Download PDF
Am J Perinatol
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 study was supported by the U.S. Department of Health and Human Services, National Institutes of Health (NIH; grant numbers: 5K12HD043483, K01DA051683, K23DA047476, R01 AG043471), and Pharmaceutical Research and Manufacturers of America Foundation.
› Further Information
    Permissions and Reprints

Abstract

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.

Keywords

maternal mortality - analgesics - opioid - postpartum period - parental death - drug prescriptions

Declarations

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


Note

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.


* 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.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Gemmill A, Kiang MV, Alexander MJ. Trends in pregnancy-associated mortality involving opioids in the United States, 2007-2016. Am J Obstet Gynecol 2019; 220 (01) 115-116
    CrossrefPubMedGoogle Scholar
  • 2 Centers for Disease Control and Prevention (CDC). Pregnancy mortality surveillance system. Accessed September 20, 2020 at: https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm
    PubMedGoogle Scholar
  • 3 Perlow JH, Lesmes H. Maternal mortality: time for national action. Obstet Gynecol 2014; 123 (2, pt. 1): 362
    CrossrefPubMedGoogle Scholar
  • 4 Ray JG, Zipursky J, Park AL. Injury-related maternal mortality. Am J Obstet Gynecol 2018; 219 (03) 307-308
    CrossrefPubMedGoogle Scholar
  • 5 Koch AR, Rosenberg D, Geller SE. Illinois Department of Public Health Maternal Mortality Review Committee Working Group. Higher risk of homicide among pregnant and postpartum females aged 10-29 years in Illinois, 2002-2011. Obstet Gynecol 2016; 128 (03) 440-446
    CrossrefPubMedGoogle Scholar
  • 6 Palladino CL, Singh V, Campbell J, Flynn H, Gold KJ. Homicide and suicide during the perinatal period: findings from the National Violent Death Reporting System. Obstet Gynecol 2011; 118 (05) 1056-1063
    CrossrefPubMedGoogle Scholar
  • 7 Mangla K, Hoffman MC, Trumpff C, O'Grady S, Monk C. Maternal self-harm deaths: an unrecognized and preventable outcome. Am J Obstet Gynecol 2019; 221 (04) 295-303
    CrossrefPubMedGoogle Scholar
  • 8 Metz TD, Rovner P, Hoffman MC, Allshouse AA, Beckwith KM, Binswanger IA. Maternal deaths from suicide and overdose in Colorado, 2004-2012. Obstet Gynecol 2016; 128 (06) 1233-1240
    CrossrefPubMedGoogle Scholar
  • 9 Schiff DM, Nielsen T, Terplan M. et al. Fatal and nonfatal overdose among pregnant and postpartum women in Massachusetts. Obstet Gynecol 2018; 132 (02) 466-474
    CrossrefPubMedGoogle Scholar
  • 10 Smid MC, Stone NM, Baksh L. et al. Pregnancy-associated death in utah: contribution of drug-induced deaths. Obstet Gynecol 2019; 133 (06) 1131-1140
    CrossrefPubMedGoogle Scholar
  • 11 Goldman-Mellor S, Margerison CE. Maternal drug-related death and suicide are leading causes of postpartum death in California. Am J Obstet Gynecol 2019; 221 (05) 489.e1-489.e9
    CrossrefPubMedGoogle Scholar
  • 12 Tennessee Department of Health. Tennessee maternal mortality review of 2017 maternal deaths. Accessed September 20, 2020 at: www.tn.gov/content/dam/tn/health/documents/mch/MMR_Annual_Report_2017.pdf
    PubMedGoogle Scholar
  • 13 Osmundson SS, Min JY, Grijalva CG. Opioid prescribing after childbirth: overprescribing and chronic use. Curr Opin Obstet Gynecol 2019; 31 (02) 83-89
