Dataset Information

Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis.

ABSTRACT: OBJECTIVES:Cannabis is a known teratogen. Data availability addressing both major congenital anomalies and cannabis use allowed us to explore their geospatial relationships. METHODS:Data for the years 1998 to 2009 from Canada Health and Statistics Canada was analyzed in R. Maps have been drawn and odds ratios, principal component analysis, correlation matrices, least squares regression and geospatial regression analyses have been conducted using the R packages base, dplyr, epiR, psych, ggplot2, colorplaner and the spml and spreml functions from package splm. RESULTS:Mapping showed cannabis use was more common in the northern Territories of Canada in the Second National Survey of Cannabis Use 2018. Total congenital anomalies, all cardiovascular defects, orofacial clefts, Downs syndrome and gastroschisis were all found to be more common in these same regions and rose as a function of cannabis exposure. When Canada was dichotomized into high and low cannabis use zones by Provinces v Territories the Territories had a higher rate of total congenital anomalies 450.026 v 390.413 (O.R.?=?1.16 95%C.I. 1.08-1.25, P?=?0.000058; attributable fraction in exposed 13.25%, 95%C.I. 7.04-19.04%). In geospatial analysis in a spreml spatial error model cannabis was significant both alone as a main effect (P?

SUBMITTER: Reece AS

PROVIDER: S-EPMC7547880 | biostudies-literature | 2020 Sep/Oct

REPOSITORIES: biostudies-literature

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Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis.

Reece Albert Stuart AS Hulse Gary Kenneth GK

Journal of addiction medicine 20200901 5

<h4>Objectives</h4>Cannabis is a known teratogen. Data availability addressing both major congenital anomalies and cannabis use allowed us to explore their geospatial relationships.<h4>Methods</h4>Data for the years 1998 to 2009 from Canada Health and Statistics Canada was analyzed in R. Maps have been drawn and odds ratios, principal component analysis, correlation matrices, least squares regression and geospatial regression analyses have been conducted using the R packages base, dplyr, epiR, p ...[more]

PMID: 32187114

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Project description:As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, vascular disruptions, double outlet right ventricle, transposition of the great vessels, hypoplastic right heart, and mitral valve anomalies from 1.75 × 10-19, 4.20 × 10-11, <2.2 × 10-16, <2.2 × 10-16, 1.58 × 10-12, 4.30 × 10-9, 4.36 × 10-16, 3.50 × 10-8, 5.35 × 10-12, <2.2 × 10-16, 5.65 × 10-5 and 6.06 × 10-10. At spatial regression, terms including cannabis were positive and significant for this same list of anomalies from 0.0038, 1.05 × 10-10, 0.0215, 8.94 × 10-6, 1.23 × 10-5, 2.05 × 10-5, 1.07 × 10-6, 8.77 × 10-5, 9.11 × 10-6, 0.0001, 3.10 × 10-7 and 2.17 × 10-7. 92.6% and 75.2% of 149 E-value estimates and minimum E-values were in high zone >9; 100.0% and 98.7% >1.25. Data show many congenital cardiac anomalies exhibit strong bivariate relationships with metrics of cannabis exposure. Causal inferential modelling for the twelve anomalies selected demonstrated convincing evidence of robust relationships to cannabis which survived adjustment and fulfilled epidemiological criteria for causal relationships. Space-time regression was similarly confirmatory. Epigenomic pathways constitute viable potential mechanisms. Given exponential genotoxic dose-response effects, careful and astute control of cannabinoid penetration is indicated.

Project description:Introduction. Of the many congenital anomalies (CAs) recently linked with community cannabis exposure, arguably the most concerning are neurological CAs (NCAs). We therefore conducted a detailed study of this in fourteen European nations. Methods. Congenital anomaly data were from Eurocat. Drug exposure data were from European Monitoring Centre for Drugs and Drug Addiction. Income from World bank. Results. The Netherlands, Spain, France and Bulgaria reported increasing rates of many NCAs. The NCA rate (NCAR) was higher in nations with increasing daily cannabis use when compared to those without (p = 0.0204, minimum E-value (mEV) = 1.35). At bivariate analysis, the mEVs of the following NCAs were significantly cannabis related: severe microcephaly 2.14 × 1013, craniosynostosis 5.27 × 1011, nervous system 4.87 × 1011, eye 2.73 × 107, microphthalmos 4.07 × 106, anencephalus 710.37, hydrocephalus 245.64, spina bifida 14.86 and neural tube defects 13.15. At inverse probability, weighted panel regression terms including cannabis were significantly related to the following series of anomalies: nervous system, anencephalus, severe microcephalus, microphthalmos, neural tube defect and spina bifida from p = 5.09 × 10−8, <2.2 × 10−16, <2.2 × 10−16, 4.84 × 10−11, <2.2 × 10−16 and 9.69 × 10−7. At geospatial regression, this same series of anomalies had terms including cannabis significant from p = 0.0027, 1.53 × 10−7, 3.65 × 10−6, 2.13 × 10−8, 0.0002 and 9.76 × 10−12. 88.0% of 50 E-value estimates and 72.0% of mEVs > 9. This analysis therefore demonstrates both close association of cannabis exposure with multiple NCAs across space-time and also fulfills the quantitative criteria of causal inferential analysis. Conclusions. Nine NCARs on bivariate and six NCARs on multivariable regression were cannabis related and fulfilled quantitative epidemiological criteria for causality and are consistent with other series. Particular concerns relate to exponential dose−response effects demonstrated in the laboratory and epidemiological studies. Great caution with community cannabinoid penetration is warranted. Data indicate that cannabis is a significant environmental teratogen and thus imply that cannabinoids should be regulated similarly to the manner in which all other important genotoxins are carefully controlled by communities for their self-sustaining longevity and the protection of generations yet to come.

Project description:IntroductionSince high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe.MethodsCA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank's online sources.ResultsOn the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the Netherlands. In the bivariate analysis, the anomalies could be ranked by the minimum E-value (mEV) as congenital glaucoma > congenital cataract > choanal atresia > cleft lip ± cleft palate > holoprosencephaly > orofacial clefts > ear, face, and neck anomalies. When nations with increasing daily use were compared to those without, the former had generally higher rates of FCAs (p = 0.0281). In the inverse probability weighted panel regression, the sequence of anomalies-orofacial clefts, anotia, congenital cataract, and holoprosencephaly-had positive and significant cannabis coefficients of p = 2.65 × 10-5, 1.04 × 10-8, 5.88 × 10-16, and 3.21 × 10-13, respectively. In the geospatial regression, the same series of FCAs had positive and significant regression terms for cannabis of p = 8.86 × 10-9, 0.0011, 3.36 × 10-8, and 0.0015, respectively. Some 25/28 (89.3%) E-value estimates and 14/28 (50%) mEVs were >9 (considered to be in the high range), and 100% of both were >1.25 (understood to be in the causal range).ConclusionRising cannabis use is associated with all the FCAs and fulfils the epidemiological criteria for causality. The data indicate particular concerns relating to brain development and exponential genotoxic dose-responses, urging caution with regard to community cannabinoid penetration.

Dataset Information

Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis.

Publications

Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis.

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