Thapa P B, Whitlock J A, Brockman Worrell K G, Gideon P, Mitchel E F, Roberson P, Pais R, Ray W A
Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Cancer. 1998 Oct 1;83(7):1461-8. doi: 10.1002/(sici)1097-0142(19981001)83:7<1461::aid-cncr25>3.0.co;2-1.
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.
为评估子宫内暴露于甲硝唑（在某些动物模型中为致癌物）的作用及后续患癌风险，作者开展了一项儿童癌症回顾性队列研究。
该队列包括328,846名5岁以下儿童，其母亲在末次月经（LMP）至分娩日期之间的任何时间参加了田纳西州医疗补助计划。通过链接1975年1月1日至1992年12月31日期间田纳西州15 - 44岁医疗补助计划母亲及儿童的档案以及儿童的出生和死亡证明来确定该队列。暴露数据从医疗补助药房记录中获取，暴露定义为在LMP前30天至分娩日期之间开具至少一日用量的甲硝唑处方。研究病例为队列中5岁前被诊断为原发性癌症的儿童，通过将队列与该研究期间的全州儿童癌症数据库链接来确定。
队列成员贡献了1,172,696人年的随访用于分析，子宫内暴露于甲硝唑的儿童（8.1%）和未暴露的儿童（91.9%）分别贡献了79,716和1,092,980人年。在全州癌症数据库中的952名5岁以下儿童中，175名符合研究纳入标准。其中，42名患有白血病，30名患有中枢神经系统（CNS）肿瘤，28名患有神经母细胞瘤，75名患有其他癌症。使用泊松回归模型，子宫内暴露于甲硝唑的儿童在所有癌症（相对风险[RR]：0.81；95%置信区间[95%CI]，0.41 - 1.59）、白血病（无暴露病例）、CNS肿瘤（RR：1.23；95%CI，0.29 - 5.21）、神经母细胞瘤（RR：2.60；95%CI，0.89 - 7.59）和其他癌症（RR：0.57；95%CI，0.18 - 1.82）方面的调整相对风险没有显著增加。
作者得出结论，虽然子宫内暴露于甲硝唑与所有癌症风险增加无关，但观察到的神经母细胞瘤风险增加，尽管不显著，仍需要进一步评估。
