Prenatal cannabis exposure associated with adverse outcomes during middle childhood
The findings are reported as use of cannabis during pregnancy has 'skyrocketed'
September 23, 2020
Science Daily/Washington University in St. Louis
While cannabis use during pregnancy is on the rise, researchers at Washington University in St. Louis have found evidence that the resulting children are more likely to have psychopathology in middle childhood.
The team's analysis are the first steps in studying the effects of cannabis on children as attitudes surrounding its use change rapidly -- recreational adult cannabis use is now legal in 11 states and the District of Columbia. Patterns of usage, too, are changing; one of the fastest-growing subsets of cannabis users may come as a surprise: the pregnant.
"There have been increasingly permissive and lenient attitudes toward cannabis use among pregnant people," said Sarah Paul, a clinical psychology graduate student. "It has skyrocketed in the past few years," she added, with data indicating a quick rise from 3% to 7% past-month use.
"Unfortunately, despite the increase in use, we know remarkably little about the potential consequences of prenatal cannabis exposure," Paul said. "Prior studies have linked prenatal cannabis exposure to birth-related outcomes such as lower birth weight and infant characteristics like disrupted sleep and movement. Relatively fewer studies have examined behavior and problems as children age," and, she said, "findings have been tenuous due to inconsistent replication and an inability to account for potential confounding variables."
Working with Ryan Bogdan, associate professor of psychological & brain sciences in Arts & Sciences, and director of the Brain Lab at Washington University, and faculty from the School of Medicine, a team of researchers led by Paul and Alexander Hatoum, a postdoc research scholar, poured through data to examine what, if any, effect maternal use of cannabis during pregnancy may have on children.
Their findings were published today in JAMA Psychiatry.
They looked at data from the Adolescent Brain and Cognitive Development Study (ABCD Study), an ongoing longitudinal study of nearly 12,000 children ages 9-11 and their parent or caregiver from 22 sites across the United States that began in 2016.
The researchers grouped participants into three mutually exclusive groups: Children who were not exposed to cannabis prenatally; children who were prenatally exposed to cannabis before the pregnancy was known, but not after; and children who had been exposed to cannabis after the pregnancy was known, regardless of exposure before.
The receptors that cannabis influences are not known to be expressed prior to five- to six-weeks' gestation. Researchers expected associations with the children's outcomes would only be present if cannabis exposure happened once those receptors had been expressed. Most people said they learned of their pregnancy after about seven weeks, which aligned with the time of endocannabinoid type 1 receptor expression.
The group hypothesized that prenatal exposure, regardless of when it occurred, would be characterized by adverse outcomes in childhood, but that only continued exposure after the pregnancy was known would have an independent association with these outcomes (after considering potential confounds -- things such as family history of psychopathology, whether alcohol or tobacco or prenatal vitamins were used during the pregnancy, as well as whether children had tried alcohol, among a host of others).
The data showed children who were exposed to cannabis in the womb (regardless of when that exposure occurred) were slightly more likely to have adverse outcomes. They had elevated psychopathology -- more psychotic-like experiences; more problems with depression and anxiety as well as impulsivity and attention; and social problems as well as sleep disturbance. They also had lower cognitive performance, lower indices of global brain structure during middle childhood as well as lower birth weight.
However, when the researchers included important familial, pregnancy and child-related covariates, Bogdan said, "This is when things got really interesting. All associations with prenatal exposure only prior to maternal knowledge of pregnancy were nowhere near significantly associated." This suggests that the association between prenatal cannabis exposure during early stages of pregnancy may not be independent of these confounding factors.
"Cutting to the chase ... clinicians and dispensaries should discourage cannabis use among those who are pregnant or are considering becoming pregnant.
