Prenatal Cannabis Exposure May Raise Risk of Autism

-Large retrospective analysis shows a 50% higher risk of diagnosis

by Zeena Nackerdien PhD, CME Writer, MedPage Today 2020-08-24 –  CME INFORMATION

Study Authors: Daniel J. Corsi, Jessy Donelle, et al.

Target Audience and Goal Statement: Obstetrician-gynecologists, pediatricians, neurologists, psychiatrists

The goal of this study was to evaluate the association between maternal cannabis use in pregnancy and child neurodevelopmental outcomes.

Question Addressed:

  • Was there an association between cannabis exposure in pregnancy and child neurodevelopmental outcomes in a Canadian cohort?

Study Synopsis and Perspective:

Healthcare professionals are mindful that greater social acceptance of cannabis may lead some prospective parents to think that it could be used to treat morning sickness.

In most U.S. studies, the self-reported prevalence of marijuana use during pregnancy ranges from 2% to 5%. Moreover, a recent investigation showed that 18.1% of pregnant women reporting marijuana use in the past year met criteria for marijuana abuse, dependence, or both.

Several other studies have also showed that disruption of endocannabinoid signaling may lead to defects in neuronal wiring, and have implications for fetal neurodevelopment.

Action Points

  • Children exposed to marijuana in utero had an elevated risk of developing autism spectrum disorder, according to a recent retrospective study in Canada.
  • Note that, although there is a need for cautious interpretation of these results, pregnant women who are currently using cannabis should be advised to talk to their healthcare providers and make an informed decision about use during pregnancy.

Due to these concerns, “as well as maternal and fetal exposure to adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use,” according to the American College of Obstetricians and Gynecologists (ACOG).

Now, a recent retrospective study in Canada found that children exposed to marijuana in utero had a moderately elevated risk of developing autism spectrum disorder.

Autism incidence was 4.0 per 1,000 person-years among children exposed to cannabis in pregnancy versus 2.42 among unexposed children (adjusted hazard ratio [HR] 1.51, 95% CI 1.17-1.96), wrote Daniel Corsi, PhD, of Ottawa Hospital in Ontario, and colleagues in Nature Medicine.

Corsi’s group created a video to summarize earlier study findings that cannabis use in pregnancy was associated with an increased risk of preterm birth. They also found that women who used cannabis during pregnancy frequently used other substances, such as tobacco, alcohol, or opioids.

Using the Ontario Better Outcomes Registry & Network (BORN), Corsi and team retrospectively analyzed all live births in Ontario, Canada, from April 2007 to March 2012. They linked birth registry data to provincial health administrative data to ascertain child neurodevelopmental outcomes up to March 31, 2017, when children would be a maximum of 10 years old.

The primary outcome of autism spectrum disorder was defined as at least two outpatient diagnoses by either a pediatrician or psychiatrist or at least one diagnosis in hospital databases, or both. Intellectual disability and learning disorders and attention deficit-hyperactivity disorder (ADHD) were among the secondary outcomes.

In the study group, 3,148 (0.6%) mothers reported using cannabis while pregnant; of these, 2,200 reported using only cannabis during pregnancy (i.e., they did not use any other substances).

To reduce imbalances in the main cohort between cannabis users and nonusers, the researchers selected 2,364 users and identified about 171,000 users who were close matches on a number of covariates, including age, education, medical comorbidities, substance use other than cannabis, and others.

An observed association between prenatal cannabis use and autism persisted in sensitivity analyses of substance use, income, and preterm birth; point estimates were somewhat lower in the smaller matched cohort but remained statistically significant.

The researchers also found trends toward increased incidence of intellectual and learning disabilities (HR 1.23, 95% CI 0.97-1.55), as well as ADHD (HR 1.11, 95% CI 0.99-1.25), in the matched cohort among children whose mothers used marijuana. These remained nonsignificant after further adjustment.

Corsi and colleagues recognized that the prevalence of cannabis use during pregnancy was significantly lower than recorded elsewhere (2% to 5% in Great Britain and the U.S.), which may limit these findings. The group did not have data on frequency, duration, or trimester of use, and acknowledged that self-reported data may lead to misclassification.

Source Reference: Nature Medicine 2020; DOI: 10.1038/s41591-020-1002-5

Study Highlights and Explanation of Findings:

Children with prenatal cannabis exposure had a 50% higher risk of an autism diagnosis in this retrospective analysis of a large Canadian cohort. Compared with unexposed children, there were also hints for developing intellectual disabilities, learning disorders, and ADHD. However, the researchers emphasized the need for cautious interpretation of the results given the likelihood of residual confounding.

Corsi and team stated that they were limited in their ability to determine causality between prenatal cannabis exposure and later childhood neurodevelopmental outcomes due to the possible involvement of other factors, such as individual genetic profile, prematurity, fetal and postnatal environment, dose and type of substance of exposure, and environmental triggers.

However, subgroup analyses of women who reported using only cannabis and no other substances during pregnancy were consistent with the overall findings, especially those related to autism spectrum disorder. Based on these results, observed associations were unlikely to have been confounded by the use of other substances.

“Our clinical recommendation based on these findings is for women who are pregnant or thinking of becoming pregnant to avoid the use of cannabis products,” Corsi said in an email to MedPage Today.

Torri Metz, MD, a maternal-fetal medicine specialist at the University of Utah, commented that this study adds to previous concerns about prenatal marijuana exposure’s potential effects on offspring.

“It is another piece of the puzzle,” Metz, who was not involved in this research, told MedPage Today. “It makes us worry about cannabis exposure in utero and whether it is influencing fetal neurodevelopment.”

While Metz underscored the need for cautious interpretation because of its limitations, she added that this research is an important step forward.

“We certainly need more information about marijuana use and downstream effects for offspring who are exposed in utero,” Metz said. “It’s exciting to see that people are evaluating this.”

Lauren Jansson, MD, the director of pediatrics at the center for addiction and pregnancy at Johns Hopkins Bayview Medical Center, said that she hopes this study will further encourage clinicians to counsel patients to avoid marijuana use, not only during pregnancy, but while breastfeeding as well.

“We know that medical providers often tend to discount cannabis use as unimportant, and we know that counseling — even during pregnancy — is inconsistent,” Jansson, who was not involved in this study, said in an interview. “With studies like this, it’s more data that will support recommendations for women to at least stop using in pregnancy.”

Jansson stated that pregnant patients who use marijuana for medical purposes should make decisions about use based on risk-benefit analyses with their providers.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College

Primary Source

Nature Medicine

Source Reference: Corsi DJ, et al “Maternal cannabis use in pregnancy and child neurodevelopmental outcomes” Nat Med 2020; DOI: 10.1038/s41591-020-1002-5.

Secondary Source

MedPage Today

Source Reference: D’Ambrosio A “Kids Exposed to Cannabis In Utero Face Higher Risk of Autism” 2020.