Health Reports
Association between mothers’ postoperative opioid prescriptions and opioid-related events in their children: A population-based cohort study

by Jennifer Bethell, Mark D. Neuman, Brian T. Bateman, Karim S. Ladha, Andrea Hill, Guohua Li, Duminda N. Wijeysundera, and Hannah Wunsch

DOI: https://www.doi.org/10.25318/82-003-x202000600002-eng

In Ontario, in 2017, there were 1,276 emergency department visits for opioid poisoning among people younger than 25. Among those aged 15 to 24, the rate more than doubled between 2013 and 2017.^{Note 1} Both Canadian and American data suggest that people younger than 25 may be experiencing disproportionate opioid-related harms. This age group makes up roughly 1 in 10 of those who were dispensed an opioid, but accounts for 1 in 5 emergency department presentations for opioid poisoning.^{Note 2Note 3Note 4} This difference may be related, in part, to illicit opioid use, but evidence also supports another explanation—that some youth access opioids that have been prescribed to others in the household. Survey data from both countries show that, among youth who use opioids, the most common source of these opioids was family or friends.^{Note 5Note 6} Two case–control studies (also from Canada and the United States) have shown that opioid prescriptions to family members are associated with an increased risk of hospital-treated overdoses in children^{Note 7Note 8} and young adults.^{Note 8}

Postoperative prescriptions are a potentially significant source of opioids. Pain after surgery is one of the most common reasons for initiating opioid use,^{Note 9Note 10} but these prescriptions tend to exceed patient need. Therefore, these medications often go unfinished,^{Note 11} and unused medications are then stored—unsecured—at home.^{Note 12} A systematic review of studies describing postoperative opioid oversupply found that, across six studies, 67% to 92% of patients reported having unused opioids, and 42% to 71% of opioids went unused.^{Note 13}

The objective of this study was to examine the association between mothers’ postoperative opioid prescriptions and opioid-related emergency department presentations or inpatient admissions by their children (aged 1 to 24 years).

Methods

Study sample

This retrospective cohort used population-based data from Ontario, Canada, which included residents eligible for universal health care coverage (nearly the entire population of roughly 14 million people) and captured inpatient admissions (Discharge Abstract Database [DAD]), same-day surgical procedures (Same Day Surgery [SDS] Database), opioid prescriptions (Narcotics Monitoring System [NMS]), emergency department presentations (National Ambulatory Care Reporting System), deaths (Office of the Registrar General – Deaths) and individual-level demographic information (Registered Persons Database). These datasets were linked using unique encoded identifiers and analyzed at ICES (a not-for-profit research institute formerly known as the Institute for Clinical Evaluative Sciences). The use of data in this project was authorized under section 45 of Ontario’s Personal Health Information Protection Act, which does not require review by a research ethics board.

The cohort was defined using the DAD and SDS surgical records^{Note 14Note 15} of females aged 15 to 64 years who had a hospital stay of seven days or less and were discharged home. The accrual period (discharge dates between July 2013 and March 2017) was selected to coincide with the introduction of the NMS in 2012, as well as with the necessary one-year review of these data (see exclusions below). Only one surgical record was retained for each individual. For those with multiple surgeries during the study period, only the first was considered for inclusion. The records of these individuals were then linked to those of their children (aged 1 to 24 years at the time of surgery) using the ICES-derived MOMBABY database, which has linked the inpatient records of delivering mothers and their newborns for births in Ontario since 1988. There are no comparable linkages for fathers or other household members. Young adults—up to age 24—were also included in the cohort, as 62.6% of Canadians aged 20 to 24 still live with their parents, but the proportion declines precipitously thereafter.^{Note 16} If the same individual appeared in both cohorts, she was excluded from the mother cohort (and all of her children were subsequently removed from the children cohort). Mothers and all of their children were excluded if either had (1) filled any opioid prescription (including for methadone or buprenorphine) within one year prior to the surgery (i.e., to create an opioid-naïve cohort), (2) experienced an opioid-related event^{Note 17} within one year prior to the surgery (see appendix) or (3) died within one year of the surgery (i.e., to ensure complete follow-up).

