February 8, 20113:30PM EST
Operator: This is a recording of the NICHD conference on February 8, 2011 at 2:30PM Central Time. Ladies and gentlemen, thank you for your patience in holding. We now have your speakers in conference. Please be aware that each of your lines is in a "listen only" mode. At the conclusion of today's presentation, the floor will be open for your questions. At that time, instructions will be given as to the procedure to follow if you would like to ask a question. It is now my pleasure to introduce today's moderator, Mr. Robert Bock, Public Information Officer, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Mr. Bock, you may begin, sir.
Robert Bock: Hi. Thank you. Welcome to this media availability. I'm Bob Bock, press officer for the Eunice Kennedy Shriver National Institute of Child Health and Human Development. I would like to introduce our Director, Dr. Alan Guttmacher, with the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Alan Guttmacher, M.D.: Thank you all for joining us this afternoon. As you just heard. I'm Alan Guttmacher, the Director of the Eunice Kennedy Shriver National institute of Child Heath and Human Development, at the National Institutes of Health. We are here to discuss the results of the Management of Myelomeningocele Study or MOMS. This study was undertaken to find out if surgery to repair a major malformation of the spinal column during early pregnancy, on a fetus in the uterus, was more effective than performing this surgery shortly after birth when it traditionally has been done.
Regardless of when it is done, the surgery consists of inserting the spinal cord back into the spinal canal and sealing the opening with sutures. Before the introduction of fetal surgery to repair myelomeningocele, fetal surgery was limited to life-threatening conditions because of the risks involved. As you will hear, on balance, infants and moms who underwent fetal surgery did better than those who had surgery after birth. However, as with other fetal surgical procedures, the MOMS trial also revealed significant risks for both mothers and infants from the intrauterine surgery. The study authors will describe the benefits and risks to you shortly.
Myelomeningocele is a form of spina bifida. Spina bifida means, literally, split spine. In this birth defect, the spinal column fails to close properly, exposing the spine. Myelomeningocele is the most severe form of spina bifida, in which the spinal cord protrudes through the spinal opening and may be enclosed in a fluid-filled sac. In the United States, about one in every 3,000 children is born with myelomeningocele. The condition often results in weakness or paralysis below the spinal opening. In addition to loss of bladder and bowel control, individuals with myelomeningocele often have motor deficits. They may need crutches and other assistance for walking, or they may need to use a wheelchair to get around. The protrusion of the spinal cord may result in hindbrain herniation, in which the base of the brain is pulled into the spinal column.
Hindbrain herniation can block the flow of fluid through the brain—known as hydrocephalus— which causes a life-threatening increase in pressure within the brain. To treat hydrocephalus, a tube or shunt is inserted into the brain to drain the excess fluid into the abdominal cavity. The shunt is susceptible to infection, however, and may need to be replaced many times during an individual's lifetime. But before we talk about any surgery to repair myelomeningocele, we should talk about prevention.
There is an important step women can take to reduce their risk of having a child with spina bifida or any other neural tube defect. In 1992, the U.S. Public Health Service recommended that all women of child-bearing age receive 400 micrograms of folic acid each day to reduce this risk. Folic acid is the synthetic form of folate, a vitamin found in green, leafy vegetables, among other sources. Because the majority of pregnancies in the United States are unintended, it is recommended that all women of child-bearing age take a supplement containing 400 micrograms of folic acid each day or eat a breakfast cereal that has been fortified with the vitamin. For women who previously have had a pregnancy affected with a neural tube defect, the recommendation is to increase folic acid intake to 4,000 micrograms per day, beginning at least one month before conception and continuing throughout the first trimester.
