Welcome to the PCSS-MAT Training module, it is entitled Treating Women for Opioid Use Disorders during Pregnancy: Clinical Challenges. My name is Dr. Hendree E. Jones, and I'm the Executive Director for UNC Horizons, and I will be leading this webinar today. As far as disclosures, I have no conflicts of interests for the disclosures that are relevant to the content of this presentation. In terms of our target audience, the overreaching goal of the PCSS-MAT, is to make available the most effective medication-assisted treatment to serve patients in a variety of settings that include the primary care setting, psychiatric care, and pain management. As far as our Educational Objectives, we have three. We're going to compare and contrast the risks and benefits of medication-assisted treatment relative to medication-assisted withdrawal, otherwise known as detoxification to the effect of treatment of women who have opioid use disorder during both the pregnancy and the post-partum period. We're then going to compare and contrast the risks and benefits of methadone as well as buprenorphine to treat the mother during pregnancy, and their relative efficacy and safety of the mother, the fetus and the child. Then we will also be identifying several factors that are associated with reducing neonatal abstinence syndrome among babies that have been prenatally exposed to medications such as methadone and buprenorphine. So in order to meet the objectives, we've crafted an outline. So basically we're going to look at the historical context of opioid use among women in the United States, particularly among childbearing age. Then we'll look at the current scope of the problem in the US, we'll be defining what is neonatal abstinence syndrome, looking at treatment options for the mother as well as for the child. Looking at agonist treatment options versus medication-assisted withdrawal, and looking at the different agonists options for the mother, including methadone, buprenorphine, alone, the combination products that buprenorphine and naloxone. Then the opioid antagonist treatment and naltrexone, which we really do not have enough data yet, but I will mention it. Then finally, a summary. So what's important is give some caveats or some historical information. One important point is that both methadone and buprenorphine have historically been labeled by the Food and Drug Administration as Category C. While there's letter categories that are no longer used, many physicians are familiar with these categories. Basically what it ended up saying was that from animal studies have shown adverse effects on the fetus, but the lack of adequate and well-controlled studies in humans, so really these medications could be used as the potential benefits outweigh that potential risks for pregnant women. As of May 2016, the FDA, the Food and Drug Administration, requires both methadone, buprenorphine, as well as other opioid agonist to have a blocked-backed warning that warned as a risk of babies developing neonatal opioid withdrawal syndrome if they've been prenatally exposed to these opioid medication. Neonatal opioid withdrawal syndrome is more commonly known as Neonatal Abstinence Syndrome or NAS. Other important point to note as we go through this webinar is that we know that women can effectively be treated with methadone or buprenorphine. The current labeling states for both of these medications, that these medications can be used as the potential benefits outweighed the risks. It's also important to note that these medications should not be considered off-label use. These medications were approved by the FDA to treat opioid use disorders or opioid dependence. Pregnancy is a condition that happens, but still first and foremost the patient, it has an opioid use disorder for which these medications are effective. In terms of current important information, SAMHSA has just released clinical guidelines in February of 2018, and there were five main recommendations that they gave for terms of clinical recommendations. First, medication assisted withdrawal, otherwise known as detoxification, is not recommended during pregnancy. They also stated, this clinical guidance, that both buprenorphine and methadone are the safest medication for managing opioid use disorder among pregnant women. They also gave the guidance that transitioning from methadone or buprenorphine or from buprenorphine to methadone is not recommended during pregnancy. Really, if you have a patient that had already stabilized on one medication and they're having a good clinical response, we want to keep them on that medication. They recommended that breastfeeding is compatible with methadone and buprenorphine. Then finally, that neonatal abstinence syndrome, that withdrawal that babies experience after delivery, should not be treated with diluted tincture of opium in part because of the other substances that are in the diluted tincture of opium, including high rates of alcohol. This clinical guide is for your reference, if you haven't seen it, I would highly encourage you to look at it. It has 16 fact-sheets that are organized into several different sections from prenatal care and postnatal care. So it makes it very user-friendly, so you can pull out the fact sheet and just get the information that you need for a particular clinical question that you have. When we look at historical context of opioid use in women, while we have our current opioid crisis in this country, we know that this is not the first time that it's happened. Opioid use was first recognized during the 1800s, and we know that the greatest proportion of individuals that were using opioids in the United States happened to be women and they were most likely to be prescribed opioids from their physician. Opioids were used to treat things in women such as menstrual cramps, or a hysteria, or even prenatal postpartum depression. The Southern United States, similar to today, has among the highest in largest per capita of women that were using opioids. Then when we look at the legislation on how things changed with opioid use access, we see that the legislation in the turn of the century really focused around immigration, particularly