Cannabis Use in Pregnancy and Downstream Effects on Maternal and Infant Health (CUPiD)

• ClinicalTrials.gov Identifier: NCT05309226
• Recruitment Status: Not yet recruiting
• First Posted: April 4, 2022
• Last Update Posted: September 21, 2022
• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Queen's University; Children's Hospital of Eastern Ontario Research Institute
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Tracking Information

• First Submitted Date: February 10, 2022
• First Posted Date: April 4, 2022
• Last Update Posted Date: September 21, 2022
• Estimated Study Start Date: October 2022
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2022)

• Appropriateness of eligibility criteria [ Time Frame: Within first year ]
  Measured by the reasons for exclusion of screened subjects
• Recruitment rate [ Time Frame: Within first year ]
  Measured by the proportion of eligible cases and controls recruited into the cohort
• Level of engagement [ Time Frame: Within first year ]
  Measured by the proportion of recruited subjects contributing data and biospecimens at each time point
• Protocol compliance [ Time Frame: Within first year ]
  Measured by attrition rate (loss to follow-up or withdrawal of consent) of enrolled subjects
• Appropriateness of sample size and time frame [ Time Frame: Within first year ]
  Measured by the timeframe required to recruit target sample size

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 24, 2022)

• Fetal and neonatal morbidity (preterm) [ Time Frame: Throughout pregnancy until 6-12 weeks postpartum ]
  Rates of: Preterm Birth (<37 weeks' gestation; 34 to 36 weeks' gestation (late preterm);32 to 33 weeks' gestation; 28 to 31 weeks' gestation; <28 weeks' gestation (very preterm birth))
• Fetal and neonatal morbidity (sga) [ Time Frame: Throughout pregnancy until 6-12 weeks postpartum ]
  Rates of: small for gestational age (<10th and <3rd percentiles)
• Neonatal morbidity (NICU) [ Time Frame: Throughout pregnancy until 6-12 weeks postpartum ]
  Rates of: neonatal ICU admission
• Neonatal morbidity (apgar) [ Time Frame: Throughout pregnancy until 6-12 weeks postpartum ]
  Rates of: low Apgar (<4 at 5 min)
• Fetal and neonatal morbidity [ Time Frame: Throughout pregnancy until 6-12 weeks postpartum ]
  Rates of: stillbirth, spontaneous abortion, elective termination
• Maternal morbidity [ Time Frame: Throughout pregnancy until 6-12 weeks postpartum ]
  Rates of: gestational diabetes, pre-eclampsia, placental abruption
• Mode of delivery [ Time Frame: Through study completion, about every 9-months ]
  Rates of cesarean sections and vaginal deliveries
• Child growth (weight) [ Time Frame: 6-12 weeks postpartum ]
  weight
• Child growth (head circumference) [ Time Frame: 6-12 weeks postpartum ]
  head circumference
• Child growth (height) [ Time Frame: 6-12 weeks postpartum ]
  length
• Child Major Illnesses/conditions [ Time Frame: Delivery to 6-12 weeks postpartum ]
  Proportion of children receiving diagnoses of major illness/conditions
• Hospitalizations [ Time Frame: Delivery to 6-12 weeks postpartum ]
  Proportion of mothers and infants re-admitted to hospital
• Emergency care visits [ Time Frame: Delivery to 6-12 weeks postpartum ]
  Proportion of mothers and infants with emergency care visits

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cannabis Use in Pregnancy and Downstream Effects on Maternal and Infant Health
• Official Title: Cannabis Use in Pregnancy and Downstream Effects on Maternal and Infant Health (CUPiD): A Pilot Prospective Cohort Study
• Brief Summary: With perinatal cannabis use rising in Canada, robust data on short-term and long-term effects on newborns are urgently needed. However, past barriers to obtain robust data included limited sample sizes, low self-reporting and no account of postpartum exposures. Therefore, this study will be conducted as a feasibility pilot study to tease out limitations that were present in previous studies. This study will help us dictate how to conduct a larger prospective cohort study to answer any knowledge gaps currently in the field of perinatal cannabis use.

Detailed Description

Since Canadian legalization of cannabis in October 2018, reports of cannabis use have increased even among pregnant women/individuals. Previous work has identified that cannabis products known as cannabinoids, such as THC, CBD, cannabinol and their metabolic by-products cross the placenta and can enter the fetal bloodstream and distribute throughout the fetal tissues, including the brain associating to neurodevelopmental outcomes. However, these studies were limited by their sample size, based on self-reporting and did not account for postpartum exposures. Notably, the CUPiD study is a pilot study to assess the feasibility for a larger prospective study and address past limitations.

We will aim to recruit 50 participants who are currently using cannabis in pregnancy and 50 participants who are not using cannabis in pregnancy within 12 months from either the Ottawa Hospital or Kingston General Hospital. The participants will be recruited prior to 20 weeks gestation and will be followed up until 4 months postpartum. Within the study period, there will be extensive data collection through surveys, diaries and medical chart reviews as well as biological sampling of the mother/birthing parent and the baby (after delivery).

