National Children’s Study to Assess Environment and Genetics

In a press release yesterday, the National Institutes of Health announced that the first Vanguard Center of the National Children’s Study had begun recruiting volunteers. Yesterday, we interviewed Dr. Phil Landrigan, who will lead the Queens, New York, site. In yesterday’s post, Landmark National Children’s Study Launches in US, Dr. Landrigan explained the purpose of the study and drew parallels with the Framingham Stroke Study.

Today, we bring you Dr. Jeff Murray, neonatologist and medical geneticist. Dr. Murray will be principal investigator for the Polk County, Iowa, research site, which is expected to begin recruiting participants in 2011. He provides us with insights into how the study will work on a local level. In future posts, we’ll introduce you to other researchers who are involved in the National Children’s Study and announce findings as they are released.

We spoke with Dr. Murray from his office at the University of Iowa Hospitals and Clinics in Iowa City. We asked him to tell us about the study from his perspective.

MURRAY: My first involvement with the study was that I was asked to serve on the committee for how the study would be implemented. A previous group of scientists and physicians based at the National Institutes of Health and the Mental Health Institute had come up with an initial plan on how to carry out the study. Then they brought in scientific expertise to help with the research design, and I was a part of that process.

As a pediatrician, I saw this as holding out the promise for providing us with much better insights into both the causes and treatment of diseases of infancy and childhood. I also saw that it had a huge amount of power to address really important questions and, as a result of that, I was certainly very enthusiastic about the study.

The National Children's Study seeks identify the causes of common childhood diseases.

One of the things the National Children’s Study is going to do will be to investigate some of those common disorders of childhood. Hopefully, that will give insights in the future into causes and outcomes. We hope to identify and enroll 100,000 infants prenatally, and then to follow them from their prenatal time through birth, and then on up until early adulthood.

The goal is to collect information on their environmental exposures as well as their genetic background, and to use that information to identify the causes of disease. While 100,000 sounds like a very big number, and it is, it will be best suited for identifying the causes and complications of common diseases of childhood, things like asthma and diabetes and autism and prematurity — things that will affect thousands of the children in the study.

BPGL: How many children will be in your portion of the research study?

MURRAY: There will be 1,000 children in Iowa. There will be 105 sites nationally, in 105 counties. There’s only one county in Iowa, which is Polk County.

BPGL: Will new babies and mothers be enrolled year after year, or will you enroll all 1,000 in the first year?

MURRAY: All the babies aren’t enrolled in one year. They’re predicted right now to be enrolled at a rate of about 250 a year in a given county. So in Polk County, we would be enrolling over probably four or five years.

Researchers will knock on 15,000 homes to identify 1,000 moms and their offspring.

Some counties are large enough that we wouldn’t be able to enroll every single pregnancy that occurs in the county. [In that case], before the study begins to enroll people formally, the team will go around to individual communities and literally knock on the door of every single person in that geographic area. In Polk County, that’s predicted to be about 15,000 households. And from those 15,000 households, they’ll ask people if they’d be willing to enroll in the study.

BPGL: How are you going to knock on 15,000 doors?

MURRAY: It’s not a volunteer effort. It’s funded by the NIH, so by the time the door knocking comes around, there’ll be in the vicinity of about 20 people doing that.

One thing I would like to emphasize is that the university and myself act as the principal investigators, but that the bulk of the work is going to take place in Polk County under the direction of Dr. Rizwan Shah, a pediatrician at the Iowa Hospital Systems. It’s probably important to note that there’s been a real coming together of the different hospital systems in making this program possible. I am honored to be a part of a community that was willing to put aside what are sometimes competitive interests to recognize that this is important for children. We had to have a buy-in from all the hospitals in Polk County to make this work. They were all very eager and very enthusiastic in their support of the project.

Children will be followed from before birth through age 21.

BPGL: Will you be doing any awareness activities so that people are anticipating that someone will knock on their doors?

