Audio News Briefing
Newborn Hypothermia Treatment
Wednesday, May 30, 2012
Listen to the briefing (MP3 - 2.68 MB)
Operator: Good morning, ladies and gentlemen, and thank you for waiting. Welcome to the Neonatal Cooling Study Media Call. All lines have been placed on listen-only mode, and the floor will be open for your questions following the presentation.
With further ado, it is my pleasure to turn the floor over to your host, Mr. Robert Bock. Mr. Bock, the floor is yours.
Robert Bock: Thank you. Welcome to the National Institutes of Health. I am Bob Bock, the Press Officer for the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The briefing will be on the forthcoming New England Journal of Medicine paper, “Childhood Outcomes Following Hypothermia for Neonatal Encephalopathy.”
Our briefing is being held under the terms of the journal’s Embargo, which lifts on Wednesday, May 30, 2012, 5 p.m. Eastern Daylight time. The study was conducted with federal funds administered by the National Institutes of Health, specifically the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Additional funding was provided by the National Center for Research Resources and the National Center for Advancing Translational Sciences. Our speakers today are study authors Rosemary Higgins, M.D., of the NICHD Pregnancy and Parent Ontology branch, and Seetha Shankaran, M.D., of Wayne State University and Detroit Medical Center.
I will now introduce Dr. Higgins, who will begin our briefing.
Rosemary Higgins: Hi. Dr. Seetha Shankaran is the lead investigator of this study of the Eunice Kennedy Shriver National Institutes of Child Health and Human Development's Neonatal Research Network, has made an enormous contribution to the field of neonatal medicine.
The follow-up study for the cooling trial has shown that lowering the body temperature of a baby who failed to receive sufficient oxygen during the birth process decreases the rate of death or having an IQ below 70 from 62 percent to 47 percent. The rate of death was significantly reduced in the children who had the cooling treatment to 28 percent compared to 44 percent with the usual treatment.
The incidence of this condition technically known as hypoxic ischemic encephalopathy ranges from approximately 0.5 to 1.0 in every 1,000 births in the United States. The condition is not common, and many physicians may go for years without seeing a case.
The central purpose of the federally funded NICHD Neonatal Research Network is to provide the means to study such uncommon conditions. By pooling cases from a large number of institutions, it’s possible to find enough affected infants to provide a significant number to have a statistically meaningful sample.
In our study, 15 institutions participated in the follow-up of children from the original study when the children were 6 to 7 years old. This is a very difficult study to perform. For the original study, the research staff members were on call nights, weekends, and holidays in order to enroll the children in the study within a six-hour window after birth.
Once in the study, each infant required constant monitoring throughout the 72-hour study period. The follow-up study was able to track as well as evaluate the infants who took part in the original cooling study when they reached school age. The NICHD Network investigators and their staff worked diligently to complete the study over a 10-year period.
The study results are extremely reassuring. Many hospitals with level 3 newborn intensive care units offer cooling therapies for infants with hypoxic ischemic encephalopathy. They have the necessary equipment and highly skilled personnel to carry out the treatment. This is the first study to show a persistent beneficial effect of cooling in an entire group of newborns at school age.
There are several published studies showing benefit of cooling at approximately two years of age. Our study provides strong evidence of long-term safety given the lower death rate and without an increase in disability in infants who underwent the cooling therapy who have now reached school age.
We are pleased that there is continued sustained benefit from cooling therapy.
Now the researchers in the network and others funded by NIH are conducting additional studies to refine the treatment and find best ways to administer it. Our current studies involve the most effective temperature for the therapy, the maximum period to cool the infant, and the most effective way to bring the infant’s temperature back to normal.
In summary, cooling for encephalopathy appears to be effective in infants and appears to have no ill effects at 6 to 7 years of age. This information provides the basis for use of cooling in infants who experience hypoxic ischemic encephalopathy.
Robert Bock: Dr. Shankaran, if you could speak (ph) a few words about your role in the study.
Seetha Shankaran: This study was conducted in the Centers of the NICHD Neonatal Research Network. We were able to follow 91 percent of the original cohort of infants who were enrolled in the study between 1998 and 2003. And as aided, we were able to show a reduction in the rate of death. All IQ scored less than 70, and we selected these outcomes because at the age of 6 to 7 years of age, children can be tested with standardized testing that looks at both the IQ, intelligence quotient.
In addition, we did do other tests of memory and visual ability and attention abilities of the infants. We found that there was no increase in the level of disability among the infants who underwent cooling. On the other hand, there was the overall reduction in death or cerebral palsy at the age of 6 to 7 years.
So we just want to acknowledge the NICHD for the support to do the study and for all the institutions and personnel who conducted the study and the parents of the infants who agreed to participate in the study.
Robert Bock: If our speakers have no further remarks, Operator, I think we can open this up for questions.
Operator: Certainly, the floor is now open for questions. If you do have a question, please press the number 7 on your telephone keypad. Questions will be taken in the order they are received. If, at any point, your question has been answered, you may press 7 again to disable your request. If you are using a speakerphone, we ask that while posing your question, you pick up your handset to provide favorable sound quality. Please hold while we wait for the first question.