Chinese immigration. Our efforts in the Philippines to reduce the control, or reduce the supply of opioids from the United States. So for the first time, we started to see the media coming into place to such a drive public policy. We saw linkages between sensationalized drug use among women and then even sexuality to stimulate public outrage at drug use to facilitate the public wanting these policies to reduce opioid use access. We certainly know that when we have women of child-bearing age who are using any substance, including opiates, that we are going to have women that become pregnant and those pregnancies are going to be prenatally exposed to that substance. In this case, since we're talking about opiates, we can see that the first documented cases in our Western culture that at least I can find, happened in 1875 and in Germany. In the United States again, it was 1892, where we saw the first case reported a neonatal abstinence syndrome. Then in the '60s, we saw Goodfriend and colleagues report on neonatal withdrawal signs, Zelson et al. reported the actual frequency of signs in the instance. Then in the 1970s we had two important publications including The Finnegan tool, for which isn't still the most commonly used tools to identify and treat Neonatal Abstinence Syndrome. So what is Neonatal Abstinence Syndrome? It is been characterized as alterations in the central nervous system, the autonomic nervous system, having gastrointestinal distress and signs of respiratory distress. So you can see on the slide examples of each of those things in the different categories to create the signs and constellation that defined NAS. It's important to note that neonatal abstinence syndrome is distinct from fetal alcohol syndrome. We know, we have a lot of data to show that babies that have fetal alcohol syndrome are at greater risk for having lifelong problems. Whereas NAS, or Neonatal Abstinence Syndrome, tends to be more treatable and appears to be more transient. That said, we know that having an NAS can set up the interaction, alterations of interaction between the caregiver and the child. Depending on how this interaction go, there can be either increased risk or less risk and more resiliency in terms of longer-term effects. Going back to the historical context, we know that there's been different eras of opioid use. We know that the first one, as I mentioned earlier, within the 1800s, in the '40s and '50s, New York saw large increases in teenage opioid use and there was actually a very prominent book called The Road to H, where for the first time, young girls or teenagers were characterized that we're using opioids as being recalcitrance, very unloving, selfish, being promiscuous, being stigmatized as being harder to treat. We also saw many more beds that were devoted to males than there were females, stigmatizing the females have continued and really until the present day, there's a myth that women are much more harder to treat than are men. In the '60s and the '70s, we saw the opioid use increase. In particular, it's been pointed to by our Vietnam veterans returning from that war. Then finally now most currently, we've had our most recent wave of opioids in this country and in part with pain as the fifth vital sign, and increased pain medication access in a variety of legitimate way. When we look at what the history is around pregnancy and opioid use disorders, in 1970s, particularly in 1973, we saw papers that were coming out after methadone had been recommended and approved for the youth of the treatment for medication to treat opioid use disorders during pregnancy. At that time in this early '70s, there was great concern about pregnant women, and so the FDA initially said that all women that were on methadone had to undergo a 21-day detoxification. There were a number of papers and medical providers wrote to the FDA, talking about the concerns around abruptly removing women on such a short detoxification from methadone. Then the FDA actually reversed that decision. We've had almost 50 years of research to show that methadone is associated with very good outcomes. So we know it can reduce maternal craving, it can reduce the fetal exposure to bullish highs and withdrawals. When we give this medication in the context of comprehensive care, which it was originally intended to be provided in, we know that we can reduce the health risk not only to the mom, but also to the fetus into the neonate. It's just a little bit more about the recent history of opioids in the United States. We had in the 1980s, two really important reports that came out that really said that patients who had been receiving legitimate prescriptions for pain relief really had very low rates of leading to addiction with opioids. That also led to Purdue Pharma developing Oxycontin and there were also aggressive marketing, changes in laws allowed drug manufacturers to more directly market to doctors as well as to patients. In the mid 1990s, the pain as the fifth vital sign of course came up and then we had the Federation of State Medical Boards talking about model guidelines for the use of controlled substances. Finally, in the early 2000, we started to see some of the effects of those policy changes, and the FTA in the DEA started to reduce Internet opioids sales which had grown greatly. Then finally, we have burgeoning of pain clinics opening across the country that George Brothers, that's only one example of that as you can see on the slide. Then unfortunately, from 2009 until the present day, we know that drug overdoses are surpassing motor vehicle accidents as the leading cause of injury. More about the current scope of the problem. These are data from 2015, which is just really showing their sheer number of individuals that are misusing prescription opioids, 12.5 million. The high rate of opioid deaths that we have. There you can see 33,091 and the economic cost, and this is probably an underestimate because it's 2013 data of 78.5 billion. So clearly, the economic and the social toll of the opioid epidemic in the United States is just been incredibly profound and it's also given us an opportunity to really make some important changes. These data come