Risk of Death at 1 Year Following Postpartum Opioid Exposure

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

Maternal Opioid Use Disorder and the Risk of Postneonatal Infant Mortality

“…These data were supplemented with birth and death certificates and data from the Tennessee Hospital Discharge Data System, an all-payers statewide registry of all hospital-based encounters in the state. This linked-data platform has been used widely in previous pharmacoepidemiology studies of pregnant individuals and children …”

“…This linked-data platform has been used widely in previous pharmacoepidemiology studies of pregnant individuals and children. [15][16][17][18] This study included infants born in Tennessee hospitals from 2007 through 2018 to individuals 15 to 44 years old with continuous TennCare enrollment (no gaps for more than 30 days) from 183 days prior to birth through 28 days postbirth (baseline period). To mitigate the influence of extreme prematurity on our assessment, we excluded infants outside the range of 28 to 42 weeks' gestation or with birth weight less than 1500 g. 19 Our cohort comprised infants who were alive at day 29 postbirth (cohort entry, t0) (eFigure in Supplement 1).…”

New Persistent Opioid Use After Childbirth

“…4,5,[9][10][11] In addition, long-term opioid use after delivery may be associated with adverse events, including unintended persistent use, opioid use disorder, and even opioid-related death. 12,13 Because more than 80% of women will have at least one birth by their mid-40s, postpartum opioid use has the potential to affect a major portion of the population. 1 In addition, awareness of factors associated with persistent opioid use after delivery might promote safer prescribing without jeopardizing pain control.…”

“…4,5,9–11 In addition, long-term opioid use after delivery may be associated with adverse events, including unintended persistent use, opioid use disorder, and even opioid-related death. 12,13…”