ArticleCureus2026
Neonatal Screening for Glucose-6-Phosphate Dehydrogenase (G6PD) Gene Variants and Their Association With Hyperbilirubinemia and Phototherapy Needs.
Article in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectivesGlucose-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.
methodsWe 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.
resultsAmong 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.
conclusionG6PD 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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