image: Infant undergoing phototherapy for newborn jaundice. view more
Credit: Katherine C. Cohen, Boston Children's Hospital
(BOSTON, May 23, 2016) -- Two new studies raise enough questions about a possible link between childhood cancer and light therapy for newborn jaundice that clinicians should exercise caution in prescribing the treatment for infants whose jaundice is likely to resolve on its own, a pediatric oncologist from Dana-Farber/Boston Children's Cancer and Blood Disorders Center argues in an editorial published today by the journal Pediatrics. The suggestion of a link, however, should not deter use of the treatment, also known as phototherapy, in babies who otherwise would be at risk of brain damage or hearing loss.
Despite the inconclusive findings, the editorial notes that the research represents an important and novel approach using "big data" to begin to discern whether environmental factors may be implicated in the development of pediatric cancer.
Two companion studies, also published today in Pediatrics, examined an association between phototherapy and pediatric cancers. The first study, the California Late Impact of Phototherapy Study (CLIPS), analyzed data from five million infants born in California hospitals between 1998 and 2007. The study used administrative data that linked the billing code for phototherapy and the diagnosis code of childhood cancer. The strongest association is a 1.6-fold increased risk of acute myeloid leukemia (AML). The risk of Wilms tumor, a kidney cancer of childhood, also rose to statistical significance. The second study -- the Late Impact of Getting Hyperbilirubinemia of photoTherapy (LIGHT) study -- analyzed data from 500,000 children born in the Kaiser Permanente Northern California healthcare system between 1995 and 2011. The associations between phototherapy and childhood cancer were not statistically significant, but an association with AML was again observed.
The studies come at a time when the number of infants receiving phototherapy is increasing, in part, the researchers suggest, because of the availability of light therapy units that can be used in the home. In the Kaiser study, 16 percent of babies received phototherapy in 2011, up from 3 percent in 1995.
In both studies, the associations were stronger and statistically significant among children with Down syndrome. Children with Down syndrome are already known to be at an increased risk of leukemia.
"Even though the results are inconclusive, they are worrisome enough that phototherapy should not be presented as risk-free. That being said, however, the brain damage and hearing loss from high bilirubin levels are real and well-documented, and the suggested risk of cancer from these new studies is both unclear and very small," says the editorial's lead author, Lindsay Frazier, MD, of Dana-Farber/Boston Children's. "What is concerning is the fact that, at least in the Kaiser Permanente Northern California healthcare system, the number of children receiving phototherapy has dramatically increased. The risks associated with such a prevalent exposure require close scrutiny."
Even in the CLIPS study, which found a statistically significant association between phototherapy and childhood cancer, the absolute numbers involved were very low. Of the 5 million infants studied, 58 who received phototherapy later developed cancer. The increased risk of AML, for instance, was based on 10 cases among the 178,000 children who received phototherapy, versus 103 cases in the 4.9 million children who did not.
"Studying why children get cancer is very difficult because it is such a rare disease," Frazier says. "The association between smoking and lung cancer was relatively easy to detect because the disease is well over 10 times more common than childhood cancer. There are about 225,000 new cases of lung cancer a year in the United States, versus 15,000 new cases of pediatric cancer. Thus, to study childhood cancer, a scientist needs to find a way to study large populations. The authors are to be commended for finding a way to do just that. But even in these studies of huge populations, the number of children who actually develop cancer remains quite small."
Despite the small numbers, the editorial advises clinicians to weigh a possible link with cancer in determining which babies need phototherapy.
"In the end, acknowledging that the information is imperfect, general pediatricians and neonatologists must make a choice," the editorial concludes. "These data suggest that phototherapy may not be harmless, and that the risks as well as the benefits need to be weighed before flipping the switch."
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Frazier was joined in writing the editorial by co-authors Mark Krailo, PhD, a biostatistician at the Keck School of Medicine at the University of Southern California, and Jennifer Poynter, PhD, an epidemiologist at the University of Minnesota.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center -- the nation's top pediatric cancer center, according to U.S. News & World Report 2015-16. - brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since 1947. The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children's Hospital and most outpatient care at Dana-Farber Cancer Institute.
(Note: See accompanying news release. Head shots available.)
Q & A: Making sense of new research on possible link between phototherapy for newborn jaundice and cancer Pediatric oncologist and neonatologist discuss new big-data studies
Two new studies published in the journal Pediatrics analyze large datasets to see if there is a link between phototherapy (light therapy) for newborn jaundice and pediatric cancer. One study found a statistically significant association; the other did not. A companion editorial explores the implications of the studies. Lindsay Frazier, MD, a pediatric oncologist at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and lead author of the editorial, and Anne Hansen, MD, MPH, a neonatologist and medical director of the Neonatal Intensive Care Unit at Boston Children's Hospital, answer questions about the new research and its implications.