In 2009, a study by our Institute found that women who were deficient in Vitamin B12 were also at increased risk for having a child with a neural tube defect. Most women who consume meat, eggs, dairy products, and other foods derived from animal sources are not deficient in Vitamin B12. However, certain digestive conditions or disorders can interfere with the absorption of Vitamin B12. Women who have a condition interfering with the absorption of B12, they should check with their doctors about the best way to obtain enough of the vitamin. In addition, vegans, those who don't consume any foods from animal sources, should also take a supplement containing B12. The recommended daily allowance of B12 for women of child-bearing age is 2.4 micrograms a day. Sometimes, however, prevention is not possible. Even women with appropriate levels of folate and Vitamin B12 may conceive a child with a neural tube defect. With us today to summarize the MOMS trial and its results are: Catherine Y. Spong, M.D., who is Chief of the Pregnancy and Prenatology branch here at the Eunice Kennedy Shriver National Institute of Child Health and Human Development; N. Scott Adzick, M.D., who is Chief of Pediatric Surgery in the division of Pediatric General and Thoracic Surgery at the Children's Hospital of Philadelphia; and Diana Farmer, M.D., who is the Division Chief of Pediatric Surgery at the University of California-San Francisco and Surgeon-in-Chief at the UCSF Benioff Children's Hospital. I would now like to introduce to you our first speaker, Dr. Spong.
Dr. Spong: Thank you. And as Dr. Guttmacher mentioned, the MOMS trial was undertaken to evaluate a prenatal surgery, [and] improve the outcome as compared to the standard treatment, which is post-natal repair after delivery. Women volunteering for our study were assigned at random to one of two groups; either to undergo prenatal surgery to close the spinal defect in their unborn child before the 26th week of pregnancy, or to have the standard surgery performed after birth. The study results were evaluated as two separate primary outcomes. The first was at 12 months and included whether a child had died at placement of a shunt or required a shunt. And the shunt is placed from the baby's brain into the abdomen to drain the excess fluid and to decrease the pressure in the baby's brain, a complication that you have with myelomeningocele.
The second primary outcome was at 30 months. This was a composite of mental and motor, or movement, assessments. The motor-assessment score was calculated as the difference between the child's functional motor ability, what they were able to do, and the expected ability given the level of the defect on the spine. The trial included three clinical institutions: The Children's Hospital of Philadelphia, University of California in San Francisco, and Vanderbilt Medical University Medical Center in Nashville. In addition, there was an independent data center, The George Washington University Biostatistics Center, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. I'd now like to introduce Dr. Scott Adzick who will give the results of the study.
Dr. Adzick: Hi. Just adversely, everyone on the phone wants to know about the results, so I thought I would start with the 30,000-foot view: and that is that prenatal repair of myelomeningocele is not a cure for this birth defect, but the results show that it reduced the need for ventricular shunting for hydrocephalus and improved motor outcomes, including the ability to walk at two and a half years of age. Now, the trial began seven years, actually in 2003, and enrollment in the trial was stopped about eight weeks ago because the Data Safety Monitoring Board reviewed the results and saw that the advocacy of prenatal surgery was shown at the recruitment of 183 of a planned sample size of 200 patients. And, the New England Journal of Medicine report that you'll be able to read after 5:00 p.m. today is based on the results in about 158 patients at one year follow up. So, in straightforward terms, there were about 80 kids in a prenatal repair group, and about 80 kids in a post-natal repair group. With regard to the first primary outcome, which is death or meeting the criteria for the need for a ventricular shunt at 12 months of age, this was much less likely in those who had prenatal repair. Sixty-eight percent of the infants in the prenatal surgery group versus 98 percent of those in the post-natal surgery group. The take-home lesson from this is when you look at the actual rates of shunt placement to treat hydrocephalus in the study, shunts were placed in only 40 percent of the prenatal surgery group, but in 83 percent of the post-natal surgery group. As the pediatric neurosurgeons have taught us, shunts are a mixed blessing. They treat the hydrocephalus problem, but the bad news is that they are life long and they frequently require revision to address shunt failure and infection. With regard to the second primary outcome at 30 months—which is that prenatal surgery resulted in improvement in the composite score for mental development and motor function of the kids at two and a half years of age—and the lesson here is that the prenatal surgery group had, on average, much better motor function of the legs than the post-natal repair group. Now, there were as well some improvements seen in the prenatal surgery group in a variety of secondary outcomes. I'll review two.
Although, the ability to walk depends on the location of the spina bifida lesion, at two and a half years of age children in the prenatal repair group were much more likely to be able to walk independently; that was true for 42 percent compared to children in the post-natal repair group, which was 21 percent. And this is true, even though the children in the prenatal repair group, as it turned out, had more severe—that is higher—lesions on average than the post-natal repair group. The other secondary outcome that I want to discuss is that fetal MRI documentation of the hindbrain herniation component of the Chiari II malformation was required for fetuses and moms to be part of the MOMS trial. And hindbrain herniation is important, of course, in the development of the hydrocephalus problem and can have other adverse effects on motor and cognitive functions after birth. When evaluated at 12 months of age, more than a third of children who had prenatal repair no longer had any evidence of hindbrain herniation compared to only 4 percent in the post-natal repair group. And, of course, it's very important to look at the risks and I think that Dr. Diana Farmer from UCSF is going to review those risks.
Dr. Farmer: Yes. I'd like to say that it's important, as Dr. Adzick indicated, that while this is a very promising and quite exciting result for this disease—which is an otherwise relatively neglected disease—not all the patients were helped here and there are significant risks. So, this procedure is not for everyone. First are the risks to the fetus. While the death rates were the same for both groups, the children in the prenatal surgery group were more likely to be born pre-term. The average gestational age at birth for the prenatal surgery group was 34 weeks, versus 37 weeks for the post-natal group. Eighty percent were likely to be born somewhat pre-term compared to 15 percent in the post-natal group. And, significantly, there were 13 percent that we would consider quite premature, before 30 weeks. So, prematurity is a significant risk. Prematurity, of course, has its own potential complications, including respiratory distress syndrome and other [problems]. And we saw that 20 percent of the infants in the prenatal group had some problems with breathing, some respiratory distress syndrome versus 6 percent in that post-natal group. So, this is significant because you add the risks of prematurity onto already having a child with spina bifida.
The other thing, of course, to consider is the maternal risk. And quite frankly, that is the primary reason and motivation for doing this study was to determine, in fact, what the maternal risks would be and whether the benefits to the child would outweigh the combined risks to the fetus and the mother. Fortunately, there were no maternal deaths in this trial, and the bar for maternal safety was set quite high. There were, in fact, very few transfusions required and not very many significant maternal risks; no ICU, hospitalizations, etc. Mothers, however, who undergo prenatal surgery must be mindful that all future deliveries need to be performed by Caesarean delivery because they could otherwise risk uterine rupture. So, the reason for this is that the incision that is made on the uterus to access the fetus has to be made in an area where the placenta is not, and an area that is relatively thin or active. And it was observed, as expected, that in one-third of the women who had the prenatal surgery, there was some thinning noticed at the site of the incision at the time of delivery. Again, because of the potential risk for rupture at this weakened site where the incision is, all future deliveries must be by C-section before labor begins.
So, in summary, even though the children who underwent this surgery while in the uterus did much better overall than those who had surgery after birth, these risks, both to the fetus and the mother, cannot be ignored. It is the feeling that this is actually quite highly specialized surgery and is, therefore, best undertaken in centers who have the experience with the ability to maintain the pregnant state while undergoing surgery; the ability to open the uterus in a bloodless fashion; and to provide maximum care throughout the remainder of the pregnancy for this individual who has had an unusual kind of incision made on the uterus. This is not a routine C-section.
Dr. Guttmacher: At this point, we're open for any questions that people might have.
Operator: Ladies and gentlemen, at this time, the floor is now open for your questions. If you would like to ask a question, you may do so at any time by pressing "star one" on your touchtone phones now. We will take all questions in the order that they are received. If at any time you need to remove yourself from the questioning queue, press "star two." Again, to ask a question, please press "star one", now. Our first question comes from Jennifer Couzin-Frankel with Science Magazine.
