in Treating Opioid Use Disorder in Pregnancy and the Perinatal Period by Dr. Davida Schiff. My name is Julie Kmick, and I'll be your moderator for this session. This is the fourth of a six hour, no, sorry, this is the fifth of a six hour webinar series on hot topics of the treatment of opioid use disorder. I'd like to introduce Dr. Schiff, who is a general academic pediatrician and health services researcher focused on understanding how substance use in pregnant and parenting women impacts the health of children and families. She's the medical director of the HOPE Clinic, Harnessing Support for Opioid and Substance Use Disorder in Pregnancy and Early Childhood at Mass General Hospital, a multidisciplinary program caring for women and families with substance use disorders from the time of conception through the first two years postpartum. Dr. Schiff's research is focused on improving care for families affected by substance use, and her past scholarship has been published in the New England Journal of Medicine, JAMA, Pediatrics, Academic Pediatrics, Journal of Substance Abuse and Treatment, and Substance Abuse, among other journals. She's an assistant professor of pediatrics at Harvard Medical School. So I'd like to turn it over to Dr. Schiff. Thanks, everybody. Thank you. Are you able to see my screen okay? Will you give me a heads up, Julie, if that works? Perfect, okay. Well, welcome, everybody. I appreciate those of you who are listening live and taking time after the end of a busy day or those who are listening later to talk about something that's near and dear to my heart, which is how we think about treating opioid use disorder in pregnancy in the perinatal period. I have no financial conflicts of interest to disclose, but I have received research and programmatic funding and consultation funding from the organizations listed on this slide. So my goal for the next 40 minutes is to review the limitations and biases in presenting existing national prevalence and incidence data in perinatal opioid use disorder, to describe some treatment considerations for women with opioid use disorder who become pregnant and during pregnancy, and explore the unique stigma and discrimination surrounding pregnancy and substance use disorder treatment in the perinatal period, identify opportunities for improved engagement, care and collaboration and preparation for delivery, and to discuss the unique risks to substance-exposed families in the early postpartum period, including what happens when the recurrence of substance use occurs. So I wanted to start off with a slide that probably for those of you who are listening is not news, that the rate of opioid-affected deliveries continues to rise. This is data that combines information from the Healthcare Utilization Project using both the National Inpatient Sample and data on pediatric admissions, looking at the rates of deliveries affected by maternal opioid use disorder in gray and deliveries that infants with a diagnosis of neonatal abstinence syndrome. And you can see over the last close to two decades, we've had a national rate that's increased by more than fourfold. And as a result, you see lots of articles in our news media where you describe kind of the condition of NIS or the condition of infants being affected by the opioid epidemic and a pretty negative and sort of sensationalized white. I wanted to take a minute and sort of debunk one of those first myths that rise in cases of neonatal abstinence syndrome or NIS may reflect an increase in women with opioid use disorder who are receiving the recommended medication treatment during pregnancy. So what does that mean? So of all the types of in utero substance exposure, you can take a look at this figure here. Our goal in getting women into treatment for their opioid use disorder is to move from this circle, which is illicit or non-prescribed opioids. So substances such as heroin or fentanyl or non-prescribed opioids and move them into this bucket here, which is a treatment of opioid use disorder, including methadone and buprenorphine. Additionally, infants can be exposed to women who take prescribed opioids for chronic conditions, such as sickle cell disease or other chronic pain conditions or other psychiatric medications can also result in withdrawal symptoms. And all of these medication can produce withdrawal symptoms in infants, a subset of those that go on to need pharmacologic treatment for their withdrawal. And there's also a small number of infants who have iatrogenically been exposed to opioids who then experience withdrawal symptoms. But I wanna make the point that if we think about ways in how we can improve our data in the way that we report our data, describing just cases of infants being exposed to neonatal abstinence syndrome really misses a key piece of the story. Here you can see data from Tennessee, which looks very similar to the national slide that I had shown you when this presentation began, where there's a steady increase in the percent of total cases of infants who were born with a diagnosis of neonatal abstinence syndrome. When you break it down and you think about those different categories of infants who were exposed only to maternal prescribed medications to treat their opioid use disorder with methadone or buprenorphine, compared to those who were exposed only to illicit or non-prescribed substances or a combination of both, you can see the story in Tennessee actually looks really different and you get a more sophisticated understanding of what's really going on, which is that the number of women who are on the recommended treatment for opioid use disorder has increased significantly due to public health and medical efforts across that state. And those babies exposed only to non-prescribed opioids has decreased. But when you just look at information focusing on cases of neonatal abstinence syndrome, you really miss the point. While this presentation is going to focus on opioids, I wanted to make sure that we're thinking about the focus beyond the immediate period around the delivery of hospitalization and really think both prenatally and postpartum and to how we can support the mother-infant diet. That's including pre-pregnancy and thinking about pregnancy intention and family planning, thinking about supporting them during the prenatal period. And then after the baby is born, I really like this graphic from Steven Patrick, who's a colleague at Vanderbilt, but I would argue that we also have this incredibly important and high-risk time for women with opioid use disorder in the postpartum year that we need to think uniquely about how to best support the diet. Similarly, while we're going to focus on opioids today, I think it's important to put it in the context of what substances we know babies are commonly exposed to and the sort of known harm to the most common licit substances used during pregnancy, and that's tobacco and alcohol. So while we see an average of, you know, somewhere between six to 20 per 1,000 births, depending on the geography, that can result in a withdrawal syndrome, you actually see many more infants who have long-term neurodevelopmental consequences from exposure