Maternal Cannabis Use in Pregnancy and Autism Spectrum Disorder in the Charge Study

Background: Cannabis use has been associated with deficits in verbal and memory domains, as well as inattention, impulsivity and hyperactivity in young children evaluated in historical cohorts likely to underestimate the impact of current fetal cannabis exposure.

Objectives: To determine whether maternal cannabis use in pregnancy is associated with adverse neurodevelopment in a case-control study designed to evaluate the effects of environmental and genetic factors on autism spectrum disorder (ASD) and developmental delay (DD).

Methods: The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a population-based, case-control investigation of ASD and/or DD origins. Children from 20 California counties aged 24 to 60 months and living in catchment areas with a biological parent fluent in English or Spanish were enrolled from 1/29/2003 to 1/23/2017. Children with ASD (n = 725) and DD (n = 288) were recruited through the California Department of Developmental Services, the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, and referrals. Controls with typical development (TD) (n = 494) were randomly selected from birth records and frequency matched on age, sex, and broad geographic region. Maternal self-report of prenatal cannabis use and other exposures were drawn from a telephone interview conducted in English or Spanish. The Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview–Revised (ADI-R) were used to confirm ASD, whereas children with DD and TD were confirmed by Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) and were free of autistic symptoms. Multinomial logistic regression models that controlled for maternal factors were developed to examine the association between cannabis and developmental outcomes.

Results: Of women who reported cannabis use, nearly all (93%) used marijuana, with only 7% using cannabinoids. Reported use in CHARGE controls reflected published prevalence: 6.1% during the 3 months prior to conception and 2.0% at any time during pregnancy, with frequencies declining across the three trimesters (1.8%, 0.9%, 0.7%). Cannabis use was most prevalent among mothers of children with ASD (4.6%) followed by mothers of children with DD (2.6%) and controls (2.0%). After adjusting for maternal race/ethnicity, education, and tobacco use during pregnancy, cannabis use was not significantly associated with ASD risk (1.76; 95%CI, 0.78, 3.97). Further preliminary analyses revealed that tobacco use operated in models both as a confounder and effect modifier (p=0.01). There was evidence of a multiplicative effect between tobacco and cannabis use on the likelihood of ASD; exposure to both substances during pregnancy compared to neither significantly increased the risk of ASD whereas exposure to either one alone did not. However, the stratified data are sparse and results are preliminary. Cannabis use was not associated with DD.

Conclusions: Widespread legislation decriminalizing cannabis use and enhancing availability has led to dramatic increases in use and a growing perception that cannabis exposure – both overall and in pregnancy – is safe. Our findings suggest that fetal exposure to cannabis alone does not increase ASD risk. However, the combined use of cannabis and tobacco may be hazardous to fetal neurodevelopment.