Jennifer Couzin-Frankel: Hi. Thanks very much for taking my question and thanks, too, for summarizing the study so helpfully. So, I had kind of a broad question. It sounds, from what you're describing, that you would now in certain cases recommend this surgery clinically. And given that, I'm trying to understand how you're balancing the risks and benefits here since we're talking about two very different problems; one of them being the long-term effects of spina bifida and the other, I suppose, being the effects of prematurity and also the health effects on the mother. How do you weigh those, in particular, given that this study did not follow the children into school age, so there may be effects from prematurity that you were not able to detect?
Dr. Adzick: So, who wants to take this?
Dr. Farmer: Scott, why don't you start with this one—Scott?
Dr. Adzick: Okay. One of the wonderful things about the MOM's trial is now we have really discrete quantitative information so that we can look at these benefits and risks and—for a mom who's carrying a spina bifida fetus prior to, say, 24 weeks gestation who may be a candidate for the operation in terms of her health and the fetus' anatomic malformation—we now have discrete information that we can give her so that we can help her come to a decision basically about whether she wants to end the pregnancy; or to carry the pregnancy to near term and have a C-section, and have repair after birth; or to consider this new therapy, which we believe is a standard of care in terms of the benefits.
Dr. Farmer: I think it's important to point out that even despite the prematurity, the composite outcome variable that included mental development at two and a half years of age showed an advantage to the patients who underwent fetal surgery, despite the fact that there was more prematurity there. And we will continue to follow these patients for the next several years of their life, and the NIH has just agreed to support us in doing so.
Jennifer Couzin-Frankel: This is Dr. Spong? Just so I know?
Dr. Farmer: Dr. Farmer; I'm sorry.
Jennifer Cousin-Frankel: Oh, Dr. Farmer; I'm so sorry.
Dr. Guttmacher: And maybe moving forward because of the multiplicity of voices, we'll ask those folks who are answering to identify themselves.
Jennifer Couzin-Frankel: Thanks very much.
Operator: Our next question comes from Miriam Falco with CNN Medical News.
Miriam Falco: Hi. Congratulations on these great results. My question to you is: why you have to do the pregnancy, I mean, surgery before 26 weeks? What's the importance of that? And can you talk a little bit more about the details about how the surgery was done and how it compares to the surgery when it's done after the baby is born?
Dr. Adzick: Alright well, this is Scott Adzick speaking. With regard to the time and gestation: for the MOMS trial prenatal repair group the operation could be done between 19 weeks gestation and 25 weeks six days, and that's based on information that we had from pre-MOMS trial patients that were done at the three sites before the trial began, where there appeared to be little benefit for doing the operation late in gestation. Probably the reason for that is… the question is: How does all this work? And there's sort of three parts to that: one is that the operation before birth, it may stop exposure of the developing spinal cord to the toxic factors in amniotic fluid and perhaps avert further neurologic damage before birth; that's the first way that this may work.
The second reason is by stopping the leak of cerebral spinal fluid that bathes the brain and the spinal cord from the myelomeningocele defect out of the back, the prenatal surgery approach reverses the hindbrain herniation that we see before birth: and we believe that this reversal of hindbrain herniation in turn may mitigate the development of the hydrocephalus problem, and may decrease the need for shunting after birth. So, that's the rationale. And the work done in fetal sheep years ago shows that there's progressive damage in that fetal-sheep model to the exposed spinal cord as gestation continues. So, in theory, the earlier the better.
Now, with regard to how the operation's done. The operation is a big deal. The mom undergoes general anesthesia, which also anesthetizes the fetus. She has the appropriate monitoring devices placed because, of course, maternal safety is paramount in all this. She has a transverse sideways laparotomy done about halfway between the belly button and her pubic bone. The uterus is exposed and intraoperative sterile ultrasound is used to determine the fetal position and the placental position. The cut in the uterus is done away from where the placenta is, and the fetus is positioned by the obstetrician so that the myelomeningocele defect is directly underneath the hysterotomy or the cut in the uterus: that's so that we don't need to manipulate the fetus during the operation, and the fetus stays inside the uterus during the operation.
