In the final episode of our four-part series “Hot Topics in Neonatology” we explore neonatal abstinence syndrome (NAS), a byproduct of prenatal drug exposure — one of the fastest growing public health problems in the world.
In the U.S., the most recent data from the CDC indicate that the number of pregnant people with opioid-related diagnoses documented at delivery increased by 131% from 2010 to 2017. The implications for their babies include preterm birth, still birth, birth defects and neonatal abstinence syndrome, or NAS.
SEGMENT 1: We talk with Dr. Ju Lee Oei from the Royal Hospital for Women in Sydney, Australia, who provides an overview NAS — what it is, how it’s diagnosed and how it’s treated.
SEGMENT 2: Andre Sukta, a research and development projects manager at the United States Drug Testing Laboratories in Chicago, joins us to talk about the recent history of newborn toxicology screening.
Guests:
Ju Lee Oei, MD, Neonatologist, Royal Hospital for Women, Randwick; Conjoint Professor at UNSW Sydney; and Honorary Associate Professor at the NHMRC Clinical Trials Centre, University of Sydney
Andre J. Sukta, MSFS, Research & Development Projects Manager, United States Drug Testing Laboratories
Producer/Host: Carol Vassar
Explore the Full Series:
Part 1, Episode 50
The NICU View: Mom & Baby
Part 2, Episode 51
Fluid Dynamics: What’s New in Treating EPRA
Part 3, Episode 52
Fragile Beginnings: Exploring NEC in Newborns
EPISODE 53 TRANSCRIPT
Carol Vassar, podcast host/producer:
Welcome to Well Beyond Medicine, the Nemours Children’s Health Podcast. Each week, we’ll explore anything and everything related to the 80% of child health impacts that occur outside the doctor’s office. I’m your host, Carol Vassar. And now that you are here, let’s go.
MUSIC:
Well Beyond Medicine!
Carol Vassar, podcast host/producer:
Prenatal drug exposure is one of the fastest-growing public health problems in the world. In the US, the most recent data from the CDC indicates that the number of pregnant people with opioid-related diagnoses documented at delivery increased by 131% from 2010 to 2017. The implications for their babies include preterm birth, stillbirth, birth defects, and neonatal abstinence syndrome, or NAS. NAS is the subject for this fourth and final segment in our hot topics in neonatology series. In a few minutes, we’ll learn about newborn toxicology testing. Right now, we hear from neonatologist, Dr. Ju-Lee Oei from the Royal Hospital for Women in Sydney, Australia, about NAS. What it is, how it’s diagnosed, and how it’s treated. Here’s Dr. Ju-Lee Oei.
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
So it stands for a withdrawal process that newborn babies undergo when they’re exposed to drugs when they’re in utero. So most commonly caused by opioids, but other substances can also cause newborn withdrawal.
Carol Vassar, podcast host/producer:
Does that mean they’re dependent on whatever drug their mother is also dependent on?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Yes. Because using the word addiction means that they have the capacity to look for those substances, but they are dependent because they’ve been exposed so long to those drugs that they become tolerant. So when you don’t get the drugs after the babies are born, they undergo a withdrawal.
Carol Vassar, podcast host/producer:
What are some of the signs and symptoms of NAS?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
So NAS can be pretty bad if you don’t find the baby and you don’t treat the baby. So, way back in the 19th century, we knew that if you didn’t find the withdrawing baby or treat them, nine out of 10 of them would die. So, signs just like an adult, the baby goes through cold turkey when the umbilical cord is cut, they start quite healthy, and it was recognized way back hundreds of years ago. But then, suddenly, they start to gradually become unwell. They can’t feed, they shake, they shiver, they may vomit, they may have diarrhea. And then the worst ones will fail to thrive. They lose weight. They may have seizures, and the very worst ones will die.
Carol Vassar, podcast host/producer:
And now, we know the opioid crisis is worldwide. It’s huge here in the US. It’s not the only, as you pointed out, the only substance on which a newborn can be dependent. But how has the crisis, as it’s grown over the years affected NAS? Has there been a larger incidence of it?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
So, especially in the US, the rates of NAS have just skyrocketed over the last couple of decades. I think Stephen Patrick’s last data showed that one baby was born with withdrawal every 18 minutes in the US. So there’s a massive number, but there’s also a worldwide problem, as you have alluded to, the United Nations is very, very concerned about the worldwide crisis for babies exposed to drugs of dependency not only opioids, because the withdrawal is probably the tip of the iceberg that these babies face. They have huge problems as they go through life.