to tobacco and alcohol. And then as we think about the importance of treating opioid use disorder in pregnancy, we also have to think about the co-occurrence of other polysubstance use, including stimulant use disorder, specifically amphetamines, and the rise in amphetamine use, particularly in rural areas over the last 10 years. Okay, so now let's focus in and dive in on treatment of opioid use disorder in pregnancy. I'll start with a case to help frame our discussion. So Kelly's a 34-year-old African-American woman who's experiencing her first pregnancy. She's had polysubstance use, including cocaine and opioid use disorder, and she's presenting to Initiate Care at 34 weeks. She's been actively using throughout her pregnancy. She has a history of Child Protective Services involvement herself as a child, and her parents both struggled with active substance use disorder while she was growing up. And she presents to your care in your clinic and desires a healthy pregnancy, but remains ambivalent about starting either methadone or buprenorphine. I really like this slide. It's been taken with permission from Mishka Turplin, where he kind of describes that pregnancy is the intersection of your addiction and reproductive life course. And I find it incredibly motivating to work with women because it's, for them, a uniquely motivating moment in a woman's life in terms of thinking about positive behavioral changes that they can make to have the healthiest pregnancy for themselves and their baby. And then the treatment of opioid use disorder in pregnancy is really no different than when you're not pregnant. And that opioid agonist treatment with methadone or buprenorphine is the standard of care for treatment of pregnant women with opioid use disorder. And that's been affirmed by all of the many professional and public health organizations and guidances, guidelines from these professional organizations below. And I think it's really important to note that pharmacotherapy is preferred to medically assisted withdrawal or detoxification because withdrawal is associated with high relapse rates, which lead to worse outcomes. I think it is common to hear, even from very well-meaning clinicians, that they tell pregnant patients that they're not allowed to discontinue or taper off of their medications to treat opioid use disorder because there's going to be poor outcomes for the fetus. And really, the biggest risk is actually not due to harm to the fetus from the withdrawal. It's the risk of relapse and potential overdose and possible death that leads to really negative outcomes for the baby. So what are some of the benefits and risks of pharmacologic treatment in pregnancy? I think, as you can see here, we would all argue that the benefits outweigh the risks. The benefits, including the reduction of illegal opioid use, helping to remove women from a drug-seeking environment, to eliminate those illegal behaviors, presenting fluctuations in maternal drug levels throughout the day, reducing mortality and morbidity, improving participation in prenatal care, improving the ability to prepare for the birth, stabilizing women in order to allow them to be more likely to have the option and ability to parent their children, and their children are more closely monitored when women are part of a treatment program and reducing their frequency of obstetrical complications. Risks that are unique to pharmacologic treatment in pregnancy is that there are symptoms of neonatal opioid withdrawal that we'll talk about, risk of low birth weight. And while this field of study in terms of looking at neurodevelopmental outcomes is growing, I think we should still say that there's limited and sort of unclear developmental risks due to exposure to opioids in pregnancy. Many of you have heard of this very important trial that was led by Andre Jones and her team, published now more than a decade ago in the New England Journal. It's called the MOTHER trial that looked at methadone versus buprenorphine in pregnancy. They randomized 175 pregnant women to either methadone or buprenorphine. It was a double-blind randomized control trial. And they did find that buprenorphine use was associated with a shortened length of hospitalization for infants who are experiencing symptoms of neonatal opioid withdrawal. But notably, sorry, it's hard to see here that the methadone group had significantly higher retention than the buprenorphine group. When you're really thinking with your patients then about what type of medication to use, and I'll get to this in the next slide, I think it really requires a shared decision-making framework to determine what medication is best for them and given their circumstances. One thing that comes up a lot now is whether to switch from the kind of combined product, buprenorphine naloxone or the brand name Suboxone to the buprenorphine monoproduct, commonly called Subutex in pregnancy. The mother trial did look at the monoproduct. And so initially it was thought of that the monoproduct was preferred in pregnancy. I think we're now seeing a shift towards continuing women on the medication that they had been on in many practices. So the advantages is that the, you know, sort of full standard clinical trial did look at the buprenorphine monoproduct compared to methadone, although potential disadvantages include possibility of diversion, injection misuse, victimization, coercion on pregnant people to sell their buprenorphine monoproduct given it has a slightly higher street value. And advantages to thinking about using the combined product is that there's no changes during pregnancy or the postpartum period, particularly that postpartum time when transitioned back to the combined product can sometimes be challenging for women due to concerns about whether there's equal effectiveness. At a time when insurance is less likely to approve it with prior authorizations. And I think notably we've seen really lack of evidence of harm with the combined product. And so many places and many clinics are really shifting towards continuing on suboxone. Our own clinical practice and the Hope Clinic where I work is it's sort of a patient preference. And we have to have a discussion of potential risks and benefits. This was the shared decision-making aid that I had mentioned earlier. Connie Gill, a researcher at the Medical University of South Carolina developed this scale to help people really think about whether they would want to be on methadone or buprenorphine or neither medication. And this is where your motivational interviewing skills are really important to think about rolling with resistance and developing the discrepancy of where people are sort of stuck in kind of their concerns or their interests in using medications. And really highlights the importance of trauma-informed care. So where in this can you offer choice, collaboration and agency? And some of the qualitative work that I've done with women around thinking about medication use during pregnancy, they've commonly shared that they feel as though particularly due to their pregnancy status, they feel forced and kind of strongly encouraged in a way that gives them little agency and