Epidemiological Patterns of Cannabis- and Substance- Related Congenital Uronephrological Anomalies in Europe: Geospatiotemporal and Causal Inferential Study

Abstract

Introduction. Recent reports linking prenatal and community cannabis exposure to elevated uronephrological congenital anomaly (UCA) rates (UCAR’s) raise the question of its European epidemiology given recent increases in community cannabinoid penetration there. Methods. UCAR data from Eurocat. Drug use data from European Monitoring Centre for Drugs and Drug Addiction. Income from World bank. Results. UCAR increased across Spain, Netherlands, Poland and France. UCAR’s and cannabis resin THC increased simultaneously in France, Spain, Netherlands and Bulgaria. At bivariate analysis all UCA’s were related to cannabis herb and resin THC concentrations. All UCAR’s were bivariately related to cannabis metrics ordered by median minimum E-value (mEV) as hypospadias > multicystic renal disease > bilateral renal agenesis > UCA’s > hydronephrosis > posterior urethral valve > bladder exstrophy/epispadias. At inverse probability weighted multivariable analysis terms including cannabis were significant for the following series of anomalies: UCA’s, multicystic renal disease, bilateral renal agenesis, hydronephrosis, congenital posterior urethral valves from P = 1.91 × 10−5, 2.61 × 10−8, 4.60 × 10−15, 4.60 × 10−15 and 2.66 × 10−10. At geospatial analysis the same series of UCA’s were significantly related to cannabis from P = 7.84 × 10−15, 7.72 × 10−5, 0.0023, 6.95 × 10−5, and 8.82 × 10−5. 45/51 (88.2%) of E-value estimates and 31/51 (60.8%) of mEV’s > 9. Conclusion. Analysis confirms a close relationship between cannabis metrics and all seven UCA’s and fulfill formal criteria for quantitative causal inference. Given the exponential cannabinoid genotoxicity dose–response relationship results provide a powerful stimulus to constrain community cannabinoid exposure including protection of the food chain to preserve the genome and epigenome of coming generations.

Congenital Gastrointestinal Anomalies in Europe 2010–2019: A Geo-Spatiotemporal and Causal Inferential Study of Epidemiological Patterns in Relationship to Cannabis- and Substance Exposure

“…Interestingly, a companion paper to the present paper was recently published and showed that VACTERL syndrome (vertebral, anorectal, cardiac, tracheo-esophageal fistulae/esophageal atresia, renal and limb anomalies) was strongly and causally linked with European cannabinoid exposure [57,92]. In that esophageal atresia is part of the VACTERL syndrome this finding provides evidence from this other reference, confirming the present findings reported herein.…”

“…Many papers demonstrate that the dose-response relationship of cannabinoids with both genomic mutagenicity and mitochondrial toxicity is strongly exponential [52][53][54][55][56]. Moreover, this exponentiation of the dose-response effect has been extended to epidemiological studies where it has been repeatedly demonstrated that the passage from the fourth to fifth quintile of cannabinoid exposure is accompanied by a discontinuous quantum jump in congenital anomaly rates [5,[57][58][59][60].…”

Clinical Epigenomic Explanation of the Epidemiology of Cannabinoid Genotoxicity Manifesting as Transgenerational Teratogenesis, Cancerogenesis and Aging Acceleration

“…There are various strengths and limitations to the present conceptualization. The strengths include the remarkable consistency across the many epidemiological studies, which clearly demonstrates the genotoxic harms of cannabis exposure in several different international jurisdictions, in relation to both the congenital anomalies [ 28 , 36 , 37 , 40 , 45 , 46 , 49 , 51 , 71 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ] and cancer [ 22 , 23 , 24 , 25 , 26 , 30 , 41 , 232 ], and, indeed, now also in aging [ 53 , 54 ]. Similar results in many different studies are clearly mutually supportive and strengthen the overall quality of the body of evidence.…”

“…For the reader who is unfamiliar with this epidemiological literature, it should be pointed out that most of the modern epidemiological studies referred to are not just observational ecological studies of convenience which happen to show a particular association. Many of the best studies used a formal space–time analysis and the quantitative tools of causal inference to introduce a pseudo-randomized quasi-experimental paradigm from which it is entirely appropriate to invoke causal associations [ 28 , 36 , 37 , 40 , 45 , 51 , 71 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ].…”

Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

“…It is therefore highly relevant that tripling levels of community cannabis exposure have been linked with a tripling of total birth defect rates in Canada’s northern provinces, and increased levels of cannabis exposure have been linked with higher rates of dozens of congenital anomalies in Hawaii, Colorado, Australia and the USA [ 44 , 45 , 46 , 47 , 48 , 49 ], affecting most major organ systems (cardiovascular, gastrointestinal, genitourinary, respiratory, neurological and body wall), including limbs and chromosomal anomalies, trisomies and monosomy [ 44 , 45 , 46 , 47 , 48 , 49 ]. Much data have come to light recently as a result of large studies of national and transnational datasets on this subject [ 44 , 46 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”