"However, when we look at exposure after maternal knowledge of pregnancy, which corresponds to when endocannabinoid type 1 receptors are expressed in the fetal brain, the associations with child psychopathology largely remain -- these children tend to have more psychotic-like experiences, more impulsivity and attention problems, and social problems," he said. "This raises the intriguing possibility that prenatal cannabis exposure may plausibly impact child behavior. It in no way shows causation, but documenting that effects are independent of common confounding factors provides incremental support for potential causation."
"There are certainly other plausible reasons for this pattern of results," Hatoum said. It could be that the behaviors are a byproduct of genetic and environmental similarity and not causally related to cannabis use.
"However, that our measures of these potential confounds accounted for the associations with use prior to maternal knowledge, but not after, suggests that prenatal cannabis exposure may independently contribute, in a small way, to child outcomes," he said. "Potential causation underlying this association should be further evaluated using experimental non-human animal models, additional replication and other approaches (e.g., siblings discordant for exposure)."
"Cutting to the chase, my interpretation of these findings, is that clinicians and dispensaries should discourage cannabis use among those who are pregnant or are considering becoming pregnant," Bogdan said.
"Being attentive to substance use problems among family members and providing them with support and access to help is critical for anyone regardless of pregnancy status," Bogdan said. "Learning of one's pregnancy may produce additional reason to stop use. Someone who has just learned of a pregnancy and has previously used cannabis, might think, well I have already exposed the fetus to cannabis, so I may as well not stop. The current data might provide the clinician and parent-to-be with evidence that stopping after learning of the pregnancy may reduce the likelihood of negative outcomes among their children."
At the same time, Bogdan said, "It is also important not to stigmatize expecting parents who may be experiencing difficulties. Quitting substance use during pregnancy, which is already a challenging time, may not be straightforward. Physician support and empirical paradigms for quitting during pregnancy will be important. Lastly, couples who are planning to have a child may wish to consider combatting cannabis use before they begin attempting to conceive and the additional stressors of pregnancy begin to mount."
From a public health perspective, Bogdan suggested looking to the highly effective public health campaigns and clinician attention directed at reducing the use of tobacco and alcohol during pregnancy. In fact, he said, "This study found that prenatal cannabis exposures were more strongly and consistently associated with adverse child outcomes than prenatal tobacco or alcohol exposure."
https://www.sciencedaily.com/releases/2020/09/200923143550.htm
Real risks associated with cannabis exposure during pregnancy
January 17, 2020
Science Daily/University of Western Ontario
A new study from researchers at Western University and Queen's University definitively shows that regular exposure to THC, the main psychoactive ingredient in cannabis, during pregnancy has significant impact on placental and fetal development. With more than a year since the legalization of recreational cannabis in Canada, the effects of its use during pregnancy are only now beginning to be understood.
The study, published today in Scientific Reports, uses a rat model and human placental cells to show that maternal exposure to THC during pregnancy has a measurable impact on both the development of the organs of the fetus and the gene expression that is essential to placental function.
The researchers demonstrated in a rat model that regular exposure to a low-dose of THC that mimics daily use of cannabis during pregnancy led to a reduction in birth weight of 8 per cent and decreased brain and liver growth by more than 20 per cent.
"This data supports clinical studies that suggest cannabis use during pregnancy it is associated with low birth weight babies. Clinical data is complicated because it is confounded by other factors such as socioeconomic status," said Dan Hardy, PhD, Associate Professor at Western's Schulich School of Medicine & Dentistry and co-author on the paper. "This is the first study to definitively support the fact that THC alone has a direct impact on placental and fetal growth."
The research team was also able to characterize how THC prevents oxygen and nutrients from crossing the placenta into the developing fetus. By studying human placental cells, the researchers found that exposure to THC caused a decrease in a glucose transporter called GLUT-1. This indicates that the THC is preventing the placental transfer of glucose, a key nutrient, from the mother to the fetus. They also found a reduction in placental vasculature in the rat model suggesting reduced blood flow from the mother to the fetus.
The researchers say both of those factors are likely contributing to the growth restriction that they observed in the offspring.
