Reece Albert Stuart, Hulse Gary Kenneth
Division of Psychiatry, University of Western Australia, Crawley, WA 6009, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
Pediatr Rep. 2023 Feb 7;15(1):69-118. doi: 10.3390/pediatric15010009.
Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred.
CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank.
CARs were higher in countries with increasing daily use overall ( = 9.99 × 10, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome ( = 1.49 × 10, mEV = 3.04). In inverse probability weighted panel regression models the series of anomalies: all anomalies, VACTERL, foetal alcohol syndrome, situs inversus (SI), lateralization (L), and teratogenic syndromes (TS; AAVFASSILTS) had cannabis metric -values from: < 2.2 × 10, 1.52 × 10, 1.44 × 10, 1.88 × 10, 7.39 × 10 and <2.2 × 10. In a series of spatiotemporal models this anomaly series had cannabis metric -values from: 8.96 × 10, 6.56 × 10, 0.0004, 0.0019, 0.0006, 5.65 × 10. Considering E-values, the cannabis effect size order was VACTERL > situs inversus > teratogenic syndromes > FAS > lateralization syndromes > all anomalies. 50/64 (78.1%) E-value estimates and 42/64 (65.6%) mEVs > 9. Daily cannabis use was the strongest predictor for all anomalies.
Data confirmed laboratory, preclinical and recent epidemiological studies from Canada, Australia, Hawaii, Colorado and USA for teratological links between cannabis exposure and AAVFASSILTS anomalies, fulfilled epidemiological criteria for causality and underscored importance of cannabis teratogenicity. VACTERL data are consistent with causation via cannabis-induced Sonic Hedgehog inhibition. TS data suggest cannabinoid contribution. SI&L data are consistent with results for cardiovascular CAs. Overall, these data show that cannabis is linked across space and time and in a manner which fulfills epidemiological criteria for causality not only with many CAs, but with several multiorgan teratologic syndromes. The major clinical implication of these results is that access to cannabinoids should be tightly restricted in the interests of safeguarding the community's genetic heritage to protect and preserve coming generations, as is done for all other major genotoxins.
近期一系列先天性异常（CA）发生率（CARs）显示，大麻暴露与许多CARs之间存在密切的流行病学因果关系。我们在欧洲调查了这些趋势，欧洲也出现了类似趋势。
来自欧洲先天性异常监测网络（EUROCAT）的CARs数据。来自欧洲药物和药物成瘾监测中心的药物使用数据。来自世界银行的收入数据。
在总体日使用量增加的国家中，CARs更高（ = 9.99 × 10，最小E值（mEV） = 2.09），特别是对于母体感染、内脏反位、致畸综合征和VACTERL综合征（ = 1.49 × 10，mEV = 3.04）。在逆概率加权面板回归模型中，一系列异常情况：所有异常、VACTERL、胎儿酒精综合征、内脏反位（SI）、偏侧化（L）和致畸综合征（TS；AAVFASSILTS）的大麻指标 -值分别为： < 2.2 × 10、1.52 × 10、1.44 × 10、1.88 × 10、7.39 × 10和 <2.2 × 10。在一系列时空模型中，该异常系列的大麻指标 -值分别为：8.96 × 10、6.56 × 10、0.0004、0.0019、0.0006、5.65 × 10。考虑E值，大麻效应大小顺序为VACTERL > 内脏反位 > 致畸综合征 > 胎儿酒精综合征 > 偏侧化综合征 > 所有异常。64个E值估计中有50个（78.1%）以及64个mEV中有42个（65.6%）大于9。每日大麻使用是所有异常的最强预测因素。
数据证实了来自加拿大、澳大利亚、夏威夷、科罗拉多和美国的实验室、临床前及近期流行病学研究中关于大麻暴露与AAVFASSILTS异常之间致畸联系的结果，满足因果关系的流行病学标准，并强调了大麻致畸性的重要性。VACTERL数据与大麻诱导的音猬因子抑制导致的因果关系一致。TS数据表明大麻素的作用。SI和L数据与心血管先天性异常的结果一致。总体而言，这些数据表明大麻在空间和时间上都有联系，并且以一种满足因果关系流行病学标准的方式，不仅与许多先天性异常有关，还与几种多器官致畸综合征有关。这些结果的主要临床意义在于，为了保护社区的遗传遗产以保护和保存后代，应严格限制大麻素的获取，就像对所有其他主要基因毒素所做的那样。