from Theodore Cicero and what we can see in these three different slides is that looking at the far left, you can see prescription opioid from the open circle and heroin in the closed squares. You can see how the heroine is actually been reducing from the 1960s to the 2010. So there's little uptick in the last 10 years, and then you can see how the prescription opioid had started to climb, and then there's a downward tick as heroin has been up taking. We traditionally thought of that males are the most common users of opioid, and you can see here that closing of the gender gap. It was very wide in the 1960s and in the 2010s, we actually saw it surpassing of women compared to men. Then finally, it's also a bit certain traditionally seen as a non-white issue and we can see here the large number of proportion of white individuals who are using opioid compared to non-white. That's not to say that we still have many minority populations that definitely need treatment. When we looked at the most recent data from 2015 and 2016, we can see the annual number and age adjusted rate of overdose deaths in the United States. If you focus on males in the blue and the red bars respectively, you can see that across all of those bars, compared to females in the green and the purple respectively. But for all of his bars males have higher overdose deaths compared to women. But you can see that when we look at the prescription bar, that seems to be a smaller gap than we have with all of the opioid. So with women, there are a few things that we know about them currently. We know that compared to men, women are more likely to be reporting chronic pain. It doesn't mean that they're more likely to have it, they're just more likely to report it. We know that women compared to men are more likely to be prescribed, prescription pain relievers and in higher doses and for longer periods of time. We know that women tend to have what we call a telescope effect, which is that short duration between their first opioid use, and they're seeking help for their opioid use disorder. We see that actually across many different substances, alcohol, cocaine, the variety of different substances when intend to have this telescoping effect. Of the great concern, is that women have been found to be less likely to receive noloxone for an overdose than their male counterparts. That is something actually that we've been working to really address. Helping to train first responders so that they know to look not just for injection paraphernalia, but really for more subtle signs, factors that can indicate an overdose by opioid for which noloxone would be an appropriate response. So when we compare women and men some more, we know that women on average tend to experience greater impairments in all aspects of their life when they are using substances compared to men. That is in terms of employment, in terms of social roles and responsibility, they tend to have greater psychiatric, co-occurring disorders, and more medical problem than men. We know that women certainly by their sheer biology can be subjected to sexual risk factors and injection practices based on the cultural norms in the drug he's in community. That we also know that very few women who actually need treatment receive it every year. So these data show you the prevalence that opioid use disorders during delivery. What we can see is that while in the United States we know when we have a greater prevalence of individuals or the general population using opioid, pregnant women are not immune. So we can see here that the rate of overall women who are pregnant delivering with an opiate exposed delivery have been growing. You can see that in that light blue star, the overall. Then we can also see in terms of the ages is that 20-34 year old age in the green with the little triangles, that you can see has tended to go up the most. So I think it's important when we talk about substance use during pregnancy that we don't forget the other types of substances that women are using and then become pregnant. So these data are from 2015, the most recent national survey on drug use and health data that we have looking at past-month use. You can see in the very non-pregnant bars to pregnant bars that for the alcohol and tobacco, that those are the most common substances that are used by both non-pregnant and pregnant women. Interestingly, in the pregnant women, it tends to be that we see a greater reduction in alcohol use in the orange bars than we do with tobacco. Tobacco tends to be the most common substance used by pregnant women. We also know that these are data from 2012 among women of childbearing age that we can see. These are opioid misuse data among females that are admitted for treatment. We can see that pregnant women are actually more likely or higher proportion or likely to receive treatment than their non-pregnant counterparts. I think that in part is to do with the federal laws and regulations that we have getting priority status to woman who are pregnant. Pregnancy is a wonderful and unique opportunity for women to think about behavioral change. However, it's also can be a double-edged sword, because I think there's a tendency for providers and family and friends to think that just because a woman is pregnant, she magically have greater motivation to change her behavior. Sometimes it leads to greater shame, guilt, and stigma, and a fear of seeking treatment. Unfortunately, mothers who have substance use disorders have a greater mortality rates than women of similar age without such a substance use disorder. We also know that prenatal care, even if a woman does not stop using substances, can have a positive impact on her and her birth outcomes. We really need to do more in this country to be able to help women access prenatal care because we know that there are a number of barriers that women that have substance use disorder face, including a huge fear of having their child taken away from them at birth. We know that we really need to have a much more therapeutic approach in terms of being able to really help the child. We absolutely have to help mom have greater well-being. So these data were republished in