    CrossrefPubMedGoogle Scholar
  • 14 Becker NV, Gibbins KJ, Perrone J, Maughan BC. Geographic variation in postpartum prescription opioid use: opportunities to improve maternal safety. Drug Alcohol Depend 2018; 188: 288-294
    CrossrefPubMedGoogle Scholar
  • 15 Badreldin N, Grobman WA, Chang KT, Yee LM. Opioid prescribing patterns among postpartum women. Am J Obstet Gynecol 2018; 219 (01) 103.e1-103.e8
    CrossrefPubMedGoogle Scholar
  • 16 Prabhu M, Garry EM, Hernandez-Diaz S, MacDonald SC, Huybrechts KF, Bateman BT. Frequency of opioid dispensing after vaginal delivery. Obstet Gynecol 2018; 132 (02) 459-465
    CrossrefPubMedGoogle Scholar
  • 17 Jarlenski M, Bodnar LM, Kim JY, Donohue J, Krans EE, Bogen DL. Filled prescriptions for opioids after vaginal delivery. Obstet Gynecol 2017; 129 (03) 431-437
    CrossrefPubMedGoogle Scholar
  • 18 Bateman BT, Cole NM, Maeda A. et al. Patterns of opioid prescription and use after cesarean delivery. Obstet Gynecol 2017; 130 (01) 29-35
    CrossrefPubMedGoogle Scholar
  • 19 Osmundson SS, Min JY, Wiese AD. et al. Opioid prescribing after childbirth and risk for serious opioid-related events: a cohort study. Ann Intern Med 2020; 173 (05) 412-414
    CrossrefPubMedGoogle Scholar
  • 20 Ailes EC, Dawson AL, Lind JN. et al; Centers for Disease Control and Prevention (CDC). Opioid prescription claims among women of reproductive age–United States, 2008-2012. MMWR Morb Mortal Wkly Rep 2015; 64 (02) 37-41
    PubMedGoogle Scholar
  • 21 Desai RJ, Hernandez-Diaz S, Bateman BT, Huybrechts KF. Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol 2014; 123 (05) 997-1002
    CrossrefPubMedGoogle Scholar
  • 22 Bateman BT, Hernandez-Diaz S, Rathmell JP. et al. Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology 2014; 120 (05) 1216-1224
    CrossrefPubMedGoogle Scholar
  • 23 Ray WA, Griffin MR. Use of Medicaid data for pharmacoepidemiology. Am J Epidemiol 1989; 129 (04) 837-849
    CrossrefPubMedGoogle Scholar
  • 24 Cooper WO, Hernandez-Diaz S, Arbogast PG. et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006; 354 (23) 2443-2451
    CrossrefPubMedGoogle Scholar
  • 25 West SL, Savitz DA, Koch G, Strom BL, Guess HA, Hartzema A. Recall accuracy for prescription medications: self-report compared with database information. Am J Epidemiol 1995; 142 (10) 1103-1112
    CrossrefPubMedGoogle Scholar
  • 26 Johnson RE, Vollmer WM. Comparing sources of drug data about the elderly. J Am Geriatr Soc 1991; 39 (11) 1079-1084
    CrossrefPubMedGoogle Scholar
  • 27 Lopata SM, McNeer E, Dudley JA. et al. Hepatitis C testing among perinatally exposed infants. Pediatrics 2020; 145 (03) e20192482
    CrossrefPubMedGoogle Scholar
  • 28 Wiese AD, Huang X, Yu C. et al. Changes in otitis media episodes and pressure equalization tube insertions among young children following introduction of the 13-valent pneumococcal conjugate vaccine: a birth cohort-based study. Clin Infect Dis 2019; 69 (12) 2162-2169
    CrossrefPubMedGoogle Scholar
  • 29 Chung CP, Callahan ST, Cooper WO. et al. Individual short-acting opioids and the risk of opioid-related adverse events in adolescents. Pharmacoepidemiol Drug Saf 2019; 28 (11) 1448-1456
    CrossrefPubMedGoogle Scholar
  • 30 Wiese AD, Griffin MR, Schaffner W. et al. Long-acting opioid use and the risk of serious infections: a retrospective cohort study. Clin Infect Dis 2019; 68 (11) 1862-1869
