Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Patterns of acute bilirubin encephalopathy in Nigeria: a multicenter pre-intervention study

Abstract

Background

Acute bilirubin encephalopathy (ABE) is an important cause of neonatal morbidity in Nigeria, accounting for 5–14% of neonatal deaths. Most newborns with severe ABE have irreversible damage before receiving treatment emphasizing the need for timely pre-admission monitoring and referral. There is limited evidence that educational interventions targeting mothers and health care providers will reduce delayed care.

Objective

To provide baseline data on the incidence of ABE and associated pre-admission risk factors in five centers of Nigeria in order to evaluate the effect of subsequent educational interventions on outcome.

Study design

The incidence of ABE among newborns treated for hyperbilirubinemia was documented prospectively. Bivariate analysis and multivariate logistic regression were used to evaluate risk factors for acute bilirubin encephalopathy and reasons for regional differences in its occurrence.

Results

Of 1040 infants, 159 treated for hyperbilirubinemia (15.3%) had mild to severe bilirubin encephalopathy (including 35 deaths), but the incidence ranged from 7 to 22% between centers. Logistic regression identified four common predictors: total serum bilirubin (odds ratio 1.007 per mg/dl rise), out-of-hospital births (OR 2.6), non-alloimmune hemolytic anemia (OR 2.8), and delayed care seeking (OR 4.3).

Conclusion

The high occurrence of bilirubin encephalopathy in Nigeria is due in large part to a delay in seeking care. A planned intervention strategy will target conditions leading to severe hyperbilirubinemia and delay.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Adebami OJ. Factors associated with the incidence of acute bilirubin encephalopathy in Nigerian population. J Pediatr Neurol. 2011;9(20):347–53.

    CAS  Google Scholar 

  2. 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):354–9.

    CAS  PubMed  Google Scholar 

  3. Owa JA, Taiwo O, Adebiyi JAO, Dogunro SA. Neonatal Jaundice at Wesley Guild Hospital. Ilesa and Ife State Hospital, Ile-Ife. Niger J Paediatr. 1989;16:23–30.

    Google Scholar 

  4. Owa JA, Osinaike AI. Neonatal morbidity and mortality in Nigeria. Indian J Pediatr. 1998;65(3):441–9.

    Article  CAS  Google Scholar 

  5. Okechukwu A, Achonwa A. Morbidity and mortality patterns of admissions into the special care baby unit of University of Abuja Teaching Hospital. Niger J Clin Pract. 2009;4(12):389–94.

    Google Scholar 

  6. Udo JJ, Anah MU, Ochigbo SO, Etuk IS, Ekanem AD. Neonatal morbidity and mortality in Calabar, Nigeria: a hospital-based study. Niger J Clin Pract. 2008;11(3):285–9.

    CAS  PubMed  Google Scholar 

  7. Ugwu R, Eneh A, Oruamabo R. Mortality in the special care baby unit of the University of Port Harcourt Teaching Hospital (UPTH). Why and when do newborns die? Nig J Paediatr. 2006;3(33):133–4.

    Google Scholar 

  8. Iskander I, Gamaleldin R, El Houchi S, El Shenawy A, Seoud I, El Gharbawi N, et al. Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy. Pediatrics . 2014;134(5):e1330–e1339.

    Article  Google Scholar 

  9. Saluja S, Agarwal A, Kler N, Amin S. Auditory neuropathy spectrum disorder in late preterm and term infants with severe jaundice. Int J Pediatr Otorhinolaryngol. 2010;74(11):1292–7.

    Article  Google Scholar 

  10. Olusanya BO, Akande AA, Emokpae A, Olowe SA. Infants with severe neonatal jaundice in Lagos, Nigeria: incidence, correlates and hearing screening outcomes. Trop Med Int Health. 2009;14:301–10.

    Article  CAS  Google Scholar 

  11. Belonwu RO, Gwarzo GD, Adeleke SI. Cerebral palsy in Kano, Nigeria-a review. Niger J Med. 2009;18:186–9.

    Article  CAS  Google Scholar 

  12. Ayanniyi O, Abdulsalam KS. Profile of children with cerebral palsy attending out-patient physiotherapy clinics in Southwest Nigeria. AJPARS. 2015;7:32–39.

    Google Scholar 

  13. Okperi BO. Neonatal jaundice and birth asphyxia as major causes of cerebral palsy in Nigeria: are doctors’ wrong beliefs and practices part of the problem? Int J Med Biomed Res. 2013;2:226–30.

    Article  Google Scholar 

  14. Olusanya BO, Ogunlesi TA, Slusher TM. Why is kernicterus still a major cause of death and disability in low and middle-income countries? Arch Dis Child. 2014;99(12):1117–21.

