Birth Defects and Environmental Contaminants
4:35 pm US Eastern Time
1. Welcome: Call Moderator: Steve Heilig, MPH, Director of Public Health & Education, San Francisco Medical Society
Thank you everyone for joining us. I am told we have approximately 50 people on the call today. We always start these calls with a science update of breaking news. Pete Myers will be giving the science update today. Many of you are familiar with his work, but I would like to point out the CHE science website at http://www.healthandenvironment.org/ and Pete’s new website Environmental Health News, at http://www.environmentalhealthnews.org/, a news summary and searchable database of environmental health news. We really encourage CHE Partners to visit both of these sites.
2. Science Update: Pete Myers, Ph.D., CEO, Environmental Health Sciences, Co-Author, Our Stolen Future
Those of you who have heard me do the science updates before will know that I always try to do something that’s quite different from the call topic. So, I’m going to talk a bit about salamanders. If you go to the Environmental Health News website, you will see that the center column is science updates. The top one is about salamanders and frogs. I would like to briefly describe that study. Of course you can read more about it by following the links from Environmental Health News.
Rick Relyea did some very interesting experiments with tadpoles of six different species of frogs, in which he exposed them to a pesticide, carbaryl, at different levels and looked at mortality rates. What’s interesting about this study was he found that if the tadpoles were by themselves, at low levels of carbaryl, there was no mortality; at high levels there was 100% mortality. So there was a good dose-response curve. But if he put into the aquarium, along with the tadpoles, a natural predator of the tadpoles, a salamander, the mortality rate was increased significantly, even though the salamanders were not able to get direct access to the tadpoles. What was happening was that the tadpoles were sensing that there was a predator present, so they were stressed. That interaction between stress and pesticide exposure, in one of the species, actually increased mortality rates by a factor of 46 (46-fold increase in mortality due to a pesticide, caused by the presence of a stressing factor in the environment).
Why is this relevant here? The bottom line is that all of the tests done by the EPA or anyone else attempting to establish safety levels for chemicals to which we are exposed in the environment, do those under extremely controlled circumstances. These tests don’t even begin to think about the complications that Rick Relyea factored in. What these experiments reveal is that the impacts of exposure can be dramatically heightened by other stressing agents. This is the message that Ted Schettler frequently gives in his public lectures.
Steve Heilig: Thank you very much for this, Pete. Dr. Tyrone Hayes from UC Berkeley, who spoke and was very well received at our conference at UCSF last November, was the subject of a very interesting article in a San Francisco newspaper recently: http://www.sfweekly.com/issues/2004-06-02/feature.html. This article discussed both his research on frogs and how that could be applicable to humans, and also his travails in getting his research reviewed and utilized in an objective manner. Dr. Hayes will also be speaking at the upcoming Bioneers conference in October.
Pete Myers: There is also a profile of Dr. Hayes in the new Sierra Club Magazine.
3. Featured Presentation: Birth Defects and Environmental Contaminants
Steve Heilig: We will turn now to the topic of the day, which is birth defects. I would like to point out that the paper that was mentioned here, which is well worth reading, was written by two of our speakers today. As an experiment I did a Google search on for this paper yesterday. I found that if I put environment and birth defects into a Google search, it was the first thing that turned up. So you can find that paper easily, but it is also posted on the CHE Science website.
Last week’s EPA report mentioned that overall toxics are up five percent. This is something of a reversal of more optimistic trends in recent years. What that means of course, is uncertain. This particular topic will highlight that quite a bit. If you look at the paper, you will see that both incidence, causes, and even the definition of birth defects is kind of flexible and there are a lot of gray areas. But a growing concern that some of the environmental factors are particularly important. You will see a chart included in the paper, which lists a lot of the particular birth defects and what the links might be.
So, we are going to start today with Ted Schettler, who is going to present some questions for discussion. He will also present some of the science, as far as what is known and what some of the uncertainties are.
* Ted Schettler, MD, MPH, Science Director, Science and Environmental Health Network
Today you are going to be hearing about birth defects. You will hear terms like structural birth defects, which are usually divided into major and minor types. In the paper we also talk about what we call functional defects, for example, immune system dysfunction or nervous system abnormalities that result from in-utero events. Finally, some people actually classify low birthrate and prematurity as being similar kinds of outcomes that are, by some people, included in the classification of birth defects. Major birth defects, in the structural realm, are the leading cause of infant mortality in the United States. Those that are most responsible for that mortality are defects of the heart, respiratory system, nervous system, and then multiple abnormalities in the same individual.
According to John Harris’ California Birth Defect Monitoring Program, the estimated lifetime costs for children born in the United States each year, with one or more of the 18 most significant birth defects, is about eight billion dollars, in 1992 dollars. So there’s a real economic consequence of these adverse outcomes, in addition to the obvious social and personal and family impacts.
The true incidence of birth defects is hard to determine because of differing definitions and inadequate tracking programs in many states. About three and a half percent of all babies will have a structural birth defect recorded on the hospital discharge record. But one large study that followed tens of thousands of children well beyond discharge into childhood found that the total rate of structural birth defects was nearly 16%, when the kids were followed up at seven years of age. About half of those, or about eight percent, were major birth defects.
The cause of most birth defects is unknown. We do know that genetic, nutritional, infectious, and other environmental factors such as radiation, pharmaceuticals, and toxic chemicals contribute to the overall incidence. The nutritional factor that we hear most about is folic acid. Low maternal folic acid consumption is associated with increased risk of spina bifida. Food fortification programs in the U.S. have helped to significantly reduce the incidence of spina bifida in this country.
Most experts believe that most birth defects result from multiple factors, such as an interaction between one or more genes and one or more environmental factors. As an example, maternal cigarette smoking and genetic variations in the production of a specific growth factor combine to increase the risk of having a child with an oral cleft defect. Similarly the risk of birth defects associated with fetal alcohol syndrome depends on both alcohol use during pregnancy and also genetically determined mechanisms for metabolizing alcohol in the mother.
Finally, there’s a large epidemiological literature that reports on the risks of birth defects associated with the exposure to a variety of toxic agents such as pharmaceuticals, solvents, pesticides, heavy metals, and other industrial chemicals. Much of this work has been done in the work place with occupational exposures, though some of it has been done in the general population. These studies are difficult to do for a number of reasons, and they have a variety of strengths and weaknesses. I won’t go into the details of that, but there’s a discussion of this in the paper that’s on the website.
Findings are often inconsistent from one study to another, but in some instances there is a consistent pattern that emerges, that begins to create a weight of evidence supporting an increased risk of birth defects with exposures to certain kinds of chemicals. For example, there does appear to be increased risk of some kinds of birth defects, in particular of the heart, with solvent exposures. There’s a fairly large literature on this. Some pesticide exposures are also associated with an increased risk of birth defects in a large number of studies. Low birth rate is consistently found to be associated with cigarette smoke exposure. Exposure to polycyclic aromatic hydrocarbons, which are the byproducts of fossil fuel combustion and other industrial combustion processes, and general air pollution, including carbon monoxide and the heavy metal lead are also all associated with low birth rate. Gene environment interactions have demonstrated in a number of interesting places, but one that stands out is in the risk for premature birth, where some interesting occupational studies have shown that maternal exposure to benzene and genetically determined enzyme levels in mom strikingly increase the risk of having a child prematurely. We also now know that prenatal exposure to lead, mercury, PCBs and some pesticides can alter normal brain development and result in impaired brain function later in life, with impacts on attention, learning, memory and behavior.
So collectively these observations all demonstrate the vulnerability of the developing fetus to environmental exposures at levels that are unlikely to have important impacts on adults, with complex interactions that make assigning the relative contributions of these various factors quite difficult to do.
Steve Heilig: Thank you very much Ted. I have seen reports from the California Birth Defects Monitoring Project for years. They are full of data and analysis of trends, so we have asked Dr. John Harris to present what he has been learning over the years and what may be contributing to the epidemiology of birth defects as well.
