Background. Downs syndrome (DS) is the commonest of the congenital genetic defects. Its incidence has been rising in recent years for unknown reasons. Objective. Investigate the relationship of DS to substance- and cannabinoid- exposure; and causality.

Methods. Observational ecological population-based epidemiological study 1986-2016. Analysis performed January 2020. Geotemporospatial and causal inference analysis.

Participants: Patients were diagnosed with DS and reported to state based registries; collated nationally. Data source: annual reports of National Birth Defects Prevention Network of Centres for Disease Control.

Exposures: Drug exposure was taken from the National Survey of Drug Use and Health (NSDUH) conducted annually by Substance Abuse and Mental Health Services Administration. Nationally representative sample 67,000 participants annually. Drug exposures: cigarette consumption, alcohol abuse, analgesic/opioid abuse, cocaine use and last month cannabis use. Ethnicity and median household income: US Census Bureau. Maternal age of childbearing: CDC births registries. Cannabinoid concentrations: Drug Enforcement Agency seizures.

Results. NSDUH report 74.1% mean annual response rate. All other data was population-wide. DS rate (DSR) was noted to be rising over time, 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), P=2.9x10-4). Ethnicity, income, and maternal age covariates were not significant. DSR in states where cannabis was not illegal was higher than elsewhere (β-est.=2.160 (1.5, 2.82), R.R.=1.81 (1.51, 2.16), P=4.7x10-10). In inverse probability-weighted mixed models terms including cannabinoids were significant (from β-estimate=18.82 (16.82, 20.82), P

Conclusions. Our data 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 causal crietria. Cannabis legalization was associated with elevated DSR’s. These findings are consistent with those from Hawaii, Colorado, Canada and Australia 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 and intergenerational health concerns is prudent.

In 2019, the global age-standardized death rate for Down syndrome was around 0.3 per 100,000 population. The most common cause of death for adults and children with Down syndrome is respiratory infection. This statistic shows the age-standardized death rate for Down syndrome worldwide in 1990 and 2019, by gender.

Legacy unique identifier: P00448

Legacy unique identifier: P00434

Raw data of 17 individuals with Down syndrome (8 girls/women; average age: 17.8 years; range: 7.2-30.8 years at the beginning of the study) in a visual learning task, a 3-item conditional learning task, and a 5-item conditional learning and transitive inference task.

Raw data of 27 individuals with Williams syndrome (16 girls/women; average age: 23.7; range: 9.4-43.8 at the beginning of the study) in a visual learning task, a 3-item conditional learning task, and a 5-item conditional learning and transitive inference task.

Raw data of 71 healthy children (31 girls; average age: 6.42 years; range: 2.95-11.64 years at the beginning of the study) in a visual learning task, a 3-item conditional learning task, and a 5-item conditional learning and transitive inference task.

Raw data of 22 healthy adults (11 femaleswomen; average age: 26.05 years; range: 20.32-29.76 years at the beginning of the study) in a visual learning task, a 3-item conditional learning task, and a 5-item conditional learning and transitive inference task.

Legacy unique identifier: P00439

Non-Invasive Prenatal Testing Kit Market Outlook

The global market size for Non-Invasive Prenatal Testing (NIPT) kits was valued at approximately USD 3.4 billion in 2023 and is anticipated to reach nearly USD 9.8 billion by 2032, showcasing a robust CAGR of 12.5% during the forecast period. This impressive growth is driven by several factors including advancements in diagnostic technology, increasing awareness among expectant parents, and the escalating incidences of chromosomal abnormalities.

One of the primary growth factors for the NIPT kit market is the rising prevalence of genetic disorders like Down syndrome, Edwards syndrome, and Patau syndrome among newborns. With an increasing number of older women opting for pregnancies, the risk of chromosomal abnormalities has surged, thereby driving the demand for non-invasive prenatal testing. Additionally, advancements in cell-free DNA technology have significantly improved the accuracy and reliability of these tests, further propelling market growth.

Another pivotal growth factor is the growing awareness and acceptance of non-invasive prenatal testing among healthcare providers and expectant parents. The non-invasive nature of these tests ensures that they pose minimal risk to both the mother and the fetus, making them a preferred option over invasive methods like amniocentesis. Furthermore, increasing educational campaigns and endorsements from healthcare organizations are enhancing the adoption rates of NIPT kits globally.

The market is also experiencing growth due to the continuous innovations and improvements in prenatal testing technologies. Companies are investing heavily in research and development to introduce advanced testing kits that offer quicker results, higher accuracy, and comprehensive genetic screening capabilities. This has led to the development of more sophisticated instruments and software that streamline the testing process and improve diagnostic outcomes.

Regionally, North America dominates the NIPT kit market due to its advanced healthcare infrastructure, high awareness levels, and supportive government policies. However, the Asia Pacific region is expected to exhibit the highest growth rate during the forecast period, driven by increasing healthcare expenditure, rising awareness, and the growing number of late maternal age pregnancies. Europe also holds a significant share, owing to advancements in healthcare technologies and increased acceptance of prenatal screening methods.

Product Type Analysis

In the NIPT kit market, the product type segment is classified into consumables, instruments, and software. Consumables, which include reagents, test kits, and other supplies used in the testing process, form a substantial part of the market. Due to the recurrent need for these items with each test conducted, consumables are expected to maintain a significant market share. The constant demand from laboratories and hospitals contributes significantly to the revenue generated in this segment.

Instruments used in NIPT, such as sequencers and analyzers, form another crucial segment. With continuous advancements in technology, newer and more efficient instruments are introduced, enhancing the accuracy and speed of prenatal tests. This segment, although requiring a higher initial investment, promises substantial growth due to the increasing adoption of advanced diagnostic tools in hospitals and diagnostic centers. The integration of AI and machine learning in these instruments further adds to their efficacy, making them indispensable in prenatal diagnostics.

Software solutions form the backbone of NIPT, as they are essential for analyzing the vast amounts of genetic data generated during testing. Robust software solutions enable precise interpretation of test results, ensuring accurate detection of genetic anomalies. Companies are focusing on developing advanced software that can handle complex genetic data and provide user-friendly interfaces for healthcare professionals. This segment is expected to grow significantly as software innovations continue to improve data analysis and reporting capabilities in prenatal testing.

Report Scope

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) a known cannabis use centre.

Methods. Design: Cohort. 2008-2015. Setting: NNSW and Queensland (QLD), Australia. Participants. Whole populations. Exposures. Tobacco, Risky Alcohol, Annual 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: 4,265/22,084 v. 96,473/490,514 >35 years, 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. In robust and mixed effects inverse probability weighted multivariable regression cannabis was related to 18defects. E-Values in spatial models were generally >1.3 ranging up to 3.8x1030 making uncontrolled confounding unlikley.

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; and that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies and is robust to adjustment for other substances.