Again, if you do have a question, please press the number 7 on your telephone keypad. The first question comes from Pat Anstett from Detroit Press. Thank you. Please state your question.
Pat Anstett: Yes, hi. I must start with an apology. I've been on vacation, I just joined the call two minutes ago. So if you prefer, I can follow up later, but my main question is how many children are born with this condition, and I apologize if I missed that explanation.
Robert Bock: No apologies necessary. I believe our researchers have an answer to your question.
Rosemary Higgins: Go ahead, Seetha.
Seetha Shankaran: Hi, Pat. This is Seetha Shankaran.
Pat Anstett: Yes, hi.
Seetha Shankaran: How are you?
Pat Anstett: I'm fine, thank you.
Seetha Shankaran: So the incidence of the abnormal neurologic examination that we see in the full-term baby with the lack of oxygen and lack of blood flow to the brain is approximately 0.5 to 1 per thousand live births.
Pat Anstett: Okay, and what do we know causes the condition?
Seetha Shankaran: It is usually caused by events that occur around the time of birth. You can have acute events in a mother who had a fairly normal pregnancy except that just before birth there was either a colon prolapse or a uterine rupture, shoulder distortia, maternal cardiac arrest, maternal trauma. So any of these conditions can lead to an acute decrease in oxygen and blood flow going to the brain.
And the babies are usually born very floppy, they don't have muscle tone, they don’t cry right away, and they don’t react as normal, healthy babies do.
Pat Anstett: Okay, thank you. I don’t know if there are other people in the queue. I’ll wait to see to ask questions. I don't want to dominate the questioning here.
Operator: The next question comes from Rachel Rettner from My Health News Daily. Rachel, please state your question.
Rachael Rettner: Hi. Thank you for taking my question. I was wondering if someone might be able to comment on the mechanism of how this therapy is working? How does cooling the body reduce the risk of infant death or disability?
Seetha Shankaran: Okay, so when there is lack of oxygen and lack of blood flow that goes to the brain, we have learned a lot about the deleterious effects, really, from looking at the laboratory animal models. And when there is lack of oxygen and lack of blood flow, then there are – there’s a cascade of events that occurs where there is an accumulation of certain proteins, certain amino acids. There is a formation of substances that can be damaging to the nerve cells called “reactive species,” such as free oxygen, free iron, et cetera, and nitric oxide. There is swelling of the tissues in the brain. This can actually lead to necrosis or cell death.
So in the animal model, when you compare animals that are treated with cooling versus those that are not treated with cooling but all the animals have a -- they have blood supply to the brain that’s been tied off, and they are given less oxygen, what’s been shown is that hypothermia actually stops or slows down each of these events that I just described.
And now, since we published our first paper in 2005, where we showed that cooling the body off the term infants who are born within six hours of birth, lowering their temperature, there have been other studies that have also published that have shown similar results of the benefit of hypothermia.
And very recently, within the last two years, MRI studies done on babies who have been cool and those who have not been cool, do show an actual decrease in the amount of brain injuries among the children who have received cooling.
So -- hypothermia seems to act at different levels in the cascade of brain injury that occurs and, as you might have heard, hypothermia is also used now for adults who have cardiac arrest and is being used in other conditions in adults and is also being evaluated in pediatric traumatic brain injury and pediatric cardiac arrest.
Rachael Rettner: That answers my question, thank you.
Operator: The next question comes from Gene Emery Reuters Health. Gene, please state your question.
Gene Emery: Hey, there, folks. I just wanted to make sure on something. If you look just at IQ scores below 70, it looks -- the suggestion seems to be, from reading this study, that there was not a difference between the two groups. Am I reading that correctly?
Seetha Shankaran: Yes. If you look at only the IQ scores among the infants who survived, those in the hypothermia group, we had IQ less than 70 in 29 percent of infants compared to the children who got intensive care alone, where it was 33 percent. So there is a 4 percent decrease in the hypothermia children compared to the control. And, certainly, that’s not a significant decrease.
However, any condition like this one, where there is lack of oxygen and lack of blood flow going to the brain, we know that there is always a high mortality associated with the condition because of multi-organ failure. So that’s why, prior to even starting the study, we assessed the outcome of not just the disability among survivors but also the impact of death. So we have what's called a “composite outcome,” which is looking at both death and IQ less than 70. And that was considered our primary outcome.
Gene Emery: And do you have a sense of how many hospitals are doing this strategy currently, and how much does it cost for the equipment and so forth to implement this?
Seetha Shankaran: Well, since 2005, when both our study of whole body cooling and the first international study of cooling the head only using a cool cap -- when those two studies came out, the use of hypothermia really started in the neonatal intensive care units. And subsequently there has been a large multi-center study from Europe, from Australia, and from China, and all have shown remarkably similar results. Of course, all the studies followed the children only up to 18 to 24 months of age.