choice to talk about type of medication or dose of medication for their own individualized treatment plan. So in summary, why do pregnant women avoid treatment? I think there's a great amount of shame and stigma of drug use during pregnancy. There's a desire to avoid child protective services reporting that may be part of a mandatory report for opiates exposed infants at birth, depending on your state's reporting requirements. There's the fear of just a punitive response. And then there's historical and community views on medication treatments that differ. There's, as we know, significant structural racism within our healthcare system as well as within the addiction treatment system. And all women have a desire to minimize potential risk to their infant and reduce the number of exposures to the fetus to avoid the risk of neonatal opioid withdrawal syndrome. This is an article that was published by the New York Times editorial board. Now, almost two years ago, they came and interviewed one of the women in our clinic, one of the first babies that we cared for. And I like this graphic because of the very powerful title that the article has, which is that the mother is that society condemns. And I think this idea that of groups of an incredibly marginalized and stigmatized group of people, which is people with a substance use disorder, pregnant women with a substance use disorder have just historically faced a litany of assaults and their liberties. And that can be shown by taking a look at how we respond to substance use in pregnancy. This is data from ProPublica and the Guttmacher Institute where they show the number of states that equate substance use during pregnancy as child abuse. And then the number of states, which is almost all of them, where there have been documented prosecution of women for drug use during pregnancy. Despite the kind of guidance from all major public health and medical organizations against the prosecution of pregnant women with substance use disorder, because it drives women from prenatal care and substance use treatment, and it risks poor outcomes for women and their children, we still see this very common negative and punitive response. And in fact, work by Dr. Faraday and colleagues has shown that over time, that that punitive response at the state level is increasing. This is a graphic from work that I've done using a statewide data set in Massachusetts where we looked at all pregnant women with a diagnosis of opioid use disorder at any point in the year before their pregnancy. And then we looked at the percent of white non-Hispanic, black non-Hispanic, and Hispanic individuals who here on the left in the darker blue received any medication. And here on the light blue, those who consistently received medication defined as receiving medications for at least six months prior to delivery. And I think there's two important findings here. The first is that there were significant differences by race and ethnicity. And the second is that overall, there's still a very low percentage of women who are consistently receiving medication or were on medications for sort of the duration of their pregnancy. So in our adjusted models, we found that black non-Hispanic and Hispanic individuals were 58 to 63% less likely to receive any medications to treat opioid use disorder compared to white non-Hispanic women in pregnancy. And that in our adjusted models for the consistent group, black non-Hispanic and Hispanic women were 66 to 76% less likely to consistently receive medication to treat opioid use disorder compared to non-Hispanic white counterparts. So I wanna shift and talk a little bit about the inpatient birth experience. For those of you who work in the outpatient setting, I think this is a real opportunity to prepare women for what is commonly a very exciting, but also a moment that often brings a lot of anxiety. And our goal as a healthcare system should be to think about creating a warm, welcoming, non-stigmatizing and trauma-informed environment. So I wanna share with you some reflections on what we've done in our clinical program in order to try to improve that inpatient birth experience. So to continue with our case before we get going, that Kelly elected to initiate buprenorphine. She was able to stabilize in her third trimester without a recurrence of non-prescribed substance use. She's picked up local shifts at a coffee shop, picked up shifts at a local coffee shop on a few days a week in order to help make ends meet. And she's really terrified about the upcoming delivery and potential child welfare involvement, including feeling a great amount of shame and stigma surrounding her infant's potential withdrawal symptoms. She has cut back to less than three cigarettes per day, but has heard that she shouldn't try to breastfeed her baby due to her hepatitis C status. She has increasing anxiety about whether she'll be able to take the baby home with her given her substance use throughout her first and second trimesters. So what we do in our clinic in order to document and highlight the recovery work that our patients in our program have gone through is develop what we call a recovery portfolio. And many states have enacted different ways of presenting this information as part of their meeting plan of safe care, plan of supportive care, plan of care requirements, depending on what it's titled in your state. But what we include in our recovery portfolio are the kind of information around an individual support network. We review their resources and community partners and agencies that they're connected to. We describe and put together a relapse prevention plan and a safety plan, including things that support their recovery, things that they identify or are areas that they know that they need to avoid, and then warning signs that a clinician or community partner should be aware of if they potentially have a risk of recurrence of use. And then we put together a safety agreement as well as a profile of treatment engagement during pregnancy. And that gets attached with, in our state, a mandated report to child welfare given in utero opiate exposure. Next is we try to make sure that all women have a prenatal newborn medicine consult to try to defray any worries that women have around the uncertainty of delivering an infant that may experience opiate withdrawal. So this is a one-on-one meeting with either a pediatrician or a newborn medicine specialist. Usually it occurs in the third trimester. And then we document maternal addiction history, known in utero exposures, and then we review the postpartum monitoring plan for the infant symptoms. So this is important because each hospital is really different, but how can you help them understand what your location of care is for infants being monitored for withdrawal symptoms, whether that changes if they need pharmacologic treatment, are parents allowed to room in? Hopefully you're promoting kind of the non-pharmacologic measures at your institution, including parental presence at the bedside, rooming in with the baby, skin-to-skin and breastfeeding, and then reviewing what pharmacologic treatment is used, if any. This is an opportunity to review