MURRAY: There will be a big community engagement effort before the study starts, where there will be posters and fliers and news announcements and radio and TV shows talking about the study to make the community aware of it. We hope that it will have a very high profile in the community before people go out and begin to knock on doors. And we’re going to work through individual communities and community organizers so just a random person won’t show up. We’ll have previously gone to the community organizations, the churches and the political organizations and the health organizations and so on, and try to work with them about the best way to contact people as well.

Volunteers have to sign a consent document in order to be able to participate. They’ll be followed until they become pregnant, and through pregnancy and beyond. We expect that by knocking on the doors of about 15,000 homes, we will end up getting somewhere in the vicinity of 250 pregnancies a year. Not every woman, of course, will want to be in the study, so we have to knock on more doors than people are likely to present with pregnancies.

BPGL: So you’re identifying moms long before they decide to get pregnant?

MURRAY: The idea is to enroll them pre-pregnancy. The perfect study subject is someone who, before she even becomes pregnant, has been enrolled in the study and has been followed along. But we also recognize that most pregnancies are unplanned, and so people can be enrolled at the time of birth.

BPGL: In Dr. Landrigan’s interview, he talked about the kinds of sampling of the mothers’ and children’s environment that will be done over the life of the study. What is the genetic element of the testing?

MURRAY: At each of the visits, the team will do blood samples that allow them to do both genetic studies and also to measure things in the blood, like chemical exposures.

Researchers will study variations in individual genes.

We’ll be looking for variations in genes that contribute to the onset of disease. All of us have thousands and thousands of individual genes, but many of us have small variations in those genes that express the work that the gene does in slightly different ways. We’ll be looking to see whether that genetic variation in the gene, things like blood groups — for example, you can be A, B, or O blood group, or Rh positive or negative — to see whether those differences affect the onset, or the likelihood of you getting a disease. And we will have, probably, millions of genetic variants studied in each individual child.

BPGL: As you are studying these children, will the parents get any advice as far as diet and so on? Or are you just observers, who are not going to influence anything?

MURRAY: The study is not meant to provide advice. But, if parents ask, we’ll provide them with resources that are available in the community or through their own physicians. It’s not meant to replace typical pediatric care, even though they will have typical assessments done, things like growth and development assessed. It’s not meant to replace what their pediatricians would normally do anyway, but if we identify relevant abnormalities in a child, for example, we would refer them back to a primary care provider to enable the child or adult to be taken care of. We’re certainly not going to hide things from anybody if we find them.

The study will not replace regular pediatric care.

BPGL: How soon do you expect to have results? Will we have to wait 21 years to learn the research findings?

MURRAY: The study itself will be putting out materials as time goes on about the results, so that people will be able to benefit from what we learn. We should begin to have findings in just a few years.

BPGL: Will the people be incentivized for their participation?

MURRAY: They’re being reimbursed for the cost of the time that they would put into the study. Depending on how much time is involved in doing an interview or having a sample taken, or so on, they’re reimbursed for that.

BPGL: What if they move, are they then eligible to go to another site in another state?

MURRAY: The hope is that they will continue to be enrolled in the study, and if they move to a place where there is also a study center, then they can continue to be followed through that study center. And there are also going to be teams who will go out and try to identify people who have moved some distance away. The retention in the study is, of course, a key factor to it being successful.

BPGL: Considering that Polk County is located in Iowa, where farmers raise a huge percentage of genetically modified crops, do you expect you’ll be able to find evidence of the presence of genetically modified organisms (GMOs) in babies?

MURRAY: The research is designed to try to address questions like that. We’ll be taking nutritional surveys from the mothers, so we’ll know what their diets are, what their food sources are, and insofar as those food sources can be traced back to genetic modifications, we will have that data. We will be collecting blood samples and urine samples from the mothers and the babies, so if elements of those foods would be present, they would be potentially detectable. I would also say that that sort of detection and the role of those remains controversial. But I don’t think that means it shouldn’t be studied, just that we should do the best job we can in studying it and determining whether those factors are both present and influencing the outcomes.

