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Significance of serum biomarkers in preterm infants screened for retinopathy of prematurity: a systematic review and meta-analysis

Eye volume 39, pages 3167–3175 (2025)Cite this article

Subjects

Abstract

Background/Objectives

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. This systematic review and meta-analysis assess the association between eight serum biomarkers and the presence of ROP in premature neonates. These biomarkers are neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), red cell distribution width (RDW), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), platelet mass index (PMI), systemic immune-inflammation index (SII), and vitamin D.

Subjects/Methods

A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Cochrane Library for studies published up to February 2025. Eligible studies included quantitative data on serum biomarker levels in premature neonates with and without ROP. A random-effects meta-analysis estimated standardised mean differences (SMDs) and 95% confidence intervals (CIs). Risk of bias was assessed using the Newcastle-Ottawa Scale.

Results

Twenty-one studies comprising 3965 participants were included. Significant associations were found for NLR (SMD = 0.43, 95% CI: 0.16–0.71, P = 0.002), RDW (SMD = 0.41, 95% CI: 0.15–0.67, P = 0.002), and vitamin D (SMD = −1.18, 95% CI: -1.47–-0.90, P < 0.00001). CRP, LMR, PLR, PMI, and SII did not show significant associations with ROP presence.

Conclusions

NLR, RDW, and vitamin D levels are potential biomarkers associated with ROP presence in premature neonates, likely reflecting systemic inflammation and vascular pathology. Further large-scale prospective studies are warranted to establish standardised cutoff values for clinical implementation.

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Fig. 1: PRISMA flow of study selection.
Fig. 2: Forest plot of meta-analysis.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Acknowledgements

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Funding

No funding was received for conducting this study.

Author information

Author notes

  1. These authors contributed equally: Shu-Han Chuang, Yen Thi Thao Le.

Authors and Affiliations

  1. Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan

    Shu-Han Chuang & Cheng-Hsien Chang

  2. International Master Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yen Thi Thao Le

  3. Department of Ophthalmology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam

    Yen Thi Thao Le

  4. Division of General Practice, Department of Medical Education, Changhua Christian Hospital, Changhua, Taiwan

    Yan-Han Li

  5. Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan

    Cheng-Hsien Chang

  6. School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan

    Yu Zhi Lian

  7. Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Yi-Jie Kuo & Yu-Pin Chen

  8. Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yi-Jie Kuo & Yu-Pin Chen

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Contributions

Conceptualisation: Shu-Han Chuang, Yen Thi Thao Le, Cheng-Hsien Chang. Data curation: Shu-Han Chuang, Yen Thi Thao Le, Yan-Han Li, Yu Zhi Lian. Formal analysis: Shu-Han Chuang, Yen Thi Thao Le, Yan-Han Li, Yu Zhi Lian. Investigation: Shu-Han Chuang, Yen Thi Thao Le, Yan-Han Li, Cheng-Hsien Chang. Methodology: Cheng-Hsien Chang, Yi-Jie Kuo, Yu-Pin Chen. Software: Yi-Jie Kuo, Yu-Pin Chen. Resources: Cheng-Hsien Chang, Yi-Jie Kuo, Yu-Pin Chen. Supervision: Cheng-Hsien Chang, Yi-Jie Kuo, Yu-Pin Chen. Validation: Shu-Han Chuang, Yen Thi Thao Le, Yan-Han Li, Yu Zhi Lian. Visualisation: Shu-Han Chuang, Yen Thi Thao Le, Yan-Han Li, Yu Zhi Lian. Writing – original draft: Shu-Han Chuang, Yen Thi Thao Le, Yan-Han Li, Yu Zhi Lian. Writing – review & editing: Cheng-Hsien Chang, Yi-Jie Kuo, Yu-Pin Chen.

Corresponding author

Correspondence to Yu-Pin Chen.

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Ethics

The Institutional Review Board Committee of Changhua Christian Hospital in Taiwan granted ethical approval for the execution of this study (IRB number: 240607).

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Chuang, SH., Le, Y.T.T., Li, YH. et al. Significance of serum biomarkers in preterm infants screened for retinopathy of prematurity: a systematic review and meta-analysis. Eye 39, 3167–3175 (2025). https://doi.org/10.1038/s41433-025-04051-2

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