Maternal medication use and the risk of brain tumors in the offspring: The SEARCH international case‐control study

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Abstract
N‐nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R1NNO·COR2), a type of NOC, are potent neuro‐carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case‐control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (≤5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case‐control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring.