Episode 2 features Dr. Adam Matson, attending neonatologist at Connecticut Children’s Medical Center-Newborn Intensive Care Unit (Hartford, CT) and Assistant Professor of Pediatrics and Immunology at the University of Connecticut School of Medicine (Farmington, CT). During this episode, Dr. Matson provides a comprehensive overview of NEC as it relates primarily to very low birth weight babies, those weighing less than 1500 grams (3 pounds 4.91 ounces) and who have the greatest risk for developing the disease. He discusses:

* The early warning signs of NEC, what steps are taken when NEC is suspected, and how X-rays are used to diagnose NEC

* How a premature baby’s immune response to the microbiome (bacterial communities) of the intestine appears to play a role in the development of NEC

* Known risk factors of NEC, and how they may affect the intestinal microbiome

* His current research focused on innate immune signaling in the developing intestine as it pertains to the development of NEC

* Current prevention strategies for NEC

* Additional research trends in NEC, and the importance of efforts to prevent prematurity

Copyright © 2015 The Morgan Leary Vaughan Fund, Inc. This episode was produced in part by the TeacherCast Educational Broadcasting Network.

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STEPHANIE VAUGHAN, HOST:

Welcome to Episode 2 of Speaking of NEC—a free, audio podcast series about Necrotizing Enterocolitis.

Produced by The Morgan Leary Vaughan Fund, and funded by The Petit Family Foundation, Speaking of NEC is a series of one-on-one conversations with relevant NEC experts—neonatologists, clinicians and researchers—that highlights current prevention, diagnosis, and treatment strategies for NEC, and the search for a cure.

For more information about this podcast series or The Morgan Leary Vaughan Fund, visit our website at morgansfund.org.

Hello, my name is Stephanie Vaughan. Welcome to the show. I’m the Co-founder and President of The Morgan Leary Vaughan Fund.

Today, my guest will be Dr. Adam Matson, attending neonatologist at Connecticut Children’s Medical Center-Newborn Intensive Care Unit in Hartford, CT, and the Assistant Professor of Pediatrics and Immunology at the University of Connecticut School of Medicine in Farmington, CT.

Dr. Matson will share with me today a comprehensive overview of NEC as it relates primarily to very low birth weight babies, those weighing less than 1500 grams or 3 pounds 4.91 ounces, who have the greatest risk for developing the disease.

During our conversation, he will discuss in varying degrees:

• Early warning signs,
• Steps that are taken when NEC is suspected,
• Diagnosis,
• Risk factors,
• Prevention,
• Current areas of research, and
• The importance of efforts to prevent prematurity

He will also discuss how a premature baby’s immune response to the microbiome or bacterial communities of the intestine appears to play a role in the development of NEC, and his current research focused on innate immune signaling in the developing intestine as it pertains to the development of NEC.

With that in mind, let me introduce my guest today.

Welcome, Dr. Matson, thank you for joining us today. I’m very excited to talk to you.

DR. ADAM MATSON, GUEST: Thanks for having me here.

STEPHANIE: As you know, we’re talking about Necrotizing Enterocolitis, but I’d love for you to tell me about your experience in the NICU and then in the NICU in relation to your experience with NEC.

DR. MATSON: Okay, well, I am an attending neonatologist at Connecticut Children’s Medical Center, which is located in Hartford, Connecticut, and there I’m involved with taking care of premature babies and infants with other types of medical problems. And unfortunately, Necrotizing Enterocolitis is one of the disease processes that does affect premature babies in our unit as like many other NICUs around the world. In our NICU, we average probably about 14 cases of Necrotizing Enterocolitis, or I’ll refer to it as NEC, per year, so it’s a major medical problem for these infants. As I mentioned before, it’s unfortunate that I do have experience in managing these infants.

STEPHANIE: So what can you tell me as a parent about I guess signs and symptoms and what you guys as the doctors and clinicians and nurses are looking for that’s, I guess raises a red flag for you that this baby might have NEC?

DR. MATSON: Sure, so NEC is most common in the very small premature babies, particularly those that are with birth weights less than 1500 grams (3 pounds 4.91 ounces). So these are infants that are typically being fed by a feeding tube that’s introduced into the nose and goes down to the stomach, or into the mouth and goes down to the stomach. Usually these babies are too small or weak to eat on their own. And it’s a gradual process. We start with small volumes of feeds and increase them gradually. And the types of symptoms that babies can start to develop when this process begins can sometimes be nonspecific. They can have decreased activity, they may have increased apnea spells (moments when the baby stops breathing) is something that we’ll see. Their abdomens can become more distended. One of the things that we’ll frequently check for are something that is referred to as aspirates. This is when a nurse is going to give a feed with feeds being given every three hours. They will check the stomach to see how much of the prior feed has actually gone out of the stomach and into the intestines. So often times if the intestine is starting to not feel too happy, that feed can sort of back up and that’s called an aspirate. If the volume becomes excessive, one of the measurements that we’ll use in our unit is more than 50% of the prior feed, that’s a red flag for us.

STEPHANIE: Okay, actually that was the first symptom that Morgan had was his aspirate they said was tinge green which was an immediate red flag and x-rays were taken bedside and that’s—rapidly they discovered that he had NEC and that’s when he had his surgery. So that was definitely a red flag with him.

DR. MATSON: Sure, those signs occur particularly when the aspirate turns green, as you had mentioned for your son that indicates that bile that’s being emptied into the intestine is not emptying down into the more distal portions of the intestines. So for his bile to start backing up, that’s absolutely a warning sign.

STEPHANIE: Okay, thank you. So is there anything else that would be a good warning for parents or questions that they should ask if something’s maybe not looking right?

DR. MATSON: Well, as I had mentioned, many of the signs can be nonspecific and they can actually often occur very fast as well. You know, we do monitor as I had mentioned for those things, bloody stools as well. And if those sort of warning signs come up, typically we’ll end up holding some feeds for a while to not overwhelm the stomach or the intestine with additional food, and as you had mentioned, we’ll end up doing x-rays and that’s the primary way that Necrotizing Enterocolitis is diagnosed. Really what we’re looking for with those x-rays is a finding referred to as pneumatosis intestinalis. And what that is is part of the pathophysiology of NEC is as bacteria are starting to invade through the intestinal wall, they can start to produce gas and make gas bubbles, and when we do x-rays looking for NEC, if we visualize those gas bubbles in the walls of the intestine, that’s diagnostic that the process is indeed happening.

STEPHANIE: Okay, so can you tell me a little bit on the flip side of your experience with NEC on the research side?

DR. MATSON: Sure, you know, perhaps I should talk a little bit about in that regard on what we think actually causes NEC. And I think that the answer to that right now is that we don’t know exactly. But it appears to be a rather complex interaction between bacteria that are inside the intestine, and exaggerated or overactive immune response that’s happening inside the intestine. The whole hypoxia or decrease in oxygen within the intestine also probably plays a role in some cases. But studies have indicated at least in many cases of NEC it’s not—it doesn’t appear to be attributable to a single bacterial species like E. coli or Salmonella. But it appears to be more related to bacterial communities or what we would say is the microbiome of the intestine which can be influenced by certain things that we know to be risk factors for Necrotizing Enterocolitis as well such as formula feeding, where breast milk—human milk is protective, excessive use of antibiotics, antacids, those sorts of things are thought to disrupt the microbiome and result in overgrowth of different species, particularly gram negative bacteria. And when there’s an overgrowth of those types of bacteria in the intestine, those appear to activate certain receptors that are inside the intestine— this is getting into a little bit of the research that I’m involved with, because these receptors primarily in premature infancy appear to be very sensitive to a large number of these gram negative bacteria, and as they start to become activated, they start to break down the intestinal epithelial lining and this results in trans-location of bacteria through the intestinal mucosa—the protective barrier, and then activation of immune cells in the deeper layers. Another feature of the premature infant is that they’re really not able to control that immune response in their intestine very well, so they end up with a very profound inflammatory response in their intestine. That’s really what Necrotizing Enterocolitis is. It’s the most common gastrointestinal emergency in premature babies. It occurs primarily in premature infants. It’s characterized by diffuse inflammation and necrosis, or tissue death inside the intestine. And it’s also associated with very significant morbidity and mortality. About 15 to 30 percent of infants who develop NEC may ultimately die. So it’s a major problem for this population.

STEPHANIE: And can you tell me, I guess a little bit more about what the hospital’s doing in their research? And more specifically, what other areas you’re researching?

