1989-2016 年美国大麻素和药物暴露及社会人口因素与肢体减少缺陷的流行病学关联：一项地理时空研究。

Epidemiological association of cannabinoid- and drug- exposures and sociodemographic factors with limb reduction defects across USA 1989-2016: A geotemporospatial study.

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

Spat Spatiotemporal Epidemiol. 2022 Jun;41:100480. doi: 10.1016/j.sste.2022.100480. Epub 2022 Jan 29.

DOI:10.1016/j.sste.2022.100480

PMID:35691647

Abstract

BACKGROUND

Reports of major limb defects after prenatal cannabis exposure (PCE) in animals and of human populations in Hawaii, Europe and Australia raise the question of whether the increasing use of cannabis in USA might be spatiotemporally associated with limb reduction rates (LRR) across USA.

METHODS

Congenital anomaly data was from the National Birth Defects Prevention Network, drug use data was taken from the National Survey of Drug Use and Health (NSDUH), cannabinoid concentration was estimated from Federal seizure data and ethnicity and income data were from the US Census bureau. Geotemporospatial analysis was conducted in R.

RESULTS

436 LRR datapoints were obtained. LRR was significantly associated with cannabis use and tetrahydrocannabinol (THC) exposure and demonstrated prominent cannabis-use quintile effects. A sharp increase in LRR occurred from the fourth to fifth quintiles of cannabis exposure (mean ± S.E.M 3.78 ± 0.38 to 6.66 ± 0.56/10,000 live births, P = 5.22 × 10). In final lagged geospatial models adjusted for ethnicity and income interactive terms including cannabinoids were highly significant and robust to adjustment. States in which cannabis was not legalized had a lower LRR (4.28 v 5.01/10,000 live births, relative risk reduction = -0.15, (95%C.I. -0.25, -0.02), P = 0.021). Internationally 37-63% of cases are estimated to not be born alive. Their inclusion in these analyzes uniformly intensified the identified effects and the significance of the effect of the cannabis legalization paradigm rose from P = 0.0256 to P = 0.0146 to P = 0.0048 with silent factors of 0%, 36% and 63%, respectively.

CONCLUSION

Therefore a spatiotemporal and dose-dependent association between several cannabinoids including THC and cannabigerol and LRR is reported, is robust to adjustment, is consistent with pathophysiological and preclinical studies, accords with findings elsewhere, is markedly exacerbated in higher exposure quintiles, is exacerbated by cannabis legalization and evidences dose-related intergenerational sequaelae.

摘要

背景

动物实验中曾有报告称，产前接触大麻（PCE）后会出现主要肢体缺陷，在夏威夷、欧洲和澳大利亚的人类群体中也有报告，这引发了一个问题，即美国大麻使用量的增加是否与全美范围内的肢体减少率（LRR）存在时空关联。

方法

先天畸形数据来自国家出生缺陷预防网络，药物使用数据来自国家药物使用与健康调查（NSDUH），大麻素浓度来自联邦缉获数据，种族和收入数据来自美国人口普查局。地理时空分析在 R 中进行。

结果

获得了 436 个 LRR 数据点。LRR 与大麻使用和四氢大麻酚（THC）暴露显著相关，并显示出明显的大麻使用五分位数效应。从大麻暴露的第四五分位数到第五五分位数，LRR 急剧增加（平均值±S.E.M. 3.78±0.38 至 6.66±0.56/10000 活产儿，P=5.22×10）。在最后调整了种族和收入交互项的滞后地理空间模型中，包括大麻素在内的模型均具有高度显著性和稳健性。未使大麻合法化的州的 LRR 较低（4.28 比 5.01/10000 活产儿，相对风险降低 0.15（95%置信区间 0.25，0.02），P=0.021）。国际上估计有 37-63%的病例未存活。将这些病例纳入分析中，一致增强了已识别的效应，大麻合法化范式的效应显著性从 P=0.0256 上升至 P=0.0146 再至 P=0.0048，沉默因素分别为 0%、36%和 63%。