Approximately 3 million vaginal deliveries occur every year in the United States, making it the most common indication for hospitalization.1 Pain after vaginal delivery frequently occurs but is generally short-lived and mild to moderate in severity, and nonopioid analgesics are recommended for pain management.2 Jarlenski and colleagues3 recently reported that among opioid-naive Medicaid patients undergoing vaginal delivery in Pennsylvania, 12% filled a prescription for opioids within 5 days postpartum. Of these women, only 28% had painful peripartum events such as tubal ligation, episiotomy, or higher order perineal lacerations. Nationwide data on opioid dispensing after vaginal delivery are lacking. Therefore, we undertook a descriptive study to examine patterns of opioid dispensing after vaginal delivery using a large, nationwide cohort of commercial insurance beneficiaries.
MATERIALS AND METHODS
The Truven Health Analytics MarketScan Commercial and Medicare Supplemental claims database includes patient demographics, insurance enrollment history, inpatient and outpatient medical claims, and outpatient prescription claims for nearly 13 million U.S. reproductive-aged women per year. The data come from a selection of large employers, health plans, and government and public organizations from all 50 states, Washington, DC, and Puerto Rico. The data are entered for billing purposes and coding is considered high-quality because the adjudication of the claim depends on accuracy; additional validation is performed after data entry to ensure accuracy of diagnosis and procedure codes.4 This claims database has been used in other pregnancy-related research.5
We identified all women hospitalized for vaginal delivery between 2003 and 2015 (all codes used to define study variables are included in Box 1). Patients in the cohort were required to have continuous medical and prescription drug benefit coverage from 12 weeks before the delivery admission (baseline period) until at least 1 week after discharge. We excluded women with a diagnosis of opioid or other substance use disorder, use of methadone, buprenorphine, or prescription opioids during the baseline period as well as women who underwent peripartum hysterectomy or had a code for cesarean delivery.
International Classification of Diseases, 9th Revision, and Current Procedural Terminology Codes for Diagnoses and List of Medications
Vaginal delivery: ICD-9 codes V27.x AND 650; or V27.x AND CPT codes 59400, 59409, 59410, 59610, 59612, or 59614
Bilateral tubal ligation: ICD-9 code 66.3x, 66.4, 66.5, 66.6 or CPT codes 58600, 58605, 58611, 58615
Higher order perineal laceration: ICD-9 code 664.2, 664.2x, 664.3, 664.3x
Operative vaginal delivery: ICD-9 code 72.0, 72.1, 72.21, 72.29, 72.31, 72.39, 72.7, 72.71, 72.79, 72.8, 72.9, 669.5, 763.2
Opioid use disorder: ICD-9 code 304.0, 304.00, 304.01, 304.02, 304.03, 304.7, 304.70, 304.71, 304.72, 304.73, 305.5, 305.50, 305.51, 305.52, 305.53
Peripartum hysterectomy: ICD-9 code 68.3, 68.4, 68.6, 68.39, 68.49, 68.69
Cesarean delivery: ICD-9 code 74.0, 74.1, 74.2, 74.4, 74.9, or 74.99; OR CPT codes 59510, 59514, 59515, 59620, or 59622
Substance use disorder: ICD-9 code 304.1, 304.10, 304.11, 304.12, 304.13, 304.2, 304.20, 304.21, 304.22, 304.23, 304.3, 304.30, 304.31, 304.32, 304.33, 304.40, 304.41, 304.42, 304.43, 304.5, 304.50, 304.51, 304.52, 304.53, 304.6, 304.60, 304.61, 304.62, 304.63, 304.8, 304.80, 304.81, 304.82, 304.83, 304.9, 304.90, 304.91, 304.92, 304.93
Smoking: ICD-9 code 305.1, 649.0, 649.00, 649.01, 649.02, 649.03, 649.04, V15.82, 989.84, or CPT codes 99406, 99407, G0436, G0437, 9016, 1034F, 4001F, 4004F, G9276, G9458, S4995, S9453
Anxiety disorders: ICD-9 code 300.00, 300.01, 300.02, 300.09, 300.20, 300.21, 300.22, 300.23, 300.29, 300.3, 308.0, 308.1, 308.2, 308.3, 308.4, 308.9, 309.81