The fetus as well gets an additional shot of muscle relaxant and narcotic to make certain the baby is anesthetized, and then the pediatric neurosurgeon does the same type of layered repair before birth that is done after birth to protect the exposed spinal cord. Now, it's important to note as well that a uterine stapling device that fires absorbable staples is used to make the cut in the uterus, and that was developed at UCSF 25 years ago and has been used in all open fetal surgery cases: and it's very important that the device be used for a quick and bloodless hysterotomy, meanwhile keeping the membranes tacked up to the muscle layer of the uterus.
During the operation, the uterus is profused with physiologic solution to keep the fetus warm and blant, and that then fills the uterus up as the uterus is closed—in a watertight manner—and then the maternal abdomen is closed with an absorbable stitch that will dissolve once she's healed. The topolysis or medications used to, hopefully, keep the uterus quiet begin during the closure of the uterus; and it requires a lot of experience by the maternal-fetal surgery team to keep the uterus quiet, so the mother can convalesce.
Miriam Falco: I was going to say, how long does that take? I'm sorry.
Dr. Farmer: This is Dr. Farmer; I'll answer that. It usually takes anywhere between an hour to two hours, depending on the requirement to put a patch or exactly how we repair the fetal back defect. But I wanted to make a comment about the importance of that stapler and the fact that is has absorbable staples as opposed to the typical metal staples that are used in routine surgery, because those metal staples were found to act like an intrauterine device and cause infertility in animal studies ahead of time. So, this stapler is an important component to create the quick bloodless incision that Dr. Adzick described.
Operator: Our next question comes from Pam Belluck with the New York Times.
Pam Belluck: Hi. Thanks very much for doing this; appreciate it. I had a couple questions. First, on the results: can you unpack those a little bit more? You talked about: you grouped deaths and the need for shunts in one category, but I believe somebody said that there was an equal number of deaths in each group. It sounds like it was very small. Can you talk about what, give us the raw numbers for that?
Dr. Adzick: Right. Well, the, and as far as deaths go, if you view it as roughly 80 kids in each group, by 12 months of age, there were two deaths in each group. So, in the prenatal surgery group, the deaths were due to either a in-utero fetal demise in one case or very premature birth at 25 weeks gestation in the other case. In the post-natal repair group, the two deaths were manifestations of the hindbrain herniation and Chiari malformation, and those children had already received a shunt but died from the Chiari manifestation.
Pam Belluck: Okay. And also in the developmental result, you measured cognitive development and you measured physical development and it sounds like the motor or the physical development was the most, the difference there, or they were the most advanced, right? And that there wasn't that much difference in the cognitive development. Is that right? Can you talk about that a little more?
Dr. Adzick: Yes, correct. You hit the nail on the head.
Pam Belluck: Okay.
Dr. Farmer: You've got it.
Pam Belluck: Okay. And, sorry, if I could ask just one more thing about the participants. So, you talk about how the women who were excluded, extremely obese women and women with other sorts of confounding factors. I'm trying to get a sense of, given that obesity is associated with neural tube defects, I'm trying to get a sense of how many women, what proportion of women we're talking about who really wouldn't be candidates for this, at least not based on the results of this study.
Dr. Farmer: I think that's a good question. This is Diana Farmer. That certainly varies by region in terms of the incidence of obesity and it is clear that the prevalence of neural tube defect exists in obesity and may be rising with the prevalence of obesity. This was the largest, the biggest reason, for excluding patients from the trial. But it also had to do primarily with the concern for maternal safety; that the risks of this general anesthetic are more significant for an obese patient who is also pregnant.
Dr. Spong: This is Cathy. If I could add on to what Dr. Farmer mentioned: if you look at the vital statistics of reproductive-age women, around 10 percent are severely obese, have a BMI of over 35. And, as Dr. Farmer mentioned, this was one of the higher exclusions. Around 13 percent of the patients who were being screened for the trial were excluded solely because their BMI was greater than 35, which is pretty consistent with what's found just in reproductive-age women. So, I think you could take from that that about 10-13 percent of women with myelomeningocele might be excluded solely because of the BMI and, as she mentioned, there are significant risks with doing surgery, any type of surgery, on women/on people who are severely obese.
