What if The Truman Show happened to you? For 100,000 children across America, it will — and Yale researchers will be behind the cameras.

The Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, part of the Yale School of Public Health, received a grant of $10.7 million Friday to widen its involvement in the National Children’s Study. Beginning in 2009, the NCS will track 100,000 children from conception to age 21, examining the role of genes, the environment and the interaction between those two factors on children’s health and development. It is believed to be the largest study of its kind ever conducted in the U.S., according to a University press release.

“This is a landmark epidemiologic study,” said Paul Cleary, dean of the School of Public Health. “It has huge scope and will give us a larger range of risk factors and greater precision than we’ve had before.”

Kathleen Belanger, research scientist at the School of Public Health and one of the study’s investigators, said the NCS is being directed by a consortium of federal agencies, including the EPA, the CDC, the National Institute of Environmental Health Sciences and the National Institutes of Child Health and Human Development. Other institutions involved include Brown University, the Johns Hopkins University Bloomberg School of Public Health and the University of California, Los Angeles.

The NCS will examine as many as 30 different hypotheses, including how environmental factors relate to early life events such as pregnancy outcomes, low birth weight and infant mortality. As the children age, the study will also look at other hypotheses related to issues like asthma, autism and obesity.

Belanger said the study is an attempt to gain more information about the underlying causes of such conditions, and why they are becoming more common than they were a number of years ago.

According to a transcript of press release remarks by Duane Alexander, director of the NICHD, the United States spends $758 billion per year on obesity, injury, asthma, diabetes, schizophrenia and autism — which make up only a handful of the conditions being examined by the NCS. Alexander estimated that if results from the NCS effect even a 1 percent reduction in the cost of these conditions, the US will save about $7.58 billion a year, which is more than double the entire $3.2 billion projected cost of the NCS by its end.

“Although this is an extremely expensive study, the cost of the diseases we’re studying are even more expensive,” Michael Bracken, lead investigator of the Yale study, said. “This will give us a chance to really understand the [causes], and if you understand that, you’ve got a chance to create therapies.”

Recruiting a base

In 2000, the Children’s Health Act authorized the consortium to begin the NCS, and preparations have been ongoing since then, Alexander said. Researchers affiliated with the study have been formulating methodologies to retrieve a sample that accurately depicts the social, geographic, economic and racial makeup of the population of the United States, he said.

In 2004, the coordinating center, located in Washington, D.C., randomly selected 105 counties that were intended to represent this diversity. In 2005, contracts for the pilot centers, known as the Vanguard Centers, were awarded. These two centers — one at the University of North Carolina at Chapel Hill, which will study Duplin County, N.C., and one at the Mount Sinai School of Medicine, which will study Queens, N.Y. — will begin recruitment in January 2009. As pilot centers, they will test the research and recruitment methods devised by investigators to ensure they work as well as anticipated, according to remarks by Peter Scheidt, director the NCS, at a press conference.

These centers will begin recruitment in January 2009, and will test the research methods that will be used in the larger study. In 2007, an additional 17 centers were awarded contracts, including the Yale Center. On Friday, 39 new locations and 27 study centers were announced.

The $15 million in funding allocated by the consortium to Yale last year will go towards implementing the study in New Haven County, while the new grant will expand the study to include Litchfield County, a more rural area. The Yale Center for Perinatal, Pediatric, and Environmental Epidemiology will carry the study out in both counties.

Within each county, a secondary sampling scheme will be implemented, splitting each county into regions, based on demographic characteristics, Belanger said. Litchfield county will be split into 13 neighborhoods, and of these, one neighborhoods will be selected, from which researchers will recruit 1,000 pregnant women.

These women will be observed and interviewed at various points throughout their pregnancies, as will their children once they are born. Using questionnaires, interviews, DNA analysis and examination of home environmental conditions, researchers will collect data that Belanger said they hope will reveal new information about children’s health.

Detailed protocols for recruitment and the first few years of follow-up study have already been created, though protocols for the later years are still in the works, Belanger said.

The study will proceed in three waves, with the first two sites beginning recruitment in January 2009, followed by four or five more in April, Belanger said. The first wave, in which a third of the sites will begin recruitment, will officially begin in July 2011, according to Scheidt, with the remaining two-thirds following in July 2011 and July 2012.

the nitty-gritty

Belanger said the NCS required institutions to compete for funding to carry out the study in a county close to them. To apply, centers had to provide a detailed proposal of how they would conduct the study, demonstrating that they could adequately protect the human subjects, that they had the professional expertise to sample, recruit and collect data according to the national protocols set by the NICHD, Belanger said.

Jessica Illuzzi, another Yale investigator, said one of the reasons Yale was eventually selected was that Litchfield County was intended to represent rural areas of the U.S. and therefore somewhat high-priority. So, she said, the coordinators were looking for a center to support it.

“We were told that we were told that we were competing with several other rural counties, but we felt confident because Yale has the Center for Perinatal, Pediatric, and Environmental Epidemiology, and they’ve conducted many cohort studies that are similar out in the New Haven County and surrounding areas,” Illuzzi said.

Belanger said the Yale Center has been conducting large-scale perinatal epidemiologic studies since the 1970s, in which they have similarly recruited women during their pregnancies.

The total number of subjects in the four large projects they have conducted since then have been in excess of 10,000 women, with around 2,500 in each study, Belanger said. In one, they recruited 1,000 mothers — just as they will for the NCS — and followed the children for eight years to examine the role environmental factors play in childhood asthma.

None of those studies operated on quite as large or expensive a scale as the NCS. But Yale’s taking on of two counties will save the NICHD money, which is why the Center’s second grant is much smaller than the first — though both are significant amounts of money.

“This is a very detailed and intensive study,” Belanger said. “In addition to the costs of going house to house to recruit, there are also the costs of providing ultrasounds during pregnancy, and collecting samples, and storing all this information.”

But the Yale Center is particularly cost-effective because it can utilize the same faculty, staff, and office base to administer the study in both counties, Belanger said.

The two grants are intended to fund the first five years of research, which Belanger said she thinks will be the most expensive, as they involve recruitment. But as the children get older, and grow and develop more slowly, contacts with the families will become less frequent, decreasing annual costs.

SIGNIFICANCE

In addition to the expense, though, the study also faces the problem of scope.

“Conducting such large cohort studies in the United States is very challenging,” Illuzzi said. “We’re not like a small Scandinavian country that has easy access to participants and records. … We have a diverse population with environmental risks and pediatric outcomes that are hard to follow.”

Bracken acknowledged that the size of the NCS requires a large investment of effort and makes it difficult to conduct effectively. He said that though there are no guarantees as to how useful the results will be, he is confident the effort will pay off. Other researchers agreed.

Illuzzi said the NCS marks the first time that scientists will have a study large enough and powerful enough to study both rare and common disease outcomes and correlate them with environmental data, as well as nutrition and psychosocial environments.

Illuzzi is an OB/GYN with an epidemiological background, and said she finds the study exciting not only from a children’s health standpoint, but from a women’s health standpoint. Being able to study a cohort of 100,000 mothers, she said, will have tremendous implications for women’s health.

The study’s range will be even further increased when investigators are able to combine U.S. data with data from similar studies currently being conducted in other countries, including the United Kingdom, Norway and Denmark, Bracken said.

Belanger said she thinks that as the study continues, the data will reveal new possible avenues for investigation.

“I suspect as it goes on, it will also develop new and additional hypotheses and it will have beneficial effects that we cannot even contemplate,” she said.