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广谱流行病学研究:新南威尔士北部地区大麻和其他物质对胎儿畸形的影响:地理空间和因果推理分析。

Broad Spectrum epidemiological contribution of cannabis and other substances to the teratological profile of northern New South Wales: geospatial and causal inference analysis.

机构信息

Division of Psychiatry, University of Western Australia, Crawley, Western Australia, 6009, Australia.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia.

出版信息

BMC Pharmacol Toxicol. 2020 Nov 12;21(1):75. doi: 10.1186/s40360-020-00450-1.

Abstract

BACKGROUND

Whilst cannabis commercialization is occurring rapidly guided by highly individualistic public narratives, evidence that all congenital anomalies (CA) increase alongside cannabis use in Canada, a link with 21 CA's in Hawaii, and rising CA's in Colorado indicate that transgenerational effects can be significant and impact public health. It was therefore important to study Northern New South Wales (NNSW) where cannabis use is high.

METHODS

Design: Cohort. 2008-2015.

SETTING

NNSW and Queensland (QLD), Australia.

PARTICIPANTS

Whole populations. Exposures. Tobacco, alcohol, cannabis.

SOURCE

National Drug Strategy Household Surveys 2010, 2013.

MAIN OUTCOMES

CA Rates. NNSW-QLD comparisons. Geospatial and causal regression.

RESULTS

Cardiovascular, respiratory and gastrointestinal anomalies rose with falling tobacco and alcohol but rising cannabis use rates across Queensland. Maternal age NNSW-QLD was not different (2008-2015: 4265/22084 v. 96,473/490514 > 35 years/total, Chi.Sq. = 1.687, P = 0.194). A higher rate of NNSW cannabis-related than cannabis-unrelated defects occurred (prevalence ratio (PR) = 2.13, 95%C.I. 1.80-2.52, P = 3.24 × 10). CA's rose more potently with rising cannabis than with rising tobacco or alcohol use. Exomphalos and gastroschisis had the highest NNSW:QLD PR (6.29(2.94-13.48) and 5.85(3.54-9.67)) and attributable fraction in the exposed (84.11%(65.95-92.58%) and 82.91%(71.75-89.66%), P = 2.83 × 10 and P = 5.62 × 10). In multivariable geospatial models cannabis was significantly linked with cardiovascular (atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus), genetic (chromosomal defects, Downs syndrome), gastrointestinal (small intestinal atresia), body wall (gastroschisis, diaphragmatic hernia) and other (hypospadias) (AVTPCDSGDH) CA's. In linear modelling cannabis use was significantly linked with anal stenosis, congenital hydrocephalus and Turner syndrome (ACT) and was significantly linked in borderline significant models (model P < 0.1) with microtia, microphthalmia, and transposition of the great vessels. At robust and mixed effects inverse probability weighted multivariable regression cannabis was related to 18 defects. 16/17 E-Values in spatial models were > 1.25 ranging up to 5.2 × 10 making uncontrolled confounding unlikely.

CONCLUSIONS

These results suggest that population level CA's react more strongly to small rises in cannabis use than tobacco or alcohol; cardiovascular, chromosomal, body wall and gastrointestinal CA's rise significantly with small increases in cannabis use; that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies, is robust to adjustment for other substances; and is causal.

摘要

背景

虽然大麻商业化在高度个体化的公众叙事的引导下迅速发展,但有证据表明,所有先天畸形(CA)都会随着加拿大大麻使用的增加而增加,夏威夷有 21 种 CA 与大麻有关,科罗拉多州的 CA 也在增加,这表明代际效应可能非常显著,并影响公共健康。因此,研究大麻使用量很高的新南威尔士州北部(NNSW)非常重要。

方法

设计:队列。2008-2015 年。

地点

新南威尔士州北部和昆士兰州(QLD),澳大利亚。

参与者

全体人群。暴露。烟草、酒精、大麻。

来源

2010 年和 2013 年国家毒品战略家庭调查。

主要结果

CA 率。NNSW-QLD 比较。地理空间和因果回归。

结果

心血管、呼吸和胃肠道异常随着烟草和酒精的下降而上升,但昆士兰州的大麻使用率却在上升。NNSW-QLD 的产妇年龄没有差异(2008-2015 年:4265/22084 与 96,473/490514>35 岁/总人数,Chi.Sq. = 1.687,P = 0.194)。与非大麻相关的缺陷相比,NNSW 与大麻相关的缺陷发生率更高(患病率比(PR)= 2.13,95%CI 1.80-2.52,P = 3.24 × 10)。CA 随着大麻使用量的增加比烟草或酒精使用量的增加更为显著。脐膨出和腹裂在 NNSW:QLD 的 PR(6.29(2.94-13.48)和 5.85(3.54-9.67))和暴露的归因分数最高(84.11%(65.95-92.58%)和 82.91%(71.75-89.66%),P = 2.83 × 10 和 P = 5.62 × 10)。在多变量地理空间模型中,大麻与心血管(房间隔缺损、室间隔缺损、法洛四联症、动脉导管未闭)、遗传(染色体缺陷、唐氏综合征)、胃肠道(小肠闭锁)、体壁(腹裂、膈疝)和其他(尿道下裂)(AVTPCDSGDH)CA 显著相关。在线性建模中,大麻使用与肛门狭窄、先天性脑积水和特纳综合征(ACT)显著相关,在边界显著模型(模型 P < 0.1)中与小耳畸形、小眼畸形和大血管转位显著相关。在稳健和混合效应逆概率加权多变量回归中,大麻与 18 种缺陷相关。空间模型中的 16/17 E-值均>1.25,最高可达 5.2 × 10,这表明无法控制的混杂不太可能。

结论

这些结果表明,人口水平的 CA 对大麻使用量的微小增加反应更强烈,而不是烟草或酒精;心血管、染色体、体壁和胃肠道 CA 随着大麻使用量的微小增加而显著增加;大麻是 AVTPCDSGDH 和 ACT 异常的双变量相关物,在调整其他物质后仍然稳健;并且是因果关系的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1456/7659114/33e8f113e544/40360_2020_450_Fig1_HTML.jpg

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