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Biochemical Measurement of Neonatal Hypoxia
Published on: August 24, 2011
Neonatal Screening for Glucose-6-Phosphate Dehydrogenase (G6PD) Gene Variants and Their Association With
Ismail M Alwadani1, Raghad Almuslim2, Mohammad Almutairi2
1Department of Neonatology, Johns Hopkins Aramco Healthcare, Dhahran, SAU.
Insights
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in newborns, with the c.563C>T variant being most prevalent. Specific G6PD variants did not predict hyperbilirubinemia severity, but Coombs test positivity and multiple gene copies did.
Area of Science:
- Medical Genetics
- Neonatology
- Pediatric Hematology
Background:
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in the Middle East.
- It is a known risk factor for neonatal hyperbilirubinemia.
- The impact of specific G6PD gene variants on hyperbilirubinemia severity is not well understood.
Purpose of the Study:
- Determine G6PD gene variant prevalence in neonates at Johns Hopkins Aramco Healthcare.
- Evaluate the association between G6PD variants and hyperbilirubinemia severity.
- Assess the link between G6PD variants and phototherapy requirements.
Main Methods:
- Retrospective cohort study of neonates with G6PD deficiency (2021-2023).
- Data collected from electronic medical records, including demographics, clinical, laboratory, and genetic information.
- G6PD variants identified via newborn DNA screening; statistical analyses performed to assess associations.
Main Results:
- 10.6% of 5,375 neonates had G6PD deficiency, predominantly males.
- The c.563C>T (Mediterranean) variant was most common (93.5%).
- Phototherapy was required for 33.7%; positive Coombs test and two mutant G6PD copies predicted need, while female sex was protective. No association found between specific variants and phototherapy need.
Conclusions:
- G6PD deficiency, primarily the c.563C>T mutation, is common in this cohort.
- Positive Coombs test and multiple G6PD gene copies predict phototherapy needs.
- Specific G6PD variants are not associated with hyperbilirubinemia severity, highlighting the need for early screening and monitoring.
Background And Objectives:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in the Middle East and is a recognized risk factor for neonatal hyperbilirubinemia. However, the clinical impact of specific G6PD gene variants on hyperbilirubinemia severity remains unclear. This study aimed to determine the prevalence of G6PD gene variants among neonates at Johns Hopkins Aramco Healthcare and to evaluate their association with hyperbilirubinemia severity and phototherapy requirements.
Methods:
We conducted a retrospective cohort study of neonates diagnosed with G6PD deficiency between January 2021 and December 2023. Demographic, clinical, laboratory, and genetic data were collected from electronic medical records. G6PD variants were identified using newborn DNA screening. Associations with phototherapy requirement were assessed using chi-square and Mann-Whitney U tests. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of phototherapy.
Results:
Among 5,375 neonatal admissions, 572 (10.6%) neonates were diagnosed with G6PD deficiency, with a male predominance (66.6%). The c.563C>T (Mediterranean) variant was the most prevalent (93.5%). Phototherapy was required in 193 neonates (33.7%). In multivariate analysis, female sex was independently protective against phototherapy (adjusted odds ratio (AOR) = 0.239; p = 0.003), while a positive Coombs test (AOR = 8.668; p < 0.001) and the presence of two mutant G6PD gene copies (AOR = 3.890; p = 0.007) were significant independent predictors of phototherapy requirement. No significant association was observed between specific G6PD variants and the need for phototherapy.
Conclusion:
G6PD deficiency was common in this cohort and was mainly associated with the c.563C>T mutation. A positive Coombs test and multiple gene copies were independent predictors of phototherapy, whereas specific G6PD variants were not associated with hyperbilirubinemia severity. These findings support the importance of early G6PD screening and vigilant monitoring to prevent severe neonatal hyperbilirubinemia.
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