BPGL: As a neonatologist and a medical geneticist, how does your background color your interest in the study?

Why are some babies born full-term and others are premature? The study should help us find out.

MURRAY: I have a particular interest in pre-term labor, and I’m very interested in some of the nutritional factors that predispose to babies being born prematurely — things related either to the mother’s health background or her diet. We’re interested in the role that some common dietary elements, things like Omega 3 fatty acids and cholesterol and others, play in preterm labor. I’m especially interested in learning about the outcomes of that, in part because, although the genetics is very exciting and interesting, it’s difficult and challenging to be able to manipulate genetics in the short term. There are lots of challenges associated with that. [On the other hand], the environment is something that we can sometimes be more effective at changing in the short term to effect preventions or cures. And so, if we could learn, either through the genetics or through the environmental studies directly, about nutritional causes or risks for preterm labor, that might be something we could offer to women as an effective preventative mechanism.

BPGL: Are you willing to speculate what you might find?

MURRAY: I’m willing to speculate in a very general sense. I think we’ll learn that both genes and environment play a role in childhood diseases. We’ll learn that some children are at much higher risk based on their genetic background than other children for acquiring certain diseases. And we’ll learn that the role of environment, nutrition, exposures to environmental toxins will probably be very important.

The National Children's Study may lead to better health for all children.

As a scientist, we want to keep our minds open and be willing to entertain all the possibilities and let the data tell us what’s happening, rather than try to make predictions which can then sometimes force things down a path.

We don’t know what is going to happen in the next 25 years. What are the dietary changes, the lifestyle changes, what are the community changes? The goal of this study is, instead of having to wait 25 years and look back to figure out what happened, we’ll be capturing that data in real time. And as soon as there’s sufficient data, we’ll be able to identify new causal mechanisms and be able to address them more quickly.

Part 1: Landmark National Children’s Study Launches in US

Part 2: National Children’s Study to Assess Environment and Genetics (Top of Page)

Julia Wasson

Blue Planet Green Living (Home Page)

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My 5: Dr. Jeff Murray, University of Iowa Hospitals and Clinics

Landmark National Children’s Study Launches in US

In the United States today, 1 in 25 children have autism spectrum disorder; 1 in 4 children in Queens, New York, have asthma; and 30% of the kindergarten children in a North Florida school district are overweight. Today, these statistics don’t seem unusual. Obesity, childhood diabetes, autism, and other diseases afflict more and more children every year. Without a doubt, these statistics should alarm us. And the trend toward increased childhood disease seems to be on an irreversible path. But what if we knew what caused these diseases? Could we then figure out how to stop them?

Yesterday, the National Institutes of Health announced the launch of the National Children’s Study, an ambitious, decades-long project that may well reveal the causative factors of a host of childhood — and adult — illnesses.

One of the key figures behind the study is Phil Landrigan, MD, MSc, who directs the Children’s Environmental Health Center at Mount Sinai School of Medicine in New York City. Landrigan is also the chairman of the Department of Community & Preventative Medicine, as well as a professor of pediatrics there.

If you don’t recognize Dr. Landrigan’s name, you will recognize his critically important contribution to your health. In 1976, Landrigan, along with Dr. Herb Needleman, documented widespread lead poisoning in children. This information persuaded the US government to mandate an end to lead in paint and gasoline. Referring to Landrigan’s and Needleman’s work, Dr. Michael Shannon, chair of the American Academy of Pediatrics Committee on Environmental Health, was quoted in The Lancet as saying, “In complete correlation with the reduction of lead from these sources, the blood lead level of every child, actually every American, fell by more than 40%. It was an absolute monumental achievement.”

Landrigan will head the first of seven Vanguard study sites, all of which will open in 2009. Some 40 centers are planned. Landrigan’s center, in Queens, New York, began to recruit study volunteers January 13.

