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

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.