Neonatal phototherapy is a widely used and generally safe short-term treatment. This review aims to explore the association between phototherapy and the risk of childhood neoplasia. A systematic search of electronic databases was conducted, including cohort or case-control studies that investigated this association. Bias and certainty assessments were performed, utilizing the DerSimonian-Laird model for random-effects analyses. Publication bias was evaluated using a funnel plot, with adjustments made through the trim-and-fill method. A total of 15 studies from nine countries were included, encompassing 7,842,858 individuals, of whom 4.8% received neonatal phototherapy The findings, rated at a medium level of evidence, indicated that those who underwent phototherapy had a 19% increased risk of developing any cancer (HR = 1.19; 95% CI = 1.07-1.32; I² = 0.0%; T² = 0.00). The risk was 22% for hematopoietic malignancies (HR = 1.22; 95% CI = 1.00-1.50) and 31% for leukemia (HR = 1.31; 95% CI = 1.26-1.53), with no significant association found for solid tumors, brain tumors, or lymphomas. Moreover, those receiving phototherapy had 44% greater odds of developing any neoplasm (OR 1.44; 95% CI = 1.07-1.93). Despite limitations regarding dosage, duration, and shared risk factors in patients receiving phototherapy, the treatment should be administered according to guidelines to minimize unnecessary exposure.
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