Pam Belluck: Thank you.
Operator: Our next question comes from Heidi Splete with OB/GYN News.
Heidi Splete: Hi. Thank you for taking my call. Part of my question was answered because I was wanting to ask what some of the exclusion criteria were: so maybe if you could elaborate on what were some of the other exclusion criteria other than obesity? And also what would be the take-home message for OB/GYNs as far as advising patients who, maybe they're early in the pregnancy, they've just found out that they have this? What would you tell doctors that they should talk to their patients about?
Dr. Spong: This is Cathy Spong. I have the inclusion criteria; do you want me to? The inclusion criteria were: the baby had to be between 19 weeks and 25 and six-sevenths weeks. The baby had to have a normal karyotype. The mother's BMI had to be less than 35, and had to have a singleton pregnancy. The upper boundary of the myelomeningocele needed to be between T-1 and S-1, and the baby had to have hindbrain herniation to participate in the trial. And, as Dr. Adzick mentioned, one of the remarkable findings from the trial was that in the children who had the prenatal surgery, at 12 months of age, one-third of those babies no longer had evidence of hindbrain herniation: all of them started with hindbrain herniation.
Dr. Farmer: This is Dr. Farmer. The other important exclusion criteria was if the deformity of the spine of the fetus was so significant that it would be a technical problem in repairing the back defect before birth—those patient were also excluded for essentially technical surgical reasons.
Heidi Splete: Okay. Thank you.
Dr. Adzick: And then you'll see when the New England Journal of Medicine article comes out that we have our entire NIH MOMS protocol, which is online as part of this, so you'll see a detailed list of all the exclusion criteria, which include factors such as maternal hypertension, infant diabetes, and so forth.
Operator: Our next question comes from Claudia Kalb with Newsweek.
Claudia Kalb: Thanks very much. I realize this is very specialized surgery, so I'm wondering how many centers can do this and is there any plan in place to train surgeons to do this across the country?
Dr. Adzick: Alright, Diana.
Dr. Farmer: Alright. I'll take this; Diana Farmer. At the present time, I would say that clearly the two centers that were active at the end of the trial, San Francisco and CHOP, have the most experience with this. That having been said, there are probably, I would say, at least three more centers in the United States at the present time who have some experience with open fetal surgery. At the present, that's Texas Children's, Cincinnati Children's, and some experience in Ann Arbor. And, I would anticipate that those centers will expand their portfolio of fetal-surgical offerings to include spina bifida as well. And we, Dr. Adzick and I in particular, are paying attention to making sure that we help expand the availability of this, but do it in a responsible way that ensures this high level of maternal safety, because I think it's important for the field going forward.
Dr. Brock: This is John Brock from Vanderbilt. Can you hear me?
Dr. Farmer: Yes.
Dr. Brock: We also will be providing the surgery as well. We have Noel Tulipan here who's done over 180 children with this particular problem. And also use specialized people with maternal-fetal medicine as well. But I agree with Diana. It is absolutely a specialized field, as necessary, but we will be providing this as well.
Claudia Kalb: Thank you.
Operator: Our next question comes from Tom Maugh with the LA Times.
Tom Maugh: Do any of you have any sense of how many women choose to undergo an abortion rather than choosing some from of surgery or not having treatment at all?
Dr. Farmer: Cathy, do you have a sense of that?
Dr. Spong: I don't have that information.
Dr. Farmer: It's difficult to; this is Diana Farmer, again. It's difficult to get at that number in a national way because data is not collected on this.
Miriam Falco: Okay. Since we don't have that data, can you go over those statistics again, that were mentioned at the very beginning? How often does spina bifida occur, and how often does this most severe form of it occur?