    CrossrefPubMedGoogle Scholar
  • 31 Ray WA, Stein CM, Murray KT. et al. Association of antipsychotic treatment with risk of unexpected death among children and youths. JAMA Psychiatry 2019; 76 (02) 162-171
    CrossrefPubMedGoogle Scholar
  • 32 Charles MK, Cooper WO, Jansson LM, Dudley J, Slaughter JC, Patrick SW. Male sex associated with increased risk of neonatal abstinence syndrome. Hosp Pediatr 2017; 7 (06) 328-334
    CrossrefPubMedGoogle Scholar
  • 33 Ray WA, Chung CP, Murray KT, Hall K, Stein CM. High-dose citalopram and escitalopram and the risk of out-of-hospital death. J Clin Psychiatry 2017; 78 (02) 190-195
    CrossrefPubMedGoogle Scholar
  • 34 Epstein RA, Bobo WV, Martin PR. et al. Increasing pregnancy-related use of prescribed opioid analgesics. Ann Epidemiol 2013; 23 (08) 498-503
    CrossrefPubMedGoogle Scholar
  • 35 Roumie CL, Choma NN, Kaltenbach L, Mitchel Jr. EF, Arbogast PG, Griffin MR. Non-aspirin NSAIDs, cyclooxygenase-2 inhibitors and risk for cardiovascular events-stroke, acute myocardial infarction, and death from coronary heart disease. Pharmacoepidemiol Drug Saf 2009; 18 (11) 1053-1063
    CrossrefPubMedGoogle Scholar
  • 36 Cooper WO, Willy ME, Pont SJ, Ray WA. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol 2007; 196 (06) 544.e1-544.e5
    CrossrefPubMedGoogle Scholar
  • 37 Thapa PB, Whitlock JA, Brockman Worrell KG. et al. Prenatal exposure to metronidazole and risk of childhood cancer: a retrospective cohort study of children younger than 5 years. Cancer 1998; 83 (07) 1461-1468
    CrossrefPubMedGoogle Scholar
  • 38 Deyo RA, Hallvik SE, Hildebran C. et al. Association between initial opioid prescribing patterns and subsequent long-term use among opioid-naïve patients: a statewide retrospective cohort study. J Gen Intern Med 2017; 32 (01) 21-27
    CrossrefPubMedGoogle Scholar
  • 39 Centers for Disease Control and Prevention. Prescription drug overdose data & statistics guide to ICD-9-CM and ICD-10 codes related to poisoning and pain. Accessed October 7, 2020 at: https://stacks.cdc.gov/view/cdc/59394
    PubMedGoogle Scholar
  • 40 Patrick SW, Fry CE, Jones TF, Buntin MB. Implementation of prescription drug monitoring programs associated with reductions in opioid-related death rates. Health Aff (Millwood) 2016; 35 (07) 1324-1332
    CrossrefPubMedGoogle Scholar
  • 41 Calcaterra S, Glanz J, Binswanger IA. National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009. Drug Alcohol Depend 2013; 131 (03) 263-270
    CrossrefPubMedGoogle Scholar
  • 42 Roehrich-Patrick L, Moreo B. Just how rural or urban are Tennessee's 95 counties. Accessed October 7 2020 at: https://www.tn.gov/content/dam/tn/tacir/documents/2016JustHowRuralOrUrban.pdf
    PubMedGoogle Scholar
  • 43 Osmundson SS, Wiese AD, Min JY. et al. Delivery type, opioid prescribing, and the risk of persistent opioid use after delivery. Am J Obstet Gynecol 2019; 220 (04) 405-407
    CrossrefPubMedGoogle Scholar
  • 44 National Center for Chronic Disease Prevention and Health Promotion Center for Disease Control and Prevention. How does CDC identify severe maternal morbidity?. Accessed February 9, 2021 at: https://www.cdc.gov/reproductivehealth/maternalinfanthealth/smm/severe-morbidity-ICD.htm
    PubMedGoogle Scholar
  • 45 Arbogast PG, Ray WA. Performance of disease risk scores, propensity scores, and traditional multivariable outcome regression in the presence of multiple confounders. Am J Epidemiol 2011; 174 (05) 613-620
