surface of red
cells, is positive. The jaundice usually peaks in
the first 12–72 h.

36. Other causes of jaundice in 1st day of
life
• Congenital infections : TORCH ( Toxoplasmosis, Rubella ,
Cytomegalovirus ,Herpes Simplex.
• Spherocytosis :autosomal dominant , but in 25% by new mutation .
The disease is caused by mutations in genes for proteins of the red
cell membrane (mainly spectrin, ankyrin or band 3). This results in
the red cell losing part of its membrane when it passes through the
spleen.
• Pyruvate kinase deficiency : one of the most common enzymatic
defects of the erythrocyte, manifests clinically as a hemolytic
anemia that can range from mild to severe.
• G6PD deficiency : Mainly in people originating in the
Mediterranean, Middle-East and Far East or in African-Americans.
Mainly affects male infants , but some females develop significant
jaundice.

37. Jaundice at 2 days to 2 weeks of age
• Physiological jaundice
• ABO incompatibility
• Breast milk jaundice
• Dehydration
• Infection
• Crigler-najjar syndrome
• Other causes

38. Breast milk jaundice
• Breast milk jaundice may be associated with
unconjugated hyperbilirubinemia without
evidence of hemolysis during the first to second
week of life. Bilirubin levels rarely increase to
more than 20 mg/dL. Interruption of
breastfeeding for 1 to 2 days results in a rapid
decline of bilirubin levels, which do not increase
significantly after breastfeeding resumes. Breast
milk may contain an inhibitor of bilirubin
conjugation or may increase enterohepatic
recirculation of bilirubin because of breast milk
glucuronidase.

39. Criggler- Najjar syndrome
• Crigler-Najjar syndrome is a serious, rare,
autosomal recessive, permanent deficiency of
glucuronosyltransferase that results in severe
indirect hyperbilirubinemia. Type II responds to
enzyme induction by phenobarbital, producing an
increase in enzyme activity and a reduction of
bilirubin levels. Type I (absent of enzyme )does
not respond to phenobarbital and manifests as
persistent indirect hyperbilirubinemia, often
leading to kernicterus .

40. Gilbert disease
• Gilbert disease is caused by a mutation of the
promoter region of glucuronosyltransferase
and results in a mild indirect
hyperbilirubinemia. In the presence of
another icterogenic factor (hemolysis), more
severe jaundice may develop.

41. Jaundice at >2 weeks of age
• Jaundice in babies more than 2 weeks old
(3 weeks if preterm), is called persistent or
prolonged neonatal jaundice. The key feature
is that it may be caused by biliary atresia, and
it is important to diagnose biliary atresia
promptly, as delay in surgical treatment
adversely affects outcome,

42. • in most infants with persistent neonatal
jaundice, the hyperbilirubinaemia is
unconjugated, but this needs to be confirmed
on laboratory testing.

43. • ‘Breast milk jaundice’ is the most common cause,
affecting up to 15% of healthy breast-fed infants;
the jaundice gradually fades and disappears by 4–
5 weeks of age.
• Infection, particularly of the urinary tract, needs
to be considered.
• Congenital hypothyroidism may cause prolonged
jaundice before the clinical features of coarse
facies, dry skin, hypotonia and constipation
become evident.

44. How can we reach
To diagnosis of the
underling cause of
jaundice ?

45. HISTORY
• Prenatal : DM , H.T ( increase risk of polycythemia
jaundice )
• Infection during pregnancy ( torch..)
• Term or preterm?
• Natal : Normal vaginal delivery or c.s?
• Any history of obstructed labour ?
• Birth trauma
• Postnatal : any delay of pass meconium?
• Poor feeding ?

