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Original Article

To Study the Prevalence of Glucose 6 Phosphate Dehydrogenase(G6PD)

deficiency in Neonates with Neonatal Hyperbilirubinemia and to
Compare the Course of the Neonatal Jaundice in deficient Versus Non
Deficient Neonates
Rahul Sinha, Badal Sachendra, V. Sabid Syed1, Lakshmi Nair2, B. M. John3

Departments of Background: The enzyme glucose6phosphate dehydrogenase(G6PD) deficiency

Pediatrics and 2Pathology
1
Commandant, Military
Abstract leads to impaired production of reduced glutathione and predisposes the red
Hospital, Jodhpur, Rajasthan, cells to damage by oxidative metabolites causing hemolysis. Deficient neonates
3
Department of Pediatrics, may manifest clinically as indirect hyperbilirubinemia or even kernicterus.
Command Hospital Air G6PD deficiency is the most common enzyme deficiency in humans affecting
Force, Bengaluru, Karnataka, around 400 million people worldwide which presents in neonatal period as
India unconjugated hyperbilirubinemia and is inherited as Xlinked recessive disorder.
It has a high prevalence in persons of African, Asian, and Mediterranean descent.
Materials and Methods: Sample size It was a prospective study conducted in
a Military Zonal Hospital of Jodhpur (Rajasthan India). A total of 400 neonates
with indirect hyperbilirubinemia were screened for G6PD deficiency from May
2014 to April 2016 in there were 165 female and 235 male neonates. The age
of the neonates varied from 2 to 10 days of life. A written informed consent was
obtained. Inclusion criteria All neonates with more than 35 weeks of gestation
with total serum bilirubin >12 mg% were included in the study. Exclusion
criteria All neonates with <35 weeks of gestation and serum bilirubin <12 mg%
and also neonates with direct hyperbilirubinemia, polycythemia, sepsis, ABO/Rh
incompatibility, and physiological jaundice(total serum bilirubin was<12 mg% and
jaundice subsided by day 10 of life) were excluded from the study. Results: The
result analysis showed ten (2.5%) neonates with indirect hyperbilirubinemia were
G6PD deficient. There was a significant statistical difference between G6PD
deficient and nonG6PD deficient group in terms of indirect bilirubin levels,
duration of phototherapy, and gender as G6PD affect only males. However,
there was no difference in terms of onset of jaundice, age and gestational age of
neonates, and reticulocyte count.
Keywords: Glucose6phosphate dehydrogenase, hyperbilirubinemia, jaundice,
neonates

Introduction the reduction of nicotinamide adenine dinucleotide

N eonatal hyperbilirubinemia (defined as a total
serum bilirubin level exceeding 5 mg/dl) is a
frequent problem as neonatal jaundice affects 65% of
fullterm infants and 85% of preterm infants after 24h of
life.[1] The glucose6phosphate dehydrogenase (G6PD)
enzyme is part of the pentose monophosphate shunt.
It catalyzes the oxidation of glucose6phosphate and
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DOI:
10.4103/jcn.JCN_59_16
phosphate to nicotinamide adenine dinucleotide
Address for correspondence: Dr.Rahul Sinha,
Military Hospital, Jodhpur, Rajasthan, India.
Email:drrahul_2000@yahoo.com
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How to cite this article: Sinha R, Sachendra B, Syed VS, Nair L, John BM.
To study the prevalence of glucose 6 phosphate dehydrogenase(G6PD)
deficiency in neonates with neonatal hyperbilirubinemia and to
compare the course of the neonatal jaundice in deficient versus non
deficient neonates. J Clin Neonatol 2017;6:71-4.

