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 December 2003 NCSAC Meeting Summary: Neurodevelopment and Behavior

Appendix II: National Children’s Study Advisory Committee 8th Meeting

Thematic Group Breakout Meeting Summary: Neurodevelopment and Behavior

December 15, 2003
Sheraton Atlanta Hotel
Atlanta, GA

Chair: Deborah A. Phillips, Ph.D., NCSAC Member, Georgetown University

Opening Remarks

Dr. Phillips welcomed the group and asked participants to introduce themselves. She stated that, in addition to a full and complete review of themes and hypotheses included in the document titled National Children’s Study:
Improving Children’s Environmental Health with High Quality Science, Formulating Hypotheses and Study Design (Interagency Coordinating Committee (ICC) Subcommittee Draft, December 1, 2003), the group would have to work through the agenda with a renewed thrust of focusing on the issues of healthy development.

Thematic Areas

Given the impetus to focus on healthy development, Dr. Phillips asked the participants if they should consider recommending healthy development as a sixth theme in the National Children’s Study. The current thematic areas for priority outcomes are:

  • Pregnancy outcomes
  • Neurodevelopment and behavior
  • Injury
  • Asthma
  • Obesity and physical development.

Neal Halfon, M.D., M.P.H., Department of Community Health Services, University of California, Los Angeles, suggested that a sixth thematic area not be added. He explained that healthy development is not just about neurocognition, but that all body systems have a normal developmental trajectory. He questioned whether the sample size in the Study was large enough to address issues of defining "normal." The challenge of the Study is to highlight outcomes given particular exposures, while retaining the overarching theme of healthy development. The ability to discern optimal development versus pathological development depends on methodology and measurement techniques.

Denise Dougherty, Ph.D., Office of Priority Populations Research, Agency for Healthcare Research and Quality, noted that the Study could focus on issues of development either way, without necessarily focusing on outcomes, or could focus on intermediate outcomes. In this context, the participants discussed the following topics:

  • Measuring ceiling effects
  • Asthma as it relates to school performance
  • Ecumenical selection of measures
  • Empirically based models
  • State of measurement and theory
  • Stress reactivity measurements as mediated by environment
  • Measuring across environments
  • Biomarkers that "travel" with certain behaviors.

Sarah S. Knox, Ph.D., National Children’s Study Program Office, NICHD, NIH, DHHS, said that there are many different perspectives when it comes to defining outcomes. She noted that developmental outcomes are not discrete (for example, adolescence) but occur on a continuum. Dr. Knox cited the difficulty in measuring the types of social relationships in adolescents.

Philip J. Landrigan, M.D., M.Sc., Mount Sinai School of Medicine, explained that social factors could be confounders when examining outcomes of exposures to lead, methyl mercury, and organophosphate pesticides.

In addition, Dr. Halfon noted that gene, cell, and social environments could all be confounders. He further noted that there is a strong reductionist biological point of view of the Study. Points of view should be integrated into two perspectives, and there should be crosscutting themes. Health outcome measures generally present on a continuum, not in a dichotomy. The process, so far, has focused on negative health outcomes.

Dr. Landrigan suggested that the Study could explore the full range of health outcomes versus ranges of exposures-both positive and negative. Exposures could be categorized into groups such as truly deleterious factors and those that are powerfully enabling. Exposures include risks (for example, lead, methyl mercury, organophosphate pesticides) and protections (for example, home environment, school, community, family). Health outcomes can ultimately be put on a single scale that reflects the relative balance of risks and protections and describes an optimum trajectory versus a less-than-optimum trajectory of development. Dr. Phillips introduced the McArthur model and drew a chart that depicted childhood variables and the effects of their interactions on the range of healthy-to-unhealthy outcomes. Dr. Halfon described two important aspects of the Study:
(1) understanding how cultural and social factors "push" on an individual and (2) understanding the timing and critical or sensitive periods of exposures.

Recommendation

The participants recommended that a sixth theme of healthy development not be added to the list of priority outcomes.

Adequacy of Hypotheses

Dr. Phillips asked participants to discuss the adequacy of the three hypotheses listed in the ICC Subcommittee Draft (dated December 1, 2003). A participant commented that although the current hypotheses are good, others have been submitted and that they have generally been narrowed, limited, or "whittled down."