any child welfare reporting mandates in your state and then to introduce any post-discharge services, including early intervention, infant developmental follow-up, or kind of parenting support groups. One other pre-COVID innovation that we had in our clinic was what we called a preparing for baby shower. This is a monthly opportunity to meet with representatives from child welfare services, early intervention, and other perinatal substance use disorder programs while women were pregnant. We would shower them with small sort of baby gifts and items to prepare for themselves and their baby and try to use it as an opportunity to debunk myths, that is, to separate child protective services from early intervention and to learn about the process of child welfare reporting. We would spend a good amount of time really thinking about identifying barriers to being at an infant's bedside. So, how, if we're going to prioritize non-pharmacologic care where parents are the primary treatment for their babies in the delivery hospitalization, how do we ensure that they are able to make it to the bedside, particularly after they may have been discharged as a patient themselves, or their transportation barriers? Do they have other competing demands with other children at home? Are they needing to get to a methadone clinic at 7 a.m. every morning, and as a result, they miss rounds because that's the time that the team comes through and discusses that baby's plan for the day? And then, what may be their recovery programming requirements? If they're in a residential treatment program, are they asked to attend six hours of group in that immediate postpartum period, preventing them from being at the bedside? And then, really thinking about the internalized stigma that each woman experiences, as many of them have experienced symptoms of withdrawal themselves, and they feel a great amount of shame watching their infants display those same symptoms of withdrawal. The postpartum period is a time where there's a lot of changes and a lot of transitions for women, but understanding and preparing ahead of time for what their goals are in terms of providing either breast or chest milk is really important. So, what we do in terms of planning for breastfeeding is to educate them around the benefits of breastfeeding for opiate-exposed infants, and then really review the myths and misperceptions around contraindications for breastfeeding. So, in the case example that I gave you, the patient had heard on the street that because she had hepatitis C, she wouldn't be able to breastfeed. That's a really common one that we hear, but in fact, unless that patient has actively bleeding cracked nipples, it is safe and effective for her to provide breast milk to her baby. It's only in the moment when she has cracked bleeding nipples that we would ask to pump their dump until they heal. Another very common one is that women don't want to go up on their methadone dose because they are worried that it's going to lead to worse withdrawal symptoms in their baby. There's a really wonderful commentary by Jack McCarthy and colleagues that highlighted that the dose that women take is really not correlated with the dose that babies receive because of the pregnancy metabolism that we will commonly see during pregnancy physiology, that methadone is metabolized at much, much higher rates. And so, it's important to really counsel women that their baby's not actually seeing the dose of methadone that they're taking, that they're seeing a small amount that's getting metabolized, particularly when they feel like they're having fears of increasing their dose, both for symptoms of withdrawal, but also for whether it's safe with breastfeeding. Particularly in the COVID era, when you may or may not be able to do a tour of your labor and delivery hospital delivery board, making sure that they understand what that environment looks like, if there's videos that you can share with them, if there's pictures of the postpartum board to describe where the NAS treatment is, is really important. And then one thing that I can't underestimate for you guys, how important it's been for us, but also one of the biggest challenges at our institution, is thinking about how we improve the collaboration between the inpatient and the outpatient teams to have a seamless delivery process for these kind of vulnerable and marginalized women. So, we've attempted to have monthly multidisciplinary teams that bring together kind of those inpatient and outpatient providers. So, looking at identifying champions from nursing, pediatrics, obstetrics, neonatology, case management, social work, and child protection. I'll tell you, this has been a little bit of a work in progress in our hospital, but it's an opportunity to discuss upcoming cases and to review missed opportunities. So, where could things have gone better? Where may have you have missed the mark in the prior month? And what are ways that you can think of that you can improve for the next delivery and sort of use it to do small PDSA cycles and quality improvement projects? I'm going to take a minute to talk about the types of assessment tools for infants, because this has changed significantly in the last five years. The assessment that we had, the majority of hospitals had used since the 1970s, was something called the FNAS scoring tool, coined by Loretta Finnegan, the neonatal abstinence scoring tool, versus a newer approach that was initially coined by Matt Grossman at Yale. It was called the eat, sleep, and console approach, really focusing on a functional assessment of the infant, and can they meet the job description of a baby, which is really to be able to eat, to sleep, and be consoled. We talked a little bit earlier about the non-pharmacologic treatment options. The pharmacologic treatment options that are commonly used, the most common agents are morphine and methadone. You can see the secondary agents listed below. This is a paper by Dr. Grossman that sort of described his institution's holistic quality improvement approach to reducing the number of infants who required pharmacologic treatment for neonatal opioid withdrawal. I think it's pretty fascinating. You can see that prior to them initiating their quality improvement efforts, they had almost more than 90 percent of their babies that were pharmacologically treated. After a series of steps, including promoting non-pharmacologic care, promoting rooming in with parents staying at the bedside, introducing this novel eat, sleep, and console approach, and then going to PRN dosing, so morphine dosing needed only as needed and not scheduling, they really reduced the length of stay and the numbers of infants who needed any pharmacologic treatment. Switching gears a little bit to talk about language. You've heard me in this presentation sort of go back and forth between NAS and NOWS, so neonatal abstinence syndrome versus neonatal opioid withdrawal syndrome. There's a lot of work that's being done to kind of standardize our definition of neonatal opioid withdrawal syndrome right now, but I wanted to just pose to you this question of where did the term NAS come from? We think it was coined