Opioid use disorder (OUD) during pregnancy presents a significant risk to maternal, fetal, and neonatal health, increasing the likelihood of adverse events, such as maternal overdose, pregnancy loss, stillbirth, preterm birth, low birth weight, and neonatal abstinence syndrome [1,2]. Although OUD during pregnancy is associated with considerable harms, the withdrawal symptoms associated with sudden cessation are also extremely harmful to both the person who is pregnant and the fetus [3,4].

In order to reduce the risk of these outcomes, the standard of care for OUD during pregnancy in many jurisdictions within the United States and Canada is opioid agonist therapy (OAT) [3]. OATs are prescription medications that alleviate or eliminate opioid withdrawal symptoms so that OUD can be managed more safely. Buprenorphine and methadone are both recommended as first-line treatments in many jurisdictions, with buprenorphine increasingly being recommended as the preferred therapeutic option, given its established safety profile and simple treatment regimen [3]. Other options, such as slow-release oral morphine, can also be used for individuals who do not respond to first- or second-line therapies [3]. The ongoing use of OAT throughout pregnancy is considered safe for both the person who is pregnant and the fetus [3-5].

Although OAT offers a relatively safe option for managing OUD during pregnancy, many health care providers are unfamiliar with how best to prescribe OAT throughout a pregnancy, and many jurisdictions do not have established treatment guidelines. A consistent dosage can be difficult to maintain as the body changes during pregnancy, putting the person who is pregnant at risk of experiencing withdrawal symptoms or overdose both during the pregnancy and post partum [6-8]. These limitations, in combination with the fact that OAT can produce side effects (eg, nausea, vomiting, and constipation) [9] and that some pregnant people may simply prefer to continue using opioids, can increase the complexity of treatment regimens and approaches for ensuring that pregnant people receive prenatal care that is the most appropriate for them.

Although there is considerable literature to suggest that OAT is preferable to opioid use during pregnancy, to our knowledge only 1 systematic review has been conducted that considers the impacts of OAT on pregnancy outcomes. This living systematic review, which was conducted by Minozzi and colleagues [10], offers the most up-to-date evidence from randomized controlled trials (RCTs) to support the use of OAT during pregnancy. However, the authors note that the small number of RCTs considering this topic (n=4) makes it difficult to draw firm conclusions about the relative benefits of different OAT regimens, and further research is still needed [10]. Given the limited number of studies and participants available for inclusion from RCTs, we sought to build upon the existing knowledge base by evaluating observational studies that have been conducted to evaluate impacts of various types of OAT on pregnancy outcomes. Although observational studies include greater bias and heterogeneity when compared to RCTs, the inclusion of additional studies containing larger numbers of participants can offer valuable insights into the real-world impacts of OAT on pregnancy outcomes.

A search strategy has been finalized with a medical librarian at the University of British Columbia. The initial search has yielded 3266 abstracts for screening. Data extraction is expected to commence in February 2023, and final results should be available within 6 months of the publication of this protocol.

Our proposed systematic review will be the first to synthesize observational data on the effect of different OAT options on pregnancy outcomes for people with OUD. The topic of OAT and its effect on pregnancy is an understudied area that has the potential to improve health outcomes, clinical practice, education, and community advocacy. The results of our review will primarily be used to inform clinical practice guidelines for OAT prescribing practices among pregnant people and subsequently improve health outcomes for both pregnant individuals and their infants. The results of our study will generate pertinent considerations for future research to continue improving the knowledge available on the effect of OAT on pregnancy.

This systematic review faces some limitations. There will be a degree of heterogeneity among the studies selected due to the variability of the research methodologies, settings, and OAT regimens and dosages being studied. We will evaluate this issue during data extraction and will adjust our analysis strategy accordingly. Further, in order to mitigate the risk of reviewer bias, we will have 2 reviewers independently screen and assess (ie, quality assessment) each study in our review. There is also a risk of missing pertinent literature on our research topic. We have consulted a medical librarian at the University of British Columbia and developed a broad search strategy to maximize the likelihood of identifying relevant articles. Lastly, publication bias is a general limitation of systematic reviews. We will attempt to mitigate this issue by including abstracts that have been published within the last 2 years, but we may miss some studies that did not reach the publication stage. We will adjust our conclusions based on evidence of publication bias as appropriate.

Our systematic review will synthesize relevant literature and integrate the vast observational data available on OAT and its impacts on adverse events during pregnancy. The findings of our study will contribute to improved clinical care and health for all pregnant people who use opioids for the duration of their pregnancies and beyond.