Abstract
Objective:
To describe the characteristics, treatment, and outcomes of pregnant women with opioid use disorder.
Methods:
Women attending an obstetric and addiction recovery clinic in Boston from 2015 to 2016 were enrolled in a prospective cohort study and followed through delivery (N=113). Buprenorphine or methadone was initiated clinically. The Addiction Severity Index (ASI) was administered at enrollment. Prenatal and delivery data were systematically abstracted from medical charts.
Results
Most women in the cohort were non-Hispanic white (80.5%), with a mean age of 28 years. Few women were married (8.9%). Over half of the cohort had been incarcerated, 29.2% had current legal involvement, and 15.0% generally had unstable housing. A majority (70.8%) was infected with hepatitis C and histories of sexual (56.6%) and physical (65.5%) abuse were prevalent. Regular substance used included heroin (92.0%), injection heroin (83.2%), other opioids (69.0%), marijuana (73.5%), alcohol (56.6%), and cocaine (26.6%). Fifty-nine women (52.2%) were treated initially with prenatal buprenorphine and 54 (47.8%) with methadone; 49.6% also were taking concomitant psychotropic medications. Employment (0.766±0.289) and psychological (0.375±0.187) ASI scores were the highest, indicating the most severe problems in these areas. Opioid use–relapse did not differ by treatment (44.7% overall)Thirteen (22.5%) of 59 women treated with buprenorphine transitioned to methadone mainly because of positive opioid screens. Overall, 23.0% (N=26) of the cohort discontinued clinical care. The number of pregnancy losses was small (three therapeutic abortions, four miscarriages, one still birth), with an overall live-birth rate of 90.8% (95% CI: 82.7, 95.9).
Conclusions:
These data on the social circumstances, substance use, treatment, and treatment outcomes of pregnant women with opioid use disorder may help clinicians to understand and treat this clinically complex population.
Précis
Pregnant women with opioid use disorder are a clinically complex population with prevalent polysubstance use, economic instability, legal problems, trauma histories, and comorbidities.
The opioid crisis is an ongoing public health issue in the United States and Canada. Of the 2.1 million initiators of opioid misuse annually in the United States, 1.2 million (57%) are women1,2. Increases in opioid use among pregnant women also have been documented3. Among pregnant women enrolled in Medicaid, 18.5% filled a prescription for an opioid during pregnancy in 2000 rising to 22.8% in 2007. Although women are increasingly affected by the opioid crisis, public health responses have not been geared towards women or pregnant women1,4.
In a population-based survey of pregnant and non-pregnant women in the United States, less than 20% of these women with substance use disorder received any treatment5. Further, 39% of pregnant women with opioid use disorder admitted to a federally funded US treatment facility in 2012 received opioid agonist therapies such as buprenorphine or methadone6. Similarly, only 41% of pregnant women with a diagnosis of opioid dependence enrolled in Medicaid in Massachusetts had any opioid agonist therapy prescription in the year before delivery7. Providers who care for women must be prepared to assess and evaluate opioid use, misuse, and addiction1. A recent survey of the American College of Obstetricians and Gynecologists Fellows and Junior Fellows identified a need to improve obstetrician-gynecologists’ knowledge of opioid use, misuse, and best prescribing practices8.
While ample research has focused on the outcomes of infants born to women with opioid use disorder, less attention has been given to the women themselves. To provide insight to the characteristics, treatment, and outcomes of this growing population we describe a prospective cohort of pregnant women with opioid use disorder. We recruited this contemporary cohort from patients attending the largest volume clinic of pregnant women with opioid use disorder in New England.