* John Harris, MD, MPH, Program Chief and Co-Founder, California Birth Defects Monitoring Project
First, I want to talk a little bit about why there has been so much interest in birth defects in relationship to the environment. Really the issue is that there’s a standard theory, which is probably correct, that the developing fetus is much more sensitive to all sorts of insults than adults. The way we know this essentially came from the thalidomide tragedy in the 50’s and earlier. Expectant mothers were taking thalidomide in doses that were nontoxic to them, but if that dose was given during a certain period of pregnancy then the child had very dramatic limb anomalies, including missing limbs and flipper hands. There have been many other instances like this, where essentially a therapeutic dose to an adult that was totally nontoxic, could affect the developing fetus. So a lot of people think the same would be true for toxic chemicals or radiation. In other words, exposures that are relatively low, which are nonharmful to an adult, could dramatically affect the developing fetus if it was exposed during the wrong time.
What epidemiology does is to study people. There are other ways of studying affects of environmental chemicals -- you can look at salamanders, you can look at cell systems -- but obviously at some point you want to look at people. But the limitation of looking at people is that people do a lot of complex things. When you actually do an animal study or you do a cell-system study you can essentially deal with one exposure, see what happens and control everything else, because that’s what an experiment does. But people live very complicated lives. We all live and work in different places, we have different lifestyle habits, we have different illnesses, and different medications. All this makes it difficult in epidemiology to pinpoint exactly what specific environmental exposure is problematic. Occasionally we’ve been able to do that. We’ve been able to do that with smoking and lung cancer and asbestos and lung cancer and smoking and cleft lip and palate. But in general, we have a lot of trouble pinpointing certain exposures, though we do not have trouble saying things like, “it looks like living near hazardous waste sites is a problem", but we don’t know exactly what chemical it is.
What epidemiology does, essentially is to first look at the presence or absence of birth defects and then perform studies to correlate that to the presence or absence of genetic and environmental exposures. When I use the word environment, because people live complex lives, we’re talking about what you eat; what infections you get exposed to; what chemicals you get exposed to in the work place; what lifestyle factors you have like smoking, drinking, drug use or any number of things; and what your social class is. All these things we know can influence whether or not you have a birth defect. It’s a complex situation whether a child will get a birth defect or not. When thalidomide happened, we thought, “oh, it’s going to be pretty simple, there was one exposure,” and if something is a strong enough teratogen (something that causes birth defects) then that’s what happens. But most things don’t work that way. As Ted said, there’s a complex interaction between genes and environments. How I want you to remember the genetic environment interaction is, if you think of a gene as a windy road and you think of an environmental factor as driving 80 miles an hour, you basically have to put both together in order to have a birth defect occur.
As Ted said, though children tend to be more susceptible at low doses, our definition of what we call birth defects is variable. In general most studies have focused on structural birth defects (neural tubes, cleft lip and palate, congenital heart disease, missing kidneys and missing limbs and conditions like prematurity) because we can easily identify those. But there’s been almost no research on functional abnormalities, like attention deficit disorder and mild mental retardation and others that people are extremely concerned about. The difficulty we have in doing studies of those conditions is that we don’t know how to count them and we certainly don’t know how to count them well in a big population. We can do small counts in a population, but we can’t do whole counts of whole populations and get a good picture about what’s going on.
I just talked about the issue of "big" in epidemiology. This is one of the few times that big is better. The reason that big is better is because, if you do a study of 1000 people with a birth defect and you study 1000 people without a birth defect and you find a relationship with, let’s say smoking and cleft, that finding is much more believable than if you study 50 clefts and 50 controls. In other words, the bigger the sample, the more apt the results are to be definitive. So this is an example where bigger is better.
Ted pointed out that the cause of most birth defects is unknown, but I think that there’s a much more hopeful message there. It is likely that if enough research is done we can certainly pinpoint many things, not all things, and reduce the incidence quite dramatically. That’s what happened with folic acid and it’s likely to happen going forward.
