University of Wisconsin–Madison ⋅ Medical College of Wisconsin
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Glucose-6-Phosphate Dehydrogenase Deficiency in Wisconsin Newborns: Missed Opportunity for Screening

Laura P. Chen, MD; Vinod K. Bhutani, MD; Paola J. Fliman, MD; Roberto Mendez, PhD; Ann H. Allen, MD

WMJ. 2024;123(6):627-628.

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic red blood cell enzyme disorder worldwide.1 Its incidence varies based on population demographics; it is more common among individuals of sub-Saharan African, Mediterranean, Middle Eastern, Asian, Latin American, and Native American descent. In a study of US military members, overall prevalence of G6PD deficiency was 2.2%; however, over 11% of non-Hispanic Black males have the disorder.2

In newborns, G6PD deficiency is often asymptomatic. However, in the first week of life, G6PD deficiency can cause unpredictable, severe hyperbilirubinemia and kernicterus if not monitored or treated appropriately. Kernicterus, or chronic bilirubin encephalopathy, occurs with severe neonatal hyperbilirubinemia. Unbound bilirubin crosses the blood-brain barrier and can cause choreoathetoid cerebral palsy, sensorineural hearing loss, and other permanent, irreversible neurologic impairments.3 Ethnic and racial disparities exist in newborns who sustain kernicterus,4 with Black infants constituting 14% of US births, yet accounting for 25% of infants with kernicterus.5 The most common condition accounting for this outcome disparity is G6PD deficiency.4,5

G6PD DEFICIENCY IN WISCONSIN

In August 2022, the American Academy of Pediatrics (AAP) released updated guidelines for treating newborn hyperbilirubinemia, emphasizing G6PD deficiency as a risk factor for severe hyperbilirubinemia and bilirubin neurotoxicity, as well as outlining clinical indications for testing.6 The University of Wisconsin American Family Children’s Hospital and SSM St Mary’s Hospital in Madison were two of the approximately 150 hospitals nationally that participated in the AAP quality improvement project called LIGHT (Learning and Implementing Guidelines for Hyperbilirubinemia Treatment). The updated clinical practice guideline recommended screening for G6PD deficiency in patients with evidence of Coombs-negative hemolysis, but our local findings from the LIGHT initiative revealed that testing for G6PD deficiency is rarely obtained. Utilizing state diversity indices and applying race-specific adult prevalence estimates, it is estimated that approximately 1350 newborns annually in Wisconsin have G6PD deficiency; however, true statewide prevalence is unknown (see Table in full-text pdf).7 Identifying statewide prevalence along with continued clinician education and surveillance for G6PD deficiency supports the advancement of equitable newborn care in Wisconsin.

SCREENING FOR G6PD DEFICIENCY

G6PD deficiency is not routinely tested or universally screened in the United States. Washington, DC, is currently the only place that mandates universal newborn screening for G6PD deficiency.8 However, the timing of diagnosis of G6PD deficiency is crucial to prevent kernicterus. The majority of infants with G6PD deficiency in the USA Kernicterus Registry were readmitted to the hospital within the first week after birth.5 Newborn state screens via dried blood spot testing typically are not available for 5 to 7 days or more,8 which is beyond the high-risk period for kernicterus.

Recent legislation in New York mandated newborn G6PD deficiency screening, but only for high-risk infants based on specific factors including race and ancestry.9 Utilizing race to guide clinical decision-making contributes to continued racial disparities in health care9,10 and G6PD deficiency can occur in racial groups that are considered low risk.11 The optimal time for testing and results is before birth hospital discharge to enhance test accuracy, facilitate family education regarding jaundice and avoidance of triggers for breastfeeding caregivers, and ensure close follow-up.12 In addition, prehospital discharge screening has been shown to be cost-effective.13 Thus, G6PD enzyme screening of newborns has been proposed with a focus on rapid turnaround time.14

NEXT STEPS

Universal G6PD enzyme screening of all newborns is the most equitable strategy for detecting G6PD deficiency.15 The emergence of quantitative, point-of-care testing opens opportunities for rapid screening results in the newborn period. There is potential for streamlining point-of-care screening utilizing umbilical cord blood or coordinating with the time of newborn screen collection.9,16 Future studies are needed to further assess the accuracy of point-of-care tests and improve turnaround time for timely delivery of results to families.

CONCLUSIONS

G6PD deficiency is an established neurotoxicity risk factor for severe hyperbilirubinemia in newborns. Identification at birth allows for timely management and intervention to prevent irreversible brain injury. Universal screening of newborns prior to discharge from birth hospitalization is a crucial step towards equitable diagnosis of G6PD deficiency, so that all G6PD-deficient individuals can lead a healthier lifestyle protected from unpredictable adverse dietary, chemical, and environmental triggers.

REFERENCES
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  15. Uduwana SR, Nemerofsky SL. Recent G6PD screening mandate: we are missing the mark. Hosp Pediatr. 2024;14(8):e369-e37. doi:10.1542/hpeds.2023-007681
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Author Affiliations: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (Chen, Mendez, Allen); Department of Pediatrics, Stanford University School of Medicine, Stanford, California (Bhutani); SSM Health St. Mary’s Hospital, Madison, Wisconsin (Fliman); Wisconsin Newborn Screening Laboratory, Wisconsin State Laboratory of Hygiene, Madison, Wisconsin (Mendez).
Corresponding Author: Laura P. Chen, MD, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792; email lpchen@wisc.edu; ORCID ID 0000-0001-5267-0565
Funding/Support: None declared.
Financial Disclosures: None declared.
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