Materials and Methods
We conducted a prospective cohort study of pregnant women and their infants. The study population was recruited from pregnant women attending the Project RESPECT (Recovery-Empowerment-Social Services-Prenatal Care-Education-Community-Treatment) Clinic in 2015 and 2016. Project RESPECT is a multidisciplinary treatment team at Boston Medical Center (BMC) consisting of three obstetric providers, a psychiatrist, a psychiatry nurse practitioner, and a licensed independent clinical social worker. BMC is an urban safety net hospital with a labor and delivery unit, high-risk maternal fetal medicine in-patient service, level three neonatal intensive care unit, and a pediatric in-patient ward for infants with neonatal abstinence syndrome. Project RESPECT operates in conjunction with local and regional methadone clinics, counseling centers, and residential treatment programs for pregnant women. Maternal criteria for opioid agonist therapy at Project RESPECT included being 18 years of age or older (the BMC adolescent clinic cares for pregnant patients with opioid use disorder who are less than 18 years of age). , DSM IV diagnosis of substance dependence for opioids, laboratory or radiographic sonographic documentation of pregnancy, and voluntary consent to engage in Project RESPECT’s comprehensive treatment program. The clinical protocol generally followed at the study site was to initiate the type of opioid agonist therapy chosen by the patient unless medically contraindicated. Clinical providers generally did not recommend methadone over buprenorphine (i.e., buprenorphine alone, Subutex) for pregnant women unless the patient preferring buprenorphine was previously or recently was unsuccessful with buprenorphine treatment. Per the clinical practice protocol, women were scheduled for prenatal care and relapse prevention visits every one to three weeks through delivery. Observed urine drug tests were done at each prenatal visit and on admission to labor and delivery. If an appointment was missed women were contacted and requested to come in for a urine drug test within 48 hours.
Women attending Project RESPECT were eligible for study participation if they were not in legal detention at enrollment, were 18 years of age or older, intended to carry the pregnancy to term, intended to receive prenatal care and deliver at Project RESPECT, and were able to provide informed consent. Women were recruited at opioid agonist treatment initiation or at the first prenatal visit (for women who were on treatment at conception); some women were recruited at subsequent visits if they presented for care on a weekend or could not be interviewed at the first prenatal visit. This study was approved by the Boston University Medical Center Institutional Review Board.
A research assistant administered the Addiction Severity Index (ASI), 5th Edition Lite—which has been widely used in patients with substance use disorders since the 1980s9—to women at study enrollment. The ASI included questions pertaining to seven domains: medical status, employment and support, drug use, alcohol use, legal status, family–social status, and psychiatric status. Interviewer ratings were summed across particular domain questions to indicate the degree of patient reported problems in each domain9. The composite scores in each domain ranged from 0 (no problems) to 1 (severe problems). Prenatal data including opioid agonist treatment use (date of initiation, starting dose, and dosing changes), urine toxicology screen results, concomitant prenatal medication use, and pregnancy outcomes were systematically abstracted from maternal medical charts from enrollment through delivery.
Differences in treatment outcomes (e.g. adherence to clinical care, urine screen results, opioid agonist therapy cessation) by first prenatal treatment with buprenorphine or methadone were assessed statistically using the Fisher exact test. The Wilcoxon signed-rank test was used to statistically assess changes in opioid agonist therapy dose from early pregnancy to delivery. The proportion of pregnancies that ended in miscarriage (defined as an unintended pregnancy loss less than 23.5 weeks gestation) or therapeutic abortion was calculated among women enrolled in the cohort in the first trimester of pregnancy. The proportion of pregnancies that ended in stillbirth (defined as a pregnancy loss ≥23.5 weeks gestation) was calculated by dividing the number of still births by the total number of stillbirths and livebirths. The proportion of pregnancies that ended in live birth was calculated by dividing the number of live births by the total number of pregnancies that had a known outcomes (i.e., women lost to follow-up in clinical care were excluded). These were reported as the proportion x 100% with the corresponding exact binomial 95% confidence interval. Analyses were performed using SAS version 9.3 (SAS Institute Inc., Cary, NC) and Stata Intercooled 11.0 (StataCorp LP, College Station, TX).
Results
From February 2015 through April 2016, 115 pregnant women with opioid use disorder attending the study clinic were enrolled in the cohort. Seven women (5.7%) who were approached declined to participate. An additional seven eligible women who were approached were not enrolled because they did not complete opioid agonist therapy titration or were admitted and discharged on a weekend and did not present for prenatal care again. Of the 115 women enrolled, two were subsequently found to be ineligible and were excluded leaving 113 women in the study cohort.