I want to talk briefly about a couple of the environmental issues that we’ve been working on. We’ve done some big interview studies regarding pesticide use at home and we’ve found that 20-30% of people use chemicals at home with very cute names like round-up. These are extremely toxic chemicals and we’ve found them to be associated with defects of the heart, cleft lip and palate and limb abnormalities. Unfortunately because people tend to use multiple chemicals, we couldn’t exactly say which one it was, but there’s very good reason to think that these chemicals are extremely toxic. They are extremely toxic to animals and we have found the same in humans.
We’ve also been collaborating with scientists at UCLA to look at air pollution. We have found that air pollution, particularly automobile air pollution, to be associated with defects of the heart. This made biological sense because of carbon monoxide levels. Again, we’re going to be following up and doing more studies on this. One of the problems in epidemiology, and this happened with tobacco and lung cancer, is that people don’t accept a result in people unless the study has been replicated numerous times. That is why it takes a long time to find causes, because one study is never looked at as being enough.
The heart disease/air pollution association is extremely interesting. But again, we couldn’t say exactly which chemical it is because carbon monoxide and other air pollutants go together.
Finally, we’ve looked at toxic waste sites. In California, if you look at an individual toxic waste site, and try to say, “are birth defects high?” You rarely can say anything definitive because the numbers are too small. There are too few people with birth defects and too few pregnancies to be able to say anything. But when you aggregate dumpsites, and we’ve done that, we’ve looked at people living near any dumpsite with certain types of exposures. We actually did find a risk for defects of the nervous system. But again, we couldn’t say whether it was heavy metals or organic solvents, because a toxic waste site is a hodge podge of chemical exposures.
The take-home message should be that research works and it’s a good thing to do, but it’s very difficult to pinpoint specific environmental chemicals and it’s much easier to say things like, “living near a freeway is harmful” or “living near a hazardous waste site is harmful” or “using pesticides is harmful.” But as long as the regulatory environment regulates chemical by chemical, we haven’t been able to contribute much to those issues. Obviously from a public health standpoint, we can contribute a lot.
Steve Heilig: Thank you John. Betty Mekdeci has been involved with CHE since the beginning and her group is one of the best examples of how health-affected groups can get involved. You can actually read her story on the CHE website at: www.healthandenvironment.org.
* Betty Mekdeci, Executive Director, Birth Defect Research for Children
Birth Defect Research for Children reaches out to families from all over the country. We provide free information about any birth defect to any family who contacts us. We also link families with children who have similar problems through our Parent Matching Program. The most interesting thing that we do is sponsor a project called the National Birth Defect Registry. The questionnaire we use for the registry was designed through the collaboration of seven scientists with expertise in things ranging from genetics to developmental biology, biometrics, epidemiology and other disciplines that would help us ask the right questions. We collect data on over 300 categories of birth defects. We collect information on both male and female exposures. I think we are probably the only project looking at the male contribution to reproductive outcomes. We ask about both prenatal and preconceptual exposure to all kinds of environmental agents including hobbies, occupational history and military history. We analyze the data to look for patterns and we do this because, when we look back in the history of birth defects, the major teratogens (major external causes of birth defects) were identified initially through pattern identification. That included thalidomide, fetal alcohol syndrome, rubella, DES, radiation, mercury and others. We thought that if we designed a large-scale project to collect data from all over the country that we might be able to identify patterns more rapidly. Some of the national issues that we’ve been able to identify and work on with the registry include the effects of the antinausea medication Benedectin , which was taken off the market. We’ve found patterns of increases in heart, limb and cleft defects and diaphragmatic hernia. We’ve done work on Agent Orange for many years and we have over 2000 veterans registered with us. That has given us an interesting snapshot of a whole different area, of what I’ll call functional birth defects. The veteran’s children have increases across the board in learning, attention, chronic skin disorders, immune system problems, asthma, and allergy and endocrine problems. This has been very consistent; it just doesn’t go away.
We also look at military exposures to the First Gulf War veterans. We identified initially a rare pattern of birth defects called Golden Hour Syndrome, which is a cranial facial birth defect that occurs between one in 15 to one in 45,000 depending on what registry you look at. We found an increase and brought it to national attention through a variety of media coverage. The Department of Defense, the VA and CDC have now funded studies, and there are four published studies that have found increases in birth defects in the children of Gulf War veterans, both male and female, who served in the First Gulf War.
