Neonatal
jaundice:
Source of bilirubin:
It is derived from breakdown of
heme containing proteins in the
RES,
Mainly from Hb,it forms about
75% of all bilirubin production.
One gm of Hb produces 34mg of
bilirubin.
25%of bilirubin is produced by
heme containing substances like
myoglobin,cytochromes,catalase…..
Etiology:
1-Increased load :by
hemolysis,polycythemia.
2-Damage or reduced activity of the
transferase enzyme like
hypoxia,hypothermia,hypothyroidism,
infection.
3-Competition or blockage of the
transferase enzyme.
4-Decreased activity of the transferase
enzyme genetically or by prematurity.
5-Hypoprotienemia.
6-Displacement of bilirubin from
combination sites by
drugs,acidosis,increased free fatty
acids secondary to
hypoglycemia,starvation and
hypothermia.,
Jaundice is the most common clinical
condition in the neonatal period, it
affects 50-60% of term newborns and
80% of prematures.It is clinically
visible when it exceeds 5mgm/dl.
Risk factors to get jaundice:
1-Low birth wt and prematurity.
2-Breast feeding.
3-Polycythemia.
4-A sibling affected.
5-Male sex.
6-Hemolytic conditions.
7-Extravasated blood.
8-Sepsis.
Physiology:Red blood cell destruction
releases globin,iron,and bilirubin which
exists in two forms:
1-Albumin bound.
bilirubin
2-Free
.
Glucoronyl transferase
conjugate bilirubin in the liver and
it becomes water soluble.
The activity of this enzyme is about
0.1 to 1% of that of adults and
reaches this level in 6-14 weeks
after birth.
Congugated bilirubin in the
intestine may be deconjugated by
beta glucoronidase and reabsorbed
to undergo reconjugation in the
liver(Enterohepatic circulation).
Indications of investigations
to determine the cause of
jaundice:
1- If it appears on the first 24-36
hours.
2- Rise of SBR >5mg/dl/24
hours.
3- SBR more than 12mg/dl in
term infants and more than
10mg/dl in preterm infants.
4- Jaundice persisting more
than 10-14 days.
5- Direct hyperbilirubinemia.
PHYSIOLOGIC
JAUNDICE:
1-It is due to increased
destruction of RBCS .
2-decreased ability of the liver to
conjugate bilirubin.
3-Increased enterohepatic
circulation.
4-Decreased uptake by the liver due
to low level of ligandin.
Characteristics:
1-Does not rise more than 12.9 ,very
rarely 15mg /dl.
2-It appears on the 3rd-4th day of
life.
3-Rarely increases by more than
5mgm/dl/day.
4-It disappears by one week in full
term infants and by two weeks in
preterm infants.
5-Healthy baby.
Etiology:
1-Decreased RBC survival(40-60
days)
2Polycythemia,bruising,cephalhemat
oma.
3-Poor feeding.
4-Dehydration.
5-Decreased glucoronyl transferase.
6-Shunt bilirubin(20%) from hem.
Pigment.
7-Maternal diabetes.
8-Prematurity.
9-Oxytocin induction. Vasopressinlike action of oxytocin causes osmotic
swelling of erythrocytes leading to
decreased deformability and hence more
rapid destruction of RBCS with resultant
hyperbilirubinaemia in the neonate.
10-Delayed bowel movement.
PATHOLOGIC
JAUNDICE:It is pathologic if:
1-Occurs in the first 24 hours.
2-If bilirubin level rises 0.5mg
/dl/hour or 5mg /dl/day.
3-If total serum bilirubin level
exceeds 15mgm/dl in term infants
or 10mgm/dl in preterm infants.
4-If there is evidence of acute
hemolysis .
5-Signs of an underlying illness
Clinical manifestations of
Neonatal jaundice:
Jaundice usually starts on the face
and proceed caudally. Rough
estimation can be done by pressing
on the nose but it needs experience,
division of the body in to zones can
be used for rough estimation, there
is interobserver variability.
Face:5mg/dl
Abdomen:15mg /dl
Soles:20mg/dl
CLINICAL
TYPES:
1-Early
jaundice(<10 days):
A-first 24 hours:Causes:
F Fetomaternal blood
group incompatibility.
I Intrauterine infection.
R RBC enzyme defect.
S Spherocytosis.
T Thalassemia.
1-Haemolytic disease of the
newborn:
This is the most important type as
SBR can rise to a dangerous level.
The most common cause is Rh
incmpatbility,the mother is Rh –ve
and the baby is Rh +ve,there is
severe jaundice,SBR increases up to
0.5mgm/dl/hour with a strong +ve
coombs test.
