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  • Clinical Research Article
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Bilirubinemia and retinopathy of prematurity in infants ≤ 29 weeks’ gestational age

Pediatric Research volume 97, pages 1065–1071 (2025)Cite this article

Abstract

Background

Bilirubin is a known antioxidant. We hypothesized that the degree of bilirubinemia is inversely associated with oxidative stress-mediated retinopathy of prematurity (ROP).

Methods

A prospective study was performed to determine if bilirubinemia is associated with ROP in infants ≤ 29 wks’ gestational age and birth weights ≤ 1000 g. Total serum bilirubin (TSB) levels were measured at least twice daily during the first week and at least daily during the second week to determine peak and mean TSB levels. The outcomes were the incidence and severity of ROP.

Results

Of 193 infants studied, 110 developed ROP: 53 had mild (stage 1 in zone 2 or 3); 31 had moderate (stage 2 in zone 2 or 3); and 26 had severe ROP ( ≥ stage 3 in any zone or any stage in zone 1). Mean TSB levels were associated with the severity (adjusted odds ratio [AOR] 0.68, 95% confidence interval [CI]:0.47–0.98, p = 0.04), but not with the incidence of ROP (AOR 0.81, 95% CI:0.52–1.27, p = 0.3). Peak TSB levels were also associated with the severity (AOR 0.71, 95% CI:0.52-0.96, p = 0.02), but not with the incidence of ROP (AOR 0.71, 95% CI:0.48–1.01, p = 0.07).

Conclusions

Bilirubinemia may be protective against severity of ROP.

Impact

  • Retinopathy of prematurity (ROP) is a disease mediated by oxidative stress. Increasing antioxidant status may decrease the incidence and severity of ROP.

  • Bilirubin is a known antioxidant; however, findings from observational studies evaluating the role of bilirubinemia against the incidence and/or severity of ROP in premature infants are conflicting.

  • Our findings from this prospective study suggests that bilirubinemia may be protective against the severity of ROP.

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Data availability

Following article publication, de-identified data that support the findings of this study are available from authors on reasonable request and proposal.

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Acknowledgements

We are thankful to the parents and the nursing staff of the NICU. We are thankful to ophthalmologists who performed standard of care evaluation for retinopathy of prematurity. We are also grateful to Hongyue Wang, a biostatistician, who performed sample size calculation and statistical analysis. We are also thankful to research coordinators involved in this study.

Funding

The authors have no financial relationships relevant to this article to disclose. The study was partly funded by NIH R21 HD078744 and NIH R21 DC021161 grants to Sanjiv Amin. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of California, San Francisco, CA, USA

    Srujana Rallabandi

  2. Division of Neonatology, Department of Pediatrics, Children’s Hospital of Michigan, Central Michigan University, Detroit, MI, USA

    Sanjiv B. Amin

  3. Department of Pediatrics, Wayne State University, Detroit, MI, USA

    Sanjiv B. Amin

Authors
  1. Srujana Rallabandi
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  2. Sanjiv B. Amin
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Contributions

Dr. Amin conceptualized the study. All authors contributed to the study design. Material preparation, interpretation of data was performed by all authors. The first draft of the manuscript was written by Srujana Rallabandi. Sanjiv Amin revised it critically for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to Sanjiv B. Amin.

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Rallabandi, S., Amin, S.B. Bilirubinemia and retinopathy of prematurity in infants ≤ 29 weeks’ gestational age. Pediatr Res 97, 1065–1071 (2025). https://doi.org/10.1038/s41390-024-03479-8

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