Carol Vassar, podcast host/producer:
Well, let’s talk about some of the other drugs or substances upon which a baby could be born dependent, aside from the opioids that we just talked about.
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Yes. So, if a mom becomes dependent on opioids, it’s quite unusual in many places for the mom just to take only opioids. So in Australia, for example, if you have an opioid-using mom, about 80% of them will use other drugs. And these could include prescription meds. They could include alcohol, nicotine, sedatives, methamphetamine, cannabis, a whole variety. And all of these have the potential to cause withdrawal and other harm to the baby.
Carol Vassar, podcast host/producer:
And you included, I heard you say alcohol and fetal alcohol syndrome is related to NAS in some way. Talk about that.
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
That’s something that we haven’t teased out, really. Fetal alcohol syndrome or fetal alcohol spectrum is another entity usually, but many times it will co-mingle because the moms can use multiple substances. So FAS D, or fetal alcohol syndrome disorder, long word has characteristics that will help us identify prenatal exposure. It is recognized as the only definitive teratogen of all the addictive substances. So it makes detecting children who have been exposed to non-alcohol drugs more difficult.
Carol Vassar, podcast host/producer:
Do they present differently depending upon what substance mom was dependent on?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Definitely. So, there’s a lot of variations with NAS, whether you’re genetically more inclined or what type of drugs your mom took, other medications she took, and what her lifestyle issues are. If you have a baby that’s born to just an opioid-using mom, strictly on the methadone program, about half of them will withdraw severely enough to need medication. But if the mom uses other things like benzodiazepines, maybe cannabis, or maybe alcohol, then the withdrawal can be more severe, and the withdrawal could be unpredictable.
Carol Vassar, podcast host/producer:
Are there guidelines that surround NAS and its diagnosis and treatment?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
We love our guidelines, but unfortunately, guidelines are guidelines. And whether we follow them depends on where we are. And many of our guidelines they don’t often go beyond the newborn period. We’re very focused as clinicians on treating with medication. But the neonatal abstinence baby has many other problems they need to deal with. They have problems with their home life, poverty, education, parental needs. So, there’s a lot of other issues that guidelines cannot cover.
Carol Vassar, podcast host/producer:
And that’s a good reminder that once the child has been withdrawn from whatever drug upon which they’re dependent, there are health issues, there are social issues that you just outlined so nicely. How does this affect society at large? What kinds of services are available for children who have been diagnosed with NAS in the long term?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Great question, because this is something we need to bring attention to. It’s only recently that we’ve been able to find out what happens to our children with NAS before, because before that, many of them died. So, in the 1950s, the death rate from NAS was still one in three. So now currently, most babies will survive NAS. And what happens to them later is something that we need to get our heads around and get help for. So, in Australia, we know we’re on an island, and not many people can escape, so we can track you. So, our studies have looked at babies with a history of NAS until they’re about 20 years old. So, in our studies, what we’ve shown is that these poor little kids, even if they survive NAS, they’re three times more likely to die, two and a half times more likely to fail at school. And their school performance goes down as they age. They keep coming back to hospital for many problems, including maltreatment, injuries, trauma, infections. So their problems don’t stop when the withdrawal ends.
Carol Vassar, podcast host/producer:
Let me ask about, do they have an increased risk of becoming dependent again in later in life?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
That’s a million-zillion-dollar question. We know that prenatal exposure to all these substances do impact brain development and function. They interfere with neurotransmitter functioning. And in adults and animal models, if you look at it biologically, that will increase your risk of dependency to other substances or other habits later on. However, that’s a very, very promising advantage of being a little baby. The brain is very plastic, and your brain undergoes rapid modifications due to environment, especially if you’re a boy. Your prefrontal lobe doesn’t develop properly until you’re 25, right? So, there’s a lot of opportunity for the environment to help prevent later problems that the baby has gone through in utero.
