On a growth curve: children's environmental health centers. (NIEHS News).

Until recently, environmental health investigations focused on adult exposures, and extrapolated potential effects in children from adult studies. This approach neglected factors that enhanced children's vulnerability, such as larger exposures on a body surface area basis and immature metabolic pathways. But the 1990s saw a change in this approach, prompted in part by reports such as the 1993 National Academy of Sciences publication Pesticides in the Diets of Infants and Children and spurred along by meetings such as a 1997 conference sponsored by the Children's Environmental Health Network, which brought together experts to identify research needs in the area of children's health. The resulting information served as a blueprint for developing a series of children's environmental health research centers.

Eight centers were established in 1998 with funding from the NIEHS and the U.S. Environmental Protection Agency (EPA), and funding for another four centers was announced in October 2001. Research at the centers is interdisciplinary, and projects draw on the expertise of pediatricians, epidemiologists, public health specialists, and others. As part of their mandate, all centers are active in community education and outreach.

Determining the causes of asthma, the role of environmental exposures, and factors in individual susceptibility are key research areas for centers housed at the University of Southern California (USC) in Los Angeles, the University of Michigan in Ann Arbor, The Johns Hopkins University in Baltimore, the University of Iowa in Iowa City, and Columbia University in New York. The centers at the Mount Sinai School of Medicine in New York, Columbia University, the University of California at Berkeley, and the University of Washington in Seattle are working to identify exposures that affect children's mental and physical development, characterize their effects, and develop methods to reduce and prevent them. Suspected exposures include pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs).

Two of the newly opened centers, at the University of California at Davis and the University of Medicine and Dentistry of New Jersey, will focus on potential environmental links to autism. A center at the University of Illinois at Urbana--Champaign will investigate the effects of dietary exposures to mercury and lead among Asian-Americans consuming large amounts of fish from the Great Lakes. At the Children's Hospital Medical Center of Cincinnati, researchers and community participants will assess the impact of reduced pollutant exposure on children's hearing, behavior, and learning.

Fighting for Air

USC researchers have shown that common genotypes of glutathione-S-transferases, a class of metabolic enzymes, are associated with lung function; other gene-environment interactions are under investigation, too. The researchers have also found that particulate matter (PM) may modulate the immune response in airways. For urban centers, the potential for information sharing and collaboration is high. Henry Gong, USC center director and a professor of preventive medicine, would like to see further developments along those lines. "There hasn't been as much as I would like, but that's certainly one of the potential interrelationships among the centers," he says.

The University of Michigan center has screened students aged 6-11 in a group of targeted schools to identify children with undiagnosed asthma. The screening revealed that large populations of Detroit children with persistent asthma are not receiving adequate medical care for their condition, according to Edith Parker, an associate professor of public health and a center investigator. Center researchers have also assessed indoor and outdoor exposures to asthma triggers, and have found that residential location is an important determinant of P[M.sub.2.5] exposure. Indoor PM, primarily environmental tobacco smoke, is another asthma trigger under investigation.

At the Johns Hopkins center, researchers have shown that airborne PM in samples taken from the inner city induces significant airway inflammation in mice. Researchers are also working on the genetic variability of individual response to ozone and other environmental pollutants. Of particular interest is toll-like receptor 4, a candidate gene for asthma susceptibility. Current community research includes a case-control epidemiology study to compare home environments of approximately 300 inner-city preschoolers with asthma with those of nonasthmatic children in the same area. An intervention clinical trial will assess the effects of reducing allergens and pollutants in asthmatic children's homes on their symptoms. "The most interesting thing we've found so far is that the exposure to airborne particulates in the homes is surprisingly high, and it is above annual index cutoff limits published by the EPA," says center director Peyton Eggleston, a professor of pediatrics.

An unexpected finding at the University of Iowa has been that the prevalence and severity of asthma in rural children rivals that of inner-city children. "The old adage was that children in these rural areas [were] protected from asthma. But that's certainly not true in Iowa," says Gary Hunninghake, center director and a professor of internal medicine. Particular rural exposures that may trigger asthma include grain dust, pesticides, and animal confinement operations. A recent statewide conference narrowed in on potential environmental health effects of animal confinement facilities, prompting a request from the state government for recommendations to minimize exposures. Iowa researchers are also studying endotoxin, a cell-wall component of gram-negative bacteria, and investigating how viral infections may predispose some children to developing asthma. They are especially interested in respiratory syncytial virus, or RSV, which particularly strikes babies born prematurely.

Columbia University, meanwhile, works with children in northern Manhattan, where childhood asthma rates are among the highest in the nation, says Frederica Perera, center director and a professor of public health. Center researchers are investigating perinatal exposures to airborne PM, PAHs, pesticides, environmental tobacco smoke, and home allergens with regard to asthma. A prospective cohort study of more than 600 pregnant women and their infants is collecting exposure data through biomarker monitoring, questionnaires, air monitoring, and a geographic information system. The children will be followed for five years to monitor potential health effects. The study has already generated several findings, including the wide prevalence of maternal and fetal pesticide exposure and the fact that in utero sensitization to multiple indoor allergens is common.

Hampered Growth and Development

At Mount Sinai, researchers focus on home pesticide exposures and dietary PCBs among inner-city residents. They have found that pesticide exposure begins before birth, and the impact is being assessed through a prospective epidemiologic study involving more than 450 mothers and their children. The study was begun about three years ago and will run indefinitely; so far there have been 400 births among the study population, and as of July 2002 the researchers had conducted 140 one-year assessments and nearly 50 two-year assessments. A preliminary finding reveals an association between prenatal exposure to organophosphate pesticides and smaller head circumference, a measure of brain growth.