We also use the registry to assist communities who are concerned that there may be too many cases of a particular birth defect in their area. A case in point is the community of Dixon, Tennessee, where we were contacted about an increase in cleft palate. Over a three-year period in a birth population of less than 1300, this community had 19 cases of cleft palate, when less than two would be expected statistically. In addition to helping the community identify this increase, we also helped them look at environmental factors in their community. We found that over a period of 20 to 30 years some companies have been hauling barrels of solvents, primarily trichloroethylene, into an unlined, uncapped landfill. Periodically, the TCE had leaked into both sources of the community water and into private wells. So a result of our work there, I think the precautionary principle has really taken hold. They have moved the source of the water supply to a river that is not adjacent to the landfill. They have capped and lined the landfill and are now warning the residents on private wells not to drink the water. We feel very good about what we’ve accomplished there.
The registry is now an online project. I think it’s the first of its kind. Any family who would like to participate can go to our website at http://www.birthdefects.org/ and fill out a questionnaire. If they choose to be in the parent matching system, we’ll send them a list of matches. Then we add their case into whatever category we’re looking at. We’ve had an unusual number of gastrisis cases (a stomach defect) coming in. We may be doing an analysis of that within the next few weeks.
Steve Heilig: Thank you Betty. So we’re going to open it up for questions now.
4. Questions, Answers and Comments:
Mark Mitchell, MD, MPH, President, Connecticut Coalition for Environmental Justice: Do you generally find only one type of birth defect or do you find multiple types of birth defects when you see birth defects? Also do you see more incidence of twins in relation to what’s happening in the environment?
John Harris: It is true that if an agent causes one birth defect, it may very likely cause others. Acutane is an example, which was first associated with a set of structural anomalies and later, on follow-up, actually caused severe mental retardation and other things. Thalidomide, even though it’s famous for causing limbs, actually looked like it causes other things. So people usually start and there’s a sentinel outcome and you see that first. But once an agent is identified with a sentinel outcome, it’s often identified with other problems as well.
Ted Schettler: I saw a recent report where people living in areas of high air pollution had higher incidence of twinning.
Anthony J. DeLucia, Ph.D., volunteer, Kingsport Tomorrow: We’ve just had meetings two weeks in a row. We had Physicians for Social Responsibility talking about the need for national health tracking. Then we had a meeting last week about our air quality problems, including ozone, which has been linked to some chromosomal damage. But I’m very interested in fine particles, has anybody been looking at the research implications since inflammation has been involved where there might be a systemic affect, which could lead to genetic problems with fine particles and birth defects? Smoking is more than just carbon monoxide and some of the gases that we’ve been looking at like ozone and CO and the mixture that Dr. Ritz and others have been looking at.
Ted Schettler: There have been a couple of interesting studies done on mice that have been published fairly recently, showing that fine particle air pollution in an area of steel production in Canada was associated with heritable mutations, in which the mice were put in an area of the air pollution for a ten-week period, removed for six weeks, and then bred. Through crossbreeding studies they were able to show that the heritable changes were passed through the male genome, not the female. I should point out that the changes in the DNA were in the non–transcribing portion of the DNA, not the areas that are responsible for creating the phenotype, but in the parts of the DNA that are not responsible for transcription. But nonetheless, it raised the interesting possibility that you could find areas in the DNA responsible for phenotype. Then they were also able to put HEPA filters on the cages, so that the effect went away when the fine particles were removed. That’s why they ascribed it to fine particles. These have been published in the Proceedings of the National Academy of Sciences and the journal Science within the past six weeks.
Tim Lambert, Ph.D., M.Sc., Manager, Environmental Health Risk Assessment and Management, Calgary Health Region, Environmental Health: Is there any biomarkers, or anything that can be used for low-level exposure to trichloroethylene in a residential environment?
Betty Mekdeci: We’ve looked at that a lot. There are markers if you’ve been exposed recently, but not as long ago as two or three years. So it’s very difficult to prove the exposure when the child is two or three years old.