Mood disorders: ICD-9 code 296.00, 296.01, 296.02, 296.03, 296.04, 296.05, 296.06, 296.10, 296.11, 296.12, 296.13, 296.14, 296.15, 296.16, 296.20, 296.21, 296.22, 296.23, 296.24, 296.25, 296.26, 296.30, 296.31, 296.32, 296.33, 296.34, 296.35, 296.36, 296.40, 296.41, 296.42, 296.43, 296.44, 296.45, 296.46, 296.50, 296.51, 296.52, 296.53, 296.54, 296.55, 296.56, 296.60, 296.61, 296.62, 296.63, 296.64, 296.65, 296.66, 296.7, 296.80, 296.81, 296.82, 296.89, 296.90, 296.99, 300.4, 311
Use of SSRI, SNRI, TCA, other antidepressants: sertraline, fluoxetine, paroxetine, citalopram, escitalopram, amitriptyline, perphenazine–amitriptyline, nortriptyline, venlafaxine, desvenlafaxine, duloxetine, bupropion, clomipramine, amoxapine, desipramine, doxepin, trimipramine, imipramine, fluvoxamine, mirtazapine, nefazodone, trazodone
Use of benzodiazepines: alprazolam, lorazepam, clobazam, clonazepam, estazolam, quazepam, chlordiazepoxide, clorazepate, midazolam, oxazepam, flurazepam, triazolam, temazepam
ICD-9, International Classification of Diseases, 9th Revision; CPT, Current Procedural Terminology; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant.
We calculated the proportion (and 95% CI) of women who had an oral opioid (tablet, capsule, or liquid formulation) dispensed within 7 days of discharge and the median (interquartile range and 10th–90th percentile ranges) total oral morphine milligram equivalent dose dispensed in this prescription.6 We investigated the relationship between calendar year and the proportion dispensed an opioid using a linear trend test.
We described patient characteristics, selected a priori, of women with and without an opioid prescription including the following: maternal age, geographic region (U.S. Census regions of South, West, Northeast, Midwest, or unknown), delivery year, delivery characteristics that may be associated with additional pain (tubal ligation, operative vaginal delivery, or higher order perineal laceration—third- or fourth-degree) as well as other comorbidities that have been previously related to opioid use (smoking, anxiety disorders, mood disorders, use of antidepressants, use of benzodiazepines). We performed multivariable logistic regression analysis to evaluate the independent association between each of these variables and having an opioid dispensed. Use of antidepressants was defined as dispensing of a selective serotonin reuptake inhibitor, serotonin norepinephrine reuptake inhibitor, tricyclic antidepressant, or other antidepressant in the 12 weeks before admission for delivery. Use of benzodiazepines was similarly defined during the same interval. We examined the median morphine milligram equivalent dose dispensed by each delivery characteristic that may be associated with additional pain.
To examine the frequency of opioid refills, we restricted the cohort to women with a follow-up period at least 6 weeks and calculated the proportion (and 95% CI) of women receiving at least one opioid refill.
All analyses were conducted using the Aetion platform r2.4, which has been validated for a range of studies including observational cohort studies, and SAS 9.4.7 The use of this deidentified database was approved by the Partners Human Research Committee.
Among the 1,345,244 vaginal deliveries included in the cohort between 2003 and 2015 (Fig. 1), 383,374 (28.5%; 95% CI 28.4–28.6%) had an opioid dispensed within 7 days of discharge. During the period of analysis, the frequency of opioid dispensing increased from 26.7% (95% CI 26.2–27.1%) in 2003 to 29.3% (95% CI 29.0–29.6%) in 2015 (P<.001 for trend). The most commonly dispensed opioids were hydrocodone (44.7% [95% CI 44.5–44.8%]), oxycodone (34.6% [95% CI 34.5–34.8%]), and codeine (13.1% [95% CI 13.0–13.2%]) (Fig. 2). Tubal ligation, operative vaginal delivery, and higher order perineal laceration occurred among 18.0% of women dispensed opioids (Table 1).
