Broad Spectrum Epidemiological Contribution of Cannabis and Other Substances to the Teratological Profile of Northern New South Wales: Geospatial and Causal Inference Analysis

Abstract

Background: Whilst cannabis commercialization is occurring rapidly guided by highly individualistic public narratives, evidence that all congenital anomalies (CA) increase alongside cannabis use in Canada, a link with 21 CA’s in Hawaii, and rising CA’s in Colorado indicate that transgenerational effects can be significant and impact public health. It was therefore important to study Northern New South Wales (NNSW) where cannabis use is high. Methods: Design: Cohort. 2008-2015. Setting: NNSW and Queensland (QLD), Australia. Participants. Whole populations. Exposures. Tobacco, alcohol, cannabis. Source: National Drug Strategy Household Surveys 2010, 2013. Main Outcomes. CA Rates. NNSW-QLD comparisons. Geospatial and causal regression. Results: Cardiovascular, respiratory and gastrointestinal anomalies rose with falling tobacco and alcohol but rising cannabis use rates across Queensland. Maternal age NNSW-QLD was not different (2008-2015: 4265/22084 v. 96473/490514 >35 years/total, Chi.Sq.=1.687, P=0.194). A higher rate of NNSW cannabis-related than cannabis-unrelated defects occurred (prevalence ratio (PR)=2.13, 95%C.I. 1.80-2.52, P=3.24x10-19). CA’s rose more potently with rising cannabis than with rising tobacco or alcohol use. Exomphalos and gastroschisis had the highest NNSW:QLD PR (6.29(2.94-13.48) and 5.85(3.54-9.67)) and attributable fraction in the exposed (84.11%(65.95-92.58%) and 82.91%(71.75-89.66%), P=2.83x10-8 and P=5.62x10-15). In multivariable geospatial models cannabis was significantly linked with cardiovascular (atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus), genetic (chromosomal defects, Downs syndrome), gastrointestinal (small intestinal atresia), body wall (gastroschisis, diaphragmatic hernia) and other (hypospadias) (AVTPCDSGDH) CA’s. In linear modelling cannabis use was significantly linked with anal stenosis, congenital hydrocephalus and Turner syndrome (ACT) and was significantly linked in borderline significant models (model P<0.1) with microtia, microphthalmia, and transposition of the great vessels. At robust and mixed effects inverse probability weighted multivariable regression cannabis was related to 18 defects. 16/17 E-Values in spatial models were >1.25 ranging up to 5.2x1013 making uncontrolled confounding unlikely. Conclusions: These results suggest that population level CA’s react more strongly to small rises in cannabis use than tobacco or alcohol; cardiovascular, chromosomal, body wall and gastrointestinal CA’s rise significantly with small increases in cannabis use; that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies, is robust to adjustment for other substances; and is causal.

Cannabinoid and substance relationships of European congenital anomaly patterns: a space-time panel regression and causal inferential study

“…It is thus of interest that total cardiovascular disorders were noted to also be increased in association with cannabis use in the northern Canadian Provinces and in the US state of Colorado [ 5 , 7 ]. Similarly, it is important to note that ASD was noted to occur with elevated rates in the US states of Hawaii and Colorado, across the USA and in Australia, (and presumably also in Canada as it is the commonest cardiovascular anomaly) [ 4–7 , 55 ]; VSD was noted to be increased in Australia, USA Colorado, Hawaii and in other series [ 4–7 , 55 , 86 ]; PDA was noted to be increased in Colorado, Australia and USA [ 5 , 8 , 55 ]; tetralogy of Fallot was increased in Hawaii, Australia and USA [ 4 , 8 , 55 , 96 ]; AVSD was noted to be elevated also in USA (manuscript submitted) and pulmonary valve atresia and stenosis was associated in USA [ 55 ].…”

“…The chromosomal disorders identified in this study as being linked to indices of cannabis exposure were: Chromosomal, Downs syndrome (Trisomy 21), Edward syndrome (Trisomy 18), Genetic syndromes, Klinefelter (Male XXY), Patau syndrome (Trisomy 13) and Turner syndrome (Female XO). It is of considerable importance that elevated rates of Downs syndrome have previously been identified in association with cannabis exposure in Colorado [ 5 ], Australia [ 8 ], Canada [ 7 ], Hawaii [ 4 ] and USA [ 11 , 55 ]; of Edwards syndrome in USA (manuscript submitted); of Patau syndrome in USA [ 18 , 55 ]; of Turner syndrome in USA [ 18 , 55 ]; of Turner syndrome in Australia [ 8 ] and of chromosomal anomalies in USA, Canada and Australia [ 7 , 8 , 18 , 55 ].…”

“…Large bowel disorders and Hirschsprung’s disease were strongly cannabis related in USA [ 55 ]. Gastrointestinal disorders, including small and large bowel stenoses and atresias, were also noted to be positively associated with cannabis exposure in Australia [ 8 ].…”

“…The body wall anomalies with which cannabis was found to be significantly associated were: abdominal wall defect, diaphragmatic hernia, gastroschisis and omphalocele. Gastroschisis has been previously linked with cannabis use also in Hawaii [ 4 ], Colorado [ 5 ], Australia [ 8 ] and Canada [ 7 , 125 , 129–131 ]. Omphalocele was also associated with cannabis use both in Australia [ 8 ] and in preclinical series in animals [ 85 ].…”

“…Whilst it is often said that prenatal cannabis exposure has relatively benign implications in postnatal life [ 1–3 ], recent independent reports from Hawaii [ 4 ], Colorado [ 5 ], Canada [ 6 , 7 ], Australia [ 8 ] and USA [ 9–11 ] indicate that dozens of congenital anomalies (CAs; birth defects) are likely epidemiologically causally associated with rising rates of community cannabis consumption. Systems that are particularly affected include the cardiovascular, gastrointestinal, chromosomal, genitourinary, limb and body wall systems.…”