DR. MATSON: Sure, so our hospital, we have a number of different projects that we’re involved in. We have a very active lactation program where we’re looking at different aspects of human milk. I had mentioned before that one of the main risk factors for Necrotizing Enterocolitis is diet and formula feeding, and we do know that providing human milk reduces the risk of NEC by about 50 to 90 percent providing a diet of exclusive human milk. So we are currently looking at factors inside of breast milk, macronutrients and how they affect the bacterial populations inside of the intestine and how that may ultimately contribute to infants developing this process. More specifically in terms of laboratory work, we’re now working with some collaborators at UConn Storrs as well and we’re doing a preemie poop project where we’re collecting a lot of fecal samples from babies inside our NICU. And we’re doing a real detailed analysis, molecular analysis where we sequence out basically all the different microbial species or bacterial species inside the intestine. And one of our hopes with this study is that we’re able to identify how diet and exposure to medications affect the bacterial populations inside the intestine, which we know has a very strong role in Necrotizing Enterocolitis. I also have a laboratory at UConn Health Center in the department of pediatrics and we’re looking a little bit deeper at some of the receptors inside the intestine. There’s a group of receptors that I refer to as toll-like receptors, and these recognize molecules that we refer to as pathogen associated molecular patterns or PAMPs. So these are the receptors that are on the surface layer of the cells that line the intestine and respond to these different bacteria. And I think this is the type of research that tying in aspects of clinical care with breast milk to knowing what’s actually growing inside the intestines in terms of bacterial populations, and then looking at more detailed molecular aspects of immune signaling inside the intestine and what’s ultimately controlling the inflammatory process.

STEPHANIE: That’s very interesting. Is there anything else that you would like to add about research specifically? I know one of our major goals is to help the doctors and researchers advance research through funding. So can you talk to me a little bit about funding for research within the NEC community?

DR. MATSON: Sure, well I think that one of the areas that would likely help the most is more funding to look at causes of premature birth. This continues to be a major problem in the United States and elsewhere. Up to ten to eleven percent of infants are born premature. And a significant number of those babies are the very premature infants that are at the highest risk for developing NEC. So I think that I need to mention that as really one of the primary areas because there’s a lot of different challenges that these babies face, and the more that we can prevent preterm birth, I think that would be advantageous for them. The other aspect I think would be important to look at is in terms of diagnosis or earlier diagnosis. Being able to identify which babies are starting to develop some changes in their intestine earlier. I have a colleague that I work with who often says that it’s when we’re diagnosing by x-ray, it’s almost like arriving at the crime scene after the crime has already been committed.

STEPHANIE: Mm-hmm.

DR. MATSON: The care that we implement at that stage is really is very supportive in terms of holding feeds, antibiotics, bringing the suction tube into the stomach, getting frequent x-rays, getting the surgeons involved to help follow the infants, and in many ways, the time that we’re diagnosing these infants at this point is the process is already much too far ahead.

STEPHANIE: It’s definitely a complex disease, and I know that with Morgan, I think within a span of five hours or so he was diagnosed and in and out of surgery and in recovery, so I know that it’s a rapid time frame. But I appreciate all of the information that you shared with us today—I think you’ve given a really good perspective on causes and signs and symptoms, and if there is anything else that you’d like to add in any area for parents that might be listening to this from your perspective as a doctor talking to parents, please feel free.

DR. MATSON: Sure, so I could mention just a little bit more about prevention of Necrotizing Enterocolitis. In some diseases, an ounce of prevention’s worth a pound of cure. When we’re looking at certain populations in the NICU, we often classify premature infants according to their weight. Those at highest risk of developing Necrotizing Enterocolitis are what we would refer to as very low birth weight infants, and those are less than 1500 grams at birth.

STEPHANIE: And that’s about three pounds?

