October 2001 Study Assembly Summary Minutes

 

 

The National Children’s Study (NCS), previously known as the Longitudinal Cohort Study of Environmental Effects on Child Health and Development, is a collaborative effort of the U.S. Environmental Protection Agency (EPA) and three components of the U.S. Department of Health and Human Services (DHHS). The National Institute of Child Health and Human Development (NICHD) serves as the administrative lead for the effort, with support from the Centers for Disease Control and Prevention (CDC) and the National Institute of Environmental Health Sciences (NIEHS).

With passage of the Children’s Health Act of 2000 (P.L. 106-310), Congress authorized NICHD to conduct a national, longitudinal study of environmental influences on child health and development. These environmental influences include physical, chemical, biological, psychosocial, and cultural factors. While still in the planning stages, the NCS will represent one of the most massive and promising child health and development studies ever funded.

On October 15-16, 2001, more than 300 of the nation’s leading experts in the fields of children’s health and environmental sciences gathered in Tysons Corner, Virginia, to share their ideas regarding how the NCS should be structured, implemented, and evaluated. The first day of the assembly offered concurrent Working Group sessions for participants. Reports from these sessions are available at the NCS Website.

This report summarizes the presentations and discussions that occurred at the first ever meeting of the Study Assembly on October 16, the second day of the meeting. All content as presented by the Working Groups is in the form of status reports. Working Groups will formally submit their interim and final findings to the Federal Advisory Committee for review before the findings are considered for final incorporation into the study design protocol. Therefore, this report represents the current thinking of the Working Groups as of October 2001, and does not represent any final adoption or integration of these ideas into the study design or protocol.

 

 

The second day of the meeting consisted of four primary agenda items:

• During the opening general session, representatives of the NCS Interagency Coordinating Committee (ICC) described the current status of the NCS, described the overarching meeting objectives for day two, invited participants to visit the Cyber Cafe, and introduced the new name of the study.
• Most of the day was dedicated to a series of 10-minute presentations by the various Working Groups’ chairs. The purpose of these presentations was to discuss the activities, decisions, and deliberations that occurred in the Working Group meetings the previous day.
• Assistant Surgeon General Samuel (Woodie) Kessel and NICHD Director Duane Alexander, shared their vision regarding the NCS and how it may revolutionize our understanding of the association between environmental factors and the health and development of children.
• The final general session provided an opportunity to receive additional public comments.

The remainder of this report summarizes the discussions that occurred during the second day of the meeting.

Opening General Session

Overview of the Study

NICHD’s Peter Scheidt welcomed the participants to the Study Assembly and thanked them for their valuable input and ideas during the Working Group meetings the previous day. Dr. Scheidt acknowledged the contributions of the ICC and thanked its members for their hard work on this important endeavor.

According to Dr. Scheidt, the idea of conducting a longitudinal study on the effects of environmental exposures on the health and development of children first emerged as a realistic proposal in 1998 in the President’s Task Force on Environmental Health Risks and Safety Risks to Children. To yield the most useful and urgently needed data, children should be identified as early as possible-ideally before conception-and followed into adulthood. The rationale for the study consists of six primary elements:

1. Children are more vulnerable to environmental exposures than adults
2. Exposures to some agents (e.g., lead and alcohol) have caused serious developmental defects
3. There are several exposures to which many children are frequently exposed
4. Previous studies of the effects of environmental exposures on child health and development have been limited in size and scope
5. A longitudinal study is needed to identify the effects of various exposures or document their safety
6. A longitudinal study design will enable researchers to identify causal relationships between specific exposures and their effects on child health and development. It also will enable researchers to examine multiple exposures and outcomes in the same study

Dr. Scheidt reported that in January 2000, the Task Force invited representatives from several longitudinal studies of children to participate in a consultation meeting. This included representatives from the Collaborative Perinatal Project, the Framingham Study, the Avon Longitudinal Study, the Bogalusa Heart Study, the Danish Initiative and Norwegian Birth Cohorts, the Kaiser Longitudinal Study, the Women’s Health Initiative, and others. The participants strongly supported the idea of a longitudinal cohort study on the impact of environmental exposures on the health and development of children. At the same time, they recognized that vibrant and meaningful partnerships among Federal, community, and professional groups would be crucial to the study’s success.

Subsequent to the consultation meeting, Congress passed the Children’s Health Act of 2000 (P.L. 106-310). The law authorized NICHD to conduct a national, longitudinal study of various environmental influences-including physical, chemical, biological, and psychosocial exposures-on child health and development. Specifically, the law mandates that the NICHD Director establish a consortium of representatives from appropriate Federal agencies, including CDC and EPA, to accomplish two key tasks. First, the consortium is to plan, develop, and implement a prospective cohort study-tracking children from birth to adulthood-to evaluate the effects of both chronic and intermittent exposures on child health and human development. Second, the consortium is mandated to investigate the basic mechanisms of developmental disorders and environmental risk and protective factors that influence child health and development.

The study is intended to be a high-quality, national, longitudinal study of children, their families, and their environment. The term "environment" is broadly defined to include chemical, physical, behavioral, social, and cultural exposures. The proposed sample size of approximately 100,000 will enable researchers to study fairly common low-level exposures and to identify infrequent outcomes. The sample size, however, is still open to discussion. The study is intended to examine environmental and genetic expression; to employ state-of-the-art technologies for tracking the cohort, measuring outcomes, and managing data; and to involve a consortium of multiple agencies representing both public and private entities. Dr. Scheidt pointed out that this study should ultimately prove to be an invaluable national resource for future studies, some of which may seek to test hypotheses that are not even imaginable today.

It is anticipated that the study will involve the participation of many geographically distributed centers that will be responsible for recruitment, measurement, and follow-up. These centers will be expected to use the most advanced technologies available, including microsampling, Web-based data collection, geomapping, and satellite monitoring.

Dr. Scheidt briefly discussed the structural approach to planning the study, which includes the ICC, the NICHD Director, the NICHD Program Office, a consortium of Federal agencies, an Advisory Committee, a series of subcommittees, numerous Working Groups, and the Study Assembly participants. Dr. Scheidt added that the National Advisory Council on Child Health and Human Development (NACCHHD) is serving as the Study’s Advisory Committee on a temporary basis until the Federally chartered committee is established. This is expected to take several months. In the meantime, however, the NACCHHD will be responsible for advising the NICHD Director and guiding the planning, design, and implementation processes. Dr. Scheidt invited Study Assembly members to nominate senior investigators to serve on the Study’s Advisory Committee.

Dr. Scheidt noted that the Working Groups will play an important role throughout the entire study. The Working Groups will include both Federal and non-Federal members, and they will help design and plan specific aspects of the study. Working Group activities will be conducted under the auspices of the Federal Advisory Committee. Guidelines still have to be established to determine how to avoid conflicts of interest. While the activities of the various Working Groups will initially focus on planning, Dr. Scheidt indicated that the Working Groups ultimately will be able to use and analyze data and publish data. This is a unique feature of this study because it represents a major departure from previous Federal studies where analytical and reporting responsibility typically have rested with principal investigators at the research centers. It is hoped that the research centers funded by this study will be actively involved in the Working Groups and that Working Group members will collaborate in analyzing and publishing findings.

According to Dr. Scheidt, one of the biggest challenges in planning a study of this magnitude will be effective and efficient decisionmaking. Some conflicts are expected, and the most appropriate group must deal with such conflicts fairly and decisively. In some cases, decisions will have to be made on the advice of the Federal Advisory Committee. In other instances, the Advisory Committee may ask that a recommendation be made by a crosscutting Working Group, such as the Study Design Working Group or the Ethics Working Group. Dr. Scheidt underscored that decisionmaking often will involve several groups, organizations, and agencies, and that a true spirit of collaboration and cooperation will be necessary to ensure that challenges are addressed in a timely and efficient manner.

