Neonatal Phototherapy and Infantile Cancer

Wickremasinghe, Andrea C.; Kuzniewicz, Michael W.; Grimes, Barbara; McCulloch, Charles E.; Newman, Thomas B.

doi:10.1542/peds.2015-1353

Cited by 99 publications

(87 citation statements)

References 36 publications

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“…One key confounder is Down syndrome. In both the California Late Impact of Phototherapy Study 20 and the current study, Down syndrome was associated not only with a markedly increased risk of leukemia but also a fivefold increase in the use of phototherapy. As reported in previous studies, other chromosomal and congenital anomalies 26 and low 5-minute Apgar score 27 were also associated with certain types of cancer and were associated with higher phototherapy rates.…”

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confidence: 50%

“…In the California Late Impact of Phototherapy Study, which used linked birth certificates and discharge abstracts, Wickremasinghe et al 20 reported statistically significant propensity-adjusted ORs for any cancer, myeloid leukemia, kidney, and other cancer diagnoses before age 1 year. A limitation of that study is that follow-up was only 1 year, raising the question of whether the increased risk persists.…”

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Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California

et al. 2016

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OBJECTIVE: To investigate the association between neonatal phototherapy use and childhood cancer.METHODS: This retrospective cohort study included 499 621 children born at ≥35 weeks' gestation from 1995 to 2011 in Kaiser Permanente Northern California hospitals, who survived to hospital discharge and were followed ≥60 days. We obtained data on home and inpatient phototherapy, covariates, and cancer incidence from electronic records. We used propensity-adjusted Cox and Poisson models to control for confounding and unequal follow-up times.RESULTS: There were 60 children with a diagnosis of cancer among 39 403 exposed to phototherapy (25 per 100 000 person-years), compared with 651 of 460 218 unexposed children (18 per 100 000 person-years; incidence rate ratio [IRR] 1.4; P = .01). Phototherapy was associated with increased rates of any leukemia (IRR 2.1; P = .0007), nonlymphocytic leukemia (IRR 4.0; P = .0004), and liver cancer (IRR 5.2; P = .04). With adjustment for a propensity score that incorporated bilirubin levels, chromosomal disorders, congenital anomalies, and other covariates, associations were no longer statistically significant: Adjusted hazard ratios (95% confidence intervals) were 1.0 (0.7-1.6) for any cancer, 1.6 (0.8-3.5) for any leukemia, 1.9 (0.6-6.9) for nonlymphocytic leukemia, and 1.4 (0.2-12) for liver cancer. Upper limits of 95% confidence intervals for adjusted 10-year excess risk were generally <0.1% but reached 4.4% for children with Down syndrome. CONCLUSIONS:Although phototherapy use was associated with increased cancer rates (particularly nonlymphocytic leukemia), control for confounding variables eliminated or attenuated the associations. Nonetheless, the possibility of even partial causality suggests that avoiding unnecessary phototherapy may be prudent.

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Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California

et al. 2016

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“…Specifically, the risk for myeloid leukemia and kidney cancer seemed slightly increased. However, after correcting for congenital and chromosomal abnormalities, the associations were no longer statistically significant [17,18]. Additionally, previous studies could not find an association between phototherapy and skin cancer [16,19].…”

Section: Intensive Phototherapymentioning

confidence: 84%

Neonatal management and outcome in alloimmune hemolytic disease

Ree

Smits-Wintjens

Bom

et al. 2017

Expert Review of Hematology

103

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Introduction: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management. Areas covered: This review focusses on the current neonatal management and outcome of hemolytic disease and discusses postnatal treatment options as well as literature on long-term neurodevelopmental outcome. Expert commentary: Despite major advances in neonatal management, multiple issues have to be addressed to optimize postnatal management and completely eradicate kernicterus. Except for strict adherence to guidelines, improvement could be achieved by clarifying the epidemiology and pathophysiology of HDFN. Several pharmacotherapeutic agents should be further researched as alternative treatment options in hyperbilirubinemia, including immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in neonates. Long-term follow-up studies are needed in HDFN, especially on thrombocytopenia, iron overload and cholestasis.ARTICLE HISTORY

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“…Some physicians may even initiate phototherapy at bilirubin levels below phototherapy limits because of the few adverse effects and convenient application. In some current publications, phototherapy has been shown to be related with increased risk of childhood and infancy cancers (21). It may be thought that the increase in the risk of cancer is related with the long-term results of the genotoxic effect of phototherapy or hyperbilirubinemia itself.…”

Section: Discussionmentioning

confidence: 99%

The effect of phototherapy on sister chromatid exchange with different light density in newborn hyperbilirubinemia

Kanmaz¹,

Okur²,

Díllí³

et al. 2018

Turk Pediatri Ars

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Aim: Concerns of possible genotoxic effects of hyperbilirubinemia and phototherapy were raised from experimental and observational studies in neonates. The purpose of this study was to assess the effect of hyperbilirubinemia and phototherapy with three different methods on DNA damage by investigating sister chromatid exchange frequency. Material and Methods: Patients whose gestational ages were >37 weeks and bilirubin levels above phototherapy limits were enrolled into three groups and each group was planned to receive 25 babies. Group 1 received enhanced light-emitting diode phototherapy, group 2 had light-emitting diode phototherapy, and group 3 received conventional phototherapy. Infants with hyperbilirubinemia but did not require phototherapy comprised the control group, which was subdivided into two groups regarding bilirubin levels (10mg/dL). Blood samples were collected before and after phototherapy for sister chromatid exchange frequency and samples were examined by a biologist who was blinded to the study groups. Results: The mean pre-treatment sister chromatid exchange frequency was 1.41±0.34/cell, post-treatment 2.65±0.68/cell, and 1.61±0.61/ cell for the control group (p<0.05). A statistically significant increase in sister chromatid exchange frequency after phototherapy was observed in all three intervention groups (p values: 0.01, 0.01, and 0.008, respectively). When the treatment groups were compared with each other in terms of irradiance, no significant difference was found (p=0.08). Conclusions: Phototherapy causes an increase in the frequency of sister chromatid exchange regardless of the irradiance. Phototherapy could have some genotoxic adverse effects on chromosomes; however, further investigations are warranted to enlighten as to whether these effects are permanent or clinically important.

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Neonatal Phototherapy and Infantile Cancer

Cited by 99 publications

References 36 publications

Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California

Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California

Neonatal management and outcome in alloimmune hemolytic disease

The effect of phototherapy on sister chromatid exchange with different light density in newborn hyperbilirubinemia

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