Pamela K. Miller, Director, Alaska Community Action on Toxics (ACAT): We work with a lot of rural communities on St. Lawrence Island and throughout Alaska. There are small isolated populations that are often affected by persistent chemicals from industry, the military and also long-range transport of persistent organic pollutants. We’ve had a lot of reports from health aides and elders who report illnesses that include low birth weight in babies and premature birth, in addition to endocrine disorders and cancers. Our health department and other regulatory agencies certainly don’t take these reports very seriously. I wonder if the speakers or anyone else on the phone might have some suggestions for how I might substantiate this and validate what the health aides and the elders are observing.
Betty Mekdeci: In Dixon the community had tried to get the regulatory agencies to listen to them and they just wouldn’t until we helped them to identify the cluster. At that time the CDC did come in and the public health department took notice. I think what you have to do is to put together some good community-based research that gives them a picture of what’s going on so they don’t see it as just an idea that someone has. We never know when we’re called to a community whether it’s going to be a true finding or whether someone just thinks there’s something going on. So if you do your community-based research, then you will get more attention from the regulatory agencies.
John Harris: If you focus on prematurity and low birth weight, then you can use vital statistics. The problem you have with the other outcomes, like endocrine problems or immune problems, is no one really knows what the baseline rates are. But we know what the baseline rates of prematurity low birth weight are. Vital statistics is usually an accessible file in every state. You could check if there are any regional differences and you can often get attention that way.
Michael Lerner, PhD, President, Commonweal: I just want to say what a wonderful call this is. Betty spoke at a regional CHE meeting in Florida and made a point that I would like to bring up here. Birth defects in a community setting are often an early warning of a wide range of health problems that may emerge later in the life cycle from environmental exposures. It seems to me; in thinking about birth defects we’ve heard a lot today about the very difficult issue of figuring out exactly what chemicals it is. It seems really important to not lose the forest for the trees. The point about half of pregnancies ending in miscarriage and the study that showed, while 3.5% of kids are identified with birth defects at birth, that if you track them for a while, that’s 16% and half of those are major. The continuum from structural birth defects, to a wide range of functional birth defects on a horizontal access and on the vertical access over time, the continuum of birth defects as an early warning into a whole pattern of other chronic diseases…
Betty Mekdeci: You got this right. A lot of people don’t actually know why thalidomide was kept off the market in this country. It had nothing to do with birth defects; they weren’t even recognizing that at that point. It was kept off the market, because in a number of people it was causing a condition called peripheral neuropathy. Most of the major causes of birth defects will also cause problems in a percentage of the people who are exposed to that substance even at ordinary doses. So, I think if you look at causes of birth defects, you have to look at a triad of possibilities. I used to give a speech, which I called the toxic triad, where the same substance that caused a birth defect might also be a carcinogen and a mutagen.
Anjuli Gupta, Health and Environment Project Coordinator, Center for Environmental Health: In response to Betty, where you said one solution for communities who see a suspected high incidence of a disease as being some sort of community-based research. My question is what resources might you recommend for communities to look to for support in doing community based research.
Betty Mekdeci: We would welcome them to fill out our questionnaire. If we’re asked by community to look a particular potential increase, we will do that. There are other organizations as well, that will help a community look at particular exposures. Certainly Environmental Scorecard is a very important resource to know what companies are releasing in the way of toxicants in their community. When we looked at Dixon, we also looked at the EPA website, we went into the archives and we went into the files of the water department in Tennessee. There are a lot of resources once the community has a picture of what’s happening. Mapping is helpful as well. If you’re looking at something that may be in the water, it’s very important to start a map of how the exposures might be occurring. So, there’s a way to do it, and it’s not rocket science. If a community wants to do it, there are resources, and we are one. There may be others looking at other health endpoints in the community as well.
Lorena Barck, PhD, JD, Program Manager, Oregon Department of Human Services, Environmental and Occupational Epidemiology, Environmental Public Health Tracking: We don’t have a birth defects registry in Oregon, and one of the arguments that people have against it is that we have such small numbers of individual types of birth defects that it wouldn’t do much good in terms of tracking for causes and other kinds of things. I’m wondering, if people classically think of birth defects registry as what shows up at birth, maybe what we can do is try to promote a registry that goes farther in years, so that the structural defects show up later and the functional defects show up later. My question for the group is, what would be your suggestion as to what age should we be tracking kids? Do we go to two years old or five years old? What would be your best suggestion?
