Dataset Information

Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends.

ABSTRACT: Rising ?9-tetrahydrocannabinol concentrations in modern cannabis invites investigation of the teratological implications of prenatal cannabis exposure. Data from Colorado Responds to Children with Special Needs (CRCSN), National Survey of Drug Use and Health, and Drug Enforcement Agency was analyzed. Seven, 40, and 2 defects were rising, flat, and falling, respectively, and 10/12 summary indices rose. Atrial septal defect, spina bifida, microcephalus, Down's syndrome, ventricular septal defect, and patent ductus arteriosus rose, and along with central nervous system, cardiovascular, genitourinary, respiratory, chromosomal, and musculoskeletal defects rose 5 to 37 times faster than the birth rate (3.3%) to generate an excess of 11?753 (22%) major anomalies. Cannabis was the only drug whose use grew from 2000 to 2014 while pain relievers, cocaine, alcohol, and tobacco did not. The correlation of cannabis use with major defects in 2014 (2019 dataset) was R = .77, P = .0011. Multiple cannabinoids were linked with summary measures of congenital anomalies and were robust to multivariate adjustment.

SUBMITTER: Reece AS

PROVIDER: S-EPMC6691650 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends.

Reece Albert Stuart AS Hulse Gary Kenneth GK

Clinical pediatrics 20190709 10

Rising Δ9-tetrahydrocannabinol concentrations in modern cannabis invites investigation of the teratological implications of prenatal cannabis exposure. Data from Colorado Responds to Children with Special Needs (CRCSN), National Survey of Drug Use and Health, and Drug Enforcement Agency was analyzed. Seven, 40, and 2 defects were rising, flat, and falling, respectively, and 10/12 summary indices rose. Atrial septal defect, spina bifida, microcephalus, Down's syndrome, ventricular septal defect, ...[more]

PMID: 31288542

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Project description:BackgroundWhilst 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.MethodsDesign: Cohort. 2008-2015.SettingNNSW and Queensland (QLD), Australia.ParticipantsWhole populations. Exposures. Tobacco, alcohol, cannabis.SourceNational Drug Strategy Household Surveys 2010, 2013.Main outcomesCA Rates. NNSW-QLD comparisons. Geospatial and causal regression.ResultsCardiovascular, 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. 96,473/490514 > 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 = 3.24 × 10- 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 = 2.83 × 10- 8 and P = 5.62 × 10- 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 5.2 × 1013 making uncontrolled confounding unlikely.ConclusionsThese 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.

Project description:The discovery of phytocannabinoid synthesizing enzymes, tetrahydrocannabinolic acid synthase (THCAs) and cannabidiolic acid synthase (CBDAs) was a breakthrough in Cannabis research. However, their evolutionary aspects and distribution across organisms has not been adequately studied. We searched for THCAs and CBDAs genes in organisms other than Cannabis plants using the database available in NCBI. Both cannabinoid synthases seem to be widely distributed in the plant kingdom. Of several complete or partial sequences of cannabinoid synthases-likes, CBDAs-like from Morus notabilis matched closely to CsCBDAs and CsTHCAs. When amino acid sequences of CsTHCAs, CsCBDAs and MnCBDAs-like were compared to each other, and to the motif database stored in Expasy, all three proteins contained the FAD_PCMH (PCMH-type FAD-binding) domain indicating the conservation of this domain in cannabinoid synthases. Apart from FAD binding, Berberine Bridge Enzyme (BBE-likes), which catalyzes the synthesis of isoquinoline alkaloids in many plants such as mulberry, poplas and citrus, were the other most closely related enzymes to CsTHCAs and CsCBDAs. We also searched for THCAs and CBDAs in fungal and bacterial kingdom but could not find any notably similar sequence. However, partial mRNA from FAD binding enzyme from Trametes versicolor and 6-hydroxy D nicotine oxidase from Aspergillus saccharolyticus matched the CsTHCA sequence and a partial mRNA from a hypothetical protein in Pneumocystis carinii was the most closely matched fungal enzyme to the CsCBDA. Our database search showed that Morus notabilis from mulberry family could be the candidate plant for further studies. Comparative transcriptomic and metabolomic studies for mulberry and Cannabis plants could provide a much clear concepts on the co-evolution of these syanthases. Moreover, the understanding of cannabinoid synthesis pathway is still evolving, in-depth bioinformatics and functional analysis of the enzymes involved are required for pharmaceutical research and industrial advancement.

Project description:BackgroundThe contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs).ResultsOverall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p < 0.001), but there was no significant difference in the frequency of P/LP CNVs between isolated and nonisolated CHD (11.7% vs. 7.7%). A total of 109 P/LP CNVs were identified in 95 fetuses, consisting of 97 (89.0%) de novo, 6 (5.5%) parental inherited and 6 (5.5%) with unavailable parental information. The 16p11.2 proximal BP4-BP5 deletion was detected in 0.9% (10/1118) of all cases, second only to the most common 22q11.21 proximal A-D deletion (2.1%, 23/1118). Most of the 16p11.2 deletions (8/10) detected were de novo, and were enriched in CHD cases compared with a control cohort from a previous study. Additionally, SV was identified in 12.9% (8/62) of cases without NCA and P/LP CNV, most of which were de novo with autosomal dominant inheritance.ConclusionsOur cohort study provides a deep profile of the contribution of genetic variants to CHDs in both singleton and twin fetuses; NCA and P/LP CNV contribute to 9.1% and 8.5% of CHD in fetuses, respectively. We confirmed the 16p11.2 deletion as a CHD-associated hotspot CNV, second only to the 22q11.21 deletion in frequency. Most 16p11.2 deletions detected were de novo. Additionally, P/LP SV was identified in 12.9% (8/62) of fetuses without NCA or P/LP CNV.

Dataset Information

Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends.

Publications

Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends.

Similar Datasets

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