By Camille Hoffman, MD, MSc

Associate Professor, Maternal Fetal Medicine, University of Colorado Departments of Obstetrics and Gynecology and Psychiatry, Aurora, CO

Dr. Hoffman reports no financial relationships relevant to this field of study.

SOURCE: Corsi DJ, Walsh L, Weiss D, et al. Association between self-reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes. JAMA 2019;322:145-152.

SYNOPSIS: Cannabis use during pregnancy has become commonplace in states and countries (Canada) where it has been legalized for medical and/or recreational use. The authors of this study attempted to determine whether associations exist between self-reported prenatal cannabis use and maternal and perinatal outcomes.

In a cohort of more than 650,000 women in Ontario, Canada, 9,428 (1.4%) reported cannabis use during pregnancy at the first prenatal care visit and/or upon admission to labor and delivery. The authors then matched 5,639 of the reported cannabis users with 92,873 pregnant women who did not report cannabis use. Both groups had complete information available for confounders, including maternal age, parity, income, pre-pregnancy BMI, maternal smoking (tobacco), alcohol use, opioid use, and psychiatric disorders.

The primary outcome was preterm birth rate

< 37 weeks. Other preterm birth (PTB) groupings (e.g. 34-36 6/7, 28-31 6/7, < 28 weeks) were also assessed, as were other obstetrical outcomes including abruption, small for gestational age (SGA) at birth, preeclampsia, and gestational diabetes.

In matched cohort analyses, PTB < 37 weeks was 1.41-fold higher (95% confidence interval [CI], 1.36-1.46) in women who reported cannabis use than in those who did not. After separating the PTB groupings, there was a categorical increase in PTB in both groups by both a risk difference (RD) calculation and using relative risk (RR) of PTB: 34-36 6/7 weeks, RD 1.75% and RR 1.31, to 28-31 6/7 weeks, RD 0.68% and RR 2.42. There was no difference in PTB < 28 weeks, although overall numbers were small. RD and RR are reported here to give the reader a sense of how distorted RR can be when overall numbers are small.

Interestingly, there was a significant (albeit not clinical) risk difference in preeclampsia and gestational diabetes favoring the cannabis-using group. Cannabis use was not associated with cesarean delivery or operative vaginal delivery risk. On the other hand, cannabis use was associated with SGA less than the third percentile (6.1% vs. 4.0%), abruption (1.6% vs. 0.9%), stillbirth (0.6% vs. 0.4%), neonatal intensive care unit (NICU) admission (25% vs. 11.9%), and five-minute Apgar score < 5 (1.4% vs. 0.7%), with RRs ranging from stillbirth RR 1.6 (95% CI, 1.24-2.08) to SGA less than the third percentile RR 2.6 (95% CI, 2.4-2.82).

When the authors compared women who reported use of cannabis but no other substances with women who used no substances, PTB rates were higher (9.1% vs. 5.9%, RR 1.34 [1.27-1.42]) in the cannabis group. As commonly seen in other obstetrical outcomes, concomitant tobacco use, alcohol use, and opioid use drove the PTB rates higher and overshadowed cannabis use as far as impact on birth outcomes. Compared to other retrospective cohort studies assessing complex interactions between pregnancy exposures and pregnancy outcomes, this study’s strength lies in a large amount of complete data (95% of included pregnancies) and more than 5,500 pregnancies with known cannabis exposure available for review. This leaves the question of confounding by other substance use less susceptible to bias.

COMMENTARY

Similar to other studies evaluating cannabis use and pregnancy, the prevalence of use in pregnancy ranges from ~2-7%.1-3 In spite of recommendations to abstain from cannabis use, women report continuing to use cannabis in pregnancy for common ailments including nausea/vomiting and anxiety.4 Previous epidemiologic studies have summarized the risks of marijuana use in pregnancy, ranging from no overall differences in several pregnancy outcomes to increased risks of low birthweight/SGA infants, increased NICU admissions, and increased stillbirths.5-7

Several factors affect the ability to understand the effects of cannabis on maternal and fetal health. Assessing the use of cannabis is challenging since detection can be through self-reporting or through laboratory confirmation testing of tetrahydrocannabinol (THC) in urine or blood, neither of which is perfect. What effect legalization has on self-reporting is unknown, since data still lag behind state legalization.

Another challenge comes from limitations in existing technologies to assess THC accurately in other tissues (breast milk), which could affect the fetus/newborn directly, and which likely influences reported “effects” and risks. Finally, marijuana strains, THC concentrations, and delivery modalities (smoking, edibles, vaping, tinctures) continue to evolve and, therefore, present day cannabis is more potent than the cannabis available 5-10 (or more) years ago. Furthermore, cannabis can be THC-heavy or cannabidiol (CBD)-heavy, or somewhere in between, and these active chemicals may have different effects on both a mother and her developing fetus.

The following are some clinical pearls to offer as the research on cannabis in pregnancy evolves:

  • Screen for tobacco, alcohol, and marijuana use in pregnancy independent from a global question about “illicit drug use.” Marijuana/cannabis must be asked about separately, as it is not an “illicit” drug in many states and, now, in Canada.
  • Just as you do with alcohol and tobacco use in pregnancy, advise patients to stop using marijuana. The data are not clear regarding the harm or benefit.
  • Recognize that women may be self-medicating mental health conditions or nausea/vomiting with marijuana. Provide safe and reasonable treatments.

REFERENCES

  1. Corsi DJ, Walsh L, Weiss D, et al. Association between self-reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes. JAMA 2019;322;145-152.
  2. Young-Wolff KC, Tucker LY, Alexeeff S, et al. Trends in self-reported and biochemically tested marijuana use among pregnant females in California from 2009-2016. JAMA 2017;318:2490-2491.
  3. Corsi DJ, Hsu H, Weiss D, et al. Trends and correlates of cannabis use in pregnancy: A population-based study in Ontario, Canada from 2012-2017. Can J Public Health 2019;1110:76-84.
  4. Brown QL, Sarvet AL, Shmulewitz D, et al. Trends in marijuana use among pregnant and nonpregnant reproductive-aged women, 2002-2014. JAMA 2017;317:207-209.
  5. Fergusson DM, Horwood LJ, Northstone K; ALSPAC Study Team; Avon Longitudinal Study of Pregnancy and Childhood. Maternal use of cannabis and pregnancy outcome. BJOG 2002;109:21-27.
  6. Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. Birth outcomes associated with cannabis use before and during pregnancy. Pediatr Res 2012;71:215-219.
  7. Varner MW, Silver RM, Rowland Hogue CJ, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network. Association between stillbirth and illicit drug use and smoking during pregnancy. Obstet Gynecol 2014;123:113-125.