Standardized regression β effect sizes and 95% CIs from mixed-effect regressions assessing the association of prenatal cannabis exposure prior to maternal knowledge of pregnancy or prior to and postmaternal knowledge of pregnancy compared with no exposure. Nonsignificant outcomes (Table; somatic problems/complaints, internalizing factor, anxious/depressed, withdrawn/depressed, and Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] [DSM-5] depression, anxiety, and oppositional defiant) are not shown. As seen by the 95% CIs, prenatal cannabis exposure pre- and postmaternal knowledge of pregnancy was associated with increased risk for all significant measures. However, exposure only before maternal knowledge of pregnancy was only significantly associated with increased risk for sluggish cognitive tempo and psychoticlike experiences. ADHD indicates attention-deficit/hyperactivity disorder; CBCL, Child Behavior Checklist; PQ-BC, Prodromal Questionnaire–Brief Child Version.
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Baranger DAA, Paul SE, Colbert SMC, et al. Association of Mental Health Burden With Prenatal Cannabis Exposure From Childhood to Early Adolescence: Longitudinal Findings From the Adolescent Brain Cognitive Development (ABCD) Study. JAMA Pediatr. 2022;176(12):1261–1265. doi:10.1001/jamapediatrics.2022.3191
Dramatic increases in cannabis use during pregnancy are alarming because of evidence that prenatal exposure may be associated with a host of adverse outcomes.1 We previously found that prenatal cannabis exposure (PCE) following maternal knowledge of pregnancy is associated with increased psychopathology during middle childhood using baseline data from the Adolescent Brain Cognitive Development (ABCD) study.2 Here, leveraging longitudinal ABCD study data (data release 4.0), we examined whether associations with psychopathology persist into early adolescence.
We estimated associations between retrospective report of maternal cannabis use during pregnancy (only before maternal knowledge of pregnancy [BK-PCE], before and after maternal knowledge of pregnancy [BAK-PCE], and no exposure [NE]) and longitudinal assessments (baseline [June 1, 2016, to October 15, 2018], 1-year follow-up, and 2-year follow-up) of psychopathology (Child Behavior Checklist3 subscales, n = 20; total reported psychoticlike experiences on the Prodromal Questionnaire–Brief Child Version4). PCE groups had greater attrition (χ2 = 34.2, P < .001). Participants provided assent and caregivers provided written informed consent to a protocol approved by the institutional review board of each data collection site. We followed the STROBE reporting guideline for cohort studies.
Associations between PCE groups (BK-PCE, BAK-PCE, and NE) and child psychopathology were estimated using mixed models. In addition to main associations of exposure and age, interactions (ie, [age + age2] × [BK-PCE + BAK-PCE]) modeled age-associated change. χ2 Tests of log likelihood compared models with and without predictors of interest (ie, PCE group, PCE group × age interaction) to determine significance.
Covariates included family and child variables (Table). False discovery rate (FDR) multiple comparison correction was used (n = 42; exposure main associations and interactions with age). Secondary analyses tested whether associations were robust to the additional inclusion of pregnancy-associated covariates with high levels of missingness in the entire sample and to polygenic risk scores for cannabis use disorder and proximal outcomes of interest (eg, polygenic risk for schizophrenia, depression) in the European ancestry subsample (n = 5110; genetic methodological details available elsewhere2).
A total of 391 individuals were in the BK-PCE group, 208 were in the BAK-PCE group, and 10 032 were in the NE group. Of those, 2379 (22%) self-reported as African American; 709 (7%), Asian/Asian American; 766 (7%), Hispanic; 378 (4%), Native American; 69 (0.6%), Pacific Islander; 8593 (81%), White; and 766 (7%), other. There were 10 631 individuals and 30 091 longitudinal assessments (baseline: n = 10 624; mean [IQR] age, 9.9 [8.9-11.1] years; 1-year follow-up: n = 10 094; mean [IQR] age, 10.9 [9.7-12.4] years; 2-year follow-up: n = 9373; mean [IQR] age, 12.0 [10.6-13.8] years). PCE was associated with persisting vulnerability to psychopathology throughout early adolescence (Figure and Table). These associations did not change with age (FDR-corrected P > .11). Significant findings were primarily driven by exposure following maternal knowledge of pregnancy (Figure and Table). Results remained FDR-significant when including covariates with high missingness (ie, pregnancy-associated covariates) with the exception of psychoticlike experiences (FDR-corrected P = .13; influential covariates were maternal age at birth and planned pregnancy). Associations remained directionally consistent and of similar magnitude in the BAK-PCE group after accounting for polygenic risk in the European ancestry subsample; 4 scales (ie, sluggish cognitive tempo, social problems, rule-breaking behavior, and Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] conduct problems) remained nominally significant.
PCE is associated with persisting vulnerability to broad-spectrum psychopathology as children progress through early adolescence. Increased psychopathology may lead to greater risk for psychiatric disorders and problematic substance use as children enter peak periods of vulnerability in later adolescence.5 Larger associations in the BAK-PCE group may be attributable to the timing of cannabinoid receptor neural expression, which onsets in rodents at the equivalent of 5 to 6 weeks.6 Limitations include the small sample of prenatal cannabis-exposed offspring, potential underreporting of use during pregnancy, imprecise data on the timing/frequency/potency of cannabis exposure, and the lack of data on some potential confounders (eg, maternal stress during pregnancy). Evidence that the impact of PCE on psychopathology does not ameliorate as children enter adolescence further cautions against cannabis use during pregnancy.
Accepted for Publication: June 22, 2022.
Published Online: September 12, 2022. doi:10.1001/jamapediatrics.2022.3191
Corresponding Author: David A. A. Baranger, PhD, Department of Psychological and Brain Sciences, Washington University in St Louis, One Brookings D, CB 1125, St Louis, MO 63110 (email@example.com).
Author Contributions: Dr Baranger had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Baranger, Paul, Bogdan.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Baranger, Bogdan.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Baranger, Paul.
Obtained funding: Bogdan.
Administrative, technical, or material support: Paul, Johnson, Hatoum, Bogdan.
Conflict of Interest Disclosures: None reported.
Funding/Support: Data for this study were provided by the Adolescent Brain Cognitive Development (ABCD) study, which was funded by the National Institutes of Health (grants U01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, and U24DA041147) and additional federal partners (https://abcdstudy.org/federal-partners.html). Dr Baranger (grants R21AA027827 and R01DA054750), Ms Paul (grant F31AA029934), Dr Karcher (grant K23MH121792-01), Dr Hatoum (grant R01DA054869), Dr Johnson (grant K K01 DA051759), Dr Bogdan (grants R01DA054750, U01DA055367, R21AA027827, R01AG061162, and R01DA061162) also received funding from the National Institutes of Health.
Role of the Funder/Sponsor: ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: This article reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health or ABCD consortium investigators.
Additional Contributions: We thank Arpana Agrawal, PhD (Department of Psychiatry, Washington University School of Medicine), for discussions about analyses and initial review of the manuscript, for which compensation [was/was not] received.
Additional Information: The ABCD data repository grows and changes over time. The ABCD data used in this report came from https://dx.doi.org/10.15154/1523041.