Georacial Epidemiological Estimates of Glucose-6-Phosphate Dehydrogenase Deficiency among Newborns in the United States

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.

[1]  A. Kemper,et al.  Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. , 2022, Pediatrics.

[2]  Randall W. Grout,et al.  Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. , 2022, Pediatrics.

[3]  Timothy M. Bahr,et al.  Thirty-five males with severe (Class 1) G6PD deficiency (c.637G>T) in a North American family of European ancestry. , 2021, Blood cells, molecules & diseases.

[4]  Y. Bahk,et al.  A Profile of Glucose-6-Phosphate Dehydrogenase Variants and Deficiency of Multicultural Families in Korea , 2021, The Korean journal of parasitology.

[5]  G. Graziadei,et al.  Epidemiological shift of glucose-6-phosphate dehydrogenase mutations in northern Italy in the last 15 years , 2021, Annals of Hematology.

[6]  J. Martin,et al.  Births: Final Data for 2019. , 2021, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[7]  J. Prchal,et al.  A Novel Variant in G6PD (c.1375C>G) Identified from a Hispanic Neonate with Extreme Hyperbilirubinemia and Low G6PD Enzymatic Activity , 2020, Neonatology.

[8]  Z. Kasemy,et al.  Prevalence of and mothers’ knowledge, attitude and practice towards glucose-6-phosphate dehydrogenase deficiency among neonates with jaundice: a cross-sectional study , 2020, BMJ Open.

[9]  D. Sridhar,et al.  Metric partnerships: global burden of disease estimates within the World Bank, the World Health Organisation and the Institute for Health Metrics and Evaluation , 2020, Wellcome Open Research.

[10]  M. Rodrigo-Domingo,et al.  Extreme neonatal hyperbilirubinemia and kernicterus spectrum disorder in Denmark during the years 2000–2015 , 2020, Journal of Perinatology.

[11]  Beth T. Poitras,et al.  Prevalence of glucose-6-phosphate dehydrogenase deficiency, U.S. Armed Forces, May 2004-September 2018. , 2019, MSMR.

[12]  G. Lippi,et al.  Updated Worldwide Epidemiology of Inherited Erythrocyte Disorders , 2019, Acta Haematologica.

[13]  B. Glader,et al.  Red Blood Cell Enzyme Disorders. , 2018, Pediatric clinics of North America.

[14]  Jacqueline E. McLaughlin,et al.  Using Simpson’s diversity index to examine multidimensional models of diversity in health professions education , 2016, International journal of medical education.

[15]  C. Hammerman,et al.  Glucose-6-Phosphate Dehydrogenase Screening in Israel-Arab and Palestinian-Arab Neonates. , 2015, The Journal of pediatrics.

[16]  M. Nock,et al.  Pediatric Provider Insight Into Newborn Screening for Glucose-6-Phosphate Dehydrogenase Deficiency , 2015, Clinical pediatrics.

[17]  Wenbin Liu,et al.  Association Between G6PD Deficiency and Hyperbilirubinemia in Neonates: A Meta-Analysis , 2015, Pediatric hematology and oncology.

[18]  C. Wusthoff,et al.  Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes. , 2015, Seminars in fetal & neonatal medicine.

[19]  B. Olusanya,et al.  Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose‐6‐phosphate dehydrogenase deficiency , 2014, Acta paediatrica.

[20]  Eileen M. Walsh,et al.  Incidence, Etiology, and Outcomes of Hazardous Hyperbilirubinemia in Newborns , 2014, Pediatrics.

[21]  Joy E. Lawn,et al.  Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels , 2013, Pediatric Research.

[22]  D. Roter,et al.  Parental discussion of G6PD deficiency and child health: implications for clinical practice , 2013, Archives of Disease in Childhood.

[23]  D. Stevenson,et al.  Should we screen newborns for glucose-6-phosphate dehydrogenase deficiency in the United States? , 2013, Journal of Perinatology.

[24]  J. Watchko.  Screening for glucose-6-phosphate dehydrogenase deficiency in newborns-practical considerations. , 2012, The Journal of pediatrics.

[25]  M. Hwang,et al.  Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations. , 2012, Blood cells, molecules & diseases.

[26]  M. Walsh,et al.  Implementation and analysis of a pilot in-hospital newborn screening program for glucose-6-phosphate dehydrogenase deficiency in the United States , 2011, Journal of Perinatology.

[27]  R. Mahdavi,et al.  The Efficacy of a Neonatal Screening Programme in Decreasing the Hospitalization Rate of Patients with G6pd Deficiency in Southern Iran , 2010, Journal of medical screening.

[28]  V. Bhutani,et al.  Clinical report from the pilot USA Kernicterus Registry (1992 to 2004) , 2009, Journal of Perinatology.

[29]  A. Mégarbané,et al.  Cost-benefit analysis of G6PD screening in Lebanese newborn males. , 2007, Le Journal medical libanais. The Lebanese medical journal.

[30]  D. Hospenthal,et al.  Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. Army personnel. , 2006, Military medicine.

[31]  P. Nair,et al.  Kernicterus and G6PD deficiency--a case series from Oman. , 2003, Journal of tropical pediatrics.

[32]  J. Crow,et al.  Hardy, Weinberg and language impediments. , 1999, Genetics.

[33]  John Wright,et al.  Epidemiological issues in health needs assessment , 1998, BMJ.

[34]  E. Beutler.  G6PD: population genetics and clinical manifestations. , 1996, Blood reviews.

[35]  D. R. Mcleod,et al.  Prevalence of glucose-6-phosphate dehydrogenase deficiency. , 1988, The Journal of pediatrics.

[36]  H. Notopuro,et al.  Glucose-6-phosphate dehydrogenase deficiency. , 1972, Paediatrica Indonesiana.

[37]  E. Beutler,et al.  The normal human female as a mosaic of X-chromosome activity: studies using the gene for C-6-PD-deficiency as a marker. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[38]  S. Al-Abdi,et al.  Readmission for neonatal hyperbilirubinemia in an area with a high prevalence of glucose-6-phosphate dehydrogenase deficiency: A hospital-based retrospective study. , 2017, Journal of neonatal-perinatal medicine.

[39]  W. Bossert,et al.  The Measurement of Diversity , 2001 .

[40]  G. Forteleoni,et al.  Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the northern Sardinian experience. , 1992, Acta haematologica.