Dr. Adzick: Alright, well, I'll handle this one. As far as live-born infants in the United States, about close to four per 10,000 live births have a myelomeningocele basically. Which when you translate that to the birth rate for the United States for live-born babies with this, it's about 1,500 each year.
Miriam Falco: But that's only this most severe form, right?
Dr. Adzick: Yes.
Miriam Falco: Can you see an application for this surgery in the less-severe cases of spina bifida?
Dr. Farmer: This is Diana Farmer. I think this will become a question for further research. As has been the history with most fetal-surgical procedures, one of the challenges is to identify which patients will respond. As you noticed, there were a significant percentage of patients who underwent this treatment who did not get a response. Can we determine from prenatal markers or prenatal imaging which patients are more likely to respond; therefore, reduce the risk to those who wouldn't? And then the next question would be: Can we help a cohort of patients that were outside of this specific trial group? And that will be a secondary research question.
Operator: Our next question comes from Jennifer Couzin-Frankel with Science Magazine.
Jennifer Cousin-Frankel: Hi. I'm back again. And my question actually builds on the one that was just asked. I was wondering if you think this study will lead to extending fetal surgery to other non-life-threatening conditions outside of spina bifida.
Dr. Adzick: Well, my own opinion is that it's very difficult to predict the future, but no indications come to mind for non-life-threatening malformations.
Pam Belluck: Hi. Thank you. So, what is the cost of the prenatal procedure versus the post-natal procedure? Is there a difference?
Dr. Adzick: Well, one of the good things about the MOMS trial is that we have wonderful information, which includes the ability to cull financial information. You know how hospitals work with charges and revenue and things of that sort, so one of the downstream things that we can actually look at is a head-to-head comparison and, with further follow up on these children, the goal would be to look at total cost of care over, say, five years or 10 years, because it may not be fair to look at the cost in the short-term of just prenatal surgery versus post-natal surgery.
Pam Belluck: Okay. I understand that, but the actual, is one procedure, if you're comparing the cost of the procedure, is there a difference?
Dr. Farmer: This is Diana Farmer. The procedure here, if you put it together, really involves one additional operation on the mother. The post-natal group requires a C-section and an operation on the child, so the operation is required on the child at one time or the other. The expectation, and one of the hopes of the trial, is that by reducing the need for shunting, you will reduce the need for multiple subsequent operations in the child and that this will, in fact, be a significant cost-saving endeavor for the families and for society.
Pam Belluck: And also, if I could ask one more, I'm wondering—as you said, there were women and babies who did not respond—and I'm wondering if you all think that that was an issue of, if that was based on something about the condition of the fetus or something about the pregnancy… or is it more of a technological question? In other words, as technology or techniques improve, are you likely to include benefits to more women and babies?
Dr. Adzick: Well, I think we need to zero in on our prenatal-diagnostic techniques to determine basically and we can cull this from the MOMS information, but I haven't had a chance to do it yet. First of all, we need to have the complete data set for all 183 patients, because keep in mind that there are 25 patients who have not hit the one year follow-up time, much less the two-and-a-half time point. So, that's very important. But one could think through, well, perhaps a fetus that already had severe ventriculomegaly might not benefit, or a fetus that had reduced leg movements might not benefit as much as a fetus that already had retained leg movements. For instance, those are theoretical, but those may be sort of problems that we can solve and understand.
Dr. Farmer: And this is Diana Farmer. I would echo what Dr. Adzick just said and say that that's one of the advantages of having this outstanding data set that we can mine for just precisely this kind of information and that that's one of the benefits of evaluating this question in such a rigorous fashion as opposed to doing cases without having such good follow up. This is really a priceless cohort of patients that we will follow for a long period of time.
Heidi Splete: Hi. I didn't get a chance to re-ask my other question from earlier, which is: So, what advice at this time would you give to OBGYNs who might be seeing women who have just found out that their babies have this?
Dr. Farmer: This is Diana. I would say that at the present time it would be responsible to inform families that this represents an additional option in care that they could consider. The decision to undergo fetal surgery is quite individual and different for every patient, but I think that families need to know that this is one option that is in the armamentarium.