Q. What is newborn jaundice?
Anne Hansen, MD: Jaundice is a yellow color that can be seen in the eyes and skin due to elevated levels of a substance called bilirubin. Bilirubin is released as part of the normal life cycle of the red blood cell. Due to immature functioning of newborns, it is common for babies to have mild jaundice between about two days and two weeks after birth. In some circumstances, if untreated, infants' bilirubin levels can get high enough to cause hearing loss and even brain injury.
Q. What is light therapy, and how is it used to treat newborn jaundice?
Anne Hansen, MD: Light therapy, also called phototherapy, is a very simple treatment in which a specific frequency of light is shined on a baby's skin. The light converts the bilirubin in the skin to a related substance that is easier for the newborn to pass from the body. We know that light therapy is effective in lowering bilirubin levels and avoiding hearing loss and brain injury. In the United States, about 250,000 babies receive light therapy every year.
Q. What, if any, association between phototherapy and childhood cancer did the two new studies find?
Lindsay Frazier, MD: Two big studies led by researchers at the University of California San Francisco looked at the issue. The first, which analyzed administrative records of five million children born in California hospitals between 1998 and 2007, found a statistically significant association between phototherapy and two types of pediatric cancers -- acute myeloid leukemia and kidney cancer. The second study examined medical records of 500,000 babies born in Kaiser Permanente Northern California hospitals between 1995 and 2011. It found no statistically significant association with childhood cancer, after adjusting for other possible risk factors.
Q. Why are big-data studies like this important to childhood cancer research?
Lindsay Frazier, MD: What causes childhood cancer remains one of the great unsolved questions in medicine. Unlike adult cancers in which we can point to many preventable causes of cancer, like smoking and obesity, we still understand virtually nothing about what elements, beside genetics, can cause a child to develop cancer. The main reason this has been such a vexing problem is that childhood cancer is very rare. For instance, with 225,000 new cases of lung cancer diagnosed annually in the United States, its association with smoking was relatively easy to establish. On the other hand, only 15,000 new cases of pediatric cancer -- of all types -- are diagnosed annually. This means that researchers who want to examine the relationship between an exposure, such as phototherapy, and childhood cancer must analyze large datasets in order to have enough cases to be statistically significant. The study of the etiology of pediatric cancer has been hampered by this fact. Large datasets, such as the ones analyzed in these California studies, present an opportunity to study an outcome as rare as pediatric cancer.
Q. What should clinicians and parents take away from these new research findings?
Lindsay Frazier, MD: Phototherapy has been perceived by most as causing minimal risk to the infant. Although these studies are inconclusive and do not prove a relationship between phototherapy and cancer, they should give us pause. One of the most striking findings was the authors' data on the dramatic increase in the number of children who are receiving phototherapy, at least in the Kaiser Permanente system, in part, they suggest, because of the availability of units that can be used in the home. In 2011, 15.9 percent of the Kaiser infants received phototherapy, up from 2.7 percent in 1995. The risks associated with such a prevalent exposure require close scrutiny. If I were the one prescribing phototherapy today, I would want to be sure it was indicated.
Anne Hansen, MD: Although one Pediatrics study found a statistically significant correlation between phototherapy and cancer, that does not mean the light therapy caused the cancer. By contrast, it is well-established that severe jaundice can cause hearing loss and brain injury if left untreated. We also know that light therapy decreases bilirubin levels and prevents hearing loss and brain injury. So, we need to balance what we do with early stage data about correlations against known, substantial neurologic risk. That said, the new research is suggestive enough that clinicians should be mindful of the possible risk in cases in which mild jaundice is likely to resolve on its own. While we must always strive to understand the possible side effects of any our treatments, light treatment, overall, is safe and the benefits of offering it, when indicated, far outweigh the risks.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center -- the nation's top pediatric cancer center, according to U.S. News & World Report 2015-16. -- brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since 1947. The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children's Hospital and most outpatient care at Dana-Farber Cancer Institute.
Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 404-bed comprehensive center for pediatric and adolescent health care. Boston Children's is also the primary pediatric teaching affiliate of Harvard Medical School. For more, visit our Vector and Thriving blogs and follow us on our social media channels: @BostonChildrens, @BCH_Innovation, Facebook and YouTube.
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