TY - JOUR
T1 - European epidemiological patterns of cannabis- and substance-related congenital cardiovascular anomalies
T2 - geospatiotemporal and causal inferential study
AU - Reece, Albert Stuart
AU - Hulse, Gary Kenneth
N1 - Funding Information:
No funding was provided for this study. No funding organization played any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. Ethics Approval and Consent to Participate. The Human Research Ethics Committee of the University of Western Australia provided ethical approval for the study to be undertaken on 24 September 2021 (No. RA/4/20/4724).
Publisher Copyright:
© The Author(s) 2022.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - alcohol
KW - cancer
KW - cancerogenesis
KW - cannabinoid
KW - cannabis
KW - epigenotoxicity
KW - genotoxicity
KW - mutagenesis
KW - oncogenesis
KW - tobacco
KW - transgenerational inheritance
UR - http://www.scopus.com/inward/record.url?scp=85136274235&partnerID=8YFLogxK
U2 - 10.1093/eep/dvac015
DO - 10.1093/eep/dvac015
M3 - Article
C2 - 35966825
AN - SCOPUS:85136274235
SN - 2058-5888
VL - 8
JO - Environmental Epigenetics
JF - Environmental Epigenetics
IS - 1
M1 - dvac015
ER -