So in the last short five years, the use of hypothermia has become standard care in the majority of larger hospitals in the United States. It was a standard of care in many countries in the high resource center countries, which are Europe and Australia (inaudible), but it’s now also being evaluated in the less resource countries like India.
Gene Emery: And the price for getting the equipment and so forth to do this?
Seetha Shankaran: The price of the equipment we used and, Rose, you can correct me -- I believe was around $6,000.
Rosemary Higgins: Yes, they're between $4,000 and $8,000 for the cooling device, the blanket.
Gene Emery: Okay. So there’s no real reason why most hospitals, if they’re delivering kids, couldn't -- ?
Seetha Shankaran: Well, I think, you know, we both will tell you that the frequency is, as we said earlier, 0.5 to 1.0. So in a hospital like the hospital where I work at, where we have 6,000 deliveries, you know, you do see six babies -- up to six babies in a year.
But other than a hospital, unless you have a big delivery system with high-risk mothers, you may not see this condition for a while. So we really caution that hypothermia, although it is, you know, compared to a lot of treatments, easy to implement. It does have side effects, and the infants receiving hypothermia must have monitoring of the core body temperature continuously from the time that this treatment is started.
And there should be monitoring of all body function, of all the organ function, because babies who have lack of oxygen, lack of blood flow, do have complications resulting from multi-organ injury.
Gene Emery: Okay, folks, thanks.
Rosemary Higgins: If I could go back to the death question that you asked --
Gene Emery: Sure.
Rosemary Higgins: -- we do have a significantly lower rate of death in the hypothermia group. It was 28 percent versus 44 percent in the usual care group. And so one of the things that we wanted to look at was in those children that had been cooled, was there a different rate of disability. And there was no increase rate of disability or an increased rate of lower IQ. In fact, that was just a few less in the hypothermia group that had lower -- that had those IQs below 70, as you alluded to. You have to look at the entire population that was part of the study, not just the survivors. Because, clearly, there is a benefit here for mortality using the cooling therapy, and that’s mainly what drives the benefit, the overall benefit.
Gene Emery: Okay, thank you.
Operator: The next question comes from Pat Anstett from Detroit Free Press. Pat, please state your question.
Pat Anstett: Yes, a couple of follow-up questions, please. Dr. Shankaran, when you said this has become the standard of care in the majority of hospitals, although it may not be widely provided, did you mean this particular therapy for this indication? I just want to be clear about that.
Seetha Shankaran: Yes.
Pat Anstett: Is that the standard of care you’re referring to?
Seetha Shankaran: Exactly. We really have stated in our manuscript and, I believe, all the other multi-center trials that have shown benefit have also published the clear indication for cooling therapy for term infants. So these have to be term infants, they have to have lack of oxygen, lack of blood flow to the brain, they have to be less than six hours of age. So it’s a very specific group of infants, and we really encourage the centers that want to use this to really follow the same detailed protocol that is available in the published study.
Pat Anstett: Okay, and if I may follow up with one other question -- you asked -- I mean -- you mentioned that this is also being evaluated for pediatric brain injury. You have the equipment, you have the expertise there at DMC, are there some research protocols underway where you are using this for other indications, and can you tell us a little about that, please?
Seetha Shankaran: Not for any other conditions for newborn infants. We are not using it, although there are published reports of it being used for other indications. But it’s really not been shown to be either safe or effective.
There is a national study funded by the NICHD to look at cardiac arrest in pediatric patients -- so these are older patients – that’s being done throughout the country in certain centers. And, yes, within the DMC, it’s being conducted at Children’s.
Pat Anstett: Okay, thank you.
Rosemary Higgins: If I could add, NICHD’s Neonatal Research Network has two additional cooling studies that are ongoing. The question is, if a baby arrives after six hours or presents with a seizure after six hours of age, should that infant be cooled? And we don’t have the evidence base as of yet to say yes or no. It’s unstudied.
And so we do have a trial ongoing that is recruiting infants who present beyond the six hours of age up until 24 hours to try to determine if the cooling is effective beyond six hours, because that’s an unanswered question.
Pat Anstett: Okay, and that study is going on right now at DMC?
Rosemary Higgins: Yes, it is, at all of our Neonatal Network sites, yes. And then the other study that’s also going on in the Neonatal Research Network, which Dr. Shankaran is the lead investigator on, is cooling for a longer period of time, meaning 120 hours instead of 72 hours. And cooling for a lower temperature, 32 degrees as opposed to 33.5 degrees, to see if we can effect more neuro-protection or protection for the brain and optimize outcome for these unfortunate babies.
Pat Anstett: Thank you.
Operator: If you do have a question, please press the number 7 on your telephone keypad.
Mr. Bock, it appears we have no further questions.
Robert Bock: All right, since we have no further questions, we will conclude our briefing for today. Thank you, everyone, for joining us.
All: Thank you.
Robert Bock: Goodbye.
Operator: Thank you. This does conclude today’s teleconference. We thank you for your participation. You may disconnect your line at this time.
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