46. Investigation

47. Clinical examination
• Yellowish discoloration of skin and sclera
• Cephalhematoma may be found
• Brusing ?
• Macrosomia “ infant of diabetic mother “
• Infection as rash “ meningococcemia”
• Hypotonia
• Lethargy

49. Treatment
• Regardless of the cause, the goal of therapy is
to prevent neurotoxicity related to indirect-
reacting bilirubin .
• Phototherapy and, if it is unsuccessful,
exchange Transfusion remain the primary
treatment modalities used to keep the
maximal total serum bilirubin below
pathologic levels

50. • The risk of injury to the central nervous system from
bilirubin must be balanced against the potential risk of
treatment. There is lack of consensus regarding the
exact bilirubin level at which to initiate phototherapy.
Because phototherapy may require 6-12 hr to have a
measurable effect, it must be started at bilirubin levels
below those indicated for exchange transfusion. When
identifi ed, underlying medical causes of elevated
bilirubin and physiologic factors that contribute to
neuronal susceptibility should be treated, with
antibiotics for septicemia and correction of acidosis

51. Phototherapy
• Clinical jaundice and indirect
hyperbilirubinemia are reduced by exposure
to a high intensity of light in the visible
spectrum. Bilirubin absorbs light maximally in
the blue range (420-470 nm).
• Broad-spectrum white, blue, and special
narrow-spectrum (super) blue lights have
been effective in reducing bilirubin levels.

52. • Bilirubin in the skin absorbs light energy,
causing several photochemical reactions. One
major product from phototherapy is a result
of a reversible photo-isomerization reaction
converting the toxic native unconjugated
4Z,15Z-bilirubin into an unconjugated
configurational isomer, 4Z,15E-bilirubin,
which can then be excreted in bile without
conjugation

53. • The other major product from photo therapy
is lumirubin, which is an irreversible structural
isomer converted from native bilirubin that
can be excreted by the kidneys in the
unconjugated state.

54. • The therapeutic effect of phototherapy depends
on :-
• 1- the light energy emitted in the effective range
of wavelengths,
• 2 the distance between the lights and the infant
• , 3 -surface area of exposed skin,
• 4- the rate of hemolysis and in vivo metabolism
and
• 5 -excretion of bilirubin

55. • The use of phototherapy has decreased the
need for exchange transfusion in term and
preterm infants with hemolytic and
nonhemolytic jaundice. When indications for
exchange transfusion are present,
phototherapy should not be used as a
substitute; however, phototherapy may
reduce the need for repeated exchange
transfusion

56. • It should be discontinued as soon as the
indirect bilirubin concentration has reduced to
levels considered safe with respect to the
infant ’ s age and condition.
• Serum bilirubin levels and hematocrit should
be monitored every 4-8 hr in infants with
hemolytic disease and those with bilirubin
levels near toxic range for the individual infant

57. Complications of phototherapy
• Loose stools,
• erythematous macular rash
• Overheating
• dehydration (increased insensible water loss,
diarrhea)
• hypothermia from exposure
• a benign condition called bronze baby
syndrome

58. • . Before Phototherapy is initiated, the infant ’ s eyes
should be closed and adequately covered to prevent
light exposure and corneal damage. Body
temperature should be monitored, and the infant
should be Shielded from bulb breakage. Irradiance
should be measured directly. In infants with
hemolytic disease, care must be taken to monitor for
the development of anemia, which may require
transfusion. Anemia may develop despite lowering of
bilirubin levels. Clinical experience suggests that
long-term adverse biologic effects of phototherapy
are absent, minimal, or unrecognized.

59. • The term bronze baby syndrome refers to a
sometimes-noted dark, grayish brown skin
discoloration in infants undergoing phototherapy.
Almost all infants observed with this syndrome
have had signifi cant elevation of direct-reacting
bilirubin and other evidence of obstructive liver
disease. The discoloration may be due to photo-
induced modifi cation of porphyrins, which are
often present during cholestatic jaundice and
may last for many months. Despite the bronze
baby syndrome, phototherapy can continue if
needed.