Dr. Scheidt indicated that a number of pilot studies already are under way or being planned to aid the planning and implementation of the study. These include:

• Systematic review of core and potential hypotheses
• Review and comparative analysis of sampling strategies
• Examination of subject recruitment and retention methods
• Systematic evaluation of personal exposure measures
• Study of biomarkers for exposure to chemical agents
• Collection and storage methods for genetic testing
• Review of emerging technologies

Additional pilot studies will be proposed by the various Working Groups to assist them in carrying out their tasks.

Dr. Scheidt reviewed the current status of the study. It is expected that $5 million in planning funds will be available for Fiscal Year (FY) 2002, while $10 million is anticipated for FY 2003. Six full-time staff currently are dedicated to supporting the study. Other key accomplishments include the following:

• Development of a working proposal for the study
• Creation of the study Web site
• Implementation of numerous pilot studies
• Approval of the Federal Advisory Committee
• Establishment of the Working Groups

Dr. Scheidt then outlined the proposed timeline for the study. This timeline is summarized in the following table:

Target Dates	Task to Be Completed
2000-2003	Develop methods and pilot studies
2001	Form the Advisory Committee and Working Groups
Ongoing	Hold meetings, peer reviews, and consultations
Fall 2001	Finalize hypotheses and develop the study design
Fall 2002	Release Request for Proposals to identify collaborating organizations
Fall 2003	Select initial sites and develop core study design
Early 2004	Pilot test the full study
Fall 2004	Begin the full study
2005	Enroll additional sites
Periodically	Analyze data as collection continues and publish early results
About 2030	Complete analyses

Dr. Scheidt completed his presentation by reminding participants to check the study Web site at www.nationalchildrensstudy.gov. He added that the Web address will change in the near future, and participants should join the listserv for news and updates. He also invited participants to share their comments and suggestions via e-mail at NCS@mail.nih.gov .

Meeting Objectives

EPA’s Carole A. Kimmel summarized the meeting objectives on behalf of the ICC. Dr. Kimmel pointed out that the Study Assembly is open to Working Group members and observers, staff of the Federal Consortium agencies, and anyone else who is interested in planning or supporting the study. She described the meeting as a continuation of the Working Group discussions on the previous day. The full Study Assembly would hear presentations from each of the Working Group chairs. She added that this was the first opportunity for the Working Groups to meet face-to-face. Most importantly, Dr. Kimmel noted, this meeting represented the first chance for the Study Assembly to provide face-to-face feedback and suggestions to the Federal Consortium, the ICC, and the Working Groups.

Dr. Kimmel described the structure of the meeting for the day, stating that participants would have the opportunity to

• Learn more about the communications portal
• See the debut of the new study name
• Hear from the NICHD Director regarding the Institute’s vision for the study and what NICHD is doing to support it
• Hear Working Group reports
• Provide feedback on the day’s discussions

Dr. Kimmel provided an overview of the Working Groups. She indicated that some of the Working Groups are integrative or crosscutting in nature, such as Study Design, Community Outreach and Communication, Ethics, Information Technology, and the Repository Working Groups. Other Working Groups are focused on a specific aspect of the study. Those that will present today include Development and Behavior, Health Disparities and Environmental Justice, Chemical Agents and Exposures, Social Environment, Injuries, Gene-Environment Interaction, and Fertility and Early Pregnancy. Other issue-specific Working Groups, though not scheduled to present to the Study Assembly, include Asthma; Birth Defects; Early Markers of Adult Disease; Health Services; Infection, Immunity, and Vaccines; Medicine and Pharmaceuticals; Mid and Late Pregnancy; Nutrition, Growth, and Oral Health; and Physical Exposures.

Each Working Group will have Federal and non-Federal co-chairs, supported by both core members and at-large members. Dr. Kimmel noted that conflict of interest is a serious concern and that discussions are under way to address that concern.

The Working Groups will inform the Federal Advisory Committee on the issues that fall under their purview. In addition, each Working Group will develop a charge for the group and a timeline for completion of tasks.

Introduction to the Portal

EPA’s Sherry G. Selevan introduced the portal to the full Study Assembly. While core Working Group members participated in portal training the previous day, at-large Working Group members and others in the full assembly had no opportunity to learn more about the portal and how it works. Dr. Selevan described the portal as an online collaboration tool for sharing information, discussing issues, and archiving information. The portal may be accessed from any location with an Internet browser. No special plug-ins are needed.

Each Working Group will have its own presence on the portal. The ICC has been using the portal to communicate schedules, post general information and fact sheets, and distribute presentations. However, the portal can be adapted to meet each Working Group’s unique needs. Dr. Selevan demonstrated some of the portal’s features, including an online calendar, document edit and comment functions, polling capability, instant messaging, and many other features.

Dr. Selevan invited the Assembly members to visit the Cyber Cafe to become more familiar with the portal and its functions.

Study Name

NICHD’s Sarah Keim discussed the new name for the study. Study planners believed it was necessary to create a more marketable and more easily identifiable name for the study than the original, The Longitudinal Cohort Study of Environmental Effects on Child Health and Human Development. After testing several possibilities with two focus groups of pregnant women and two focus groups of general population adults, the project will now be known and marketed as the National Children’s Study. A tagline and logo will be developed in the near future.

Study Design Working Group Progress Report

Peter Gergen of the Agency for Healthcare Research and Quality, is Chair of the Study Design Working Group. Dr. Gergen began his presentation by describing the role of the Study Design Working Group. He identified five overarching goals: 1) to provide feedback on proposed core hypotheses and questions to other Working Groups; 2) to collaborate with the Working Groups and the ICC in refining core proposals; 3) to develop evaluation criteria for proposed hypotheses and questions; 4) to integrate hypotheses and questions through Working Group collaboration; and 5) to address basic study design issues.

Dr. Gergen then described what the Study Design Working Group sees as their key study design issues. These include:

• Target population (e.g., how well delineated, geographic distribution, etc.)
• Sample size or power
• Duration of follow-up
• Burden on individuals and families
• Safety and institutional review board (IRB) issues (as this will be a healthy and free-living cohort)
• Number of enrollees in families (e.g., multiple births, multiple pregnancies, etc.)
• Addition of new hypotheses and technologies over time

Dr. Gergen noted that this was a preliminary list of study design issues. The Study Design Working Group will continue to explore these issues throughout the planning process.

The Study Design Working Group plans to select the core set of hypotheses and questions by summer 2002. He defined core hypotheses and questions as those that will drive the overall study design and sample size, although additional hypotheses and questions will be studied. Dr. Gergen added that core hypotheses and questions should capture both positive and negative outcomes for the study to provide a better understanding of successes and failures.

Dr. Gergen requested that all core hypotheses and questions be submitted to the Study Design Working Group through the Working Group chairs to ensure that the chairs are informed of all their Working Group members’ submissions. In the next few weeks, the Working Group chairs will receive a form for submitting by December 2001 their list of ideas for core hypotheses and questions. The Study Design Working Group anticipates that the Working Group chairs will share the form with all core and at-large Working Group members, who should submit their hypotheses ideas through the appropriate Working Group chair.

Dr. Gergen described the kind of information the Study Design Working Group needs to start evaluating core hypotheses and questions. Working Groups submitting prospective hypotheses will need to address the following five key issues:

• Public health significance of the hypothesis or question
• Why a large, prospective study is necessary to test the hypothesis or question
• Scientific merit of the proposal
• Potential for innovative research
• Feasibility of the proposal, including critical periods for exposure and outcomes, frequency and type of contact, the nature of measurement (e.g., biologic testing or interviews), and ethical considerations associated with the hypothesis (e.g., testing results in the discovery of an illness)

The evaluation process also will be an interactive process in which the Study Design Working Group will collaborate with the other Working Groups and the ICC to refine and further develop core hypotheses and questions.

Development and Behavior Working Group Progress Report

NICHD’s Marc H. Bornstein serves as Chair of the Development and Behavior Working Group. Dr. Bornstein identified the following three key roles for the Development and Behavior Working Group: 1) to suggest a research framework for the NCS; 2) to develop hypotheses and questions to be included in the study design; and 3) to recommend measures for investigating those hypotheses and questions.

The Development and Behavior Working Group has adopted a contextual and bidirectional framework for determining core hypotheses and questions associated with child development and behavior. According to Dr. Bornstein, the Working Group sees settings distal to child development (e.g., culture, social status, etc.) as well as settings proximal to child development (e.g., parent-child interactions, the immediate environment, etc.) as directly and indirectly related to numerous aspects of child development and specific points in the life course. This idea reflects the contextual part of the framework. At the same time, children exercise multiple influences on those settings and their development. This idea reflects the bidirectional nature of the framework.

With those beliefs in mind, the Working Group identified settings for development, determined domains of development, and developed global and specific hypotheses and questions to identify links between those settings and domains. The Working Group identified the following settings:

• Health settings, such as parents’ genotypes, prenatal and birth events, continuing health care, chemical exposures, and micronutrients
• Social settings, such as parenting, peer interactions, nonparental caregiving, teachers, ethnicity, socioeconomic status, and religion
• Physical settings, such as characteristics of the home, school, daycare, neighborhood, and region

According to Dr. Bornstein, specific domains identified by the Working Group include the following:

• Health functioning, such as child genotype, sensory capacities, and motor development
• Socioemotional functioning, such as personality, attachment, and social skills
• Cognitive functioning, such as perception, memory, intelligence, and language
• Behavioral functioning, such as self-regulation and specific disorders

Dr. Bornstein then described the following examples of questions that may be submitted by the Development and Behavior Working Group for inclusion in the study design:

• Are early and significant exposures to certain chemical agents during the first two years of life associated with adverse developmental consequences after infancy?
• Do varying levels of maternal thyroid hormone in pregnancy differentially affect cognitive development?
• Is early child care related to high-risk problem behavior in adolescence?
• Are there regional differences in the United States in children’s development trajectories, and do similar environmental experiences affect children’s development in separate regions of the country similarly or differently?

These questions were merely examples of the 40 or 50 hypotheses that will be generated by the Working Group. He added that the Working Group’s next steps are as follows:

• Review setting-specific and domain-specific theory and research at different stages of development
• Refine hypotheses that relate settings to domains at different stages of development
• Prioritize aspects of those settings and domains most critical to measure at different stages of development
• Evaluate extant measurement strategies and study designs used to investigate relationships between specific settings and domains at different developmental stages
• Recommend strategies and measures to best assess settings and domains at different stages of development
• Conduct pilot studies to evaluate and test recommendations

The Working Group proposes to hold two workshops in early 2002. The first workshop would invite selected principal investigators and researchers from large-scale longitudinal studies to review proposed hypotheses and measures and to discuss logistical issues associated with investigating those hypotheses and selecting appropriate measures. During the meeting, the invited experts would be asked to describe their study discoveries, the gaps in their studies that could be filled by the NCS, and what they consider to be the most urgent questions in child development and behavior-today, and in the years to come. They also would be given an opportunity to apply their experience in specific settings and domains toward enhancing the proposed hypotheses and clarifying the proposed measures.

The second workshop would consist of reconvening the Development and Behavior Working Group to discuss what has been learned and how to proceed. Most likely, the Working Group will devote its time in this meeting to generating additional hypotheses, refining existing hypotheses, acquiring and assessing developmental and behavioral measures appropriate for the hypotheses, and determining the logistical issues associated with implementation. In the end, according to Dr. Bornstein, the Working Group will submit its findings concerning the research framework and design, the hypotheses to be tested, and the best measures for various settings and developmental domains.

Comments on Study Design and Development/Behavior Working Group Presentations

At the conclusion of Dr. Bornstein’s presentation, the Study Assembly members were invited to ask questions and share comments. Several issues were discussed during the open comment period. They include the following:

• The timeline for submitting core hypotheses (December 2001) presents a serious problem for Working Groups that have not been formed and constituted yet. EPA’s Pauline Mendola who serves on the ICC, indicated that the ICC liaisons will work closely with Working Groups that do not have chairs to ensure they are able to participate in the process effectively.
• It is important to ensure in the sample adequate representation of communities that disproportionately experience health disparities and populations that frequently live in areas with potential environmental hazards-either through sampling strategies or sample size. Dr. Gergen indicated that the sample size and sampling strategies have not yet been determined. However, he agreed that this merits further consideration.
• The timeframe for recruiting subjects is an important issue with many of the Working Groups for the hypotheses they hope to test, and the Study Design Working Group hopes to discuss this in more detail in the future.
• One participant encouraged other Working Groups to model their approach after the framework developed by the Development and Behavior Working Group.
• A participant encouraged study planners to consider adding a record-based data collection effort involving a much larger sample-perhaps even 500,000 pregnancies. This would enable the study to test additional layers of hypotheses and lay the groundwork for innovative research.
• Another participant encouraged the ICC to explore the possibility of creating an additional Working Group to focus on risk management decisions made by parents and caregivers and the subsequent impact on outcomes.
• It was recommended that national and international researchers involved in other child-specific cohort studies be engaged to plan and implement the NCS. It also was recommended that efforts to involve them be adequately coordinated to reduce confusion.

Ethics Working Group Progress Report

Diane Wagener of DHHS serves as Chair of the Ethics Working Group. She opened her presentation by saying that the Working Group is looking for non-Federal participants. She invited interested persons to contact her directly via e-mail.

Dr. Wagener noted that the NCS raises a broad range of complex ethical issues-all of which are amplified by the size, scope, and magnitude of the study. Some of these issues include the following:

• The children recruited for the cohort will be accessed via pregnant women.
• Because some children may be recruited through adoptive parents, guardians, and perhaps through child care centers and other settings, there will be several third parties involved.
• The study design is evolving and will continue to evolve throughout the course of the study.
• There are concerns about how to communicate to participants that they be identified as subjects for other studies.
• It is expected that a large amount of data will be collected on each participant, but how they will be identified in the study is undetermined.

Dr. Wagener described the goals the Working Group hopes to accomplish in the next 12 months. They include the following:

• To review the roles and interrelationships of the various study components, including the Ethics Subcommittee of the Chartered Advisory Committee, local IRBs, central IRBs, data safety monitoring groups, and others
• To conduct a series of discussion meetings to clarify the ethical issues involved
• To draft an Ethics Resource Guide for the NCS covering many topic areas that will serve as a resource for investigators
• To conduct pilot research studies and commission papers from investigators
• To coordinate with other Working Groups on ethical issues
• To respond to queries from other Working Groups

Dr. Wagener then outlined the preliminary contents for the resource guide, which is expected to address several key issues, including the following:

• Application and interpretation of Federal regulations
• Ethical oversight and administration (e.g., how to promote local ethical review, what should be reviewed locally, what should be reviewed centrally, how and who monitors substudies, how investigators can use data for corporate or personal use, etc.)
• Community and family involvement
• Recruitment, retention, and withdrawal (e.g., when the child and parent(s) disagree, tracing participants, ensuring adequate recruitment from underserved communities, etc.)
• Informed consent (e.g., storing biological samples, disagreement between parents, etc.)
• Ethical concerns related to third parties
• Safeguarding privacy and confidentiality of data and samples
• Sharing results with participants and others (e.g., when child abuse or neglect is discovered)
• Presentation and dissemination of the study findings

Dr. Wagener described the Working Group’s initial activities and the plans to coordinate activities with the ICC and other Working Groups, including the Health Disparities and Environmental Justice Working Group, the Repository Working Group, the Community Outreach and Communications Working Group, and the Recruitment and Retention Working Group. The Ethics Working Group also plans to commission a series of reviews and annotated bibliographies on incentives in the use of children, assent, Federal regulations, and informed consent.

Over the next six months, the Working Group intends to conduct four discussion meetings, some involving collaborating with other Working Groups. These meetings will focus on participant recruitment and retention, recruiting intermediaries, informed consent issues related to teenage mothers, and assent of children. The Working Group also expects to begin categorizing the content of available documents on informed consent. To identify researchers to aid their efforts, the Working Group plans to use the NIH CRISP system.