In multivariable regression analysis, the adjusted odds ratio (OR) for filling an opioid was 4.70 (95% CI 4.63–4.77) among women from the South, adjusted OR 2.94 (95% CI 2.90–2.99) among women from the West, and adjusted OR 2.77 (95% CI 2.72–2.81) among women from the Midwest region as compared with women from the Northeast (Table 2). Women using benzodiazepines or antidepressants also had greater odds of filling an opioid after vaginal delivery (adjusted OR 1.87 [95% CI 1.73–2.02] and adjusted OR 1.63 [95% CI 1.59–1.66], respectively). Characteristics potentially associated with increased pain after vaginal delivery—tubal ligation, operative vaginal delivery, and third- or fourth-degree perineal laceration—were also associated with an increased odds of having an opioid dispensed with the highest odds among women undergoing tubal ligation (adjusted OR 3.77, 95% CI 3.67–3.87) (Table 2).
The median total opioid dose dispensed was 150 morphine milligram equivalents (interquartile range 113–225; 10th–90th percentile 80–345) (Fig. 3). This dose is equivalent to prescribing a median 20 (interquartile range 15–30, 10th–90th percentile 11–46) tablets of 5 mg oxycodone. The median morphine milligram equivalent dose was 150 morphine milligram equivalents for each delivery characteristic potentially associated with pain.
Follow-up data to 6 weeks were available for 1,282,135 women (95.3% of initial cohort) and baseline characteristics in this subset were similar to the overall cohort (data not shown). The frequency of opioid dispensing was 28.6% (95% CI 28.5–28.6%), and the median total opioid dose dispensed was 150 morphine milligram equivalents (interquartile range 113–225, 10th–90th percentile 80–345). Among the 366,691 women with at least 6 weeks follow-up who were dispensed an opioid at the time of discharge after vaginal delivery, 8.5% (95% CI 8.4–8.6%) had at least one refill within 6 weeks.
Nearly 30% of women undergoing vaginal deliveries in this nationwide sample of commercially insured beneficiaries were dispensed an opioid after their delivery hospitalization, often in high quantities. Additional procedures at the time of vaginal delivery, which may be associated with increased pain, accounted for less than one fifth of the cases where opioids were dispensed. The median opioid dose dispensed was the same after deliveries with additional procedures or complications as those without these features. The proportion of patients dispensed an opioid was stable over the study interval.
Excessive opioid use unnecessarily exposes women to these addictive medications and generates leftover medications that are available for misuse or diversion.8 Multiple studies suggest that opioid exposure for acute indications can be a trigger for long-term opioid use and misuse.9–11 Furthermore, the most common source of opioids used nonmedically is from family or friends, likely from leftover medication from legitimate prescriptions.12 Given these risks, it is imperative for clinicians to consider whether an opioid is necessary for the treatment of pain or whether other, safer analgesics such as acetaminophen or nonsteroidal antiinflammatory drugs are adequate. Pain for the great majority of patients after vaginal delivery is in the mild-to-moderate range, suggesting that use of opioids in this clinical setting should be rare.2
When prescribed, guidelines suggest that opioids should be dispensed at the lowest effective dose for the shortest duration necessary to treat anticipated severe pain.13 We found the median opioid dose prescribed to be 150 morphine milligram equivalents, equivalent to 20 tablets of 5 mg oxycodone; at the 90th percentile, the amount prescribed was equivalent to 46 tablets. A recent analysis of 99 primiparous women after vaginal delivery found that for those using opioids, the median time to opioid cessation was less than 1 day (interquartile range 0–2) after delivery.2 These data suggest that the quantity of opioids prescribed after vaginal delivery greatly exceeds the needs for postpartum pain management for most women.
Notably, codeine accounted for 15.2% of opioids dispensed after vaginal delivery in our data in 2015. This is worrisome in light of the U.S. Food and Drug Administration's warning against the use of codeine among breastfeeding women given variable metabolism and risk to the breastfed infant.14 Specifically, infants of mothers who are “ultrarapid” metabolizers of codeine are at risk for respiratory depression, and rare cases of neonatal deaths have been attributed to exposure to codeine through breast milk.
We also observed strong regional differences in opioid dispensation with women in the South, West, and Midwest regions having much higher odds of opioid dispensing than those in the Northeast. These regional differences are consistent with other data analyzing contemporary opioid prescribing from pharmacy records, which highlight the South and West as regions of high opioid prescribing.15,16 Although the frequency of opioid dispensings after vaginal delivery in our national cohort of commercially insured beneficiaries are twice as high as the 12% observed by Jarleenski et al3 among Medicaid beneficiaries in Pennsylvania, the proportion among commercially insured beneficiaries in the state of Pennsylvania was similar (14.8%, 95% CI 14.5–15.1%). Similar to our findings, pain-inducing delivery complications and procedures such as bilateral tubal ligation, perineal laceration, and episiotomy were associated with receiving an opioid prescription in Pennsylvania, but they were not associated with the number of days supplied.
Our study is subject to limitations inherent in its design. First, our analysis describes opioid dispensings when a prescription drug benefit was used. This analysis inherently does not capture the number of opioid prescriptions written and not filled or filled and paid for out of pocket. Moreover, the quantity of opioids consumed (as opposed to dispensed) cannot be determined from these data. The results of our analysis are generalizable only to opioid-naive women with commercial insurance with a prescription drug benefit. Because a significant proportion of U.S. deliveries are covered by Medicaid, nationwide analyses of opioid prescribing and dispensing after vaginal delivery in this population are also needed. Finally, the procedure and diagnostic codes used to define deliveries favored specificity over sensitivity, because a linkage to infants (which is sometimes used in claims-based studies to confirm that the encounter resulted in a birth) was not done for these analyses.
Assuming our results are generalizable to all women delivering vaginally in the United States, our results suggest that approximately 850,000 women are dispensed an opioid prescription each year. Given the large number of vaginal deliveries each year, curbing unnecessary opioid prescribing in this clinical situation could have a significant public health effect.
1. Martin J, Hamilton B, Osterman M, Driscoll A, Matthews TJ. Births: final data for 2015. Natl Vital Stat Rep 2017;66:1.
2. Komatsu R, Carvalho B, Flood PD. Recovery after nulliparous birth: a detailed analysis of pain analgesia and recovery of function. Anesthesiology 2017;127:684–94.
3. Jarlenski M, Bodnar LM, Kim JY, Donohue J, Krans EE, Bogen DL. Filled prescriptions for opioids after vaginal delivery. Obstet Gynecol 2017;129:431–7.
4. Hansen L. The Truven Health MarketScan databases for life sciences researchers. White paper. Truven Health Analytics. Available at: https://truvenhealth.com/Portals/0/Assets/2017-MarketScan-Databases-Life-Sciences-Researchers-WP.pdf
. Retrieved April 13, 2018.
5. Tepper NK, Boulet SL, Whiteman MK, Monsour M, Marchbanks PA, Hooper WC, et al. Postpartum venous thromboembolism: incidence and risk factors. Obstet Gynecol 2014;123:987–96.
6. Von Korff M, Korff MV, Saunders K, Thomas Ray G, Boudreau D, Campbell C, et al. De facto long-term opioid therapy for noncancer pain. Clin J Pain 2008;24:521–7.
7. Wang SV, Verpillat P, Rassen JA, Patrick A, Garry EM, Bartels DB. Transparency and reproducibility of observational cohort studies using large healthcare databases. Clin Pharmacol Ther 2016;99:325–32.
8. Kennedy-Hendricks A, Gielen A, McDonald E, McGinty EE, Shields W, Barry CL. Medication sharing, storage, and disposal practices for opioid medications among US adults. JAMA Intern Med 2016;176:1027–9.
9. Bateman BT, Franklin JM, Bykov K, Avorn J, Shrank WH, Brennan TA, et al. Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naive women. Am J Obstet Gynecol 2016;215:353.e1–18.
10. Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med 2016;176:1286–93.
11. Brat GA, Agniel D, Beam A, Yorkgitis B, Bicket M, Homer M, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. BMJ 2018;360:j5790.
12. Jones CM, Paulozzi LJ, Mack KA. Sources of prescription opioid pain relievers by frequency of past-year nonmedical use United States, 2008–2011. JAMA Intern Med 2014;174:802–3.
13. Centers for Disease Control and Prevention. CDC guideline for prescribing opioids for chronic pain—United States, 2016. Available at: https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm
. Retrieved January 24, 2018.
14. U.S. Food and Drug Administration. Use of codeine and tramadol products in breastfeeding women—questions and answers. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm118113.htm
. Retrieved July 31, 2017.
15. Guy GP. Vital signs: changes in opioid prescribing in the United States, 2006–2015. Available at: https://www.cdc.gov/mmwr/volumes/66/wr/mm6626a4.htm
. Retrieved April 3, 2018.
16. McDonald DC, Carlson K, Izrael D. Geographic variation in opioid prescribing in the U.S. J Pain 2012;13:988–96.