Pallor,reticulocytosis,hepatospleno
megaly,+ve family history.
When RBCS of Rh+ve fetus pass
through the placenta of Rh –ve
mother ,antibodies are formed in
the mother which pass through the
placenta to the fetus to cause
hemolysis.
Size of blood needed to cause
sensitization is about one ml.The
first baby escapes affection unless it
is preceded by sensitization due to
abortion or ameniocentesis.
Not all Rh-ve mothers
produce hemolysis in their
babies because:
1-The baby may be Rh-ve.
2-Not all mothers produce enough
Abs.
3-The mother might have been
immunized by anti D
immunoglobulin.
4-Fetomaternal transfusion occurs
only in 50% of pregnancies.
5-Small family.
6-When the mother and baby are
ABO incompatible.
Hypoglycemia is common and is
due to hyperinsulinism or
hyperplasia of the islets cells of the
pancreas.
Hemolysis in utero causes severe
anemia associated with low albumin
presented as hydrops fetalis
Treatment:The aim of treatment
is to correct anemia and to prevent
neurotoxicity.
Intrauterine blood exchange
transfusion is done for hydrops
fetalis and fetal anemia PCV<37,it
is done by canulation of the
umbilical vein to raise PCV to 4555%.
After birth cord Hb of 10gm/dl and
SBR of 5mgm/dl are predictors of
early blood exchange
transfusion.Hb,PCV,Retics,should
be measured 4-6 hourly.
2- ABO incompatibility:
The mother is O and the baby is A
or B.IgG antibodies are
responsible,coombs test is
–ve,blood film shows
microspherocytes.It occurs in 2025% of pregnancies but hemolysis
occurs in 10% only.Rarely the
mother is A blood group and the
baby is B and the opposite is true.
3- Rare causes of blood group
haemolytic jaundice:
subgroups,C,E,Kell,Duffy……
Other causes of haemolysis
which present on the first
day:G6PD deficiency,Pyrovate
kinase deficiency,congenital
spherocytosis,elliptocytosis,thalasse
mia……………
4-Sepsis.
5- Crigler-Najjar syndrome:
can present early and continues
beyond 10 days,It is due to
glucuronyl transferase deficiency.
.
General investigations:
SBR,Both direct and indirect,ABO
and Rh, coombs test,Hb and
Retics,blood film,G6PD
assessment,blood sugar .
Prolonged jaundice:>10 days in
term and >14 days in preterm babies:
Unconjugated hyperbilirubinemia.
1-Breast
milk jaundice:
The patient is usually well.2% of
infants get the problem after the 7th
day of life, maximum concentration
is 10-30mg/dl reached during 2nd-3rd
week.No signs of other
illnesses,kernicterus has been
reported but it is rare.
Needs no
treatment but phototherapy may be
of help..
Usually
settles by 6 weeks,but may go on
longer up to three months..
Discontiuation of breast feeding for
48 hours is rarely needed, but it can
reduce the level of jaundice.
Betaglucoronidase in milk causes
deconjugation of bilirubin
diglucoronide in the intestine or it is
due to an unidentified factors..
Good wt gain,normal liver,no
evidence of hemolysis.
Recurrence 70% in future
pregnancies
Breast feeding jaundice:
Early onset of hyperbilirubinemia
in the first week,occurs in 43% of
infants due to decreased milk intake
and dehydration.
Treatment: Encourage breast
feeding especially at night, no
glucose water to enhance high
density caloric milk.
2-Congenital hypothyroidism.
3-Intestinal
stasis,obstruction,hirschsprung
disease,atresia,meconium ileus.
4-sepsis
5-Galactosemia,fructosemia.
6-Cystic fibrosis by causing
intestinal.ileus and its’effect on the
liver.
7-Criggler Najjar syndrome.
Prolonged conjugated
hyperbilirubinemia:
A value greater than 1.5mgm/dl or
a fraction >10% of the total SBR is
considered abnormal:
Causes:
1-Infections.
2-Metabolic:
galactosemia,fructosemia,ty
rosinemia.
3-cystic fibrosis.
4-Dubin Johnson
syndrome.
5-Rotors syndrome.
6-Idiopathic neonatal
hepatitis.
7-Biliary atresia ,bile duct
stenosis.
8-Choledical cyst.
9-Alpha one antitrypsin
deficiency.
10-Hypothyroidism.
Investigations
(3)
It depends on the situation.
SBR,ABO and Rh of baby and
mother,Hb,Retics,blood
film,coombs test,blood
culture,TORCH screen,reducing
subs. in urine for
galactosemia,G6PD screen,osmotic
fragility test,T4,TSH,liver function
tests,sweat test,abdominal
ultrasound.