During fall 2001, the Working Group hopes to expand to include non-Federal participants and to develop an outline for the Ethics Resource Guide. It also plans to develop a list of pilot research studies to resolve ambiguous guidance and begin conducting its discussion meetings. Other activities for the coming year include selecting priority research topics, monitoring the pilot research, obtaining background information for the Ethics Resource Guide, and developing findings for the study protocol and the forms to be used.

Community Outreach and Communications Working Group Progress Report

ATSDR’s Diane Dennis-Flagler focused on the activities of the Community Outreach and Communications Working Group. According to Ms. Dennis-Flagler, the overarching purpose of the Working Group is to develop and recommend guidelines and protocols for NCS outreach and communication activities. The first step for the Working Group will be to evaluate and examine past studies to gain a better understanding of current research and communication methods. This most likely will involve conducting a literature search, reviewing pilot demonstrations, and conducting a series of focus groups early on in the planning and implementation process.

Ms. Dennis-Flager indicated that creating strong, effective, and sustainable partnerships with communities will be critical to the overall success of the study. She emphasized that the Working Group views "communities" in the broadest sense of the word so that it captures not only the people who live in a particular community but also the organizations, industries, associations, and other entities that make up the community. The Working Group suggests that communities be given the freedom to select their own community partners so they can invest a sense of ownership in the study and its findings. However, the Working Group would set some parameters for partnership development.

Another important concern for the Working Group is to encourage effective communications throughout the study with messages tailored to each community’s diversity and social context, while communicating the need for active community involvement in the decisionmaking process, including development of the study design as early as possible.

Ms. Dennis-Flagler said that the Working Group is aware of the importance of documenting the lessons they learn throughout the study. Ultimately, the Working Group plans to establish a resource repository so that future research efforts do not have to "reinvent the wheel" when developing communications strategies. The Working Group hopes to assemble a body of information to share with community stakeholders and has discussed the possibility of conducting occasional national working sessions of community partners so they can share and exchange information and experiences.

In the near future, the Working Group plans to begin collecting data on current and past community-based research, as well as coordinating its activities with the other Working Groups. The Working Group also expects to begin clarifying the parameters for community-based partnership agreements and conducting preliminary focus group meetings with women to find out what appeals to them and what does not.

Ms. Dennis-Flagler concluded by underscoring the importance of getting community input as soon as possible-before the study design is completed-and being as flexible as possible in working with communities. She also encouraged other Working Groups and entities involved to begin thinking about creating a mechanism for evaluating the overall study and the activities of each Working Group.

Health Disparities and Environmental Justice Working Group Progress Report

Allen Dearry of NIEHS serves as Chair of the Health Disparities and Environmental Justice Working Group. Dr. Dearry began his presentation by saying that, although the Working Group currently has both Federal and non-Federal participants, it is still looking for new members.

Dr. Dearry highlighted four preliminary hypotheses identified by the Working Group. They are as follows:

• Environmentally related stressors have disproportionate adverse effects among low-income people and people of color.
• Low-income people and people of color bear a disproportionate burden of exposure to hazardous environments. (Dr. Dearry added that, while many believe this hypothesis is already established and does not merit further study, the Working Group members believed that this is not yet substantiated or disproved by present data.)
• Low-income people and people of color have greater incidence and severity of adverse health effects than do other groups when equally exposed.
• Environmental sources of psychosocial stress are associated with impaired fetal development-low birthweight, preterm delivery, and infant mortality.

Dr. Dearry noted that, when his Working Group refers to environmentally related stressors, it is meant to convey a broad and encompassing set of environmental exposures. These include chemical (e.g., pesticides), physical (e.g., radiation), and biological (e.g., diet and nutrition) exposures, as well as individual (e.g., socioeconomic status, education), community (e.g., housing and transportation), and systemic (e.g., racism, classism, and sexism) social exposures.

Dr. Dearry also indicated that the Working Group had developed some guiding principles for the overall NCS. The first principle is that communities should be involved in all aspects of study design, conduct, and analysis. The Working Group believes that this will safeguard the scientific validity of the study by promoting recruitment and retention, ensuring fairness, and improving data collection. The Working Group also proposed that environmental justice principles be incorporated into each Working Group and the overall NCS.

Dr. Dearry then presented what the Working Group believes are seven of the key study design issues. The Working Group believes it is important for the study to have sufficient expertise in population diversity, ethnography, demographics, and genetics. In addition, a model-based approach to stratifying the NCS sample would help ensure that at-risk populations are adequately represented. Mobility-in both geographic and environmental terms-also is an important concern in generating new knowledge on why certain populations experience specific health disparities.

The Working Group is developing a set of measures and has identified some potential pilot studies. One pilot study would focus on determining culturally and linguistically appropriate design, assessment, and interview tools. The other would be designed to enhance the capacity of communities and universities to work in partnership.

The Working Group hopes to have a workshop next spring to gather scientific and public input. Meanwhile, Dr. Dearry indicated that the group’s immediate efforts will focus on collaborating with other Working Groups and identifying a final set of priorities for Working Group activities.

Comments on Ethics, Community Outreach/Communications, and Health Disparities/Environmental Justice Working Group Presentations

At the conclusion of Dr. Dearry’s presentation, the Study Assembly members were invited to ask questions and share comments. Several issues were discussed during the open comment period. They include the following:

• Privacy and confidentiality of information gathered in the study also must include not making the information available to insurers and others who finance health care services.
• A mechanism should be developed to help study subjects locate affordable health insurance or a source of follow-up care if they need it.
• It will be difficult to involve communities in the study design process because the communities will not be selected in the near future. This fact underscores the need for a flexible and adaptable study design structure that can be responsive to communities once they become engaged.
• Separating the outcomes (e.g., asthma) associated with certain types of exposures, such as housing location and poverty, will present a serious challenge. The Health Disparities and Environmental Justice Working Group will attempt to resolve such issues in close collaboration with the Study Design Working Group and other relevant Working Groups.
• Communication, community outreach, and recruitment are critical issues to the study’s success. Study planners should begin exploring bold and innovative ways to market the study and its goals to parents. Creating a national awareness of this effort also will enhance retention efforts as families move from one location to another.
• It may be necessary to oversample some groups to ensure the outcomes adequately reflect the risks faced by certain subpopulations.
• To engage disenfranchised populations, it may be necessary to reach them at their homes rather than waiting for them to present at an academic center.
• From time to time, the work of the Ethics Working Group will enter the legal arena (e.g., when a three-year-old is diagnosed with a sexually transmitted disease). Dr. Wagener agreed and encouraged participants to share their ideas about the kinds of challenges that may be experienced during the course of the study. Dr. Scheidt added that, based on his discussions with the HHS Office of General Counsel, it is appropriate for the Ethics Working Group to fill gaps in guidance that have not yet been addressed by the policy and legislative arenas.
• Because the public health infrastructure extends to the county and community levels (e.g., maternal and child health programs, Head Start, etc.), these programs should be engaged as active partners in the study.
• Because the study will span nearly 30 years, ways should be explored to involve student scientists in the conduct of this study so they can fill the gaps left by the researchers of today and make this study a major part of their research careers.

Remarks by Samuel (Woodie) Kessel, M.D., M.P.H., HHS Office of the Secretary

The next session of the Study Assembly consisted of remarks by Assistant Surgeon General and ICC member Woodie Kessel. Dr. Kessel also serves as the executive director of the President’s Task Force on Environmental Health Risks and Safety Risks to Children. Dr. Kessel stated that the composition of the Task Force, which includes senior officials from numerous Cabinet agencies and the White House, underscores the fact that addressing the impact of environmental exposures on children’s health is a national priority. He added that HHS Secretary Tommy Thompson and EPA Administrator Christine Todd Whitman have both been briefed about the NCS and are excited about the opportunities it presents to forge new scientific ground. This potential, he said, holds great promise for improving the system of care for children, reducing disparities, promoting primary prevention and early treatment, and reducing the burden of illness on the nation’s children.

