Advertisement

The Indian Journal of Pediatrics

, Volume 81, Issue 6, pp 599–607 | Cite as

Prevention of Kernicterus in South Asia: Role of Neonatal G6PD Deficiency and its Identification

  • Yassar H. Arain
  • Vinod K. BhutaniEmail author
Review Article

Abstract

Extreme hyperbilirubinemia (EHB) caused by neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency is strongly associated with mortality and long-term neurodevelopmental impairment, yet there are limited national strategies to reduce this burden in South Asia. Current known and predicted prevalence of G6PD deficiency in Afghanistan, Bangladesh, Bhutan, India, Nepal, and Pakistan ranges from 3.8 to 15 %, with regional “hot spots” exceeding 22 %. Annually, 3.14 million infants are born at risk for this condition. In 2010, South Asian countries reported 37 million (27 %) of world-wide livebirths ≥ 32 wk gestational-age and G6PD deficiency accounted for > 33 % of the global EHB burden, in contrast to 2.2 % for those born in high-income nations. Traditional national approach includes universal newborn screening in malaria-endemic countries or those with prevalence >3.5 %. However, screening implementation should be best optimized using timely quantitative enzyme assay and identification of at-risk female newborns. Furthermore, economic and social constraints, in context of sub-regional variances, call for flexible problem-solving methods in anticipation of changing community demographics. Thus, incremental and need-based newborn screening programs could be the most optimal approach. A human-centered design (HCD) approach, as an alternate pathway, could build the evidence to translate the complex biology of G6PD deficiency and the biodesign of affordable technologies, allowing facilitation of access to knowledge and services, in order to deliver on a long-term public health mandate. Key steps would encompass the initiation of local inquiry of both quantitative and qualitative data to identify at-risk communities and to prospectively design for local innovative solutions.

Keywords

Neonatal Jaundice Hyperbilirubinemia G6PD deficiency Impairment Disability Mortality Deafness 

Notes

Acknowledgements

The authors would like to thank Global Prevent Kernicterus Network (Stanford): Lois Johnson (USA); Ronald J. Wong (Stanford University); Shanmukha Srinivas for data collection and map design, Martin Castillo Cuadrado for statistical analysis, and Dr. Matthew B. Wallenstein for his editing.

Contributions

YA: Conducted the research on the model design, its application, review of literature and initial draft of the manuscript; VKB: Conducted the research, assessed the burden, conceptualized the study design and completed the final version of the manuscript, and will act as guarantor of this paper.

Conflict of Interest

None.

Role of Funding Source

No specific financial assistance was received in support of this study. This work was partially funded by SBIR; VKB has received grant support from the National Institutes of Health (NIHSBIR Sub-Award: HD062316).