by Dr. Finnegan, who came up with that famed scoring tool while she was understanding the symptoms of withdrawal in babies exposed to opioids in the 1970s, but if you take a look at the dictionary definition of abstinence, that being the practice of abstaining from something or the practice of not doing or having something that is wanted or enjoyable or the practice of restraining oneself from indulging in something, typically alcohol, it doesn't really fit the description of a baby who has physiologic dependence on opioids in utero who then is experiencing withdrawal symptoms, and so since 2016, SAMHSA's favored the term neonatal opioid withdrawal syndrome. I think what's notable about that is that it doesn't account for polysubstance exposure, which we know is really the norm these days, so in that case, I think the jury's still out on the right language, but you'll see both of these kind of used throughout the literature. One place where I think we really can be quite clear is the impact of sensationalized reporting and stigmatizing language, and you can see in these headlines from news articles that were published over the last several years the way in which babies are described, and what I would say is that we, as a medical community, have a real strong need to be consistent about our language that an infant who is exposed to opioids in utero is born physiologically dependent to opioids and not, quote, born addicted, as you see in those news headlines in the prior slide. So then next, what does a substance-exposed infant look like? For those of you who are on the more adult side of treating opioid use disorder in pregnancy, you may sort of see those sensationalized reports in the media of a baby who's screaming and crying and looks miserable and is shaking and is jittery, and that's what your understanding or certainly the public's understanding of neonatal opioid withdrawal syndrome, but really an infant who's been substance-exposed who's treated with optimized non-pharmacologic and is needed pharmacologic care should look just like your or my infant. So in this slide are two of my children when they were babies, and one of them is one of the first babies that I took care of as a pediatrician in the clinic. The other thing is the language that we use when describing families who've been impacted by substance use disorder matters. So you'll often hear people say, well, that woman is just making a scene because she wants attention. A helpful response could be that she's crying out for our help or those moms have poor coping methods. You could sort of offer a refrain that they have survival skills that have gotten them to where they are now, and then you'll hear negative comments like, well, they're weak, they'll never get over it, but really you can reframe the discussion in a trauma-informed way to say that recovery is a process that takes time and that these women or these families are stronger for having experienced trauma. I wanted to take a minute to address the issue of behavioral escalation and substance use in the hospital setting, and I realize we are crossing a number of domains, including the outpatient treatment of these patients, and then thinking about what happens when recurrence of use in the prenatal period happens and a patient may be admitted for stabilization during pregnancy. So I'll give you an example of a case. So Evie is a 26-year-old white, non-Hispanic woman with methamphetamine and opioid use disorder and tobacco dependence who's presenting with severe lower back pain at 36 weeks. She was found to have an epidural abscess and was admitted for IV antibiotics and methadone stabilization. The hospital policy does not allow patients with PICC lines to leave the floor to smoke, and this patient, to give you a little bit more of her history, has experienced significant early traumatic experiences, began injecting drugs at 15 after being introduced to substances by her mother, and after a period of sobriety for more than two years when she became pregnant, she had a recurrence of use. This prenatal period has been complicated by in addition to her active substance use street homelessness where she's exchanged sex for drugs and intimate partner violence. During her inpatient admission, her partner comes to visit, and the two are found agitated and arguing with drug paraphernalia in the bathroom. I don't know if this is a familiar situation to any of those of you who may work on addiction consult teams or more in the inpatient setting, but it's these stressful moments that I think really test our ability to provide trauma-informed care. And so I wanted to highlight the importance of trauma-informed care under moments of stress. So in order to do this, I think we need more proficient de-escalation training among hospital-based staff or outpatient providers as well, thinking about how you offer choice, the sort of core tenet of trauma-informed care. So when can we provide supervised smoke breaks? Can we, are there peers in your hospital setting in order to provide engagement at times when people are often just sitting and waiting, particularly with prolonged hospital courses due to IV antibiotics or medication stabilization? Is there a way to offer a behavioral health response team rather than hospital security in order to de-escalate when situations like the one I described arise? And then how critically important it is to debrief with hospital staff after stressful situations occur. And then finally, to celebrate the victories. When you're seeing women who get admitted in kind of these moments of active use that are really struggling, you see them at their worst. And can you take those women who then are seven months down the road, have stabilized and are parenting their kids and bring them back and allow those providers who've often been really traumatized from experiencing that active substance use in the hospital and bring them to talk and to show them how they look in recovery. In the last 10 minutes, I want to go through some postpartum risks, which is an area as a pediatrician is very near and dear to me. Our recovery coach at MGH said this in her early weeks of working with us, and I think it's really resonated with me and has been our experience in caring for families across the perinatal continuum, that the truth is getting through pregnancy is the easiest part. This is data using the same public health data set in Massachusetts that I described earlier, where we looked at the opioid overdose rates among pregnant and postpartum women in Massachusetts. This is both fatal and non-fatal overdose. And you can see that as we progress throughout pregnancy, overdose rates decrease. And then in the year following delivery, overdose rates rise to actually level prior to what they were when women became pregnant. We see overall that pharmacotherapy, so treatment with either methadone or buprenorphine, leads to a reduction in the overdose events during the month that they were on that pharmacotherapy. Although there is an important sort of bump here that needs further explanation in terms of thinking about what happens in the 6 to 12 months after delivery when we see that increase