CATR: Could you tell us what your role is and what you do?
Dr. Forray: I’m an associate professor of psychiatry at Yale and I do research on treatments for pregnant and postpartum patients with substance use disorders (SUDs). Clinically, I’m the interim chief of the Section of Psychological Medicine at Yale New Haven Hospital and work with patients in our adult sickle cell clinic.

CATR: Can you give our readers an understanding of the scope of addiction in pregnancy?
Dr. Forray: The majority of substance use in pregnancy is with legal substances. Anywhere from 8% to 10% of pregnant patients use alcohol, and a similar percentage use cigarettes. About 6% use some illicit substance, predominantly cannabis, followed by cocaine, heroin, and ­amphetamines. Around 2.5% use prescription opioids (www.datafiles.samhsa.gov). Use of hypnotics, psychedelics, and inhalants is much lower. We lack data on what proportion of these patients have diagnosable SUDs, but I would venture to guess that it would match the non-pregnant population of reproductive-age patients.

CATR: Another area in which we lack data is how shame and stigma might prevent pregnant patients from receiving adequate care. How should practitioners handle this issue?
Dr. Forray: There are anecdotal reports that pregnant patients feel shamed by providers when seeking treatment, particularly medications for opioid use disorder (MOUDs). In fact, proper MOUD treatment during pregnancy is shockingly low (Tiako MJN et al, Obstet Gynecol 2021;137(4):687–694). Patients feel that providers are thinking, “Why are you using? You’re harming your baby.” But remember, 99.9% of pregnant patients want to do what’s right for their pregnancy. That’s why patients are coming to you; they are overcoming a lot of shame and they’re very vulnerable. It’s important to mindfully set aside any personal bias or preconceived notions before the interview.

CATR: How do you recommend we do this?
Dr. Forray: Ask yourself: “Where is this patient right now, where do they want to go, and how can I help them get there?” During the encounter itself, try to positively frame the interaction and do not shy away from directly acknowledging the patient’s difficulties. It lays the foundation for a strong therapeutic rapport that the patient can make use of later on as you hopefully continue to work together. I always say something like, “I can tell that it was very hard for you to come here today. Thank you for trusting me and being open because I can see that this is very difficult for you.”

CATR: Let’s talk about alcohol use in pregnancy. Fetal alcohol syndrome (FAS) is well known, but there are other teratogenic effects that providers should be aware of and need to counsel their patients about.
Dr. Forray: That’s right. FAS is the most well known and is the leading cause of a nongenetic developmental delay, but the full syndrome is relatively rare. However, fetal alcohol effects lie along a spectrum, and it’s much more common that children suffer a less severe, but still significant, neurodevelopmental disorder with behavioral issues and cognitive delays. This milder syndrome is less studied and less well known, so patients may think that a little drinking is OK, when really it might still confer risk for these fetal alcohol effects.

CATR: And how do you recommend that providers address these effects with patients, given how common alcohol use is?
Dr. Forray: A lot of reproductive-age patients, who might not have an alcohol use disorder, still binge drink. To give you some background, about 45% of pregnancies in the US are unplanned. For patients with an SUD, it’s 60% to 90%, and many don’t find out that they’re pregnant until late in their first trimester, which is already past the critical period of exposure to alcohol. So it is very important for providers to consider birth control for reproductive-age patients who binge drink.

CATR: There is a sense in the community that the recommendation for abstinence from alcohol during pregnancy is overblown. What should we tell a patient who hears or reads that it is actually OK for them to drink moderately?
Dr. Forray: Well, there is no time in pregnancy when it’s safe to drink; there simply is no amount of alcohol that has been shown to be safe. While critical organ formation occurs early in pregnancy, the brain continues to develop throughout pregnancy and beyond. A recent paper found that even light to moderate prenatal alcohol exposure was associated with increased psychopathology, attention deficits, and impulsivity compared to unexposed children (Lees B et al, Am J Psychiatry 2020;177(11):1060–1072). So the recommendation remains that there is no safe amount and no safe time for alcohol use in pregnancy. It’s also important to emphasize that the type of alcohol doesn’t matter either. Beer is no safer than wine, which is no safer than liquor; it is the overall amount of alcohol consumed that counts.

