Episode 5 features Dr. Naveed Hussain, Associate Professor of Pediatrics at the University of Connecticut School of Medicine and Director, Neonatal Research and Neonatologist at Connecticut Children’s NICU at University of Connecticut Health Center in Farmington, CT. During the episode, Dr. Hussain provides an overview of transfusion associated NEC, or TANEC, as it relates primarily to extremely low birth weight babies, those weighing less than 1000 grams (2 pounds 3 ounces) or those born very premature at less than 28 weeks gestation, and who have the greatest risk for developing the disease. He discusses:
* The significant role of blood transfusions in the NICU, and the frequency with which they may be required
* What constitutes transfusion associated NEC, and some of the controversies surrounding TANEC
* The critical period after a blood transfusion when a premature baby may be most at risk for developing NEC
* Some of the correlations between blood transfusions, feedings, and NEC
* His current research focused on the epidemiology (patterns of occurrences) of NEC
* Additional technology and protocol trends in the prevention of NEC.
Copyright © 2015 The Morgan Leary Vaughan Fund, Inc. This episode was produced in part by the TeacherCast Educational Broadcasting Network.
STEPHANIE VAUGHAN, HOST:
Welcome to Episode 5 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. Naveed Hussain, Associate Professor of Pediatrics at the University of Connecticut School of Medicine and Director of Neonatal Research and Neonatologist at Connecticut Children’s NICU at the University of Connecticut Health Center in Farmington, CT.
Dr. Hussain will share with me today an overview of transfusion associated NEC, or TANEC, as it relates primarily to extremely low birth weight babies, those weighing less than 1000 grams (or 2 pounds 3 ounces) or those born very premature at less than 28 weeks gestation, and who have the greatest risk for developing the disease.
During our conversation, he will discuss in varying degrees:
- The role of blood transfusions in the NICU,
- The frequency with which they may be required,
- How transfusion associated NEC is defined,
- The correlation between transfusions, feedings, and the development of NEC,
- Current areas of research, and
- Some of the controversies surrounding the TANEC
With that in mind, let me introduce my guest today.
STEPHANIE: This is Dr. Naveed Hussain. How are you? Thank you for joining us.
NAVEED HUSSAIN, GUEST: I am very good Stephanie. Thank you for the opportunity to communicate with a host of people on this topic of NEC.
STEPHANIE: Thank you. So before we get into NEC in general, if you want to give a little bit of your background and sort of your work with patients that have NEC and their families?
DR. HUSSAIN: Yeah sure. I am an attending neonatologist at The University of Connecticut Health Center and The Connecticut Children’s Medical Center, and I have been interested in NEC for a very long time, since 1994 when I finished my training and joined the faculty here.
STEPHANIE: Okay. And you’re going to talk to us today about blood transfusion-associated NEC, if that’s the proper term. So I guess this is a fairly new concept or this is something that’s fairly new in research studies?
DR. HUSSAIN: Yes it is. In fact, we have known about NEC for a very long time, since the 1960s, and it’s been very frustrating that we have not been able to really figure out what begins the process and how to prevent it. And one of the things that recently came to light was in actually about 2004, 2005. People started looking at babies that were developing NEC and started noticing that some of them had been tranfused with red blood cells about 24-48 hours before they develop NEC. And a very good study was published from Westchester, New York, where they actually made an association, and then suddenly everybody started noticing it. And so it’s only in the last 10 years we have really started paying attention to this entity which we are calling transfusion associated NEC, and some people call it TANEC—T-A-N-E-C.
STEPHANIE: Okay. So can you talk to me a little bit about maybe why babies would be having a transfusion and sort of what you would be seeing afterwards that would be causal to NEC?
DR. HUSSAIN: Yeah, so the use of blood transfusion, especially transfusion of red cells, is very common in the neonatal intensive care unit just because babies when they’re born premature, especially when they’re very small in size, they do not have the ability to make their own red blood cells. And the red blood cells are very important to carry oxygen to the different tissues in the body. So without being able to make the red cells, the little preemies are actually dependent on blood transfusions. And an average preemie who’s less than 1500 grams (3 pounds 4.91 ounces) gets at least four to five transfusions during the stay in the neonatal intensive care unit.
