Geotemporospatial and causal inference epidemiological analysis of US survey and overview of cannabis, cannabidiol and cannabinoid genotoxicity in relation to congenital anomalies 2001-2015

• Published in: BMC pediatrics 2022-01, Vol.22 (1), p.47-47, Article 47
• Main Authors: Reece, Albert Stuart, Hulse, Gary Kenneth
• Format: Article
• Language: English
• Subjects: Analgesics; Birth defects; Cannabidiol; Cannabigerol; Cannabinoid; Cannabinoids; Cannabinoids - adverse effects; Cannabinoids - analysis; Cannabis; Cannabis - adverse effects; Chromosomes; Complications and side effects; DNA Damage; Epidemiology; Epigenetics; Genetic toxicology; Humans; Laws, regulations and rules; Marijuana; Mechanisms; Medical profession; Pediatric research; Pediatrics; Pregnancy; Risk factors; Spina bifida; Δ9-tetrahydrocannabinol
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/s12887-021-02996-3

Cannabinoids including cannabidiol have recognized genotoxic activities but their significance has not been studied broadly epidemiologically across the teratological spectrum. We examined these issues including contextual space-time relationships and formal causal inferential analysis in USA. State congenital anomaly (CA) rate (CAR) data was taken from the annual reports of the National Birth Defects Prevention Network 2001-2005 to 2011-2015. Substance abuse rates were from the National Survey of Drug Use and Health a nationally representative longitudinal survey of the non-institutionalized US population with 74.1% response rate. Drugs examined were cigarettes, monthly and binge alcohol, monthly cannabis and analgesic and cocaine abuse. Early termination of pregnancy for abortion (ETOPFA) rates were taken from the published literature. Cannabinoid concentrations were from Drug Enforcement Agency. Ethnicity and income data were from the US Census Bureau. Inverse probability weighted (IPW) regressions and geotemporospatial regressions conducted for selected CAs. Data on 18,328,529 births from an aggregated population of 2,377,483,589 for mid-year analyses 2005-2013 comprehending 12,611 CARs for 62 CAs was assembled and ETOPFA-corrected (ETOPFACAR) where appropriate. E-Values for ETOPFACARs by substance trends were elevated for THC (40 CAs), cannabis (35 CAs), tobacco (11 CAs), cannabidiol (8 CAs), monthly alcohol (5 CAs) and binge alcohol (2 CAs) with minimum E-Values descending from 16.55, 1.55x10 , 555.10, 7.53x10 , 9.30 and 32.98. Cardiovascular, gastrointestinal, chromosomal, limb reductions, urinary, face and body wall CAs particularly affected. Highest v. lowest substance use quintile CAR prevalence ratios 2.84 (95%C.I. 2.44, 3.31), 4.85 (4.08, 5.77) and 1.92 (1.63, 2.27) and attributable fraction in exposed 0.28 (0.27, 0.28), 0.57 (0.51, 0.62) and 0.47 (0.38, 0.55) for tobacco, cannabis and cannabidiol. Small intestinal stenosis or atresia and obstructive genitourinary defect were studied in detail in lagged IPW pseudo-randomized causal regressions and spatiotemporal models confirmed the causal role of cannabinoids. Spatiotemporal predictive modelling demonstrated strongly sigmoidal non-linear cannabidiol dose-response power-function relationships (P = 2.83x10 and 1.61x10 respectively). Data implicate cannabinoids including cannabidiol in a diverse spectrum of heritable CAs. Sigmoidal non-linear dose-response relationships are of grave concern. Thes