The beneficial effect of sleep on behavioral health problems in youth is disrupted by prenatal cannabis exposure: A causal random forest analysis of ABCD data

ABSTRACT Importance Declining risk perceptions and touted medicinal claims about cannabis are likely related to the increasing prevalence of cannabis use during pregnancy. Yet, it remains unclear if prenatal cannabis exposure yields lasting neurodevelopmental alterations in children, and which facets of their behavioral health might be affected. Objective To determine if prenatal cannabis exposure moderates the relationship between changing sleep hours on changing mood and behavioral problems in youth. Design Causal random forest analysis of ABCD cohort data using baseline (ages 9-10) and year-1 follow up information. Setting 11,875 children and their parents were assessed at 21 acquisition sites across the United States between July 2016 to October 2018. Participants Participants with prenatal drug use data were included, and 94% of the baseline sample also had year-1 follow up data. Exposures A change in sleep hours from baseline to year-1 was conceptualized as the dimensional “treatment” variable, and self-reported drug uses of the biological mother were conceptualized as moderators of that “treatment”. Main Outcomes and Measures A change in internalizing (anxious/depressed mood) and externalizing (disruptive behavior) problems from baseline to year-1 were the two outcome measures. Sociodemographic and other prenatal drug exposures were included as covariates. Given the observational nature of the multi-site ABCD study, all hypotheses tested here were formulated after data collection. Results There were n=9,826 children (4,663 female) included in analyses, of which n=605 (303 female) had any prenatal cannabis exposure. On average, internalizing problems largely remained stable from baseline ( M =48.54, SD =10.56) to year-1 ( M =48.75, SD =10.64)( t 9,825 =2.40, p =.016), as did externalizing problems (baseline M =45.64, SD =10.21; year-1 M =45.23, SD =10.09) ( t 9,825 =5.44, p <.001). Significant average treatment effects indicated that participants with more sleep hours reported less internalizing (ATE=-.35, SE =.08, p =.003) and externalizing (ATE=-.28, SE =.07, p =.028 ) problems over time. However, a significant heterogeneous treatment effect by prenatal cannabis exposure (conditional-ATE=.92, SE =.36, p =.011) was found for the internalizing model, such that participants with this exposure did not show a beneficial effect of changing sleep on changing mood ( B =.06, SE =.25). This finding was specific to cannabis, as no such effect was found for any sociodemographics or prenatal alcohol or tobacco exposures for the internalizing or externalizing models. Conclusions and Relevance This study uncovers an actionable target (sleep) to improve mood and behavioral problems in typically developing children not prenatally exposed to cannabis. However, changing sleep may not have a similar effect for youth prenatally exposed to cannabis. Given the importance of the endocannabinoid system in regulating perinatal neurodevelopment and sleep, these findings suggest that cannabis exposure may interact with those processes to diminish the beneficial effects of sleep on mood in children, and thus calls into question the safety of cannabis use during pregnancy. KEY POINTS Question Do children exposed to cannabis during pregnancy exhibit differences in the effect of sleep on their mood and behavior? Findings Causal inference analyses of baseline (ages 9-10) and year-1 follow up data of the Adolescent Brain Cognitive Development™ (ABCD) study (N=9,826) suggested that increasing sleep hours lowered mood and behavioral problems in children without prenatal cannabis exposures, however, children with exposures did not exhibit similar beneficial effects of sleep on their mood. This finding was specific to cannabis, as other drug use and sociodemographic information did not influence treatment effects. Meaning Prenatal cannabis exposure likely interferes with neurodevelopmental processes related to sleep, and these differences persist into at least early adolescence to alter the beneficial effects of sleep on mood.