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  • Clinical Research Article
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Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study

Pediatric Research volume 95, pages 285–292 (2024)Cite this article

Abstract

Background

Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD.

Methods

The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT).

Results

Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3–12 months, with 50–100% sensitivity.

Conclusions

Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention.

Impact

  • The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life.

  • Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD).

  • Brain MRI at 3 or 12 months can confirm KSD.

  • The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD.

  • The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

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Fig. 1: Hyperbilirubinemia Imaging Rating Tool (HIRT): MRI of infants with hyperbilirubinemia are visually scored using this newly developed rating scale.
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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was funded by a Children’s Mercy Hospital internal grant to J.B.L.P. R.G.-M. is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number T32HD069038). The funding sources had no role in study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.

Author information

Author notes

  1. These authors contributed equally: Rose Gelineau-Morel, Fatima Usman.

  2. These authors jointly supervised this work: Jean-Baptiste Le Pichon, Zubaida L. Farouk.

Authors and Affiliations

  1. Division of Neurology, Children’s Mercy Hospital Kansas City, Kansas City, MO, USA

    Rose Gelineau-Morel & Jean-Baptiste Le Pichon

  2. University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

    Rose Gelineau-Morel, Hung-Wen Yeh, Timothy P. Zinkus, Hayden W. Head & Jean-Baptiste Le Pichon

  3. Department of Pediatrics, Bayero University Kano & Aminu Kano Teaching Hospital, Kano, Nigeria

    Fatima Usman, Saadatu Shehu, Mohammed Abdulsalam & Zubaida L. Farouk

  4. Division of Health Services & Outcomes Research, Children’s Mercy Hospital Kansas City, Kansas City, MO, USA

    Hung-Wen Yeh

  5. Department of Radiology, Bayero University Kano & Aminu Kano Teaching Hospital, Kano, Nigeria

    Mohammad A. Suwaid

  6. Department of Otorhinolaryngology, Aminu Kano Teaching Hospital, Kano, Nigeria

    Yasir Jibril

  7. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Katherine M. Satrom

  8. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA

    Steven M. Shapiro

  9. Division of Radiology, Children’s Mercy Hospital Kansas City, Kansas City, MO, USA

    Timothy P. Zinkus & Hayden W. Head

  10. Department of Pediatrics, Global Health Program, Critical Care Division, University of Minnesota, Minneapolis, MN, USA

    Tina M. Slusher

  11. Department of Pediatrics, Hennepin Healthcare, Minneapolis, MN, USA

    Tina M. Slusher

Authors
  1. Rose Gelineau-Morel
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  13. Jean-Baptiste Le Pichon
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  14. Zubaida L. Farouk
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Contributions

R.G.-M. contributed to conceptualization, investigation, methodology, data curation, visualization, and writing the original draft. Fatima Usman contributed to conceptualization, investigation, data curation, and project administration. S.S., Y.J., and M.A. contributed to investigation and data curation. H.-W.Y. contributed to formal analysis and visualization. Mohammad Suwaid contributed to methodology, data curation, investigation, and project administration. K.S. contributed to data interpretation and visualization. S.S. contributed to conceptualization, investigation, and methodology. T.Z. and H.H. contributed to investigation. T.S., J.-B.L.P., and Z.F. contributed to conceptualization, methodology, and supervision. All authors contributed to writing- review and editing and approved the final version of the manuscript.

Corresponding author

Correspondence to Rose Gelineau-Morel.

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Competing interests

R.G.-M. is supported by the NICHD (grant number T32HD069038). She has received a travel grant from the American Society of Clinical Pharmacology and Therapeutics and has a provisional patent for a novel drug for the treatment of movement disorders. F.U. and S.S. declared internal funding from Children’s Mercy Hospital to support patient MRI costs for the study. T.S. declared internal funding for travel and hotel only from Children’s Mercy Hospital related to this study. J.-B.L.P. declared internal funding from Children’s Mercy Hospital to support the costs of this study. He also serves on the editorial board of Pediatric Neurology and Annals of Child Neurology Society and is a clinical advisory round table member for the Firefly Fund for Neimann Pick type C. J.-B.L.P. also provides medical expertize on an occasional basis to various law firms. All other authors declare no conflicts of interest.

Informed consent

Participant families provided informed consent for this study through the Aminu Kano Teaching Hospital, Nigeria.

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Gelineau-Morel, R., Usman, F., Shehu, S. et al. Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study. Pediatr Res 95, 285–292 (2024). https://doi.org/10.1038/s41390-023-02810-z

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  • DOI: https://doi.org/10.1038/s41390-023-02810-z

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