We spoke with Dr. Landrigan by phone from his New York office. What follows is the first of two interviews. Our second interview, with Dr. Jeff Murray of the University of Iowa Hospitals and Clinics, will run tomorrow.

Every child deserves a healthy environment in which to grow and learn.

BPGL: Tell us about the National Children’s Study.

LANDRIGAN: The National Children’s Study is the largest research study of children’s health that’s ever been undertaken in this country. It’s what we call a prospective epidemiologic study, which means it’s going to enroll moms very early in pregnancy and follow the children out to at least age 21.

The goal of the study is to identify factors in the environment that cause disease in children, like autism and childhood cancer, attention deficit disorder, asthma, diabetes, birth defects, prematurity, and low birth weight.

To assess environmental exposure, we’ll do a history for every mom in the study during her pregnancy. We’re going to get samples of blood and urine from each mom at several points in pregnancy, to measure levels of several hundred chemicals in the blood of each mother. We will also be assessing personal behaviors such as drug, alcohol and tobacco consumption, the social environment and the environment of the community in which each mom resides. We are looking at those issues, because we strongly suspect that social and community factors interact with chemical exposures in the causation of disease in children.

We’ll get a sample of umbilical cord blood from each baby at the time of delivery. We’ll be tracking the babies very closely as they grow up, with exams at 1, 2, 3, 5, 8, and 10 years of age, with very thorough developmental assessments at several points along that ladder. The overall goal is basically to link environmental exposure in early life to the subsequent development of these kinds of diseases in kids.

Children in the study will be followed from before birth through young adulthood.

BPGL: I understand the NCS is similar to the Framingham Study of heart disease and stroke. Can you elaborate on that?

LANDRIGAN: The Framingham Heart Study is the model for the National Children’s Study. Back in 1948, at a time when rates of heart disease and stroke were rapidly skyrocketing in this country, the Public Health Service went to the city of Framingham and undertook a prospective study of the population of the whole city. They signed up people for the study, took a history and physical examination on each person, measured their blood pressure, and so on. They tracked the people prospectively through the years to see what the risk factors were for heart disease and stroke. It was out of Framingham that we learned everything that we now understand today about the risks for cardiovascular disease.

So, for example, it was Framingham that taught us about cigarette smoking, high blood pressure, cholesterol, triglycerides, obesity, diabetes, sedentary lifestyle — all that information came first from Framingham and has since been replicated in other studies. It’s acting on that information about preventable risk factors for disease that we have succeeded in this country in knocking down the rates of heart disease and stroke by about 60 percent. It’s really one of the biggest triumphs in public health in this country in the last half century — and one of the least broadcast.

Study results will be used to improve children's health and well-being.

BPGL: I read on the NCS website that finding the causes of diabetes one of the primary foci. What else are you planning to study?

LANDRIGAN: There are about 20 primary foci. And they’re all specified in the planning of the study. I mentioned autism, diabetes, childhood cancer, asthma, attention deficit disorder, also in older children, mental health problems like depression and schizophrenia.

BPGL: Will you follow diet as well?

LANDRIGAN: Yes. We’re also getting DNA on everybody, so we’ll have a chance to look at genetic factors.

BPGL: Are you also looking at immunizations?

LANDRIGAN: Absolutely.

BPGL: Since most kids are required by their school system to be immunized, will you have enough controls for comparison?

LANDRIGAN: The study is going to be following 100,000 children. So, in a population as large as this, there will be children who do not get immunized. We know from national vaccine rates that this large number of children will give us a substantial number of kids who are not immunized.

If you’re thinking about autism, the math says that 1 in 150 children is currently diagnosed with autism. In a population of 100,000, we will have about 600-700 hundred kids with autism, or at least with autism spectrum disorder. So that should be enough to really take a very careful look at if vaccines are related to autism or not. If they are, we’ll have a chance to look at that. And we’ll also have a chance to look at a lot of other potential factors for autism, like prenatal exposure to pesticides or lead or other chemicals.

