What is the clinical evidence from this study?

Study design: Observational. Population: Atrial septal defect (n=17751437). Intervention: Cannabis use and legalization vs. States where cannabis was not legal. Primary outcome: Atrial septal defect rate (ASDR) (OR 2.73, 95% CI 2.66-2.80, p=0.00002).

What question did this study set out to answer?

The research aims to explore the increasing rates of atrial septal defects (ASDs) in the USA and their potential relation to cannabis use and legalization.

April 16, 2026Open Access

Space-Time Analysis of Burgeoning US Atrial Septal Defect Rates Driven by Cannabis

Key Result

Cannabis legalization was associated with a significantly higher prevalence of atrial septal defects compared to states where cannabis was not legal (OR 2.73; 95% CI 2.66-2.80).

Key Points

The research aims to explore the increasing rates of atrial septal defects (ASDs) in the USA and their potential relation to cannabis use and legalization.
Analyzed ASD rate data from the National Birth Defects Prevention Network (2003–2020).
Utilized substance use data from the National Survey of Drug Use and Health.
Conducted spatial regression analysis using R package splm on the Non-Hispanic White population.
Created time-sequential maps for substance use and ASD outcomes, focusing on cannabis-related statistics.
Identified 110,107 ASD cases among 17,751,437 live births across 27 states.
Found significant correlation between cannabis use indices and ASDR, with p = 0.00002 for cannabidiol.
In cannabis-legal states, ASD rates were 2.73 times higher compared to non-legal states (95% CI).
Higher E-values suggest a potential causal relationship between cannabis use and ASD rates.

Study Design

Type

Observational (n=17,751,437)

Multicenter

Yes

Structured PICO

Does cannabis use and legalization increase the rate of atrial septal defects in live births?

Population

110,107 ASD cases amongst 17,751,437 live births in 27 US states across 10 reporting periods (2003-2020), limited to the Non-Hispanic White population.

Intervention

Cannabis use and cannabis legalization status

Comparator

States where cannabis was not legal

Outcome

Atrial septal defect rate (ASDR)hard clinical

State-level cannabis legalization and use are associated with significantly higher rates of atrial septal defects in live births, suggesting potential cannabinoid teratogenicity.

Main Result

Effect estimate: OR 2.73 (95% CI 2.66-2.80)

p-value: p=0.00002

Limitations

Analysis was limited to the Non-Hispanic White population by technical factors
7.6% of data was interpolated by linear regression

Abstract

Atrial septal defect (ASD) has become increasingly common in the USA and now affects 1 in 11.3 children in some places, but space–time analysis has not been applied to this emerging trend. ASD rate (ASDR) data were obtained from the National Birth Defects Prevention Network 2003–2020. Substance (cigarettes, alcohol, cannabis, analgesics, cocaine) use data were obtained from the National Survey of Drug Use and Health. Income data were obtained from the US Census. Analysis was limited to the Non-Hispanic White population by technical factors. Time-sequential univariate and bivariate maps were prepared for both covariates and outcomes and their combinations. Spatial regression of the ASDR was performed using the R package splm. A total of 7.6% of data was interpolated by linear regression. A total of 110,107 ASD cases were identified amongst 17,751,437 live births in 27 US states across 10 reporting periods. Time series maps showed that ASDR showed concordant patterns with indices of cannabis use rather than other substances. This was confirmed by multivariate spatial regression where cannabis and cannabinoids alone were found to significantly relate to ASDR, with p = 0.00002 for cannabidiol. Cannabis legal status similarly tracked with ASDR. Compared to states where cannabis was not legal, ASDR was more prevalent in cannabis-legal states (OR = 2.73 (2.66, 2.80); E-Value 4.90 (lower C.I. 4.76)). Twenty-seven of 34 (79.4%) E-values were >9 (high range) and 34/34 were > 1.25 (causal threshold). Data show that cannabis, including cannabis legalization, is driving the US ASD epidemic. While most high-ASDR states have high rates of cannabis use, Midwestern states where cannabis is farmed, such as Kentucky, Tennessee and Missouri, do not, suggesting other routes of exposure, potentially implicating environmental contamination. ASD is a bellwether marker for cannabinoid teratogenicity, indicating that communities should carefully control cannabinoid exposure and limit transgenerational cannabinoid genotoxicity more generally.