This work will address key issues such as recruitment rate, level of engagement, protocol compliance and appropriateness of sample size and timeframe. By piloting a pregnancy cohort from which robust data on cannabis practices can be gathered, this project will lay the foundation for downstream research in this area.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Consenting participants will be asked to contribute biological samples.

We will allow participants to choose the scope of sample collection at each time-point. Sampling will be coordinated alongside routine clinical collections where possible to minimize burden to participants.

Samples will be collected at 5 timepoints throughout the study time period: in each trimester of pregnancy, at delivery and at 6-12 weeks postpartum. Maternal blood and urine will be collected at all visits. During the delivery admission, cord blood, cord tissue, placenta, meconium, and breastmilk will be collected. At the postpartum visit, baby urine and blood (dried blood spot) and breastmilk will be collected.

Partners will not be asked to contribute biological samples.

• Sampling Method: Non-Probability Sample
• Study Population: The primary study population will consist of pregnant individuals who are or are not using cannabis in pregnancy, and their infants. Partners will be invited to participate in a one-time survey.

Condition

• Cannabis Use
• Marijuana Use

Intervention

Other: Cannabis use in pregnancy or cannabis exposure in utero

Cannabis-related product use in pregnancy. Cannabis-related products will include all forms (e.g., dry flower, edibles, extracts, etc.) and formats of consumption (e.g., joint, bong, capsule, tincture, etc.).

Study Groups/Cohorts

• Pregnant Cannabis User

  Pregnant individuals who disclose cannabis use in pregnancy

  We will examine patterns of cannabis use including the type of cannabis used, amount and frequency of cannabis use during the perinatal and postpartum periods. If participant decides to stop using cannabis in pregnancy, they will not be excluded from the study.

  Intervention: Other: Cannabis use in pregnancy or cannabis exposure in utero
• Pregnant Cannabis Non-User
  Pregnant individuals who report not using cannabis in pregnancy and who have not used cannabis products for at least 3-months prior to pregnancy.
• Offspring of Pregnant Cannabis User
  Infants born to pregnant participants who disclose cannabis use in pregnancy
  Intervention: Other: Cannabis use in pregnancy or cannabis exposure in utero
• Offspring of Pregnant Cannabis Non-User
  Infants born to pregnant participants who report no cannabis use in pregnancy
• Partners
  Partners of pregnant participants enrolled in this study.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: March 24, 2022): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

MOTHER INFANT DYADS

Inclusion Criteria:

Exposed and unexposed pregnant women/individuals must meet all of the following inclusion criteria at the time of enrollment to be eligible:

• Capacity to provide informed consent and to comprehend and comply with the study requirements
• Planning to deliver at TOH or KGH, or The Ottawa Birth and Wellness Centre (affiliated with TOH)
• Be ≥ 16 years of age at the time of consent
• Be ≤ 20 weeks' gestation on the day of enrollment.

Exposed group: pregnant women/individuals who are using any cannabis-related product in pregnancy at the time of enrollment, or have used cannabis-related products in the current pregnancy for any reason (including but not limited to recreational use, to ease nausea and vomiting, use for chronic pain management or other medical indications).

Unexposed group: pregnant women/individuals who are not using cannabis-related products in pregnancy, and who have not used any cannabis-related product for at least 3-months prior to pregnancy.

Exclusion Criteria:

• Women/Individuals who self-report non-prescription use of controlled and illegal drugs in their current pregnancy (i.e., benzodiazepines, cocaine and crack, fentanyl, heroin, ketamine, lysergic acid diethylamide, magic mushrooms, MDMA, methamphetamine, gamma hydroxybutyrate, opioids, phenylcyclohexyl piperidine, salvia) or report their use in the 3-months prior to pregnancy. (**Use of alcohol or tobacco products prior to pregnancy or during pregnancy will not be an exclusion criterion**)
• Women/Individuals who self-report prescription use of opioid medications including methadone, Subutex, buprenorphine, tramadol, oxycodone, hydrocodone, and hydromorphine in their current pregnancy, or report their use in the 3 months prior to pregnancy
• Surrogate or planning to give child up for adoption

PARTNERS 'Partner' will be broadly defined as any individual identified as such by an enrolled pregnant participant (any sex or gender, any status - marital, common-law, or otherwise). Thus, eligible partners must meet all of the following inclusion criteria at the time of enrollment:

• Pregnant partner is enrolled in the CUPiD cohort study
• Have capacity to provide informed consent and to comprehend and comply with the study requirements
• Be ≥ 16 years of age at the time of consent

There are no pre-defined exclusion criteria for partners.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Alysha Harvey, MSc, PMP; 613-737-8899 ext 73838; alyharvey@ohri.ca

Contact: Serine Ramlawi, MSc; 613-737-8899; sramlawi@ohri.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT05309226
• Other Study ID Numbers: CTO 3791
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ottawa Hospital Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Ottawa Hospital Research Institute
• Original Study Sponsor: Same as current

Collaborators

• Queen's University
• Children's Hospital of Eastern Ontario Research Institute

Investigators

• Principal Investigator: Mark Walker, MD, MSc, MHM; Ottawa Hospital Research Institute
• Principal Investigator: Daniel Corsi, PhD; Ottawa Hospital Research Institute

• PRS Account: Ottawa Hospital Research Institute
• Verification Date: March 2022