European Epidemiological Patterns of Cannabis- and Substance-Related Body Wall Congenital Anomalies: Geospatiotemporal and Causal Inferential Study

Abstract

As body wall congenital anomalies (BWCAs) have a long history of being associated with prenatal or community cannabis exposure (CCE), it was of interest to investigate these epidemiological relationships in Europe given the recent increases in cannabis use prevalence, daily intensity, and Δ9-tetrahydrocannabinol (THC) potency. Methods: This study makes use of BWCA data from Eurocat, drug exposure data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Results: The mapping analysis showed that BWCARs increased in France, Spain, and the Netherlands. The bivariate mapping analysis showed that the BWCA rates (BWCAR) and the cannabis resin THC concentration rose simultaneously in France, the Netherlands, Bulgaria, Sweden, and Norway. The bivariate ranking of the BWCARs by median minimum E-value (mEV) was omphalocele > diaphragmatic hernia > abdominal wall defects > gastroschisis. With inverse probability weighted multivariable panel regression, the series of BWCAs, including gastroschisis, omphalocele, and diaphragmatic hernia, was positively related to various metrics of cannabis use from p = 2.45 × 10−14, 4.77 × 10−7 and <2.2 × 10−16. With geospatial regression, the same series of BWCAs was related to cannabis metrics from p = 0.0016, 5.28 × 10−6 and 4.88 × 10−9. Seventeen out of twenty-eight (60.7%) of the E-value estimates were >9 (high range), as were 14/28 (50.0%) of the mEVs. Conclusion: The data confirm the close relationship of the BWCARs with the metrics of CCE, fulfill the quantitative criteria of causal inference, and underscore the salience of the public health impacts of cannabinoid teratogenicity. Of major concern is the rising CCE impacting exponential cannabinoid genotoxic dose-response relationships. CCE should be carefully restricted to protect the food chain, the genome, and the epigenome of coming generations.

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

“…Recent reports demonstrate increasing concern at the genotoxic activities of cannabinoids expressed as congenital anomalies, cancer and aging [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Recent epidemiological teratological reports have causally linked cannabis exposure with cardiovascular, chromosomal, central nervous system, limb, gastrointestinal, orofacial and body wall congenital anomalies [ 6 , 7 , 8 , 12 , 15 , 18 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. A prominent part of cannabis teratology is uronephrological (urinary tract and renal) congenital anomalies (UCA’s) which have featured in reports of elevated rates of renal agenesis in Colorado [ 13 ], obstructive genitourinary defect in Hawaii [ 19 ], congenital posterior urethral valve, obstructive genitourinary defect, renal agenesis/hypoplasia, hypospadias and epispadias in USA [ 7 ] and hypospadias in Australia [ 8 ].…”

Prenatal Exposure to Cannabis and Risk of Major Structural Birth Defects

“…An ecologic study using data from Europe reported that at the country level, cannabis resin tetrahydrocannabinol concentration rose simultaneously with gastroschisis incidence. 9 Using similar methods, the same authors reported positive associations between territory-level cannabis use and gastroschisis incidence in Canada. 10 Because the unit of analysis for these studies was at the country and territory levels, no inferences can be made at the individual level.…”

“…[3][4][5] Ecologic studies have reported that geographic regions with higher levels of cannabis consumption also have higher incidence of congenital anomalies. [6][7][8][9][10] However, human studies with individual-level data on prenatal cannabis exposure and risk of birth defects are limited.…”

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 ].…”