The Impact of Opioid and Cannabis Exposure on Fetal Growth (IMPACT)

IMPACT: a Prospective Cohort Study of the Impact of Opioid and Cannabis Exposure on Fetal Growth

Individually, both opioid and cannabis exposure during pregnancy are associated with changes in fetal growth. The extent to which opioid and cannabis exposure affect fetal growth is unknown. The Investigators hypothesize that the combination of both substances will impact placental function and subsequent fetal growth more severely than either substance alone. The primary objective is to determine the extent to which fetal growth profiles in opioid-exposed pregnancies are influenced by cannabis exposure. This prospective cohort study will consist of opioid-exposed pregnancies and pregnancies without opioid exposure recruited from 5 obstetrical clinics from across Ontario. A total of 546 participants will be recruited.

Study Overview

• Status: Terminated
• Conditions: Placenta Diseases; Pregnancy Related; Substance Use; Fetal Growth Retardation

Detailed Description

As cannabis exposure is prevalent in opioid-exposed pregnancies (36-75%), it is vital to understand the potential additive effect of these two concurrent exposures on the development and health of the feto-placental unit. This information would allow for informed decision making about cannabis use and can serve as an important starting point in the design of effective harm reduction strategies in this patient population. From our professional experience, the majority of opioid-using pregnant individuals are motivated to make lifestyle modifications. Eliminating cannabis may be a realistic change these individuals can make to improve outcomes for their infants.

Individually, both opioid and cannabis exposure during pregnancy are associated with altered fetal growth. The extent to which opioid and cannabis exposure affect fetal growth trajectories is unknown. The Investigators postulate that the combination of both substances will impact placental function and subsequent fetal growth more severely than either substance alone. Delineating this relationship may allow for the development of evidence-based harm reduction strategies focused on eliminating cannabis use in opioid-exposed pregnancies to improve fetal growth.

The overarching hypothesis of this research is that opioid exposure compromises placental growth and function, with significant impacts on vascular development, nutrient transport and metabolic signaling, ultimately impacting fetal growth trajectories. The Investigators further propose that the additive effects of cannabis use, extremely common in these pregnancies, may exacerbate this placental dysfunction.

Thus, the primary objective of this study is to determine the extent to which fetal growth profiles in opioid-exposed pregnancies are influenced by cannabis exposure.

The study population will consist of opioid-exposed pregnancies recruited from 5 obstetrical clinics from across Ontario. A total of 546 participants will be recruited.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from participating antenatal clinics at five sites across Ontario. Individuals with sustained opioid exposure during pregnancy will be eligible for inclusion into the study. Most individuals who use opioids/OATs in pregnancy smoke cigarettes (>90%). Thus, opioid unexposed groups will also be recruited.

Description

Inclusion Criteria:

1. Participant who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
2. Participant has given written consent after study has been explained according to local regulatory requirements and before any study specific procedures.
3. Age ≥16 years at the time of consent.
4. Singleton pregnancy.
5. Live fetus (documented positive fetal heart beat prior to recruitment)
6. ≥18 0/7 weeks of gestation and documented anatomy ultrasound at the time of consent.
7. No known significant fetal genetic abnormalities (based on genetic testing, if performed).
8. No significant congenital malformations (such as abnormal fetal morphology, abnormal amniotic fluid levels, significant abnormalities in placenta or umbilical cord), as assessed by fetal anomaly ultrasound scan (also known as a level 2 ultrasound or fetal morphology assessment) conducted at or beyond 18 0/7 weeks of gestation.
9. Willing to provide cord blood.
10. Willing to provide placenta.
11. Willing to provide urine sample for drug testing.
12. Plan to reside in the study area at least until delivery.

Exclusion Criteria:

1. Sustained use of substances other than opioids and cannabis, including methamphetamines, benzodiazepines, alcohol, and cocaine. This is defined as any use after the patient is aware that they are pregnant OR as per the discretion of the investigator.
2. Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities or any other clinical conditions, as determined by physical examination or standard of care laboratory tests, that, in the opinion of the investigator, might confound study results.
3. Known abnormal placentation including accrete, increta and percreta.
4. Any conditions that, in the Investigator's judgement, may interfere with participant's ability to comply with study procedures or receipt of prenatal care, such as behavioural or cognitive impairment or neuropsychiatric illness.
5. Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product.
6. COVID-19 infection being diagnosed within 14 days of consent - recruitment may be delayed until required isolation period is over.