The sociodemographic and clinical characteristics of the 113 women in the cohort are shown in Table I. Most women were non-Hispanic white (80.5%), with a mean age of 28 years. Women had, on average, 12 years of education, and few were married (8.9%). Over half of the cohort had ever been incarcerated, almost 29.2% had current legal involvement (were on parole, had charges pending or were incarcerated the past 30 days), and 15% generally had unstable housing. Most women were multiparous and multigravida… A majority of the cohort (70.8%) was infected with hepatitis C. Histories of sexual abuse (56.6%) and physical abused (65.5%) were prevalent. Fifty-nine women (52.2%) were treated initially with buprenorphine and 54 (47.8%) with methadone, and 49.6% also were taking concomitant psychotropic medications.
Table I.
Demographic and Clinical Characteristics of 113 Pregnant Women with Opioid Use Disorder in the Study Cohort
| Characteristic | Distribution* |
|---|---|
| Age | 28.3 ± 4.4 |
| Race | |
| Non-Hispanic white | 91 (80.5) |
| Non-Hispanic black | 11 (9.7) |
| Hispanic | 11 (9.7) |
| Years of education | 12.0 ± 1.7 |
| Employment income | 30 (26.5) |
| Income from illegal activity | 21 (18.6) |
| Income from social assistance | 69 (61.1) |
| Trimester of cohort enrollment | |
| 1st | 48 (42.5) |
| 2nd | 45 (39.8) |
| 3rd | 20 (17.7) |
| Married | 10 (8.9) |
| Ever incarcerated | 58 (51.3) |
| Parole, charges pending or incarcerated 30 days prior to enrollment | 33 (29.2) |
| Generally had unstable housing past 3 years | 17 (15.0) |
| Gravida‡ | |
| 1 | 22 (19.5) |
| 2–3 | 49 (43.4) |
| ≥ 4 | 42 (37.2) |
| Parity | |
| 0 | 43 (38.1) |
| 1 | 33 (29.2) |
| 2–3 | 34 (30.1) |
| ≥ 4 | 3 (2.7) |
| Singleton pregnancy | 108 (95.6) |
| Hepatitis C infected | 80 (70.8) |
| Ever been sexually abused | 64 (56.6) |
| Ever been physically abused | 74 (65.5) |
| Initial prenatal opioid agonist therapy | |
| Buprenorphine | 59 (52.2%) |
| Methadone | 54 (47.8%) |
| Psychotropic medications | |
| Any | 56 (49.6) |
| SSRI | 23 (20.4) |
| Benzodiazepines | 27 (23.9) |
| Anticonvulsant | 265 (23.0) |
| Other | 33 (29.2) |
ASI: Addiction Severity Index, ER: emergency room, SSRI: selective serotonin reuptake inhibitor
Number and proportion or mean ± standard deviation
Includes current pregnancy
Polysubstance use was common among the cohort (Table II). Almost all women smoked (86.7%), and had ever regularly used heroin (92.0%) and injection heroin (83.2%). Women also reported ever having regularly used marijuana (73.5%), opioids other than heroin (69.0%), alcohol (56.6%), and cocaine (26.6%). A history of methadone treatment was reported by 59.3% of the women.
Table II.
Substance Use Histories of 113 Pregnant Women with Opioid Use Disorder in the Study Cohort *
| Characteristic | Distribution* |
|---|---|
| Smoking recorded in medical record | 98 (86.7) |
| Self-reported ever regularly used‡ | |
| Alcohol | 64 (56.6) |
| Heroin | 104 (92.0) |
| Heroin injection | 94 (83.2) |
| Methadone | 67 (59.3) |
| Other opioids | 78 (69.0) |
| Cocaine | 30 (26.6) |
| Cocaine injection | 14 (23.7) |
| Marijuana | 83 (73.5) |
| Self-reported age at first use | |
| Alcohol | 13.9 ± 2.6 |
| Heroin | 20.4 ± 4.3 |
| Other opioids | 17.7 ± 3.5 |
| Cocaine | 17.5 ± 3.9 |
| Marijuana | 13.7 ± 1.9 |
| Self-reported lifetime years of regular use‡ | |
| Alcohol | 5.3 ± 4.6 |
| Heroin | 6.0 ± 4.1 |
| Methadone | 2.3 ± 2.5 |
| Other opioids | 3.3 ± 3.1 |
| Cocaine | 4.1 ± 3.9 |
| Marijuana | 6.5 ± 5.3 |
| ASI Scores | |
| Alcohol | 0.027 ± 0.121 |
| Drug Use | 0.217 ± 0.142 |
| Employment | 0.766 ± 0.289 |
| Family/Social | 0.190 ± 0.226 |
| Medical | 0.171 ± 0.260 |
| Legal | 0.156 ± 0.241 |
| Psychological | 0.375 ± 0.187 |
ASI: Addiction Severity Index
Regular use on the ASI refers to use ≥3 times per week, binges, or problematic irregular use in which normal activities are compromised.