Carol Vassar, podcast host/producer:
It sounds like there’s a sliver of hope right there.
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Definitely, always.
Carol Vassar, podcast host/producer:
The baby’s mind is a brain, is plastic, elastic still working to create the synapses. Let’s talk about moms. I want to know how often a mother comes in, and you know she’s addicted. How important is it for you to have an antenatal analysis of mom and clinical checkup of her to see what’s been going on in her life that might affect the child?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
It’s so important to start engaging with moms before they give birth as soon as you can, even if it’s one day before birth. That’s important. It depends on where you are. There are a lot of different rules and regulations in a country like the United States, for example. In Australia and in New Zealand, we have a harm minimization approach. So we don’t have criminal prosecutions for moms who admit to using drugs. We try to get them as much help as early as possible. And look, there’s a lot of things that moms who use substances have to deal with. I remember when I was pregnant, I had my baby, I couldn’t get out of the house for six weeks, out of my pajamas. And these poor ladies have to go to all these treatment programs, and they’ll go and present to parole boards, whatever. You can’t imagine the stress they have. So the most important thing is to make sure mom’s okay. Unfortunately, at the moment, despite this, half the babies with NAS in Australia land up in foster care by the time they’re one year old.
Carol Vassar, podcast host/producer:
Let me ask: what kinds of interventions are helpful for babies with NAS and for their moms?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Oh, I tell you, look, I’ve looked after the clinic… We’ve looked after more than 2,000 families with neonatal abstinence. And one of our moms came back with a fourth baby. She had four children with us. The oldest is 25 now, and they’ve all done really well. And what we do is, first of all, you try to help mom with the drug use, moderate the drug use, and accept that many women who use substances will not be completely abstinent. After the baby is born, the crucial time is the first 2000 days of life. So that’s when all the services will impact most on how the family functions and how the baby develops. So supportive treatment.
And in our service in Australia, we’ve recognized that children with NAS have certain biological needs that need intervention, just like preterm babies. So, in our service, what we do is we provide continued intervention or clinic visits for at least two years. We check up on their eyes because many of our children are shortsighted or they have eye problems from the effects of the drugs. And if you don’t fix eyes, the baby can’t see. When they go to school, they can’t read, and they go downhill. And the third thing is that we check up on their neurodevelopment, just like any high-risk baby from a NICU. So we offer them developmental tests and interventions as they need to,
Carol Vassar, podcast host/producer:
As long as they’re identified at birth?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
That’s right or identified even later on. As soon as you can is better, but better late than never.
Carol Vassar, podcast host/producer:
What would you like to see in five years, 10 years the outcomes for children who have been diagnosed with NAS?
Dr. Ju-Lee Oei, Royal Hospital for Women, Sydney, Australia:
Okay. That’s a great question because, at the moment, what we have been doing for the last few decades is just to make sure that they’re alive at the end of their withdrawal. So I think we’ve gone beyond that. We’ve got clinical tools to make sure that the children are treated sufficiently well for the withdrawal. But what I would like to see is some acknowledgment that prenatal drug exposure, just like any other maternal illness, can have a longstanding impact and that we need to provide help for the children and the families even outside of our neonatal nurseries.
Carol Vassar, podcast host/producer:
Dr. Ju-Lee Oei is a neonatologist with the Royal Hospital for Women in Sydney, Australia.
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Carol Vassar, podcast host/producer:
Diagnosing NAS begins with a maternal history of substance use during pregnancy and the appearance of withdrawal symptoms in the baby, usually in the first 72 hours after birth. These symptoms, including tremors, twitching, excessive or high-pitched crying, poor feeding, fever, diarrhea, and throwing up, are scored according to severity, which helps determine what immediate treatments are required. Newborn toxicology testing of the baby’s urine, umbilical cord or meconium, or baby’s first poop is also available. While not routine, this testing can confirm a baby’s dependency on opioids and other illicit substances. Andre Sukta, a research and development projects manager at the United States Drug Testing Laboratories in Chicago, joined us to talk about the recent history of newborn toxicology screening.
