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

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.