Manage opioid use disorder in pregnancy. Learn how to counsel patients about the importance of medication and medication options, how to think about neonatal abstinence syndrome and recommendations for the postpartum period. We are joined by Dr. Mishka Terplan, on Twitter @do_less_harm (Friends Research Institute).
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Untreated opioid use disorder (OUD) is associated with preterm birth and low birth weight as OUD treatment reduces these risks (Piske 2021). Opioids themselves are not teratogenic (do not cause birth defects), but pregnant people who use them may be required to engage in a criminal economy to obtain them. This confers its own risks (e.g. involvement in the family policing system, the possibility of losing housing or employment). In the case of opioid use during pregnancy, the primary risks are social and contextual rather than chemical.
Medications play an important role in care for OUD during pregnancy. About one-third of pregnant people with OUD receive some form of treatment, but only 50% of those report receipt of any medication (Short 2018). Additionally, racial inequities persist in terms of who can access treatment (Schiff 2020). White women also receive higher doses of methadone around the time of delivery compared to women of color (Rosenthal 2021).
Randomized trials have not resulted in any measurable benefit from psychosocial or behavioral interventions for OUD (Amato, 2011; Mayet, 2004; Minozzi 2020), but in Dr. Terplan’s expert opinion, we should support access to any type of behavioral support that a particular person finds helpful.
Three medications are available for the treatment of OUD in pregnancy: methadone, buprenorphine, and naltrexone.
Methadone and buprenorphine are both the first line. Both are very effective, and the two show no difference in terms of fetal outcomes (Jones 2010). Since these medications are long-acting, they prevent the cycles of stress that accompany repeated episodes of withdrawal that pregnant people likely experience without treatment. Repeated episodes of withdrawal can lead to a cascade of events that can culminate in preterm birth.
The choice between methadone and buprenorphine should depend on an individual’s particular needs and the structural limitations of your practice environment. For instance, starting methadone for a patient without access to a nearby methadone clinic is not a feasible long-term plan.
Note that original studies in pregnancy were done with the mono-product of buprenorphine rather than combined buprenorphine-naloxone, but the combination product does not have any known harms. One study compares the mono- versus combination product with no difference in outcomes (Perry, 2022). If the combination product is the medication that will continue to be most available after birth, it is likely the safest option to start with in order to avoid medication changes during the high-risk postpartum period.
The evidence base for naltrexone is more limited, so it is generally not the best new medication to start during pregnancy (Towers 2020). However, avoiding major medication changes is an important goal to consider because “you cannot make an asymptomatic person better, but you can make them worse.” In other words, it is likely safest to continue this medication for women who are already doing well on it.
In Dr. Terplan’s expert opinion, we can think about injectable buprenorphine in a similar manner – if someone is already taking it prior to pregnancy, it is fine to continue, but likely should not be the go-to option for someone hoping to start a medication during pregnancy until additional research is completed.
Generally, pregnant people start to metabolize both buprenorphine and methadone more rapidly than non-pregnant people, so the medication is cleared more rapidly (Caritis 2017). For this reason, we tend to underdose MOUD in people who are pregnant. Remember that the lowest possible dose is not the safest dose – rather, the goal is to avoid withdrawal symptoms and help the pregnant person feel ok.
Pregnant people may require split dosing for both buprenorphine and methadone, meaning more frequent administration. Ask about cravings and withdrawal, adjust doses as needed based on these symptoms, and continue to ask these questions as pregnancy progresses.
NAS is a complex disorder that is variably expressed from one infant to the next (Jansson 2018). Unlike with tobacco, where there is a well-documented dose-dependent relationship between the number of cigarettes smoked and withdrawal symptoms experienced (Law, 2003), the relationship between opioid dose and withdrawal is much less predictable. NAS is expected and treatable, so fear of NAS should not delay treatment for OUD. Important components of NAS treatment include promoting attachment and encouraging mother-infant bonding (Wachman 2018).
Clinicians can push back at the notion that a baby will be born “addicted.” A baby cannot meet the Diagnostic and Statistical Manual 5 (DSM5) criteria for a substance use disorder (i.e. continued use despite negative consequences, compulsive use). In addition, we should avoid the term “addicted” as it can be stigmatizing.
