The Efficacy of a Neonatal Screening Programme in Decreasing the Hospitalization Rate of Patients with G6pd Deficiency in Southern Iran

Introduction

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked, hereditary genetic disorder with a wide range of clinical and biochemical phenotypes ¹ and main clinical manifestations of acute or chronic haemolytic anaemia and neonatal jaundice. ² G6PD deficiency is more prevalent throughout tropical and subtropical regions, Africa, the Mediterranean region and Middle East. ³ It is estimated that more than 400 million people worldwide are affected ⁴ and the World Health Organization recommends screening for all male newborns in countries with a prevalence higher than 3-5%. ⁵ In Iran, where prevalence is high (12% in males and 1.8% in females), a screening programme for all newborns was introduced in 2004. ⁶ The aim of this study was to investigate whether the neonatal screening programme for G6PD deficiency has decreased acute haemolysis attack and hospitalization in the Fars province of southern Iran.

Methods

We performed a cross-sectional study to evaluate the efficacy of the neonatal screening programme for G6PD deficiency in southern Iran. All newborns from private and governmental hospitals were referred to a central laboratory for screening of G6PD deficiency in Shiraz (southern Iran). A total of 929 patients referred to our paediatric emergency ward due to G6PD deficiency were enrolled in the study. Seventy-nine patients born before 2005 and hospitalized after 2005 were excluded from the study, leaving 833 males and 17 females, divided into two groups: 553 patients with a haemolytic crisis due to G6PD deficiency who were admitted before the G6PD screening programme (2001-2004) consisted of 542 males and 11 females with an age range of 4-8 years, and 297 patients who were admitted due to G6PD deficiency after G6PD screening (2005-2008) consisting of 291 males and 6 females with an age range of 1-4 years. All of the variables including age, sex, time and cause of hospitalization, cause of haemolytic crisis, positive history of blood transfusion, G6PD enzyme deficiency, blood urea nitrogen (BUN) and creatinine were recorded based on a standard questionnaire. As soon as patients with haemolytic crisis were referred, the G6PD enzyme level was checked; two months after discharge the G6PD enzyme level was checked again. G6PD deficiency status in the neonatal screening programme was performed by a qualitative fluorescent spot test, but we evaluated the enzyme levels by a quantitative spectrophotometric method (Sigma, USA). This study was approved by the medical ethics committee of Shiraz University of Medical Sciences, and written consent was provided from all parents.

Results

Five hundred and fifty-three G6PD deficient patients were hospitalized before the introduction of the screening programme. Of the 297 patients who were hospitalized for the deficiency after the introduction of screening, 237 had been wrongly classified as normal, and 60 had been correctly identified during the neonatal screening programme. The main significant symptoms of patients included jaundice, tea-coloured urine and pallour.

The main causes of haemolytic crisis in G6PD deficient patients was fava bean consumption (88.2%), drugs (0.8%) and underlying infection (10.9%). About 85% of patients had blood transfusions, 2% had abnormal BUN and creatinine levels, and 71% had abnormal urine analysis.

Discussion and Conclusion

This is the first study to evaluate the efficacy of a neonatal screening programme for G6PD deficiency in decreasing hospitalization rates in southern Iran. The study showed that the screening programme was relatively successful in the reduction in hospitalization rates of patients with G6PD deficiency, from 553 patients before the introduction of the screening programme, to 297 after screening started.

Khneisser et al. ⁷ showed significantly decreased hospitalization (95%) rates among patients screened for G6PD, compared with those who had not been screened among Lebanese newborn males. They also demonstrated that G6PD screening is cost-effective compared with anaemia-related hospitalization. The study by Munyanganizi et al. ⁸ showed that screening for G6PD deficiency seems reasonable and lowers hospitalization rates and the incidence of red blood cell disorders. In comparison with these studies, our study was conducted over a longer period of time, and so was able to survey more cases.

The neonatal G6PD screening programme in Iran is based on a qualitative fluorescent spot test. The test has some false-negative results that misclassify some G6PD deficient subjects as normal. In this study of 297 patients hospitalized after the introduction of the neonatal screening programme, 237 were wrongly detected to have sufficient enzyme activity at their neonatal screen. There were 60 patients correctly reported as deficient in enzyme activity, and their haemolytic attack was due to fava or drug consumption.

In conclusion, the study shows the effectiveness of a neonatal screening programme in decreasing the hospitalization rate. The screening programme does not eliminate hospitalization entirely; initial screening is likely to be erroneous, with a very high false-positive rate. It is therefore recommended that children should be retested several (at least two) months later. It is also important that quantitative methods are used for neonatal screening programmes in countries such as this, with a high prevalence of G6PD deficiency, in order to avoid misdiagnoses, and that education programmes for parents and doctors in the prevention of haemolytic attacks are improved.