DR. MATSON: Yes, pretty close to that. And I had mentioned efforts to prevent prematurity is a major goal, also diet. The American Academy of Pediatrics came out with a statement in 2012 really encouraging the provision of human milk to all of these babies. We do know that human milk does help protect against Necrotizing Enterocolitis. And if mom’s milk is not available for these infants, many units including ours are now using pasteurized donor human milk. It’s a very safe product, and that has been shown to help as well. Other potential preventative measures is—one would be using a standardized feeding protocol. There is very good data on that. That means really sort of having a very strict protocol for each size baby and how much milk you start with with the feeds, how rapidly you advance them, and what sort of warning signs that the healthcare team should be observing for. So that has been shown to be very important. Limited use of antibiotics appears to be very important. It’s a difficult task for us while we’re inside the Newborn Intensive Care Unit because these babies are at such high risk for infection. But one of the things that data has shown is that the more antibiotics, the more unnecessary antibiotics, that these babies receive increases their chances of getting Necrotizing Enterocolitis, so that probably relates to overgrowth of gram negative and other bacteria inside the intestine that activate the inflammatory cascade. There’s a few interesting other preventative measures that are topics of conversation within our field and one is using probiotics. There is good data out of other countries. So, I should say that probiotics are live bacteria. They’ve been using older children and adults for some time for various reasons. Bifidobacterium and Lactobacillus are the most common probiotics. Those are bacteria that are typically found in the stool of breastfed infants. And many units outside of the United States are now giving these probiotics, which they’re giving them to extremely premature infants in an effort to prevent NEC from happening. And the thought is that these help to prevent some of the pathogenic bacteria from growing, they also help to mature the intestinal barrier inside the intestine. At this point in time in the United States, however, there has not been a—at least to my knowledge—there has not been a properly randomized, controlled trial to study these here. And also another major issue using probiotics in the United States is how are they regulated by the FDA as they’re considered a food. So really you can go to GNC or CVS to buy probiotics over the counter. So with that type of designation by the FDA, they don’t have the same oversight as a drug would, and one of the concerns with many of the NICUs in using a product like that is it doesn’t have the same consistent quality oversight, meaning that we don’t know how pure it is or how consistent the actual dose would be that we’re giving to premature infants, so hopefully some research down the line will help answer those questions.

STEPHANIE: Well, I think you’ve given us a lot of information, a lot of really good information I think, and a lot of really relevant information for parents that will be listening. So I really appreciate you sharing your time with us, and joining us today. And so with that, I will let you go. And…

DR. MATSON: Okay, well thank you very much.

STEPHANIE: we will talk again.

DR. MATSON: Sounds great.

STEPHANIE: Thank you.

DR. MATSON: Okay, take care Steph.

STEPHANIE: Thank you.

STEPHANIE: For more information about Dr. Matson and his research in NEC, visit: connecticutchildrens.org. A direct link can also be found in this episode’s show notes: http://www.connecticutchildrensfoundation.org/document.doc?id=402

In closing, I’d like to share a few thoughts about today’s conversation with Dr. Matson.

One of Morgan’s former doctors described NEC to me as “an inflammatory response gone haywire.” That simple, but vividly descriptive, phrase gave me pretty quick understanding of the disease that nearly took my son’s life.

The inability of a very premature baby to regulate their immune response, and in turn their inflammatory response, appears to be a crucial factor in the development of NEC. And as Dr. Matson mentioned, understanding not only how diet and exposure to medications affect the bacterial populations inside the intestine, but also understanding the immune signaling inside the intestine and what’s ultimately controlling the inflammatory process are critical to fully understanding, and preventing, NEC.

Show your support for our smallest and most fragile babies, those who have the greatest risk for developing NEC. Show your support for continued research in NEC. And join our effort to raise awareness about, and funds for research in NEC by making a donation to Morgan’s Fund at morgansfund.org/donate.

If you’ve had a personal experience with NEC and would like to share your story, or have a question or topic that you’d like to hear addressed on our show, e-mail us at feedback@morgansfund.org. We’d love to hear from you!

Additional Information

You can make a donation directly to Dr. Matson’s research in NEC at Connectiut Children’s Medical Center by visiting https://www.connecticutchildrensfoundation.org/giving/nec

Copyright © 2015 The Morgan Leary Vaughan Fund, Inc.

The opinions expressed in Speaking of NEC: Necrotizing Enterocolitis (the Podcast series) and by The Morgan Leary Vaughan Fund are published for educational and informational purposes only, and are not intended as a diagnosis, treatment or as a substitute for professional medical advice, diagnosis and treatment. Please consult a local physician or other health care professional for your specific health care and/or medical needs or concerns.

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