Maternal prenatal exposure to nitrosatable drugs and childhood brain tumours

Abstract

Background. A compelling hypothesis was proposed that childhood brain tumours are associated with maternal exposure to N-nitroso compounds during the prenatal period. Many common drugs, such as antihistamines, aspirin, and antibiotics, are nitrosatable and depending upon the product, potentially carcinogenic. We hypothesized that maternal ingestion of certain subgroups of nitrosatable drug products during pregnancy increases the risk of brain tumour development in offspring. Methods. Data were collected as part of a population-based case-control study of childhood brain tumours and mothers' sell-reported exposure to therapeutic drugs and dietary nitrites. Cases were enrolled from three US West Coast SEER tumour registries: Seattle-Puget sound, Los Angeles County, and the San Francisco-Oakland Bay Area. Tumours were grouped into three major histological tumour subtypes: astroglial, primitive neural ectodermal tumours, and all remaining glial tumours ('other glial'). Therapeutic drugs reported by mothers were translated into active chemical compounds and classified as secondary amines, tertiary amines, amides, or none of the three. Risk estimates were computed according to classes of nitrosatability, potential carcinogenicity, teratogenicity, and predicted end product. Results. We found no significant association between maternal use of nitrosatable drugs, either overall or within any of the nitrosatable drug classifications, and subsequent development of brain tumours in children. Nitrite consumption from cured meats was not an effect modifier. However, exposure to nitrosoephedrine during pregnancy was associated with significantly increased risk of 'other glial' tumours (OR = 3.1; 95% CI: 1.1-9.2). Conclusions. These findings do not support an association between maternal use of nitrosatable drugs during pregnancy and brain tumour risk in offspring. While exposure to the nitrosation end product nitrosoephedrine was associated with increased risk for other glial tumours, the finding was not specific to any one type of tumour.