Robert H. Yolken, M.D., Johns Hopkins University Medical Institutions, asked why the group was being asked to add more hypotheses if they are going to be ultimately excluded. Participants wanted to know what the ICC had said about the hypotheses. There were some concerns about power calculation analyses for the Study. The participants also expressed some concern and confusion about the meaning of "adequacy" and the necessity for discussing "adequacy."

According to Dr. Phillips, there were basically two issues to discuss:
(1) the status of the existing array of hypotheses and (2) the need to identify what’s missing from the hypotheses. In their discussion of development and behavior, the participants mentioned the following aspects that may need to be reconsidered for incorporation into the hypotheses:

  • Memory, planning, impulsivity, attention
  • Self-regulation
  • Stress reactivity
  • Temperament
  • Cognition and language development
  • School engagement and academic success
  • Social (that is, peer) adaptation/competence
  • Risk-taking behaviors (sex, drugs, videos).

According to Dr. Phillips, the three hypotheses are defensible. She allowed, however, that two considerations may be missing:
(1) the psychosocial environment and (2) positive developmental outcomes.

Dr. Landrigan told the group that the two New York counties with the highest pesticide use are Manhattan and Brooklyn. These counties also have high levels of other compounds that are considered neurotoxins. What is not currently known is the extent of interactions among neurotoxins such as lead, methyl mercury, and organophosphate pesticides. The interactions among neurotoxins may affect neurobehavioral and cognitive outcomes. Dr. Landrigan cautioned that the relevant developmental outcomes of these interactions are not known. As an example, he cited the correlation of incarceration rates and lead levels in bone. He also noted that for most chemical neurotoxins, there are no minimum threshold levels; that is, any amount of exposure to these chemicals, no matter how small, should be considered neurotoxic to humans.

Recommendations

In considering the adequacy of the three existing core hypotheses for neurodevelopment and behavior, the participants made the following four recommendations:

  • Include greater specificity in outcome measures
  • Examine the interactions among chemical neurotoxins
  • Add social environments, psychosocial factors, and/or socioeconomic factors, particularly cumulative aspects
  • Add exposure to infectious disease
  • Include a broader range of developmental outcomes.

Dr. Knox noted that there are pollutants with known threshold levels, yet these pollutants are difficult to measure in the environment. An example, she said, is sick building syndrome, for which it is difficult to assess causes because the purported pollutants simply cannot be measured. Another example of threshold levels involves stress in daycare centers. There are endocrine changes associated with stress, but it is not known whether these changes lower threshold levels in response to stressors. Another example, noted by Dr. Landrigan, is paraoxinase expression in response to exposure to certain chemicals. Maternal genotype affects paraoxinase expression, which in turn affects intrauterine exposure. Key factors in this circumstance include level of exposure, timing of exposure, and cumulative exposure (time/duration). Exposure during pregnancy is generally thought to be worse than postnatal exposure. Participants also mentioned exposure to alcohol and other drugs, variations in maternal metabolism, and correlations of maternal age.

Hypothesis 3

During a discussion of Hypothesis 3, the following aspects were mentioned:

  • Developmental status variables
  • Including autism with schizophrenia and studying them on a continuum
  • Expanding all hypotheses to include positive outcomes
  • Multi-modal aspects, for example, of schizophrenia
  • A child’s strengths playing a role in modulating effects of exposures.

Dr. Knox added the following comments:

  • The consequences of lead exposure are manifold.
  • Lead exposure affects several outcomes and measures.
  • There are perverse interactions between lead and other exposures (for example, community, psychosocial environment, socioeconomic status [SES]).

Additional Core Hypotheses to Include

Dr. Phillips distributed a handout titled Development and Behavior:
Integrating Priority Exposures of the Psychosocial Environment (see Attachment A). She asked participants to review the items listed in part II of this handout. Items 1-7 in part II are related to core hypothesis 1; items 8 and 9 are related to core hypothesis 3; items 10-12 are related to psychiatric outcomes; and items 13-16 are related to altered neurobehavioral development.

Dr. Phillips asked the participants to discuss the items in sequence.

Prematurity

The participants acknowledged that because much is known about prematurity and outcomes, there are no additional questions concerning prematurity that should be elevated to a core hypothesis 1. Discussion points included:

  • What are the interactions of prematurity with other variables?
  • Does prematurity affect an individual throughout the lifespan?
  • What are the environmental effects on pregnancy outcomes?
  • What is the correlation of early exposures and later outcomes?
  • What are the cardiovascular outcomes (for example, heart disease) of prematurity?
  • What are some of the very early biomarkers of these outcomes (participants cited two studies in Louisiana and Finland)?

