Prenatal exposure to metronidazole and risk of childhood cancer: a retrospective cohort study of children younger than 5 years.
ABSTRACT To evaluate the role of in utero exposure to metronidazole (a carcinogen in some animal models) and the risk of subsequent cancer, the authors conducted a retrospective cohort study of childhood cancer.
The cohort included 328,846 children younger than 5 years born to women enrolled in Tennessee Medicaid at any time between the last menstrual period (LMP) and the date of delivery. The cohort was identified by linking files of Tennessee Medicaid mothers ages 15-44 years and children and the children's birth and death certificates for the period January 1, 1975 through December 31, 1992. Exposure data were obtained from Medicaid pharmacy records and exposure was defined as filling a metronidazole prescription that had at least a day's supply between the 30 days prior to the LMP and the date of delivery. Study cases were cohort children diagnosed with a first primary cancer before age 5 years, identified by linking the cohort with a statewide childhood cancer database for the study period.
Cohort members contributed 1,172,696 person-years of follow-up for analysis, with children exposed (8.1%) and not exposed (91.9%) in utero to metronidazole contributing 79,716 and 1,092,980 person-years, respectively. Of 952 children younger than 5 years in the statewide cancer database, 175 met study eligibility criteria. Of these, 42 had leukemia, 30 had central nervous system (CNS) tumors, 28 had neuroblastoma, and 75 had other cancers. Using Poisson regression modeling, children exposed to metronidazole in utero had no significant increase in adjusted relative risk (RR) for all cancers (RR: 0.81; 95% confidence interval [95% CI], 0.41-1.59), leukemia (no exposed case), CNS tumors (RR: 1.23; 95% CI, 0.29-5.21), neuroblastomas (RR: 2.60; 95% CI, 0.89-7.59), and other cancers (RR: 0.57; 95% CI, 0.18-1.82).
The authors conclude that although there was no increase in risk for all cancers associated with in utero exposure to metronidazole, the observed increased risk for neuroblastomas, although not significant, requires further evaluation.
- SourceAvailable from: Daniel Menendez
Article: Is metronidazole carcinogenic?[Show abstract] [Hide abstract]
ABSTRACT: Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs. MTZ is potentially carcinogenic to humans due to the following facts: it is a proven mutagen in bacterial systems, it is genotoxic to human cells and also, it is carcinogenic to animals. However, due to inadequate epidemiological evidence, it is not considered as a risk factor for cancer in humans. As it will be discussed here, the existing population studies are deficient since they have not included sufficient sample size, the follow-up time has not been long enough, and the individual sensitivity to the drug might have been acting as a confounding factor. Due to the increasing use of this drug, more and improved studies are needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 07/2002; 511(2):133-44. DOI:10.1016/S1383-5742(02)00007-8 · 4.44 Impact Factor
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ABSTRACT: In economically developed countries up to 90% of women are prescribed medications, including vitamins and supplements, during pregnancy. Whilst a number of adverse health outcomes in their offspring have been related to prescription drug use, associations with childhood cancer are less clear and most investigations have been reliant on maternal self-report. With a view to providing new insight we investigated maternal prescription drug use and risk of childhood cancer primary care medical records collected as part of the United Kingdom Childhood Cancer Study, a national population-based case–control study conducted between 1991 and 1996. There was evidence that mothers of children with acute lymphoblastic leukaemia (OR 1.36, 95% CI 1.14–1.63), medulloblastoma (OR 1.79, 95% CI 1.00–3.22) and Wilms tumour (OR 1.79; 95% CI 1.05–3.04) were more likely to have been prescribed iron when compared to mothers of controls. In addition, systemic anti-infectives were positively associated with acute myeloid leukaemia (OR 1.58, 95% CI: 1.05–2.38) and rhabdomyosarcoma (OR 1.80, 95% CI 1.03–3.16), and analgesic use (NO2B) was positively associated with Hodgkin lymphoma (OR 5.02, 95% CI 2.16–11.82) and neuroblastoma (OR 1.99, 95% CI 1.07–3.69). Whilst our findings suggest that maternal use of antibiotics, iron, and nervous system drugs during pregnancy may be associated with some childhood cancer subtypes these associations need to be confirmed elsewhere. Unravelling the mechanisms that may underpin these associations is complex and research is needed to determine whether they are directly related to the drugs themselves, or the illnesses for which they were prescribed.Cancer Epidemiology 12/2014; 39(1). DOI:10.1016/j.canep.2014.10.008 · 2.56 Impact Factor
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ABSTRACT: Metronidazole (MTZ), an antiparasitic and antibacterial compound, is one of the world’s most widely used drugs. Despite being considered as a rodent mutagen and a carcinogen, it is still widely used in humans for the treatment of infections with anaerobic organisms. Therefore, the main objective of the current study was to evaluate the in vivo toxicity of MTZ using the micronucleus (MN) assay and random ampliﬁed polymorphism DNA (RAPD-PCR) analysis as well as histopathological examination in Tilapia zillii. Moreover, the protective effect of vitamin C (VitC) against toxi- city of MTZ was investigated in the present study. Fish were treated with three doses of MTZ (5, 10 and 20 mg l−− −− −1) alone or in combination with VitC (200 mg kg−− −− −1 food) at several time intervals (2 days, 7 days and 14 days). The results of the present study showed a signiﬁcant effect of MTZ on micronucleus formation and changes in polymorphic band patterns as well as induction of different histopathological alterations in Tilapia zillii. The effects of the drug were reduced when ﬁsh were exposed to a combination of MTZ and VitC.Journal of Applied Toxicology 01/2007; 27:380-390. · 3.17 Impact Factor