The researchers point out that there are currently no clear guidelines from Health Canada on the use of cannabis in pregnancy and some studies have shown that up to one in five women are using cannabis during pregnancy to prevent morning sickness, for anxiety or for social reasons.
"Marjiuana has been legalized in Canada and in many states in the US, however, its use during pregnancy has not been well studied up until this point. This study is important to support clinicians in communicating the very real risks associated with cannabis use during pregnancy," said David Natale, PhD, Associate Professor at Queen's and co-author on the paper.
https://www.sciencedaily.com/releases/2020/01/200117104756.htm
Potential therapy to treat detrimental effects of marijuana
October 15, 2019
Science Daily/University of Maryland School of Medicine
A new study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain's dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence.
As a growing number of U.S. states legalize the medicinal and recreational use of marijuana, an increasing number of American women are using cannabis before becoming pregnant and during early pregnancy often to treat morning sickness, anxiety, and lower back pain. Although emerging evidence indicates that this may have long-term consequences for their babies' brain development, how this occurs remains unclear.
A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain's dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.
The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.
More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.
"This is an exciting finding that suggests a therapeutic approach for children born to mothers who used cannabis during pregnancy," said Joseph Cheer, PhD, a Professor of Anatomy & Neurobiology and Psychiatry at the University of Maryland School of Medicine. "It also raises important questions that need to be addressed such as how does pregnenolone exert its effects and how can we improve its efficacy? Do these detrimental effects persist into adulthood, and if so, could they also be treated in a similar way?"
The researchers concluded that as physicians caution pregnant women against alcohol and cocaine intake because of their detrimental effects to the fetus, they should also, based on these new findings, advise them on the potential negative consequences of using cannabis
More women using cannabis daily before and during pregnancy
Current advice is to avoid cannabis exposure during pregnancy
July 19, 2019
Science Daily/Kaiser Permanente
The number of women using cannabis in the year before they get pregnant and early in their pregnancies is increasing, and their frequency of use is also rising, according to new data from Kaiser Permanente.
The research, published July 19, 2019, in JAMA Network Open, examined self-reported cannabis use among 276,991 pregnant women (representing 367,403 pregnancies) in Northern California over 9 years and found that cannabis use has increased over time.
From 2009 to 2017, the adjusted prevalence of self-reported cannabis use in the year before pregnancy increased from 6.8% to 12.5%, and the adjusted prevalence of self-reported cannabis use during pregnancy increased from 1.9% to 3.4% (rates were adjusted for demographics). Annual rates of change in self-reported daily, weekly, and monthly-or-less cannabis use increased significantly, though daily use increased most rapidly.
Among women who self-reported cannabis use during the year before pregnancy, the proportion who were daily users increased from 17% to 25%, and weekly users increased from 20% to 22%, while monthly-or-less users decreased from 63% to 53% during the study period. Similarly, among women who self-reported cannabis use during pregnancy, the proportion who were daily users increased from 15% to 21%, and weekly users from 25% to 27%, while monthly users decreased from 60% to 52%.
"These findings should alert women's health clinicians to be aware of potential increases in daily and weekly cannabis use among their patients," said lead author Kelly Young-Wolff, PhD, MPH, a research scientist with the Kaiser Permanente Division of Research. "The actual numbers are likely higher, as women may be unwilling to disclose their substance use to a medical professional."
In addition, the prevalence of daily and weekly cannabis use may have risen even further in the past year and a half following legalization of cannabis for recreational use in California in 2018, Young-Wolff said.
The data come from women's initial prenatal visits at Kaiser Permanente in Northern California, which usually take place at around 8 weeks gestation, and do not reflect continued use throughout pregnancy. Investigators were unable to differentiate whether self-reported cannabis use during pregnancy occurred before or after women were aware that they were pregnant.
While the current findings are based on women's self-reporting, the results are supported by the Kaiser Permanente research team's December 2017 JAMA Research Letter showing an increase in prenatal cannabis use via urine toxicology testing. In this newer study, the authors focus on trends in frequency of use in the year before and during pregnancy.