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort
1 - Opioid Only; Illicit and/or sustained prescription opioids only (no cannabis use)
2 - OAT Only; Opioid agonist therapy (OAT) only (no cannabis use)
3 - Opioid and Cannabis; Illicit and/or sustained prescription opioids with concurrent cannabis use
4 - OAT and Cannabis; Opioid agonist therapy (OAT) with concurrent cannabis use
5 - Nicotine Only; Nicotine users without opioid exposure
6 - Cannabis Only; Cannabis-users without opioid exposure
7 - Unexposed; Non-substance exposed healthy pregnancies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birthweight	The primary outcome of interest is difference in birthweight (grams) between the exposure groups.	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant length	Infant length at birth (cm) will be compared between the groups.	At delivery
Incidence of Neonatal Morbidity	The incidence of neonatal morbidity will be compared between the groups. Severe neonatal morbidity (SNM) will be defined as the presence of at least one of the following elements: Apgar score < 4 at 5 min or severe respiratory distress requiring respiratory support, severe neonatal acidosis (cord artery pH < 7.0 or base excess <-12 mmol/L), admission to the neonatal intensive care unit (NICU), cystic periventricular leukomalacia (cPVL), intraventricular haemorrhage (IVH grades III and IV), surgical necrotizing enterocolitis (NEC requiring surgical treatment or peritoneal drainage) or retinopathy of prematurity (ROP≥stage 3).	From recruitment until 6 weeks postpartum
Length of Stay at Delivery	Length of hospital stay in hours for delivery between the groups. This will be measured from the date of admission to delivery till the date of discharge from the hospital after delivery.	From admission for delivery until discharge from hospital after delivery
Length of Antepartum Hospital Stay	Length of antepartum hospital admissions in hours between the groups. This will be measured from the date of admission to the date of discharge for any maternal hospital admissions before the admission for delivery.	From admission to discharge for each hospital stay that does not include delivery
Readmission rates	Readmission rates between the groups	From discharge from hospital at delivery till 6 weeks postpartum
Placental Weight	Placental weight (grams) between the groups.	At delivery
Placental gene expression profiles	Placental gene expression profiles related to vascular development, nutrient transport and metabolic signaling between the groups. These will be assessed using RNA sequencing and spatial transcriptomics.	At delivery

Collaborators and Investigators

• Sponsor: Dr. Laura Gaudet
• Collaborators: University of Ottawa
• Investigators: Principal Investigator: Laura Gaudet, MD, Kingston Health Sciences Centre

Publications and helpful links

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2022
• Primary Completion (Actual): October 15, 2024
• Study Completion (Actual): November 30, 2024

Study Registration Dates

• First Submitted: May 19, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: opioid; cannabis; nicotine; opioid agonist therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Fetal Diseases; Growth Disorders; Chemically-Induced Disorders; Fetal Growth Retardation; Substance-Related Disorders; Placenta Diseases
• Other Study ID Numbers: CTO 3968

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The objectives of the IMPACT Biobank are to provide a basis for future research on pregnancy and newborn health. The IMPACT consent for Future Research on Stored Biological Samples obtained from Participants is broad enough to support a range of research on fetal growth, pregnancy and the health of mothers and their children. Biobanking is an optional part of the IMPACT study. Participants may decide not to participate in the optional biobanking research and still participate in the main study.

The IMPACT Biobank is managed in accordance with the principles set forth in:

• The Canadian Charter of Rights and Freedoms
• The World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects
• The Universal Declaration on Bioethics and Human Rights
• The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans
• The Canadian Institutes of Health Research Best Practices for Protecting Privacy in Health Research

• IPD Sharing Time Frame: Up to 25 Years

IPD Sharing Access Criteria

The IMPACT Biobank Management Committee (IBMC) makes its decisions, including decisions relating to the future direction of the IMPACT Biobank, on the basis of these standards, objectives and the best available scientific evidence. Only research studies that entail, at most, a minimal risk to Participants will be granted access to the IMPACT Biobank.

The criteria for granting access include:

• feasibility;
• scientific value;
• minimal risk;
• availability of Material;
• contribution to the IMPACT Research Study;
• public health importance to Canadians.

The IMPACT Biobank is managed on a not-for-profit basis. The IBMC sets access fees with a view to covering the costs of operating the IMPACT Biobank. To help preserve the integrity and volume of the specimens for future users, part of the access fees will pay for the micro-aliquoting of specimens.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No