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Maternal Complications and Prescription Opioid Exposure During Pregnancy: Using Marginal Structural Models

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Abstract

Introduction

Prescription opioids are frequently used for pain management in pregnancy. Studies examining perinatal complications in mothers who received prescription opioids during pregnancy are still limited.

Objectives

The aim of this study was to assess the association of prescription opioid use and maternal pregnancy and obstetric complications.

Methods

This retrospective cohort study with the Rhode Island (RI) Medicaid claims data linked to vital statistics throughout 2008–2015 included pregnant women aged 12–55 years with one or multiple live births. Women were excluded if they had cancer, opioid use disorder, or opioid dispensing prior to but not during pregnancy. Main outcomes included adverse pregnancy and obstetric complications. Marginal Structural Cox Models with time-varying exposure and covariates were applied to control for baseline and time-varying covariates. Analyses were conducted for outcomes that occurred 1 week after opioid exposure (primary) or within the same week as exposure (secondary). Sensitivity studies were conducted to assess the effects of different doses and individual opioids.

Results

Of 9823 eligible mothers, 545 (5.5%) filled one or more prescription opioid during pregnancy. Compared with those unexposed, no significant risk was observed in primary analyses, while in secondary analyses opioid-exposed mothers were associated with an increased risk of cesarean antepartum depression (HR 3.19; 95% CI 1.22–8.33), and cardiac events (HR 9.44; 95% CI 1.19–74.83). In sensitivity analyses, results are more prominent in high dose exposure and are consistent for individual opioids.

Conclusions

Prescription opioid use during pregnancy is associated with an increased risk of maternal complications.

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Acknowledgements

We thank the Rhode Island Department of Health and the Executive Office of Health and Human Services for providing the data access. Samara VinerBrown, MS, and William Arias, MPH, provided comments on the clarification of study population. Samara VinerBrown, MS, William Arias, MPH, and Ellen Amore, MS in the Center for Health Data & Analysis, Rhode Island Department of Health, and Dr Rebecca Lebeau’s team in Rhode Island Executive Office of Human and Health Services provided data linkage, data cleaning, and data preparation. No financial compensation was provided.

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Authors and Affiliations

  1. Health Outcomes, Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA

    Xuerong Wen & Shuang Wang

  2. Department of Obstetrics and Gynecology, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, RI, USA

    Adam K. Lewkowitz & Erin Christine Brousseau

  3. Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA

    Kristina E. Ward

  4. Department of Neurology, Stanford University, Palo Alto, CA, USA

    Kimford J. Meador

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  1. Xuerong Wen
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Correspondence to Xuerong Wen.

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Funding

The study is funded by grants from the National Institute of Health (NIH)/National Institute of Child Health and Human Development (NIH/NICHD Grant number: 1R15HD097588-01; Principal Investigator: Xuerong Wen). The funding source had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Conflicts of interest/Competing interests

Dr Meador has received research support from the National Institutes of Health and Sunovion Pharmaceuticals, and travel support from UCB Pharma. The Epilepsy Study Consortium pays Dr Meador’s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, and UCB Pharma. Other authors, XW, SW, AKL, KEW, and ECB have no conflicts of interests to declare.

Availability of data and material

The study data was linked and deidentified by the RI DOH and RI EOHHS. The deidentified data was released to Dr Wen’s research team as per the Data Utilization Agreement.

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Ethics approval

This study was considered exempt by the RI DOH IRB and URI IRB.

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Not applicable.

Author contributions

Dr Xuerong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Wen, Meador, Wang. Acquisition, analysis, or interpretation of data: Wen, Wang. Drafting of the manuscript: Wen, Wang, Meador, Lewkowitz. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Wang. Clinical, technical, or material support: Lewkowitz, Ward, Brousseau. Supervision: Wen, Meador. All authors read and approved the final version.

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Wen, X., Wang, S., Lewkowitz, A.K. et al. Maternal Complications and Prescription Opioid Exposure During Pregnancy: Using Marginal Structural Models. Drug Saf 44, 1297–1309 (2021). https://doi.org/10.1007/s40264-021-01115-6

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