Among the many consequences of the opioid epidemic in the United States is increasing numbers of pregnant women seeking treatment for opioid use disorder, increasing rates of neonatal abstinence syndrome and other adverse fetal outcomes, and associated treatment costs.1
Several professional societies and public health organizations, including the American College of Obstetricians and Gynecologists and the World Health Organization, recommend medication-assisted treatment with methadone or buprenorphine in these patient populations.2,3
These recommendations were initially formulated after a case report published in 1973 described a stillbirth after detoxification with ”evidence of increased catecholamine release (measured by serial amniocentesis) indicating fetal stress during maternal withdrawal.”1 Subsequent reports indicted comparable birth outcomes in women receiving methadone for opioid addiction and women who did not have a substance abuse disorder.1
Investigators evaluated research examining the risks and benefits associated with detoxification using methadone, buprenorphine, sedation, clonidine, or drug-free residential detoxification during pregnancy.1 Based on 15 studies that included a total of 1997 women, they concluded that the quality of evidence was fair to poor due to issues including “the largely retrospective approaches to data collection, minimal information about the detoxification and comparison group populations, insufficient detail about inclusion and exclusion criteria, self-selection of patients into detoxification groups, and failure to account for [patients] lost to follow-up and missing data.”
The research showed a wide variation in treatment setting and circumstances, fetal monitoring, and behavioral counseling, as well as detoxification completion rates (9% to 100%) and relapse rates (0% to 100%). Fetal loss rates were similar in pregnant women with opioid use disorder who underwent detoxification (n=14; 1.24%; 95% CI, 0.70-2.21) and pregnant women who did not (n=17; 1.95%; 95% CI, 1.10-3.10).
Taken together, the findings of the current review support existing recommendations promoting “pharmacotherapy over detoxification for opioid use disorder in pregnancy as a result of low detoxification completion rates, high rates of relapse, and limited data regarding the effect of detoxification on maternal and neonatal outcomes beyond delivery,” the authors concluded.
To learn more about this issue, Clinical Pain Advisor interviewed review co-author Mishka Terpan, MD, MPH, FACOG, FASAM, professor of obstetrics-gynecology and psychiatry, and associate director of addiction medicine at Virginia Commonwealth University in Richmond, as well as 2 experts who have also recently published studies on the topic: Samantha L. Wiegand, MD,5 an obstetrician-gynecologist with Premier Health’s Premier Physician Network at Miami Valley Hospital in Dayton, Ohio, and clinical instructor at the Boonshoft School of Medicine at Wright State University; and Craig V. Towers, MD, FACOG, professor and vice chair of obstetrics and gynecology at the University of Tennessee Medical Center in Knoxville.6
Clinical Pain Advisor: Is there support for the use of opioid detoxification vs pharmacotherapy for opioid use disorder during pregnancy?
Dr Terplan: The evidence base for the management of opioid use disorder in pregnancy is clear: pharmacotherapy with either methadone or buprenorphine is recommended. In our review, we found that the risk for fetal demise or stillbirth was the same in women who were detoxed vs women maintained on pharmacotherapy. However, women who were detoxed had higher rates of relapse and, consequently, a rate of neonatal abstinence syndrome similar to that in women on pharmacotherapy. In other words, there is no evidence that detoxification prevents neonatal abstinence syndrome .
In addition, the overall quality of the published literature on detoxification during pregnancy is poor — and almost no studies followed women past delivery. Given that postpartum is a time of increased stress during which relapse and overdose occur, we can surmise that the relapse rates reported in the included studies would have only been higher had the authors followed the patients beyond delivery. Finally, fetal monitoring was rarely performed in the trials, and behavioral counseling was not well-detailed overall.
Dr Wiegand: The bottom line is that evidence does not support detoxification in pregnancy. What pregnant women need is comprehensive support, which includes medication-assisted treatment, to provide stability during pregnancy. The high failure rates of detoxification in pregnancy result in a return to drug use and the medical morbidity associated with it — infections, repeated intoxification and withdrawal, overdose, poor adherence to prenatal care, and immersion in the drug culture and environment.
Dr Towers: The overall success rate is not very high for detoxification, and the relapse rate is high. However, one issue not discussed in great detail in this review is that if you add behavioral health to the process of detoxification, the success rate is higher (>50%) and the relapse rate is lower (< 20%) at delivery. No study has looked at maternal relapse post-delivery for any significant length of time following delivery, which is another area that needs further study. Therefore, the current medical approach is to take all pregnant women with opioid use disorder and put them in maintenance therapy, and I concur with that practice.
The different approach that I use, once the patient is stable, is to offer women the option of tapering and possibly full detoxification if desired. However, the mother needs to be motivated, to keep appointments with behavioral health specialists, and have good follow-up post-delivery. In addition, there is one issue that is not fully addressed in the current literature: the outcome in and long-term follow-up of the newborn, both in babies who are maintained on methadone and/or buprenorphine and babies who undergo tapering and detoxification.
