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Parental education and the WHO neonatal G-6-PD screening program: a quarter century later

Journal of Perinatology volume 35, pages 779–784 (2015)Cite this article

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Abstract

Neonatal screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in any population with a male frequency >3–5%, combined with parental education regarding the dietary, environmental and sepsis-related triggers for hemolysis was recommended by the WHO (World Health Organization) Working Group in 1989. As the aim of identifying G-6-PD deficiency in the newborn period is to avert or detect extreme hyperbilirubinemia developing at home, before the development of kernicterus, the parental role in identifying evolving icterus was considered integral to any screening program. Now, a quarter century after publication of this report, severe bilirubin neurotoxicity associated with G-6-PD deficiency continues to be encountered worldwide. Screening programs have not been universally introduced but several national or regional maternal child health programs have implemented neonatal G-6-PD screening. Some reports detail the role of parental education, based on the above mentioned principles, through a variety of audio–visual materials. The paucity of randomized controlled trials or validated evidence to demonstrate the effectiveness of the contribution of parental education fails to meet the ideal testable evidence-based approach. However, our review of the cumulative experience and evidence currently available does supply certain information reflecting a positive impact of screening programs combined with parental input. We propose that the current information is sufficient to continue to support and apply the Working Group’s recommendations. In order not to waste unnecessary time available, data may be used in lieu of randomized trials to continue to recommend screening programs, as suggested, in high-risk regions. If the incidence of kernicterus associated with G-6-PD deficiency is to be diminished, G-6-PD screening in combination with parental explanation may be one instance in which the consensus approach suggested by the WHO Working Group, rather than reliance on (nonexistent) evidence-based studies, should continue to be practiced.

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References

  1. Beutler E . G6PD deficiency. Blood 1994; 84 (11): 3613–3636.

    CAS  Google Scholar 

  2. Cappellini MD, Fiorelli G . Glucose-6-phosphate dehydrogenase deficiency. Lancet 2008; 371 (9606): 64–74.

    Article  CAS  Google Scholar 

  3. Olusanya BO, Emokpae AA, Zamora TG, Slusher TM . Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6-phosphate dehydrogenase deficiency. Acta Paediatr (e-pub ahead of print; doi:10.1111/apa.12735).

  4. Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM . Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol 2009; 29 (Suppl1): S25–S45.

    Article  Google Scholar 

  5. Sgro M, Campbell D, Shah V . Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006; 175 (6): 587–590.

    Article  Google Scholar 

  6. Manning D, Todd P, Maxwell M, Jane Platt M . Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed 2007; 92 (5): F342–F346.

    Article  Google Scholar 

  7. WHO Working Group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989; 67 (6): 601–611.

    Google Scholar 

  8. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E . The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis 2009; 42 (3): 267–278.

    Article  CAS  Google Scholar 

  9. Howes RE, Piel FB, Patil AP et al. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-basedmap. PLoS Med 2012; 9 (11): e1001339.

    Article  CAS  Google Scholar 

  10. Monteiro WM, Val FF, Siqueira AM, Franca GP, Sampaio VS, Melo GC et al. G6PD deficiency in Latin America: systematic review on prevalence and variants. Mem Inst Oswaldo Cruz 2014; 109 (5): 553–568.

    Article  CAS  Google Scholar 

  11. Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M, Ebbesen F et al. Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res 2013; 74 (Suppl 1): 86–100.

    Article  Google Scholar 

  12. Arain YH, Bhutani VK . Prevention of Kernicterus in South Asia: role of neonatal G6PD deficiency and its identification. Indian J Pediatr 2014; 81 (6): 599–607.

    Article  Google Scholar 

  13. Kaplan M, Hammerman C . Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: a complexity of interactions between genes and environment. Semin Fetal Neonatal Med 2010; 15 (3): 148–156.

    Article  Google Scholar 

  14. Kaplan M, Hammerman C . Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies. Semin Perinatol 2011; 35 (3): 155–161.

    Article  Google Scholar 

  15. Slusher TM, Vreman HJ, McLaren DW, Lewison LJ, Brown AK, Stevenson DK . Glucose-6-phosphate dehydrogenase deficiency and carboxyhemoglobin concentrations associated with bilirubin-related morbidity and death in Nigerian infants. J Pediatr 1995; 126 (1): 102–108.