2017 Journal of Clinical Neonatology | Published by Wolters Kluwer - Medknow 71

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Sinha, etal.: To study the prevalence of Glucose 6 phosphate dehydrogenase deficiency in neonates with neonatal hyperbilirubinemia
phosphate (NADPH). NADPH maintains glutathione
in its reduced form, which acts as a scavenger for
dangerous oxidative metabolites. The erythrocytes
do not generate NADPH in any other way; they are
more susceptible than other cells to destruction from
oxidative stress. The most common clinical feature
of G6PD deficiency is a lack of symptoms. However,
in symptomatic neonates, the presenting features are
neonatal jaundice and/or acute hemolytic anemia.
Jaundice usually appears by age 14 days, at the same
time as or slightly earlier than physiological jaundice.
The prevalence of neonatal hyperbilirubinemia is twice
that of the general population[2] in males who carry the
defective gene and in homozygous females. It rarely
occurs in heterozygous females.[3,4] Infants with the
severe variant of G6PD deficiency may develop severe
hyperbilirubinemia to cause kernicterus.[5,6]
Aim of the study
To study the prevalence of G6PD deficiency in neonates
with neonatal hyperbilirubinemia and to compare the
course of neonatal jaundice in G6PD deficient versus
nondeficient neonates.
Materials and Methods
A total of 400 neonates with indirect hyperbilirubinemia
were screened for G6PD deficiency from May 2014
to April 2016 in a Military Zonal Hospital of Jodhpur
(Rajasthan). There were 165 female and 235 male
neonates whose age varied from 2 to 10 days of life.
A written informed consent was obtained before the
study.
Inclusion criteria
All neonates with indirect hyperbilirubinemia with
serum bilirubin>12 mg% were included in the study.
Exclusion criteria
All neonates with <35 weeks of gestation and serum
bilirubin <12 mg% and also neonates with direct
hyperbilirubinemia, polycythemia, sepsis, ABO/Rh
incompatibility, and physiological jaundice (total serum
bilirubin was <12 mg% and jaundice subsided by day
10 of life) were also excluded from the study.
All cases were subjected to detail history and clinical
examination as per predesigned pro forma. Each neonate
was subjected to blood test which included total and
direct bilirubin, complete blood count, reticulocyte
count, direct Coombs test, maternal and neonatal
blood group/Rh factor, and G6PD enzyme assay. The
G6PD deficiency was screened by qualitative test, and
neonates found deficient were subjected to quantitative
test. The phototherapy was started as per Bhutani chart,
and it was stopped when total serum bilirubin reached
72 Journal of Clinical NeonatologyVolume6Issue 2April-June 2017
nontoxic level. The phototherapy machine used was
double surface LED with irradiance of 8 mcw/cm2/
nm. The neonates were discharged after the levels were
nontoxic and there was no rebound of jaundice. The
parents were counseled about the use of certain drugs
which can cause hemolysis.
Statistical method
The collected data were analyzed using Statistical
Package for the Social Sciences software version 16
(IBM, India). For data analysis, mean, standard
deviation, Students ttest, and Chisquare test were
used. P< 0.05 was considered statistically significant.
Results
The result analysis showed ten (2.5%) neonates with
indirect hyperbilirubinemia were G6PD deficient. There
was a significant statistical difference between G6PD
deficient and nonG6PD deficient group in terms of
indirect bilirubin levels, duration of phototherapy, and
gender as G6PD affect only males. However, there
was no difference in terms of onset of jaundice, day of
life and gestational age of neonates, and reticulocyte
count[Tables1 and 2].
Discussion
G6PD deficiency is an Xlinked recessive disorder, the
most common enzyme deficiency worldwide, affecting
around 400 million people. It can cause a spectrum
of disease including neonatal hyperbilirubinemia,
acute hemolysis, and chronic hemolysis. The gene
that codes for G6PD is located in the distal long arm
of the X chromosome at the Xq28 locus. The G6PD
gene is 18 kb long with 13 exons, and the G6PD
enzyme has 515 amino acids. More than 60 mutations
in the G6PD gene have been documented. The World
Health Organization has classified the different G6PD
variants according to the degree of enzyme deficiency
and severity of hemolysis, into Classes IV. Class I
deficiencies are the most severe. G6PD Mediterranean
deficiency usually is a Class II deficiency and
G6PD A deficiency is a Class III deficiency. Classes
IV and V are of no clinical significance. It has
been reported that onethird of children with G6PD
deficiency develop neonatal jaundice.[7,8] In our study,
2.5% of neonatal jaundice cases were due to G6PD
deficiency all of them responded to treatment with
phototherapy except two in whom serum bilirubin rise
required further treatment with an exchange transfusion.
The prevalence of G6PD in neonates with indirect
hyperbilirubinemia varies worldwide according to
ethnic variations. Our finding of 2.5% of the cases of
neonatal indirect hyperbilirubinemia was the result of
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Sinha, etal.: To study the prevalence of Glucose 6 phosphate dehydrogenase deficiency in neonates with neonatal hyperbilirubinemia

Table1: Comparison between hyperbilirubinemic neonates without glucose6phosphate dehydrogenase deficient

versus glucose6phosphate dehydrogenase deficient
Variable Hyperbilirubinemic neonatestotal number(n) = 400 P
Without G6PD deficient, 390(97.5%) With G6PD deficient, 10(2.5)
Age(day), meanSD 3.162.0 4.01.50 0.80
Age(day), n(%)
3 156(40) 4(40) 0.37
4-6 180(46.16) 6(60)
7 54(13.84) 0
Gestational age, meanSD 37.402.05 37.61.95 0.08
Gestational age, n(%)
35-37weeks 190(48.72) 4(40) 0.28
>37weeks 200(51.28) 6(60)
Gender, n(%)
Female 165(42.31) 0 0.02
Male 225(57.69) 10(100)
Duration of double phototherapy(days) 2.971.68 4.112.88 0.03
Need for DVET 0 2(20) 0.27
DVETDouble volume exchange transfusion; SDStandard deviation; G6PDGlucose6phosphate dehydrogenase

Table2: Comparison between glucose6phosphate Hyperbilirubinemia in G6PDdeficient neonates is

dehydrogenase normal and abnormal group in terms of thought to be secondary to reduced hepatic conjugation
investigation report and excretion of bilirubin, rather than increased
Variable Hyperbilirubinemic P bilirubin production resulting from hemolysis. In our
neonatestotal number(n)=400 study, we found no statistical difference in onset of
Without G6PD With G6PD jaundice, gestational age of neonates, day of life, and
deficiency(390), deficiency(10), reticulocyte count[Tables1 and 2]. In some populations,
meanSD meanSD hyperbilirubinemia secondary to G6PD deficiency results
Total bilirubin 17.362.80 25.175.60 <0.0002
in an increased rate of kernicterus and death, whereas
Direct bilirubin 1.20.50 2.201.30 0.0004
in other populations, this has not been observed. This
WBC 8.652.51 9.262.20 0.78
Neutrophil 1.621.30 1.800.76 0.63
may reflect genetic mutations specific to different
Lymphocytes 6.362.60 5.801.76 0.22 ethnic groups.[9,10] In our study, we reported no cases of
RBCs 3.780.60 3.500.36 0.14 kernicterus in neonates with hyperbilirubinemia whether
Hb 12.632.20 10.241.23 0.13 G6PD deficient or not. However, two cases developed
HCT 37.507.2 31.554.12 0.09 clinically significant rise in serum bilirubin requiring
MCV 94.166.5 90.606.85 0.41 double volume exchange transfusion.
MCH 28.712.70 29.653.15 0.81
The age of onset of jaundice was 4.00 1.50 days in
MCHC 31.882.0 33.51.20 0.18
G6PDdeficient neonates. This was not significantly
PLT 360.98116.83 386.40168.31 0.51
different from the finding in G6PD normal
Reticulocytes 2.722.66 4.152.87 0.26
RBCs Red blood cells; Hb Hemoglobin; HCT Hematocrit;
neonates. This finding should be underlined to state
MCV Mean corpuscular volume; MCHC Mean corpuscular the importance of early screening programs for
hemoglobin concentration; PLTPlatelet; MCHMean corpuscular G6PDdeficiency which could cause severe neonatal
hemoglobin; WBC White blood cell; SD Standard deviation; morbidity.[10] Our study showed that all G6PD deficient
G6PDGlucose6phosphate dehydrogenase neonates were males [Table 1] which is in agreement
with Bayoumi RA et al. (1996) who has reported that
G6PD deficiency was lower than African American G6PD deficient females were not at increased risk of
males where incidence varies from 11% to 13%. neonatal hyperbilirubinemia. There was a statistical
Acombination of genetic and environmental risk factors difference between G6PD deficient and nonG6PD
will determine the individual infants risk of neonatal deficient group in terms of indirect bilirubin levels and
hyperbilirubinemia. Different subtypes of the disease duration of phototherapy. The mean value of total serum
could explain the different presentations in different bilirubin level in G6PD deficient was 25.17 5.60
geographical locations worldwide. compared to G6PD nondeficient group [Table 2] which

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Sinha, etal.: To study the prevalence of Glucose 6 phosphate dehydrogenase deficiency in neonates with neonatal hyperbilirubinemia

is in agreement with other studies such as Kaplan References

etal. (1999) Furthermore, the duration of phototherapy
given to G6PD deficient neonates was statistically
significant (P = 0.03) compared to nondeficient
group[Table1].
Conclusion
The analysis of the results indicated that ten neonates
(2.5%) with indirect hyperbilirubinemia were G6PD
deficient. No statistically significant difference was detected
between G6PD deficient and nonG6PD deficient groups
in relation to onset of jaundice, day of life and gestational
age of neonates, and reticulocyte count. However,
phototherapy duration, duration of hospitalization, and
levels of total bilirubin were statistically significant in
G6PD deficient group compared to nondeficient group.
From this study, we conclude that G6PD deficiency
is a common enzyme defect in our neonatal
population (especially male) causing severe indirect
hyperbilirubinemia requiring treatment; however, a larger
study is required to validate the same. Early neonatal
screening programs should be instituted to anticipate and
institute early treatment to prevent morbidity and mortality.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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5. Bayoumi RA, NurEKamal MS, Tadayyon M, Mohamed KK,
Mahboob BH, Qureshi MM, etal. Molecular characterization
of erythrocyte glucose6phosphate dehydrogenase deficiency
in AlAin District, United Arab Emirates. Hum Hered
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6. Beutler E. Glucose6phosphate dehydrogenase deficiency: A
historical perspective. Blood 2008;111:1624.
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newborn infant whose mother ingested fava beans before
delivery. JPediatr 1995;127:8078.
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LevyLahad E, Renbaum P, etal. Neonatal hyperbilirubinemia
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