in the number of overdose rates. This is Kaplan-Meier survival curves using that same data set to look at individuals who are on pharmacotherapy with methadone or buprenorphine at time of delivery and what happens to them. So overall, we actually saw that about 60% of our sample who were on medications of delivery continued. There were no differences by those who received only methadone or any buprenorphine, but there was a significant difference, again by race and ethnicity, where white and Hispanic individuals are more likely to continue on medications than other races and ethnicities. And that the degree of medication used during pregnancy, so those that were on medications all of pregnancy, were significantly more likely than those who are medications for four or fewer months. So why are postpartum women vulnerable? We know that there's a loss of access to specialized services for caring for pregnant women. Depending on your state, there's often loss of access to even insurance for any basic medical needs. There's high rates of postpartum depression among women with substance use disorder. There's the shame and stigma that women feel watching their infants experience symptoms of neonatal opioid withdrawal, and that's all in the addition to the stresses of having a new baby. There can be heartbreak from being separated from a baby if loss of custody occurs, and there's commonly a desire to discontinue medication treatment as we saw on the slide before. Yet I think that the postpartum period presents a real opportunity, particularly those of you who are working with families and working with children, to screen for parental substance use disorder and relapse. So in this public health data set that I mentioned previously, of the 189 overdoses that we identified among women the year following their delivery, less than half of those were to women who had a diagnosis of opioid use disorder in the year prior to the delivery in their medical record. So are those women who have developed a new opioid use disorder following delivery? It's possible. Are those women who had an opioid use disorder that may not have been active during their pregnancy? That's possible. Or did we miss it due to the shame and stigma that we know exists around disclosing substance use in the perinatal period? I think the most important thing is in order for families to feel like they could acknowledge that they're struggling, it requires parental trust and non-punitive responses in order for someone to disclose when recurrence of use occurs. This is a paper by Kenneth Federer and his colleagues while he was at the John Hopkins School of Public Health, where they used the National Survey of Drug Use and Health to look at adults who had unmet treatment needs. Those who are living with a child compared to those who are not living with a child had about three times the odds of reporting treatment access barriers, and four times the odds of reporting stigma as a barrier to treatment. And overall, among adults with opioid use disorder, only 27% of those who are living with a child reported any past year treatment. So how do you address substance use recurrence while parenting? I wanted to share with you our clinic approach, because this is one of the hardest things that we've dealt with in our multidisciplinary clinic, caring for families across the perinatal continuum. So when a patient is identified as using non-prescribed substances from either self-report or from toxicology testing, we perform a full safety assessment, which we divide into five domains. And that's really thinking about the safety of the child. So where was the child when the use happened? The parental engagement in treatment. Are they willing to either initiate medications to treat their opioid use disorder or are they willing to more frequent visits in monitoring? Are they willing to think about an increased level of care depending on their type of use? And then really thinking about the safety of use. So is there the potential for works and needles and substances that the child living in the home could be part of? Are people using alone in which there's a higher risk for an overdose when they're using in an unsupervised way? And then just a question of the stability of the home environment. I like this quote from a now, I'm no longer meeting, Massachusetts Family Recovery Collaborative, where they say that no one organization or system can address all the substance use challenges facing families and communities. Ensuring child safety and family health requires a collaboration and partnership among families, professionals, agencies, organizations, and communities. So how have we worked to support families through challenging times in our co-located model? So when we know that relapse is an expected part of recovery, how do we approach this? When children are involved, everything's a little bit trickier. Our approach has been to encourage open communication with community partners and providers to have tough conversations with DCF or your child welfare organization together with the patient. And then promoting shared dyadic visits following the loss of custody in order to continue to engage parents in their addiction treatment. So in summary, I wanted to offer you some, what I hope are concrete ways that you can think about decreasing stigma and advocating for opiate-exposed dyads that you may be treating and caring for. The first is that I think we need to push our public health organizations and hospitals to separate out the reporting of deliveries to women receiving medication treatment for substance use disorder versus those with untreated addiction in order to try to de-stigmatize NAS as sort of a transient, treatable, unexpected, albeit often unwanted, outcome for women who are on the recommended medication to treat their opioid use disorder during pregnancy. Next, to advocate for the dual notification pathways so that you remove a child welfare reporting mandate for in utero substance exposure without concerns for child abuse and neglect. And this requires kind of knowing your specific state mandate. Evaluating for disparities in care by stratifying data by key characteristic groups. So we won't know if there's disparities unless you look for it. And so key places where we've identified disparities in our data is with respect to age, race, ethnicity, and insurance status, using person-centered medically appropriate language when talking to and about substance-exposed dyads, and then meeting patients where they're at requires patient-centered, trauma-informed care in order to bring them to patients where they need to be. So with that, I will stop sharing my screen and eager to hear any questions or any feedback that you guys might have. Okay, thank you so much for that lecture. That was very good information, a lot of new stuff that I haven't heard before. So thank you so much. We do have quite a few questions from the audience. So some of them are about the treatment and providing buprenorphine or methadone treatment. So the first one is, can you talk about the maximum dose of buprenorphine that can be used in pregnancy? Have you used up to 32 milligrams a