JAMA. First off, there was Steven Patrick. These data were the first national data that we had, that we really looked at the weighted estimates of rape through maternal opioid use and hospital birth that showed the increasing use of opioid among pregnant women. So you can see there in 2000, that only 1.2 per 1000 births had an opioid use versus in 2009 that was 5.63. They're more recent data that continue to show the escalation and rate continuing to go up. But these data were really important in terms of turning on the faucet around the national conversation around neonatal abstinence syndrome. Because when you have greater opioid exposed pregnancies, you often have a risk of having more rates of NAS and that's what we can see in that other graph there. These are the current data that we have which shows that every 15 minutes, a baby is born with a diagnosis of neonatal abstinence syndrome. We know that costs have also grown, it tends to be that babies that are covered by Medicaid had been the incident less than growing greater than when all babies in the United States are compared. The really wonderful thing about this fact, about this graphic, is that now we see that moms are actually part of the discussion, meeting more resources and compassionate care, not just before and during, but also after pregnancy. When we talk about neonatal abstinence syndrome, if you remember nothing else, from this webinar, I hope you will remember this slide because newborns by definition, cannot be born addicted. They don't have enough life course to meet the definition of addiction, which is use despite negative adverse physical relationship consequences among one other things. We know that babies that are born, that are abruptly discontinued from that opioid exposure can be born physically dependent on that opioid and can have a withdrawal, but it is not the same as addiction. It's also important to be very careful when you're looking at the literature. To be very careful to delineate what is a neonatal withdrawal, and thinking about our ICD-9 and ICD-10 Codes, which those are the data that are being published now, and that not all of the ICD-10 and ICD-9 codes really are neonatal abstinence syndrome, and not all neonatal abstinence syndrome equals an opioid use. I'll show you the next slide in a minute that'll show that. But it's really important to also remember that neonatal abstinence syndrome is not a diagnosis for a mom if she has an opioid use disorder. So this is a slide I had alluded to. So we know that certainly heroin, methadone, buprenorphine, and other opioids are related to having a neonatal abstinence syndrome. You can see here the onset, the frequency, and the duration for the different types of opioid substances. So that's something that expected. But I think it's also important to show that that last part of the table for the non-opioids, that we see just first, even selective serotonin reuptake inhibitors, that it's debatable whether or not the actual toxicity of the drug that is causing the signs and symptoms of a baby altered behavior. But it's been attributed to the neonatal abstinence syndrome or if it's an actual withdrawal from the SSRI. But you can still see here that onset, it's happening 1-2 days after birth. At 20-30 percent of babies that are exposed to SSRIs in-utero, are being identified as having an NAS. Also you'll note in this slide are the inhalants that also if expressed 24-48 hours after birth and almost half of babies exposed to inhalants had been diagnosed with having a neonatal abstinence syndrome. So the important point is NAS can be a variety of different substances and not just opiates. We can't make that assumption. We often know, when we're looking at the NAS literature, that there are a variety of factors that can contribute to how long an NAS lasts and how severe it is determined to be. We know that genetics can increase the length of stay, where it's been associated with longer lengths of stay. We know that tobacco use, benzodiazepine use, and as we saw in the previous slide, SSRI use can also lead to longer lengths of stay. More medication used to treat neonatal abstinence syndrome. There are things or a note that hospitals can do to actually reduce the length of hospital stay and the severity, the overall generalized attribution of severity, to NAS. That includes looking at are babies treated in a neonatal intensive care unit? Babies that tend to be treated with their mother, there are fewer babies that actually need medication to treat their NAS. The choice of tools to examine and assess NAS can make a difference, as is supporting breast-feeding. Then keeping that mom and baby together can all the constellation help reduce the amount of medications babies are exposed to and the time that they stay in the hospital. There are a couple of predictors that have been noted in the literature, in terms of receipt of NAS treatment, having a higher birth weight can lead to a higher risk for having medication to treat NAS, as can more nicotine use. I'll show you specific data on that later. There's often an over-reliance on urine testing in our field. I think it's really important to note that just because a baby has a positive urine test for a specific substance or a mother has a positive urine tests for a specific substance, that this does not determine parenting. All it tells you is that there has been recent use of a substance. Really, having a substance use disorder if that is found in the mom should really only be one factor in determining overall safety for children to go home with mom. If urine toxicology or any other type of biological matrices is used to look for the substances that had been used during pregnancy, there needs to be confirmatory testing and not to rely on quick-dipstick methods or non confirmed quick tests to make such life changing decisions for mother and child. It's also important to remind you that patient consent, maternal consent, is needed before specimens can be collected from the mother. Maternal consent is not needed for neonatal collection. It's important for you to know about changes in federal policy that has happened. So the CAPTA, which is the Child Abuse