STEPHANIE: Oh wow.
DR. HUSSAIN: Yeah. And it’s quite common for us to transfuse these babies not only because they are sick but also sometimes we have to transfuse them because we have to draw blood for testing from these babies quite often, and that blood has to be replaced. And it is not uncommon that within the first week or so, they have lost about 10 to 15% of their blood volume because of the tests that we are doing. And a lot of units just replace that with packed red blood cells.
STEPHANIE: Okay. So I guess talk to me a little bit about, is transfusion-associated NEC NEC? Or is it its own issue? Or what are the features between that and—I’ll say—the standard thought of NEC?
DR. HUSSAIN: So the standard NEC is basically inflammation of the gut, and sometimes that can spread and cause rupture of the intestine and leakage of the bowel contents into the abdomen. So that’s the typical N-E-C, or NEC. And it has various stages. The earlier stages are when there’s just inflammation of the gut without any leakage of the intestinal contents. But the more severe ones are associated with perforation of the gut. Transfusion associated NEC looks exactly as the regular NEC except that the connection is that it happens right after a blood transfusion. And that association is still being studied. So we are not really sure whether this is a totally different entity, or is it one of the risk factors that makes NEC happen? So that’s still being investigated. In fact, a number of places actually are quite skeptical that this is actually a new entity or association. They feel like this is just two separate things that are unrelated but happen to happen at the same time.
DR. HUSSAIN: So there’s a lot of controversy. And if you look at the literature currently, there are studies that say that this is a real entity and some studies that say that this is just an association. It’s contextual. It is not real.
DR. HUSSAIN: So we are still studying it, but the important thing is it has created quite a scare whenever we are transfusing babies now, as I told you, about four to five times their hospital stay, the babies get transfused. And now every time we are transfusing a baby, everybody is scared. Is this going to lead to NEC? And that’s the big conundrum that we are in right now.
STEPHANIE: Okay. So with that being said, I guess, what precautions are being taken, or how are you trying to, I guess, prevent it in the best way possible or talking to parents about the sort of causal or associated risk factor?
DR. HUSSAIN: Yeah. Since it’s still very controversial, there’s not a lot of information we can provide to the parents because it depends on—some places actually do not believe in this entity and some places are very—they are very certain that this is real. And one of the things that is always associated with NEC is feeding babies. You know, the food in the stomach and the intestines is very important in the development of NEC. And one of the things that has happened is that some people have noticed that if you stop feeding the babies before a transfusion, you may be actually helping prevent transfusion-associated NEC. So there are different centers that are starting to develop some protocols to stop feeds about 4 hours before transfusion and then during the transfusion and then 4 hours after and then start feeds in a very gradual manner, trying to prevent this transfusion-associated NEC. So there are certain centers that are doing that, and there are certain centers that are continuing with regular feeds because there’s still, as I said, controversy about this. So the current trust of research is actually try to figure out the associations between transfusion, feeding, and Necrotizing Enterocolitis. How do they interact, and what are the different risk factors that play a part in making this happen? Is it just transfusion, or is it related to what kind of transfusion it is? It’s a packed red cell transfusion of young, fresh blood, or is it transfusion of blood that’s been kept for a few weeks so it’s kind of losing its potency? Is that the one that makes the baby have NEC? Is it related to some elements in the blood, some immune complexes or bodies that are initiating an immunologic response that is causing NEC? Or is it related to some kind of an organism or virus that’s present in this blood that is precipitating a reaction? Or is it just a chemical or entity that we don’t know of that may be precipitating NEC? So all these things are being investigated at this point.
STEPHANIE: Okay. And are you in particular doing any research specific to this? Or can you talk a little bit about, I guess, studies that are coming along?
DR. HUSSAIN: Yeah sure. So I told you the first studies started coming in mid-2005-2006, and since then there’s been a flood of information on this subject. But one of the things that we’re doing here at Connecticut Children’s and The University of Connecticut Health Center is that we’re taking an epidemiologic approach to this looking at various known and unknown risk factors that could potentially be involved and doing a statistical analysis of this based on a huge database that we have on babies that have been admitted to our unit since 1990. And so we’ve got a huge amount of database that we can search and start looking at different risk factors that may be associated with this entity. So we have been doing this work and presenting it at conferences and trying to understand the epidemiologic basis of this problem.