Number and proportion or mean ± standard deviation
The prenatal treatment of the 59 women initially treated with buprenorphine and the 54 with methadone is detailed in Table III. Within each treatment group, women who were on treatment at conception had a significantly higher daily dose at conception than the initiation dose for those who started treatment prenatally. More women in the buprenorphine group than in the methadone group had a least one urine toxicology screen after opioid agonist therapy initiation (98.3% vs. 87.0%, p=0.027). The mean total number of toxicology screens was higher in the buprenorphine than methadone group (12.7 vs. 7.6, p <0.001). Among women with at least one urine toxicology screen, the proportion with continued opioid use or relapse did not differ by prenatal treatment (44.7% overall). Buprenorphine treated women, however, were less likely to have urine screens positive for cocaine than methadone treated women (12.1% vs. 27.7%, p=0.049).
Table III.
Treatment and Outcomes of Pregnant Women with Opioid Use Disorder by Initial Opioid Agonist Therapy *
| Treatment/Outcome | Buprenorphine (N=59) |
Methadone (N=54) |
P-value |
|---|---|---|---|
| Time of opioid agonist therapy initiation | 0.158 | ||
| Before conception | 20 (33.9) | 18 (33.3) | |
| 1st trimester | 20 (33.9) | 15 (27.8) | |
| 2nd trimester | 16 (27.1) | 11 (20.4) | |
| 3rd trimester | 3 (5.1) | 10 (18.5) | |
| Dose among women on opioid agonist therapy at conception |
16.2 ± 4.4 | 79.2 ± 34.9 | - |
| Dose at prenatal initiation among pregnancy initiators |
10.4 ± 4.3 | 55.6 ± 22.0 | - |
| ≥1 urine toxicology screen after opioid agonist therapy initiation |
58 (98.3) | 47 (87.0) | 0.027 |
| Number of urine toxicology screens after opioid agonist therapy initiation§, |
12.7 ± 6.9 | 7.6 ± 5.1 | <0.001 |
| ≥1 urine toxicology screen positive after opioid agonist therapy initiation§ |
|||
| Opioids | 27 (46.6) | 20 (42.6) | 0.698 |
| Cocaine | 7 (12.1) | 13 (27.7) | 0.049 |
| Other non-prescribed licit or illicit drugs | 9 (15.5) | 11 (23.4) | 0.329 |
| Lost to follow up in clinical care | 11 (18.6) | 15 (27.8) | 0.271 |
| Stopped opioid agonist therapy | |||
| ≥ 1 time | 6 (10.2) | 4 (7.4) | 0.745 |
| Not on opioid agonist therapy at delivery‡ | 1 (2.1) | 2 (5.1) | |
| Dose at delivery‡ | 14.7 ± 5.4 | 97.9 ± 39.1 | - |
Women with delivery information and includes those who underwent therapeutic abortion or miscarried.
Number and proportion or mean and standard deviation
Women with at least one urine toxicology screen after treatment initiation
Of the 59 women in the buprenorphine group, 13 (22.0%) were transitioned to methadone treatment because of urine screens positive for opioids (N=9), incarceration (N=3, all of whom also had positive urines screens prior to incarceration), or adverse treatment effects (N=1). Three women transitioned to methadone in the first trimester of pregnancy, five in the second trimester, and five in the third trimester. One women who initiated treatment with buprenorphine was transitioned to methadone for 12 days while incarcerated then resumed care at the study clinic and transitioned back to buprenorphine. Finally, one woman in the buprenorphine group was initially treated with methadone at the study site, but three days after treatment initiation she transitioned to buprenorphine at another clinic and subsequently continued to be cared for at the study site on buprenorphine .