    Article  Google Scholar 

  15. Owa JA, Ogunlesi TA. Why we are still doing so many exchange blood transfusion for neonatal jaundice in Nigeria. World J Pediatr. 2009;5(1):51–55.

    Article  Google Scholar 

  16. Ogunlesi TA, Ogunfowora OB. Predictors of acute bilirubin encephalopathy among Nigerian term babies with moderate-to-severe hyperbilirubinaemia. J Trop Pediatr. 2011;57(2):80–86.

    Article  Google Scholar 

  17. Ogunlesi TA, Abdul AR. Maternal knowledge and care-seeking behaviors for newborn jaundice in Sagamu, Southwest Nigeria. Niger J Clin Pract. 2015;18(1):33–40.

    CAS  PubMed  Google Scholar 

  18. Ogunlesi T, Ogunlesi F. Family socio-demographic factors and maternal obstetric factors influencing appropriate health-care seeking behaviours for newborn jaundice in Sagamu, Nigeria. Matern Child Health J. 2012;16(3):677–84.

    Article  Google Scholar 

  19. Goodman OOK, Odugbemi BA, Femi-Adebayo TT, Odusanya OO. Neonatal jaundice: knowledge, attitude and practices of mothers in Mosan-Okunola community, Lagos, Nigeria. Niger Postgrad Med J. 2015;22(3):158–63.

    Article  Google Scholar 

  20. Egube BA, Ofili AN, Isara AR, Onakewhor JU. Neonatal jaundice and its management: knowledge, attitude, and practice among expectant mothers attending antenatal clinic at University of Benin Teaching Hospital, Benin City, Nigeria. Niger J Clin Pract. 2013;16(2):188–94.

    Article  CAS  Google Scholar 

  21. Eneh AU, Ugwu RO. Perception of neonatal jaundice among women attending children out patient and immunization clinics of the UPTH Port Harcourt. Niger J Clin Pract. 2009;12(2):187–91.

    CAS  PubMed  Google Scholar 

  22. 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(1):192–192.

    Article  Google Scholar 

  23. 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:S25–45. Suppl 1

    Article  Google Scholar 

  24. El Houchi SZ, Iskander I, Gamaleldin R, El Shenawy A, Seoud I, Abou-Youssef H, et al. Prediction of 3- to 5-month outcomes from signs of acute bilirubin toxicity in newborn infants. J Pediatr. 2017;183:51–55. e1

    Article  CAS  Google Scholar 

  25. Radmacher PG, Groves FD, Owa JA, Ofovwe GE, Amuabunos EA, Olusanya BO, et al. A modified Bilirubin-induced neurologic dysfunction (BIND-M) algorithm is useful in evaluating severity of jaundice in a resource-limited setting. BMC Pediatr. 2015;15:28.

    Article  Google Scholar 

  26. Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). J Perinatol. 2005;25(1):54–59.

    Article  CAS  Google Scholar 

  27. Watchko JF, Oski FA. Bilirubin 20 mg/dL = vigintiphobia. Pediatrics. 1983;71(4):660–3.

    CAS  PubMed  Google Scholar 

  28. 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):504–9.

    Article  Google Scholar 

  29. 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 

  30. Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33:1.

    Article  Google Scholar 

  31. Hoerl AE, Kennard RW. Ridge regresssion: biased estimation for nonorthogonal problems. Technometrics. 1970;12:55–67.

    Article  Google Scholar 

  32. Tibshirani R. Regression shrinkage and selection via the lasso. J Royal Stat. Soc. Series B Methodol. 1996;58(1):267–88.

    Google Scholar 

  33. Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM. Toward understanding kernicterus: a challenge to improve the management of jaundiced newborns. Pediatrics. 2006;117(2):474–85.

    Article  Google Scholar 

  34. Olusanya BO, Iskander IF, Slusher TM, Wennberg RP. A decision-making tool for exchange transfusions in infants with severe hyperbilirubinemia in resource-limited settings. J Perinatol. 2016;36(5):338–41.

    Article  CAS  Google Scholar 

  35. 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):102–8.

    Article  CAS  Google Scholar 

  36. Williams O, Gbadero D, Edowhorhu G, Brearley A, Slusher T, Lund TC. Glucose-6-phosphate dehydrogenase deficiency in Nigerian children. PLoS One. 2013;8(7):e68800.

    Article  CAS  Google Scholar 

  37. 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. 2014;103(11):1102–9.

