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Original Investigation
September 23, 2020

Associations Between Prenatal Cannabis Exposure and Childhood Outcomes: Results From the ABCD Study

Author Affiliations
  • 1Department of Psychological and Brain Sciences, Washington University in St Louis, St Louis, Missouri
  • 2Department of Psychiatry, Washington University in St Louis School of Medicine, St Louis, Missouri
  • 3Department of Obstetrics and Gynecology, Washington University School of Medicine in St Louis, St Louis, Missouri
JAMA Psychiatry. Published online September 23, 2020. doi:10.1001/jamapsychiatry.2020.2902
Key Points

Question  Is prenatal exposure to cannabis associated with child outcomes?

Findings  This cross-sectional analysis of 11 489 children (655 exposed to cannabis prenatally) found that prenatal cannabis exposure after maternal knowledge of pregnancy was associated with greater psychopathology during middle childhood, even after accounting for potentially confounding variables.

Meaning  Prenatal cannabis exposure may increase risk for psychopathology; consistent with recent recommendations by the Surgeon General of the United States, these data suggest that cannabis use during pregnancy should be discouraged by clinicians and dispensaries.

Abstract

Importance  In light of increasing cannabis use among pregnant women, the US Surgeon General recently issued an advisory against the use of marijuana during pregnancy.

Objective  To evaluate whether cannabis use during pregnancy is associated with adverse outcomes among offspring.

Design, Setting, and Participants  In this cross-sectional study, data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development Study, which recruited 11 875 children aged 9 to 11 years, as well as a parent or caregiver, from 22 sites across the United States between June 1, 2016, and October 15, 2018.

Exposure  Prenatal cannabis exposure prior to and after maternal knowledge of pregnancy.

Main Outcomes and Measures  Symptoms of psychopathology in children (ie, psychotic-like experiences [PLEs] and internalizing, externalizing, attention, thought, and social problems), cognition, sleep, birth weight, gestational age at birth, body mass index, and brain structure (ie, total intracranial volume, white matter volume, and gray matter volume). Covariates included familial (eg, income and familial psychopathology), pregnancy (eg, prenatal exposure to alcohol and tobacco), and child (eg, substance use) variables.

Results  Among 11 489 children (5997 boys [52.2%]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal cannabis exposure data, 655 (5.7%) were exposed to cannabis prenatally. Relative to no exposure, cannabis exposure only before (413 [3.6%]) and after (242 [2.1%]) maternal knowledge of pregnancy were associated with greater offspring psychopathology characteristics (ie, PLEs and internalizing, externalizing, attention, thought and, social problems), sleep problems, and body mass index, as well as lower cognition and gray matter volume (all |β| > 0.02; all false discovery rate [FDR]–corrected P < .03). Only exposure after knowledge of pregnancy was associated with lower birth weight as well as total intracranial volume and white matter volumes relative to no exposure and exposure only before knowledge (all |β| > 0.02; all FDR-corrected P < .04). When including potentially confounding covariates, exposure after maternal knowledge of pregnancy remained associated with greater PLEs and externalizing, attention, thought, and social problems (all β > 0.02; FDR-corrected P < .02). Exposure only prior to maternal knowledge of pregnancy did not differ from no exposure on any outcomes when considering potentially confounding variables (all |β| < 0.02; FDR-corrected P > .70).

Conclusions and Relevance  This study suggests that prenatal cannabis exposure and its correlated factors are associated with greater risk for psychopathology during middle childhood. Cannabis use during pregnancy should be discouraged.

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    2 Comments for this article
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    Perception of Risk in Study Objects
    pamela mccoll, BA | Clear the Air
    Studying pregnant women who are cannabis users calls into question serious issues over human rights and raises ethical questions, including mandatory reporting pertaining to substance abuse in pregnancy. As the September 23/2020 calls for further research on the impact of prenatal cannabis exposure and childhood outcomes the following is relevant to the discussion.