Prevention and Treatment Act, has been updated recently when the Comprehensive Addiction and Recovery Act was passed in 2016. What CAPTA really does is it removed the word illegal from the definition and also put much more emphasis on a plan of safe care. If you see that last part is read on the slide, you can see that the development and implementation by states of monitoring systems that regard the implementation of these plans of safe care became very important. All states are required, if they're receiving money for child protective services, they need to be reporting very specific data to the federal government, around plans of safe care, and who's receiving them, and how they're being implemented. I'd encourage you to know what your plans and how your state has been responding to this new federal policy. We often think that any woman that has a positive urine test for a substance, has a severe substance use disorder when in fact, we know that there's a wide range of substance morbidity or severity. It can be from no use, to more just occasional mild issues, all the way to the severe use. So I think it's important to really think about what type of treatment is really needed, in order to best respond to the level of severity of a substance use that a woman has. So that brings me to a case study that I'm going to ask you to think about, as we walk through the rest of this webinar together. So how would you approach this woman who's a 24-year-old woman, who's coming to you for opioid disorder treatment? She's now 13 weeks pregnant so she's in her first trimester. She'd never been pregnant before and she's been using opioids continuously for seven years, and just started injecting. What are the things that you would want to know and how would you respond to her to manage this patient? I would encourage you to spend two minutes and write down a few things. What are the first things? How would you address it? What would you do? Then see if your answers will be changed or augmented in some way by the end the webinar. As you're thinking about how you're going to respond to this patient, thinking about it's not just the substance use disorder for what she needs treatment, that there are a whole range of possible issues that are facing pregnant women who come into treatment and their subsequent children. So thinking about what are the risks and resiliencies that moms bring to treatment, in terms of limited parenting exposure, the psychiatric issues, there's also a dad that's involved, and thinking about history of neglect and abuse for the entire diet. Then thinking too about children's temperaments, their own medical issues, and neurobehavioral, and the developmental age of the child. All these different things that you see on the slide can be important factors that can influence outcomes for both mother and child, independent or related to the substance that's being used. As we think about that case, we need to remember that not all opioid exposure is the same, that we have a whole range of different types of patient scenarios. So you can have women that have an untreated opioid use disorder, as you can see there in terms of heroin. You can also have patients that are being treated with methadone, buprenorphine, and obviously no medications to treat opioid use disorder during pregnancy is without a risk-benefit ratio. That's true for opioids, it's true for any medication that we give to a pregnant woman. We need to really balance that against what happens to or not treating it at all. Where will she be and what will happen to her and her child? Then we have another scenario, there are a myriad of different scenarios, but this is just sort of a third common patient situation; is where you have women that have been receiving opioids for pain management but they don't have an opioid use disorder. So again, thinking about what are the relative risks and benefits of maintaining that patient on her opioids to treat her pain. What happens if we don't treat her pain? Women, I can tell you, are incredibly scared of coming to treatment. Their fear of going to jail for their drug use, they have fear of losing their children, once that child is delivered. They have a tremendous amount of shame and fear of stigma. They have a lot of guilt, they have remorse. Many of the women at least that I work with at horizons have incredibly limited resources. So they really need help and support of how are they going to get to treatment every day? Who's going to take care of their child if there's an all day intensive out-patient program or even more intensive, for example, residential programs that where children can come? So in thinking about those barriers: that fear, that discrimination, the prejudice that women face, let's think about a new clinical question. This would be a woman who's 32 years old. She's four months pregnant, has lost custody of her three-year-old, clearly has a number of other medical issues going on, and she's denying her drug use. How do you respond to her? What do you need to say to her to make her feel more comfortable and to trust you to be able to provide the best possible care for her? Now, we're going to turn to talking about medication assisted treatment versus medication-assisted withdrawal, otherwise known as detoxification. So WHO, the World Health guidelines in 2014, it was the first guidelines that I'm aware of that really talked about using opioid medication and the terms in the forms of methadone or buprenorphine as a first line approach over some kind of detoxification for women during pregnancy. So we know that using detoxification for non-pregnant patients hasn't really been found successful, there's a high attrition in treatment and a rapid return to illicit opioid use. So it's curious to think why we would want to try and use this ineffective approach for non-pregnant patients with pregnant patients. We know that medications is facilitated pretension of patients and has reduced substance use comparative, no medications or no treatment. We also recognized certainly if we talked about earlier, the risk-benefit ratio and neonatal abstinence syndrome is a risk and the author note that it is a treatable