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Frequecy of G6PD deficiency in neonatal hyperbilirubinemia.

Byline: Syed Sajid Munir Nafisa Batool Tahir and Tahir Uddin Qazi

Abstract

Background: Glucose-6-phosphate dehydrogenase is the commonest enzymopathy in human beings. Acute hemolytic crisis is the most common presentation of G6PD deficiency but in neonatal period it usually presents as jaundice. The objective of this study is to determine the frequency of G6PD deficiency in jaundiced neonates.

Material and Methods: This study was conducted at Children Hospital Pakistan Institute of Medical Sciences Islamabad from 27th March 2009 to 27th September 2009. One hundred and sixty-three jaundiced neonates were included. Screening for G6PD deficiency was done by dye decolorization test which is semi quantitative visual colorimetric assay.

Results: The study included 163 neonates with jaundice. 72.4% were males and 27.6% were females. 16% were pre-term and 84% were full term babies. The mean age was 4.772.80 days. 11(6.7%) were G6PD deficient. 46% were anemic. Maturity at birth time of presentation presence of anemia and hyperbilirubinemia and reticulocytosis were not significantly different between G6PD deficient and G6PD normal neonates.

Conclusion: Frequency of G6PD defffiency is higher in neonatal hyperbilirubinemia. G6PD assay should be included in all jaundiced neonates for earlier detection and timely prevention of complication like kernictrus.

KEY WORDS: Neonates; Jaundice; G6PD deficiency.

Introduction

Glucose 6-phosphate dehydrogenase (G6PD) deficiency an X-linked disorder is the most common enzymatic disorder of red blood cells in humans affecting more than 400 million people worldwide.1

About 60% of term babies and 80% of pre-term infants develop some degree of jaundice during their first week of life.2 But the jaundice due to G6PD deficiency occurs in the 1st day of life and usually severe (pathological) in nature. 3 The clinical expression of G6PD variants encompasses a spectrum of hemolytic syndromes. Affected patients are usually asymptomatic but many patients have episodic anemia while a few have chronic hemolysis.

With the most prevalent G6PD variants (G6PD Aand G6PD Mediterranean) hemolysis is induced in children and adults by the sudden destruction of older more deficient erythrocytes after exposure to drugs having a high redox potential (including the antimalarial drug primaquine and certain sulfa drugs like sulfanilamide sulfamethoxazole mafenideor) or to fava beans selected infections or metabolic abnormalities. However in the neonate with G6PD deficiency decreased bilirubin elimination may play an important role in the development of jaundice.4 5

Although G6PD deficiency is global in its distribution it occurs most often in the tropical and subtropical zones of the Eastern Hemisphere. As examples G6PD deficiency is present in approximately 20 percent of African Bantu males 8 percent in Brazilian blacks 20 to 35 percent in the lowlands of Sardinia and Greece (with a much lower prevalence at higher altitudes) as high as 60 to 70 percent in Kurdish Jews and in Asia 5.5 percent in South China 2.6 percent in India and less than 0.1 percent in Japan.6-12

In the United States G6PD deficiency is present in about 12 percent in African-American men. In addition as many as 20 percent of African-American women are heterozygous for G6PD mutants and as many as 1 percent are homozygous. G6PD deficiency is rare among Native Americans. 13-16

The objective of this study is to determine the frequency of G6PD deficiency in jaundiced neonates.

MATERIAL AND METHODS

This study was conducted at Children Hospital Pakistan Institute of Medical Sciences Islamabad from 27th March 2009 to 27th September 2009.

One hundred and sixty-three jaundiced neonates were included in the study. Screening for G6PD deficiency was done by dye decolorization test which is semi quantitative visual colorimetric assay. Those having congenital defect autoimmune hemolysis in moribund condition low APGAR (Appearance Pulse Grimace Activity Respiration) score acute hemolysis characterized by reticulocytosis and established maternal positive status for hepatitis B and C virus were excluded from study. All the patients meeting the inclusion criteria from all incoming sources to hospital like outpatient department Emergency department and hospitalized patients were included. Approval was taken from hospital ethical committee. Informed written consent was taken from the parents/ caretakers.

Blood samples were taken for blood complete picture (CP) G6PD test and serum bilirubin level. Screening for G6PD deficiency was done by the dichlorophenol-indophenol (DPIP) dye decolorization method (Bernstein 1962).17 Bilirubin was measured by the Van Den Bergh method.18

Hematological parameters were measured using an automatic hematology analyzer (Nihon Khoden) as per the manufacturers' instructions.

The data was analyzed using SPSS version 12. Mean and standard deviation were calculated for numerical variables like age bilirubin reticulocytes count and hemoglobin levels. Frequencies were represented for categorical variables i.e. age gender preterm full term and G6PD deficiency.

RESULTS

The study included 163 neonates with jaundice. 118 (72.4%) were males and 45 (27.6%) were females. 26 (16%) were preterm and 137 (84%) were full term babies. The mean age was 4.77 2.80 days. The age ranged from 1 to 17 days. 11 (6.7%) were G6PD deficient. 152 (93.3%) had normal G6PD levels. 22 (13.5%) presented within the first 24-hour after birth 112 (68.7%) presented between 2-7 days and 29 (17.8%) presented after the first week of birth.