Some women may use cannabis during pregnancy to manage morning sickness, the authors noted. The authors' previous work published in JAMA Internal Medicine in 2018 found women with severe nausea and vomiting in pregnancy were nearly 4 times more likely to use cannabis during the first trimester of pregnancy.
Women may get the impression from cannabis product marketing and online media that cannabis use is safe during pregnancy, said Young-Wolff. However, there is substantial evidence that exposure to cannabis in pregnancy is associated with having a low-birthweight baby, and the American College of Obstetricians and Gynecologists recommends women who are pregnant or contemplating pregnancy discontinue cannabis use because of concerns about impaired neurodevelopment and exposure to the adverse effects of smoking.
"There is still much that is unknown on the topic, including what type of cannabis products pregnant women are using and whether the health consequences differ based on mode of cannabis administration and frequency of prenatal cannabis use," Young-Wolff noted.
More research is needed to offer women better, specific advice, said study senior author Nancy Goler, MD, an obstetrician/gynecologist and associate executive director of The Permanente Medical Group.
"There is an urgent need to better understand the effects of prenatal cannabis exposure as cannabis becomes legalized in more states and more widely accepted and used," Dr. Goler said. "Until such time as we fully understand the specific health risks cannabis poses for pregnant women and their fetuses, we are recommending stopping all cannabis use prior to conceiving and certainly once a woman knows she is pregnant."
The study was supported by a grant from the National Institute on Drug Abuse.
Young-Wolff and Kaiser Permanente Division of Research colleague Lindsay Avalos, PhD, MPH, have received a new 5-year grant from NIDA to support further research on maternal cannabis use during pregnancy. They plan to study whether prenatal cannabis use is associated with increased risk of adverse maternal, fetal, and neonatal outcomes using data from urine toxicology testing, self-reported frequency of prenatal cannabis use, and mode of cannabis administration. They will also test whether legalization of cannabis for recreational use in 2018 and local regulatory practices (such as retailer bans) are associated with variation in prenatal cannabis use.
https://www.sciencedaily.com/releases/2019/07/190719173602.htm
Cannabis during pregnancy bumps psychosis risk in offspring
With marijuana use rising among pregnant women, study raises new concerns
March 27, 2019
Science Daily/Washington University in St. Louis
Pregnant women who use cannabis may slightly increase the risk their unborn child will develop psychosis later in life, suggests new research from Washington University in St. Louis.
"Our research shows that prenatal marijuana exposure after maternal knowledge of pregnancy is associated with a small increase in psychosis proneness during middle childhood or about age 10," said Jeremy Fine, an undergraduate majoring in psychological & brain sciences in Arts & Sciences at Washington University and the study's lead author.
The findings come on the heels of several national studies documenting a dramatic increase in marijuana usage by pregnant women, including a 2018 study from Washington University School of Medicine in St. Louis that found past-month marijuana use among pregnant mothers in the United States increased by 75 percent between 2002 (2.85 percent) and 2016 (4.98 percent).
As more states legalize medicinal and recreational use of cannabis, other reports suggest that many marijuana dispensaries commonly suggest cannabis as a natural cure for pregnancy related nausea.
This latest study, published March 27 in the journal JAMA Psychiatry, suggests that pregnant women should be discouraged from using cannabis at any time in their pregnancy because so little is yet known about its health effects.
But its findings also raise new concerns that prenatal exposure to cannabis may pose a greater risk after the fetal brain begins to develop a receptor system for endocannabinoids, which are part of the naturally occurring neurotransmitter network through which cannabis affects the brain.
"One possible explanation for the finding of increased psychosis risk for marijuana use following, but not before, knowledge of pregnancy is that the endocannabinoid receptor system may not be in place during the early weeks of pregnancy," said Ryan Bogdan, associate professor of psychological & brain sciences and senior author of the paper. "Prenatal cannabis exposure may be associated with later psychosis proneness in offspring only when there is sufficient fetal endocannabinoid type 1 receptor expression, which may not occur until after many mothers learn they are pregnant."