The NCS enjoys enthusiastic, broad-based support, including that from members of Congress who recognize the importance of generating new science on the impact of environmental exposures on child health and development. Dr. Kessel underscored the urgent need to better determine precisely which environmental exposures are harmful and which are harmless. Dr. Kessel informed the Study Assembly that on September 9 the President signed an Executive Order extending the Task Force for an additional two years. Dr. Kessel added that the terrorist attacks of September 11 should serve as a "clarion call" that all children-not only those in the United States, but also those abroad-must be protected. He added that the NCS provides an important opportunity to better protect the nation’s children in the decades to come.

Remarks by Duane Alexander, M.D., NICHD Director

NICHD Director Duane Alexander thanked the Study Assembly attendees for their important contribution to the NCS and for sharing their time and experience, noting that 350 people had participated in the two-day event.

Dr. Alexander said that, when the idea for the NCS first emerged some three years ago, no one would have thought that the effort would come so far so fast. This congressionally mandated study represents a daunting responsibility for those involved. However, much of the progress thus far can be attributed to the work of an experienced and dedicated staff.

In addition, Dr. Alexander stated that the NCS will provide an opportunity to shed new light on the impact of all types of environmental exposures on child health and development, along with a scientific basis for high-quality clinical care, future public policy, and the healthy growth and development of generations of children to come. It also will prove to be an invaluable resource for future child health research.

Dr. Alexander noted that the NCS is the first of its kind. The Collaborative Perinatal Project included a cohort of approximately 60,000 pregnancies that were followed for seven years to test a single outcome. The recent Women’s Health Initiative, which included a cohort of 100,000, employed three different protocols and studied three interventions over 10 years. Similarly, the Framingham Study, while longitudinal, is studying adults at a single site. The NCS, on the other hand, will include a cohort of at least 100,000 families followed for more than 21 years at approximately 50 diverse sites. There will be a large number of variables, observations, tests, and outcomes to assess among a diverse cohort. It will afford an unprecedented opportunity to test a large number of hypotheses and interventions. Nothing of this magnitude has ever been done before in the field of child health and development.

Dr. Alexander spoke briefly about the progress that has been made to date. A structure has been established for engaging the best Federal and non-Federal scientists available for planning and oversight of the study. The NCS enjoys broad-based interagency participation and cooperation from more than 40 organizations. The Advisory Committee’s charter has been approved, and several of the pilot studies are funded and under way. Most of the Working Groups have been established, and an independent NCS Web site is being developed.

Dr. Alexander briefed the Study Assembly about the funding status of the NCS. NICHD, EPA, NIEHS, and CDC invested approximately $3 million in resources in FY 2001. Up to $6 million in funding is expected for FY 2002, while some $10 million is anticipated for FY 2003. According to Dr. Alexander, budget projections indicate that, at peak enrollment periods, the NCS may cost $150 million per year for several years. NICHD is working with its HHS and EPA partners to plan for future funding of the study. The study will be funded entirely by the Federal Government. However, Dr. Alexander indicated that there may be some additional or adjunct studies funded by non-Federal public-private partnerships. While these are uncertain times in the Federal arena, Dr. Alexander indicated that the broad-based enthusiasm about the NCS-stretching from Congress to the research community to the health care field-bodes well for the appropriate allocation of resources necessary to get the job done.

Exposure to Chemical Agents Working Group Progress Report

EPA’s Halûk Özkaynak, Co-chair of the Exposure to Chemical Agents Working Group, reported on the activities of his Working Group. He stated that he was impressed by the diverse qualifications and expertise of the Working Group members, many of whom have experience in the fields of pediatrics, general medicine, epidemiology, occupational health, and exposure assessment. One of the biggest challenges the Working Group faced was formulating hypotheses that not only reflect the range of chemical exposures involved but also the various health outcomes that may be linked to those exposures.

The Working Group broke down the chemical exposures they identified into two groups-chemical exposures and environmental agents. The chemical exposures (List A) included the following:

• Metals (e.g., lead, mercury, arsenic, and numerous other metals)
• Pesticides (e.g., organophosphates, carbamates, pyrethroids, and triazines)
• Persistent organic pollutants (e.g., PCBs, dioxins and furans, chlorinated hydrocarbons, and VOCs)
• Disinfection by-products
• Ethanol
• Tobacco smoke
• Carbon monoxide

Environment agents (List B exposures) were as follows:

• Criteria pollutants
• VOCs
• PAH
• Metals
• Tobacco smoke
• Pyrethroids and pyrethrins
• Aldehydes
• Aeroallergens (e.g., molds, pollens, dust mites, endotoxins, and animal dander)
• Other agents (e.g., isocyanates, latex, and food allergens)

Using the identified List A and List B exposures as a starting point, the Working Group developed two preliminary hypotheses. The first hypothesis is that preconceptional, prenatal, and/or early childhood exposure to List A agents alone or in combination increases the risk of neurodevelopmental disorders. A related subhypothesis is that both chronic and intermittent exposures to these chemicals are associated with an increased risk for neurodevelopmental disorders.

The second preliminary hypothesis states that preconceptional, prenatal, and/or early childhood exposure to List B agents alone or in combination increases the risk of asthma. A subhypothesis to this is that both chronic and intermittent exposures to these chemicals are associated with an increased risk for asthma. Dr. Özkaynak pointed out that both of these hypotheses are designed to capture varying dose rates for List A and List B exposures and the subsequent health outcomes. He added that these hypotheses and subhypotheses are uniquely suited for longitudinal study because they will capture short-term and chronic exposures, and the only way to study that reliably is within a longitudinal context.

Dr. Özkaynak indicated that Working Group members had identified several important study design issues relevant to their work. These include the following:

• Single exposure versus multiple exposures versus mixed exposures Timing of measurement (preconception, in utero, pregnancy, and after birth)
• Chronic, acute, and intermittent exposure measurements
• Prioritization of cohort selection
• Identification of key routes and pathways by stage of life

Dr. Özkaynak pointed out that, in some cases, retrospective studies will be required to examine these issues effectively.

There are a number of ways to collect this information, according to Dr. Özkaynak. These include environmental samples, biological samples, and survey samples. Survey questions may focus on issues related to socioeconomic status, housing, urban versus rural residency, geographic region, time/activity, and product use. Videography also may provide another means to collect data.

In terms of pilot studies and other preliminary research, the Working Group believes that additional information may be necessary for detection methods, analytical and experimental approaches, and surrogate measures for predicting exposure and dosages so that researchers are not always collecting physical samples.

In the coming months, the Working Group plans to

• Develop a detailed list of chemical exposures Review existing literature to examine prevalence and use of various chemicals
• Perform a media-specific analysis of chemical concentrations and variability
• Identify available methods by chemical and matrix, which will involve evaluating method performance
• Develop criteria for choosing the optimal analytical or survey method
• Consult with health outcome experts to reach consensus on core literature and to refine chemical lists, which will be an ongoing task
• Convene a workshop to identify a visionary strategy for remaining abreast of emerging exposures and new technologies

Dr. Özkaynak stated that the Working Group hopes to complete these activities within 18 months.

Repository Working Group Progress Report

Previously known as the Sample Collection, Storage, and Archiving Working Group, the Repository Working Group is co-chaired by Mark Cosentino of BBI Biotech Research Laboratories, and Barbara Porter of the National Institute of Standards and Technology. Dr. Cosentino delivered the Working Group’s progress report to the Study Assembly.

Dr. Cosentino stated that the purpose of the Repository Working Group is to propose standard operating procedures (SOPs), quality assurance measures, and associated data systems focusing on specimen collection, storage, transport, and archiving. While all of these are important, Dr. Cosentino placed strong emphasis on establishing SOPs that are clearly defined and explained so that anyone can follow established procedures regardless of who is in charge of the specimens at any given time. This approach enables those in charge of keeping specimens to safeguard quality and to keep specimens in pristine condition throughout the course of the study. Also, the data systems employed must be able to track a large volume of specimens over many years. Consequently, data systems must be user-friendly and, the Working Group hopes, Internet accessible.

