A genome-environment analysis of infant deaths found prenatal cannabis use was associated with a 3.7-fold higher risk of sudden unexpected infant death, rising to 6.0-fold after removing cases with strong genetic risk factors.
Pregnant individuals, obstetricians, SUID researchers, pediatricians
3.7x higher SUID risk with prenatal cannabis (6.0x in non-genetic cases)
What the researchers found
Among 212 SUID cases and 620,392 controls born in San Diego County (2005-2018), prenatal cannabis use was associated with an adjusted hazard ratio of 3.7 for SUID. When cases with strong genetic risk factors were removed, the cannabis association strengthened to aHR 6.0. WGS identified probable or possible genetic etiologies in 16% and 48% of SUID cases, with extreme genetic heterogeneity (144 loci, 173 risks).
Why it matters
This is the first large-scale study to combine genetic and environmental risk factors for SUID. The finding that cannabis risk strengthens after removing genetic cases suggests it operates through a different mechanism than the genetic causes, possibly representing a truly environmental risk.
The numbers in context
212 SUID cases; 620,392 controls; cannabis aHR 3.7 (overall), 6.0 (after removing genetic cases); 16% probable genetic etiology; 48% possible genetic etiology; 144 loci contributing 173 risks.
How the study worked
Genome-environment analysis linking births in San Diego County (2005-2018) to hospital discharge summaries and death files. 212 SUID cases vs. 620,392 controls. Whole genome sequencing of SUID cases combined with environmental risk factor analysis.
What this study cannot tell us
Preprint (not yet peer-reviewed). Prenatal cannabis identified from hospital records, likely underestimating true exposure. Cannot separate cannabis from polysubstance use entirely. San Diego County may not represent all populations. Genetic analysis of cases only, not controls.
How to read the evidence
Large cohort with novel genome-environment design, but preprint status, hospital-record cannabis ascertainment, and single-county sample limit strength.
When this study was published
2025 preprint with 2005-2018 data
The bigger picture
SUID (including SIDS) is the third leading cause of infant death with increasing incidence. The finding that prenatal cannabis is a strong risk factor, especially in non-genetic cases, adds to growing concerns about cannabis use during pregnancy and has implications for public health messaging.
Questions still open
- Through what biological mechanism might prenatal cannabis increase SUID risk?
- Would these findings replicate in cohorts with more detailed cannabis exposure data?
Common questions
Does cannabis use during pregnancy increase SIDS risk?
What causes sudden infant death?
Read the original research
Genome x Environment analysis of Sudden Unexpected Infant Death unveils etiologic heterogeneity and strong cannabis and genetic disease risks.
medRxiv : the preprint server for health sciences
Citation
Kingsmore, Stephen F; Bandoli, Gretchen; Helbling, Daniel C; Baer, Rebecca; Blincow, Eric; Cao, Bryant; Frise, Erwin; Heinen, Alaina; Jelliffe-Pawlowski, Laura; Kobayashi, Erica Sanford; Kraan, Lucita Van Der; Kwon, Hugh; Lavy, Rishona; Moore, Barry; Oh, Danny; Oltman, Scott; Eric Ontiveros; Protopsaltis, Liana; Yandell, Mark; Chambers, Christina D. (2025). Genome x Environment analysis of Sudden Unexpected Infant Death unveils etiologic heterogeneity and strong cannabis and genetic disease risks.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.11.26.25341098
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