The Impact of Opioid and Cannabis Exposure on Fetal Growth

Study Overview
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Brief Summary
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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
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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.

Official Title
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IMPACT: A Prospective Cohort Study of the Impact of Opioid and Cannabis Exposure on Fetal Growth

Conditions
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Pregnancy Related, Substance Use, Fetal Growth Retardation, Placenta Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Participant has given written consent after study has been explained according to local regulatory requirements and before any study specific procedures. Age ≥16 years at the time of consent. Singleton pregnancy. Live fetus (documented positive fetal heart beat prior to recruitment) ≥18 0/7 weeks of gestation and documented anatomy ultrasound at the time of consent. No known significant fetal genetic abnormalities (based on genetic testing, if performed). 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. Willing to provide cord blood. Willing to provide placenta. Willing to provide urine sample for drug testing. Plan to reside in the study area at least until delivery. Exclusion Criteria: 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. 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. Known abnormal placentation including accrete, increta and percreta. 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. 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. COVID-19 infection being diagnosed within 14 days of consent - recruitment may be delayed until required isolation period is over.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid, cannabis, nicotine, opioid agonist therapy