In‐utero cannabis exposure and long‐term psychiatric and neurodevelopmental outcomes: The limitations of existing literature and recommendations for future research

Abstract

Given increases in cannabis use in pregnancy and animal model researchshowing effects of in-utero cannabis exposure, high-quality information on long-term consequences of in-utero cannabis exposure in humans is needed. While reviews have summarized findings from observational studies with humans, reviews have not focused on limitations of these studies and recommendations for future research. Therefore, we critically reviewed observational research on in-utero cannabis exposure and psychiatric and neurodevelopmental outcomes measured at or after age 3 and provided recommendations for future research. We used Web of Science, Google Scholar, and work cited from relevant identified publications to identify 46 papers to include in our review. Our review includes two main sections. The first section highlights the extensive limitations of the existing research, which include small and nongeneralizable samples, reliance on self-reported data, lack of detail on timing and amount of exposure, inclusion of older exposure data only, not accounting for important confounders, inclusion of potential mediators as covariates, not including outcome severity measures, and not assessing for offspring sex differences. The second section provides recommendations for future research regarding exposure and outcome measures, sample selection, confounder adjustment, and other methodological considerations. For example, with regard to exposure definition, we recommend that studies quantify the amount of cannabis exposure, evaluate the influence of timing of exposure, and incorporate biological measures (e.g., urine toxicology measures). Given that highquality information on long-term consequences of in-utero cannabis exposure in humans does not yet exit, it is crucial for future research to address the limitations we have identified.

A systematic review of in utero cannabis exposure and risk for structural birth defects

“…There were several limitations of the included studies that may have contributed to the mixed findings on in utero cannabis exposure and birth defects. These limitations are similar to those of studies on in utero cannabis exposure and other outcomes, such as long-term neurodevelopmental and psychiatric problems (15). First, many of the studies had samples that were relatively small (e.g., 6 of the 20 studies had samples under 500) and reported findings with wide confidence intervals.…”

“…The causes and risk factors for many structural birth defects remains unknown, and understanding preventable causes and risk factors for structural birth defects is particularly important given the strong association between birth defects and morbidity/mortality ( 16 ). Given this need, we conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate whether in utero cannabis exposure is associated with structural birth defects compared to pregnancies with no cannabis exposure (Prospective Register of Systematic Reviews [PROSPERO] registration number: CRD42022308130; ( 17 )].…”

“…Therefore, there is a great public health need to understand the consequences of in utero cannabis exposure on offspring development. Several meta-analyses and reviews have summarized the evidence of in utero cannabis exposure on adverse obstetric outcomes (e.g., low birth weight and preterm birth) and long-term offspring development (8,(10)(11)(12)(13)(14)(15). However, reviews to date have not focused on research regarding in utero cannabis exposure and risk for structural birth defects.…”

Association of cannabis use during pregnancy with severe acute respiratory syndrome coronavirus 2 infection: a retrospective cohort study

“…It is critical to note that cannabis use during pregnancy is associated with adverse perinatal outcomes, including low offspring birth weight and pre‐term delivery [ 46 , 47 ], and may increase risk for offspring psychopathology in childhood, including externalizing, attention, thought and social problems [ 48 ]. Because of concerns regarding these health risks, national organizations recommend that pregnant women abstain from prenatal cannabis use [ 49 ].…”

The unseen patient: competing priorities between patients and providers when cannabis is used in pregnancy, a qualitative study

“…However, there are limitations to the conclusiveness of the current body of evidence ( 19 ). Limitations of current evidence include sample size and generalizability, self-reported data, lack of data on timing and dosing of cannabis ingestion, as well as a lack of focus on social environmental contexts influencing use of cannabis during pregnancy ( 20 , 21 ). The extant data has identified that more research is needed on maternal cannabis use to optimize public health promotion and intervention development ( 22 – 24 ).…”