    Article  CAS  Google Scholar 

  16. Nair PA, Al Khusaiby SM . Kernicterus and G6PD deficiency–a case series from Oman. J Trop Pediatr 2003; 49 (2): 74–77.

    Article  Google Scholar 

  17. Mallouh AA, Imseeh G, Abu-Osba YK, Hamdan JA . Screening for glucose-6-phosphate dehydrogenase deficiency can prevent severe neonatal jaundice. Ann Trop Paediatr 1992; 12 (4): 391–395.

    Article  CAS  Google Scholar 

  18. Ogunlesi TA, Dedeke IO, Adekanmbi AF, Fetuga MB, Ogunfowora OB . The incidence and outcome of bilirubin encephalopathy in Nigeria: a bi-centre study. Niger J Med 2007; 16 (4): 354–359.

    CAS  PubMed  Google Scholar 

  19. Al-Naama LM, Al-Sadoon IA, Al-Naama MM . Neonatal jaundice and glucose-6-phosphate dehydrogenase deficiency in Basrah. Ann Trop Paediatr 1987; 7 (2): 134–138.

    Article  CAS  Google Scholar 

  20. Du L, Ma X . International perspectives: hyperbilirubinemia and kernicterus in neonates in China. NeoReviews 2012; 13: e141–e144.

    Article  Google Scholar 

  21. Kaplan M, Hammerman C . The need for neonatal glucose-6-phosphate dehydrogenase screening: a global perspective. J Perinatol 2009; 29 (Suppl 1): S46–S52.

    Article  CAS  Google Scholar 

  22. Watchko JF, Kaplan M, Stark AR, Stevenson DK, Bhutani VK . Should we screen newborns for glucose-6-phosphate dehydrogenase deficiency in the United States? J Perinatol 2013; 33 (7): 499–504.

    Article  CAS  Google Scholar 

  23. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (1): 297–316.

    Article  Google Scholar 

  24. Russell JC, Smith S, Novales W, Massi Lindsey LL, Hanson J . Use of the extended parallel processing model to evaluate culturally relevant kernicterus messages. J Pediatr Health Care 2013; 27 (1): 33–40.

    Article  Google Scholar 

  25. Waldrop JB, Anderson CK, Brandon DH . Guideline-based educational intervention to decrease the risk for readmission of newborns with severe hyperbilirubinemia. J Pediatr Health Care 2013; 27 (1): 41–50.

    Article  Google Scholar 

  26. Ezeaka CV, Ugwu RO, Mukhtar-Yola M, Ekure EN, Olusanya BO . Pattern and predictors of maternal care-seeking practices for severe neonatal jaundice in Nigeria: a multi-centre survey. BMC Health Serv Res 2014; 14: 192.

    Article  Google Scholar 

  27. Lau HK, Li CH, Lee AC . Acute massive haemolysis in children with glucose-6-phosphate dehydrogenase deficiency. Hong Kong Med J 2006; 12 (2): 149–151.

    CAS  PubMed  Google Scholar 

  28. Khneisser I, Adib SM, Loiselet J, Megarbane A . Cost-benefit analysis of G6PD screening in Lebanese newborn males. J Med Leban 2007; 55 (3): 129–132.

    Google Scholar 

  29. Padilla CD, Therrell BL . Newborn screening in the Asia Pacific region. J Inherit Metab Dis 2007; 30 (4): 490–506.

    Article  Google Scholar 

  30. Jiang J, Li B, Cao W, Jiang X, Jia X, Chen Q et al. Screening and prevention of neonatal glucose 6-phosphate dehydrogenase deficiency in Guangzhou, China. Genet Mol Res 2014; 13 (2): 4272–4279.

    Article  CAS  Google Scholar 

  31. Missiou-Tsagaraki S . Screening for glucose-6-phosphate dehydrogenase deficiency. J Pediatr 1992; 121 (1): 165–166.

    Article  Google Scholar 

  32. Missiou-Tsagaraki S . Screening for glucose-6-phosphate dehydrogenase deficiency as a preventive measure: prevalence among 1,286,000 Greek newborn infants. J Pediatr 1991; 119 (2): 293–299.

    Article  CAS  Google Scholar 

  33. Lin Z, Fontaine JM, Freer DE, Naylor EW . Alternative DNA-based newborn screening for glucose-6-phosphate dehydrogenase deficiency. Mol Genet Metab 2005; 86 (1-2): 212–219.