STEPHANIE: Okay. And I guess my other question would be, with blood transfusions and/or NEC in general, are there any suggestions that you would have for parents on how to talk to the doctors when anything is coming up or things that you’ve seen—anything that you would want to talk to about that?
DR. HUSSAIN: Yeah. So the issue of blood transfusion has always been front and center in the neonatal intensive care unit because everybody’s worried about blood transfusions because previously we used to be worried about transmission of different kind of infections such as hepatitis and HIV with blood transfusions. So whenever we transfuse blood, we have a conversation with the family about the risks and benefits of blood transfusion and why it is needed and what would be the problems with that—expected problems and unexpected problems. So that conversation still continues but now there is an added twist to it because of this association with NEC. And so that’s becoming part of the conversation now. And fortunately or unfortunately, because we have to do this blood transfusion and this conversation has to happen, the anxiety in parents is increased because of this because now it’s like a ticking bomb. When you’re giving a transfusion, everybody’s worried. In the next 48 hours, is this baby going to develop NEC? And so this is an unfortunate thing that happens. Now the anxiety is higher. But since we have recognized this entity, we are starting to educate the families on that. And we share with them the information about this and then make an assessment of the baby’s need for transfusion and what’s the best time to do it? And what should we do to minimize the risk for NEC?
STEPHANIE: Right. And you said that this is for babies that are—the most potential risk is for babies that are under 1500 grams, which is about 3 pounds. So is there less of a chance when they’re a little bit bigger that this is going to be a problem? Or are there other factors that parents need to be aware of where something like this is seen?
DR. HUSSAIN: Yeah sure. I mean, so that actually has just come out. We’ve done some work on this trying to figure out when is it most likely to happen? And when is it least likely to happen? And what we have found actually is that it’s most likely to happen in the youngest of the babies, the extremely low birth weight babies or the very premature babies born at less than 28 weeks gestation or less than 1000 grams (2 pounds 3 ounces). So that’s where it’s most common. And also what we have found when we looked at over 6,800 admissions over many years is that we didn’t see a single case of transfusion-associated NEC after 33 weeks of corrected gestational age. So in a way, it’s kind of reassuring that if a baby needs a transfusion after the gestational age is corrected to 33 weeks, then the chances of this entity happening is extremely low. By corrected gestational age, I mean the gestational age at birth plus the gestational age in weeks after birth. So that 33 weeks seems to be the cut-off where this entity does not occur after that. And that’s one thing that we found with our research that’s reassuring.
STEPHANIE: That’s great. So do you think that that’s probably because by then the babies are less likely to need a transfusion or because they’ve got a better blood supply? Because I’ve heard that NEC can be associated with lack of oxygen to the intestine.
DR. HUSSAIN: That’s correct. NEC has been related to decreased blood supply or decreased oxygen to the gut at various times. So it could be related to that, but I think it’s a maturational process of the gut. The gut is maturing, and I think it develops probably some protective responses after a particular age when this risk due to blood transfusion is extremely low or absent. And we’re still trying to understand what those mechanisms may be. And maybe this entity would help us figure out why the regular NEC occurs also, because this seems to be a precipitating factor, a risk factor, and if you can understand these kind of risk factors, we may be able to understand the disease overall much better and then try to figure out mechanisms to prevent this.
STEPHANIE: Um hmm. And is there anything that you’d like to talk to specific about NEC in general and preventative strategies or research that you’ve got going on maybe not specific to blood transfusions?
