Am J Perinatol 2024; 41(07): 949-960
DOI: 10.1055/s-0042-1745848
Original Article

Risk of Death at 1 Year Following Postpartum Opioid Exposure

Arlyn Horn*
1   Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
Margaret A. Adgent*
1   Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
Sarah S. Osmundson
2   Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
Andrew D. Wiese
1   Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
Sharon E. Phillips
3   Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Stephen W. Patrick
1   Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
4   Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
5   Vanderbilt Center for Child Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
Marie R. Griffin
1   Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
6   Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Carlos G. Grijalva
1   Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
7   Veterans' Health Administration, Tennessee Valley Healthcare System, Geriatric Research Education and Clinical Center (GRECC), Nashville, Tennessee
› Author Affiliations
Funding This work was funded in part by National Institutes of Health R01 AG043471. A.D.W. was supported by a PhRMA Foundation Fellowship Award, the Building Interdisciplinary Research Careers in Women's Health program supported by the National Institutes of Health (NIH) (grant number 5K12HD043483) and by the National Institute on Drug Abuse (NIDA) (grant number K01DA051683). S.S.O. was supported by NIH award K23DA047476.


Objective Opioids are commonly prescribed to women for acute pain following childbirth. Postpartum prescription opioid exposure is associated with adverse opioid-related morbidities but the association with all-cause mortality is not well studied. This study aimed to examine the association between postpartum opioid prescription fills and the 1-year risk of all-cause mortality among women with live births.

Methods In a retrospective cohort study of live births among women enrolled in Tennessee Medicaid (TennCare) between 2007 and 2015, we compared women who filled two or more postpartum outpatient opioid prescriptions (up to 41 days of postdelivery discharge) to women who filled one or fewer opioid prescription. Women were followed from day 42 postdelivery discharge through 365 days of follow-up or date of death. Deaths were identified using linked death certificates (2007–2016). We used Cox's proportional hazard regression and inverse probability of treatment weights to compare time to death between exposure groups while adjusting for relevant confounders. We also examined effect modification by delivery route, race, opioid use disorder, use of benzodiazepines, and mental health condition diagnosis.

Results Among 264,135 eligible births, 216,762 (82.1%) had one or fewer maternal postpartum opioid fills and 47,373 (17.9%) had two or more fills. There were 182 deaths during follow-up. The mortality rate was higher in women with two or more fills (120.5 per 100,000 person-years) than in those with one or fewer (57.7 per 100,000 person-years). The risk of maternal death remained higher in participants exposed to two or more opioid fills after accounting for relevant covariates using inverse probability of treatment weighting (adjusted hazard ratio: 1.46 [95% confidence interval: 1.01, 2.09]). Findings from stratified analyses were consistent with main findings.

Conclusion Filling two or more opioid prescriptions during the postpartum period was associated with a significant increase in 1-year risk of death among new mothers.

Key Points

  • Opioid prescribing in the postpartum period is common.

  • Prior studies show that >1 postnatal opioid fill is associated with adverse opioid-related events.

  • > 1 opioid fill within 42 days of delivery was associated with an increase in 1-year risk of death.

Previous Presentation

This work was presented as a poster at the 36th International Society for Pharmacoepidemiology Annual Meeting, ICPE All Access Virtual Event, September 16–17, 2020.


We are indebted to the Tennessee Division of TennCare of the Department of Finance and Administrationwhich provided data for the study. We are also indebted to the Tennessee Department of Health for providing data for the study.

* Authors contributed equally to this work.

Supplementary Material

Publication History

Received: 12 May 2021

Accepted: 17 February 2022

Article published online:
31 May 2022

© 2022. Thieme. All rights reserved.

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