Reece Albert Stuart, Hulse Gary Kenneth
Division of Psychiatry, University of Western Australia, Crawley, WA 6009, Australia.
Environ Epigenet. 2022 Jul 5;8(1):dvac016. doi: 10.1093/eep/dvac016. eCollection 2022.
Cannabinoid exposure is increasing in some European nations. Europe therefore provides an interesting test environment for the recently reported link between cannabis exposure and congenital limb anomaly (CLA) rates (CLARs). Exponential genotoxic dose-response relationships make this investigation both intriguing and imperative. Annual CLAR in 14 nations were from Epidemiological Surveillance of Congenital Anomalies. Drug use rates were from European Monitoring Centre for Drugs and Drug Dependency. Median household income was from the World Bank. -values provide a quantitative measure of robustness of results to confounding by extraneous covariates. Inverse probability weighting is an important technique for equalizing exposures across countries and removing sources of bias. Rates of CLA, hip dysplasia and the whole group of limb anomalies were higher in countries with increasing daily cannabis use ( = 1.81 × 10, 0.0005 and 2.53 × 10, respectively). In additive inverse-probability-weighted panel models, the limb reduction-resin Δ9-tetrahydrocannabinol (THC) concentration -value estimate was 519.93 [95% lower bound (mEV) 49.56], order Resin > Herb ≫ Tobacco > Alcohol. Elevations were noted in 86% -value estimates and 70.2% of mEVs from 57 -value pairs from inverse-probability-weighted panel models and from spatial models. As judged by the mEV the degree of association with metrics of cannabis exposure was hip dysplasia > polydactyly > syndactyly > limb anomalies > limb reductions with median -value estimates from 3.40 × 10 to 7.06 and median mEVs from 6.14 × 10 to 3.41. Daily cannabis use interpolated was a more powerful metric of cannabis exposure than herb or resin THC exposure. Data indicate that metrics of cannabis exposure are closely linked with CLAR and satisfy epidemiological criteria for causality. Along with Hawaii and the USA, Europe now forms the third international population in which this causal link has been demonstrated. Cannabis as a predictor of limb anomalies was more potent than tobacco or alcohol. Cannabinoid access should be restricted to protect public health and the community genome/epigenome transgenerationally.
在一些欧洲国家，大麻素暴露情况正在增加。因此，欧洲为最近报道的大麻暴露与先天性肢体异常（CLA）发生率（CLARs）之间的联系提供了一个有趣的测试环境。指数性遗传毒性剂量反应关系使得这项研究既引人入胜又势在必行。14个国家的年度CLAR数据来自先天性异常流行病学监测。药物使用率来自欧洲药物和药物依赖监测中心。家庭收入中位数来自世界银行。P值提供了一种对结果受无关协变量混杂影响的稳健性的定量衡量。逆概率加权是一种重要技术，用于均衡各国的暴露情况并消除偏差来源。在每日大麻使用量增加的国家，CLA、髋关节发育不良和整个肢体异常组的发生率更高（P值分别为1.81×10⁻⁴、0.0005和2.53×10⁻⁴）。在加性逆概率加权面板模型中，肢体减少-树脂Δ9-四氢大麻酚（THC）浓度的P值估计为519.93[95%下限（mEV）为49.56]，顺序为树脂＞草药≫烟草＞酒精。在逆概率加权面板模型和空间模型的57对P值中，86%的P值估计和70.2%的mEV出现升高。根据mEV判断，与大麻暴露指标的关联程度为髋关节发育不良＞多指畸形＞并指畸形＞肢体异常＞肢体减少，中位数P值估计为3.40×10⁻⁴至7.06，中位数mEV为6.14×10⁻⁴至3.41。内插的每日大麻使用量是比草药或树脂THC暴露更强有力的大麻暴露指标。数据表明，大麻暴露指标与CLAR密切相关，并满足因果关系的流行病学标准。欧洲现在与夏威夷和美国一起，成为第三个已证明这种因果联系的国际人群。大麻作为肢体异常的预测指标比烟草或酒精更强有力。应限制大麻素的获取，以保护公众健康以及跨代的群体基因组/表观基因组。