day? Yeah, we have had patients that have needed up to 32 milligrams. While I know that there's many places that sort of think about 24 milligrams as a ceiling, we've definitely seen women who have not had their symptoms of craving and withdrawal stabilized until they've received 32 milligrams divided TID or occasionally in a rare occurrence QID. I know down below too, there was a question asking if you can use buprenorphine extended-release during pregnancy. Yeah, so that's a great question. There's several different types of extended-release buprenorphine. The kind of FDA approved one right now is sublocade. There has been one case series that was published about this in the Green Journal. And then I think there will be more to come because there's a randomized clinical trial looking at a second, just recently, soon to be FDA approved and marketed medication with the brand name Brixadi or CAM2038 is the generic name. Our site, as well as 11 other sites across the country, are participating in a clinical trial looking at the use of Brixadi in pregnancy. But currently, sublocade is not recommended because there is an excipient that was found to be teratogenic in animal studies. And that's the reason why Brixadi is being used in this clinical trial. Our clinical approach, and we've now had several women during pregnancy, but a number of women postpartum who've really done well on sublocade. And if a woman comes to us who's stabilized significantly on sublocade, we'll have a shared decision-making conversation with them and weigh the risks and benefits and talk with them about the potential risk of teratogenic effects that we know of from animal studies versus the risk of potentially destabilizing their recovery. And several have made the decision to continue with their sublocade. OK, what if you decide in that shared decision-making process that the woman wants to change over to buprenorphine transmucosal formulation? Yeah, I think that's probably the recommended decision. And at this point, we would wait until that person kind of made it to their fourth or fifth week post their sublocade injection, and then start them on sublingual and kind of titrate the dose off as needed. Women are actually pretty good at titrating their dose to what they need based on their symptoms. And so I think you'll see that that transition can be pretty smooth for several women. We have had a patient who actually got destabilized in the transition from her sublocade to sublingual buprenorphine. And that's just an N of 1, and that's me sharing my clinical experience. But it did give us pause for thinking about medications that have stabilized individuals and kind of taking them and messing with that during pregnancy. Right. Is there a role for microinduction in pregnant women? Has this been done? Are there any studies? Yeah. So Larry Lehman's group, the FOCUS Clinic, and his program in New Mexico, forgive me for misstating the name, but the FOCUS Clinic is the pediatric program that he cares for, that they care for afterwards. But his group has been really working on microdosing as well as a group out in Washington to try to microdose people into bup. But I think in our experience, we've had much more success with microdosing onto buprenorphine while patients are admitted. We have a much easier way to get pregnant people admitted for antepartum stabilization. And so if you're thinking about using a microdosing protocol and you're connected to a hospital that has the ability to admit for antepartum stabilization, I think your microdosing likely would be more successful with an inpatient stabilization. Next one is, can you talk about transitioning somebody from buprenorphine to methadone during pregnancy or vice versa? Are there methods to do this different than in the general population? Yeah. I don't think that there are differences between pregnant people's physiology and non-pregnant people's in these switches. It's obviously much more challenging to go from a full mu methadone to partial opioid agonist with buprenorphine. So that would require significant tapering down, and then we would microdose onto buprenorphine in order to try to stabilize individuals. To go from buprenorphine to methadone is quite simple because you're able to sort of oversaturate those new receptors with a full agonist and that we see commonly. So for women who struggle to stabilize in buprenorphine, I think our common step up is to refer them to methadone. How often do you see anybody transition from methadone to buprenorphine during pregnancy? We don't usually. Yeah. I do know that Vanya Rudolph's group out of the University of Washington is trying to do this, and they have a microdosing protocol in order to attempt this when that's the patient's preference, and they have had some successful microdosing transitions, but it's not, I think, the common clinical sequence. What resources can we provide for patients receiving buprenorphine treatment to better prepare for delivery and treatment of pain during delivery or C-section? Often in a rural area, we are seeing a trend of OB providers not being familiar with how to care for patients receiving OUD treatment and resulting in a traumatic experience for our patients. Yeah, I think that's a great question. Maybe that's something that I can kind of bring up with some resources in the cases for next week, but our recommendation is to continue the patient's current dose of buprenorphine and to use full opioid agonists for pain control as well as epidural analgesic if that's something that a patient chooses to have as part of their delivery pain management and to not decrease the dose of buprenorphine. Okay. Well, we'll look forward to hearing more about that one next week as well. There was a comment about a study last year that showed 54% of infants had withdrawal with the buprenorphine monoproduct versus 34% with the combination product buprenorphine naloxone. Can you talk more about that? Yeah. If you're willing to put in a reference and a citation so I can take a good look at it and we could review it more with the case discussion. I haven't seen that specific paper. And in general, when you kind of think about the components, I wouldn't really expect that the difference between having the naloxone component would really impact neonatal opioid withdrawal. And so it makes me wonder a little bit about confounders. And so what else were sort of the polysubstance exposures that those two groups may have had? And those things may have contributed to the sort of difference between groups rather than the different buprenorphine components, although I'm sure that they adjusted for many. So happy to take a look at it with you and think through it and thinking about how that might influence how you would kind of guide or recommend your patients make decisions about those two medications. Yeah. I think if this is a study that I'm familiar with, I believe that once they controlled for some variables, that effect went away. So you stated that the reason to keep pregnant women on medications for opioid use disorder was to prevent relapse and the danger wasn't in detoxing. While I agree relapse is the biggest all around