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ORIGINAL ARTICLE
Year : 2017  |  Volume : 6  |  Issue : 2  |  Page : 71-74

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


1 Department of Pediatrics, Military Hospital, Jodhpur, Rajasthan, India
2 Commandant, Military Hospital, Jodhpur, Rajasthan, India
3 Department of Pathology, Military Hospital, Jodhpur, Rajasthan, India
4 Department of Pediatrics, Command Hospital Air Force, Bengaluru, Karnataka, India

Date of Web Publication13-Apr-2017

Correspondence Address:
Rahul Sinha
Military Hospital, Jodhpur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_59_16

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  Abstract 

Background: The enzyme glucose-6-phosphate dehydrogenase (G6PD) deficiency leads to impaired production of reduced glutathione and predisposes the red cells to damage by oxidative metabolites causing hemolysis. Deficient neonates may manifest clinically as indirect hyperbilirubinemia or even kernicterus. G6PD deficiency is the most common enzyme deficiency in humans affecting around 400 million people worldwide which presents in neonatal period as unconjugated hyperbilirubinemia and is inherited as X-linked 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 non-G6PD 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: Glucose-6-phosphate dehydrogenase, hyperbilirubinemia, jaundice, neonates


How to cite this article:
Sinha R, Sachendra B, Syed V S, Nair L, John B M. 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

How to cite this URL:
Sinha R, Sachendra B, Syed V S, Nair L, John B M. 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 [serial online] 2017 [cited 2017 Jun 25];6:71-4. Available from: http://www.jcnonweb.com/text.asp?2017/6/2/71/204515


  Introduction Top


Neonatal hyperbilirubinemia (defined as a total serum bilirubin level exceeding 5 mg/dl) is a frequent problem as neonatal jaundice affects 65% of full-term infants and 85% of preterm infants after 24 h of life.[1] The glucose-6-phosphate dehydrogenase (G6PD) enzyme is part of the pentose monophosphate shunt. It catalyzes the oxidation of glucose-6-phosphate and the reduction of nicotinamide adenine dinucleotide phosphate to nicotinamide adenine dinucleotide 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 1–4 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 Top


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 nontoxic level. The phototherapy machine used was double surface LED with irradiance of 8 mcw/cm 2/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, Student's t-test, and Chi-square test were used. P< 0.05 was considered statistically significant.


  Results Top


The result analysis showed ten (2.5%) neonates with indirect hyperbilirubinemia were G6PD deficient. There was a significant statistical difference between G6PD deficient and non-G6PD 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 [Table 1] and [Table 2].
Table 1: Comparison between hyperbilirubinemic neonates without glucose-6-phosphate dehydrogenase deficient versus glucose-6-phosphate dehydrogenase deficient

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Table 2: Comparison between glucose-6-phosphate dehydrogenase normal and abnormal group in terms of investigation report

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  Discussion Top


G6PD deficiency is an X-linked 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 I-V. 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 one-third 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 G6PD deficiency was lower than African American males where incidence varies from 11% to 13%. A combination of genetic and environmental risk factors will determine the individual infants' risk of neonatal hyperbilirubinemia. Different subtypes of the disease could explain the different presentations in different geographical locations worldwide.

Hyperbilirubinemia in G6PD-deficient neonates is thought to be secondary to reduced hepatic conjugation and excretion of bilirubin, rather than increased bilirubin production resulting from hemolysis. In our study, we found no statistical difference in onset of jaundice, gestational age of neonates, day of life, and reticulocyte count [Table 1] and [Table 2]. In some populations, hyperbilirubinemia secondary to G6PD deficiency results in an increased rate of kernicterus and death, whereas in other populations, this has not been observed. This may reflect genetic mutations specific to different ethnic groups.[9],[10] In our study, we reported no cases of kernicterus in neonates with hyperbilirubinemia whether G6PD deficient or not. However, two cases developed clinically significant rise in serum bilirubin requiring double volume exchange transfusion.

The age of onset of jaundice was 4.00 ± 1.50 days in G6PD-deficient neonates. This was not significantly different from the finding in G6PD normal neonates. This finding should be underlined to state the importance of early screening programs for G6PD-deficiency which could cause severe neonatal morbidity.[10] Our study showed that all G6PD deficient neonates were males [Table 1] which is in agreement with Bayoumi RA et al. (1996) who has reported that G6PD deficient females were not at increased risk of neonatal hyperbilirubinemia. There was a statistical difference between G6PD deficient and non-G6PD deficient group in terms of indirect bilirubin levels and duration of phototherapy. The mean value of total serum bilirubin level in G6PD deficient was 25.17 ± 5.60 compared to G6PD nondeficient group [Table 2] which is in agreement with other studies such as Kaplan et al. (1999) Furthermore, the duration of phototherapy given to G6PD deficient neonates was statistically significant (P = 0.03) compared to nondeficient group [Table 1].


  Conclusion Top


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 non-G6PD 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.

 
  References Top

1.
Pao M, Kulkarni A, Gupta V, Kaul S, Balan S. Neonatal screening for glucose-6-phosphate dehydrogenase deficiency. Indian J Pediatr 2005;72:835-7.  Back to cited text no. 1
    
2.
Naik SN. Glucose-6-phosphate dehydrogenase deficiency in India and its clinical significance. J Assoc Physicians India 1994;42:229-34.  Back to cited text no. 2
    
3.
Ahmed H, Yukubu AM, Hendrickse RG. Neonatal jaundice in Zaria, Nigeria – A second prospective study. West Afr J Med 1995;14:15-23.  Back to cited text no. 3
    
4.
Atay E, Bozaykut A, Ipek IO. Glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia. J Trop Pediatr 2006;52:56-8.  Back to cited text no. 4
    
5.
Bayoumi RA, Nur-E-Kamal MS, Tadayyon M, Mohamed KK, Mahboob BH, Qureshi MM, et al. Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Al-Ain District, United Arab Emirates. Hum Hered 1996;46:136-41.  Back to cited text no. 5
    
6.
Beutler E. Glucose-6-phosphate dehydrogenase deficiency: A historical perspective. Blood 2008;111:16-24.  Back to cited text no. 6
    
7.
Corchia C, Balata A, Meloni GF, Meloni T. Favism in a female newborn infant whose mother ingested fava beans before delivery. J Pediatr 1995;127:807-8.  Back to cited text no. 7
    
8.
Kaplan M, Beutler E, Vreman HJ, Hammerman C, Levy-Lahad E, Renbaum P, et al. Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. Pediatrics 1999;104(1 Pt 1):68-74.  Back to cited text no. 8
    
9.
American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316.  Back to cited text no. 9
    
10.
Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ 1989;67:601-11.  Back to cited text no. 10
    



 
 
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