Socioeconomic, Ethnocultural, Substance- and Cannabinoid-Related Epidemiology of Down Syndrome USA 1986-2016: Combined Geotemporospatial and Causal Inference Investigation.

backgroundDown syndrome (DS) is the commonest of the congenital genetic defects whose incidence has been rising in recent years for unknown reasons. This study aims to assess the impact of substance and cannabinoid use on the DS Rate (DSR) and assess their possible causal involvement.

methodsAn observational population-based epidemiological study 1986-2016 was performed utilizing geotemporospatial and causal inferential analysis. Participants included all patients diagnosed with DS and reported to state based registries with data obtained from National Birth Defects Prevention Network of Centers for Disease Control. Drug exposure data was from the National Survey of Drug Use and Health (NSDUH) a nationally representative sample interviewing 67,000 participants annually. Drug exposures assessed were: cigarette consumption, alcohol abuse, analgesic/opioid abuse, cocaine use and last month cannabis use. Covariates included ethnicity and median household income from US Census Bureau; maternal age of childbearing from CDC births registries; and cannabinoid concentrations from Drug Enforcement Agency.

resultsNSDUH reports 74.1% response rate. Other data was population-wide. DSR was noted to rise over time and with cannabis use and cannabis-use quintile. In the optimal geospatial model lagged to four years terms including Δ9-tetrahydrocannabinol and cannabigerol were significant (from β-est. = 4189.96 (95%C.I. 1924.74, 6455.17),

conclusionsData show that the association between DSR and substance- and cannabinoid- exposure is robust to multivariable geotemporospatial adjustment, implicate particularly cannabigerol and Δ9-tetrahydrocannabinol, and fulfil quantitative epidemiological criteria for causality. Nevertheless, detailed experimental studies would be required to formally demonstrate causality. Cannabis legalization was associated with elevated DSR's at both bivariate and multivariable analysis. Findings are consistent with those from Hawaii, Colorado, Canada, Australia and Europe and concordant with several cellular mechanisms. Given that the cannabis industry is presently in a rapid growth-commercialization phase the present findings linking cannabis use with megabase scale genotoxicity suggest unrecognized DS risk factors, are of public health importance and suggest that re-focussing the cannabis debate on multigenerational health concerns is prudent.