The MOTHER trial was a non-inferiority trial evaluating NAS for women randomized to buprenorphine versus methadone (Jones 2010). Attrition was higher for the buprenorphine arm, meaning more people left the study in that arm. Similar numbers of infants developed NAS in the two arms, but the severity of NAS (measured by the total amount of morphine that the infant required after birth) was lower in the buprenorphine arm. The authors concluded that buprenorphine, like methadone, can be considered a first-line option.
There has been a marked increase in Child Protective Services (CPS) reports and family separations in parallel with the opioid crisis (Haffajee 2021), and healthcare professionals are a driver of this increase.
The federal Child Abuse Prevention Treatment Act (CAPTA) requires health professionals to notify a state agency, as well as develop a “family care plan,” for each substance-affected infant. CAPTA does not equate substance use during pregnancy with child abuse, or equate “substance-exposed” with “substance-affected,” but many states have taken interpretations of this law a few steps further. Testing and reporting requirements differ significantly from one state to the next, so it is important to familiarize yourself with local requirements (Guttmacher Institute 2023). The American College of Obstetricians and Gynecologists (ACOG) continues to recommend universal verbal screening for substance use during pregnancy; They do not recommend routine urine drug screening during pregnancy and delivery or for the newborn. Even a NAS diagnosis “does not imply harm, nor should it be used to assess child social welfare risk or status. It should not be used to prosecute or punish the mother or as evidence to remove a neonate from parental custody” (Jilani 2022).
People who use drugs during pregnancy are more likely to be reported, and family separation carries significant harms. Children in the foster care system are more likely than children in the general population to experience abuse or neglect (Landers 2021). Black and indigenous parents are more likely to be reported and more likely to be separated from their families, and racial inequities persist in the termination of parental rights (Font 2012; Wildeman, 2020). We should weigh the behavioral health burden and grief of family separation when determining whether to generate a report (again, reporting requirements differ significantly from one state to the next).
Remember that CPS was intended to be a surveillance agency, not a service delivery organization. Ideally, we should find ways to connect families to services without involving policing systems or conflating poverty with child abuse. We can continue to advocate for our patients and support them after a report, and ensure the provision of adequate legal counsel. We can advocate for transparent hospital policies and the reduction of punitive policies at the state level.
Breastfeeding is encouraged for women on medications for opioid use disorder (ACOG, 2017). The associated attachment, bonding, and soothing will all benefit both parent and baby.
Since substance use disorder is a chronic and recurring condition, the continuation of care is extremely important. Overdose deaths are one of the leading causes of maternal deaths in the United States (Bruzelius 2022).
Listeners will learn how to counsel and treat patients who have opioid use disorder during pregnancy.
After listening to this episode listeners will be able to counsel and treat patients who have opioid use disorder during pregnancy.
Dr. Mishka Terplan reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Mullins K, Terplan M, Sonoda K, Chan CA. “#13 Opioid Use Disorder in Pregnancy with Dr. Miska Terplan”. The Curbsiders Addiction Medicine Podcast. https://thecurbsiders.com/addiction July 13th, 2023.
Pregnancy, maternity, opioid use disorder, substance use disorders, addiction, methadone, buprenorphine, neonatal abstinence syndrome, primary care, assistant, care, doctor, education, family, FOAM, FOAMim, FOAMed, health, hospitalist, hospital, internal, internist, meded, medical, medicine, nurse, practitioner, professional, primary, physician, resident, student
Debelak K, Morrone WR, O’Grady KE, Jones HE. Buprenorphine + naloxone in the treatment of opioid dependence during pregnancy-initial patient care and outcome data. Am J Addict. 2013;22(3):252-254. doi:10.1111/j.1521-0391.2012.12005.x
Petrich M, Battin M, Walker E, et al. Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone. J Matern Fetal Neonatal Med. 2022;35(26):10481-10486. doi:10.1080/14767058.2022.2130238
Ordean A, Tubman-Broeren M. Safety and Efficacy of Buprenorphine-Naloxone in Pregnancy: A Systematic Review of the Literature. Pathophysiology. 2023;30(1):27-36. Published 2023 Feb 11. doi:10.3390/pathophysiology30010004
Writer, Producer, Show Notes, Infographic, Cover Art: Kat Mullins, MD
Hosts: Carolyn Chan, MD, MHS and Kat Mullins, MD
Reviewer: Kento Sonoda, MD
Showrunner and CME: Carolyn Chan, MD, MHS
Technical Production: Podpaste
Guest: Mishka Terplan, MD
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