A small proportion of women had interruptions in their opioid agonist therapy during pregnancy or were weaned off treatment prior to delivery (one women treated with buprenorphine and two treated with methadone, Table III). The daily dose significantly increased from early pregnancy to delivery in both the buprenorphine and methadone groups. Finally, 23.0% of women did not continue clinical care and thus were lost to follow-up. Compared with women who continued clinical care, those who were lost to follow up were more likely to have legal involvement 30 days prior to cohort enrollment (46.2% vs. 24.1%, p=0.048), less likely to use other opioids (53.9% vs. 73.6%, p=0.089) and more likely to have greater mean ASI drug (0.288 vs. 0.195, p=0.004), family (0.308 vs. 0.155, p=0.008), and legal (0.234 vs. 0.133, p=0.017) scores.
The absolute number of pregnancy losses was small (Table IV). Among women who enrolled in the study cohort in the first trimester, two women in the buprenorphine group and one in the methadone group underwent therapeutic abortions, and four women the buprenorphine group miscarried. One woman in the methadone group had a still birth at 35.7 weeks gestation. The remaining pregnancies were live-births. Five women delivered at a site other than the study clinic because of admission to a residential treatment program outside of the area and a coordinated transfer of prenatal–obstetric care (N=2), overdose and cardiac arrest (N=1), withdrawal from residential treatment and clinical care (N=1), ambulance transport to closest hospital at delivery (N=1), and unknown (N=1). Finally, in terms of neonatal outcomes, among live-born infants 20.3% were born preterm and 73.1% were pharmacologically treated for neonatal withdrawal .
Table IV.
Pregnancy Outcomes of Women with Opioid Use Disorder
| Initial Prenatal Opioid Agonist Therapy | |||
|---|---|---|---|
| Buprenorphine | Methadone | Overall Rate (95% CI)* | |
| Therapeutic abortion | 2 | 1 | 6.3 (1.3, 17.2) |
| Miscarriage | 4 | 0 | 8.3 (2.3, 20.0) |
| Still birth | 0 | 1 | 1.4 (0.0, 7.7) |
| Live birth | 42 | 37 | 90.8 (82.7, 95.9) |
Denominator for miscarriage and therapeutic abortion is women who enrolled in the cohort in the 1st trimester of pregnancy only; denominator for live births is pregnancies with a known outcome; denominator for still births is still birth plus live births; Rate is the proportion x 100%.
Discussion
We describe a contemporary cohort of pregnant women treated for opioid use disorder enrolled and followed at a high volume obstetric and addiction recovery clinic in Boston. The complexity of this patient population in terms of their social and living conditions, their addiction and its treatment, and their treatment outcomes is presented.
As evident from our data, obstetric providers have the challenge of addressing multiple substance use and the effects of these substances on both the pregnant women and the fetus. Opioid exposure is associated with preterm birth, NAS, and vision abnormalities10,11. Prenatal cocaine use has been associated preterm birth, low birth weight, small head circumference, intrauterine fetal growth restriction, placental abruption, prelabor rupture of membranes, and maternal migraines and seizures12,13. Similarly, pregnant women who smoke have an increased risk for ectopic pregnancy, premature rupture of membranes, placental abruption, placenta previa, and stillbirth14. Risks to the fetus include preterm birth, low birth weight, intrauterine growth restriction, birth defects such as cleft lip or palate, and sudden infant death syndrome14. This polysubstance exposure, in addition to prescribed psychotropic medications, may exacerbate the assessment, treatment and risk of neonatal opioid withdrawal15,16. The risks of poor pregnancy outcomes in women who use substances likely reflect not just the substances themselves, but also the social and environmental circumstances that surround substance use17.
