White Light Versus Blue Light Phototherapy

UNIVERSITY OF KHARTOUM
Faculty of Medicine
Postgraduate Medical Studies Board
White light versus Blue light phototherapy in

reducing serum bilirubin in neonatal jaundice
in Sudanese patients
By
Dr. Abu Obieda Bala Mohammed Abusharib
M.B.B.S (University of Kassala)
A thesis Submitted in partial fulfillment for the requirements of the Degree

of Clinical MD in Pathology,
August, 2004
Supervisor
Dr. Abdel Hafiz Hassan Khatab
MBBS, FRCPath
Associate Professor of Pathology
Department of Pathology
Faculty of Medicine, U of K
To
my parents, teachers
&
friends
I like to express may gratitude and thanks to my supervisor Prof. Abdul-Hafiz

Hassan Khatab for supervision, constant support, criticism, guidance and
encouragement and also special thanks extended to the members of Pathology
Department, University of Khartoum.
I am also thankful for the staff of the Nursery Unit, Omdurman Maternity
Hospital, doctors, sisters and nurses for their help, phoning and assisting me in taking
samples.
May I seize this opportunity to thank Dr. Widad ElShiekh who helped me so
much in making this work successful.
Gratitude and appreciation are extended to Miss Widad A/Magsood for typing
this manuscript.
Finally, my gratitude are forwarded to my parents, brothers, and sisters for their
patience, support and encouragement.
LIST OF ABBREVIATIONS
Abbreviation
Meaning
BBB
Blood brain barrier
U.D.P.G.T
Uridine diphosphoglucuronyl transferase
Rh.
Rhesus
H.D.N
Haemolytic disease of the newborn
G.6.P.D
Glucose 6-phosphate dehydrogenase
T.O.R.C.H
Toxoplasmosis, others, Rubella, cytomegalovirus herpes
A.S.T
Aspartate transaminase
S.G.P.T
Serum glutamate pyruvate transferase
G.G.T
Gama-glutamyl transferase
S.G.O.T
Serum glutamate oxalate transferase
ETCO
End-tidal carbon monoxide in breath
U/S
Ultrasound
AAP
American Academy of Paediatrics
ED.T.A
Ethyline diamine tetraacetic acid
U.C.B
Unconjugated bilirubin.
EL C/S
Elective Caesarean section
Em C/S
Emergency Caesarean section
ABSTRACT
This is a prospective comparative study conducted at the Nursery Unit at Omdurman

Maternity Hospital in the period between January 2003 to September 2003.
In this study, 80 newborns presented with moderate jaundice for phototherapy according to
their serum bilirubin and gestation age. Fourty cases planned for treatment with white light
phototherapy and 40 cases planned for treatment with blue light phototherapy.
Selection criteria were, full term babies with unconjugated serum bilirubin between (11-20
mg/dl).
The objective of this study to determine the effectiveness of white light phototherapy
compared to blue light, expressing the difference in terms of reduction in serum bilirubin in 24
hours and 48 hours exposure.
The study concluded that, there was statistically significant difference in favour of blue light,
with a mean reduction of 1.6 mg/dl versus 1.2 mg/dl for white light for the first 24 hours and
2.7 mg/dl versus 2 mg/dl after 48 hours exposure.
Also this study reported 9(11.3%) failures of phototherapy who were treated with exchange
blood transfusion, 5 cases had been treated under white light, 4 cases under blue light,
revealing a failure rate of (1 in 10) under blue light, and (1in 8) under white light.
Concerning the etiology of jaundice, 46.3% of the studied group had septicemia, which was a
significantly high percentage. Moreover the study revealed that ABO and Rh incompatibility
were (25%), and (10%) respectively.
However, 3.8% of the studied group had cepahlohematoma after forceps delivery. The study
showed that males predominated, i.e. 60% of the studied group.
Finally this study recommendeds the use of blue lamps instead of white ones in locally made
machines, also it is recommended to setup guidelines for phototherapy management and to
minimize forceps delivery, and revise diagnosing septicemia and antibiotic prescription.

-
2003 2003.
) (80
.
(40) . ) (40
.
) (
) 20-11/(.

24
48 .

1.6/ 1.2/
24 48
2.7/ 2/ .
9 ) (%11.3
5 4
. 10
8 .
%46.4
) ( %10
%25 . %3.8
. .%60

.

.
LIST OF TABLES & FIGURES

Page
Table and Figure 1: Distribution of studied population
According to sex
52

according to home origin
53

According to maternal age
54
Table and Figure 4: Distribution of studied population according

to parity of the mother
55

to weight of newborns
57

to mode of delivery
58

to time of onset of jaundice
59
Table 8: Distribution of studied population according to mother's

blood group
60
Table 9: Distribution of studied population according to blood

group of the baby
61
Table 10: Distribution of total serum bilirubin before

Phototherapy
63
Table and Figure 11: Distribution of indirect serum bilirubin

before phototherapy
64

after 48 hours of phototherapy
65
Table 13: Distribution of indirect serum bilirubin reduction after

the first 24 hours of phototherapy
66

67
Figure 15: Distribution of direct Coomb's test result in

studied population
68
Table and Figure 16: Distribution of causes of jaundice among

studied groups
69
Table 17: Distribution of the studied population according to

Haemoglobin level
70
Table 18: Comparison between white light and blue light treated
neonates in relation to the cause of jaundice
72
Table 19: Comparison between white and blue light treated

neonates in relation to the level of indirect SB
73
Table 20: Response to phototherapy among the

studied population
74
Table 21a: Statistical test comparing reduction of indirect S.B in

white & blue light treated neonates in the 1st 24 hours 75
Table 21b: Statistical test comparing reduction of indirect S.B in
white & blue light treated neonates in the 1st 48 hours 76
Fig. 21:
Mean reduction of indirect serum bilirubin during the

1st 48 hours in blue and white light
77
Table 22: Causes of jaundice in relation to response

to phototherapy
Table 23: Level of indirect serum bilirubin (base-line) in relation
78
to response
79
Table 24: Reduction in serum bilirubin versus exchange blood

Transfusion
Table 25: Mode of delivery in relation to cause of jaundice
80
81
Table 26: Level of indirect serum bilirubin (S.B) base-line in

relation to causes of jaundice
Fig. 22:
Final outcome of the studied population
82
84
CONTENTS
Page
I
Dedication
Acknowledgment
II
Abbreviations
III
English abstract
Arabic abstract
VI
List of tables and figures
VIII
CHAPTER ONE
INTRODUCTION AND LITERATURE REVIEW
1.1. Definition
1.2. Background
1.3. Bilirubin metabolism
1.3.1. Source of production
1.3.2. Binding and transport
1.3.3. Hepatic uptake
1.3.4. Conjugation
1.3.5. Excretion and enterohepatic circulation
1.4. Etiology
1.4.1. Physiological hyperbilirubinemia
1.4.2. Pathological jaundice
1.5. Clinical consideration
15
1.6. Investigation
16
1.6.1. Approach to diagnosis
16
1.6.2. Total serum bilirubin and its fractions
17
1.6.3. Other studies
21
1.7. Treatment of hyperbilirubinemia
25
1.7.1. Phototherapy
25
1.7.2. Exchange transfusion
33
1.7.3. Other therapeutic considerations
35
1.8. Kernicterus
36
JUSTIFICATION
38
OBJECTIVES
39
CHAPTER TWO
2. METHODOLOGY
40
CHAPTER THREE
3. RESULTS
51
3.1. Socio-demographic characteristics of the studied population 51

3.2. Clinical factors that affect the studied population
56
3.3 Comparison between those treated with blue light and

white light
71
3.4 Clinical factors affecting response to phototherapy
77
3.5. Phototherapy versus exchange blood transfusion
79
3.6. Clinical factors that have an effect on the etiology of

jaundice among the studied population
80
CHAPTER FOUR
4. DISCUSSION
85
CONCLUSION
92
RECOMMENDATIONS
93
REFERENCES
94
INTRODUCTION AND LITERATURE REVIEW
1.1. Definition:
Jaundice refers to the yellowish discoloration of the skin,
mucous membranes and sclera(1).
Jaundice is observed during the first week of life in
approximately 60% of term infants and 80% of preterm infants.
The color usually results from accumulation in the skin of
unconjugated, lipid soluble bilirubin pigment (2).
This is due to increased production (accelerated red blood
cell break down), decreased removal (transient liver enzyme
insufficiency), and increased reabsorption (enterohepatic circulation
leading to hyperbilirubinemia (3).
1.2. Background:
Moderate hyperbilirubinemia is a common and in most
cases benign problem in neonates. The unconjugated form is
neurotoxic for infants at certain concentration and under various
conditions. Conjugated bilirubin is not neurotoxic but indicates a
potentially serious disorder (2).
The fetus excretes unconjugated bilirubin via the placenta

and maternal liver, however postnatally most newborns exhibit
elevation in serum bilirubin, when the mechanisms for liver uptake,
transport, and conjugation are immature(4).
Severe hyperbilirubinemia shows yellow staining of the basal
gangilia and brain stem. This pathological appearance is described
as kernictrus, so levels of total and unconjugated bilirubin must be
carefully monitored and if they exceed a preset level (20mg/dl)quick
intervention must be instituted (5).
1.3. Bilirubin metabolism:

1.3.1. Source of production:
Bilirubin is derived from the breakdown of the heme proteins that are present in
hemoglobin, myoglobin and certain heme containing enzymes. Three fourths of the bilirubin comes
from hemoglobin catabolism.
One gram of hemoglobin yields 35 mg of bilirubin. A normal

term newborn produces about 6-10 mg/kg/day of bilirubin that is
nearly 2-3 times compared to adults(6,7).
Bilirubin is produced at the reticuloendothelial system as the end product of heme
catabolism and is formed through oxidation-reduction reactions.
In the first step, biliverdin is formed from heme through the

action of heme oxygenase. The rate-limiting step in the process,
releasing iron and carbon monoxide, the iron is conserved for reuse,
while carbon monoxide is excreted through the lungs and can be

measured in the patients breath to quantify bilirubin.
Next, biliverdin is reduced to bilirubin, which because of the
intermolecular hydrogen bonds, is almost insoluble in water in its
most common isomeric form (bilirubin IXZ, Z)(7,8).
1.3.2. Binding and transport:
Due to its hydrophobic nature, unconjugated bilirubin is
transported in the plasma tightly bound to albumin. Binding to other
protein and erythrocytes also occurs, but the physiologic role is
probably limited. Binding of bilirubin to albumin increases postnatally
with age and is reduced in infants who are ill or preterm(8,9).
The albumin bound bilirubin is unable to cross the intact
blood brain barrier (BBB), but once bilirubin sites on albumin are
saturated, free bilirubin appears in serum. This free bilirubin can
cross the BBB and produce bilirubin brain damage.
in cases of existing insult to BBB; even albumin bound
bilirubin can get access to the central nervous system.(7,8) Decreasedbinding capacity can occur in hypoalbuminemia or if the binding sites
are filled with other anions.
Controversy exists regarding whether parenterally administered lipid can displace bilirubin
from its albumin-binding site. If faced with dangerously high levels of serum bilirubin, restricting lipid
administration to less than maximal levels may be prudent(9).
Drugs, such as sulfisoxazole and ceftriaxone can also

compete for bilirubin-binding sites on the albumin molecule and must
be used with caution or avoided in the neonatal period(9).
1.3.3. Hepatic uptake:
When bilirubin-albumin complex reaches the hepatocyte,
bilirubin is transported into the cell, where it partially binds to ligandin
called Y protein. Uptake of bilirubin into hepatocytes increases with
increasing ligandin concentrations. Ligandin concentrations are low at
birth, but they increase rapidly over the first few weeks of life.
Ligandin concentration may be increased by the administration of
pharmacological agents such as Phenobarbital(4,8).
1.3.4. Conjugation:
Once inside the hepatocyte, bilirubin is conjugated to a sugar
moiety, glucuronic acid in the smooth endoplasmic reticulum to form
water-soluble mono-and diglucuronides of bilirubin. The microsomal
enzyme
(hepatic
uridine
diphosphoglucuronosyl
transferase)
catalyzes these reactions(12,10,37).