condition.These are data that are retrospective record review that are still the best data that I can find that really looks at a head-to-head comparison of various types of the declassification protocols versus a methadone maintenance protocol. So what we see here on the top graph is that patients that had only received medication assisted withdrawal in the light blue which was three days or the green which is seven days that we see high rates of loss treatment or very low rates of being routine in treatment. Whereas, if women were receiving methadone maintenance that we have seen much higher days retained in treatments. Then when we looked urine-positive drug screen [inaudible] we can again see higher rates of urines that are positive in the medication assisted blood draw groups compared to the methadone maintained groups. So what that tells us is that methadone's maintenance is a good way to retain patients in treatment and also to reduce drug use. This in a lot of attention looking at medication assisted withdrawal, this is one of the most recent studies we have like [inaudible] all. There were four different groups of patients that received detoxification. Group one was in an inpatient setting, and then other groups were outpatient setting with various forms of more support in group two, much less support in group three, and then a slower win in group four. One of the reasons it was said that the study was done was to look at avoidance of neonatal abstinence syndrome. Whereas, if you look down below, in terms of pregnancy outcomes, the rate of NAS, they're all groups, they'll have some proportion of babies that had neonatal abstinence syndrome and in some cases, it was even 70 percent. So I think we need to be very careful when we think about why we're using detoxification or medication-assisted withdrawal when it really isn't avoiding the incidence of NAS. These data did show, which is consistent with past literature, that it is possible to withdraw women without obstetric complications during pregnancy. Then it did have lower rates of relapse than some of the other studies that we've seen. Unfortunately, we don't have much information about women who are lost to follow-up to know what their longer-term outcomes look like. So with the data that we have collapsing across a variety of different studies, old as well as new, we know that relapse remains a very significant clinical concern for detoxification during pregnancy and you can see the range there from 17 to 96 percent. We really don't have data to support that this is a way to reduce neonatal abstinence syndrome once the baby is born. This can actually increase the risk of maternal relapse in portrait and engagement, which we know is not going to be helpful to improve either mother or child outcomes. So really, we need to be thinking about how we can better treat this maternal chronic disease and not use it to an acute approach, but really looking at more optimal long-term approaches. The SAMHSA guidance document also recommended against using medication assisted withdrawal and you can see there that they're advising that patients need to be advised that such withdrawal can increase the risk of relapse and doesn't have much fetal or maternal benefits. I'm want to get it setup. So Tricia Wright who has been really a leader and looking at maternal mortality in this field, and as you can see here, these are data that show over the last 40 years that we've got an increase in rate of maternal mortality. Well, we've done a good job with reducing neonatal mortality, maternal mortality is going up. Looking more closely at this data, we know that it can be attributed to a variety of factors including suicide and including overdose. So we really need to be taking a much closer look at what we're doing for our women postpartum. So now, let's take a closer look at the different medication options that we have. In terms of methadone and buprenorphine, they're actually very similar advantages and disadvantages for the pregnant patients. We know that methadone, historically and in the collective literature, tends to be much better at retaining patients in treatment than the buprenorphine. We also know that the buprenorphine has a lower risk of overdose and fewer drug interactions and also has the advantage of being able to take it in an office based treatment which can be a double-edged sword if patients need a greater structure that is helpful and place for methadone provided. In terms of disadvantages, every medication has a disadvantage, you can see those here on the slide. Certainly, one of methadone's disadvantages had been a longer neonatal abstinence syndrome compared to buprenorphine. In terms of buprenorphine disadvantages, the induction can be a bit more tricky, and there can often be a greater risk of diversion because we've got more access because of the way it's described in an office-based setting. The next couple of slides just show an example of an outpatient induction, it is not a purely home induction but it is an induction that we've used at UNC Horizons where we bring them in, we provide them with the COWS, they give us that clinical opioid withdrawal score, and then we provide them with their first medication, wait a couple of hours and then we'll be reassessing the COWS score again, they can go home, they end up taking their next dose of medication at home, then they're having good clinical contact with our nursing staff over the next couple of days to adjust their doses. You can just see that on days one through four with the different dose scenarios and what's happening and how you have a flexible way of responding to our patients. You've had good clinical responses to this type of induction. Here's the primary outcomes or what type of data in order to feel more comfortable to prescribe buprenorphine to pregnant women. There are another study that was published in 2010 is one such study where we were able to do a double-blind comparison of methadone and buprenorphine. It was an efficacy study. What we showed was that the proportions of babies that were treated for neonatal abstinence syndrome were not different between methadone and buprenorphine. But what