.
Transcutaneous bilirubinometry.
Acute bilirubin
encephalopathy:
It describes the acute
manifestations of bilirubin toxicity
seen in the first weeks after birth
manifested by poor feeding,high
pitched cry,hypotonia.
Chronic bilirubin
encephalopathy:
It is marked by
athetosis,deafness,mild mental
handicap,dental dysplasia.
Kernicterus:
Yellow staining of the brain with
neuronal injury,there is
necrosis,neuronal loss and gliosis.It
is commonly seen in the basal
ganglia,hypocampus,cerebellum,br
ainstem and spinal cord.It is a
pathological term.
.
Brain damage caused by
bilirubin depends on:
1-Level of serum bilirubin
and albumin.
2-Bilirubin binding by
albumin
3-Status of the blood brain
barrier.
4-Susceptibility of the CNS
5--Bilirubin is also
produced in situ in the
brain and metabolized by
bilirubin oxygenase.
damage to this mechanism may
elevate local brain bilirubin level,
in addition heme degradation in the
brain produces carbon monoxide
which may act as a local neurotoxin
in some patients.
Bilirubin gets entry to the brain cell
by binding to membrane
phospholipids and changed to
bilirubin acid which is highly toxic
to cell membrane and respiratory
organells like mitochodria and
endoplasmic reticulum.
Clinical manifestations:
Important points:
1-The level at which the baby is
liable to get kernicterus is not well
known.
2-Up to 15% of babies with
subsequent kernicterus failed to
show any definite neonatal
neorologic symptoms.
Clinical features:signs of
Encephlopathy appear at 2-5 days
after birth in term infants and as
late as the 7th day in preterm
infants,signs may simulate birth
asphyxia,septicemia,hypothermia,h
ypoglycemia,intracranial
hemorrhage.
Risk factors for
bilirubin
encephalopathy:
1-Severe
hyperbilirubinemia.
2-Prematurity.
3-Asphyxia.
4-Acidosis.
5-Hypoglycemia.
Pathology:
Unconjucated bilirubin is deposited
in the basal ganglia and the corpus
subthalamicus,hypocompus,striate
bodies,thalamus,globus
pallidus,putamen,cerebellum.
Preventable causes:
1- Early discharge.
2- Failure to check SBR.
3- Failure to recognize
risk factors.
4- Underestimation of
severity.
5- Lack of concern.
6- Delay in treatment.
7- Failure to respond to
parental concern.
Acute encephalopathy
A-Phase1 :(1st 1-2 days):poor
sucking,stupor,convulsions.
B-Phase 2(middle of 1st
week):hypertonia of extensor
muscles,opisthotonus,retracted
neck,fever,high pitched cry.
C-Phase 3(after the 1st
week):hypotonia.
Chronic
encephalopathy:
First year:hypertonia,active deep
tendon reflexes,delayed motor
skills.
After first year:movement
disorders(choreoathetosis,tremor, jerking movement,abnormal
slurred speech,sensorineural
deafness).dental dysplasia,mental
retardation may be present.
What makes kernicterus
an imminent problem?
1-Absence
pathognomonic signs.
of
2-Delayed presentation.
3-Failure to respond to
parental worries.
4-Failure to recognize risk
factors of kernicterus.
5-Failure of follow up of
babies discharged early
from the obstetric ward.
6-Failure to check SBR by
depending
on
visual
assessment.
7-Parental ignorance.
Remember:
1-Direct bilirubin more than 20%
of total is dangerous.
2-Dark yellow urine and pale stool
are dangerous signs.
Treatment of
hyperbilirubinemia:
The aim of therapy is to
prevent neuronal damage by
bilirubin.
Treat the underlying cause
like
septicemia,acidosis,hypoglyc
emia and ensure adequate
hydration.
Phototherapy:
Bilirubin absorbs light in the
blue range (Wave length420-
470nm).,however white
,narrow spectrum blue(super
blue),green lights were also
used.By photoisomerization
unconjugated bilirubin is
converted into non toxic
conjugated
bilirubin(lumirubin)..
Bilirubin level decreases
by2.5-3mgm/dl/day and 12mgm/dl in first 4-6 hours of
phototherapy.Phototherapy
works on the skin to a depth
of 2mm from the epidermis.
Because phototherapy
“bleaches” the skin, both
visual assessment of
jaundice and
TcB(Transcutaneos
Bilirubinometry)
measurements in infants
undergoing phototherapy
are not reliable.
