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The children of mothers who used cannabis during pregnancy had a heightened risk of developing behavioral or mental health problems, a cross-sectional study found.

Compared to unexposed children, kids who had an in utero exposure to marijuana were more likely to develop a range of adverse outcomes in childhood, including psychopathology, reduced cognition, and lower brain volume, according to Ryan Bogdan, PhD, of Washington University in St. Louis, and colleagues.

Although children exposed at any stage of pregnancy were at a slightly increased risk for several adverse outcomes, those who were exposed after their mothers learned they were pregnant were at a significant risk of psychotic-like experiences, impulsivity and attention issues, and social challenges, the researchers wrote in .

"Prenatal exposure to cannabis was associated with a host of adverse outcomes in childhood," Bogdan told 番茄社区 in an interview. When Bogdan's group controlled for confounders, the risks associated with cannabis use before a mother learned of her pregnancy went away, he said, raising the possibility that associations in early pregnancy are not causal.

But after adjustment, when the researchers looked at cannabis exposure in the later stages of pregnancy -- when a mother learned she was pregnant -- the associations between cannabis exposures and psychopathology remained robust.

"That raises the possibility that prenatal cannabis exposure in the later stages of pregnancy could potentially have a causal impact," Bogdan said.

One of the possible reasons for that association, he stated, is that the endocannabinoid system (the system that THC exerts its effects on) is not expressed until around 6 weeks gestation -- around the same time that mothers in the study became aware of their pregnancy. Bogdan said that it's possible that there could be neurodevelopmental consequences from THC binding to these receptors in the fetus.

Cannabis use during pregnancy increased by more than 100% from 2002 to 2017, Bogdan and colleagues stated. This jump prompted the U.S. Surgeon General to issue an advisory warning in the summer of 2019.

The findings present an opportunity for clinicians to warn pregnant patients of the risks of marijuana use during pregnancy, which Bogdan said often gets neglected in physician-patient conversations.

"There is a small increase in risk for child psychopathology, and based on that I would personally recommend discouraging use, both with clinicians as well as dispensaries," he said.

Asked for his perspective, Daniel Corsi, PhD, a professor of perinatal epidemiology at the University of Ottawa in Ontario, who was not involved in the research, said "we should continue to advise women against the use of cannabis in pregnancy." Based on these findings, he added, conversations about marijuana use should take place when couples are planning a pregnancy, but may not know if they have yet conceived.

"Cannabis should be treated in a similar way to cigarettes and alcohol as substances to avoid in pregnancy," Corsi said in an interview. He stated that as marijuana has been legalized in Canada and more U.S. jurisdictions, he would like to see more labelling and warning signs on packaging against use during pregnancy.

In this study, Bogdan and colleagues used data from the , which investigates brain development and child health in a cohort of nearly 12,000 U.S. youth. Data were collected between June 2016 and October 2018 from children ages 9 to 11.

The researchers analyzed three different groups: children unexposed to cannabis, in utero exposures prior to a mother's knowledge of pregnancy, and exposures after mothers learned they were pregnant.

In each of the three groups, the study authors measured the risk of psychopathology symptoms, cognition, sleep, birth weight, gestational age at birth, body mass index (BMI), and brain structure. Child exposure to cannabis was based on self-reported data from parents and caregivers.

Bogdan's group adjusted for several covariates, including race and ethnicity, familial history of psychopathology, prenatal exposure to tobacco or alcohol, prenatal vitamin use, child sex, socioeconomic status, birth weight, maternal age at birth, and maternal education.

In a cohort of nearly 11,500 children, 655 were exposed to cannabis in utero, with 413 exposed only before their mother learned of her pregnancy, 235 exposed both before and after maternal knowledge, and 7 exposed only after knowledge of the pregnancy. On average, mothers found out that they were pregnant at around 7 weeks. There was a modest correlation between rates of tobacco and alcohol use during pregnancy and cannabis use.

Before adjustment for covariates, prenatal cannabis exposure before and after maternal pregnancy knowledge was associated with more psychotic-like experiences, higher BMI, internalizing, externalizing, and social and sleep problems. In addition, the researchers found a relationship with lower cognition and gray matter volume.

Psychopathology characteristics remained strongly associated with later-stage prenatal cannabis exposure after adjustment for confounders.

Because child cannabis exposure was based on retrospective, self-reported data, Bogdan and colleagues recognize that this study may be limited by recall bias. In addition, the dataset had no available information on frequency of marijuana use.

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