Fetal Exposure to Cannabinoids: Exposure, Methylation and Neurodevelopmental Effects

NCT04422600 | Completed DMC

• 1 other identifier: 239611
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Cannabis is a very popular drug for both recreational and medicinal use. An estimated 20% of adults in the United States report using cannabis in the past month, and this number continues to increase each year. As of 2018, medical use of cannabis is legal in 33 states and the District of Columbia. Recreational use is legal in 10 states, and it is decriminalized in 15 states. Hemp-derived cannabidiol (CBD) is legal in all states. Due to the rapidly changing legal status across the country, the demand for cannabinoids (which are specific components of cannabis), such as THC and CBD, are also rapidly increasing. Studies have shown a significant increase in marijuana use among pregnant and parenting women following state-wide legalization, and this could have significant implications for the health and development of children born to these women. While there is a growing effort to evaluate the health effects of cannabinoids, especially during pregnancy, there is still relatively little known about the long term neurodevelopmental outcomes, such as emotional regulation, attention, and intelligence, in children born to mothers who used any sort of cannabinoid during pregnancy. The few studies that have been performed that look at longer term outcomes were epidemiological and self-reported in nature, and cannot accurately correlate neurodevelopmental outcomes with precise dosage and exposure levels during pregnancy. Importantly, the THC content of marijuana has dramatically increased in recent years, with THC concentration and purity being the highest in history. It is estimated that cannabis potency has increased 3-fold over the past 2 decades. Many of the previous studies examining prenatal cannabis use and fetal outcomes reflected lower potency cannabis, which is not relevant to today's exposure levels. Additionally, there are no published studies to-date that evaluate fetal exposure to CBD or neurodevelopmental outcomes in infants who were exposed to CBD prenatally. Finally, the causes behind possible neurodevelopmental changes in children exposed to cannabis prenatally have not been thoroughly explored, particularly in humans. It is thought that epigenetic modifications, or changes to DNA, may play a role in changes to the developing fetal brain after prenatal exposure to cannabis, but few studies have evaluated this quantitatively in humans.

Conditions

Fetal Exposure Timing Unspecified

Keywords

Fetal Exposure; Cannabinoids; Methylation; Neurodevelopmental Effects

Outcome Measures

Primary Outcomes (8)

• THC and CBD metabolite levels in maternal neonatal blood

  Levels of THC and CBD metabolites will be measured in maternal blood following prenatal drug use. These levels will be measured via liquid chromatography-mass spectrometry.

  Within three months prior to the estimated due date

• THC and CBD metabolite level in umbilical cord blood

  Levels of THC and CBD metabolites will be measured umbilical cord blood following prenatal drug use. These levels will be measured via liquid chromatography-mass spectrometry.

  Immediately after birth

• THC and CBD metabolite levels in neonatal blood

  Levels of THC and CBD metabolites will be measured in neonatal blood following prenatal drug use. These levels will be measured via liquid chromatography-mass spectrometry.

  24 hours after birth

• Infant motor, cognitive, and social development at 6 months of age using the Ages and Stages Questionnaire

  To measure infant neurodevelopment, we will use the Ages and Stages Questionnaire (ASQ). The ASQ measures 5 domains/scales of child development: communication, gross motor, fine motor, problem solving, and personal-social. Each scale ranges from 0 to 60, with lower scores being indicative of deficits or poor outcomes.

  6 months after birth

• Infant motor, cognitive, and social development at 12 months of age using the Ages and Stages Questionnaire

  To measure infant neurodevelopment, we will use the Ages and Stages Questionnaire (ASQ). The ASQ measures 5 domains/scales of child development: communication, gross motor, fine motor, problem solving, and personal-social. Each scale ranges from 0 to 60, with lower scores being indicative of deficits or poor outcomes.

  12 months after birth

• Infant motor, cognitive, and social development at 6 months of age using the Bayley Scales of Infant Development

  To measure infant neurodevelopment, we will use the Bayley Scales of Infant and Toddler Development. The Bayley Scales measures 5 domains of child development: adaptive behavior, cognitive, language, motor, and social-emotional. Each scale ranges from 40-160, with higher scores indicative of better outcomes.

  6 months after birth

• Infant motor, cognitive, and social development at 12 months of age using the Bayley Scales of Infant Development

  To measure infant neurodevelopment, we will use the Bayley Scales of Infant and Toddler Development. The Bayley Scales measures 5 domains of child development: adaptive behavior, cognitive, language, motor, and social-emotional. Each scale ranges from 40-160, with higher scores indicative of better outcomes.

  12 months after birth

• DNA methylation profiles in infants at 12 months of age

  Buccal samples from infants at 12 months of age will be used to evaluate DNA methylation profiles.

  12 months after birth

Study Arms (3)

Mothers who report use of THC with or without CBD

Mothers who report THC and CBD usage during the trimester month of pregnancy, at a frequency of at least three time per week. Information will be collected from mothers receiving their obstetrical care at UAMS and will include data on the exact products used and the frequency of use.

Other: There is no other intervention, only clinical treatment.

Mothers who report use of CBD only

Mothers who report CBD usage during the trimester month of pregnancy, at a frequency of at least three time per week. Information will be collected from mothers receiving their obstetrical care at UAMS and will include data on the exact products used and the frequency of use.

Other: There is no other intervention, only clinical treatment.

Control Mothers

Recruitment of pregnant women who do not use THC or CBD will be conducted using the Epic MyChart research participant recruitment tool

Other: There is no other intervention, only clinical treatment.

Interventions

There is no other intervention, only clinical treatment. OTHER

The investigators will then correlate that exposure with neurodevelopmental outcomes.

Control Mothers; Mothers who report use of CBD only; Mothers who report use of THC with or without CBD

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pregnant women and infants
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Mothers who report use of THC and /or CBD and pregnant women who do not use THC or CBD. Babies will be enrolled (consent given by mothers) following birth.

You may qualify if:

• Pregnant women
• Age 18 and older
• Must plan to give birth at UAMS
• Report regular (at least 3x per week) use of THC- and/or CBD-containing product anytime during pregnancy (for experimental groups). Women who discontinue use of marijuana and/or CBD during pregnancy will still be allowed in the study.
• Pregnant women who do not use THC or CBD will be enrolled as controls.

You may not qualify if:

• Any other illicit drug use during pregnancy
• Plan to give birth anywhere other than UAMS

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (21)

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Biospecimen

Retention: SAMPLES WITH DNA

Five (5) mL of blood will be collected from mothers at some point in the third trimester of pregnancy. Five (5) mL of umbilical cord blood will be collected from the baby immediately after birth, followed by a 1 mL venous blood sample collected 24 hours or later following birth during the routine blood sample collection for newborn screening. Buccal swabs will be collected from infants at 6 and 12 months of age for DNA methylation.

Study Officials

• Stefanie Kennon McGill, Ph.D.

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 9, 2020
• Study Start: February 26, 2020
• Primary Completion: May 1, 2023
• Study Completion: August 1, 2023
• Last Updated: September 3, 2024

Record last verified: 2023-09

Locations

US (1)