    The Office of Human Research Protection regulations read as follows (https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/ ): "Subpart B presumption that pregnant women may be included in research, provided certain conditions are met. According to Subpart B, the permissibility of research with pregnant women hinges on a judgment of the
    potential benefits and risks of the research. Approval of proposed research carrying no “prospect of direct benefit” to the woman or fetus requires that the risk to the fetus be judged “not greater than minimal”. Fetal risk that exceeds that standard is permissible only when the proposed research offers a prospect of direct benefit to the pregnant woman, the fetus, or both. Notably, if the proposed research does not fit within either of those two parameters, Subpart B offers an additional mechanism at the national level for approval by the Secretary of Health and Human Services."
    The federal definition of minimum risk reads: “That the magnitude and probability of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

    In principle, any study that tracks the consequences of administering a drug to a developing fetus should be carried out in animal models first, and not in humans until the animal results point towards safety. The evidence of decades of research on marijuana in pregnancy does not point to safety but rather to risk and harm.

    Two basic principles in bioethics are relied upon to determine the merit of research that involves human subjects: Is the study necessary and can the research be done without the use of human subjects? There now exists a significant body of scientific evidence that warrants and justifies warning women not to use marijuana products at pre-conception, while pregnant, or breast-feeding. Is further study necessary to conclude that marijuana use is associated with risk to the child (and also the mother). I would argue it is not, especially if it allows in any measure a diminishment of the perception of risk associated with prenatal cannabis use.
    CONFLICT OF INTEREST: None Reported
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    Research into cannabis and mental health must adjust for diet type and B12 transport status
    George Henderson |
    Epidemiological research into cannabis use and mental health outcomes will be more robust if it is adjusted for diet type and genetic determinants of nutritional status. Methods, including adjustments, should be described in the abstract of such a paper; I note they are not mentioned in publicity materials for this study either.

    Cannabis users may be more likely to be vegan or vegetarian because cannabis has long been seen as a "clean" and "plant-based" intoxicant, and because hemp use is seem as environmentally friendly.

    Hibbeln et al. found that both maternal meat avoidance, and maternal soy exposure, were
    associated with an increased risk of cannabis use in offspring, OR = 2.70, 95% CI = (1.89, 4.00), p < 0.001 for vegetarian diet.[1] This study also showed an effect of a TCN2 mutation impairing vitamin B12 transport.

    After controlling for potential confounders, researchers looking at Stockholm Youth Cohort data (n=532,232) observed that anemia diagnosed during the first 30 weeks of pregnancy but not later was associated with increased risk of neurodevelopmental disorders - ASD (odds ratio [OR], 1.44; 95% CI, 1.13-1.84), ADHD (OR, 1.37; 95% CI, 1.14-1.64), and ID (OR, 2.20; 95% CI, 1.61-3.01).[2]

    The Stockholm researchers, who attempted to control for malnutrition, inadequate prenatal care, poor adherence to prenatal vitamins, hypothesized that iron deficiency anemia disrupts fetal brain development, noting that iron is essential for processes including myelination, dendrite arborization, and synthesis of monoamine neurotransmitters. To this I would add, iron is also required for brain l-carnitine synthesis, allowing normal brain energy use.

    Parents who are vegetarian or vegan may also feed such diets to children, so that maternal exposure may be compounded by post-natal exposures. In a recent systematic review, 11 of 18 studies demonstrated that meat-abstention was associated with poorer psychological health, 4 studies were equivocal, and 3 showed that meat-abstainers had better outcomes. The most rigorous studies demonstrated that the prevalence or risk of depression and/or anxiety were significantly greater in participants who avoided meat consumption. [3]

    This is not only a major confounder in cannabis research, one that is crying out for adjustment, it may well be the more valuable area of research for those seeking to improve community mental health.




    [1] Hibbeln, J.R., SanGiovanni, J.P., Golding, J., Emmett, P.M., Northstone, K., Davis, J.M., Schuckit, M. and Heron, J. (2017), Meat Consumption During Pregnancy and Substance Misuse Among Adolescent Offspring: Stratification of TCN2 Genetic Variants. Alcohol Clin Exp Res, 41: 1928-1937. doi:10.1111/acer.13494

    [2] Wiegersma AM, Dalman C, Lee BK, Karlsson H, Gardner RM. Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders [published online ahead of print, 2019 Sep 18]. JAMA Psychiatry. 2019;76(12):1-12. doi:10.1001/jamapsychiatry.2019.2309

    [3] Urska Dobersek, Gabrielle Wy, Joshua Adkins, Sydney Altmeyer, Kaitlin Krout, Carl J. Lavie & Edward Archer (2020) Meat and mental health: a systematic review of meat abstention and depression, anxiety, and related phenomena, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2020.1741505
    CONFLICT OF INTEREST: None Reported
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