was different is when a baby had an neonatal abstinence syndrome and with buprenorphine exposed, it requires much less medication to treat that neonatal abstinence syndrome and stayed in the hospital for a significant shorter period of time. That said, both medications in the context of comprehensive care produce very similar other treatment and delivery outcomes. While that was a very well-controlled study with a very particular questions to be answered, we now have another analysis of the whole variety of other studies that we have comparing methadone and buprenorphine. You can see those outcomes summarized here where buprenorphine-exposed neonates in his [inaudible] analysis were shown to have higher mean gestational age, greater birth weight, longer length, and greater head circumference at birth compared to their methadone counterparts. That said, methadone and buprenorphine are both efficacious medications. Now that we have two medications, we have more ability to be able to match patients and medications. Another clinical issue in the field has been about the issue of the combination products, and whether that effect on pregnancy. It's the main medication that has been used since then, the mono product of buprenorphine alone. So there are a number of papers that have looked at comparing the combination products to either methadone or buprenorphine, and pretty much the take-home message is that these outcomes tend to be very similar between the two buprenorphine formulation. These data are among my very favorite data that we'd ever published, and really what this shows is that combining methadone and buprenorphine together from the MOTHER study, looking at categorizing across the rates of self-reported rates of smoking, what we can see is that it's really the severity of smoking that are driving a lot of the outcomes. So we can see for all four outcomes that are looked at, there was a dose relationship between better birth outcomes with less to no smoking, compared to those that have an average or greater than average smoking. Another issue that has been very concerning to the field is what happens to the long-term outcomes in children that had been prenatally exposed to buprenorphine or methadone. These data are the most recent data that we have from, again, the MOTHER study. That was blinded assessments of children, and what we felt was really no pattern of differences in physical or behavioral development between those babies that were prenatally exposed to methadone or buprenorphine, or those that have been treated or not treated for a neonatal abstinence syndrome. Other clinical issues to touch on in this field include pain management. We know that we should not be interrupting the methadone or buprenorphine treatment that patients receive, we should not be taking them off of their medication before they deliver, and that every patient needs an individual pain management plan before she delivers. The SAMHSA guidelines has given some nice composition about what type of pain medications to use, and I would just highlight that we want to not be giving large numbers of opiate pills to patients that just postpartum, particularly if it's vaginal. Postpartum patients without other types of complications, and that we want to be avoiding those partial agonists because they can throw women into acute opiate withdrawal, and you can see those on the slide. In terms of breastfeeding, breastfeeding we know in and of itself has great advantage to both mother and child in terms of the most complete nutrition for a child. We also know that the amounts of medication from methadone or mono-buprenorphine are incredibly low that are getting infant milk, and then even with buprenorphine, because it's so poorly bio-available, the infant is even getting even less of that medication. So the most recent guidelines suggests that both medications are compatible with breastfeeding and stabilized women. In terms of the combination products, we don't really have data on this product yet. So the product label says we need to exercise caution, but we really need to consider this development on health benefits with breastfeeding, along with the mom's need for the medications. In terms of naltrexone, we have very little data on this. We know it's an antagonist that can reduce opioid cravings, but the expert panel of SAMHSA couldn't agree whether or not it should be recommended. So again, thinking about that risk-benefit ratio for the individualized patient will be important. Some of the issues to think about with naltrexone include induction, that if there's a one that's not already maintained on naltrexone, it's certainly going to be a challenge and could create great fetal stress. Thinking about pain relief options if when mom goes to deliver, and postpartum can be an issue. Then there are issues around breastfeeding in terms of the possibility of reduced milk production. So we really need a randomized or some prospective trial looking at the relative safety and efficacy of naltrexone. We know that rates of naltrexone are increasing in the country. It's yet another option for how to address opioid-use disorder. So we really need those data sooner rather than later. Whatever conversation that you're having with women around an opioid-use medications to treat them, we need to be making sure that our documentation is very clear and very rigorous. Documenting the conversations that you've had with women around the risks and benefits, documenting how you're going to address their pain relief during labor, delivery, and postpartum. What breastfeeding recommendations you have, and where the woman is going to deliver in the hospital, what those protocols are for her, and what the protocols are around neonatal abstinence syndrome. There are huge variations in what's happening in this country, and she really needs a compassionate and informed response. I really wanted to make sure that we talked about screening versus urine testing. There seems to be a lot of confusion in both practice, as well as the literature right now. So screening for substance use really should be a verbal, or a written, or a computer questioning about patient history. Having a