    CrossrefPubMedGoogle Scholar
  • 46 Cumpston M, Li T, Page MJ. et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev 2019; 10: ED000142
    PubMedGoogle Scholar
  • 47 Lee EW, Wei LJ, Amato DA. Cox-type regression analysis for large numbers of small groups of correlated failure time observations. In: Klein JP, Goel PK. eds. Columbus, OH: Survival Analysis: State of the Art Kluwer Academic Publishers; 1992: 237-247
    Google Scholar
  • 48 VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med 2017; 167 (04) 268-274
    CrossrefPubMedGoogle Scholar
  • 49 Lamping M, Gajus J, Gonzalez A. A project to reduce opioid administration for women in the postpartum period. Nurs Womens Health 2020; 24 (05) 325-331
    CrossrefPubMedGoogle Scholar
  • 50 ACOG Committee Opinion No. ACOG committee opinion no. 742: postpartum pain management. Obstet Gynecol 2018; 132 (01) e35-e43
    PubMedGoogle Scholar
  • 51 Bateman BT, Franklin JM, Bykov K. et al. Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naïve women. Am J Obstet Gynecol 2016; 215 (03) 353.e1-353.e18
    CrossrefPubMedGoogle Scholar
  • 52 Peahl AF, Morgan DM, Dalton VK. et al. New persistent opioid use after acute opioid prescribing in pregnancy: a nationwide analysis. Am J Obstet Gynecol 2020; 223 (04) 566.e1-566.e13
    CrossrefPubMedGoogle Scholar
  • 53 Mehta PK, Bachhuber MA, Hoffman R, Srinivas SK. Deaths from unintentional injury, homicide, and suicide during or within 1 year of pregnancy in Philadelphia. Am J Public Health 2016; 106 (12) 2208-2210
    CrossrefPubMedGoogle Scholar
  • 54 Patrick SW, Richards MR, Dupont WD. et al. Association of pregnancy and insurance status with treatment access for opioid use disorder. JAMA Netw Open 2020; 3 (08) e2013456
    CrossrefPubMedGoogle Scholar
  • 55 Saadeh FB, Clark MA, Rogers ML. et al. Pregnant and moving: understanding residential mobility during pregnancy and in the first year of life using a prospective birth cohort. Matern Child Health J 2013; 17 (02) 330-343
    CrossrefPubMedGoogle Scholar
  • 56 Bell ML, Belanger K. Review of research on residential mobility during pregnancy: consequences for assessment of prenatal environmental exposures. J Expo Sci Environ Epidemiol 2012; 22 (05) 429-438
    CrossrefPubMedGoogle Scholar
  • 57 Catalano A, Davis NL, Petersen EE. et al. Pregnant? Validity of the pregnancy checkbox on death certificates in four states, and characteristics associated with pregnancy checkbox errors. Am J Obstet Gynecol 2020; 222 (03) 269.e1-269.e8
    CrossrefPubMedGoogle Scholar
  • 58 Singh GK. Trends and social inequalities in maternal mortality in the United States, 1969-2018. Int J MCH AIDS 2021; 10 (01) 29-42
    CrossrefPubMedGoogle Scholar
  • 59 Badreldin N, Grobman WA, Yee LM. Racial disparities in postpartum pain management. Obstet Gynecol 2019; 134 (06) 1147-1153
    CrossrefPubMedGoogle Scholar
  • 60 St Marie B, Coleman L, Vignato JA, Arndt S, Segre LS. Use and misuse of opioid pain medications by pregnant and nonpregnant women. Pain Manag Nurs 2020; 21 (01) 90-93
    CrossrefPubMedGoogle Scholar
  • 61 Lapham G, Boudreau DM, Johnson EA. et al; PROUD Collaborative Investigators. Prevalence and treatment of opioid use disorders among primary care patients in six health systems. Drug Alcohol Depend 2020; 207: 107732
    CrossrefPubMedGoogle Scholar