BPGL: Will you be sampling the air in the environment as well?

The National Children's Health Study will assess physical and mental development over two decades.

LANDRIGAN: Yes. We’ll doing sampling in the home, in the air, and as I mentioned, sampling of the mother herself during pregnancy, so that we can see what chemicals the baby is seeing during the nine months of pregnancy.

BPGL: In the recruitment process, is there any danger that parents may be self-selecting?

LANDRIGAN: We hope not. There’s an element of risk of that, of course. The study is set up according to very strict principles of statistical sampling so that it can be conducted in 105 counties across the U.S. Those counties were selected entirely according to statistical methodology. Then within the counties, we’ll be going to certain communities and certain neighborhoods, which again, have been selected entirely according to principles of statistical sampling. And then, the way we try to avoid self-selection is that we try to maximize the percentage of families that join the study. The higher the percentage of families in a given community that join the study, the less the risk of self-selection. It’s always a concern. We’re always worried about it, but we try hard to avoid it.

BPGL: I’m curious why the research study is just getting started in 2009, when it was authorized in 2000.

LANDRIGAN: There are a couple of factors. This was an enormous planning effort. So, from 2000 to 2005, we spent planning. The first contracts to actually do the study were awarded in September of 2005. Our group in New York was one of seven groups around the country who got contracts in the first wave. If all had gone according to schedule, we would have started sometime in 2006.

But what happened was, in February of 2006, President Bush declared that the study was not a funding priority, and he directed the NIH to close it down. We therefore had to postpone our fieldwork and instead work through the Congress to save the study. We had to do that each of the last three years. So, only now, we’re getting into the field.

All children will benefit from the results of the study in years to come.

BPGL: Do you have confidence that you’ll receive steady government funding once the study launches, so that you can continue your important work?

LANDRIGAN: We’ll be working to ensure that. We’ve survived so far through some very tough times, so we hope that we can continue [for the full term of the project]. Because we’re increasingly concerned that early exposures may be the root cause of disease later in life, things like cancer, Parkinson’s disease, dementia … my own feeling is that once you launch a study like this and once you invest the extraordinary amount of energy that you must invest to sign up families and keep them with the study for 21 years, that nobody, least of all the families themselves, are going to want to break away at that age.

The Framingham study is still going after 60 years. They’re now in the third generation. In Framingham, they were signed up as adults, but they picked up the kids who were born to those adults and followed them through. And now they’re into the third generation.

BPGL: Could you tell me briefly about your instrumental role in setting this study up?

Dr. Philip Landrigan, one of the driving forces behind the National Children's Study and head of a Vanguard study center in Queens

LANDRIGAN: I was part of it. Back in ’96 – 97, I served for about a year as a special assistant to Carol Browner, when she was the administrator of the US EPA. I set up the Office of Children’s Environmental Health at EPA. It was basically out of the work of that office that we conjured up the idea for this study.

We came to realize that rates of disease like cancer, asthma, autism, were rising in this country. We realized that kids are surrounded by chemicals, that kids are very susceptible, very vulnerable to chemicals, and that we knew far too little about the effects of the chemicals on kids’ health. So we said to ourselves, Hey, we need a big study that builds on the little bits and pieces of evidence that we have, and create a much more systematic body of knowledge about the impact of chemicals on children’s health.

BPGL: Was Carol Browner supportive of that?

LANDRIGAN: Extremely.

BPGL: Is there anything else you’d like to our readers to know?

LANDRIGAN: Here at Mt. Sinai Medical School, where I’m situated in New York City, we’re not only doing the National Children’s Study, we’re also very much involved in training the next generation of pediatricians who are going to be the leaders in this country in the field of environmental pediatrics. Be sure to mention that it’s so important to couple research with training and education.

Part 1 of 2

Part 1: Landmark National Children’s Study Launches in US (Top of Page)

Part 2: National Children’s Study to Assess Environment and Genetics

Julia Wasson

Blue Planet Green Living (Home Page)