Systematically Testing the Evidence on Marijuana

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 common illicit drug used among women of childbearing age and during pregnancy.
  • Frequency of cannabis use during pregnancy has more than doubled in the US the past decade with past-month cannabis use increasing from 3.4% In 2002 to 7% In 2017.
  • At present, the US Surgeon General and American College of Obstetricians and Gynecologists advise pregnant and lactating women to abstain from using cannabis.
  • A 2016 systematic review assessing the adverse neonatal outcomes from maternal cannabis use identified few studies. We updated this review to capture the most current evidence.
Methods

Living systematic review

Search: 

  • Ovid
  • Embase
  • Scopus
  • Cochrane Library
  • Google Scholar
  • PubMed

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: 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 48 eligible studies. Of these, 47 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 uncertain (n = 29 studies; very low CoE)
    • Following statistical adjustment, we observed increased odds of PTB (n = 36 studies; low CoE) and SGA (n = 17 studies; low CoE) in women who used cannabis in pregnancy
    • Unadjusted estimates suggest that the odds of perinatal mortality were increased with cannabis use in pregnancy (n = 15 studies; very low CoE)
      • We found insufficient data on the relationship between cannabis use in pregnancy and perinatal mortality that accounted for confounders (e.g., maternal age, prenatal smoking)

Summary of Findings (GRADE)

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

Birthweight (mean)

29 studies

N = 176, 055

 ⨁◯◯◯Very low Unclear relationship between cannabis use in pregnancy and birthweight Downgraded 1 level for inconsistency

Preterm Birth (<37 weeks)

36 studies

N = 14,144,430

 ⨁⨁◯◯Low After adjustment, increased odds of PTB with cannabis use during pregnancy Downgraded 1 level for inconsistency ; upgraded 1 level for accounting for all plausible confounders

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

15 studies

N = 13,518,099

 ⨁◯◯◯Very low Increased odds of perinatal mortality with cannabis use during pregnancy (unadjusted association) Downgraded 1 level for inconsistency

SGA (<10th percentile)

17 studies

N = 836,118

 ⨁⨁◯◯Low After adjustment, increased odds of SGA birth with cannabis use during pregnancy Downgraded 1 level for inconsistency; upgraded 1 level for accounting for all plausible confoundersAbbreviations. SGA: small-for-gestational age

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 birthweight, PTB, perinatal mortality, and SGA.
  • Despite our findings indicating potential perinatal harm 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. https://www.cannabisevidence.org/evidence-syntheses/cannabis-use-in-pregnancy/

Citations

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

United Nations Office on Drugs and Crime (UNODC). World Drug Report 2017 – United Nations Office on Drugs and Crime. 2017

Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. 2017 National Survey on Drug Use and Health: Methodological Resource Book. https://www.samhsa.gov/data/report/nsduh-2017-methodological-resource-book-mrb. Accessed August 24, 2021

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.

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

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.

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.

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.

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