Another study at Mount Sinai has found that in utero exposure to PCBs is linked in a dose--response fashion with behavioral and psychological dysfunction in adolescence and adulthood. A cornerstone community project is a longitudinal study with more than 200 expectant mothers who are using individually tailored integrated pest management in their homes to effectively reduce pest infestation and reduce chemical use. The project has already resulted in an 80-90% reduction in roach counts in homes and virtually 100% reduction in the use of toxic pesticides.

The Columbia cohort study, in addition to looking at asthma, is evaluating the impact of perinatal exposures to PAHs and nonpersistent pesticides on fetal and child growth and development. Preliminary analyses show that prenatal exposure to both airborne PAHs and chlorpyrifos is associated with reduced birth weight, length, and head circumference in one or both of the ethnic groups--Dominicans and African Americans--being studied. In addition to a communitywide educational campaign on environmental hazards to children, an intervention is in progress in collaboration with the New York City Housing Administration to reduce pesticide use in New York City apartment buildings.

The Berkeley center is participating in a study of the environmental health risks among farmworkers in the Salinas Valley. Children in this area receive chronic low-level exposures to organophosphate pesticides, often through the clothes their parents wear home from work, and the effects on growth and development are unknown. Center researchers are conducting a prospective cohort study of 600 pregnant women and their children, who will be followed for two years. Brenda Eskenazi, center director and a professor of epidemiology, notes that the cohort study design is very similar to those at Mount Sinai and Columbia. "That's one of the beauties of having centers starting up at the same time doing similar things--they are overlapping but not redundant," she says. The center is heavily involved in the farmworker community and active in many community-based projects to reduce children's exposures to pesticides and other environmental agents. "One of our major strengths is that we have developed a good community base. We have the support of politicians, growers, and farmworkers," says Eskenazi.

The center at the University of Washington also is interested in agricultural pesticides. "We want to understand how, when, and why children are at greater risk from pesticide exposure," explains center director Elaine M. Faustman. "We have established a risk assessment framework to integrate the spectrum of biochemical, molecular, genetic, and exposure data." The center works through an advisory board made up of growers and workers in the Yakima Valley to develop and evaluate outreach and education programs. Through biomonitoring, Seattle researchers have found similar pesticide exposures among urban and rural children through most of the year, with higher levels among rural children during specific periods of agricultural spraying. Researchers have identified specific targets for preventive intervention action, and the center has developed culturally appropriate intervention approaches, reaching over 18,000 participants in over 12 distinct agricultural communities.

Centers as a Whole

Besides researching long-term issues, the established framework of the centers permits quick response to unexpected environmental exposures. For instance, after the 11 September 2001 destruction of the World Trade Center, when massive amounts of airborne PM and toxic pollutants were billowing into lower Manhattan, staff at the Mount Sinai and Columbia centers quickly developed a prospective epidemiologic study to measure the exposures and assess how they might affect the physical and mental health of infants whose mothers were pregnant at the time of the attack.

In the coming years, researchers hope to more clearly define the relative contributions of different immune responses and triggers in asthma. At certain centers, continued funding would allow longer tracking of study cohorts, possibly beyond early childhood. A longer time frame would also permit more thorough assessments of intervention and prevention methods. Other center goals include exploring further gene--environment interactions, expanding outreach and communication efforts, identifying currently unknown environmentally linked health effects, and continuing work to prevent the environmentally linked illnesses that affect too many children.

Despite the centers' promising start, continued funding from the EPA is currently uncertain. Losing this funding would cause work at several centers to slow or even cease, consequently delaying answers to several environmental health questions, says Daniel Swartz, executive director of the Children's Environmental Health Network, a multidisciplinary research and education organization. He says that defunding the centers might also indirectly affect the multiagency National Children's Study by depriving it of relevant models for study designs.

"I do think that it's very important that the government maintains its commitment to funding the children's environmental health research centers," says Elizabeth Sword, executive director of the Children's Health Environmental Coalition, an education group based in Princeton, New Jersey. "Everyone in the human race benefits from research done on children's health. The degree to which we improve children's health is the degree to which we improve human health."

Children's Environmental Health Centers

Cincinnati Children's Environmental Health Center Children's Hospital Medical Center, Cincinnati http://www.cincinnatichildrens.org/Research /Divisions/General_and_community_pediatrics/enviro_health/default.htm

Center for Children's Environmental Health Columbia University, New York http://cpmcnet.columbia.edu/dept/sph/ccceh/index.html

Center for Childhood Asthma in the Urban Environment The Johns Hopkins University, Baltimore http://www.jhsph.ed u/ehs/urban.html

Center for Children's Environmental Health and Disease Prevention Research Mount Sinai School of Medicine, New York http://www.mssm.edu/cpm/dept_research.shtml

Center for Children's Environmental Health University of California, Davis http://www.vetmed.ucdavis.edu/cceh/

Center for the Health Assessment of Mothers and Children of Salinas University of California, Berkeley http://ehs.sph.berkeley.edu/chamacos/

Center for Childhood Asthma University of Iowa, Iowa City http://www.uiowa.edu/~vpr/research/organize/cca_0320.htm

Michigan Center for the Environment and Children's Health University of Michigan, Detroit http://www.sph.umich.edu/cbph/partnerships/mcech.html

Friend's Children's Environmental Health Center University of Illinois, Urbana-Champaign

Center for Childhood Neurotoxicology and Exposure Assessment Rutgers University/University of Medicine & Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway http://www.eohsi.rutgers.edu/childhood/index.shtml

The Children's Environmental Health Center University of Southern California, Los Angeles http://www.usc.edu/schools/medicine/academic_departments /preventive_med/occ_environmental/cehc/index.html

Center for Child Environmental Health Risks Research University of Washington, Seattle http://depts.washington.edu/chc/