Measures

Exposure, i.e., a mother’s postoperative opioid analgesic prescription, was defined as a prescription for oral tablet forms of codeine, fentanyl, hydromorphone, meperidine, morphine, oxycodone, pentazocine, tapentadol or tramadol filled within seven days of the surgery (i.e., on the surgery discharge date or within the six subsequent days). The first prescription filled during these seven postoperative days was defined as the index prescription. If more than one opioid prescription was filled on the first day, all records were retained. The primary outcome was an opioid-related event^{Note 17} within one year of the mother’s surgery discharge date or index prescription date (as applicable). Opioid-related events included emergency department presentations and inpatient admissions for opioid poisoning, or mental and behavioural disorders resulting from opioid use (see appendix for a list of diagnosis codes). Information on age, sex and residential postal code of the mothers and children at the time of surgery was also retained. Postal codes were used to assign rural residence (community with a population of fewer than 10,000 people) and neighbourhood income quintile.^{Note 18} Mothers’ Charlson comorbidity scores were determined using data from the index surgical record,^{Note 19} and their surgeries were categorized by year, as either inpatient or outpatient, and according to the Canadian Classification of Health Interventions.^{Note 20} Index prescriptions were described according to days’ supply and total morphine milligram equivalent (MME)^{Note 21} dose and categorized by type (codeine, hydromorphone, morphine, oxycodone, tramadol, other or multiple).

Statistical analysis

Frequencies and proportions (with chi-square tests) means and standard deviations (with t-tests) and medians and interquartile ranges (IQR) were reported to describe characteristics of the mothers and children. The association between mothers’ postoperative opioid prescriptions and the risk of opioid-related events in their children was assessed using logistic regression, first unadjusted, then adjusted for child’s age, mother’s age, rural residence and neighbourhood income quintile—variables selected based on previous findings.^{Note 1Note 2Note 3Note 4Note 22} Four sensitivity analyses were conducted: (1) to account for the potential clustering of children (by mother), one child was randomly selected per mother; (2) to assess for likely diversion (rather than unintentional poisoning), the analysis was restricted to children aged 12 to 24 years; (3) to acknowledge the unique postoperative context of the first year postpartum (i.e., mother’s new baby or child’s new sibling), children of mothers who underwent a caesarean section were excluded; and, (4) to account for the possibility of opioid-related deaths, the cohort was recreated without applying the final exclusion, and opioid-related deaths were included in the outcome. Statistical significance was interpreted at p<0.05. Analyses were carried out using SAS software, Version 9.4 (SAS Institute, Cary, North Carolina).

Results

Cohort characteristics

After exclusions were applied (see Figure 1), the cohort consisted of 283,550 children (see Table 1) linked to 170,156 mothers (see Table 2). Overall, 60.4% of the children had mothers who filled a postoperative opioid prescription. The children of mothers who filled a prescription were older, had older mothers, and were more likely to live in non-rural areas and higher-income neighbourhoods. The most commonly dispensed opioids were oxycodone, codeine, tramadol and hydromorphone, which together accounted for 92.6% of postoperative opioid prescriptions. The median prescription duration was three days (IQR:3 to 5 days) and the median total MME was 150.0 (IQR:112.5 to 225.0).

Opioid-related events

Opioid-related events in children in the first year after a mother’s surgery were rare (n=36/283,550, 0.01%). However, the incidence of opioid-related events was higher among the children of mothers who filled a postoperative opioid prescription (n=29/171,139, 0.02% vs. n=7/112,411, 0.01%; unadjusted odds ratio [OR] 2.72 [1.19 to 6.21] p=0.02), including in the adjusted analysis (adjusted OR 2.42 [95% CI, 1.05 to 5.54], p=0.04) (see Table 3). Sensitivity analyses produced similar results, although some associations lost statistical significance (see Table 3). Nevertheless, the unadjusted, adjusted and sensitivity analyses’ odds ratio estimates all fell between 2 and 3. The differences observed were not entirely explained by adjustment variables or clustering (by mother) and also held for specific subpopulations within the cohort.

