David A. A. Baranger, PhD1, Sarah E. Paul, MA, Sarah M. C. Colbert, BA
September 12, 2022
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.
Baranger, D. A., Paul, S. E., Colbert, S. M., Karcher, N. R., Johnson, E. C., Hatoum, A. S., & Bogdan, R. 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 pediatrics.