Monoconjugates are formed first, and predominate in the
newborn. Diconjungates appears to be formed at the cell membrane
and may require the presence of the UDPGT tetramer.
Bilirubin conjugation is biologically critical because it

transforms a water-insoluble bilirubin molecule. The activity of
UDPGT is low at birth, but increases to adult values by age 4-8
weeks. In addition, certain drugs (Phenobarbital, dexamethasone,
and clofibrate) can be administered to increase UDPGT activity(10,11).
1.3.5. Excretion and enterohepatic circulation:
Once conjugated, water soluble bilirubin is excreted in an
energy-dependent manner into the bile canaliculi for ultimate delivery
into the small intestine. Disruption in this system or obstruction in the
biliary system results in accumulation of conjugated bilirubin in the
serum, identified by an elevation in the direct fraction of total bilirubin.
Direct hyperbilirubinemia in the neonate (defined as a direct
fraction greater than one third of total bilirubin) is always pathologic,
and an etiology must be pursued (9).
In adults, most of the conjugated bilirubin is converted by
colonic flora to urobilinogen before elimination in the stool. In the
newborn, however, a significant proportion is hydrolyzed by small gut
B-glucuronidase to yield glucuronic acid and unconjugated bilirubin.
This
bilirubin
readily
re-enters
enterohepatic circulation(4).
the
circulating
pool
via
the
Breast milk also contains beta-glucuronidase, and breast milk

feedings increase the level of this enzyme in the neonatal intestine.
Combined with slow intestinal motility in the first few days of life, the
above factors result in increased enterohepatic circulation of bilirubin
back into the blood stream (9).
Jaundice is common in the neonate for many reasons:
1. The red cells have a shortened half-life (60-70) days at term,
30-40 days in premature infants.
2. A high hemoglobin from placental transfusion-delayed cord
clamping increases the incidence from 5% in infants whose
cords were clamped early, to 30% in late clamped infants.
3. Bruising
even
from
normal
delivery
causes
some
extravasation of red cells into the tissues.

4. Low levels of ligandin and glucuronyl transferase which rise
rapidly during the first week.(6)
1.4. Etiology:
Jaundice may be present at birth or may appear at any time
during the neonatal period, depending on the cause(2). Generally it
can be divided in two groups.
1. Physiological jaundice.
2. Pathological jaundice (non physiological hyperbilirubinemia).
1.4.1. Physiological hyperbilirubinemia:
This is due to immaturity of liver metabolism, particularly the
enzyme glucuronyl transferase. Physiological jaundice is a diagnosis
of exclusion i.e. if any of the following features are present, an
alternative cause for jaundice is very likely.
1. Clinically observed jaundice within 24 hours of life.
2. High level of total bilirubin (12.5 mg/dl).
3. A conjugated level of bilirubin above 30 mmol/L (4
mg/dl).
4. Persistent jaundice lasting more than 10 days in a full
term infant or 14 days in a pre mature infant.
5. An infant who is ill (5).
Physiologic jaundice is an event that is linked to normal
development, is benign and self-limited, resolves by the end of the
first week and requires no treatment (11).
Overall 6.7% of full-term infants have indirect bilirubin levels
greater than 12.5 mg/dl and less than 3% have levels greater than 15
mg/dl, which is referred to as exaggerated physiologic jaundice (2).
Epidemiology:
Chinese, Greek and Japanese babies develop hyper
bilirubinemia unrelated to their higher incidence of G.6.P.D
deficiency, also male infants have higher bilirubin levels than female,
and Caucasians higher than blacks (4).
The obstetric practices of oxytocin infusion and delivery by
ventose extraction have been associated with a mild increase in
jaundice of the newborn. In the cases of maternal diabetes, jaundice
may be the result of polycythaemia(4).
The potentially important factors in the genesis of physiological jaundice include the
following:
Discontinuation of placental mechanisms for bilirubin removal

and detoxification.
A greater rate of bilirubin production in the infant (6-8) mg/kg
every 24 hours than in the adult, secondary to larger blood
mass and shortened red blood cell survival time.
Diminished binding of U.C.B. to neonatal serum albumin
Diminished levels of intracellular bilirubin binding (Y) protein
Impaired canalicular excretion of the organic anions in the
developing human(11).
1.4.2. Pathological jaundice:
Jaundice
and
its
underlying
hyperbilirubinemia,
are
considered pathologic if their time of appearance, duration or pattern

of
serially
determined
serum
bilirubin
concentrations
significantly from that of physiologic jaundice.
varies
or if the course is
compatible with physiologic jaundice, but other reasons exist to

suspect that the infant is at risk of neurotoxicity(2).
Factors suggesting non-physiological cause of jaundice are, family history of hemolytic
disease, pallor, and hepatomegally. Spleenomegaly, vomiting, lethargy fever and poor feeding.
Pathologic jaundice is divided into two types:

Indirect hyperbilirubinemia.
Direct hyperbilirubinemia.
1.4.2.1. Indirect hyperbilirubinemia "unconjugated" and this can
occur due to:
Excessive bilirubin production.
Decreased clearance of bilirubin.
1.4.2.1.1. Excessive bilirubin production:
i. Immune hemolysis: secondary to maternal-fetal blood groups
incompatibility, hence sensitization of the mother's immune
system to red cell antigens of the fetus. This sensitization results
in the transplacental red cell passage of maternal IgG antibodies
that bind to the fetal red cells causing hemolysis and as a
consequence
of
the
haemolytic
process,
anemia
and
hyperbilirubinemia occurs (12).

Although more than 60 different RBC antigens capable of
eliciting antibody response in a suitable recipient have been
identified, significant disease is associated primarily with the D
antigen of the Rh group and with incompatibility of A.B.O. factors.
Rarely, hemolytic disease may be caused by c or E antigen or by
other RBC antigens, such as Cw, Cx, Du, K (Kell), M, Duffy, S, P,
MNS, and Lutheran and Kidd (2).
Rhesus incompatibility occurs in infants who are Rh- positive,
and are born to mothers who are Rh-negative.
approximately 15%
of Caucasian women, but only 1% of black women are Rh negative.

Within the Rh blood group system the most immunogenic
antigens after D are c and E.(4) This disease begins in intrauterine life
and may result in death in utero.
Nowadays with screening
programs and prophylactic anti D therapy there is a decrease in

incidence of haemolytic disease of the newborn (4).
A.B.O. incompatibility is the most frequent cause of HDN
(haemolytic disease of the newborn), the incidence in the U.K. has
been found to be approximately 2% of all births and it is a mild

disease and only 5% require phototherapy (4).
Rh incompatibility is shown to be more serious in western
countries and ABO incompatibility appears to be more serious in
Blacks,
(13,14,15)
and in Sudan no studies done to evaluate this facts
but clinical observations show that there is still increase incidence of

maternal fetal blood incompatibility.
ii. Hereditary haemolytic anemia: Hemolysis can result from other
inherited or congenital causes, hereditary spherocytosis or
eleptocytosis can be present in the newborn. Glucose-6phosphate dehydrogenase deficiency is difficult to recognized and
unique because jaundice may not develop until the fourth day
post delivery.(16) Studies show high incidence of glucose-6phosphate dehydrogenase deficiency (G.6.P.D.D) but it is less
common in Sudan and very rare according to hospital data and
experience reports. However no studies were published to
evaluate the prevalence of G.6.P.D deficiency in Sudan (17,18).
iii. Neonatal sepsis: Hemolysis resulting from bacterial endotoxin as
in group B Streptococcal or Escherichia coli septicemia
(6)
Although these changes may be produced by disseminated

intravascular coagulation associated with the infection (4).
iv. Extra vasation of blood: As a cause of neonatal jaundice is seen
in infants with cephalohematoma or any other birth trauma. (19)
1.4.2.1.2. Decreased clearance of bilirubin:
a. Inborn errors of metabolism: include familial non-hemolytic
jaundice type 1 and II Criggler-Najjar syndrome Gilbert
syndrome, galactosemia, tyrosinosis and hyper methioninemia.
All of these are due to inherited disorders that lead to enzymatic
deficiency, they are associated with other clinical findings in
infants, but they are not frequent causes of neonatal
hyperbilirubinemia although some of them are very serious and
are the cause of death in early infancy.(20)
ii- Prematurity: Because liver enzymes are not mature to carry out
their activity in conjugation of bilirubin, Prematurity in most of
the cases is associated with unconjugated hyperbilirubinemia
and it is one of the major risk factor for the physiological
jaundice. (19)
iii- Hypothyroidism: Is a cause of persistent unconjugated
hyperbilirubinemia, which may be the presenting sign of thyroid
hormone deficiency because diagnosis is through assay of

thyroxin (T4) and thyroid stimulating hormone levels, neonatal
screening programs offer an early opportunity for detection of
this disorder.
iv- Infants of diabetic mother: Often have polycythaemia, with an
increased red cell mass leading to an increased daily rate of
bilirubin formation, they may have some structural or metabolic
instability of the red cell related to their glucose metabolism. (11)
v- Breast feeding: is an important risk for hyperbilirubinemia,
probably owing to high levels of beta-glucuronidase in breast milk
and if maternal milk supply is not yet adequate in the first few
days, decreased caloric intake and delayed passage of
meconium.(16)
1.4.2.2. Direct hyperbilirubinemia:
In these cases direct or conjugated bilirubin is greater than
15% of the total bilirubin.
Major causes are:
I- Intrahepatic and extrahepatic biliary obstruction:
this may be
anatomical at the level of the bile ducts (atraesia, choledochal

cyst), but also occurs at a cellular level with failure of excretion
from the hepatocytes. Most causes of obstructive jaundice rapidly

go on to hepatocellular dysfunction with a secondary rise in indirect
bilirubin. This mixed picture with raised direct and indirect bilirubin
is characteristic of biliary atrasia and also the various forms of
neonatal
hepatitis
including
-1-antitrypsin
deficiency
and
glactosemia. (21)
ii- intrauterine infection:
the commonest intrautrine infections that
lead to direct hyperbilirubinemia are cytomegalovirus, others, they

present with jaundice early and usually it persists to be prolonged
jaundice. Other clinical features like hepatosplenomagaly may be
found in children with congenital viral infections because they are
not uncommon; any neonate with jaundice whom the cause is not
clear
should
be
investigated
for
toxoplasmosis,
rubella,
cytomegalovirus herpes infection (TORCH) (2).