John Harris: If you want to track functional birth defects, you need to track kids at least to six or seven years old. Because you want them to enter school and see what happens. We’re now tracking mental retardation through age eight.
Betty Mekdeci: If you really want to know what’s happening, you’ve got to track them all the way through adolescence and into adulthood. We’re seeing some interesting increases in endometriosis in the daughters of Vietnam Veterans. Whether this is a true effect, we don’t know, but it has been identified in animal studies. What if some of the environmental exposures were actually predisposing people to cancers in early adulthood? In fact, there’s a whole body of research called the fetal origins of adult disease, where researchers have looked at things happening in the prenatal period as setting how your life may turn out, at least from a health standpoint, for the rest of your life.
Ted Schettler: The other piece of the answer seems to depend on what the purpose of the tracking is. If for example, you’re interested in the experience in Oregon, than obviously, you’re going to need to set up a birth defect tracking program in Oregon. You’ll have to do it as well as you can, and whether you use passive reporting, or actively solicit cases, or whatever, you’ll have to figure that out. But in an earlier conversation with John Harris, he made the case that if, for example, your interest is in doing research on environmental contributors to this problem, irrespective of the geography, you can then make an interesting case for setting up just a few tracking programs that really do a first class job, that are very comprehensive and very well funded, and carried out very well, so that you get around this problem of having a whole lot of programs that aren’t particularly big or comprehensive and you end up with a lot of data that aren’t very useful. So, I think you have to ask yourself what sort of question you’re trying to answer.
Steve Heilig: Ted, a lot of people are pinning hopes on the National Children’s Study which has been proposed for next year if it is funded. That is supposed to do a biomonitoring study and follow children as they grow up. Can you comment on this?
Ted Schettler: Well, the National Children’s Study, which has been proposed, has two major advantages, provided it gets full funding. One is that it’s big, so we can get around these small number issues, because it would be hundreds of thousands of mother/infant pairs enrolled. The second advantage is that it is prospective. That is, data would be collected early in pregnancy, and even in a small subset, in prepregnancy. The outcomes would then be noted. But because it’s prospective, you would be able to quantify a number of the potentially contributing variables, not only the environmental factors, but diet, infectious disease, social circumstances and so forth. So it really is a model that holds great promise for those reasons, but it would of course, be very expensive and take a long time to get results.
Steve Heilig: They are looking to kick it off next year, in 2005, with $27 million, but the funding is still uncertain. So that is something we will be keeping people informed about.
Marget Braun, author, DES Stories: These have been great presentations, thank you. I want to mention the classic case study, which is the ongoing living laboratory of DES-exposed populations. It’s such a perfect example of the complexity that we find in the epidemiological approach. Most importantly, the sentinel outcome didn’t really appear until decades after prenatal exposure and the health outcomes are still unfolding. The population’s average age is now in the 40s and 50s and long-term follow-up is still finding functional birth defects. So I understand thalidomide is often used as a reference, but DES is such a classic example of teratagen, mutagen and carcinogen.
Pete Myers: I would like to add that DES is opening up a whole new chapter, as work proceeds, looking at not just the effects on the daughters but the effects on the granddaughters and grandsons. Both in the lab, and with people, we’re starting to see those effects. One of the most interesting aspects is that they’re starting to get into the molecular genetics of how it happens. In essence, something called DNA methylation takes place, which leaves chemical signatures on the DNA that prevent certain genes from being turned on and turned off at the same time and this methylation pattern is transmitted past the first generation.
Steve Heilig: Thank you Pete. We are out of time, so I would like to thank all of our speakers who have joined us today. Would any of you like to specify your websites?
John Harris: Our website is: http://www.cbdmp.org/. We have a lot of information on environmental factors there.
Betty Mekdeci: Our website is: http://www.birthdefects.org/.