60. Brownish pigmentation seen over the abdomen.
Bronze baby syndrome

61. Exchange transfusion
• Double-volume exchange transfusion is performed if
intensive phototherapy has failed to reduce bilirubin
levels to a safe range and if the risk of kernicterus
exceeds the risk of the procedure.
• Potential complications from exchange transfusion are
not trivialand include metabolic acidosis, electrolyte
abnormalities, hypoglycemia,
• hypocalcemia, thrombocytopenia, volume overload,
arrhythmias, NEC, infection, graft versus host disease,
and death.
• This widely accepted treatment is repeated if necessary
to keep indirect bilirubin levels in a safe range

62. • Various factors may influence the decision to
perform a double-volume exchange transfusion in
an individual patient. The appearance of clinical
signs suggesting kernicterus is an indication for
exchange transfusion at any level of serum
bilirubin. A healthy full-term infant with
physiologic or breast milk jaundice may tolerate a
concentration slightly higher than 25 mg/dL with
no apparent ill effect, whereas kernicterus may
develop in a sick premature infant at a
significantly lower level.

63. Intravenous Immunoglobulin
• The administration of intravenous
immunoglobulin is an adjunctive treatment for
hyperbilirubinemia due to isoimmune hemolytic
disease. Its use is recommended when serum
bilirubin is approaching exchange levels despite
maximal interventions including phototherapy.
Intravenous immunoglobulin (0.5-1.0 g/ kg/dose;
repeat in 12 hr) has been shown to reduce the
need for exchange transfusion in both ABO and
Rh hemolytic disease, presumably by reducing
hemolysis.

64. Metalloporphyrins
• A potentially important alternative therapy is the use
of metalloporphyrins for hyperbilirubinemia. The
metalloporphyrin Snmesoporphyrin (SnMP) offers
promise as a drug candidate. The proposed mechanism
of action is competitive enzymatic inhibition of the
rate-limiting conversion of heme-protein to biliverdin
(anintermediate metabolite in the production of
unconjugated bilirubin) by heme-oxygenase. A single
intramuscular dose on the 1st day of life may reduce
the need for subsequent phototherapy. Such therapy
may be beneficial when jaundice is anticipated,
particularly in patients with ABO incompatibility or
G6PD deficiency .

65. Kernicterus
• Kernicterus, or bilirubin encephalopathy, is a neurologic
syndrome resulting from the deposition of unconjugated
(indirect) bilirubin in the basal ganglia and brainstem nuclei.
The pathogenesis of kernicterus is multifactorial and involves
an interaction between unconjugated bilirubin levels,
albumin binding and unbound bilirubin levels, passage
across the blood-brain barrier, and neuronal susceptibility to
injury. Disruption of the bloodbrain barrier by disease,
asphyxia, and other factors and maturational changes in
blood-brain barrier permeability affect risk.

66. Clinical presentation
• The precise blood level above which indirect-reacting
bilirubin or free bilirubin will be toxic for an individual infant is
unpredictable, but in a large series, kernicterus occurred only
in infants with a bilirubin > 20 mg/dL. Ninety percent of the
infants in whom kernicterus developed were in previously
healthy, predominantly breast-fed term and near-term
infants. The duration of exposure to high bilirubin levels
needed to produce toxic effects are unknown. The more
immature the infant is, the greater the susceptibility to
kernicterus.

67. • Signs and symptoms of kernicterus usually appear 2-5
days after birth in term infants and as late as the 7th day
in premature infants, but hyperbilirubinemia may lead to
encephalopathy at any time during the neonatal period.
The early signs may be subtle and indistinguishable from
those of sepsis, asphyxia, hypoglycemia, intracranial
hemorrhage, and other acute systemic illnesses in a
neonate. Lethargy, poor feeding, and loss of the
Mororeflex are common initial signs. Subsequently, the
infant may appear gravely ill and prostrate, with
diminished tendon reflexes and respiratory distress

68. • Opisthotonos with a bulging
fontanel,twitching of the face or limbs, and a
shrill high-pitched cry may follow. In advanced
cases, convulsions and spasm occur, with
affected infants stiffl y extending their arms in
an inward rotation with the fists clenched.
Rigidity is rare at this latestage.