The Working Group has identified six categories of environmentally influenced specimens: biological, chemical, physical, behavioral, social, and cultural. Dr. Cosentino indicated that they will be contacting other Working Group chairs to have a better sense of what types of specimens their groups believe should be collected. In the meantime, he encouraged participants to share their ideas.

Dr. Cosentino described the goals of the Repository Working Group. These include the following:

• Ensuring consistency among collaborating repository facilities via SOPs and a quality management plan
• Proposing quality assurance/quality control procedures to support the study’s quality systems plan
• Proposing chain of custody (i.e., ownership) procedures for the study design
• Linking specimen information to the Information Management System while maintaining individual and family privacy and confidentiality
• Proposing SOPs for various types of environmentally influenced specimen collections, including acquisition techniques, processing, and aliquoting
• Proposing and sharing SOPs associated with shipping, handling, and transporting specimens to and from the repository
• Proposing SOPs for label design, state-of-the-art storage conditions, storage vessels, and related monitoring devices required to safeguard sample integrity
• Developing SOPs for the disposal and culling of specimens in the inventory
• Proposing pilot studies, based on input of the other Working Groups

As for next steps, Dr. Cosentino indicated that the Working Group will focus its immediate efforts on gaining a better understanding of the kinds and volume of samples to be collected. The Working Group plans to hold several discussion meetings in the coming months to prioritize its activities and review the input of other Working Groups.

Gene Environment Interactions Working Group Progress Report

CDC’s Paula Yoon presented on the activities of the Gene Environment Interactions Working Group, which currently consists of 13 core members spanning the fields of genetics, epidemiology, and statistics. About half of its members are non-Federal representatives. Dr. Yoon stated that the Working Group sees itself as cross-cutting, to serve as a resource as the national study tackles gene disease associations, gene environment interactions, and gene-gene interactions. They also plan to collaborate with other Working Groups on study design, data collection, laboratory, and data analysis issues. Their activities will focus on reviewing literature on genetic epidemiology as it relates to specific health outcomes and exposures, collaborating with the other Working Groups to develop study protocols for data collection and analysis, reviewing study protocols, and making recommendations on issues related to the field of genetics.

The Working Group sees the study design as a critical aspect of their work. Dr. Yoon indicated that a sample of 100,000 probably will not be sufficient for examining multiple genes, environmental factors, and their interactions. Other key study design issues include the prevalence of the diseases under consideration, population sampling, family studies, and how including genetics in the study design may affect participation rates.

In terms of data collection, the Working Group expects to deal with issues related to determining what types of biological specimens should be collected, biomarkers, proteomics, and the kinds of information to collect on families, family histories, and pedigrees. As for laboratory methods, the Working Group plans to be involved in issues related to genotyping methodologies, gene expression profiles, inherited susceptibilities versus somatic mutations, and whether the study will only use candidate genes or if gene findings or gene discovery will be involved.

Dr. Yoon reported that the methods for studying multiple comparisons and multiple interactions are limited. New methods are currently being explored, so it will be critical for the NCS to keep abreast of these advances. Population stratification, tests of interactions, and haplotypes also are important data analysis issues that the Working Group expects to examine.

Another potential challenge for the NCS is educating communities effectively to explain what "genetics" means, confront misconceptions, and change public perceptions. Decisions will have to be made regarding how to handle new findings that may affect a person’s future disease risk, reproductive choices, and other health-related issues. The Working Group can collaborate with the Ethics Working Group to address these issues. Dr. Yoon reported that several Working Group participants had raised issues important to them. For example, some participants were interested in how genetics relates to developmental disorders, autoimmune diseases, immune function, psychopathology, hearing, and infectious diseases. She added that the Working Group needs additional expertise in the fields of population genetics, genetic susceptibility to infectious agents, proteomics, gene expression profiling, and haplotype analysis.

Dr. Yoon concluded by proposing two additions to the Working Group’s charge: developing a plan for dealing with genetic findings and educating communities about the field of genetics and the benefits it offers.

Comments on Chemical Exposures, Repository, and Gene Environment Interaction Working Group Presentations

At the conclusion of Dr. Yoon’s presentation, the Study Assembly members were invited to ask questions and share comments. Several issues were discussed during the open comment period. They include the following:

• Given that this is a longitudinal study and that new findings will evolve throughout the course of the study, it will be necessary to develop a participant consent form that will enable researchers to examine new hypotheses as they arise.
• The preliminary hypotheses developed by the Exposure to Chemical Agents Working Group place a great deal of emphasis on disorder-related outcomes rather than outcomes related to reduced performance or functioning. Dr. Özkaynak responded that the Working Group used the term "developmental disorders" as an umbrella definition for a range of disorders that encompass performance- and function-related problems such as lead exposure effects, learning disabilities, speech and language problems, and compromised brain development. He added that the Working Group was attempting to keep the definition as general as possible, but more specific hypotheses ultimately may be developed and tested.
• Timing of exposure is a critical issue, especially because even small exposures in early pregnancy critical windows can have devastating effects. Questionnaire instruments may be able to address this effectively.
• Exposure to electromagnetic fields, wire codes, and similar exposures should be measured. ICC representatives indicated that this issue will fall under the purview of the newly formed Physical Exposures Working Group.
• Placental samples are often overlooked in pathology and may be extremely useful samples in the NCS.
• Given how precious the samples will be to the identification of new findings, serious consideration should be given to creating a repository system that uses back-up systems and redundancy as a safeguard. SOPs and technological advances will help ensure the safety of the samples in the inventory.
• An embryologist would be a valuable addition to the Gene Environment Interactions Working Group.
• Because of the potential for environmental contamination, breast milk should be included in the list of agents identified by the Exposure to Chemical Agents Working Group.

Injury Working Group Progress Report

Fred Rivara of the University of Washington briefed the Study Assembly on the progress of the Injury Working Group. Dr. Rivara presented eight preliminary hypotheses developed by the Working Group. They are as follows:

• Components of the physical environment are significant risk and protective factors for injury occurrence. Two subhypotheses associated with this core hypothesis suggest that: 1) this effect is modified by genetics, caregiver-child interaction, and other family and community factors, and 2) the degree of effect modification varies with age and developmental level.
• Components of the psychosocial (and sociocultural) environment are significant risk and protective factors for injury occurrence.
• The functional outcome following an injury is affected by antecedent psychosocial factors as well as psychosocial factors consequent to the injury.
• Chemical agents in the environment affect the risk of injury and violence. This effect is mediated through the effects of chemicals on neurological development and is modified by genetic, individual, family, and community factors.
• There is a cumulative effect of repeat injury over time on subsequent development, subsequent functioning and health status, and risk of new injury. A subhypothesis associated with this hypothesis suggests that this effect is greatest for severe injuries and repeated brain injury.
• Intergenerational transmission of antisocial behavior and violence is determined by genetics, prenatal and perinatal events, and early parenting.
• The impact of the early environment on the developmental trajectory of antisocial behavior is exerted through the biological effects of the brain and other organ development. Critical biological windows of heightened vulnerability exist for these environmental influences.
• Early risk-taking and risk-avoidance behaviors influence later risk-taking and risk-avoidance behaviors.