    Article  CAS  Google Scholar 

  34. Genetic Alliance, District of Columbia Department of Health. Newborn Screening, in Understanding Genetics. A Guide for Parents and Health Professionals. Chapter 4. Posted in the Resource Repository at http://www.resourcerepository.org/documents/1869/understandinggenetics:adistrictofcolumbiaguideforpatientsandhealthprofessionals/.

  35. Nock ML, Johnson EM, Krugman RR, Di Fiore JM, Fitzgerald S, Sandhaus LM et al. Implementation and analysis of a pilot in-hospital newborn screening program for glucose-6-phosphate dehydrogenase deficiency in the United States. J Perinatol 2011; 31 (2): 112–117.

    Article  CAS  Google Scholar 

  36. Meloni T, Forteleoni G, Meloni GF . Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the northern Sardinian experience. Acta Haematol 1992; 87 (1-2): 29–31.

    Article  CAS  Google Scholar 

  37. Meloni T, Cagnazzo G, Dore A, Cutillo S . Phenobarbital for prevention of hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborn infants. J Pediatr 1973; 82 (6): 1048–1051.

    Article  CAS  Google Scholar 

  38. Lam ST, Cheng ML . Neonatal screening in Hong Kong and Macau. Southeast Asian J Trop Med Public Health 2003; 34 (Suppl 3): 73–75.

    PubMed  Google Scholar 

  39. Joseph R, Ho LY, Gomez JM, Rajdurai VS, Sivasankaran S, Yip YY . Mass newborn screening for glucose-6-phosphate dehydrogenase deficiency in Singapore. Southeast Asian J Trop Med Public Health 1999; 30 (Suppl 2): 70–71.

    Google Scholar 

  40. Joseph R . Mass newborn screening in Singapore–position and projections. Ann Acad Med Singapore 2003; 32 (3): 318–323.

    CAS  PubMed  Google Scholar 

  41. Algur N, Avraham I, Hammerman C, Kaplan M . Quantitative neonatal glucose-6-phosphate dehydrogenase screening: distribution, reference values, and classification by phenotype. J Pediatr 2012; 161 (2): 197–200.

    Article  CAS  Google Scholar 

  42. Riskin A, Gery N, Kugelman A, Hemo M, Spevak I, Bader D . Glucose-6-phosphate dehydrogenase deficiency and borderline deficiency: association with neonatal hyperbilirubinemia. J Pediatr 2012; 161 (2): 191–196.

    Article  CAS  Google Scholar 

  43. Bhutani VK, Johnson L, Sivieri EM . Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999; 103 (1): 6–14.

    Article  CAS  Google Scholar 

  44. Kaplan M, Bromiker R, Schimmel MS, Algur N, Hammerman C . Evaluation of discharge management in the prediction of hyperbilirubinemia: the Jerusalem experience. J Pediatr 2007; 150 (4): 412–417.

    Article  CAS  Google Scholar 

  45. Newborn Screening Authoring Committee (E. Stephen Edwards, MD, Chairperson). Newborn screening expands: recommendations for pediatricians and medical homes—implications for the system. Pediatrics 2008; 121 (1): 192–217.

    Article  Google Scholar 

  46. Smith-Greenaway E . Mothers' reading skills and child survival in Nigeria: examining the relevance of mothers' decision-making power. Soc Sci Med 2013; 97: 152–160.

    Article  Google Scholar 

  47. Kuzniewicz MW, Wickremasinghe AC, Wu YW, McCulloch CE, Walsh EM, Wi S et al. Incidence, etiology, and outcomes of hazardous hyperbilirubinemia in newborns. Pediatrics 2014; 134 (3): 504–509.

    Article  Google Scholar 

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Acknowledgements

We are grateful to Ann R Stark, MD, for her thoughtful review of the manuscript and valuable suggestions.

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Authors and Affiliations

  1. Faculty of Medicine (Pediatrics), Hebrew University, Jerusalem, Israel

    M Kaplan & C Hammerman

  2. Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel

    C Hammerman

  3. Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA

    V K Bhutani

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  1. M Kaplan
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Correspondence to M Kaplan.

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Kaplan, M., Hammerman, C. & Bhutani, V. Parental education and the WHO neonatal G-6-PD screening program: a quarter century later. J Perinatol 35, 779–784 (2015). https://doi.org/10.1038/jp.2015.77

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