CATR: And what if the patient continues to drink even after pregnancy has been confirmed?
Dr. Forray: None of the medications that we typically use for alcohol use disorder, such as naltrexone or acamprosate, have been studied for efficacy in pregnancy. That being said, naltrexone appears to at least be safe and has been studied for efficacy in opioid use disorder (OUD) during pregnancy (Wachman EM et al, Clin Ther 2019;41(9):1681–1689). So naltrexone is a potential option, along with evidence-based psychotherapies such as motivational interviewing, cognitive behavioral therapy, or mutual help groups such as AA. I would avoid disulfiram altogether given the physiological stress a disulfiram-alcohol reaction might put on the fetus.

CATR: Many prescribers, especially those without expertise, can be hesitant to prescribe to pregnant patients. What kind of safety issues exist for medications prescribed for SUDs?
Dr. Forray: Other than for opioids, we don’t have studies that evaluate the efficacy of most medications for addiction in pregnancy. In fact, the safety profile of many of these medications is, in a way, a secondary issue, because we don’t know if they work in pregnancy at all.

CATR: There are substantial data for OUD treatments.
Dr. Forray: Yes, that’s right. For decades, the only medication for OUD was methadone, and that was the gold standard. Methadone is not known to lead to any congenital malformations and is effective; it reduces cravings, prevents use of other illicit substances, decreases risky behavior, enhances prenatal care, and enhances nutrition (Mozurkewich EL and Rayburn WF, Obstet Gynecol Clin North Am 2014;41(2):241–253). In 2010, there was a sentinel paper by Hendrée Jones, called the MOTHER study, which compared methadone and buprenorphine with the primary outcome of neonatal opioid withdrawal syndrome (NOWS). NOWS, formerly known as neonatal abstinence syndrome, manifests with babies being jittery, more difficult to console, and having difficulty feeding (Jones HE et al, N Engl J Med 2010;363(24):2320–2331). If not treated, babies can develop seizures. That paper caused a paradigm shift and brought buprenorphine to the forefront of MOUD in pregnancy because it showed that, relative to methadone, buprenorphine decreased the length of stay, decreased the amount of morphine infants required, and decreased the duration of NOWS. Since then, either methadone or buprenorphine are acceptable MOUDs in pregnancy.

CATR: Let’s say a pregnant woman presents to your office seeking MOUDs. What is the proper way to start her on methadone or buprenorphine?
Dr. Forray: In non-pregnant patients, methadone is almost always started in a methadone clinic. But during pregnancy, it is often started on an obstetrical floor, where mental health clinicians with little experience prescribing methadone might be asked to weigh in as a psychiatric consultant. Luckily, it’s pretty straightforward. Just like in non-pregnant patients, the initial starting dose for methadone is anywhere between 10 and 30 mg, depending on how much they are using at baseline. I rarely give the 10 mg dose unless the patient is using small amounts of opioids, because you really want to avoid opioid withdrawal during pregnancy. Two to four hours after the initial dose, you reassess with the Clinical Opiate Withdrawal Scale (COWS). Re-dose with another 5–10 mg of methadone if the COWS is 8 or above. Reassess in another 2–4 hours, re-dose if the COWS is greater than 8 again, and simply repeat for the first 24 hours. After 24 hours, calculate the dose that they’ve received, and that becomes their daily maintenance dose. Given that adjustments are typically made every 3–5 days, most patients can transition to outpatient follow-up on this dose without requiring any further adjustment.

CATR: And what about buprenorphine?
Dr. Forray: Ideally, outpatient buprenorphine induction should be reserved for a pregnancy of less than 24 weeks gestation. If there is any medical comorbidity, or greater than 24 weeks gestation, it’s best to start buprenorphine inpatient due to risks to the fetus during opioid withdrawal. In pregnancy, you want to start buprenorphine at a COWS of 8 with a dose of 2 or 4 mg. If the COWS is 10 or above, I favor the 4 mg dose. From there, the protocol is the same as with methadone.

CATR: Is it necessary for prescribers to stick to the monoproduct buprenorphine (Subutex) instead of the co-formulated buprenorphine/naloxone (Suboxone)?
Dr. Forray: Traditionally, the recommendation had been for buprenorphine alone (Subutex). More recently, as we have gathered data on the safety of buprenorphine/naloxone, we have moved away from that strict recommendation. The inclusion of naloxone does not seem to have any negative impacts in pregnancy (Jumah NA et al, BMJ Open 2016;6(10):e011774; Nguyen L et al, Am J Addict 2018;27(2):92–96). In fact, some providers prefer to prescribe buprenorphine/naloxone if they have a particular concern for diversion.

