Cannabis exposure during pregnancy was associated with an increased risk of psychopathology into adolescence, especially if exposure continued later into the pregnancy, according to longitudinal findings from the Adolescent Brain Cognitive Development (ABCD) study, with researchers observing that during the pandemic, cannabis use during the early stages of pregnancy increased by 25%.
Among more than 10,000 youngsters, prenatal cannabis exposure (PCE) was associated with “persisting vulnerability” to psychopathology throughout early adolescence compared with no prenatal exposure, reported David Baranger, of Washington University in St Louis, Missouri, and colleagues.
These findings were primarily driven by cases where cannabis exposure continued even after maternal knowledge of pregnancy, possibly due to the timing of cannabinoid receptor neural expression, they noted in JAMA Pediatrics.
“Increased psychopathology may lead to greater risk for psychiatric disorders and problematic substance use as children enter peak periods of vulnerability in later adolescence,” Baranger and team wrote.
MedPage Today reports that among the psychopathologies significantly associated with PCE were rule-breaking behaviour, aggressive behaviour, social problems, thought problems, attention problems, and conduct problems. The current findings are in line with previous findings from the ABCD study from 2020, which showed that kids exposed to cannabis in utero were at greater risk for psychopathology during middle childhood.
“During the first wave, they were just children. Now they're edging up on adolescence,” said Baranger. “We know this is a period when a large proportion of mental health diagnoses occur. “Once they hit 14 or 15, we’re expecting to see further increases in mental health disorders or other psychiatric conditions – increases that will continue into the children’s early 20s,” he added. Of note, during the COVID-19 pandemic, cannabis use in the early stages of pregnancy increased by 25%. Previous research had also shown that women are more likely to use cannabis in pregnancy if they are depressed, anxious, or have experienced trauma.
For this study, data were collected at baseline from June 2016 to October 2018 and at two follow-up points at one year and two years for 10,631 kids. Cannabis exposure was put into three categories: use only before maternal knowledge of pregnancy (BK-PCE), continued use after maternal knowledge of pregnancy (BAK-PCE), and no exposure (NE).
A total of 391 participants were in the BK-PCE group, 208 were in the BAK-PCE group, and 10,032 were in the NE group. Collectively, 81% self-reported as white and 22% self-reported as African American. Baseline mean age was 9.9 years, while mean age at 1-year follow-up was 10.9, and 12.0 at 2-year follow-up. The authors used the Child Behaviour Checklist subscales and the Prodromal Questionnaire-Brief Child Version to assess psychopathology. The associations did not change with age (false discovery rate [FDR]-corrected P>0.11). Results also remained FDR-significant when including covariates with high missingness, such as pregnancy-associated covariates like maternal age at birth and planned pregnancy, except for psychotic-like experiences (FDR-corrected P=0.13).
In addition, associations remained directionally consistent and of similar magnitude in the BAK-PCE group after accounting for polygenic risk in the European ancestry subsample, Baranger and colleagues said.
The small sample size of prenatal cannabis-exposed offspring was a limitation to the study, they acknowledged. Other limitations included potential underreporting of cannabis use during pregnancy; inexact data on the timing, frequency, and potency of cannabis exposure; and a lack of data on certain potential confounders, such as maternal stress during pregnancy.
Study details
Association of Mental Health Burden With Prenatal Cannabis Exposure From Childhood to Early Adolescence
Longitudinal Findings From the Adolescent Brain Cognitive Development (ABCD) Study
David Baranger, Sarah Paul, Sarah Colbert, et al.
Published in JAMA Pediatrics on 12 September 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. 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. Here, leveraging longitudinal ABCD study data (data release 4.0), we examined whether associations with psychopathology persist into early adolescence.
Methods
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 Behaviour Checklist subscales, n = 20; total reported psychotic-like 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]) modelled 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. 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). Results 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. These associations did not change with age (FDR-corrected P > .11). Significant findings were primarily driven by exposure following maternal knowledge of pregnancy. Results remained FDR-significant when including covariates with high missingness (ie, pregnancy-associated covariates) with the exception of psychotic-like 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 behaviour, and Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] conduct problems) remained nominally significant.
Discussion
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. 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. 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.
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Pregnancy – Cannabis use linked to autism; alcohol raises miscarriage risk
Cannabis use in pregnancy boosts risk of child sleep problems
Effect on infants from mothers’ multiple substance use in pregnancy – SA study