Dr. Rivara then outlined the study design issues identified by the Working Group. They include the following:

• Oversampling twins and high-risk families for violence and injury, and migrant populations
• Collecting data from fathers as early as possible, since they often disappear
• Embedding experimental interventions in the longitudinal design
• Collecting measures on at least some siblings
• Clustering the design and sampling within neighborhoods to assess impact on risk factors
• Recognizing that injury outcomes will change with the age and development of children
• Determining at what age to begin interviewing children

Dr. Rivara described possible measures and methods for assessing risk and protective factors. For individuals, these may include age and gender; genotype; temperament; personality; aggressiveness; health; mental health; cognitive ability; past experience with injuries and violence; substance use among parents; risk-taking behavior; beliefs and attitudes; activity level; attention; vigilance; sensation seeking; agility, balance, and coordination; anger; anxiety; prosocial behaviors; hormone levels; vagal tone; brain imaging; and neurotransmitters. Family-related risk and protective factors could include composition; parenting style; parental mental health; health of family members; social support; socioeconomic status; stress; substance use; mobility; primary mode of transportation; housing arrangements; health care utilization; supervision; ethnicity and race; culture; home environment; family safety norms; family discord; religiosity; history of parental antisocial behavior; acculturation; family functioning; parental social adjustment; the quality and quantity of day care; and parental work environment. Community-specific risk and protective factors could include chemicals; housing age and quality; population density; rural versus urban setting; traffic patterns; demographics; safety programs; quality of schools; community norms; cultural norms; collective efficacy; social capital; income disparity; school characteristics; physical environment (including sports); community assessment; level of emergency medical services, firefighting, police, and trauma centers; crime rate (real and perceived); and observations of the community.

Dr. Rivara identified several areas for potential pilot studies and white papers. These studies would focus on developing measurements for risk-taking behaviors, parental risk-taking history, supervision and parenting of young children, home environment, sibling interactions, physical activity in infants and toddlers, exposure to violence, play fighting, transportation modes and mixtures, reliability of self- and proxy-report of injuries, and severity scaling for minor injuries (including head and sports injuries).

Over the next six months, the Working Group plans to determine issues for which white papers should be developed, assign white papers to Working Group members, review the white papers developed, and recommend areas for future pilot studies. Dr. Rivara added that the Working Group is planning face-to-face meetings in January 2002 and May 2002.

Fertility and Early Pregnancy Working Group Progress Report

NICHD’s Germaine Buck, Chair of the Fertility and Early Pregnancy Working Group, reported that a diverse range of disciplines is represented in the Working Group. The Working Group has spent a great deal of time talking about critical windows for exposures and how to examine these exposures over a continuum of time. The Working Group also is interested in maternal, paternal, and parentally mediated effects.

Dr. Buck presented three preliminary hypotheses identified by the Working Group. The first hypothesis states that there is an association between preconceptional, periconceptional, and postconceptional parental factors (up to 12 weeks postconception) and short-term or long-term outcomes in offspring. Three potential subhypotheses were presented: 1) Maternal preconceptional exposure to allergens may increase intrauterine sensitization of the offspring; 2) loss of cells during early embryogenesis may be associated with autism; and 3) preconceptional exposures may increase the occurrence of aneuploidy in gametes.

The second hypothesis suggests that early exposures capable of altering sexual differentiation may contribute to developmental defects during puberty or adulthood. Two potential subhypotheses were presented. First, life-stage exposures or outcomes can result in cross-generational effects. Second, developmental exposures can alter reproductive development and subsequent fecundity and fertility in the offspring.

The third hypothesis presented by Dr. Buck suggests that children born to couples with impaired-fecundity may be at increased risk of short-term or long-term health outcomes. Two potential subhypotheses are as follows: 1) ICSI-conceived children may be more likely to have developmental delays and adult sterility than other children, and 2) sex chromosome aneuploidy may be associated with developmental delays in early childhood.

The Working Group identified several major study design issues. These include identifying subgroups of pregnant women; addressing how couples come to be pregnant; developing recruitment and retention strategies tailored for population subgroups; and field monitoring strategies related to early pregnancy issues at ovulation, conception, and implantation. However, Dr. Buck noted a few limiting factors associated with these design issues, including external validity, the absence of registries or readily available sampling frameworks for women of reproductive age, and adapting current technology for field use.

Dr. Buck summarized the proposed measures and methods identified by the Working Group. The first measure would occur at preconception. The second measure would capture parental exposures. The third measure would consist of prospective inquiry.

Potential areas for pilot studies to be conducted by the Working Group would focus on using technology effectively and identifying promising recruitment strategies for enrolling subjects early and keeping them involved in the study. The Working Group also recognizes a need to convene a series of workshops on a broad range of issues related to fertility and early pregnancy. These workshops would address both disease-specific and exposure-related biomarkers; multiple exposures, interactions, and evaluation of sparse exposure data; promising methodologies (e.g., hair follicles) for assessing puberty; and consultation on designing and implementing prospective early pregnancy studies. The Working Group is discussing how it may contribute to the body of knowledge available in the field. For example, the Working Group is considering developing a white paper on what is known from existing laboratory animal, wildlife, and human studies. The Working Group also is interested in daily and cumulative fecundability as it relates to time to pregnancy and how time to pregnancy is related to neurodevelopmental status. Finally, the Working Group hopes to explore developmental outcomes following assistant reproductive technologies and other areas of future research.

Social Environment Working Group Progress Report

NICHD’s Christine Bachrach serves as co-chair of the Social Environment Working Group with Linda Burton, professor of human development and sociology at Pennsylvania State University. The Social Environment Working Group report was given by Dr. Bachrach. The Working Group plans to assemble its core membership in the next few weeks. The group’s meeting on the previous day involved approximately 15 at-large members.

According to Dr. Bachrach, the Working Group’s purpose is to develop and identify research strategies to study the influence of the social environment on child health and development. The Working Group views the social environment as including a range of environmental factors that affect family or individual resources and constraints, such as job markets and crime levels in neighborhoods. It also encompasses social norms and values shared by members of social groups; factors related to the quality, content, and volume of interpersonal interactions within groups; and economic, cultural, social, family, policy, institutional, and other factors.

Dr. Bachrach stated that the social environment directly influences child health and development. It also moderates and, perhaps, mediates the effects of physical and chemical exposures on health; confounds the effects of the physical environment; and varies over time, developmental stages, and physical and social space. She added that this presents a range of measurement challenges. In the social environment, there are several levels of influence, including family, peers, church, schools, neighborhood, community, media, employers, and Federal policy.

Dr. Bachrach presented several illustrative hypotheses that describe the areas being explored by the Working Group. These hypotheses were broken down at different levels of the social environment-national and governmental levels, the community level, and the family level.

Four hypotheses focused on national and governmental factors:

• Social and economic policies (e.g., relating to health, child care, or employment) affect child health and development outcomes. These effects are mediated through effects on communities, health care systems, institutions, and families.
• Economic swings influence the types and amounts of resources that parents invest in their children.
• The representation of health and parenting behaviors in the national media influences parents’ own health behaviors and parenting practices, with effects on child health and development.
• "National" events experienced by children and families (e.g., terrorist attacks) influence children’s health and development both directly (via stress and anxiety) and indirectly (through effects on communities and families).

Dr. Bachrach presented four illustrative hypotheses focusing on community-level factors, viewing the community as a social group that includes institutions which support the community:

• Engagement in a spiritual community fosters individual and family values and behaviors as well as social bonds that influence parenting, health, and children’s engagement in risky behaviors.
• The structure, policies, curricula, and social organization of schools influence children’s exposure to safe and unsafe environments; healthy or risky peer groups; health-related knowledge, values, and beliefs; and behavior (e.g., aggression, substance abuse, etc.).
• · Social cohesion within neighborhoods and neighborhood residents’ perception of "collective efficacy" contribute to child health by improving supervision, social control, and social supports for children.
• Concepts of health, childhood, effective parenting, and gender roles are influenced by membership in "social communities," and these concepts influence parenting and investments in children.

Viewing the community as a physical, geographic place, the Working Group identified two additional illustrative hypotheses:

• Poverty, income, inequality, racial and ethnic segregation, and crime in neighborhoods influence resources and norms that contribute to parenting and the development of healthy children.
• Access to transportation systems, recreational facilities, health care services, and other community resources affect families’ ability to invest in health promotion and to respond effectively to health concerns.

