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Association between neonatal phototherapy and future cancer: an updated systematic review and meta-analysis

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Abstract

Phototherapy is the main treatment of neonatal hyperbilirubinemia to prevent encephalopathy. It is generally believed to be safe; however, some studies have shown it might be associated with cancer development. In this systematic review and meta-analysis, we aimed to assess the effect of neonatal phototherapy on future cancer risk. A systematic search in 13 databases was conducted in December 2018 and updated in August 2022 to identify studies that report cancer development after exposure to phototherapy. Throughout the study period, regular manual searches were also conducted to include new studies. A meta-analysis using R programming language was done in which the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated and pooled using the reported adjusted and unadjusted data. Fifteen studies were included. A statistically significant association was detected between neonatal phototherapy and any type of cancer (OR 1.24; 95% CI 1.1, 1.4), any hematopoietic cancer (OR 1.49; 95% CI 1.17, 1.91), any leukemia (OR 1.35; 95% CI 1.08, 1.67), and myeloid leukemia (OR 2.86; 95% CI 1.4, 5.84). The other investigated cancers (lymphoid leukemia, Hodgkin’s lymphoma, kidney cancer, nervous system cancer, and skin cancer) were not associated with phototherapy.

  Conclusions: Phototherapy may carry a possible risk of future cancers. Future research is needed to quantify the magnitude of the cancer risk. These future studies should consider predictors of preterm birth or exclude premature babies from their analysis.

What is Known

• There were various reports about the possible association between phototherapy in neonates and the increased risk of cancer in the future.

What is New

• A statistically significant association between phototherapy and various hematopoietic cancers (especially myeloid leukemia) was recorded.

• The effect of the duration of phototherapy on the increased risk of hematopoietic cancers is yet unclear.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available. However, the data can be provided by the corresponding author (Nguyen Tien Huy, tienhuy@nagasaki-u.ac.jp) on reasonable request.

Abbreviations

CI:

Confidence interval

GHL:

Global Health Library

ICD:

International Classification of Diseases

NHL:

Non-Hodgkin’s lymphoma

NIH:

National Institutes of Health

NYAM:

New York Academy of Medicine

OR:

Odds ratio

PRISMA:

Preferred Reporting Items for Systematic review and Meta-Analysis

PT:

Phototherapy

SD:

Standard deviation

SIGLE:

System for Information on Grey Literature in Europe

VHL:

Virtual Health Library

WHO:

World Health Organization

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Acknowledgements

We are very grateful to Professor Thor Willy Ruud Hansen (t.w.r.hansen@medisin.uio.no) for his thorough revision and his contributions to improving the overall quality of the manuscript. We also thank Lina Hemmeda for her contributions to the previous version of the manuscript. Finally, we would like to express our gratitude to Dr. Julia Wang (wang.julia.m@gmail.com) for proofreading and editing the manuscript before its publication.

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Author notes

  1. Mohammed Abdellatif, Gehad Mohamed Tawfik, and Abdelrahman M. Makram equally contributed to the manuscript and share first authorship.

Authors and Affiliations

  1. Starcare Hospital, Muscat, Oman

    Mohammed Abdellatif

  2. Online Research Club, Nagasaki, Japan

    Mohammed Abdellatif, Gehad Mohamed Tawfik, Abdelrahman M. Makram, Mostafa Khaled Abdelsattar, Monica Dobs, Dimitrios N. Papadopoulos, Bao-Long Hoang-Trong, Esraa Mahmoud Mostafa & Nguyen Tien Huy

  3. http://www.onlineresearchclub.org

    Mohammed Abdellatif, Gehad Mohamed Tawfik, Abdelrahman M. Makram, Mostafa Khaled Abdelsattar, Monica Dobs, Dimitrios N. Papadopoulos, Bao-Long Hoang-Trong, Esraa Mahmoud Mostafa & Nguyen Tien Huy

  4. Department of Otorhinolaryngology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Gehad Mohamed Tawfik

  5. Faculty of Medicine, October 6 University, Giza, Egypt

    Abdelrahman M. Makram

  6. School of Public Health, Imperial College London, London, UK

    Abdelrahman M. Makram

  7. Faculty of Medicine, Cairo University, Cairo, Egypt

    Mostafa Khaled Abdelsattar

  8. Faculty of Medicine, Assiut University, Assiut, Egypt

    Monica Dobs

  9. Aristotle University of Thessaloniki, Thessaloniki, Greece

    Dimitrios N. Papadopoulos

  10. Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam

    Bao-Long Hoang-Trong

  11. Faculty of Medicine, Port Said University, Port Said, Egypt

    Esraa Mahmoud Mostafa

  12. Pediatric Department, Faculty of Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

    Pham Diep Thuy Duong

  13. School of Tropical Medicine and Global Health, Nagasaki University, 1–12–4 Sakamoto, Nagasaki, 852-8523, Japan

    Nguyen Tien Huy

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Contributions

NTH developed the idea. All authors screened the articles for eligibility and collected the data using the standardized extraction Excel sheet. MA, AMM, and NTH performed the data analysis. MA created the tables and figures. All authors contributed to writing the manuscript. All authors approved of the final version of the manuscript before submission for publication.

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Correspondence to Nguyen Tien Huy.

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Abdellatif, M., Tawfik, G.M., Makram, A.M. et al. Association between neonatal phototherapy and future cancer: an updated systematic review and meta-analysis. Eur J Pediatr 182, 329–341 (2023). https://doi.org/10.1007/s00431-022-04675-6

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