Due to challenges with participant recruitment the propsective study was terminated.

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.

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.

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.

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.

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

Up to 25 Years

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.