iii- Metabolic diseases: some metabolic diseases usually present
with
jaundice
in
the
neonatal
period
like
galactosemia,
tyrosinemia, -1-antitrypsin deficiency and cystic fibrosis may lead

to a sort of obstruction or disturbed liver functions with
hyperbilirubinemia(2,4).
iv- Drugs:
Maternal administration of oxytocin, diazepam, or
promethazine may result in increased serum bilirubin in the

infant. Similarly, neonatal administration of chloral hydrate
increases bilirubin levels.
Additionally some drugs such as sulfonamide and some
penicillins can displace bilirubin from its albumin binding site,
effectively increasing the serum concentration of free bilirubin
available to cross the blood-brain barrier.(6)
1.5. Clinical consideration:

The time of appearance of jaundice may give an important clue to likely etiology. Thus
jaundice on day one should be presumed haemolytic; jaundice on day three in a vigorous preterm infant
is likely be enhanced physiological, jaundice noticeable after the first week is characteristic of biliary
atresia.
Important information may be derived from the history of the

labour, e.g. prolonged rupture of membranes, asphyxia, traumatic
bruising, maternal rubella, syphilis, hepatitis, and the family history
e.g. hereditary spherocytosis, glucose 6-phosphate dehydrogenase
deficiency.(21)
Physical examination:
In most infants, yellow color is the only finding on physical examination. Jaundice first
becomes visible in the face and forehead. Identification is aided by pressure on the skin, since
blanching reveals the underlying color, jaundice then gradually becomes visible on the trunk and
extremities.
More intense jaundice may be associated with drowsiness,

overt neurological findings, such as changes in muscle tone, seizers,
or altered crying characteristics, in a significantly jaundiced infant are

danger signs and require immediate attention to avoid kernicterus(8).
Hepatosplenomegaly, petechiae, and microcephaly are associated with hemolytic anemia,
sepsis and congenital infection.
1.6. Investigation:
1.6.1. Approach to diagnosis:
Jaundice usually becomes apparent when total bilirubin level
exceeds 3-5 mg/dl. Estimation of total serum bilirubin levels based
on visual evaluation is often inaccurate because of interobserver
variability, especially in dark-skinned infants.
Laboratory testing should be reserved for infants with non-physiologic jaundice, routine
measurement of total serum bilirubin level in infants who do not meet the criteria for non-physiologic
jaundice is not warranted.
Laboratory evaluation should be fairly minimal because test

results are often non-revealing, even in the presence of hemolysis. In
up to 50% of infants with severe jaundice, breast-feeding and lower
gestational age is the only causes identified despite extensive workup(4).
The priority in investigation is given to the level of serum
birlirubin, the proportion of direct and indirect bilirubin, hemoglobin,
blood film for red cell morphology, reticulocyte or normoblast count,
blood group and Coombs test in infants and mother, infection
screening
and
where
appropriate;
glucose-6-phosphate
dehdydrogenase level. Galactosemia can be excluded in most cases

by a simple urine test for reducing substances in selected cases, liver
function tests are indicated and for surgical obstructive jaundice,
more formal investigation by ultrasound and laparotomy may be
required(21).
Generally any newborn who presented with jaundice should be evaluated with
investigations for assessment of the jaundice itself and then to reach the cause of jaundice by the
following studies.
1.6.2. Total serum bilirubin and its fractions:

Jaundice usually begins on the face, and as the serum level increases, progresses to the
abdomen and then the feet. Dermal pressure may reveal the anatomic progression of jaundice (face ~
5 mg/dl, mid abdomen ~ 15 mg/dl, soles ~ 20 mg/dl) but cannot be depended on to estimate blood
levels.
In general a search to determine the cause of jaundice, should be made if: (1) it appears in
the first 24 hr of life. (2) serum bilirubin is rising at a rate greater than 5-mg/dl/24 hr. (3) serum
bilirubin is greater than 12 mg/dl in full term or 10 mg/dl in preterm infants. (4) direct-reacting bilirubin
of greater than 2 mg/dl at any time.
Direct hyperbilirbuinemia may signify serious cause and indirect

hyperbiliruinemia carries risk of neurotoxicity. Serum bilirubin needs
to be assessed continuously to determine whether intervention is
needed or not(22,23).
A total serum bilirubin level is the only test required in a
moderately jaundiced infant who presents on the typical second or
third day of life without a history and physical findings suggestive of a
pathological process(24,25).
Method of detection serum bilirubin:
I- Bed side testing:
Because of the frequent sampling and relatively large amount

of the blood taken, worldwide advanced techniques are developed to
estimate serum bilirubin.
Transcutaneous bilirubinometry can be
performed using handling devices that incorporate sophisticated

optical algorithms to filter out most of the unreflected light, from light
that comes from bilirubin molecules.(22,23)
In
infants
with
moderate
jaundice,
transuctaneous
bilirubinometry may be useful in selecting patients who require

phlebotomy for serum bilirubin measurement(24,25).
ii- classical methods:
In 1883, Ehrlich first described a reaction in urine samples of
the formation of a red or blue pigment when bilirubin was coupled
with a diazotized sulfanilic acid solution. In 1913, Van-den Bergh
applied the Ehrilich reaction to serum bilirubin, he also used alcohol
as an accelerator for the coupling of bilirubin to diazotized sulfanlic
acid(26).
Malloy and Evelyn developed the first useful quantitative
technique for bilirubin in 1937 by accelerating the reaction with 50%
methanol solution, a technique that avoided the precipitation of
proteins that was a source of error in the Van-den Bergh method.
In 1938, Jendrassik and Grof used a procedure containing

caffeine and Benzoate acetate as an accelerator for the azo-coupling
reaction(26).
iii- Direct spectrophotometric method:
Bilirubin has been quantitated by dilution in a buffer, followed
by direct measurement of the absorption, using a well-calibrated
spectrophotometer. This method is used in the pediatric laboratory
on newborns whose serum does not yet contain the interfering yellow
lipochromes. The hemolysis that is so often a problem with pediatric.
Specimens is "blanked out" by measuring at a second wavelength(26).
Method Selection:
Unfortunately, no single method for the determination of bilirubin will meet al the
requirements of the clinical laboratory. For the evaluation of jaundice in newborns, the direct
spectrophotometric method is satisfactory.
The sources of error in this technique are turbidity, hemolysis,

and yellow lipochrome pigments.
Hemolysis and turbidity can be
"blanked out" by measuring at second wave length, but the yellow

lipochromes cannot be "blanked out". This method is, therefore, only
valid for newborns whose serum does not contain lipochromes for
patients older than age one month a diazo colorimetric procedure is
necessary.
Most investigators who have compared the different methods for the measurement of
bilirubin agree that the majority of techniques available today will give accurate results for total
bilirubin, provided that good standards are available.
The choice of method, then, should be based on whether direct bilirubin is to be
determined. The choice of direct bilirubin method poses the greatest problem because there is no
reference method or adequate standardization available.
If a manual procedure is desired, then either the Evelyn

Malloy or Jendrassik Grof method is suitable. The Jendrassik Grof
method is slightly more complex but has the following advantages
over the Evelen Malloy:
1. It is insensitive to sample pH changes.
2. It is insensitive to 50-fold variation in protein concentration of
the sample.
3. It has adequate optical sensitivity even for low bilirubin
concentration.
4. It has minimal turbidity and a relatively constant serum blank.
5. It is not affected by hemoglobin up to 750 mg/dl.
Since the development of the original procedure by Jendrassik-Grof, a number of modifications have
been made to speed up the reaction, reduce interference, and so on(26). There are now several
commercial bilirubin procedures that use a modified JendrassiK-Grof method. It seems to be a
particularly popular technique for the discrete sample analyzers currently on the market(26).
1.6.3. Other studies:
1- Blood grouping and Rhesus determination in

the infant to prove or exclude blood group
incompatibility.
2-Direct and indirect Coomb's testing in infant to prove or exclude
immune hemolysis.(4)
3-Hemoglobin and hematocrit values for

assessment of the infant and when, and how to
intervene.
4- Peripheral blood film for erythrocyte morphology and for the shape
of white blood cells and others. This is significant in cases of
spherocytosis, eliptocytosis and some other hemolytic problems,
presence of toxic granulation may indicate septicemia.(2)
5- Reticulocyte count: reticulocytosis if present indicate hemolysis
and it may be used for assessment of severity of the hemolysis and
is helpful to determine when intervention is necessary.(27,28)
6- Screening test for enzymatic deficiencies, example in case of
glucose-6-phosphate dehydrogenase deficiency.(29)
7- Red blood cell fragility test is helpful to

diagnose congenital spherocytosis.
8- Reducing substances in the urine for
glactosemia is a useful screening test,
provided that the infant has received sufficient

quantities of milk.
9- Thyroid function test: as a routine in any child with jaundice in the
neonatal period serum level of T3, T4 and TSH as congenital
hypothyroidism may present with jaundice commonly in the
neonatal period.
10- Liver function test: Aspartate transaminase
glutamate
oxaloacetate
transferase
SGOT,
(AST), serum
and
alanine
transaminase (ALT), serum glutamate pyruvate transferase SGPT

are elevated in hepatocellular disease as in cases of neonatal
hepatitis and cytomegalovirus infection. Alkaline phosphatase and
gamaglutamyltransferase GGT level are often are elevated in
cholestatic
jaundice.
gama-glutamyl
transferase/alanine
aminotransferase ratio greater than one is strongly suggestive of

biliary obstruction.
11-Tests for viral infections may be indicated in

infants with hepatosplenomegally or evidence
of hepatocellular disease, so serology for viral
hepatitis and cirrhosis, IgG or IgM levels for
congenital infections is very important.
12- Serum albumin level: this may be useful
adjunct in evaluating risk of toxicity levels,
since albumin binds bilirubin in a ratio of 1: 1 at
the primary high affinity binding sites.
13- Blood gas measurements: because the risk of neurotoxicity is

increased in acidosis particularly respiratory acidosis.
14- Measurement of end-tidal carbon monoxide in breath (ETCO):
which may be used as an index of bilirubin production.
Measurement of ETCO may assist in identifying individuals with
increased bilirubin production and, thus, at increased risk of
developing high bilirubin levels. An apparatus has been
developed that make measuring of ETCO simple(30,31).
15- Imaging studies: Ultrasound (U/S) examination of the liver and
bile ducts may give clue about neonatal hepatitis, also it may
diagnose biliary atrasia, bile duct stones or choledochal cyst,
annular pancreas or other causes of biliary obstruction.
16- From the above mentioned, it appears that a lot of investigations
are needed to be performed to reach a diagnosis in neonatal
jaundice. however, these tests are not needed for every individual
subject. So, investigations are lead by history and examination,
e.g. if a child has no family history of G-6-PD and signs do not
suggest that diagnosis, no need for G-6-PD test.
or if the
newborn has clear evidence of septicemia, no need to screen for

metabolic causes of neonatal jaundice, and may not need to be
evaluated by ultrasonography, unless there is evidence of

cholestasis.(32)
1.7. Treatment of hyperbilirubinemia:

Regardless of the cause, the goal of therapy is to prevent the
concentration of indirect reacting bilirubin in the blood from reaching
levels at which neurotoxicity may occur.
it is recommended that
phototherapy, if unsuccessful, exchange transfusion be used, to keep

the maximum total serum bilirubin below the levels indicated for
preterm and for healthy term infants.
The risk of injury to the central nervous system from bilirubin must be
balanced against the risk inherent in the treatment for each infant.
1.7.1. Phototherapy:
The criteria for initiating phototherapy are not generally
agreed on, because phototherapy may require 6-12 hours to have a
measurable effect, it must be started at bilirubin levels below those
indicated for exchange transfusion. Also the underlying cause of
jaundice should be treated(2).
To address the controversy and confusion regarding levels of
hyperbilirubinemia that require treatment, the American Academy of
Pediatrics
(A.A.P)
has
developed
practice
parameter
for
management of hyperbilirubinemia in full term newborns.
Table 1.a: Guidelines for measurement of term babies with hyperbilirubinemia.
Age (in hours)
Total serum bilirubin (mg/dl)

Consider phototherapy Exchange transfusion
25* - 48
12
20
49 72
15
25
> 72
20
25
* Full terms who are clinically jaundice at < 24 hours old require further evaluation.
For preterm intervention is required for low levels of indirect

hyperbilirubinemia as follows:
Table 1b: Guideline for measurement of preterm babies with indirect hyperbilirubinemia
Birth weight (g)
Serum level for
Serum level for exchange
phototherapy (mg/dl)
transfusion (mg/dl)
indirect fraction
Indirect fraction
< 1,000
17
1001 1500
10
17
1501 2000
11
18
2001 2500
12
20
The use of phototherapy has decreased the need for

exchange transfusion in term and preterm infants with hemolytic and
non-hemolytic jaundice. When there are indications for exchange
transfusion, phototherapy should not be used as a substitute.
However, phototherapy may reduce the need for repeated exchange
transfusions in infants with hemolysis.(2,16)
1.7.1.1. Biochemical basis of phototherapy:
Phototherapy detoxifies bilirubin and facilitates its excretion
from the body via routes other than conjugation in the liver(33,34).
There are three photochemical reactions that occur when bilirubin
interacts with photons of light energy. These are:
Photo oxidation.
Configuration isomerizatoin.
Structural isomerizatoin.
Photo-oxidation, the first of these reactions to be discovered,
involves disruption of the bilirubin molecule to form colorless polar
fragments that are readily excreted in urine. Although this process

reminds us of the need to avoid exposing serum samples to direct
sunlight(35), it is thought to play only a minor role in bilirubin exertion
during phototherapy.
The bilirubin molecule remains intact in the other two
reactions, undergoing either a configuration or structural change.
Configuration isomerization occurs by virtue of the double bonds
between carbon atoms 4-5 and 15 16 of the molecules. In the
natural form the arrangement of these double bonds and hence the
alignment of the end pyrrole rings is classified as bilirubin 4z, 15z.
Photons of light striking the double bond, initiate a 180 rotation
of one or both end pyrrole rings, to produce three isomeric forms,
Designated 4Z, 15Z, 15E. The conformation of bilirubin Z, E
maintains the exposure of polar groups at one end of the molecule,
enabling it to be excreted unconjugated in bile.
Once incorporated into bile, a rapid reversal of the reaction occurs, such
that unconjugatd bilirubin Z, E enters the gut and is available for up take
via the enterohepatic circulation(4).
Configuration isomerization was originally thought to be the principal
excretory mechanism of Phototherapy. It is now realized that, although
rapidly produced, these isomers are only slowly cleared in humans.
The serum half- life of bilirubin Z, E is about 15 hours, and
after some 6-12 hours of Phototherapy a steady state is achieved in
which approximately 20% of the total serum bilirubin is in the form of

the configuration isomer(2).
Importantly, this means that up to one fifth of the circulating
bilirbin is detoxified, despite not being in a form that is readily
excreted.
The structural isomer lumirubin, is currently considered to be
the major excretory product of Phototherapy(33). Lumirubin is formed
by cyclization of one end of the bilirubin molecule. This structural
change is irreversible and allows the more polar product to be
excreted in bile and urine.
Lumirubin's more efficient elimination is reflected in its half
life of less than 2 hours, and steady state concentration of 2-6% of
the total serum bilirubin. The production of lumirubin follows a dose
response relationship with the irradiance of phototherapy applied.
And may be favored by use of light of a longer wavelength than that
of conventional phototherapy(36).
1.7.1.3. The optimal dose of phototherapy:
The efficacy of phototherapy depends on the dose and
wavelength of light color used, and the proportion of the infants
surface area to which it is applied. The dose administered is
conventionally
expressed
in
terms
of
spectral
irradiance
MW/cm2/nm. (4) The dose applied to the skin, ideally 5 to 10 spectral

irradiance, doses of less than 3 to 4 spectral irradiance produce
inefficient photo conversion where as the effectiveness of doses
greater than 10 to 12 uw/cm2/nm. is limited by a plateau in the
photoconversion response(11). However new studies proved that high
intensity phototherapy used when indirect bilirubin level approach
those need exchange transfusion, such therapy include special
fluorescent tubes; placing within 15 20 cm of the infant and with 2030 spectral irradiance,(2) or by using double phototherapy system
(conventional and fiberoptic phototherapy in the same time).
1.7.1.4. Conventional phototherapy:
By using over head phototherapy units, with white day light
lambs, blue, green or combination of two color. Green light
penetrated skin better but clinically it's proved not more efficient than
white or blue florescent tube(9,36).
Pure blue light is poorly tolerated by staff and can mask
cyanosis in a sick infant; combination of white light and blue light has
proved more acceptable (4).
However, in other study that compare between the efficacy of

fluorescent green light and that of blue light phototherapy, in the
treatment of full-term infants with hemolytic disease and jaundice,
caused by ABO incompatibility. Resulted in no statistically significant
difference in the rate of serum bilirbin photo degradation between the
two groups after treatment (36).
In developing countries where the cost of blue lamps may be
prohibitive as the case in Sudan, efficient phototherapy is
accomplished with white lamps (37).
1.7.1.5. Fibreoptic photo therapy:
Newly developed systems for delivering phototherapy via
body pad or wrap (blanket), have made its application more versatile.
These devices are likely to gain greater acceptance in the context of
healthily term infants nursed without eye pads and alongside their
mothers.
Trials have shown fibreoptic phototherapy to be as effective
as conventional phototherapy in preterm infants but less so in term
infants (4).
The fibreoptic pad device can, however be put to greater
advantage in combination with a conventional light unit to provide
double phototherapy, that used in high intensity phototherapy(38). This

type of phototherapy inspite of the fact that it present world wide, in
Sudan it dose not exist.
Studies show the advantages of fibreoptic phototherapy units
versus conventional phototherapy as follows:
1-
Low risk of overheating the infants.
2-
No need for eye shields.
3-
Ability to deliver phototherapy with infant in a bassinet

next to the mothers bed.
4-
Simple deployment for home phototherapy.
5-
When combined with overhead phototherapy units large

surface area is irradiated(39).
1.7.1.6. Effective phototherapy:
The therapeutic effect depends on the light energy emitted in
the effective range of wavelengths, The distance between the lights
and the infants. The amount of the skin exposed, The duration of
phototherapy, and gestational age as well as the rate of hemolysis.
Dark skin doesnt reduce the efficacy of phototherapy(2).
1.7.1.7. Side effect of phototherapy:
As phototherapy is valuable, easy, and effective, but its not

without risks, the following are possible side effects.
Insensible water loss may occur, but newer data suggest that
this is not as important as previously believed. So fluid status
should be evaluated and supplementation may be needed.
Phototherapy may be associated with loose stools so fluid
supplementation may be needed.
Retinal damage has been observed therefore covering eyes
of infant undergoing phototherapy should be routine.(40,41)
The combination of phototherapy and hyperbilirubinemia can
produce DNA strand breakage and other effects on cellular
genetic materials; therefore, the issue of gonadal shielding may be
moot.
Skin blood flow increases during phototherapy in premature
and this increases the incidence of patent ductus arteriosus has
been reported.
Hypoglycemia also appears to be more common in
premature infants under phototherapy lights.
1.7.2. Exchange transfusion:
Exchange transfusion remain necessary for infants who fail to

respond to adequate phototherapy, or who present late with bilirubin
levels in excess of a given value for phototherapy.
In the latter case the infant should be placed under double
phototherapy, pending the availability of blood for the exchange.
Attention should also be paid to correcting disturbances of any
underlying infection.
Symptoms
and
signs
characteristic
of
acute
bilirubin
encephalopathy is an absolute indication for exchange transfusion.(4)

This widely accepted treatment should be repeated as
frequently as necessary to keep indirect bilirbin level in the serum
under those noted in table 1.A and 1.B for term and preterm babies.(2)
Other indications of early exchange transfusion:
1-
Cord indirect bilirubin more than 5 mg/dl.
2-
Cord hemoglobin less than 10g/dl.
3-
Postnatal increase in bilirubin more than 1 mg /dl/hr.
4-
Anemia with hemoglobin 10 to 12 g/dl plus postnatal

increase in bilirubin more than 0.5 mg/dl/hr (11).
In addition to controlling the existing hyperbilirbuinemia, exchange

transfusion also washes out about one third of the anti D anti body
in the neonatal circulation.
A two-volume exchange, will remove 35 90% of the infants
circulating Rh-D positive cells, which would otherswise contribute to
the bilirubin pool, but only 25% of the infants total bilirubin, because
a large part of the total bilirubin level may rapidly rebound to 70- 80%
of the pre-exchange values(4).
Blood chosen for the exchange should be ABO compatible,
Rh negative, negative for the antigen responsible for the hemolytic
disease, and cross matched against the mothers blood. Irradiated
citrate phosphate dextrose blood is prepared as whole blood, or
reconstituted whole blood (red cells suspended in saline solution,
albumin or plasma) with hematocrit of 40 to 50% and warmed.
Potential
complications
of
exchange
transfusion
include
hypocalacemia, hyper-or hypoglycemia, thrombocytopenia, dilution

coagulopathy, neutropenia, disseminated intravascular coagulation,
umbilical veins and or arterial thrombosis, necrotizing enterocolitis,
and infection.
Despite advances in the management of critically ill newborn

infants, morbidity and mortality associated with exchange transfusion
remain high (12).
1.7.3. Other therapeutic considerations:
Medications like Phenobarbital in low doses, stimulate the
conjugating enzymes, and the hepatic excretory system for bilirubin.
Thus,
infants
with
family
history
of
significant
neonatal
hyperbilirubinemia or those with contraindications to exchange

transfusion may benefit from the maternal or early neonatal
administration of Phenobarbital in low doses, usually lower than
would be required to achieve therapeutic level for seizure control.
Enterohepatic circulation of bilirbin can be reduced by feeding
agar or charcoal to the newborn.
A new therapy focuses on the inhibition of bilirubin formation
from its hemoglobin precursor, called tin proto- porphyrin is also in
use now(6).
1.8. Kernicterus:
Severe hyperbilirubinemia could result in kernicterus. this
condition is characterized by bilirubin staining of the basal ganglia
and involves diffuse neuronal damage, which results in severe

neurologic sequel.
Kernicterus rarely occurs with bilirubin levels lower than 20
mg/dl but typically occurs when the level exceeds 30 mg/dl. When
levels are between 20 and 30 mg/dl concomitant conditions such as
prematurity and hemolytic disease may increase the risk of
kernicterus.
Clinically, bilirubin encephalopathy progresses through three
phases. In the first 2 to 3 days the infant is lethargic and hypotonic
and sucks weakly. Progression is marked by hypertonia especially of
the extensor muscles, arching, opsthotonic posturing, fever, seizures,
and high pitched crying. in the final phase, the patient is hypotonic for
several years, then gradually becomes hypertonic.
Affected children have marked developmental and motor
delays in the form of choreoathetoid cerebral palsy. Mental
retardation may also be present. Other are sequel includes extra
pyramidal disturbances, and auditory abnormality.(8)
JUSTIFICATION
Sixty percent of term babies and 80% of

preterm babies develop jaundice, so effective
treatment
is
very
important
to
prevent
Kirnicterus.
Fluorescent daylight lamps that are used
now, give white light spectrum, and they are
less costly compared with blue light spectrum,
which need a special tube. However, bilirubin
absorbs light maximally at the blue-green
spectrum, thus not all the white light spectrum
is effective, so comparison between the two
sources of light needs to be made.
No similar study has been published in our
country.
OBJECTIVES
To evaluate the effectiveness of white light

spectrum
phototherapy
in
reducing
unconjugated serum bilirubin, compared with

blue light spectrum phototherapy.
To
evaluate
using
phototherapy
in
management of neonatal jaundice in Sudanese

patients.
2. METHODOLOGY
2.1. Study design:

This is a prospective comparative hospital based study.
2.2. Study area and duration:

This study was conducted at the Nursery Unit at Omdurman
Maternity Hospital, in the period January 2003 to September 2003.
2.3 Study population:

All newborns admitted to the hospital during the period of the
study (80 newborns) who presented with jaundice for phototherapy,
according to their serum bilirubin and gestational age.
2.4 Inclusion criteria:

Full term newborns admitted to the mentioned hospital who
had clinical jaundice and where planned for phototherapy treatment,
according to screening test of unconjugated serum bilirubin, which
ranged between (11-20 mg/dl), without considering the cause of
hyperbilirubinemia.
2.5 Exclusion criteria:

Preterm babies less than 37 weeks gestation.
Active hemolysis indicated by sudden drop of hemoglobin or
increase of serum bilirubin more than 5-mg/dl/24 hrs.
Patients waiting for exchange transfusion.
2.6 Tools and methodology:

2.6.1 Consent:
Verbal consent was taken from the administration of the
hospital, treating doctors and from parents of every newborn.
2.6.2 Questionnaire:
A questionnaire (appendix) was designed, containing data
regarding the mother age, residence, and blood group. Also it
contains past obstetrical history, neonatal deaths, and information
about the newborn weight, blood group, serum bilirubin, Hb% before
and after phototherapy, Coombs test were recorded. Any other
investigations for the cause of jaundice were also recorded.
Examination was done recording the abnormal symptoms
and signs other than jaundice, and if there were any congenital
anomalies.
2.6.3 White-light system:

Locally made machine with overhead fluorescent daylight
lamps were used. Adjusted to give the optimal dose of phototherapy,
which equals 10 spectral irradiance, after consulting the Department
of Physics, Faculty of Science in the University of Khartoum.
2.6.4 Blue-light system:
Special machine from Drger Medizintechnic Company In

Germany, using over head fluorescent blue lamp that gives 10
spectral irradiance was used in the study.
Constants in the study:
1- The dose of phototherapy in white and blue light system was the
same, 10 spectral irradiance considering the intensity and
distance of light source.
2- Frequency and duration of phototherapy in both groups were the
same.
3- Gestational ages, all were term newborns.
2.6.5 Application of phototherapy:
After fulfillment of selection criteria, one patient was put in white light system, the other in
blue light system and so on alternatively till the end of the study.
Phototherapy was applied continuously, infants were kept naked except for eye patches, and
facemask. The babies were turned every two hours for maximum skin exposure. Babies were removed
from phototherapy for feeding, and to let the baby and the mother enjoy visual and tactile contact, for
one hour every 4 hours. Patients were hydrated well, orally or I.V as the daily requirement plus 30% of
the body weight, antibiotic was given if indicated.
The effect of phototherapy is followed over a period of 48

hours, by doing total serum bilirubin and its fractions on day zero
(as base line), day I, day II of phototherapy, Hb also was done
serially to exclude active hemolysis. Temperature, color of the
skin and eyes, respiratory rate and heart rate, feedings were
checked. Complications of phototherapy were also checked.
2.6.6 Methods of blood collection:
Blood was collected from newborn under aseptic condition as
far as possible by femoral sampling. 5 ml of blood were taken initially.
2.5 ml were put in EDTA container for Hemoglobin and reticulocyte
count the other 2.5 ml clotted sample was put in a disposable syringe
for estimation of blood group and Coombs test, and serum bilirubin.
also 1 ml of blood was taken from the mother as clotted sample for
checking her blood group.
2.6.6.1 Serum bilirubin:
This was done by reagent kit from Spinreact Company, for in
vitro quantitative determination of total and direct bilirubin in serum.
The principle is that bilirubin react with diazotized sulphanilic acid to
form an Azo compound, the color of which is measured at 560 580
nm and is proportional to the concentration of bilirubin D.M.A was
used as an accelerator.
Reagent used:
Reagent
1:
for
hydrochloric acid.
direct
bilirubin,
sulphanilic
acid
and
Reagent 2: for total bilirubin, sulphanilic acid, hydrochloric

acid and Dimethyl sulfoxide.
Reagent 3: Sodium nitrite.
Procedure:
Reagent
Total blank
Total
Direct blank
Direct
test
test
R1 Direct bilirubin
1.5 ml
1.5 ml
R2 Total bilirubin
1.5 ml
1.5 ML
R3 Sodium nitrite
50L
50L
100L
100L
100L
100L
Sample
Mixed and wait for 5 minutes at room temperature, then

calculate concentration with a fixed factor (given by the
manufacture).
Total bilirubin (mg/dl) = Total O.D Total blank O.D 19.1.
Direct bilirubin (mg/dl) = Direct O.D Direct blank O.D 15.
mg/dl 17.1 = mol/L.
Linearity of the method was given up to 15mg/dl, if greater,
dilute the sample with saline solution and multiply by the dilution
factor.
Quality control:
To ensure adequate quality control we used commercial

control material with each batch, and this checked both the
instrument and the reagent.
By using normal and abnormal control material from LinearChemicals Company, lypholized material from human serum,
provided for many parameters with range equivelent to (mean 2
SD).
Bilirubin present in the material was light sensitive, so stored
in the dark, if it's reading out of the range provided, the whole batch
was repeated.
2.7. Blood grouping for ABO and Rhesus:

By tube method, in which two drops of blood were added in a
test tube to two drops of antisera were shaked, incubated for 2 hours,
then we looked macroscopically for agglutination, if there is any doubt
looked under the microscope. For Rhesus grouping if no agglutination
we added antihuman immunoglobulin, then incubated in water bath
for 20 minutes, then read macroscopically or microscopically.
Quality control:
The antisera were tested before use by known blood group

cells.
Each batch of grouping was controlled by parallel test setup
using cells of known group.
In each batch of test included Rh +ve and Rh -ve control
samples.
2.8 Coombs test:

Direct Coombs test from clotted sample, put in test tube and
washed by normal saline three times to wash antibodies, then one
drop of Coomb's reagent was added to one drop of cells in the test
tube and incubated for two hours and read macroscopically or
microscopically. If agglutination occurred is said to be positive.
Quality control:
The reagent was tested before used with a known positive
and negative samples.
In every batch of test we had included known Coomb's
positive and negative samples.
2.9 Haemoglobin testing:
Blood was taken in a container, which contains ethylediamine
tetra-acetic acid (EDTA). 0.02 ml of blood was added to 5 ml of
Drabkin solution. Drabkin solution consists of potassium ferric

cyanide, potassium cyanide, and potassium phosphate. and after 5
minutes read by colorimeter, in which we use a filter of 540
nanaometer. Then we get the exact concentration from a preformed
haemoglobin standard curve, the test was done in a duplicate method
if the difference between them was more than 2 standard deviation,
the result was not accepted.
2.10 Reticulocyte counts:
Brilliant crystal blue stain was used mixed with blood in a
ration of 1: 2 if the patients was markedly anemic, and in ratio of 1:1 if
the patient was not anemic. then incubated for 20 minutes in 37C in
water bath ,and spread in a slide, then dried and read by oil
immersion lens. reticulocyte is then counted in one thousand
erythrocyte. and use the formula.
Reticulocyte % = Number of reticulocyte 100
1000 Erthyrocytes
Normal range 0.2 2%.

2.11 Basis of diagnosis in the study:
a. Diagnosis of neonatal sepsis as a cause of jaundice:
It is difficult to diagnose neonatal sepsis based on clinical

findings and investigations, however, in this study blood culture was
not done. For the diagnosis of septicemia in jaundiced newborn we
depend on the following:
Symptoms:
i- Fever.
ii- Refusal of feedings.
Signs:
i- Temperature > 38.5C.
ii- Umbilical discharge or redness.

iii- Pustules.
iv- Abdominal distension.
v- Peripheral blood picture with high WBC and toxic granulation.
vi-Also we had accepted the diagnosis of the treating consultant.
b. Diagnosis of ABO incompatibility as a cause of jaundice:

This was diagnosed when:
The mother blood group is A,B, or O and the newborn blood group is either B, A or AB
respectively.
Coombs test positive.