Andre Sukta, United States Drug Testing Lab, Chicago:
Our owner, Doug Lewis, was working in a hospital, and he was approached by a doctor who had a newborn that was going through withdrawal symptoms, and they were requested to try to figure out what was going on in this newborn because drug testing and newborns didn’t exist at this point. They eventually figured it out, and it was cocaine, cocaine’s metabolite, benzoylecgonine, and that’s what the baby was addicted to, and that’s what the withdrawal symptoms were from. And they started creating this whole drug testing in the newborn population because he wanted to give voice to the most vulnerable segment of our society, which are our children. And he wanted to be able to allow doctors and physicians to use this testing in appropriate ways because we need to protect and enrich these children’s lives. And that’s our vision is to protect and enrich lives. And so what we learned is as we kept going on and furthered our testing in our panels, in about 20% of cases, the meconium passes during the birthing process. So, those specimens are lost.
And so when you have these unique specimen types, if you lose it and you can’t test for it’s a struggle. So we started developing umbilical cord testing because every baby is born with an umbilical cord, and so we actually take the tissue, and we actually ask the doctors and nurses who collect it to rinse it with saline, pad it dry, and then ship it to us. And so we’re actually testing the tissue, not the blood, but the blood incorporates the drug into the tissue, and so it’s a homogenous sample. And so, depending on whatever six inches we get from the newborn side, we want those six inches. Doesn’t matter where it is in those six inches, it’s homogenous. So we get the same results. And so we keep trying to expand upon this, and our panels are very extensive.
The fentanyl struggle in the United States currently has been one of those big challenges, and so there are a lot of fentanyls. What our friends over in the crime labs and the DEA are finding in all of those C-samples, they still contain fentanyl. So as long as you’re testing for fentanyl, you’re going to see it regardless of its para-fentanyl or alpha-fentanyl or any of these new ones that are coming out.
Carol Vassar, podcast host/producer:
It falls in the fentanyl category?
Andre Sukta, United States Drug Testing Lab, Chicago:
Yeah, it’s still there. And so the testing is still appropriate, and that’s the key, right? We want to make sure that we’re doing appropriate testing. And so now the new thing is this adulteration of our drug supply with veterinary products. So we have recently launched xylazine in our test panels. And xylazine is a tranquilizer that’s commonly used in the veterinary world, specifically in horses, because it’s a really good way to sedate the horse while you do some minor procedures to it.
I started my career testing racehorses, so I am familiar with the veterinary drugs. So to hear them come back around some 20 years later, it’s unnerving because these are all veterinary drugs. They’re not meant for human use. But xylazine is one that it’s a sedative, and it acts like an opiate, but it’s not an opioid. And so the typical treatment for opioids is Narcan or Naloxone, and so that will then help remove those effects. The drugs that are then also laced with xylazine, it looks like the Narcan had no effect because they’re still having significant CNS depression. So what needs to happen in those cases is they still need to have lifesaving measures taken. And so in adults, it’s important that somebody’s there watching their breathing, watching their pulse rate, and putting them on oxygen or hooking them up to a heart-lung machine in order to help them breathe and keep their heart going because those sedative effects are so strong.
Xylazine is one of the interesting ones because it actually did attempt to go through human trials and during the human trials, they pulled it. They said-
Carol Vassar, podcast host/producer:
It wasn’t right.
Andre Sukta, United States Drug Testing Lab, Chicago:
It’s not right. This is not going to work. The sedative effects are too great. So this was tried, but they said it’s fine for veterinary use. And so that’s where it is today. And so what we’re starting to see in our population set is this increase. The DEA has recently published their findings in regards to xylazine, and from 2020 to 2021, in the south, they’ve seen an increase of almost 200% of xylazine being found in products and street drugs. And so that’s where it’s the most significant. And then on the West Coast, they found 100% increase. In the other areas, there’s still increases, but they’re a little bit smaller.
Carol Vassar, podcast host/producer:
So we’re seeing new drugs that need to be detected in babies because moms might be using these kinds of things during pregnancy. This is an important step toward detection. How important is it, and how widespread is the testing of newborns for these drugs? And xylazine and fentanyl are not the only… You have a full panel on both the meconium side and the umbilical cord side. Talk about how widespread testing is.