DR. HUSSAIN: Sure. So there are a number of approaches to figuring out the problem of NEC. One is that something that’s coming through the system—through the bloodstream—some entity or some factor that’s causing injury or damage to the gut such as low blood supply or some toxin or something that’s coming systemically from the blood. But another approach could be that there’s something in the gut lumen or the contents in the gut that are setting up an injury in the epithelium or the lining of the intestines which is initiating NEC. And so that’s the big debate. Was it starting from inside or is it starting from the system outside? Because a blood transfusion is something that’s not—there’s nothing happening in the lumen of the gut. It’s coming from the system. And so if NEC is related to some systemic process that is affecting the gut, this transfusion-associated NEC would be a real good model to kind of study that. But if it is something in the lumen of the gut, then this transfusion-associated NEC is maybe a separate entity. We are trying to figure this out. In the lumen of the gut, we know that what is inside the lumen of the gut is important in setting up the inflammative process inside. It depends on what kinds of feeds have been given, whether it’s breast milk, human milk, or formula; what kind of bacteria are present, whether they are the good bacteria that are supposed to be helpful for the gut or the bad bacteria that set up an inflammatory reaction. So people are looking into the effect of probiotics or the good bacteria that we can help promote in the gut so that they can counteract the bad bacteria that are trying to invade. The other part is something called prebiotics where people are looking into, what does bacteria feed on, the sugars that they feed on? If you provide the right kind of sugars for the good bacteria, they can flourish and prevent the bad bacteria from growing. So what we give to the babies in terms of feeds is extremely important in looking at NEC. And in the transfusion-related NEC research, the presence of food in the stomach during the process of transfusion is being studied because when babies are being fed, there’s a change in the blood flow to the gut. And when you’re giving a transfusion at the same time, that’s another factor that’s changing blood flow to the gut. So you can get a double whammy in the gut if the effect of the two are additive. So one of the research is looking at actually the blood supply to the gut during the feeding process and how the transfusion may actually modify it. We have new tools to look at blood supply in the gut. One of the new tools is called near infrared spectroscopy. It is a way to look at the total amount of oxygen that’s present in an organ, like the gut. And then you can see whether the gut’s getting enough oxygen or less oxygen during a transfusion or a feed. And so these are the kind of processes and researches that are ongoing trying to understand not only just NEC but transfusion-related NEC.
STEPHANIE: And you had said earlier, just to reiterate, that after the feeds or when particular centers are holding feeds, it’s upwards of about 48 hours. After that, it seems not to be a risk factor?
DR. HUSSAIN: Yes, that’s correct. So people have arbitrarily defined transfusion-associated NEC as any NEC occurring within 48 hours of a blood transfusion. That’s an arbitrary definition. But it seems like that’s the highest risk point for developing of this entity. People have looked at what happens in 3 days, 7 days, 5 days after a blood transfusion and found that if it’s going to be related to NEC, it’s going to be within the 48 hours.
DR. HUSSAIN: So what is going on within that 48 hours related to blood transfusion is extremely important. And there are a number of different protocols being developed by different centers trying to figure out the best way to deal with that. Should we stop feeds before? Should we stop feeds during? Should we stop feeds after or during the whole 48-hour period? The problem is that feeds are very important for babies. That’s how they get nourishment. And feeding is important for the gut activity as well. So it’s like a balancing act because you don’t want to stop the feeds and compromise on nutrition, but also you want to protect the baby from the potential of this transfusion-associated NEC. So the neonatologist community is in a big debate right now in terms of, is it good to stop feeds? Is it good to stop feeds for the whole 48 hours or just a few hours? And so that’s where we’re all trying to kind of study this problem and learn. Unfortunately right now we are in the beginning stages of this research, so we don’t really have many answers. But, you know, we’re starting to look.
STEPHANIE: That’s great. Yeah, it seems like it’s—I’ve heard the word multifactorial disease many times, and it does seem like there’s a lot that goes into the development of NEC, and potential risk factors are sort of looming everywhere in the NICU. So I appreciate you bringing this to our attention and sharing what is known and sort of giving people at least a window of when babies need to be monitored even more vigilantly than they already are. Is there anything else that you would like to add in any way about NEC or anything in general about the babies or families or the NICU in general?
DR. HUSSAIN: Well, one of the things that’s—I think it’s pretty exciting new stuff that’s happening is that we are figuring out that we may not understand the entity completely, but we could at least figure out what are the things that when they come together are a bad combination for NEC? So we are able to start developing algorithms and protocols that kind of highlight when the baby is most at risk.
