Medication-Associated Phthalate Exposure and Childhood Cancer Incidence.
Level 3 - non-randomized controlled study
Nationwide population-based cohort study using registry linkage.
PubMed 35179607 · doi:10.1093/jnci/djac045
What was done
This nationwide cohort study analyzed all live births in Denmark between 1997 and 2017. Investigators linked drug ingredient formulations with the Danish National Prescription Registry to estimate phthalate exposure through filled prescriptions during pregnancy (gestational exposure) and throughout childhood up to age 19 years. Incident childhood cancers were ascertained from the Danish Cancer Registry, and associations were evaluated using Cox proportional hazards models across 13.1 million person-years of follow-up.
What was found
Among 1,278,685 children, 2,027 childhood cancer cases were identified. Childhood phthalate exposure was associated with a higher incidence of osteosarcoma (HR = 2.78, 95% CI = 1.63 to 4.75) and lymphoma (HR = 2.07, 95% CI = 1.36 to 3.14). The lymphoma association was driven by Hodgkin and non-Hodgkin lymphoma, with no association seen for Burkitt lymphoma. Associations were apparent only for low-molecular-weight phthalate exposures.
Why it matters
These findings suggest that inactive phthalate excipients in pharmaceutical formulations may contribute to specific pediatric cancer risks, highlighting the potential need to reduce or eliminate phthalate content in medications.
Limits
As an observational registry study, it is subject to potential confounding by indication (the underlying conditions for which medications were prescribed). Phthalate exposure was estimated from filled prescription records rather than biomonitoring, and non-medication phthalate exposures from diet, plastics, and consumer products were not captured.
Cited by
- supports A 2022 Danish nationwide study of 1.3 million children found childhood exposure to phthalates in medications was associated with a 20% higher overall childhood cancer risk, nearly 3-fold higher osteosarcoma, and 2-fold higher lymphoma.