By Kate Marino 

Knowing whether an infant has Glucose-6-Phosphate Dehydrogenase Deficiency (G6PDD) can help doctors decide how closely to monitor an infant’s bilirubin (jaundice) level and know when to start phototherapy. Screening for G6PDD could reduce the risk of infants developing severe hyperbilirubinemia as well as a permanent form of brain damage called kernicterus. 

Unfortunately, the genetic disorder is not routinely included in infant evaluations at hospitals across the United States. The inconsistent testing for the disorder after birth is thought to be a major contributor to the racial disparities seen in kernicterus. 

To reduce these gaps in diagnosing G6PDD, new research involving Virginia Commonwealth University evaluated the effectiveness of different newborn-screening approaches in detecting the condition to determine the optimal approach. 

“We hope our study sheds light about how to best screen newborns for this important genetic condition,” said Elizabeth Wolf, M.D., MPH, a pediatrician at Children’s Hospital of Richmond at VCU and an associate professor in the Department of Pediatrics at VCU School of Medicine. 

The research was led by Wolf and her co-authors Colin Orr, M.D., MPH of Vanderbilt University, and Alex Kemper, M.D., MPH, MS, of Nationwide Children’s Hospital. The study, published in JAMA Pediatrics, is the first large-scale evaluation of newborn screenings conducted in the United States for this genetic condition. 

Nationwide hospital data helps evaluate newborn screening approaches for G6PDD 

In the U.S., each infant born in a hospital receives a standard evaluation including a hearing test, heart screening for critical congenital heart disease, and a blood test for a group of genetic and metabolic conditions. The specific conditions included in the blood test vary depending on which state a child is born, as state health departments determine these policies.  

G6PDD is a genetic disorder that causes the body to not produce enough of the enzyme needed to protect red blood cells from oxidative stress. G6PDD affects about 400 million people worldwide, about 5% of the global population, and is most common in infants with African, Asian, Mediterranean or Middle Eastern ancestry. 

In most states, evaluating newborns for G6PDD often only happens when a doctor suspects the condition (usual care). However, for over a decade, some localities such as Pennsylvania and Washington, DC, have tested all newborns as part of their newborn metabolic screening program (universal strategy). New York mandated screening newborns with a hospital-based test based on ancestry or clinical criteria in December 2021 (at-risk strategy).  

The research team used a database to compare the screening methods — universal, at-risk and usual care — and G6PDD diagnosis rates for all births across more than 2,000 U.S. hospitals between January 1, 2020, and December 31, 2025.  

The researchers’ comparison of the screening methods found that universal and at-risk screening strategies identified G6PDD in 7.14 and 5.39 births, respectively, out of 1,000 newborns on average, while the diagnosis rate for usual care was 0.38 births per 1,000.  

“The study included more than 4 million infants and found that both universal and at-risk screening strategies outperformed usual care overall, and across categories of sex, race and ethnicity,” Wolf said. “This tells us that these strategies have the potential to reduce racial disparities in hyperbilirubinemia and, with proper monitoring and treatment, prevent cases of kernicterus.” 

The evaluation of the hospital birth data revealed that the universal screening process used in Pennsylvania and Washington, DC, proved somewhat more effective at identifying non-Hispanic Asian and Black and Hispanic infants with G6PDD than the at-risk screening used in New York. However, the researchers note that the lengthy turnaround time for universal newborn metabolic screening results limits the ability of doctors to provide effective care in the immediate newborn period. 

Next steps in reducing diagnostic disparities for newborns 

This nationwide analysis of newborn screening tests serves as an essential stepping stone for ongoing research to reduce gaps in care for populations most affected by G6PDD. 

“Our study suggests that a third strategy should be considered — a universal hospital-based screening with quick turnaround time,” Wolf added. “This option offers the potential for both increased yield and timeliness.” 

Wolf says further studies can determine how different screening strategies impact treatment of hyperbilirubinemia and the incidence of kernicterus.

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