A majority of women in our cohort had experienced physical abuse and sexual abuse. Studies have shown deleterious sequelae of abuse including cognitive deficits, depression, dissociative symptoms, maladaptive sexual development, high rates of obesity, dropping out of high school, persistent post-traumatic stress disorder, self-mutilation, physical and sexual revictimization, premature delivery, drug and alcohol use disorders, and domestic violence among others18. Obstetricians are in a unique position to respond to sexual abuse disclosure, even when a woman declines mental health referral19. Guidelines exist so that obstetricians can make preparations and modifications to help the patient cope with stressors that may arise during prenatal care or delivery20,21. Long-term counselling and the involvement of expertise in abuse counseling for these pregnant women with opioid use disorder is recommended19.
The multitude of issues faced by these women in pregnancy likely cannot be addressed and resolved in the prenatal period alone. Comprehensive, postnatal medical care, counseling and social support should be accessible for all women. Few women in our study had legal employment and employment problems were significant as measured by the ASI. Evolving current treatment approaches to address employment, financial insecurity, and safe housing should be considered. With the growth of this population it is critical to create a compassionate comprehensive care model for women to address the complex physical, emotional, social, and environmental characteristics of addiction22,23. While the obstetric provider appropriately manages the medical and obstetric consequences that may arise from these many issues, a multidisciplinary team is needed.
While fewer methadone than buprenorphine treated women had a urine toxicology screen after opioid agonist therapy initiation and there were fewer tests per woman in the methadone group, we observed higher continued cocaine use or relapse—as detected by urine screens—in women treated with methadone than buprenorphine. This likely reflects the higher prevalence of concomitant cocaine dependence in women treated with methadone at our site. Importantly, we found no clinically or statistically significant difference between the buprenorphine and methadone treated groups in opioid use, consistent with observations in a prior randomized controlled trial (RCT) of pregnant women24. The rate of continued opioid use or relapse overall in our clinical cohort was 44.7%, which is higher than the rate among women in the RCT (9% buprenorphine, 15% methadone). This is expected given that 84% of opioid dependent pregnant women receiving care at the RCT sites were excluded from the RCT due to eligibility criteria or non-participation12, while few women who presented for care at our study site during the recruitment period did not enroll in our study cohort. Compared to women in the RCT, more women in our cohort were Hispanic and fewer were white, and the duration of heroin and cocaine use was considerably longer; ASI drug and alcohol scores were similar among women in the two studies.
Buprenorphine treatment failure, described as transition to methadone because of continued opioid use or relapse, occurred in 22.0% of the study cohort, which is higher than the rate of 1.5% observed at our clinic from 2006 through 201025. This may reflect changes in the clinic protocol to offer buprenorphine as a treatment option, even for women with higher risk profiles, in an effort to expand buprenorphine access and increase patient autonomy. Some women with opioid use disorder may not have been adequately treated by the partial agonist effects of buprenorphine and required transitioned to the full opioid agonist effects of methadone to adequately manage symptoms.
The complex needs of these pregnant women pose challenges for both the patient and obstetrician. Even at a dedicated high-risk obstetric and addiction recovery clinic with a multidisciplinary treatment team, 23.0% discontinued prenatal care and were lost to follow-up. The challenging circumstances of pregnant women with opioid use disorder observed in our cohort may have contributed to discontinuation of clinical care. In addition, although some women continued prenatal care at the study site, delivery sometimes occurred at other sites due to the need for urgent care or changes in residential treatment programs.
The problem of opioid use and addiction during pregnancy has become prominent in recent years 26,27. Our study provides insight on the clinical complexity of pregnant women with opioid use disorder treated at a leading United States clinic that serves the largest population of Medicaid patients in Massachusetts28. Compared with other settings in the US, our clinic may have more women with high ASI scores arising from low socioeconomic status, urban environment, or social determinants of health (i.e. women with longer history of substance use). In addition, patient choice and access to treatment with buprenorphine or methadone may differ in other prenatal settings. These data may, however, provide insight to prenatal care providers.
Acknowledgements:
This publication was supported by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development under grant number 1R21HD081271–01 REVISED (S. Brogly). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Footnotes
Financial Disclosure
The authors did not report any potential conflicts of interest.
Each author has indicated that he or she has met the journal’s requirements for authorship.
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