urine testing is only one piece of that information as a screening. But urine drug-testing is distinct from screening for substance use. We know that such urine drug-testing really can't replace screening and a conversation with the patient. And so we need to be very careful too about what type of trends testing that we are doing. We need to be getting content, and we need to be knowing, recognizing, and acknowledging the limitations of both screening, as well as testing. So let's talk a little bit about should all pregnant patients who have had an opioid use disorder be considered high risk? The answer is no, that we really need to be thinking about each patient individually and just because they have a substance use disorder, particularly an opioid-use disorder, doesn't necessarily qualify them for being high risk. We need to be looking at all of the issues that are happening with the patient to determine if they're high risk. There's also a question commonly about, well, what if the mum gets from her treatment and she delivered her baby, should we then the tapering her off her medication? That needs to be a very careful documented conversation, and really thinking about what is best for mom and baby. We know that if mom is stable on her medication, that the likelihood of her continuing to have stable outcomes improves. So before you consider tapering off her medication, you really need to have a very good safety plan, if that's really what she wants to do, she needs to be thinking about how is she going to maintain that social environment, that stability at home. What kind of partner support that she had? What kind of support does she have in her community? She needs that safety plan to be in place before that tapering starts. What's going to happen to her and her child if she does return to substance use? If that decision is made to discontinue, slower is better to ensure that there's an opportunity to talk about the role that medication is playing in her life at each stage, and that there can be a reduction or an increase in dose if that that's what she needs to make sure that she's continuing to be stable. Another important piece of that plan is giving every patient that is prescribed an opioid agonist naloxone she knows how to provide, and that her caregivers also know how to provide. I think all of this, everything that we do in terms of treatment needs to be grounded in a recovery oriented system of care that includes supporting not only treatments, but those dimensions of recovery that helped keep patients well, including women in a postpartum period. So what does her overall health look like? Her physical health from head to toe? What does her home look like? What do we need to do to help get her the safe place to live, and help herself get a safe place she needs to live? What is that purpose that she's living for? How does she feel connected and grounded to not only herself, but others and community? The opposite of addiction really is connection. So maintaining a healthy systems of connections is an important part of that recovery oriented system of care. So coming full circle to where we started, thinking about that patient that came to you in the beginning where she's 24, in the first trimester, first pregnancy, and using opioids for seven years, how have your answers changed in how you would manage this patients since the start of the presentation? I would encourage you to take one or two minutes to jot a few things down. So just to summarize, we know that it opioid use disorder is growing among women, and pregnancy certainly is not a protective factor for this. We know that it's at great risk to have an untreated opioid use disorder during pregnancy, not only for the woman, but also for the fetus and her child. We know that NAS is certainly a serious condition that's gotten tremendous amount of attention, but it can also be treatable. We really need to be working with mum and baby to build up those resiliency factors and reduce the risk factors. There are a lot of different factors that healthcare providers can do to help reduce, like state an amount for medications that are given to babies needlessly to treat NAS at the same time. Our whole goal shouldn't be to avoid all medications for babies that have NAS for which it's truly needed. Then finally, medication assisted withdrawal, otherwise known as the detoxification. We just don't have the evidence to recommend it as a treatment for pregnant women. We know that both methadone and buprenorphine are FDA products. There's a great discussion around pregnancy and related issues, and there's products inserts, I would encourage you to read them. We know that they are the safest medications that we have right now for treating opioid use disorder during pregnancy. We know that induction doesn't really have to be any more complicated during pregnancy than it does in a non-pregnant period. Certainly, breastfeeding is recommended for women who are stable on their medication. Like any medication, both methadone and buprenorphine have advantages and disadvantages to each other, and we really need a tailored approach and a good conversation that's documented about which medication is best for what type of woman. We need to know more about naltrexone, and we need to have more information around breast milk. It would be great to have a predictive algorithm to know which type of patient is going to respond best to which type of medication. We have a whole host of references. I will end with just saying something about the PCSS mentoring program, that's designed to offer mentoring assistance to those in need of one-on-one interaction with colleagues to address those clinical questions that you might have. You certainly have the option of requesting a mentor from the mentoring directory, and I know that the staff would be happy to pair you with somebody. To find that information, I would encourage you to visit their website. There is a discussion forum that can be really helpful for asking a colleague if you have any type of different questions that can be answered by a whole variety of fantastic clinical experts. With that, I will thank you for your time and attention.