Discussion

Incidence of opioid-related events in children in the first year after their mother’s surgery was low overall, but comparable to previously published estimates.^{Note 1} However, the children of mothers who filled a postoperative opioid prescription had an increased risk of an opioid-related event during this time. These results mirror findings from two previous case–control studies that found that the presence of household opioid prescriptions more than doubles the risk of opioid overdose.^{Note 7Note 8} However, the focus on surgery identifies a specific context for opioid prescribing and intervention.

Strengths of this study include a large, population-based cohort assembled through a unique mother–child linkage. The results likely generalize to other populations, particularly where the over-prescribing of opioids after surgery appears to be common.^{Note 23} In particular, beyond the Canadian context, recent data show that comparable proportions of Canadian and American patients are dispensed a postoperative opioid prescription. However, American patients received significantly higher total quantities of opioids,^{Note 19} suggesting an even greater opportunity for diversion.

However, this study has limitations. First, there was no direct measure of whether children lived with their mother or accessed their mother’s prescription opioids. Second, similar to previously published estimates for this age group and time period,^{Note 1} opioid-related events were rare. Health administrative data are widely used for researching and reporting opioid-related harms,^{Note 1Note 2Note 3Note 4} but include only those who present to hospital. These data likely underestimate the actual extent of opioid diversion in this population, particularly for older children who may be less likely to present to hospital in the context of opioid use^{Note 1Note 2Note 3Note 4Note 5Note 6} or self-harm.^{Note 24} Furthermore, given the infrequency of the outcome, the analyses were not elaborated upon, including to disaggregate events by intent (e.g., self-harm or unintentional poisoning), assess risk according to opioid prescription characteristics (e.g., type of opioid, dose–response relationship or number of refills), analyze trends over time, test hypotheses of mediation or stratify analyses to examine specific subpopulations of mothers and children—all of which merit further research. Still, these data provide some insights into prescription opioid availability for nonmedical use, which is an area that typically relies on survey data and represents a key data gap in addressing public health issues associated with opioid analgesics.^{Note 25} Third, there may be residual confounding. However, a previous case–control study that assessed the association between opioid prescriptions to family members and opioid overdoses and included a range of covariates reported almost identical unadjusted and adjusted odds ratios.^{Note 8} Regardless, the potential impact of opioid use in other household members^{Note 26} could not be assessed with these data.

Opioids are important for managing pain after surgery. However, concerns over the potential negative impacts of excessive opioid prescribing in this context have prompted efforts to reduce these prescriptions, including through interventions implemented at the individual, health care system and policy levels. These findings suggest that postoperative opioid prescriptions may contribute to opioid-related events among others in the household. These results have implications for both clinical practice and future research. First, taken in context with the tendency for postoperative opioid prescriptions to exceed patient need,^{Note 11Note 12Note 13} these results reinforce the importance of “right-sized” postoperative opioid prescriptions and further highlight the roles of prescribers, dispensers and public health campaigns in educating patients and the public about the safe use, storage and disposal of these medications.^{Note 27Note 28} For research purposes, better evidence is needed to establish optimal postoperative opioid prescribing practices and develop interventions to support their implementation.^{Note 29}

Funding statement

This study was funded by the National Institute on Drug Abuse, National Institutes of Health (grant number 1R01DA042299-01A1 to HW, BB, MDN, GL and DNW). This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported in this paper are those of the authors and do not reflect those of the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this study are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI) and the Ontario Office of the Registrar General (ORG). However, the analyses, conclusions, opinions and statements expressed in this study are those of the authors and not necessarily those of CIHI or ORG. The authors would like to thank IMS Brogan Inc. for the use of its Drug Information Database. Dr. Wunsch is supported by an Excellence in Research Award from the Department of Anesthesia at the University of Toronto. Dr. Wijeysundera is supported in part by a New Investigator Award from the Canadian Institutes of Health Research, an Excellence in Research Award from the Department of Anesthesia at the University of Toronto, and the Endowed Chair in Translational Anesthesiology Research at St. Michael’s Hospital and the University of Toronto.

Appendix