danger, I was taught that detox can be very damaging to the fetus because of potential repeated cycles of withdrawal, compromising blood flow, oxygen, and other elements vital to proper growth and development. Were we taught detox only close obstetric supervision? Has something changed? Yeah. So Michiko Triplin and colleagues did a systematic review that was published in the Green Journal a few years ago. I'm also happy to dig that up and kind of review it for everybody. And I think it really debunked some of these myths around exactly that guidance that I think has historically been taught to us, that you are able to medically supervise withdrawal. So I wouldn't just tell a pregnant person to go on and decrease their dose or make changes on their own, but under supervision of sort of a trained obstetrician or trained addiction medicine physician to think about solely decreasing and weaning them off, if that should be their decision, there has been safe for the fetus in pregnancy. And there's actually a prospective trial that Andre Jones and Michiko Triplin are doing right now that's looking at how that goes. If you prospectively identify women who are interested in weaning off of medication treatment during pregnancy, how do they do? So I'd be happy to share that citation with you all. Great. A little bit of an extension here. What about if you had a woman who was stable on the naltrexone extended release injection, how would you approach that? Yeah, I think our clinical approach is that when a woman has stabilized on a medication that's working for them, the risks of relapse and potential overdose most often will outweigh the unknown potential tragegenic effects of these substances that haven't been studied in pregnancy. There's also now a randomized trial, or I'm sorry, a prospective trial looking at the use of naltrexone in pregnancy. Our colleagues at Boston Medical Center, as well as the University of North Carolina are looking at the kind of pharmacokinetics of naltrexone use in pregnancy. And I think similarly, for women that have stabilized using naltrexone that are in a good place with their recovery, we would continue them on the medication. Somebody asked, in your experience, what is the maximum dose of methadone you have seen pregnant women require? We've had women who've, because of their rapid metabolism, require over 300 milligrams of methadone. I think the most important thing when you like guess that how high that number is, is that if you were to actually take a look at that woman's blood level and take a look at the baby's blood level, is that they're not seeing that dose of methadone, they're seeing a much smaller amount of it because it's being very, very rapidly metabolized. You noticed any correlation with the amount of fentanyl that's in the heroin supply with the requirement of higher methadone doses over the past several years? Yeah, it's a great question. What we're really seeing is that due to, at least in our area, a full contamination of fentanyl in the heroin supply is that it's much harder to stabilize ampupenorphine. So we're actually seeing women struggle, even with our microdosing protocols, to stabilize ampupenorphine, even though that's often seen as the desired first treatment option during pregnancy, and that methadone turns out to be a better drug for them, and that people are able to capture their symptoms on methadone when they weren't able to capture their symptoms of cravings and withdrawal on ampupenorphine. So you're saying that it was easier, or it's easier to do the induction with the methadone versus the buprenorphine, even with a microinduction protocol, because of the fentanyl and having difficulties with induction, as well as then treating cravings and withdrawal symptoms. Okay. Somebody had mentioned about a problem with split dosing in pregnancy, especially in the third trimester. State and federal centers are not set up to allow providers to comply with appropriate standards of care. How do you handle this? Yeah, we pull our hair out and yell a little bit. Our team has spent a lot of time calling methadone clinics, sending methadone metabolite ratios. This is something that Jack McCarthy published in a paper in JAM to sort of highlight how you can, not even with a peak and trough, but just a methadone metabolite ratio, identify who's a fast metabolizer or not, and then use that, bring his paper, and show it to methadone clinics to sort of argue for split dosing. Each time, in our state, still requires a lot of extra effort. Not all places have the ability to do two twice-daily dosing windows, and so then they're only eligible if they've met the stability requirements for take-homes. It is an area that we need change from a regulatory standpoint on. Okay. Just a couple minutes left. I'm going to ask this one real quick. Is there a point in pregnancy when home initiation with buprenorphine is not considered safe, like after 20 weeks? Yeah, we offer for all women of sort of viable pregnancy age the opportunity to have an in-person induction, sorry, an in-hospital induction. I don't know that we have had or we've come up with sort of a set time where we wouldn't offer a home induction. Usually, once the pregnancies are beyond 22 to 24 weeks, though, we offer them in the hospital, and most people choose that as an opportunity to sort of get out of their drug-use environment. What percentage of your patients might have already started on buprenorphine at home on their own, or are already on buprenorphine maintenance versus people that are brand new to treatment and getting started on it during pregnancy? And question being sort of what's the difference? Well, the question is, what percentages have you seen in your clinic, if you had to take a guess? Yeah, it's a really good question. At this point, almost nobody is treatment naive when they come to us. Most individuals have used buprenorphine on the street to kind of curb cravings and withdrawal symptoms at some point. And honestly, I think it's led to some people having a negative experience with buprenorphine and may have negative views towards that medication treatment because of their use in a non-prescribed way. Yeah, at this point, we rarely have individuals who haven't tried buprenorphine outside of the clinical setting before they come to us. Okay, I think that's going to do it for today. If you have questions for Dr. Schiff that you would like to have answered during next week's question and answer session, please go to our website, the AOAAM education page, and you'll enter your questions on the discussion board, and we'll forward those to her. Our next webinar is on September 22nd at 5 p.m. Eastern, and Dr. Schiff's going to have case discussions and additional Q&A session. So thank you so much for the presentation and the Q&A session this afternoon. We look forward to seeing you again next week, and thank you all for attending. Thanks, everybody. Looking forward to it. Great questions.

opioid use disorder

pregnancy

perinatal period

substance use

treatment considerations

stigma and discrimination

postpartum period

opioid-affected deliveries

non-pharmacologic care

trauma-informed care