References

  1. 1.
    Kaplan M, Bromiker R, Hammerman C. Severe neonatal hyperbilirubinemia and kernicterus: Are these still problems in the third millennium? Neonatology. 2011;100:354–62.PubMedCrossRefGoogle Scholar
  2. 2.
    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 andglobal levels. Pediatr Res. 2013;74:86–100.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Bhutani VK, Stark AR, Lazzeroni LC, Poland R, Gourley GR, Kazmierczak S, et al; Initial clinical testing evaluation and risk assessment for universal screening for Hyperbilirubinemia Study Group. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr. 2013;162:477–82.PubMedCrossRefGoogle Scholar
  4. 4.
    Weng YH, Chiu YW, Cheng SW, Hsieh MY. Risk assessment for adverse outcome in term and late preterm neonates with bilirubin values of 20 mg/dL or more. Am J Perinatol. 2011;28:405–12.PubMedCrossRefGoogle Scholar
  5. 5.
    Newman T, Xiong B, Gonzales V, Escobar G. Prediction and prevention of extreme neonatal hyperbilirubinemia in a mature health maintenance organization. Arch Pediatr Adolesc Med. 2000;154:1140–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Keren R, Luan X, Friedman S, Saddlemire S, Cnaan A, Bhutani VK. A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants. Pediatrics. 2008;121:e170–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Dennery PA, Seidman DS, Steveson DK. Neonatal hyperbilirubinemia. N Engl J Med. 2001;344:581–90.PubMedCrossRefGoogle Scholar
  8. 8.
    Bhutani VK, Johnson LH, Maisels MJ, Newman TB, Phibbs C, Stark AR, et al. Kernicterus: Epidemiological strategies for its prevention through systems-based approaches. J Perinatol. 2004;24:650–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Bhutani VK. Jaundice due to glucose-6-phosphate dehydrogenase deficiency. NeoReviews. 2012;13:e166–77.CrossRefGoogle Scholar
  10. 10.
    Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ. 2006;175:587–90.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Manning D, Todd P, Maxwell M, Platt MJ. Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed. 2007;92:F342–6.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    IDEO. Human-centered design toolkit: An open-source toolkit to inspire new solutions in the developing world. IDEO, 2011.Google Scholar
  13. 13.
    Shapiro SM. Hyperbilirubinemia and therisk for brain injury. In: Perlman J, Polin R, eds. Neurology: Neonatology Questions and Controversies. Philadelphia: Saunders Elsevier; 2008. p. 195–209.Google Scholar
  14. 14.
    Bhutani VK, Wong RJ. Bilirubin neurotoxicity in preterm infants: Risk and prevention. J Clin Neonatol. 2013;2:61–9.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage–mechanisms and management approaches. N Engl J Med. 2013;369:2021–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Maisels MJ, Bhutani VK, Bogen D, Newman T, Stark A, Watchko JF. Hyperbilirubinemia in the newborn infant or = 35 weeks’ gestation: An update with clarifications. Pediatrics. 2009;124:1193–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371:64–74.PubMedCrossRefGoogle Scholar
  18. 18.
    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;42:267–78.PubMedCrossRefGoogle Scholar
  19. 19.
    Luzzatto L, Metha A, Vulliamy T. Glucose 6-phosphate dehydrogenase deficiency. In: Scriver C, Beaudet A, Sly W, eds. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill; 2001. p. 4517–53.Google Scholar
  20. 20.
    Kaplan M, Rubaltelli TM, Hammerman C, Vilei MT, Leiter C, Abramov A, et al. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency. J Pediatr. 1996;128:695–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Lin Z, Fontaine J, Watchko JF. Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics. 2008;122:e156–62.PubMedCrossRefGoogle Scholar
  22. 22.
    Luzzatto L, Malaria NN. Protecting against bad air. Science. 2001;293:442–3.PubMedCrossRefGoogle Scholar
  23. 23.
    Luzzatto L. Glucose 6-phosphate dehydrogenase deficiency: From genotype to phenotype. Haematologica. 2006;91:1303–6.PubMedGoogle Scholar
  24. 24.
    Howes R, Piel F, Patil A, Nyangiri OA, Gething PW, Dewi M, et al. G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: A geostatistical model-based map. PLoS Med. 2012;9:e1001339.Google Scholar
  25. 25.
    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;33:499–504.PubMedCrossRefGoogle Scholar
  26. 26.
    Leslie T, Moiz B, Mohammad N, Amanzai O, Ur Rasheed H, Jan S, et al. Prevalence and molecular basis of glucose-6-phosphate dehydrogenase deficiency in Afghan populations: Implications for treatment policy in the region. Malar J. 2013;12:230.Google Scholar
  27. 27.
    Saha N, Tay JSH. Genetic studies among the Nagas and Hmars of eastern India. Am J Phys Anthropol. 1990;82:101–12.PubMedCrossRefGoogle Scholar
  28. 28.