Reticulocytosis.
c. Diagnosis of Rhesus incompatibility as a cause of jaundice:
When the mother blood group was Rh. -ve, and the baby was
Rh. +ve
Coombs test positive.
Reticulocytosis.
d. Diagnosis of exaggerated physiologic jaundice:
Normally physiologic jaundice not reach such level that need
phototherapy, so exaggerated physiologic jaundice is said to be
when:
Jaundice appeared in the second or third day.
Peaking between the second and fourth days.
Decreasing between fifth and seventh days.
Not persisting after tenth to fourtenth days.
Serum bilirubin does not exceeds 15 mg/dl.
Exclusion of all other causes.
e. Diagnosis of jaundice in infants of diabetic mothers:
Such a diagnosis is said to be when the mother is a known
diabetic.
f. Jaundice due to cephalohematoma:
Such a diagnosis is said to be if clinically there is Haematoma
and no other identifiable cause of jaundice.
g. Downs syndrome with jaundice:

If there were features of trisomy 21.
h. Undiagnosed jaundice:
In this study the newborn is said to be undiagnosed for the
cause of jaundice if the newborn did not fit with any of the diagnoses
listed and the cause of jaundice in this case may be a metabolic or
any other cause which is out of the scope of this study.
3. RESULTS
3.1. Socio-demographic characteristics of the studied population:

3.1.1. Sex characteristic of the studied population:
A total of 80 newborns who presented with jaundice were

studied, 48(60%) were males and 32(40%) were females (Figure 1 &
Table 1).
3.1.2. Distribution of studied population according to home of origin:
The majority, 27 (33.8%) of the studied newborns were from
the West of the Sudan, 22(27%) were from the North, 18(22.5%) from
the central Sudan, 6(7.5%) from South and 7(8.8%) from East of the
Sudan (Figure 2 & Table 2).
3.1.3. Maternal age and parity:
Among the studied population, the majority, 57(71.3%) had
maternal age between (20-30 years), 18(22.5%) with maternal ages
between (31- 40 years), 3 (3.8%) had maternal age more than 40
years and only 2(2.5%) with maternal age less than 20 years (Table 3
& Figure 3).
Regarding the parity state of the mothers, 33(41.3%) were
multigravidae, 28(39.0%) were primigravidae, 19(23.8%) were grand
multipara (Figure 4 & Table 4).
to sex
Sex
Frequency
Percentage
Males
48
60%
Females
32
40%
Total
80
100%
Female
40%
Male
60%

to home of origin
Home origin in Sudan
Frequency
Percentage
West
27
33.8%
North
22
27.4%
Central
18
22.5%
East
8.8%
South
7.5%
Total
80
100%
35%
33.80%
30%
27.4%
25%
22.50%
20%
15%
8.80%
7.50%
10%
5%
0%
West
North
Central
East
South
Home origin

to maternal age
Age (in years)
Frequency
Percentage
< 20
2.5%
20 - 30
57
71.2%
31 - 40
18
22.5%
> 40
3.8%
Total
80
100%
80%
71.20%
70%
60%
50%
40%
30%
22.50%
20%
10%
3.80%
2.50%
0%
< 20
20--30
31--40
Maternal age (in years)
> 40

to parity of the mother
Parity
Frequency
Percentage
Primigravidae
28
35.0
Multigravidae
33
41.2%
Grand multiparaous
19
23.8%
Total
80
100%
Grandmultipara
23.8%
Multigravida
41.2%
Primigravida
35%
3.2. Clinical factors that affect the studied population:

3.2.1. The weight characteristic of the studied population:
Fifty (62.5%) of studied population had normal birth weight
(2.6 -3.5 kg), 18 (22.5%) had low birth weight (2-2.5kg), only one
case (1.3%) had birth weight less than 2 kg, and 4(5.0%) had birth
weight above 4 kg (Table 5 & Figure 5).
3.2.2. Mode of delivery:
Thirty (37.5%) were delivered by Em C/S (22.5%), El C/S,
28(35.0%) were normal vaginal delivery and 4(5%) were delivered by
using forceps (Figure 6 and Table 6).
3.2.3. Date of onset of jaundice:
Among the studied newborn 62(77.5%) had jaundice, which
appeared on the second or third day.
Seventeen (21.3%) in the
fourth to seventh day and one case (1.3%) after first week, no case
had jaundice in the first day (Figure 7 & Table 7).

to weight of newborns
Weight (Kg)
Frequency
Percentage
<2
1.3%
2 - 2.5
18
23%
2.6 - 3.5
50
63%
3.6 - 4
8.7%
>4
5.0%
Total
80
100%
70%
63%
60%
50%
40%
30%
23%
20%
8.70%
10%
5.00%
1.30%
0%
<2
2 - 2.5
2.6 - 3.5
Weight of the baby (kg)
3.6 -4
>4

to mode of delivery
Mode
Frequency
Percentage
Emergency Caesarean section
30
37.5%
Elective Caesarean section
18
22.5%
Normal vaginal delivery
28
35.0%
Forceps
5.0%
Total
80
100%
40%
37.50%
35.00%
35%
30%
25%
22.50%
20%
15%
10%
5.00%
5%
0%
Emergency C/S
Elective C/S
Normal vaginal
delivery
Forceps
Mode of delivery

to time of onset of jaundice
Time (days)
Frequency
Percentage
0%
2-3
62
77.5%
4-7
17
21.2%
>7
1.3%
Total
80
100%
77.50%
80%
70%
60%
50%
40%
30%
21.20%
20%
10%
1.30%
0.00%
0%
1
2--3
4--7
>7
Time of onset of jaundice (days)
3.2.4. Blood group of the mother and the baby:

Among the studied newborn, 12(15%) had Rh negative
maternal blood group and 68(85%) had Rh positive blood group.
The distribution of ABO group shown in Table 8. In the

studied newborn, 7(8.75%) had Rh negative blood group, and
73(91.25%) had positive blood group (Table 9).
Table 8: Distribution of studied population according to mother's

blood group
Blood group
Frequency
Percentage
A +ve
12
15.0%
A -ve
2.5%
B +ve
11
13.8%
B -ve
3.8%
AB +ve
2.5%
AB -ve
1.3%
O -ve
7.5%
O +ve
43
53.8%
Total
80
100%
Table 9: Distribution of studied population according to blood

group of the baby
Blood group
Frequency
Percentage
A +ve
14
17.5%
A -ve
1.3%
B +ve
22
27.5%
B -ve
2.5%
AB +ve
3.8%
AB -ve
2.5%
O -ve
2.5%
O +ve
34
42.5%
Total
80
100%
3.2.5. Serum bilirubin levels:

Table 10 shows the distribution of total serum bilirubin level
before phototherapy was done, as a base line in the first day. Twentyfive (31.3%) had a level between (12.1 -14 mg/dl), 22 (27.5%) had a
level (14.1 -16 mg/dl), 15 (18.8%) had a level between (16.1 -18
mg/dl), 12(15%) had a level between (18.1 - 20 mg/dl). Only one case
had a bilirubin level more than 20 mg/dl.
Figure 11 and Table 11 show the distribution of indirect

serum bilirubin level before phototherapy was done as a base line in
the first day. Nine (11.3%) of the studied group had a level between
(10.1 - 12 mg/dl), 28 (35.0%) had a level between (12.1 -14mg/dl),
19(23.8%) had a level between (14.1 -16 mg/dl), 17(21.3%) had a
level between (16.1 - 18 mg/dl) and only 7(8.8%) had a level between
(18.1 - 20 mg/dl).
Figure 12 and Table 12 show the distribution of indirect
serum bilirubin level after 48 hours of phototherapy, 29(36.3%) had a
level between (10.1 -12 mg/dl), 18(22.5%) had a level between (8-10
mg/dl), 13(16.3%) had a level between (12.1-14 mg/dl), 11(13.8%)
had a level between (14.1 - 16 mg/dl).
Nine (11.3%) failure of phototherapy were treated with
exchange blood transfusion.
Tables 13 and 14 show distribution of reduction of indirect
serum bilirubin in the first 24 hours and 48 hours of phototherapy
respectively, 9(11.3%) failed to respond to phototherapy, so treated
with exchange transfusion.
Table 10: Distribution of total serum bilirubin before Phototherapy

Serum bilirubin (mg/dl)
Frequency
Percentage
12.1 - 14
25
30.3%
14.1 - 16
22
25.2%
16.1 - 18
25
28.2%
18 - 20
12
15.0%
20 - 22
1.3%
Total
80
100%

before phototherapy
Frequency
Percentage
10.1 - 12
11.2%
12.1 - 14
28
36%
14.1 - 16
19
24.8%
16.1 - 18
17
21.2%
18.1 - 20
8.8%
Total
80
100%
40%
36%
35%
30%
24.80%
25%
21.20%
20%
15%
11.20%
8.80%
10%
5%
0%
10.1 - 12
12.1 - 14 14.1 - 16 16.1 - 18 18.1 - 20

Indirect serum bilirubin level

after 48 hours of phototherapy
Frequency
Percentage
8 -10
18
22.3%
10.1 - 12
29
36.3%
12.1 - 14
13
16.3%
14.1 - 16
16
13.8%
Not done*
11.3
Total
80
100%
* not done due to failure of phototherapy.
22.3%
35%
30%
23.80%
25%
21.30%
20%
15%
11.30%
11.30%
10%
5%
0%
8--10
10.1 -12
12.1 -14
14.1 -16 Not done
Indirect serum bilirubin level

Reduction of serum bilirubin (mg/dl)
Frequency
Percentage
0.5
3.8%
0.8
1.3%
1.0
15
18.8%
1.1
3.8%
1.2
1.3%
1.3
3.8%
1.4
2.5%
1.5
7.5%
1.8
7.5%
1.9
2.5%
15
18.8%
2.1
3.8%
2.2
7.5%
2.6
1.3%
2.7
2.5%
2.9
1.3%
1.3%
Not done*
11.3%
* Not done (failure of phototherapy).

Table 14: Distribution of indirect serum bilirubin reduction after the
first 48 hours of phototherapy
Reduction of serum bilirubin (mg/dl)
Frequency
Percentage
1.4
1.3%
1.6
1.3%
1.8
1.3%
2.0
10.0%
2.2
8.8%
2.3
1.3%
2.4
5.0%
2.5
10
12.5%
2.6
2.5%
2.7
1.3%
2.8
3.8%
3.0
10
12.5%
3.2
5.0%
3.3
7.5%
3.4
1.3%
3.5
7.5%
3.7
1.3%
2.5%
4.5
1.3%
Not done*
11.3%
* Not done (failure of phototherapy).