Three illustrative hypotheses presented focused on family-level factors:

• Family resources (economic, time, and human) affect parenting practices and investments in child health and development.
• Family values and norms relating to health and health-related behaviors influence parental and child behaviors that contribute to or compromise health.
• Parental engagement in community institutions increases access to resources (economic and social) that contribute to positive health.

Dr. Bachrach then discussed some study design issues associated with measuring the social environment. These include the following:

• Measuring not only individual perceptions of the social environment but also direct or independent measures that are not affected by people’s perceptions
• Tracking changes in the social environment over time, including when families move or change their environment
• How samples are designed (clustered versus dispersed samples) and the subsequent cost implications
• Human subjects issues such as using geocoding techniques while also protecting confidentiality

The Social Environment Working Group plans to work closely with other Working Groups in determining the most critical dimensions of the social environment to measure and integrate hypotheses of mutual interest. In addition, the Working Group hopes to collaborate with other Working Groups to develop coordinated approaches to measuring the impact of the social environment and integrate those measures into the overall study design.

In conclusion, Dr. Bachrach summarized the Working Group’s timeline for the coming months. Once the core Working Group is established, they hope to conduct reviews of existing research and measurement strategies, to develop study design and measurement strategies and tools, and to conduct whatever pilot studies may be necessary. If no pilot studies are necessary, the Working Group may be able to submit its recommended protocols to the Federal Advisory Committee in July 2002.

Comments on Injury, Fertility and Early Pregnancy, and Social Environment Working Group Presentations

At the conclusion of Dr. Bachrach’s presentation, the Study Assembly members were invited to ask questions and share comments. Several issues were discussed during the open comment period. They include the following:

• The Fertility and Early Pregnancy Working Group may want to consider potential hypotheses that could be tested beyond the age of 21. This could open the door to a range of exciting and innovative research areas in the future. An example of this might involve relating pregnancy and birth complications to outcomes such as heart disease.
• One of the potential drawbacks of such a large, longitudinal study might be that the field does not want to wait 15 to 20 years for data. Whenever possible, efforts should be made to get data published early in the life of the study (e.g., examining seat belts and/or airbags as a cause of injury).
• The NCS is being conceptualized and planned at a time when there is a shrinking population of clinicians and scientists prepared to participate in the study. Efforts should be undertaken to recruit and train the next generation of clinician investigators who can participate in the study and carry it out.
• The timing of chemical exposures also may affect fathers and influence some parameters associated with sperm production. This study presents an opportunity to explore these issues, including how exposures affect fathers.
• Once the Nutrition, Growth, and Oral Health Working Group is established, it should explore vitamin D deficiency in children and the relationship to rickets, immunosuppression, and perhaps some neurological problems. Other issues might include the relationship between folic acid and neurological outcomes, and the association between iron overdose by mothers and cardiovascular vessel viability problems in children.

Pregnancy and Infant Ad Hoc Working Group Report

NICHD’s Catherine Spong reported on the activities of the Pregnancy and the Infant Working Group. The Working Group’s purpose is to evaluate the association of environmental exposures to the outcome of pregnancy, child health, and development. According to Dr. Spong, the Working Group recognizes that the characteristics of the child at birth, which may reflect in utero conditions, are related to a variety of health conditions during adulthood decades later. This type of longitudinal study will allow the examination of these factors and their potential effects on the long-term health and development of children-perhaps into adulthood. The Working Group also discussed maternal, fetal, and infant characteristics, conditions, and physiologic states that may be associated with the duration of gestation, fetal growth, and complications of pregnancy. Examples include evidence of markers of inflammation and defective placentation.

The group recognizes that its work will have serious implications for researchers hoping to review what happened during a specific pregnancy and whether any of the events associated with that pregnancy are related to the outcomes they observed at that particular time. As a result, data and samples must be collected in an orderly fashion to evaluate rare occurrences and adverse outcomes in health exposures and interventions. The Working Group also is interested in collecting data and samples to evaluate normal changes in pregnancy and less common maternal conditions, and to probe unexpected long-term outcomes. Dr. Spong added that the Working Group also realizes that genetic susceptibility to adverse pregnancy outcomes should be considered in light of the interaction that occurs between the genes of the fetus and mother and that of the environment.

The hypotheses developed by the ad hoc Working Group are as follows:

• Prenatal infection or inflammation increases the risk of adverse pregnancy and long-term neurodevelopmental outcomes such as cerebral palsy, autism, and schizophrenia.
• Endocrine and immune disruptions and/or dysfunction can increase the risk of adverse pregnancy and long-term developmental outcomes of the offspring.
• Pre- and perinatal diagnostic and therapeutic interventions may have long-term maternal and child development and health consequences, including medication such as antenatal and postnatal steroid use, sonography, antibiotics, and medications for acute and chronic maternal conditions.
• A suboptimal fetal environment can increase the risk of chronic child and adult diseases.
• The maternal diet is related to pregnancy outcome and long-term health and development of the child.

Dr. Spong described some of the study design issues that will affect the Working Group’s activities. For example, pregnant women are a difficult population to engage. Similarly, not all patients present at the same time, so collecting data from women who enroll at different gestational stages will lead to a lack of uniform information. However, limiting enrollment to a specific gestational age also is not representative of the population.

Asthma Ad Hoc Working Group Progress Report

EPA’s Lucas Neas reported on the discussions of the Asthma Ad Hoc Working Group. Dr. Neas requested that the ICC formally constitute the Working Group as soon as possible so it can move forward with developing hypotheses for inclusion in the study design.

Health Services Ad Hoc Working Group Progress Report

Bill Lawrence of the Agency for Healthcare Research and Quality reported that the Health Services Ad Hoc Working Group has been working on developing a mission statement and a conceptual framework to include health services issues in the NCS. The Health Services Working Group will focus its efforts on examining the relationships between health care and child health over time to produce new information that can be incorporated into practice and policy. The Working Group defines health care to include coverage, access to health care, and the processes that mediate between genes, the environment, and child health. Dr. Lawrence added that the ad hoc Working Group already has begun formulating hypotheses. Meanwhile, the group is still seeking individuals interested in serving on the Working Group.

Closing General Session-Public Comments

Participants were invited to share final comments and made the following remarks:

• The NCS organizational chart should be revised to reflect a less linear organization structure, conveying the need for maximum collaboration and cooperation among the Working Groups and other NCS entities.
• Where overlap occurs in Working Group activities and the scope of their efforts, the activities must be adequately coordinated to reduce redundancy, integrate functions, and limit duplication of effort. The ICC already is examining mechanisms for promoting effective communication between and among the Working Groups and for convening more frequent meetings of the Working Group chairs. Dr. Scheidt noted that the portal presents an ideal opportunity for Working Groups to collaborate and share information.
• Technologies such as the audio computer-assisted self-interview should be used whenever possible. Such technologies offer the capacity to collect data and put it in the hands of Working Groups that can use it. It also might be useful in retaining women who may be apprehensive about answering sensitive questions. The EPA already has commissioned a paper on how emerging technologies can be used for data collection and reduction.
• Academic departments can support the study in a variety of ways, such as conducting pilot studies and supplying experts to participate in Working Groups. Once the NCS is implemented, academic centers can become partners in enrolling subjects, collecting data, and participating as co-investigators. There is also a possibility that some investigator-initiated grants may be awarded. In the meantime, academic centers are free to share their ideas on how the study should be planned and implemented.
• Allowing for locally initiated hypotheses, in addition to the hypotheses developed by the Working Groups, will help keep local academics, providers, and others involved in the study and enhance the body of knowledge generated by the study.
• Serious consideration should be given to having nested, randomized control trials and other design strategies included in the NCS. Some outcomes, such as asthma, would benefit from such an approach.

Given the longitudinality of the NCS, this project provides an ideal training opportunity for young scientists. Resources should be allocated to support such training opportunities so that young investigators can develop the skills necessary to analyze, interpret, and report NCS data for many decades to come.

At the conclusion of the public comment period, the Study Assembly was adjourned.