Abstract
Objective Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common inherited enzyme deficiency disorder worldwide and a major risk factor for the development of severe hyperbilirubinemia. Racial diversity of phenotypes and genotypes in affected individuals is likely to exist in the United States because of changing population demographics. The aim of the present study was to predict an empirical estimate of annual prevalence of G6PDd in newborns adjusted for geography (state of birth), maternal racial identity, and sex of the infant.
Study Design Birth statistics (2019) from National Center for Vital Statistics and CDC-WONDER data and race-specific prevalence of G6PDd in the United States were evaluated from published sources. We developed Simpson's diversity index (DI) for each State and correlated these to rates of G6PDd in neonates. Descriptive statistics including modeled prevalence and its association with DI were assessed using the Spearman's rho correlation test. We modeled state-specific prevalence for six states (California, Washington DC, Illinois, Massachusetts, New York, and Pennsylvania) using population-level allele frequencies and race, based on Hardy–Weinberg equilibrium.
Results We estimated 78,010 (95% confidence interval: 76,768–79,252) newborns had G6PDd at birth in 2019 with cumulative median prevalence of 17.3 (interquartile range: 12.4–23.2) per 1,000 live births for United States. A strong association was noted for DI and prevalence of G6PDd (p < 0.0005). Five states (Washington DC, Mississippi, Louisiana, Georgia, and Maryland) have the highest projected G6PDd prevalence, with a range of 35 to 48 per 1,000 live births. The probability of G6PDd for female heterozygotes, based on male prevalence, ranged from 1.1 to 7.5% for each cohort in the select six states.
Conclusion States with diverse populations are likely to have higher rates of G6PDd. These prevalence estimates exceeded by several-fold when compared with disorders screened by existing state mandated newborn screening panels. These discrepancies are further confounded by known risk of severe neonatal hyperbilirubinemia that results with G6PDd and the life-long risk of hemolysis. Combined universal newborn predischarge screening for G6PDd and bilirubin could alert and guide a clinician's practices for parental education and closer medical surveillance during the vulnerable neonatal time period.
Key Points
G6PDd is a common X-linked disorder that can present with varied phenotypes among newborns.
Prevalence of G6PDd and genotype distribution varies with sex, race, and ethnicity.
We present regional race- and sex-based estimates of G6PDd in the United States.
Keywords G6PDd deficiency - epidemiology - race - newborns - United States
