Children who take medications containing phthalates may have an increased risk of developing childhood cancer, particularly osteosarcoma and lymphoma, according to a study published in the Journal of the National Cancer Institute.1

The study included nearly 1.3 million children born in Denmark between 1997 and 2017. Researchers used national registries to track prescriptions the children received from birth to 19 years of age, as well as those their mothers filled during pregnancy, and cancer diagnoses among the children.

The researchers also searched a national database, maintained by the Danish Medicines Agency, that lists all the ingredients in drugs on the market in Denmark to determine which products contained phthalates.

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During the study period, mothers and their children filled prescriptions for 25 oral medications with a phthalate in their formulations. The most common were clarithromycin, erythromycin, ibuprofen, and naproxen.

Results: ‘Solid Evidence’

Children prescribed a medication containing a phthalate had a 19% higher risk of developing any childhood cancer, compared with children who did not receive any medications containing phthalates during childhood.

Although the 19% increase was not quite statistically significant, it likely represents a real trend, particularly because the researchers were careful to reduce sources of nonrandom errors, according to study author Thomas Ahern, PhD, of the University of Vermont Larner College of Medicine in Burlington.

For example, the researchers detected an elevated risk at both 6 months and 12 months after the prescription was filled, which argues against a reverse causation relationship, whereby cancer development may be leading to the use of a pain medication and not the other way around.

Furthermore, the signal was not found in the group of children who received formulations of the same medications that did not contain phthalates.

The researchers found that childhood exposure to phthalates in medications was associated with a roughly 3-fold higher risk of osteosarcoma and a roughly 2-fold higher risk of lymphoma (driven by Hodgkin and non-Hodgkin lymphoma but not Burkitt lymphoma).

The study is “very solid evidence for the impact of phthalates on cancer development,” Dr Ahern noted.

He added that the link was bolstered by the fact that the researchers found a higher risk (66%) for any childhood cancer associated with medications containing diethyl phthalate (DEP) or dibutyl phthalate (DBP), which are low-molecular weight phthalates thought to have greater biological activity.

Although the researchers were not able to study how long children took the medications, Dr Ahern suspects the medications were generally longer course, such as anti-inflammatories taken for inflammatory bowel disease and other chronic conditions.

The study did not show an association between gestational exposure to phthalate-containing medications, based on prescriptions women filled during pregnancy, and the risk of childhood cancer.