Heidi Splete: Thank you.
Operator: Our next question comes from Ron Winslow with the Wall Street Journal.
Ron Winslow: Hi. Thank you for having this meeting. I want to go back to the outcomes, looking at the age, the gestation period from 19 -26 weeks and also you mentioned the level of the lesion in the spine. How do the interplay of those two variables affect outcome if you haven't done [research] earlier in the gestation period. Is there a risk? Is there better improvement or less or how do those two things work?
Dr. Adzick: Well, that's a very good question. Basically. As it turns out, the average gestational age when the operation was done was at about 24 weeks and it was pretty tight. So, I don't know whether we have information, at least, now in terms of whether an earlier gestation approach was better or worse. With regard to the anatomic level of the lesion, it's quite clear when we look at the New England Journal of Medicine data here that the fetuses who underwent surgery before birth had a higher and, thus, more severe lesion on average.
Dr. Spong: This is Cathy Spong. I don't think we have the analysis to say that the higher the lesion the better the outcome.
Dr. Adzick: Oh, I'm not saying that. I'm just saying that when you look at the two groups and compare the superior aspect of the anatomic lesion, on average it was more severe in the prenatal group, so we don't know whether that has an affect on outcome or not.
Dr. Spong: Right. And this is Cathy Spong again. And so I think what Dr. Adzick is saying is incredibly important. The way that the groups were randomized; in fact, the more severe lesions were in the prenatal group, and yet the outcomes were much better for the prenatal group. I think the question that's being asked is: "Can we say that if we did the operation earlier—or if we did the operation on a more severe or less severe lesion—are we going to have a better outcome?" Those are very important analyses. We don't know that given the number of patients we have enrolled in this trial, that we're going to be able to answer those questions, but those are things that we will be looking at.
Claudia Kalb: Hi, Dr. Farmer. Just a quick follow up on looking forward. Can you give a little more detail on what you're, how long you're going to study these patients, and what you're going to be looking at beyond the two-and-a-half years or so?
Dr. Farmer: Yes. The NIH has agreed to fund additional follow up of these patients, looking at them between the 6-year- and 9-year-old age group: and we are looking for many things, but primarily the durability of this result. Do they still remain shunt free? Is the improvement that is seen in the motor function, does that maintain itself or is that lost over time? And particularly the financial aspect of this: the goal was really to reduce the number of procedures that these children are subjected to through the course of their life. So, we'll be looking quite detailed at this activity and also their developmental milestones in their neurologic functioning and their intelligence.
Dr. Brock: This is John Brock, too. We're also looking at the bowel and bladder function of these children. They have a lifelong problem with bowel and bladder functions, requiring several procedures, intermittent catheterization requiring surgery for this, and we are still evaluating the patients for this issue as well.
Dr. Farmer: Oh, that's a good point.
Dr. Adzick: So, I would note that the further follow-up study is known as MOMS II.
Claudia Kalb: Thank you. Operator: Our next question comes from Miriam Falco with CNN Medical News.
Miriam Falco: Thanks for the follow up. Just a quick clarification. It's supposed to be random. Why did more of the severe lesions end up in the prenatal surgery group?
Dr. Adzick: Just pure chance.
Dr. Spong: Randomization simply means; this is Cathy Spong. It simply means no one knows what the person's going to get.
Miriam Falco: Oh, I understand that. It just seems odd, but I guess it's just the luck of the draw.
Dr. Farmer: Yeah, the luck of the draw. It's nice just for the validity of the results to a certain extent that it happened that way.
Operator: At this time, we have no further questions in the queue.
Robert Bock: Thanks very much. This is Bob Bock, NICHD press officer. I want to remind everyone on the call that the New England Journal of Medicine embargo is 5PM Wednesday, February 9 on this article. That is once again, the embargo for this article is 5PM Wednesday, February 9. Thank you very much and, since there are no further questions, we will end our call.
Operator: Ladies and gentlemen, that concludes our conference. You may disconnect at this time.
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