Cannabis use in Pregnancy

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Visual Abstract

Summary

Cannabis use in pregnancy and neonatal outcomes: A systematic review and meta-analysis

Background
  • In the US, cannabis is the most commonly used illicit drug among women of childbearing age and during pregnancy.
  • Approximately half of pregnant individuals who use cannabis continue to use throughout pregnancy, particularly in the first trimester.
  • At present, the US Surgeon General and American College of Obstetricians and Gynecologists advise pregnant and lactating individuals to abstain from using cannabis due to concern over detrimental fetal outcomes.
  • Prior reviews have been limited by lack of adjustment for important confounding factors (e.g., prenatal tobacco use) and inclusion of studies mostly published before the recent legalization of cannabis by many states.
  • This review provides a contemporary understanding of the association between prenatal cannabis exposure and fetal and neonatal outcomes after accounting for tobacco use.
Methods

Living systematic review

Search:

  • CINAHL (EBSCOHost)
  • EBM Reviews Cochrane Database of Systematic Reviews (Ovid)
  • Global Health (Ovid)
  • MEDLINE (Ovid)
  • PsycInfo (Ovid)

Screening: Cohort or case-control studies assessing the effects of prenatal cannabis use on risk of preterm birth (less than 37 weeks of gestation; PTB), low birth weight (less than 2,500 grams; LBW), small-for-gestational-age (weight less than the 10th percentile given sex and gestational age; SGA) and perinatal mortality.

Risk of Bias (RoB): Newcastle-Ottawa tool for cohort studies and case-control studies

GRADE: Overall certainty of evidence (CoE) for each outcome using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach

Meta-Analysis: Pairwise meta-analyses using adjusted and unadjusted data.

Updates: Search to be updated every 6 months with new reports as needed

Findings
  • We identified 53 eligible studies. Of these, 52 were cohort studies and 1 was a case-control study. In general, we rated these studies as low to moderate risk of bias:
    • The relationship between cannabis use in pregnancy and birthweight is unclear (n = 31 studies; low CoE)
    • Following statistical adjustment, we observed increased odds of PTB (n = 41 studies; low CoE) and SGA (n = 21 studies; low CoE) in infants of individuals who used cannabis in pregnancy
    • After adjustment, the odds of perinatal mortality were increased with cannabis use in pregnancy, but the CoE was very low (n = 17 studies)

Summary of Findings (GRADE)

Outcome Studies;
Sample Size
Certainty of the Evidence Relationship Rationale for CoE Rating

Birthweight (mean)

31 studies  

N = 282,699

⨁⨁◯◯

Low

Unclear relationship between cannabis use in pregnancy and birthweight Downgraded 1 level each for RoB and inconsistency

Preterm Birth (<37 weeks)

41 studies

N = 17,943,871

⨁⨁◯◯

Low

After adjustment, increased odds of PTB with cannabis use during pregnancy Downgraded 1 level each for RoB and inconsistency

Perinatal mortality (e.g., stillbirth, fetal demise)

17 studies

N = 14,141,101

⨁◯◯◯

Very low

After adjustment, increased odds of perinatal mortality with cannabis use during pregnancy Downgraded 1 level for RoB and 2 levels for indirectness

SGA (<10th percentile)

21 studies

N = 4,582,445

⨁⨁◯◯

Low

After adjustment, increased odds of SGA birth with cannabis use during pregnancy Downgraded 1 level each for RoB and inconsistency

Abbreviations. RoB: risk of bias; SGA: small-for-gestational age; PTB: preterm birth
GRADE certainty of evidence: Very low ⨁◯◯◯; Low ⨁⨁◯◯; Moderate ⨁⨁⨁◯; High ⨁⨁⨁⨁

Conclusions
  • Overall, we found very low to low CoE of the associations of cannabis use in pregnancy and preterm birth, perinatal mortality, and small-for-gestational-age.
  • Despite our findings indicating potential perinatal harms of cannabis use during pregnancy, our certainty in them is low. As prenatal cannabis use becomes more commonplace, this review can help guide healthcare providers with counseling, management, and addressing the limited existing safety data.
Gaps in Evidence
  • High quality studies that consider formulation and dosing of cannabis, as well as the timing and duration of use, are needed to help elucidate the associations between prenatal cannabis exposure and perinatal outcomes.
  • High quality studies that fully report both unadjusted and adjusted data are also needed.

Lo J, Shaw B, Robalino S, Durbin S, Ayers C, Olyaei A, Rushkin M, Kansagara D, Harrod C. Cannabis use in pregnancy and neonatal outcomes: A systematic review and meta-analysis. The Systematically Testing the Evidence on Marijuana Project; 2021; revised February 2023.  Accessed (Month DD, YYYY). https://www.cannabisevidence.org/evidence-syntheses/cannabis-use-in-pregnancy/

Citations

Brown QL, Sarvet AL, Shmulewitz D, Martins SS, Wall MM, Hasin DS. Trends in Marijuana Use Among Pregnant and Nonpregnant Reproductive-Aged Women, 2002-2014. JAMA. 2017;317(2):207-209. doi:10.1001/jama.2016.17383

Conner SN, Bedell V, Lipsey K, Macones GA, Cahill AG, Tuuli MG. Maternal marijuana use and adverse neonatal outcomes: a systematic review and meta-analysis. Obstet Gynecol. 2016;128(4):713-723. 

Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926.

Marchand G, Masoud AT, Govindan M, et al. Birth Outcomes of Neonates Exposed to Marijuana in Utero: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022;5(1):e2145653. Published 2022 Jan 4. doi:10.1001/jamanetworkopen.2021.45653

Marijuana use during pregnancy and lactation. Committee Opinion No. 637. American College of Obstetricians and Gynecologists. Obstet Gynecol 2015;126(1):234–238.

Martin CE, Longinaker N, Mark K, Chisolm MS, Terplan M. Recent trends in treatment admission for marijuana use during pregnancy. J Addict Med. 2015;9(2):99-104. doi: 10.1097/ADM.0000000000000095

U.S. Surgeon General’s Advisory: Marijuana use and the developing brain. https://www.hhs.gov/surgeongeneral/reports-and-publications/addiction-and-substance-misuse/advisory-on-marijuana-use-and-developing-brain/index.html Last accessed August 24, 2021.

Volkow ND, Han B, Compton WM, McCance-Katz EF. Self-reported Medical and Nonmedical Cannabis Use Among Pregnant Women in the United States. JAMA. 2019;322(2):167-169. doi:10.1001/jama.2019.7982 

Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2013, http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Last accessed August 25, 2021.

Full Report

This is the accepted version of the following article: Jamie O. Lo, Beth Shaw, Shannon Robalino, Chelsea K. Ayers, Shauna Durbin, Megan C. Rushkin, Amy Olyaei, Devan Kansagara, and Curtis S. Harrod. Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis [published online ahead of print, 2023 Feb 1]. Cannabis Cannabinoid Res. 2023;10.1089/can.2022.026., which has now been formally published in final form at Cannabis and Cannabinoid Research at doi:10.1089/can.2022.0262. This original submission version of the article may be used for non-commercial purposes in accordance with the Mary Ann Liebert, Inc., publishers’ self-archiving terms and conditions.

Archived Versions of this Review

January 2021

Page Last Reviewed:  March 2023