CATR: You mentioned the importance of avoiding withdrawal.
Dr. Forray: Yes. Opioid withdrawal causes a catecholamine surge, which leads to increased uterine contractions and decreased placental blood flow. At the same time there is fetal motor hyperactivity, leading to increased oxygen demands. This creates a dangerous mismatch that can lead to fetal demise. For that reason, I am very aggressive in keeping pregnant patients out of withdrawal. The stakes are much higher than just physical discomfort.

CATR: What dose adjustments might be required as pregnancy progresses?
Dr. Forray: Usually patients will need higher doses as pregnancy progresses due to increased volume of distribution and changes in hepatic metabolism. Patients in the late second or third trimester metabolize methadone and buprenorphine much more quickly, so they should receive split dosing to maintain a steady state. Some may require doses that are higher than you’d normally expect: frequently 100–120 mg of methadone, or higher.

CATR: What about tapering after delivery?
Dr. Forray: There’s no consensus on how to do it. I recommend switching to once-a-day dosing soon after delivery. There is obviously a significant volume of distribution shift right away, but a lot of other physiologic changes take time, so for the first 2 weeks I will only decrease the dose slightly and taper more aggressively afterwards. Since there is no standardized protocol, doses should be adjusted according to the clinical picture. Let the signs and symptoms of the patient guide the taper. Cravings mean the dose is too low, for example, and sedation means the dose is too high.

CATR: Let’s talk about smoking in pregnancy. What should clinicians know?
Dr. Forray: Tobacco is one of the most common substances used in pregnancy. We did a prospective study and found that 96% of patients who drank alcohol were able to stop, and around 70% of patients who used cannabis or cocaine were able to stop during pregnancy. But only 32% who smoked managed to achieve abstinence (Forray A et al, Drug Alcohol Depend 2015;150:147–155). Smoking also is associated with a host of poor outcomes. Preterm delivery, ectopic pregnancy, placental abruption, fetal growth restriction, and placenta previa—all are increased with smoking. Postpartum smoke exposure increases the risk of sudden infant death syndrome threefold, and long-term impacts include cognitive effects, attention deficits, and even an increased risk of schizophrenia (Quinn PD et al, JAMA Psychiatry 2017;74(6):589–596). Unfortunately, we don’t have any good treatments for it other than contingency management, behavioral interventions, and behavioral counseling. Nicotine replacement, varenicline, and bupropion haven’t been adequately evaluated to make recommendations one way or another.

CATR: What about stimulants?
Dr. Forray: Stimulants are the worst class of drugs when it comes to pregnancy outcomes because they are powerful vasoconstrictors and disrupt placental function and placental blood flow. Like smoking, there are risks of preterm delivery, placental abruption, low birth weight, and placenta previa, but the risk is even higher with stimulants. Long-term developmental effects, hyperactivity, and behavioral dysregulation are seen as well, though the epidemic of “crack babies” that people worried about in the late 1980s and early 1990s did not quite come to pass.

CATR: The prevalence of cannabis and vaping has increased drastically in recent years. What is known about the effects of these on pregnancy?
Dr. Forray: There is much less tar content in vaping, which is a good thing, but we don’t know whether any of the other constituents are harmful, so I never explicitly recommend vaping, even as a tool to quit smoking. In terms of cannabis, risk of preterm birth, low birth weight, and placental abruption are present but less than for tobacco or stimulants. Developmental delays seem to be directly related to the amount of THC consumed. So a harm reduction strategy for patients who simply cannot abstain from using cannabis is to recommend using products with lower THC content.

CATR: What are some resources that providers can utilize when treating pregnant patients?
Dr. Forray: Reprotox is a really good specialist website with the latest evidence for medications during pregnancy and lactation, including commonly prescribed psychotropics (www.reprotox.org). And don’t underestimate the power of Micromedex, which has a pregnancy and lactation section for all its medication listings (www.micromedexsolutions.com). In fact, providers who have institutional access to Micromedex also will have access to Reprotox. Other resources include the American Society of Addiction Medicine (ASAM) website, which has useful guidance for treating pregnant patients (www.asam.org). The CDC also has some fantastic resources under their reproductive health section (www.cdc.gov/reproductivehealth/maternalinfanthealth/substance-abuse/substance-abuse-during-pregnancy.htm). Finally, the Providers Clinical Support System (PCSS), which is a national training and clinical mentoring project, has online courses for providers specifically interested in learning more about MOUDs in pregnancy (www.pcssnow.org/education-training/training-courses/treating-women-for-opioid-use-disorder-during-pregnancy-clinical-challenges/).

CATR: Thank you for your time, Dr. Forray.