Media exposure

Discussion points included:

  • What is the relationship between sleep dysfunction/sleep patterning and stress reactivity?
  • What in the environment leads to sleep dysfunction?

Government policies

Discussion points included:

  • How does a researcher measure public policy changes/variations?
  • How are policy changes/variations captured?
  • What is the relationship between how stringent a policy is and the extent to which it’s enforced?

Marriage

Discussion points included:

  • What are the effects of married parents on development?
  • What are the effects of unmarried parents on development?
  • What is the role of stability of family relationships in development?
  • What are the effects of same-sex parents on development?

Stress associated with SES.

Discussion points included:

  • What are the effects of a single parent’s financial status on development?
  • What are the effects of social networks and stress in the home on development?
  • What is the role of internalized or perceived racism as a stressor?
  • Can perceived racism or discrimination be measured?
  • What is the role of institutionalized racism such as disparities in the quality and allocated resources of school systems?
  • What proposals have been made to measure parenting behaviors?
  • Is job stress more relevant to minorities?

Childcare

Discussion points included:

  • What measures of childcare are feasible?
  • What measures of childcare are valid?

Recommendation

Participants recommended that validated measures of childcare be included in the core data set of the Study.

Policy variations

See earlier discussion on government policies.

Dopamine receptor subtypes

Participants stated the need for more general information on the genes involved in neurotransmission and reiterated the importance of assessing gene-environment interactions.

Violence and depression

Participants emphasized the importance of including an assessment of family violence in the Study.

Psychiatric outcomes

Discussion points included:

  • Genes that control neurotransmission
  • Concept of neighborhood
  • Gene-environment interactions
  • Postpartum depression
  • Maternal mental health, including timing, duration, and intensity.

Altered neurobehavioral development.

Discussion points included:

  • Social factors that modulate chemical exposures
  • The critical need to measure social environment variables and a validated index
  • Special consideration of children with development and learning disabiliti
  • Measures of community social support
  • Multiple concepts of community engagement.

Conclusion

In response to a participant’s question, Dr. Phillips said that the group would list the additional core hypotheses to include, refine them, rank them, and then report them to the NCSAC. A list of alternate hypotheses may be included. Dr. Phillips summarized the group’s recommendations for refinements of the core hypotheses as:

  • Include assessment of interactions among chemicals.
  • Add more social environmental influences.
  • Expand the range of outcomes.

In Attendance

Thematic Group Members

Chair: Deborah A. Phillips, Ph.D., Georgetown University
Gerry G. Akland, M.S., retired
Denise Dougherty, Ph.D., AHRQ, DHHS
Barbara R. Foorman, Ph.D., University of Texas-Houston Health Science Center
Neal Halfon, M.D., M.P.H., University of California, Los Angeles
Sarah S. Knox, Ph.D., National Children’s Study Program Office, NICHD, NIH, DHHS
Philip J. Landrigan, M.D., M.Sc., Mount Sinai School of Medicine
Roderick Joseph A. Little, Ph.D., University of Michigan
Gladys H. Reynolds, Ph.D., CDC, DHHS
Marshalyn Yeargin-Allsopp, M.D., CDC, DHHS
Robert H. Yolken, M.D., Johns Hopkins University Medical Institutions
Paula W. Yoon, Sc.D., M.P.H., CDC, DHHS

Observers and Other Participants

Marion J. Balsam, M.D., National Children’s Study Program Office, NICHD, NIH, DHHS
Stephen J. Bedosky, B.A., M.S., LFR Levine Fricke
Arthur M. Bennett, M.E.A., B.E.E., NICHD, NIH, DHHS
Rebecca Brown, M.P.H., M.E.M., EPA
Fletcher S. Crowe, Ph.D., Science Applications International Corporation
William E. Ebomoyi, Ph.D., University of Northern Colorado
Doris B. Haire, American Foundation for Maternal and Child Health
Carl E. Hunt, M.D., NHLBI, NIH, DHHS
Carol Jones, M.A., Psychotherapist
Toyojiro Matsuishi, Kurume University School of Medicine
Rick A. Rader, M.D., Exceptional Parent Magazine
Beth D. Roy, Society for Scientific Systems, Inc.
Kathy Schneider, Ph.D., Iowa Foundation for Medical Care
Ann Marie White, Ed.D., Office of the Director, NIH, DHHS

  6/26/2008
  6/26/2008