69. • Many infants who progress to these severe
neurologic signs die; the survivors are usually
seriously damaged but may appear to recover
and for 2-3 mo show few abnormalities. Later in
the 1st yr of life, opisthotonos, muscle rigidity,
irregular movements, and convulsions tend to
recur. In the 2nd yr, the opisthotonos and
seizures abate, but irregular, involuntary
movements, muscle rigidity, or, in some infants,
hypotonia increase steadily.

70. • By 3 yr of age, the complete neurologic
syndrome is often apparent; it consists of
bilateral choreoathetosis with involuntary
muscle spasms, extrapyramidal signs, seizures,
mental defi ciency, dysarthric speech, high-
frequency hearing loss, squinting, and
defective upward eye movements. Pyramidal
signs, hypotonia, and ataxia occur in a few
infants.

71. • In mildly affected infants, the syndrome may
be characterized only by mild to moderate
neuromuscular incoordination, partial
deafness, or “ minimal brain dysfunction, ”
occurring singly or in combination; these
problems may be inapparent until the child
enters school

73. INCIDENCE AND PROGNOSIS
• By pathologic criteria, kernicterus develops in
30% of infants (all gestational ages) with
untreated hemolytic disease and bilirubin
levels > 25-30 mg/dL. The incidence at
autopsy in hyperbilirubinemic premature
infants is 2-16% and is related to the risk
factors Reliable estimates of the frequency of
the clinical syndrome are not available
because of the wide spectrum of
manifestations.

74. • Overt neurologic signs have a grave prognosis;
more than 75% of infants die, and 80% of
affected survivors have bilateral
choreoathetosis with involuntary muscle
spasms. Mental retardation, deafness, and
spastic quadriplegia are common.

75. prevention
• Although kernicterus has been thought to be a
disease of the past, there are reports of
neurotoxic effects of bilirubin in term and near-
term infants who were discharged as healthy
newborns.
• Some but not all experts recommend universal
screening for hyperbilirubinemia in the 1st 24-48
hr of life to detect infants at high risk for severe
jaundice and bilirubin-induced neurologic
dysfunction.

76. • Effective prevention requires ongoing vigilance
and a practical, system-based approach in order
to distinguish infants with benign newborn
jaundice from those whose course may be less
predictable and potentially harmful. Protocols
using the hourspecific bilirubin nomogram
physical examination, and clinical risk factors
have been successful in identifying patients at
risk for hyperbilirubinemia and candidates for
targeted management.

77. preventable causes of kernicterus,
• The American Academy of Pediatrics (AAP) has identified potentially
preventable causes of kernicterus, as follows:
• (1) early discharge ( < 48 hr) with no early follow-up (within 48 hr of discharge);
this problem is particularly important in near-term infants (35-37 wk of gestation);
• (2) failure to check the bilirubin level in an infant noted to be jaundiced
in the first 24 hr;
• (3) failure to recognize the presence of risk factors for hyperbilirubinemia;
• (4) underestimation of the severity of jaundice by clinical (visual) assessment;
• (5) lack of concern regarding the presence of jaundice;
• (6) delay in measuring the serum bilirubin level despite marked jaundice or delay
in initiating phototherapy in the presence of elevated bilirubin levels; and
• (7) failure to respond to parental concern regarding jaundice, poor feeding, or
lethargy.

78. • The following approach is further
recommended: (1) any
• infant who is jaundiced before 24 hr requires
measurement of serum bilirubin level and, if it
is elevated, evaluation for possible hemolytic
disease and
• (2) follow-up should be provided within 2-3
days of discharge to all neonates discharged
earlier than 48 hr after birth.

79. • Early follow-up is particularly important for
infants younger than 38 wk of gestation. The
timing of follow up depends on the age at
discharge and the presence of risk factors.
• In some cases, follow-up within 24 hr is
necessary.
• Postdischarge follow-up is essential for early
recognition of problems related to
hyperbilirubinemia and disease progression

80. THANK YOU