.
The efficacy of
phototherapy depends on:
1-The light energy emitted.
2-The distance between the light
source and the baby(average 60
cm).
3-Amount of skin exposed ,the baby
should be turned frequently.
4-The rate of haemolysis.
5-Hydration.
6-Intensity of light(double
phototherapy,fibreoptic blankets)
and type of light bulbs.
Home
phototherapy:
This is an option way of treatment
where facilities are available and
fiber optic blankets are commonly
used. The family should be well
instructed and a well trained nurse
should be present, it is usually used
for simple jaundice.
Complications of
phototherapy:
1-Equipment failure.
2-Dehydration.30ml/kg/day fluid is
added.
3-Loose stool.
4-Parental anxiety and interaction
with their infant.
5-Skin rash.
6-Skin burn.
7-Bronze baby syndrome.
8-Eye damage.
9-Nasal obstruction.
10-Over heating.
11-In vitro DNA damage.It may be
wise to shield the scrotum.
12-Decrease LV output and renal
blood flow.
13- Hypocalcemia in preterm
infants.
Blood
exchange
transfusion:
Exchange is done when the risk of
kernicterus is imminent.
A double volume exchange replaces
85% of the infant RBCS,and
reduces pre-exchange bilirubin
level to 50%.
Volume of blood
needed=85x2xbody weight.
The time needed is about one and a
half to two hours.
There is no strict rule for
indications of exchange
transfusion,but by checking all the
variables and risk factors,the table
below is a guide:
Age in days and serum bilirubin
level
1234567
we
igh
t
<1 8 8 8 1 1 1 1
00
0000
0
10 1 1 1 1 1 1 1
00- 0 0 0 0 0 5 5
12
49
12 1 1 1 1 1 1 1
50- 2 2 2 5 5 5 5
14
99
15 1 1 1 1 1 1 1
00- 5 5 5 5 5 5 6
17
49
17 1 1 1 1 1 1 1
50- 5 5 5 6 6 7 7
19
99
>2 1 1 1 1 1 1 1
00 8 8 8 8 8 8 8
0
Term babies 20 mgm/dl.BET
should be done at low level if there
is a risk of kernicterus,the baby is
acidotic,septicemic,hypothermic,hy
poglycemic,or another baby had
kernicterus,
The best guide is the
clinical judgment.
BET is usually done by canulation
of the umbilical vein but a
peripheral vein and artery can be
canalized this is called
isovolumetric exchange.
BET is done for other diseases
like septicemia,severe
anemia,DIC,poisoning….
Complications of blood
exchange transfusion:
1-Early complications:
acidosis,electrolyte
disturbances,hypoglycemia,bradyca
rdia,
Hypocalcemia,hypomagnesemia,thr
ombosis,apnea,hypothermia,
infection ,gangrene of a leg, death
in 0.3/100 procedures.
2 -Late complications:
1-portal vein thrombosis
and portal hypertension.
2-Late onset anemia.
3-Graft versus host disease.
4-Inspissated bile syndrome.
Blood typing and cross
matching:
1-Rh isoimmunization:The blood
must be type O,Rh negative,low
titer anti A ,anti B blood,it must be
cross matched against the
mothers’plasma and red cells.
2-ABO incompatibility:the blood
must be type O,Rh compatable with
the mother and the infant or Rh
negative ,low titer anti A,anti B
blood.It must be cross matched
with the mother’s and the infant’s
blood.
3-Haemolysis from other causes like
metabolic causes,other haemolytic
anemias ,the blood should be cross
matched against the infant’s plasma
and RBCs,the blood should be
fresh(<48 hours) and should be
agitated frequently.
Other therapies:
Protoporphyrins:It may inhibit
the conversion of biliverdin to
bilirubin by heme oxygenase.
2-IV immunoglobulin,500mg/kg
per dose, twice daily for three
days,useful in coomb's +ve infants
by reducing hemolysis.
3-Phenobarbital?
Key Messages:
Promote and support
successful breastfeeding.
2.
Recognize that visual
estimation of the degree of
jaundice and those under
1.
phototherapy can lead to
errors.
3.
Interpret all bilirubin levels
according to the infant's age in
hours.
4.
Recognize that infants at
less than 38 weeks' gestation
are at higher risk of
developing hyperbilirubinemia
and require closer surveillance
and monitoring.
5.
Perform a systematic
assessment on all infants
before discharge for the risk of
severe hyperbilirubinemia.
6.
Provide appropriate followup based on the time of
discharge and the risk
assessment.
7.
Treat newborns, when
indicated,phototherapy or
exchange transfusion
.