Bogdan, who directs the Washington University BRAIN Lab where the research took place, said these latest findings build on other basic research suggesting that endocannabinoid signaling may contribute to processes, such as neurogenesis and neural migration, that play important roles in early development of brain structure and connections.
"This study raises the intriguing possibility there may be developmental windows during which cannabis exposure may be more likely to increase psychosis risk," he said.
Tetrahydrocannabinol (THC), which is the principal psychoactive component of marijuana, mimics our body's endocannabinoids and binds to endocannabinoid receptors to exert its effects. Various studies have confirmed that THC crosses the placental barrier to gain access to the developing fetus.
"Data from rodent studies suggest that the endocannabinoid type 1 receptor, through which the psychoactive effects of THC largely arise, is not expressed until the equivalent of 5-6 weeks of human gestation," Fine said. "Given that mothers in our study on average learned of their pregnancy at 7.7 weeks, it is plausible that any impact of THC on psychosis risk would not arise until sufficient endocannabinoid type 1 receptors are expressed."
The BRAIN Lab findings are based on data from the Adolescent Brain Cognitive Development (ABCD) study, an ongoing longitudinal study of child health and brain development with data collection sites throughout the nation. They used data from the initial ABCD baseline data release which included survey responses from 3,774 mothers about marijuana usage during 3,926 pregnancies. Risk of psychosis in the 4,361 children born from these pregnancies between 2005 and 2008 was measured using a questionnaire administered to the children between ages 8.9 and 11 years.
Among the 4,361 children sampled in this study, 201 (4.61 percent) were reported to have been exposed to marijuana before birth. Of these, 138 were exposed only before mothers knew they were pregnant; two were exposed only after the mother knew she was pregnant.
Bogdan and his co-authors acknowledge that the study has many limitations, including the small sample of prenatal cannabis-exposed offspring; potential maternal underreporting of use during pregnancy; imprecise data on timing, amount, frequency and potency of cannabis exposure; absence of data on whether childhood psychosis proneness is associated with conversion to psychosis; and lack of data on some potential confounders, such as maternal stress and genetic risk of psychosis among parents.
"Our research is correlational and as such cannot draw causal conclusions," said Allison Moreau, study co-author and a graduate student in psycholody at Washington University. "However, that the relationship between prenatal marijuana exposure following maternal knowledge of pregnancy was associated with offspring psychosis proneness after accounting for potentially confounding variables -- such as maternal education, prenatal vitamin usage, prenatal alcohol and nicotine use, child substance use, and so on -- increases the plausibility that prenatal cannabis exposure may contribute to a small risk of increased psychosis liability in children."
The study provides further evidence that expectant mothers should think twice before considering cannabis usage during pregnancy.
"Given increasing cannabis accessibility and potency, as well as growing public perceptions that it's safe to use, it is critical for additional research to understand the potential adverse consequences and benefits of cannabis throughout development and how these associations may arise." Bogdan said. "In the meantime, evidence that prenatal marijuana use is associated with a small increase in offspring psychosis proneness suggests that marijuana use during pregnancy should be discouraged until more is known."
Other Washington University co-authors include Nicole Karcher, post-doctoral research scholar; Arpana Agrawal, professor of psychiatry; and Cynthia Rogers, assistant professor of child psychiatry, all in the Department of Psychiatry in the School of Medicine; and Deanna Barch, chair of the Department of Psychological & Brain Sciences in Arts & Sciences and the Gregory B. Couch Professor of Psychiatry at the School of Medicine.
Funding for this study was provided by the Adolescent Brain Cognitive Development (ABCD) study, which was funded by awards from the National Institutes of Health and additional federal partners.
https://www.sciencedaily.com/releases/2019/03/190327112617.htm