DR. HUSSAIN: So these are called—there’s one called GutCheckNEC. It’s a protocol that’s developed looking at about nine risk factors and two protective factors that, when in combination are all present, the risk of NEC is the highest. And that’s where you can be the most vigilant and most careful and you can try to mitigate the stress to the gut. So these kind of things are coming up based on computer technology where they’re kind of—you can look at the change in the vital signs of the baby at different time points and say, “The vital signs are changing in one direction that makes it more likely that the baby is going to have a problem.” So these are new technologies using computers and continuous monitorings and the epidemiologic work that we’re doing, putting it all together in developing algorithms and protocols that could be what we call early warning signs. So I would call it NEWS—Neonatal Early Warning System—that we are trying to develop to counteract some of these major problems like NEC.
STEPHANIE: That’s great. Yeah, my son, when he developed NEC it was very quickly and the doctors told us that it was sort of, I guess, out of the ordinary—atypical is what they said.
DR. HUSSAIN: Right.
STEPHANIE: So, you know, anything that parents can be aware of and knowing what doctors are looking for and monitoring for, I’m sure, gives added security to the parents.
DR. HUSSAIN: At that time when your son was in the NICU, I’m not sure we were even fully aware of this entity. Was it related to a blood transfusion at all? Do you remember?
STEPHANIE: I don’t know. I know that both he and his brother did get transfusions, but to be honest, I don’t know when in relation to when he developed NEC because he was only 4 days old when he developed it.
DR. HUSSAIN: Yeah, it’s only about a third of the NEC—or about a quarter of NEC—that is related to blood transfusion. Most of NEC is not. So we still—this is maybe one part of the problem. We are not really solving the whole, but at least it gives us insight into some of the processes that may be involved in NEC.
STEPHANIE: Right, right. Yeah, no one used that term, and no one even—really you’re the first person to actually ask that question. No one that I’ve talked to even in general terms has brought that up. So it would be interesting for me to go back and look and see if there was a transfusion at any point.
DR. HUSSAIN: Yeah. Some people actually think that it’s not the transfusion but the baby’s anemia. Before you think you want to transfuse the baby, the baby is probably too anemic, and so there’s some centers that are not letting the babies get very anemic now. So in fact, they are doing more transfusions to prevent this entity. It’s kind of paradoxical but—
DR. HUSSAIN: Yeah, because some people believe that it is the anemia that, if you let the baby get too anemic and then you give a transfusion, there’s a big change in the system, and that may be precipitating NEC. So these are all things that we need answers for. Unfortunately I don’t have answers, but we are actively looking into that.
STEPHANIE: And I think—I mean, for the mom of a surgical NEC survivor, I think that even just knowing what people are looking into and that people are looking into it gives me a sense of something good is going on and eventually the puzzle will be solved.
DR. HUSSAIN: Yes, and hopefully we can get the right clues from all these different things that we are learning. And that’s the goal, to make NEC an entity of the past.
STEPHANIE: Right. Right. And that’s our goal as well. So I really appreciate you talking to me today. And this is very interesting and I think new for a lot of people, so I appreciate you taking the time to talk to us.
DR. HUSSAIN: Thank you for the opportunity to share my thoughts and some of our work with you.
STEPHANIE: For more information about Dr. Hussain 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. Hussain.
I looked back at Morgan’s medical records, which stated that “He did require packed RBC (Red Blood Cell) transfusions x2 during his hospitalization”. However, his first transfusion was after his initial surgery, and his second was before his second surgery. So for him, there was no correlation between a blood transfusion and the development of NEC. He remains an anomaly.
A definitive causal link between blood transfusions and NEC has yet to be found. As Dr. Hussain mentioned, the term “transfusion associated NEC” is currently somewhat controversial. However, I believe that the suggested association not only targets another risk factor for development of NEC, but it also targets another area of potential discovery in the prevention of 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 firstname.lastname@example.org. We’d love to hear from you!
You can make a donation directly to Dr. Hussain’s research in NEC at Connecticut Children’s Medical Center by visiting https://www.connecticutchildrensfoundation.org/giving/nec
Copyright © 2015 The Morgan Leary Vaughan Fund, Inc.
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