    Article  CAS  Google Scholar 

  38. Owa JA. Relationship between exposure to icterogenic agents, glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Nigeria. Acta Paediatr Scand. 1989;78(6):848–52.

    Article  CAS  Google Scholar 

  39. Sodeinde O, Chan MC, Maxwell SM, Familusi JB, Hendrickse RG. Neonatal jaundice, aflatoxins and naphthols: report of a study in Ibadan, Nigeria. Ann Trop Paediatr. 1995;15(2):107–13.

    Article  CAS  Google Scholar 

  40. Israel-Aina YT, Omoigberale AI. Risk factors for neonatal jaundice in babies presenting at the University of Benin Teaching Hospital Benin City. Niger J Paediatr. 2012;39:159–63.

    Google Scholar 

  41. WHO Working Group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ. 1989;67:601–11.

    Google Scholar 

  42. Kaplan M, Hammerman C, Bhutani VK. Parental education and the WHO neonatal G-6-PD screening program: a quarter century later. J Perinatol. 2015;35:779–84.

    Article  CAS  Google Scholar 

  43. Ogunfowora OB, Daniel OJ. Neonatal jaundice and its management: knowledge, attitude and practice of community health workers in Nigeria. BMC Public Health. 2006;6:19.

    Article  Google Scholar 

  44. Moawad EM, Abdallah EA, Ali YZ. Perceptions, practices, and traditional beliefs related to neonatal jaundice among Egyptian mothers: A cross-sectional descriptive study. Med (Baltim). 2016;95(36):e4804.

    Article  Google Scholar 

  45. National Population Commission (NPC) [Nigeria] and ICF International. Nigeria Demographic and Health Survey 2013. NPC and ICF International. NPC and ICF International Abuja, Nigeria, and Rockville, Maryland, USA: 2014.

  46. Federal Ministry of Health. Saving newborn lives in Nigeria: Newborn health in the context of the Integrated Maternal, Newborn and Child Helath Strategy. 2nd ed. Abuja: Federal Ministry of Health, Save the Children; 2011.

  47. Olusanya BO, Osibanjo FB, Mabogunje CA, Slusher TM, Olowe SA. The burden and management of neonatal jaundice in Nigeria: A scoping review of the literature. Niger J Clin Pract. 2016;19(1):1–17.

    Article  CAS  Google Scholar 

  48. World Health Organisation. Pocket book of hospital care for children. Guidelines for the management of common childhood illnesses. 2nd edn. Geneva, Switzerland: WHO; 2013.

    Google Scholar 

  49. Coda Zabetta CD, Iskander IF, Greco C, Bellarosa C, Demarini S, Tiribelli C, et al. Bilistick: a low-cost point-of-care system to measure total plasma bilirubin. Neonatology. 2013;103:177–81.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was made possible in part through the generous support of the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, and the UK Government. It was prepared by the “Stop Kernicterus in Nigeria” consortium and Bilimetrix, srl and does not necessarily reflect the views of the Saving Lives at Birth partners.”

Author contributions

The study results from the concerted contributions of the entire “Stop Kernicterus in Nigeria” (SKIN) team who also reviewed and approved the manuscript. Trieste (ITA): C Greco, C Tiribelli; Asaba (NGA): A Okolo, OU Chima; Lagos (NGA): Z Imam,; A Odunsi, S Olaifa; Jos(NGA): F Bode-Thomas, C Isichei, CS Yilgwan, Z Hassan, D Shwe, AO Ofakunrin, H Abdu, E Olagbaju, VC Pam, JO Abba, SN Attah; Zaria(NGA): WN Ogala, LHassan, F Abdullahi, S Purdue; Kano(NGA): BW Jibir, IY Mohammed, HA Usman, M Abdusalam, SU Abdullahi, F Usman, A Kuliya-Gwarzo, FI Tsiga-Ahmad, L Umar.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Udochukwu M Diala.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Table 1. (supplemental) PARTICIPATING CENTERS(DOCX 17 kb)

Table 2 (supplemental) Database(DOCX 17 kb)

41372_2018_94_MOESM3_ESM.docx

Supplement Figure 1. Receiver-Operator-Characteristic (ROC) curve measuring the power of the Multiple Logistic Regression model for predicting ABE(DOCX 35 kb)

Supplement Table 3. Regional variations in incidence of ABE and associated risk factors(DOCX 35 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diala, U.M., Wennberg, R.P., Abdulkadir, I. et al. Patterns of acute bilirubin encephalopathy in Nigeria: a multicenter pre-intervention study. J Perinatol 38, 873–880 (2018). https://doi.org/10.1038/s41372-018-0094-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-018-0094-y

This article is cited by

Search

Quick links