    Ramadevi R, Savithri HS, Devi AR, Bittles AH, Rao NA. An unusual distribution of glucose-6-phosphate dehydrogenase deficiency of south Indian newborn popluation. Indian J Biochem Biophys. 1994;31:358–60.PubMedGoogle Scholar
  29. 29.
    Dash S, Chhanhimi L, Chhakchhuak L, Zomawaia E. Screening for haemoglobinopathies and G6PD deficiency among the Mizos of Mizoram: A preliminary study. Indian J Pathol Microbiol. 2005;48:17–8.Google Scholar
  30. 30.
    Sharma M, Dass J, Dhingra B, Saxena R. G6PD deficiency in females screened at tertiary care hospital. Indian J Pathol Microbiol. 2011;54:850–1.PubMedGoogle Scholar
  31. 31.
    Balgir RS. Community expansion and gene geography of sickle cell trait and G6PD deficiency, and natural selection against malaria: Experience from tribal land of India. Cardiovasc Hematol Agents Med Chem. 2012;10:3–13.Google Scholar
  32. 32.
    Bisoi S, Chakraborty S, Chattopadhyay D, Biswat B, Ray S. Glucose-6-phosphate dehydrogenase screening of babies born in a tertiary care hospital in West Bengal. Indian J Public Health. 2012;56:146–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Matsuoka H, Jichun W, Hirai M, Yoshida S, Arai M, Ishii A, et al. Two cases of glucose-6-phosphate dehydrogenase-deficient Nepalese belonging to the G6PD Mediterranean-type, not India-Pakistan sub-type but Mediterranean-Middle East sub-type. J Hum Genet. 2003;48:275–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Stern MA, Kynoch PA, Lehmann H. Beta-thalassaemia, glucose-6-phosphate-dehydrogenase deficiency, and haemoglobin D-Punjab in Pathans. Lancet. 1968;291:1284–5.CrossRefGoogle Scholar
  35. 35.
    Nair H. Neonatal screening program for G6PD deficiency in India: Need and feasibility. Indian Pediatr. 2009;46:1045–9.Google Scholar
  36. 36.
    Bhutani VK. Public policy to prevent severe neonatal hyperbilirubinemia. In: Stevenson DK, Maisels MJ, Watchko JF, eds. Care of the Jaundiced Neonate. New York: McGraw-Hill; 2012. pp. 243–62.Google Scholar
  37. 37.
    Kaplan M, Hammerman C. Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: Biochemical versus genetic technologies. Semin Perinatol. 2011;35:155–61.Google Scholar
  38. 38.
    Abu-Osba YK, Mallouh AA, Hann RW. Incidence and causes of sepsis in glucose-6-phosphate dehydrogenase-deficient newborn infants. J Pediatr. 1989;114:748–52.PubMedCrossRefGoogle Scholar
  39. 39.
    Gamaleldin R, Iskander I, Seoud I, Aboraya H, Aravkin A, Sampson PD, et al. Risk factors for neurotoxicity in newborns with severe neonatal hyperbilirubinemia. Pediatrics. 2011;128:e925–31.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Crosse VM, Meyer TC, Gerrard JW. Kernicterus and prematurity. Arch Dis Child. 1955;30:501–8.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Ahlfors C, Amin S, Parker A. Unbound bilirubin predicts abnormal automated auditory brainstem response in a diverse newborn population. J Perinatol. 2009;29:305–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Trotman H, Henny-Harry C. Factors associated with extreme hyperbilirubinaemia in neonates at the University Hospital of the West Indies. Paediatr Int Child Health. 2012;32:97–101.PubMedCrossRefGoogle Scholar
  43. 43.
    WHO WG. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ. 1989;67:601–11.Google Scholar
  44. 44.
    Padilla CD, Krotoski D, Therrell Jr BL. Newborn screening progress in developing countries—overcoming internal barriers. Semin Perinatol. 2010;34:145–55.PubMedCrossRefGoogle Scholar
  45. 45.
    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;119:293–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Joseph R, Hoy 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;30:70–1.PubMedGoogle Scholar
  47. 47.
    Slusher T, Zipursky A, Bhutani VK. A Global need for affordable neonatal jaundice technologies. Semin Perinatol. 2011;35:185–91.PubMedCrossRefGoogle Scholar
  48. 48.
    Nair H, Panda R. Quality of maternal health care in India: Has the National Rural Health Mission made a difference? J Glob Health. 2011;1:79–86.Google Scholar
  49. 49.
    Weiss MG, Ramakrishna JR, Somma D. Health-related stigma: Rethinking concepts and interventions. Psychol Health Med. 2006;11:277–87.Google Scholar
  50. 50.
    Solanki KK. Training programmes for developing countries. J Inherit Metab Dis. 2007;30:596–9.PubMedCrossRefGoogle Scholar
  51. 51.
    WHO. WHO Collaborating Centres. 2013. http://www.who.int/collaboratingcentres/en/. Accessed on 21 Oct 2013.

Copyright information

© Dr. K C Chaudhuri Foundation 2014

Authors and Affiliations

  1. 1.Division of Neonatal and Developmental Medicine, Department of PediatricsStanford University School of Medicine, Lucile Packard Children’s HospitalStanfordUSA
  2. 2.Department of Pediatrics, Division of Neonatal and Developmental MedicineStanford University School of MedicinePalo AltoUSA

Personalised recommendations