3.2.6. Direct Coomb's tests:
Among the studied population 27(33.8%) had a positive
Coomb's tests, and 53(66.2%) had a negative Coomb's test (Figure
15).
3.2.7. Etiology of jaundice:
thirty-seven
(46.3%)
of
the
studied
population
had
septicemia, 20(25.0%) had ABO incompatibility, 8(10%) had Rh

incompatibility, 5(6.3%) had exaggerated physiologic jaundice,
3(3.8%) had diabetic mother, only one case had a feature of Down's
syndrome (Table 16 and Figure 16).
Figure 15: Distribution of direct Coomb's test result in
studied population
Positive
33.8%
Negative
66.2%
Table and Figure 16: Distribution of causes of jaundice among

studied groups
Causes
Frequency
Percentage
Septicemia
37
46.3%
ABO incompatibility
20
25.0%
Rh. incompatibility
10.0%
Cephalohaematoma
3.8%
Diabetic mother
3.8%
Down's syndrome
1.3%
Undiagnosed
3.8%
Exaggerated physiologic jaundice
6.3%
Total
80
100%
Exaggerated physiologic
jaundice
Undiagnosed
Down's syndrome
Diabetic mother
Cephalohaematoma
Rh. incompaibility
ABO incompatibility
Seticemia
0%
10%
20%
30%
40%
50%
3.2.8. Birth trauma:

Three (3.8%) had cephalohematoma, all of them were
forceps delivery.
* Presence of fever and antibiotics administration:
Fifty-five (68.8%) among the studied newborns developed
fever and 25(31.2%) had no fever.
Fifty-eight (72.5%) of the studied population were given
antibiotics and 22(27.5%) were not given antibiotics.
3.2.9. Haemoglobin level:

Twenty-six (32.5%) had Hb level between (15.1 -17 mg/dl),
23(28.8%) had HB level between (12.1 -15 g/dl), 16(20.0%) had Hb
level between (17.1 -20% g/dl), 12(15.0%) had Hb level between
(10.1 -12 g/dl. Only 3 cases (3.8%) had Hb level less than 10 g/dl
(Figure 17).
Table 17: Distribution of the studied population according to
Haemoglobin level
Hb (g/dl)
Frequency
Percentage
< 10
3.8%
10 - 12
12
15.0%
12.1 - 15
23
28.8%
15.1 - 17
26
32.5%
> 17
16
20.0%
3.3 Comparison between those treated with blue light

and those with white light phototherapy:
3.3.1 Causes of jaundice in the two groups:
37 had septicaemia, among which 18(48.6%) were treated under
while light, and 19(51.4%) were treated under blue light phototherapy.
20 had ABO incompatibility, 9(45.0%) were treated under the white

light and 11(55.0%) were treated under blue light phototherapy.
8 had Rh. in compatibility, 3(37.5%) were treated under white light
and 5(62.5%) were treated with blue light.
3 cases had cephalohaematoma, two were treated with white light
and one case with blue light.
3 cases were of diabetic mother, two of them treated under white
light and one under blue light.
5 cases had exaggerated physiologic jaundice, three were treated
under white and 2 under blue light.
Statistical test revealed that X2 = 2.927, df = 7, P = 0.892.
So the difference between the two groups is not statistically
significant (Table 18).
Table 18: Comparison between white light and blue light treated
neonates in relation to the cause of jaundice
Causes
Septicemia
White light
Blue light
Total
18
19
37
ABO incompatibility
11
20
Rh. incompatibility
Cephalohaematoma
Diabetic mother
Down's syndrome
Undiagnosed
Exaggerated physiologic jaundice
Total
40
40
80
X2 = 2.927,
df = 7,
P = 0.892.
3.3.2. Level of indirect serum bilirubin (base line) among the two
groups:
Table and figure 19 show the level of indirect serum bilrubin
in neonates treated under white light compared with those treated
under blue light.
Statistical tests result in X2 = 2.341, df = 4, P =< 0.673.
So there is no statistically significant difference between the two
groups.
Table 19: Comparison between white and blue light treated
neonates in relation to the level of indirect SB (baseline)
Level of SB
Total
Type of light used
(mg/dl)
White
Blue
10.1 - 12
12.1 - 14
13
15
28
14.1 - 16
11
19
16.1 - 18
11
17
18.1 -20
Total
40
40
80
P = 0.673
15
16
13
14
11
12
10
8
6
11
White
Blue
5
4
2
0
10.1 - 12
12.1 - 14
14.1 - 16
16.1 - 18
Serum bilirubin level (mg/dl)
18.1 -20
3.3.3. Failure rate in white light compared with blue light

phototherapy:
Table 20 shows that 9(11.3%) of the studied neonates failed
to respond to phototherapy, so treated with exchange blood
transfusion, 5 of them treated under white light, and 4 treated under
blue light phototherapy.
Failure rate in white light equal five cases out of fourty
(1 in 8), while failure rate in blue light four cases out of fourty
(1
in10).
Table 20: Response to phototherapy among

the studied population
Type of light used
Failure
Response
Total
White
35
40
Blue
36
40
Total
71
80
3.3.4. Reduction of indirect serum bilirubin in white light

compared with blue light phototherapy:
Mean reduction of indirect Serum bilirubin in the first 24 hours

in white light treated neonates was 1.27 mg/dl, while in blue light
was 1.62 mg/dl.
Maximum reduction achieved in the first 24 hours under white
light was 2.7 mg/dl, while under blue light was 3 mg/dl.
Statistical test, based on two independent samples, t. test (P
= 0.038), which shows statistically significant difference between
mean reduction in white light compared with blue light (Table 21a,
and figure 21).
Table 21a: Statistical test comparing reduction of indirect S.B in

white and blue light treated neonates in the 1st 24 hours
Statistical result
Type of light used

White
Blue
Mean (mg/dl)
1.27
1.618
Std. Error
0.116
0.118
2.7
1.036
1.379
Maximum reduction (mg/d)

Minimum reduction
95% confidence interval for the mean:
Lower bound
Upper bound
1.504
1.856
P < 0.05
Mean reduction of indirect serum bilirubin in the first 48 hours

of phototherapy under white light was 2.08 mg/dl, while in blue
light was 2.74 mg/dl, the maximum reduction achieved under white
light was 3.7 mg/dl, while under blue light was 4.5 mg.
Statistical test based on two independent samples t.test (P =
0.006), which statistically highly significant difference between the
two groups (Table 21.b & Fig. 21).
Table 21b: Statistical test comparing reduction of indirect S.B in

white and blue light treated neonates in the 1st 48 hours
Statistical result
Type of light used

White
Blue
Mean (mg/dl)
2.08
2.735
Std. Error
0.160
0.168
3.7
4.5
Maximum reduction (mg/d)
Minimum reduction
Lower bound
1.756
2.396
Upper bound
2.404
3.074
95% confidence interval for the mean:
P < 0.05
Fig. 21: Mean reduction of indirect serum bilirubin during the 1st
48 hours in blue and white light
Reduction in S.B (Mg/dl)
3
Blue
2.5
White
2
1.5
1
0.5
0
0
24
48
Time (in hours)
3.4 Clinical factors affect response to phototherapy:

3.4.1 Cause of jaundice and response to phototherapy:
Table 22 shows causes of jaundice and their response to

phototherapy. Statistical test result in X2 = 7.134, P = 0.415, so there
is no statistically significant difference. This means response to
phototherapy does not depend on the cause of jaundice.
Table 22: Causes of jaundice in relation to response

to phototherapy
Causes
Repose to
Failure of
Total
phototherapy
phototherapy
Septicemia
35
27
ABO incompatibility
17
20
Rh. Incompatibility
Cephalohematoma
Diabetic mother
Down's syndrome
Undiagnosed
Total
71
80
3.4.2. Level of indirect serum bilirubin (base line) and response

to phototherapy:
Nine (11.3%) of the studied population failed to response to
phototherapy, all of them presented with indirect serum bilirubin
above 16 mg/dl. Statistical tests results in X2 = 52.87 P< 0.05 shows
statistically significant difference in responder
and non responder
groups in relation to the serum bilirubin base-line level, so response

to phototherapy depends on base line serum bilirubin (Table 23).
Table 23: Level of indirect serum bilirubin (base-line) in

relation to response
Level of serum bilirubin
Response to
Total
phototherapy
Yes
No
10 - 12
12.1 - 14
28
28
14.1 - 16
19
19
16.1 - 18
10
17
18.1 - 20
Total
71
80
P < 0.05
3.5. Phototherapy versus exchange blood transfusion:

Nine (11.3%) of the studied population treated with exchange
blood transfusion with double of their whole blood volume and
showed excellent response with mean reduction of indirect serum
bilirubin
(5.944 mg/dl) after only one time transfusion. While the
mean reduction in serum bilirubin by phothotherapy (blue or white

light) was 2.40 after 48 hours exposure (Table 24).
Table 24: Reduction in serum bilirubin versus exchange

blood transfusion
Mean
Maximum
Minimum
reduction
reduction
reduction
(mg/dl)
(mg/dl)
(mg/dl)
Phototherapy (48 hrs)
2.40
4.5
Exchange blood transfusion
5.944
4.5
Type of treatment
3.6. Clinical factors that have effect on the etiology of

jaundice among the studied population:
3.6.1. Presence of fever and the cause of jaundice:
All neonates with septicemia had fever.
55% of ABO incompatibility neonates had fever.
25% of Rh. Incompatibility neonates had fever.
20% of neonate with exaggerated physiologic jaundice had
fever.
3.6.2. Mode of delivery and aetiology of jaundice:
Three
(3.75%)
of
the
studied
population
had
cephalohematoma, all of them were delivered by using forceps (Table

24).
Table 25: Mode of delivery in relation to cause of jaundice

Causes
Em C/S
EL C/S
NVD
Forceps
Total
Septicemia
11
16
37
ABO incompatibility
20
Rh. Incompatibility
Cephalohematoma
Diabetic mother
Down's syndrome
Undiagnosed
Total
35
18
80
28
3.6.3. Level of indirect serum bilirubin in relation to the cause of

jaundice (Table 25):
Four (20%) of ABO incompatibility cases presented with high

level of indirect serum bilirubin of more than 18 mg/dl.
Two (25%) of the Rh. incompatibility presented with high level

of indirect serum bilirubin of more than 18 mg/dl.
One (33%) of cephalohematoma cases presented with high

level of indirect serum bilirubin of more than 18 mg.
All other cases presented with indirect serum bilirubin level

below 18 mg/dl.
Table 26: Level of indirect serum bilirubin (S.B) base-line in
relation to causes of jaundice
Causes
Septicemia
S.B level < 18
S.B level > 18
Total
37
37
ABO incompatibility
16
20
Rh. Incompatibility
Cephalohematoma
Diabetic mother
Down's syndrome
Undiagnosed
Total
73
80
3.6.4. Etiology of jaundice and failure of phototherapy in the

studied population:
Some etiological agent presented with high level of serum

bilirubin and most likely to reach the level of exchange blood
transfusion more than other cause.
Two (5.4%) of cases with septicemia treated with exchange

blood transfusion after failure of phototherapy.
Three (15%) of cases with ABO treated with exchange blood

transfusion.
Two (25%) of cases with Rh. incompatibility treated with

exchange blood transfusion.
One (33%) of undiagnosed group treated with exchange blood

transfusion.
One (33%) of diabetic mother treated with exchange blood

transfusion.
Neonates
with
cphalohematoma
and
exaggerated
Down's
physiologic
syndrome
showed
jaundice,
complete
response to phototherapy.
3.6.5. Final outcome of the studied population:
All patients treated under phototherapy developed loose stool

and increase frequency. No other complications developed.
Two (2.5%) of patients died, one treated with blue light, the
other under white light, both of them had septicemia.
Seventy-eight (97.5%) of studied population discharge well