Andre Sukta, United States Drug Testing Lab, Chicago:
Yeah, so testing is unfortunately not widespread. It depends on the hospital system and what they’re willing to do. Some of them are still doing urine testing in newborns. We know urine testing has its challenges in newborns. There’s not a lot of specimen, so they end up a lot of times having to do minimal testing. We provide a service where we do a forensic test, and so the big difference between a forensic test versus the clinical test that some typical hospital labs are doing is we have to do chain of custody. And what that allows is for us to be able to use our results in future litigation or future issues that may come up down the road. If your state or locality requires DCFS involvement or family services, whatever your system is called, our result will hold up in any kind of challenge to that. We can go anywhere from criminal, civil to administrative. Our result is legally valid versus a clinical test, none of the chain of custody is followed, and so it doesn’t hold up in a legal challenge.
Carol Vassar, podcast host/producer:
So when testing takes place, how long until results become available? Because neonates, newborns need care right away.
Andre Sukta, United States Drug Testing Lab, Chicago:
Yes, absolutely. The turnaround time for neonates for us is negatives are reported within 24 hours of receipt at the laboratory, and then positives are an additional one to two days. So, within about 72 hours, you should have your results. And that’s for umbilical cord and meconium.
Carol Vassar, podcast host/producer:
You mentioned that not a lot of hospitals have this and are testing it on every single newborn, but are there some hospitals that are using it when they may have either a suspicion or perhaps mom has said, “Yeah, I’ve been using fentanyl or I’ve been using opioids,” in those situations?
Andre Sukta, United States Drug Testing Lab, Chicago:
Yeah. If the mother’s admitting to it, we will typically get a specimen from the hospitals that we work with because, again, they want to know what the baby’s being exposed to. We would love to see it for everybody. The other side of it is that every hospital sets their process up a little differently. Some of them are going to send it because it’s a high-risk birth. And so how they define that high risk is variable from hospital system to hospital system. But if they didn’t have prenatal care and they just showed up and were pregnant, those typically will get sent because there’s suspicion around that. And with no prenatal care, you wonder what’s going on. So you want to have that testing. If the doctors see the mom is going through withdrawals or during the mother’s intake, they did a drug test, and they popped positive for something, they may send us that sample.
Some hospitals will collect every umbilical cord and then hold onto it in their refrigerator. And then, if they see the baby going through withdrawal symptoms, then they send it to us. So that creates a delay. So when we talk about turnaround time, we can only talk about once we receive it, right? That system works for a lot of hospitals because then they don’t have to send every single one. But the babies that show issues with neonatal abstinence syndrome, withdrawal symptoms, then they’ll send us that test and then we will get on it and get those results within about 72 hours.
Carol Vassar, podcast host/producer:
What’s the future for this kind of testing?
Andre Sukta, United States Drug Testing Lab, Chicago:
There’s some papers coming out that are starting to look at some of the genetic changes that are being caused by drugs of abuse. And so I think that epigenetic work is probably going to be the future, is looking at how the drugs are affecting the genome and changing it and causing methylation. And that will cause the future significant issues. And so if you can start diagnosing it even earlier in the genome side, there is potential downstream that we’ll be able to figure out how to fix the genome problem, and if we can fix it when they’re still really early in developing, hopefully they won’t have those issues downstream. So what I think is going to be the future is really targeted genetic healthcare.
Carol Vassar, podcast host/producer:
Andre Sukta is a research and development projects manager at the United States Drug Testing Laboratories in Chicago.
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Well Beyond Medicine!
Carol Vassar, podcast host/producer:
Many thanks to today’s guests, Dr. Ju-Lee Oei and Andre Sukta, for sharing their time and expertise at the recent Hot Topics in Neonatology conference. And thank you for listening. That’s it for our series on Hot Topics in Neonatology. What do you think? Let us know what you thought by leaving a voicemail at nemourswellbeyond.org. That’s nemourswellbeyond.org where you can also find all of our previous episodes, all the episodes in this series, and subscribe to the podcast and leave a review. Our podcast production team for this episode includes Che Parker, Susan Masucci, Cheryl Munn, and Yari Payne. Join us next time as we learn why the doors of pediatric hospitals like Nemours are swinging open for some adults with cardiac disease. I’m Carol Vassar. Until next time, remember, we can change children’s health for good, well beyond medicine.
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Well Beyond Medicine!
