The Impact of Opioid and Cannabis Exposure on Fetal Growth

Terminated

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

• Registration Number: NCT05899101
• Lead Sponsor: Dr. Laura Gaudet

Brief Summary

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.

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 Timeline

• Study Start: 2022-09-23
• Study First Submitted: 2023-05-19
• Study First Submitted QC: 2023-06-02
• Study First Posted: 2023-06-12
• Primary Completion: 2024-10-15
• Study Completion: 2024-11-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 20

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Birthweight	At delivery	The primary outcome of interest is difference in birthweight (grams) between the exposure groups.

Secondary Outcome Measures

Name	Time	Method
Placental gene expression profiles	At delivery	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.
Length of Antepartum Hospital Stay	From admission to discharge for each hospital stay that does not include delivery	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.
Infant length	At delivery	Infant length at birth (cm) will be compared between the groups.
Incidence of Neonatal Morbidity	From recruitment until 6 weeks postpartum	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).
Length of Stay at Delivery	From admission for delivery until discharge from hospital after 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.
Placental Weight	At delivery	Placental weight (grams) between the groups.
Readmission rates	From discharge from hospital at delivery till 6 weeks postpartum	Readmission rates between the groups

Trial Locations

Locations (5)

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada