Search the Library

This is the primary outcomes article for CTN-0080-A-2. Introduction: Racial and ethnic inequities persist in medication treatment initiation and adherence for pregnant and postpartum people with opioid use disorder (OUD). Our objective was to understand the experiences of “positive outliers,” specifically pregnant and postpartum people of color with OUD who utilized medication treatment and engaged in a randomized clinical trial for buprenorphine despite historical, cultural, and structural barriers.

Methods: We conducted two sets of semi-structured qualitative interviews. First, trained peers with lived expertise as mothers in recovery interviewed individuals who identified with a non-white race and/or ethnicity and enrolled in the Medication Treatment for OUD in Expectant Mothers (MOMs) trial (NCT03918850). Second, we interviewed principal investigators, clinicians, and research coordinators from the 13 MOMs trial sites. We used an inductive thematic approach informed by the Social Ecological Model of Racism and Anti-Racism. Transcripts were double-coded and reviewed until consensus was reached. Preliminary findings from participant and staff interviews were merged and triangulated with peers to inform theme development.

Results: We completed 17 interviews with MOMs trial participants from 7 sites. Participants identified as Hispanic (29%), Black non-Hispanic (24%), multi-racial Hispanic (18%), multi-racial non-Hispanic (18%), and American Indian, Native Hawaiian, or Pacific Islander (12%). Thirty-two interviews with trial staff were also completed. Three themes emerged: (1) Although some participants expected racist treatment and research exploitation, all participants interviewed reported non-discriminatory, non-judgmental care within the MOMs trial; (2) Compassionate care, frequent, personalized, and integrated encounters, and emotional support helped counteract prior stigmatizing and discriminatory health care interactions, enabling participants of color to feel particularly supported, trusted, and empowered during the MOMs trial; and (3) Despite pervasive cultural stigma around addiction and concerns about taking an investigational drug while pregnant, participants expressed that pregnancy status, care team trust, and transparent communication with MOMs trial staff encouraged medication utilization and adherence.

Conclusion: Facilitators of successful engagement in the MOMs trial and retention in medication treatment among pregnant and postpartum people of color with OUD included non-judgmental care, sustained trust, and frequent contact. Key perinatal OUD clinical interventions and trial improvements include personalized communication and scheduling flexibility to promote engagement of marginalized populations.

Related protocols: CTN-0080-A-2

This is the primary outcomes article for CTN-0080. Importance: Treating opioid use disorder (OUD) in pregnancy with sublingual buprenorphine is an evidence-based practice, but it has disadvantages that could be addressed with an extended-release formulation.

Objective: To evaluate the effectiveness and safety of extended-release buprenorphine vs sublingual buprenorphine for OUD in pregnancy through 12 months post partum.

Design, setting, and participants: This 2-group, open-label, noninferiority, randomized clinical trial was conducted between July 2, 2020, and October 30, 2024, among adults with OUD and a singleton pregnancy of 6 to 30 weeks’ gestational age at 13 outpatient cross-disciplinary peripartum OUD treatment sites.

Interventions: Randomization to sublingual or extended-release buprenorphine (weekly formulation during pregnancy, monthly formulation optional post partum if not breastfeeding).

Main outcomes and measures: The primary and key secondary outcomes were illicit opioid abstinence during pregnancy and the postpartum period, respectively, defined as the proportion of weekly collected urine samples negative for illicit opioids. If noninferiority was demonstrated at a margin of 0.15, testing for superiority was planned. Key secondary infant outcomes from medical records were opioid treatment for neonatal opioid withdrawal syndrome (NOWS; yes or no) and number of opioid treatment days for NOWS.

Results: Among 140 randomized participants, the mean (SD) age was 31.2 (4.6) years. There were 10 Black participants (7.1%), 10 Hispanic participants (7.1%), 116 (82.9%) White participants, and 14 participants (10.0%) who belonged to additional groups. All but 2 were already prescribed sublingual buprenorphine. Study completion was 98% through pregnancy (137 participants) and 81% through 12 months post partum (114 participants). Illicit opioid abstinence was higher during pregnancy for participants receiving extended-release vs sublingual buprenorphine (82.5% vs 72.6%; mean difference, 9.84 [95% CI, 1.72 to 17.95] percentage points; P = .009). Postpartum abstinence rates declined and were similar in both groups (60.2% vs 59.5%; mean difference, 0.65 [98% CI, -12.72 to 14.02] percentage points; P = .45). Those receiving extended-release buprenorphine experienced fewer serious adverse events during pregnancy (8.7% vs 26.8%; P = .007) and post partum (6.0% vs 18.6%; P = .04). Nonserious adverse events rates did not differ between groups, but more were deemed medication-related for extended-release participants during pregnancy (26.1% vs 7.0%; P = .003). Infants exposed to extended-release vs sublingual buprenorphine did not differ in need for opioid treatment (30.2% vs 26.5%; relative risk, 1.14 [98% CI, 0.54 to 1.99]; P = .64) or mean (SE) treatment days (10.9 [2.2] vs 14.8 [3.0] days; relative risk, 0.73 [98% CI, 0.36 to 1.51]; P = .28). At birth, extended-release-exposed neonates had larger mean (SE) head circumferences than those exposed to sublingual buprenorphine (34.0 [0.2] vs 33.4 [0.2] cm; mean difference, 0.63 [95% CI, -0.00 to 1.26] cm; P = .049).

Conclusions and relevance: The findings of this randomized clinical trial support weekly extended-release buprenorphine for OUD treatment during pregnancy.

Related protocols: CTN-0080

Objective: Identify sociodemographic and substance use characteristics associated with pregnancy intention and explore the relationship between pregnancy intent and postpartum contraception interest among pregnant individuals with opioid use disorder (OUD).

Methods: Secondary analysis of baseline data collected in the Medication Treatment for OUD in Expectant Mothers trial (CTN-0080), which evaluated injectable versus sublingual buprenorphine. Current pregnancy intention was classified as “intended,” “mistimed,” “unwanted,” or “ambivalent.” Postpartum contraceptive interest was categorized into highly effective, effective, less effective, or none. Participant characteristics and contraceptive interest was compared across intention categories using Fisher’s Exact and Kruskal-Wallis tests.

Results: Of 155 participants who completed baseline screening, 137 (88%) did not report any contraceptive use prior to their current pregnancy. Twenty-eight percent reported intended pregnancies, 27% mistimed, 15% never wanted, and 30% were ambivalent towards their current pregnancy. Individuals reporting intended pregnancies disclosed less substance use in the past ninety days and twelve months compared to other categories. Forty-seven percent of participants desired highly effective contraception after delivery, 28% desired effective contraception, 4% desired less effective contraception, and 21% did not desire any contraception. Participants reporting an unwanted pregnancy were significantly more interested in sterilization, while participants reporting a mistimed pregnancy were significantly more interested in a postpartum long-acting reversible contraception.

Conclusions: Our findings that individuals with intended pregnancies report less recent substance use suggests that reproductive health decision-making may be difficult to prioritize during periods of active addiction. In addition, the lack of association between pregnancy intention and postpartum contraceptive interest underscores a need for novel ways to support perinatal individuals with OUD in family planning conversations that honor their reproductive autonomy, values, and desires.

Related protocols: CTN-0080

Background: Opioid use disorder (OUD) during pregnancy is a leading contributor to peripartum morbidity and mortality, with overdose deaths rising significantly in recent years. Despite the identification of various factors associated with overdose events, including social, demographic, psychiatric, and neonatal outcomes, the relative contributions of these factors to peripartum overdose history (or lack thereof) remain unclear. Thus, this study aims to characterize factors associated with lifetime opioid-involved overdose events among currently pregnant individuals receiving buprenorphine (BUP) treatment for OUD.

Methods: Treatment-seeking pregnant individuals with an estimated gestational age of 6 to 30 weeks were enrolled in a large multisite randomized controlled trial evaluating 2 BUP formulations for OUD. Participant baseline demographic, substance use, and mental health data were collected using validated measures, and random forest modeling identified key factors associated with lifetime opioid overdose events.

Results: The 140 pregnant participants (Mage = 31.2 years, SD = 4.7; 87.1% White) reported an average of 8.7 years (SD = 5.8) of opioid use, with 92.1% endorsing lifetime prescription opioid use and 82.9% reporting heroin use. The average lifetime number of nonfatal opioid overdose events was 4.8 (SD = 12.1); an overdose was reported by 55% of the sample (n = 77). Random forest analysis (area under the receiver operating characteristic curve = 0.797) incorporating sociodemographic, substance use, and mental health characteristics found that the most important factors associated with lifetime overdose events were, in order, lifetime heroin use, trauma exposure, reliance on partners or parents for financial support, depressive symptoms, and lifetime cocaine use.

Conclusions: These findings underscore the critical need to address substance use, co-occurring mental health, and socioeconomic challenges that are associated with previous opioid overdose. Identifying and targeting key modifiable overdose risk factors can inform the development of tailored interventions to improve outcomes for this population.

Related protocols: CTN-0080

Introduction: Cigarette smoking rates among pregnant women with opioid use disorder (OUD), are significantly higher than those found in the general population.

Methods: We conducted a secondary analysis of baseline data from a multisite, randomized clinical trial comparing two different buprenorphine formulations on outcomes during pregnancy. Cigarette use and smoking cessation goals were evaluated with the Fagerström Test for Nicotine Dependence and the Thoughts About Abstinence (TAA) questionnaire respectively. Factors associated with differences in cigarette use and smoking cessation goals were compared.

Results: Among 156 participants, 85 (54.5 %) reported that they currently smoked cigarettes. Most participants had a desire to quit smoking (TAA score = 6), but they had low expectations of success (TAA score = 4) and a relatively high perceived difficulty (TAA score = 6.5) of quitting during pregnancy. Among participants who smoked, less than half (45.5 %) had a smoking cessation goal. Participants who had a smoking cessation goal were significantly more likely to have a stronger desire to quit and higher expectations of success in quitting than participants who did not have a goal.

Conclusions: Many pregnant women with OUD would like to quit or reduce smoking during pregnancy. A combination of pharmacologic and non-pharmacologic interventions to reduce or eliminate cigarette use should be incorporated into obstetric and substance use treatment clinical settings. Smoking cessation interventions should be aligned with patients’ goals and preferences.

Related protocols: CTN-0080

Introduction: Given the continued rise in opioid exposed pregnancies and overdose during the postnatal period, it is critical to identify risk characteristics among this population to enable clinicians to better tailor interventions. This exploratory study sought to develop a deeper understanding of overdose risk characteristics among pregnant people with opioid use disorder and which characteristics may contribute to differing risk profiles.

Methods: Design and participants. This exploratory secondary analysis utilized baseline data from a large-scale national multi-site randomized controlled trial that compared two buprenorphine formulations among treatment seeking pregnant individuals with opioid use disorder.

Assessments: For risk group identification, the Personal Opioid-Overdose Risk Survey was used. Trauma history experience was assessed using the Trauma History Screen and substance use history was captured using the DSM-5 Checklist and Treatment Services Review V6.

Analyses: Latent class analysis identified unique subgroups of participants based on overdose risk factors. Latent class group membership was associated with trauma history and substance use characteristics using logistic and stepwise logistic regression.

Results: Three distinct classes of overdose risk emerged: the tolerance and polysubstance/alcohol use (HIGH-ALC) class (n = 14, 10 %), synthetic opioid and polysubstance use (LOW-ALC/FENT) class (n = 65, 46.4 %), and the low risk (LOW-RISK) class (n = 61, 43.6 %). The HIGH-ALC class reported the most (non-opioid) substance use in the last 12 months with 6 times higher odds of marijuana use (95 % CI, 1.01-35.67) and 17.48 times higher odds of cocaine use (95 % CI, 3.45-88.48) compared to the LOW-RISK class. The LOW-ALC/FENT class (n = 65, 46.4 %) had the highest reports of childhood physical abuse, greater odds of experiencing intimate partner violence regarding recovery (OR = 4.82, 95 % CI = 1.90-12.26), and greater odds of a threat to safe living (OR = 3.35, 95 % CI = 0.72-15.66). The LOW-RISK class (n = 61, 43.6 %) had the lowest reports of polysubstance use in the last 12 months and the least reports of both childhood sexual trauma and adulthood sexual trauma.

Conclusions: Through better understanding distinct patient overdose risk profiles, healthcare providers can deliver more targeted prevention interventions to address individual needs and improve maternal outcomes.

Related protocols: CTN-0080

Objectives: Despite drug overdose deaths increasing among peripartum persons, little is known about how to increase naloxone acceptance in this population. This study evaluated the effect of a brief 15-min computer facilitated personally-Tailored Opioid-overdose and Medication for opioid use disorder (MOUD) Educational intervention (TOME) on naloxone uptake and compared participant characteristics based on naloxone acceptance.

Methods: This secondary analysis of data is from an outpatient randomized multisite trial with peripartum individuals receiving MOUD treatment (CTN-0150). Participants were randomized to TOME or control. TOME participants met 1:1 with research staff to review a printout of missed pre-test opioid overdose and MOUD knowledge questions that explained the correct answer. Control participants received educational materials from the Substance Abuse and Mental Health Services Administration. Baseline demographics, treatment characteristics, opioid overdose and MOUD knowledge, and self-report MOUD stigma ratings were compared between participants who accepted versus declined free study-provided naloxone because they already had it or for other reasons. The intervention’s effect on naloxone acceptance was evaluated after delivery of TOME or control among those accepting versus those declining naloxone for other reasons.

Results: Of 111 participants, 90 accepted naloxone, 14 declined due to already having naloxone, and seven declined for other reasons (e.g., not affiliating with people who would need it, not wanting it in their house, allergy), These three groups significantly differed on past stigma from family (p = 0.007) and employers (p = 0.013) whereby participants declining naloxone due to already having it had the lowest stigma. Those accepting naloxone (n = 90) were nearly evenly split between TOME (n = 48) and control (n = 42). Six of the seven declining naloxone for other reasons were control participants. Among the 97 accepting naloxone or declining it for other reasons, TOME trended toward increasing naloxone acceptance (OR: 6.857, CI: 0.793, 59.291, Fisher Exact test p = 0.0592). There was a higher percentage of correct MOUD answers in the 90 accepting naloxone (66.8 %) vs. the 7 declining for other reasons (55.7 %; p = 0.0471).

Conclusions: These preliminary results suggest the need for further work to determine if educational interventions can enhance naloxone acceptance and suggest that stigma and medication treatment knowledge may be important factors influencing naloxone acceptance.

Related protocols: CTN-0150

This is the primary outcomes article for CTN-0150.

Overdose is a leading cause of pregnancy-associated mortality in the US. Our personally-tailored opioid-overdose (OOD) and medication for opioid use disorder (MOUD) education intervention has been shown to significantly improve MOUD/OOD knowledge in out-of-treatment persons using illicit opioids. We evaluated the ability of the intervention modified for peripartum (pregnant or within one year postpartum) individuals, the personally-tailored OOD and MOUD education (TOME) intervention, to increase MOUD (primary) and OOD (key secondary) knowledge.

Methods: A six-site, two-arm, open-label, trial with 131 peripartum individuals receiving MOUD (methadone or buprenorphine) randomized to TOME, a 15-minute, computer-facilitated, individually-tailored intervention, or Control. TOME participants received education on MOUD and OOD questions they missed in a pre-test. Control participants received SAMHSA handouts on OOD and MOUD. All participants were scheduled for a 3-week post-test.

Results: Participants were enrolled in MOUD for an average of 15.6 months (SD=20.4) at baseline, with 30.5% enrolled in methadone and 69.5% enrolled in buprenorphine treatment. On the pre-test, participants answered 66.7% of the MOUD and 82.1% of the OOD questions correctly on average. Linear regressions indicated that participants’ MOUD (X2=33.96, p<0.001) and OOD (X2=45.78, p<0.001) knowledge increased significantly more in the TOME, relative to Control, group.

Conclusions: In a sample of peripartum patients enrolled in MOUD for a substantial length of time, TOME significantly increased MOUD and OOD knowledge. Taken together with past research, these findings suggest that there are gaps in MOUD and OOD knowledge in individuals with opioid use disorder that can be addressed with brief personally-tailored education.

Related protocols: CTN-0150

Opioid use disorder (OUD) and resulting opioid-related overdoses are significant contributors to maternal morbidity and mortality. Yet very few clinical trials focus on evaluating the efficacy of medications for OUD among pregnant populations. Understanding challenges to the recruitment and retention of pregnant participants with OUD in clinical trials and identifying effective strategies to overcome these barriers are urgently needed to help improve outcomes.

The SUCCESSful recruitment and retention in a randomized controlled trial of pregnant participants with opioid use disorder (SUCCESS, CTN-0080-A-1) study was conceptualized and designed by researchers from the Medication treatment for Opioid use disorder in expectant Mothers (MOMs) trial (NIH NIDA NCT03918850). The objective of the SUCCESS study is to identify strategies, facilitators, and barriers to recruiting and retaining pregnant and postpartum participants with OUD in the MOMs trial.

The SUCCESS study entails (1) semi-structured interviews with researchers from all 13 MOMs sites, (2) focus groups with MOMs trial participants, and (3) a modified Delphi process to develop data-driven guidance for future clinical trials.

This commentary describes the motivation to conduct this study, presents our conceptual framework and critical decision points in protocol development, and describes the proposed product of this study.

Related protocols: CTN-0080-A-1

Objectives: Assessment and counseling are recommended for individuals with prenatal cannabis use. We examined characteristics that predict prenatal substance use assessment and counseling among individuals who screened positive for prenatal cannabis use in prenatal settings.

Methods: Electronic health record data from Kaiser Permanente Northern California’s Early Start perinatal substance use screening, assessment, and counseling program was used to identify individuals with =1 pregnancies positive for prenatal cannabis use. Outcomes included completion of a substance use assessment and among those assessed, attendance in Early Start counseling only or Addiction Medicine Recovery Services (AMRS) treatment. Predictors included demographics and past-year psychiatric and substance use disorder diagnoses evaluated with GEE multinomial logistic regression.

Results: The sample included 17,782 individuals with 20,398 pregnancies positive for cannabis use (1/2011-12/2021). Most pregnancies (80.3%) had an assessment. Individuals with Medicaid, anxiety, depression and tobacco use disorders, compared to those without, had higher odds and those with greater parity, older age (=35) and in later trimesters, had lower odds of assessment. Among 64% (n = 10,469) pregnancies needing intervention based on assessment, most (88%) attended Early Start counseling only or AMRS (with or without Early Start). Greater parity and later trimester assessment was associated with lower odds, while Medicaid was associated with higher odds of Early Start counseling. Nearly all diagnosed psychiatric and substance use disorders were associated with higher odds of AMRS treatment.

Conclusions: A comprehensive prenatal substance use program engaged most pregnant individuals with prenatal cannabis use in substance use assessment and counseling. Opportunities to improve care gaps remain.

Related protocols: CTN-0140

Trauma screening is recommended for pregnant persons with opioid use disorder (OUD), but there is limited literature on screening results from buprenorphine treatment. This study’s objectives were to 1) describe the types, and severity, of traumatic events reported and 2) evaluate the associations between trauma and health-related quality of life (HRQoL).

Baseline data from an ongoing trial were analyzed (CTN-0080). Participants were 155 pregnant persons with OUD receiving, or enrolling in, buprenorphine treatment at one of 13 sites. The experience, and relative severity, of 14 high magnitude stressors were assessed with the trauma history screen. The Patient-Reported Outcomes Measurement Information System-29+2 was used to assess 8 HRQoL domains.

Traumatic stressors were reported by 91% of the sample (n = 155), with 54.8% reporting a lifetime persisting posttraumatic distress (PPD) event and 29.7% reporting a childhood PPD event. The most prevalent lifetime PPD event was sudden death of a close family/friend (25.8%); physical abuse was the most prevalent childhood PPD event (10.3%). Participants with lifetime PPD, relative to no PPD, reported significantly greater pain interference (P = 0.02). Participants with childhood PPD, relative to no PPD, had significantly worse HRQoL overall (P = 0.01), and worse pain intensity (P = 0.002), anxiety (P = 0.003), depression (P = 0.007), fatigue (P = 0.002), and pain interference (P < 0.001).

Conclusions: A majority of pregnant persons enrolled/enrolling in buprenorphine treatment reported persisting posttraumatic distress with sudden death of close family/friend being the most prevalent originating event; clinicians should consider the impact that the opioid-overdose epidemic may be having in increasing trauma exposure in patients with OUD.

Related protocols: CTN-0080

This brochure, intended for clinicians participating in the CTN-0013 clinical trial (MET to Improve Treatment Utilization and Outcome in Pregnant Substance Users), provides an overview of Motivational Enhancement Therapy (MET) and answers to questions participants might have about being involved in the research project.

This population-based cross-sectional study, supported by CTN-0140, analyzed electronic health record data of pregnant individuals in an integrated health care delivery system in California to examine changes in prenatal cannabis use through self-report and urine toxicology testing during standard prenatal care between 2012 (n=33,546) and 2022 (n=43,415) and to test whether trends differed by race and ethnicity or age. The prevalence of prenatal cannabis use increased from 5.5% in 2012 to 9% in 2022, with similar increases by toxicology test and self-report. The increase in prevalence varied significantly across racial and ethnic and age groups, with the highest prevalence among Black individuals and those aged 13-24 across years. Although rates increased more slowly among groups with the highest prevalence of use, disparities persisted over time. These increases highlight the need to inform all pregnant individuals of the potential risks associated with prenatal cannabis use and connect them with nonjudgmental, culturally sensitive interventions, as needed.

Related protocols: CTN-0140

The goal of this study, part of CTN-0140 (Cannabis Use Among Pregnant Women with Polysubstance Use and Psychiatric Problems), was to estimate the strength of association between psychiatric disorders and substance use disorders (SUD), and cannabis use and cannabis use disorder (CUD) during early pregnancy. Participants were 299,496 pregnancies from 227,555 individuals screened for cannabis use by self-report and a urine toxicology test at entrance to prenatal care in Kaiser Permanente Northern California during January 2011-December 2021 (excepting year 2020). The sample was 62.5% non-White, with a mean (standard deviation) age of 31.1 (5.5) years; 6.8% used cannabis; 0.2% had a CUD.

Exposure variables included electronic health record-based psychiatric diagnoses of attention deficit hyperactivity, anxiety, bipolar, depressive, personality, posttraumatic stress and psychotic disorders; and alcohol, opioid, stimulant and tobacco use disorders, during the two years prior to pregnancy up to the day before the prenatal substance use screening date. Outcome variables were any cannabis use, frequency of self-reported cannabis use and CUD during early pregnancy.

Psychiatric disorder prevalence ranged from 0.2% (psychotic) to 14.3% (anxiety), and SUD ranged from 0.3% (stimulant/opioid) to 3.8% (tobacco). Psychiatric disorders were associated with cannabis use and CUD, with the strongest association for any use found for bipolar disorder (adjusted odds ratio [aOR] = 2.83; 95% confidence interval [CI] = 2.53-3.17) and the strongest association for CUD found for psychotic disorders (aOR = 10.01, 95% CI = 6.52-15.37). SUDs were associated with cannabis use and CUD, with the strongest association for any use found for tobacco use disorder (aOR = 4.03, 95% CI = 3.82-4.24) and the strongest association for CUD found for stimulant use disorder (aOR = 21.99, 95% CI = 16.53-29.26). Anxiety, bipolar, depressive disorders and tobacco use disorder were associated with greater odds of daily than monthly or less cannabis use.

Conclusions: Psychiatric disorders and substance use disorders appear to be associated with elevated odds of any and frequent cannabis use as well as cannabis use disorder during early pregnancy. In most cases, the associations with cannabis outcomes were stronger for substance use disorders than other psychiatric disorders.

Related protocols: CTN-0140

Weekly and monthly CAM2038 (Brixadi®) extended-release subcutaneous buprenorphine (XR bup) has been available in Europe and Australia for several years and was approved by the Food and Drug Administration in May 2023. Little is known about the clinical experience of patients and providers using this new medication during prenatal care. Two cases of pregnant persons with opioid use disorder receiving weekly XR bup in an ongoing randomized multi-site outpatient clinical trial (CTN-0080) are presented along with a brief review of the pharmacology and literature on XR bup formulations. The cases in pregnancy illustrate how treatment with the weekly formulation is initiated including how to make dose adjustments, which may be necessary given the longer half-life; it takes 1 month to achieve steady state. Injection site pain with medication administration was time limited and managed readily. Other injection site reactions experienced included subcutaneous erythema and induration that was delayed in onset and typically mild, resolving with minimal intervention. Delivery management and breastfeeding recommendations while on weekly XR bup were not different compared to sublingual buprenorphine (SL bup).

Conclusions: Weekly XR bup is a new treatment for opioid use disorder that may be used in the obstetric population. Obstetric and addiction medicine clinicians should be aware of this new formulation as its use is expected to increase.

Related protocols: CTN-0080