after treatment with phototherapy or exchange blood transfusion
(Figure 25).
Fig. 22: Final outcome of the studied population
Died
2.5%
Discharged
well
97.5%
4. DISCUSSION
This study compared white light versus blue light phototherapy
in newborn with jaundice in terms of reduction of indirect serum
bilirubin after 24 hours and 48 hours exposure to light.
Comparing the two studied group there were no statistically
significant difference regarding the cause of jaundice and indirect
serum bilirubin done initially before exposure, however, this study
showed that response to phototherapy depended on initial serum
bilirubin level, but not on the cause of jaundice and this agrees with
Alfaky' study and Wu, et al in China.(42,43)
It was clear in this study that, the mean reduction of indirect
serum bilirubin achieved under blue light (1.62 mg/dl) was greater
than that achieved under white light group (1.27 mg/dl), in the first 24
hours, however, more reduction had been achieved after 48 hours
exposure of blue light with a mean of 2.73 mg/dl versus 2.08 mg/dl in
white light phototherapy group. These results agree with Carvelho, et
al in Brazilia,(44) who reported that, blue light is superior to white light
in treating neonatal hyperbilirubinemia.
However, Tan, et al in Singapore stated that standard white
light phototherapy is usually adequate, but blue light phototherapy
would be preferable where a more rapid and greater response is

desirable,(45) but Danzelli, et al in Italy reported that, white light is less
effective than blue light in a study done in low birth weight
neonates.(46)
Amato and Inaebnit studies in Switzerland reported that, green
light phototherapy is also useful, but not preferable to blue light in
treatment of neonatal jaundice,(47) this agreed with a study done at
Saint-Joseph Hospital in France.
Ayyash, et al at University of Athens Medical School in Greece
comparing blue light phototherapy with green light phototherapy in
treating neonatal jaundice in full term babies reported that no
significant difference was found between the two groups.(48)
Concerning complications of phototherapy, there were no
complications reported in this study apart from loose stools and
increased frequency in almost all neonates up to time of discharge,
and this is comparable to Alfaky's study in Sudan,(43) but late
complications were not checked in this study.
Of the studied newborns, 11.3% received exchange transfusion
after failure of phoyotherapy to produce satisfactory reduction in
serum bilirubin, this is significantly lower than Elfaky (17.9%).(43) This
is probably because preterms were excluded in this study, neonates

with initial serum bilirubin more than 20mg/dl were also excluded.
Regarding failure rate in white light phototherapy were reported
five cases out of fourty (1 in 8), while in blue light group were four out
of fourty (1 in 10). This is a clear difference reflecting that blue light is
superior to white light phototherapy.
Most of the newborn who received exchange transfusion were
those with ABO and Rh incompatibility and this comparable to study
done in Middle-east,(49) Australia and to Alfaky's study in Sudan.(43,50)
Although it is recommended as second line of treatment,
exchange blood transfusion achieved more reduction in serum
bilirubin if compared with phototherapy, but associated complications
limits its use. Although in this study no complications had been
associated with exchange transfusion, this agreed with Alfaky's
result,(43) unlike other studies from America, which showed special
complications associated with exchange transfusion.(51)
This study quoted 46.3% of newborns with jaundice to have
had septicemia, which is higher than a study done recently at
different Khartoum State hospitals.(43) And also higher than another
study done in United Arab Emirates by Jeffirey, et al(52) and Adekunle,
et al.(49) This simply can be explained by that preterm (as a cause of

jaundice) had been excluded in this study, and also because
neonates with serum bilirubin less than the level of phototherapy
were excluded in this study. However, over diagnosing septicemia
may be an issue for discussion, and this strengthened moreover by
the reported tendency to prescribe antibiotic (72.5%) of the studied
group, which can hardly be justified.
ABO incompatibility had appeared in 25% as a cause of
jaundice in this study, which is not far from different studies done in
middle-east,(49) Asia,(53,54) and Africa,(55) but higher if compared with
another study done in Australia.(50)
Concerning Rh. incompatibility that had appeared in 10% as a
cause of neonatal jaundice in this study, which is a bit higher than a
study done by Swar (1981) in Khartoum Teaching Hospital, which
quoted 8.1% Rh. incompatibility as a cause of neonatal jaundice.(65)
Regarding physiologic jaundice in Swar study is much higher
(52.5%) than in this study (6.3%), but this could be partially justified
by the exclusion criteria system in this study, because physiologic
jaundice as reviewed in the literature rarely reaches phototherapy
level,(2) However, another Sudanese study reported 8.5%.(43)
Neonatal jaundice with undiagnosed causes quoted 3.8% in

this study, which was very low if compared with a recent study done
in April (2003) by ElFaky (11.2%) in Sudan.
Regarding infant of diabetic mothers who had developed
jaundice in this study were 3.8%, which agreed with some studies
done in Middle-east,(49) while a bit lower than Elfaky's study (5%).(43)
Cephalohematoma had appeared in 3.8% as a cause of
jaundice in this study, all of them were delivered using forceps and
this comparable to Elfaky's study, reflecting the hazardous practice of
forceps delivery. Also Elfaky's study revealed that, Down's syndrome
as a cause of jaundice is 1%, which agreed with this study (1.3%).
No case had been diagnosed as having jaundice in the first 24
hours, most probably because they presented with initial serum
bilirubin exceeding the level of phototherapy, hence, excluded in this
study, also babies might not be checked early enough to detect slight
jaundice. However, 77.5% had jaundice appeared on second and
third day of life, this high percentage might be due to septicemia
(major cause of jaundice in this study), which appeared in the second
and third day of life.
This study quoted (35%) were normal vaginal delivery, this

probably reviewed to the practice of giving oxytocin before delivery,
as recent studies claimed that.(43) Also four cases (5%) were
delivered
using
forceps,
three
of
them
developed
large
cephalohematoma and relatively high serum bilirubin showed hazard

of forceps delivery.
Significant number of the studied population with a low birth
weight (22.5%), this agree with a study done by Linn, et al (1985)
showed the relation between low birth weight and neonatal
jaundice.(57)
Males with neonatal jaundice predominated females (60%), this
comparable to study done by Jeffiry, Maisels and Elizabeth(52) the
reason is not known.
In this study the majority (97.5%) were improved at time of
discharge with serum bilirubin below 10mg/d and clinically well, while
only 2.5% died, these result were quite acceptable and comparable to
other studies.
Surprisingly all deaths had serum bilirubin less than18mg/dl, so
most likely the cause of death was not related to hyperbilirubinemia.
This hypothesis is strengthened by the fact that all deaths were
diagnosed as having septicemia and had received antibiotics, but

none of them had undergone exchange transfusion.
Finally most of the results in this study agreed with studies
conducted worldwide, however, there were some differences in
results. This could be due to differences in diagnosis and
management of neonatal jaundice in Sudan. Any way, these results
add something to our knowlege in neonatology in Sudan.
CONCLUSION
This study concluded that patients treated under blue light

phototherapy had better outcome than those treated under white
light photothery. Achieving greater reduction in serum bilirubin with
mean reduction of 2.7 mg/l for blue light, and
2 mg/l for white
light phototherapy after 48 hours exposure to light.
More over concluded that failure of phototherapy is less in blue

light than white light treated group, indicating that, blue light is
superior to white light phototherapy.
Also
concluded
that
septicemia
had
significantly
high
percentage among the studied group, this may be due to over

diagnosing septicemia.
In addition, concluded that ABO and rhesus in compatibility still

important causes of neonatal jaundice, reflecting poor screening
and antenatal care programs for Rh incompatibility.
RECOMMENDATIONS
Locally made phtotherapy machine should use blue lamps

instead of white one, which are now available in the market, and
not so much expensive, or using blue filter under the white light to
select a narrow beam of blue light.
Locally made machine should be revised to meet a standard

criteria concerning intensity of light, distance of light source,
duration of phototherapy, and safety of the machine.
Setup and application of guide lines for phototherapy

management, including level of serum bilirubin, gestational age,
weight of the baby, time of onset of jaundice, and strict follow up
system to determine failure of phototherapy early on.
Minimizing forceps delivery as possible as it could be, and

should be done by the most trained personnel.
Promote screening system for ABO and Rh incompatibility

within antenatal care programs.
Diagnosing septicemia and antibiotic prescription in neonatal

jaundice should be revised.
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White Light Versus Blue Light Phototherapy

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UNIVERSITY OF KHARTOUM

White light versus Blue light phototherapy in

A thesis Submitted in partial fulfillment for the requirements of the Degree

I like to express may gratitude and thanks to my supervisor Prof. Abdul-Hafiz

Blood brain barrier

Uridine diphosphoglucuronyl transferase

Haemolytic disease of the newborn

Glucose 6-phosphate dehydrogenase

Toxoplasmosis, others, Rubella, cytomegalovirus herpes

Serum glutamate pyruvate transferase

Serum glutamate oxalate transferase

End-tidal carbon monoxide in breath

American Academy of Paediatrics

Ethyline diamine tetraacetic acid

Elective Caesarean section

Emergency Caesarean section

This is a prospective comparative study conducted at the Nursery Unit at Omdurman

LIST OF TABLES & FIGURES

Table and Figure 2: Distribution of studied population

Table and Figure 3: Distribution of studied population

Table and Figure 4: Distribution of studied population according

Table and Figure 5: Distribution of studied population according

Table and Figure 6: Distribution of studied population according

Table and Figure 7: Distribution of studied population according

Table 8: Distribution of studied population according to mother's

Table 9: Distribution of studied population according to blood

Table 10: Distribution of total serum bilirubin before

Table and Figure 11: Distribution of indirect serum bilirubin

Table and Figure 12: Distribution of indirect serum bilirubin

Table 13: Distribution of indirect serum bilirubin reduction after

Table 14: Distribution of indirect serum bilirubin reduction after

Figure 15: Distribution of direct Coomb's test result in

Table and Figure 16: Distribution of causes of jaundice among

Table 17: Distribution of the studied population according to

Table 19: Comparison between white and blue light treated

Table 20: Response to phototherapy among the

Table 21a: Statistical test comparing reduction of indirect S.B in

Mean reduction of indirect serum bilirubin during the

Table 22: Causes of jaundice in relation to response

Table 24: Reduction in serum bilirubin versus exchange blood

Table 26: Level of indirect serum bilirubin (S.B) base-line in

Final outcome of the studied population

List of tables and figures

INTRODUCTION AND LITERATURE REVIEW

1.3. Bilirubin metabolism

1.3.1. Source of production

1.3.2. Binding and transport

1.3.3. Hepatic uptake

1.3.5. Excretion and enterohepatic circulation

1.4.1. Physiological hyperbilirubinemia

1.4.2. Pathological jaundice

1.5. Clinical consideration

1.6.1. Approach to diagnosis

1.6.2. Total serum bilirubin and its fractions

1.6.3. Other studies

1.7. Treatment of hyperbilirubinemia

1.7.2. Exchange transfusion

1.7.3. Other therapeutic considerations

3.1. Socio-demographic characteristics of the studied population 51

3.3 Comparison between those treated with blue light and

3.4 Clinical factors affecting response to phototherapy

3.5. Phototherapy versus exchange blood transfusion

3.6. Clinical factors that have an effect on the etiology of

INTRODUCTION AND LITERATURE REVIEW