Clinical Pain Advisor: What are the top takeaways for clinicians treating pregnant women with opioid use disorder?
Dr Terplan: The main takeaway is that our review strengthens current recommendations to initiate or continue pharmacotherapy with either methadone or buprenorphine during pregnancy in women with opioid use disorder. However, clinical care should not be strictly evidence-based, but also patient-centered. Therefore, if a patient wishes to taper off pharmacotherapy during pregnancy, we must respect that. She should be counseled that the evidence base supports pharmacotherapy, be provided continuing — or even increased — behavioral health services, and receive care from a provider skilled and knowledgeable in addiction medicine. Finally, if she desires a medication taper, she must also be allowed to change her mind and continue pharmacotherapy at any time during or after her pregnancy.
Dr Wiegand: Addiction is a chronic neurobehavioral disease that is best treated by a knowledgeable and multidisciplinary team. Clinicians are encouraged to screen all patients for addiction and mental health disorders. When a substance use disorder is identified, referral is indicated if the clinician is not able to directly treat this condition. In the setting of pregnancy, the mother-infant dyad should be supported with accurate information on how opioid use disorder affects the pregnancy and vice-versa. Pregnancy is a vulnerable time for women; it is also an opportunity for healthcare interventions. Women should be given standard of care options, and for opioid use disorder, the treatment of choice is generally pharmacotherapy combined with support and ongoing behavioral therapy, which should be offered before, during, and after pregnancy.
Dr Towers: Clinicians need to identify women with opioid use disorder and get them off street drugs or nonprescribed drugs. This is because many of these drugs can be tainted with stronger medications, like fentanyl, which is leading to the prominent issue of fatal and nonfatal overdoses that we currently are experiencing in the United States. Depending on where patients live, maintenance would come as either methadone or buprenorphine; neither treatment is used nationwide. If tapering or detoxification were to occur, the medical program must include intense behavioral health management during the process, which needs to continue post-delivery.
Clinical Pain Advisor: What research is needed in this area?
Dr Wiegand: Many questions remain for pregnant women with substance use disorder, including best medications to use, dosing, medication interactions, care of additional co-existing medical or mental health issues, pain control during labor and post-partum, support services during and — especially — after pregnancy, the effects of stable housing and environment within this population, long-term outcomes in women and children regarding many issues … I could go on and on! This is a difficult population to study in the short- and long-term. However, supporting these women and their diagnosis as a disease and not a moral or legal failing with punitive consequences, will expand our ability to offer help and to study these women and their children. One effect of criminalizing substance use disorder in pregnancy is the fear of seeking help, which further marginalizes this population.
Dr Towers: Research is still needed regarding the short- and long-term outcomes in newborns and infants following maintenance therapy, as well as the outcomes in newborns born to mothers who were tapered and/or detoxed during pregnancy. This is an unanswered question that makes this discussion with the mother difficult. The primary concern for detoxification would be if the mother were to relapse and overdose in the process of relapse.
The benefit of detoxification would primarily be in the newborn, and that is where more information is needed. Mothers getting off opiates prior to delivery results in less neonatal abstinence syndrome. We just finished a large prospective birth study on newborns born to mothers with opioid use disorder (87% of whom were on maintenance therapy) and were treated for neonatal abstinence syndrome. This study showed that head sizes were smaller in infants with neonatal abstinence syndrome. Therefore, this is the beginning of evidence suggesting that there could be harm associated with the current process, but further research is needed.
Clinical Pain Advisor: Would you like to add any additional points on this topic?
Dr Wiegand: I would like to say that it is a privilege to care for people. The more we reach out to women with substance use disorder and welcome them as patients, the more we can help them. We should all be invested in a healthier community and empowering patients with knowledge and accurate information, no matter their diagnosis. Treatment should be based on the best evidence we have available.
- Terplan M, Laird H, Hand D, et al. Opioid detoxification during pregnancy: a systematic review. Obstet Gynecol. 2018; 131(5):803-814.
- Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) national practice guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med. 2015; 9(5):358-367.
- World Health Organization (WHO). Community management of opioid overdose. www.afro.who.int/sites/default/files/2017-06/9789241548816_eng.pdf Accessed May 4, 2018.
- Wiegand SL, Stringer EM, Stuebe AM, Jones H, Seashore C, Thorp J. Buprenorphine and naloxone compared with methadone treatment in pregnancy. Obstet Gynecol. 2015; 125(2):363-368.
- Bell J, Towers CV, Hennessy MD, Heitzman C, Smith B, Chattin K. Detoxification from opiate drugs during pregnancy. Am J Obstet Gynecol. 2016; 215(3):374.e1-6.