Article

Prenatal exposure to metronidazole and risk of childhood cancer: a retrospective cohort study of children younger than 5 years.

Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Cancer (Impact Factor: 4.89). 11/1998; 83(7):1461-8.
Source: PubMed

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.

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    • "MTZ, (1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an antiparasitic and antibacterial compound, is one of the world's most used drugs and 100 most prescribed drugs in the US (www.rxlist.com). It is one of the 10 most used drugs during pregnancy (Thapa et al., 1998). The drug can induce alterations in somatic and germinal cells (Grover et al., 2001). "
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    ABSTRACT: Metronidazole (MTZ) is a common antiparasitic and antibacterial drug. The drug and X-ray induced effects in mouse sperm count, sperm head abnormality and some oxidative stress parameters have been studied. Simultaneously the protective role of curcumin has been evaluated. MTZ, 40 mg/kg bw and 13.4 mg/kg bw × 3 days exposure induced abnormal sperm head and reduced total sperm count in Swiss albino mice both after 24 h and 35 days of exposure. However, MTZ treatment in mice receiving X-ray irradiation (0.5 Gy) did not changed the incidence of abnormal sperm population or decrease in the total sperm count. Hepatic glutathione (GSH), superoxide dismutase (SOD) declined significantly during the treatment phase with significant rise in lipid peroxidation of the tissue. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS). Elevated TBARS is indicative of oxidative stress in treated mice. Furthermore, curcumin pre-treatment apparently reduced the frequency of sperm head abnormality and TBARS induced by MTZ alone or in combination with X-ray and increased the levels of hepatic GSH and SOD. The additive effects of MTZ and X-ray could not be observed with regards to sperm head abnormality and total sperm count in the tested dose range although the cellular antioxidants were found to be significantly lowered and lipid peroxidantion increased. The possible role of MTZ and X-ray inducing sperm abnormality, decreased sperm count and alteration in GSH, SOD and TBARS and defensive role of curcumin have been evaluated.
    Full-text · Article · Jun 2013 · Prague medical report
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    • "Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole) is an antibacterial and antiprotozoal drug that has been in use for over 35 years. Currently, it is among the top 100 most prescribed drugs in the USA (Bendesky et al., 2002) and one of the 10 most widely used drugs during pregnancy (Thapa et al., 1998). It appears on the essential drug list of the World Health Organization (WHO, 1999). "

    Full-text · Article · Jan 2009 · Journal of Applied Toxicology
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    • "Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole) is an antibacterial and antiprotozoal drug that has been in use for over 35 years. Currently, it is among the top 100 most prescribed drugs in the USA (Bendesky et al., 2002) and one of the 10 most widely used drugs during pregnancy (Thapa et al., 1998). It appears on the essential drug list of the World Health Organization (WHO, 1999). "
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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 toxicity 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.
    Full-text · Article · Jul 2007 · Journal of Applied Toxicology
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