75 (46%) were anemic with a hemoglobin less than the reference value for their age. The hemoglobin ranged from 7 to 20 g/dl with a mean of 15.432.81 g/dl. The total bilirubin ranged from 6.3 to 36 mg/ dl with a mean of 18.98 6.20 mg/dl. The direct bilirubin ranged from 0.5 to 22.5 mg/dl with a mean of 2.401.94 mg/dl. The indirect bilirubin ranged from 0.90 to 32 mg/dl with a mean of 16.326.31 mg/dl. The retics count ranged from 0.4 to 25% with a mean of 4.114.1.

Table 1: Characteristics of patients with hyperbilirubinemia (n=163).

###G6PD defi###Non-G6PD

###cient###deficient

Total number###11###152

Preterm###3/11###23/152

Full term###8/11###129/152

Mean###Age###5.31.36###4.7+2.88

(Days)

Mean Hb (g/dl)###14.7+2.84###15.4+2.81

Anemia###7/11 (63.6%)###68/152

Mean Total Bil###22.23+7.65###18.75+6.05

irubin (mg/dl)

Mean Retic###2.94+1.86###4.19+4.29

count (%)

Mean direct bil###3.09+2.03###2.35+1.93

irubin (mg/dl)

Mean indirect###19.9+6.68###16.08+6.24

bilirubin (mg/

dl)

Among the 11 G6PD deficient neonates 10 were males and one female. Among 152 non-G6PD deficient neonates 108 were males and 44 females. (p=0.15). Among G6PD deficient neonates 1/11 (9.1%) had total bilirubin less than 20 mg/dl 4/11 (36.4%) had bilirubin between 20-30 mg/dl and 6/11 (54.5%) had bilirubin greater than 30 mg/dl. Among normal G6PD neonates 23/152 (15.1%) had total bilirubin less than 20 mg/ dl 73/152 (48%) had bilirubin between 20-30 mg/ dl and 56/152 (36.8%) had bilirubin greater than 30 mg/dl; this difference was not statistically significant. (p= 0.49)

DISCUSSION

G6PD deficiency is the most important disease of hexose monophosphate pathway. G6PD is an x-linked recessive disease where the deficiency of the enzyme causes a spectrum of clinical manifestations ranging from neonatal jaundice to chronic nonspherocytic anemia to infection and drug-induced hemolysis.19

Local data on the subject is scarce. Siddiqi et al reported G6PD deficiency in 5.4% of neonates with jaundice; these results were in conformation with our study.20 In a study by Alvi et al21 10% of the neonates with pathological hyperbilirubinemia were found to be G6PD deficient.Rehman et al22 reported that 8.2% babies admitted for neonatal jaundice were G6PD deficient. In another study from Peshawar Imran et al found that 11.2% of the neonates admitted for neonatal jaundice were G6PD deficient.23 This difference could be due to the different incidence of G6PD deficiency in different parts of the world and ethnic groups within the same country.

At Khyber Teaching Hospital Peshawar in 2003 out of 200 adult patients studied 24 (12%) patients were found to be deficient in G6PD enzyme.24 In our study we detected a male to female ratio of 10: 1. So the number of girls with G6PD deficiency should not be underestimated.

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 heamolysis. In our study we found no difference in reticulocyte count and hemoglobin level between G6PD-deficient and normal groups. In our study among G-6-PD deficient neonates 1/11 (9.1%) has total bilirubin less than 20 mg/dl 4/11 (36.4%) had bilirubin between 20-30 mg/dl and 6/11 (54.5%) had bilirubin greater than 30 mg/dl. Among normal G-6PD neonates 23/152 (15.1%) has total bilirubin less than 20 mg/dl 73/152 (48%) had bilirubin between 20-30 mg/dl and 56/152 (36.8%) had bilirubin greater than 30 mg/dl.; of the G6PD deficient neonates had a peak serum bilirubin greater than 20 mg/dl. .

Our results were consistent with study by Alvi et al21 in which 90% neonates developed jaundice within first 7 days of life and also with the study from Peshawar in which 80% babies with G6PD deficiency developed jaundice in first 7 days of life. This difference was not statistically significant (p= 0.498). Evidence of hemolysis was lacking in most of the G6PD deficient babies in our study as reticulocytes was not evident in most of the G6PD deficient neonates in our study. G6PD deficiency associated with neonatal jaundice was considered to be hemolytic in origin but a number of studies have proven that heamolysis is not the only reason for jaundice in these. It is now considered predominantly to be caused by G6PD deficiency being expressed in the liver resulting in partial defect of bilirubin conjugation and its decreased excretion. More studies on a larger scale are required to document the prevalence of G6PD among jaundiced neonates in different regions and races of Pakistan

CONCLUSION

Frequency of G6PD deficiency is higher in neonatal hyperbilirubinemia. G6PD assay should be included in all jaundiced neonates for earlier detection and timely prevention of complications like kernictrus.

REFERENCES

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Publication:Gomal Journal of Medical Sciences
Article Type:Report
Geographic Code:9PAKI
Date:Jun 30, 2014
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