Dr. Judy S. LaKind and Dr. Cheston M. Berlin, Jr.organized a workshop on neurodevelopmental effects from in utero chemcial exposures. Information on this Workshop may be found below and at related links:
Steering Committee:
Cheston Berlin, Jr., MD,
University Professor of Pediatrics, Professor of Pharmacology, Department of
Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University
College of Medicine
Judy S. LaKind, Ph.D.,
President, LaKind Associates, LLC, Adjunct Assoicate Professor, Hershey Medical
Center, Penn State College of Medicine, University of Maryland School of Medicine
Ann Mason, Managing Director
Research Foundation for Health and Environmental Effects
Bob Sonawane, Ph.D., Chief,
Effects Identification and Characterization Group, NCEA/ORD USEPA
Janice Yager, Ph.D., MPH, Research Program Manager Environment Division, Electric Power Research Institute
The Workshop was held at the 22nd International Neurotoxicology Conference. The panel deliberations are described in the following publication:
NeuroToxicology
Volume 27, Issue 5 , September 2006, Pages 861-874
Environment and Neurodevelopmental Disorders
Title: Hershey Medical Center Technical Workshop Report: Optimizing the design and interpretation of epidemiologic studies for assessing neurodevelopmental effects from in utero chemical exposure
Robert W. Amler, School
of Public Health, New York Medical College
Stanley Barone, Jr., National Center for Environmental Assessment, Office of
Research and Development, US Environmental Protection Agency
Aysenil Belger, Department
of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill
Cheston M. Berlin, Jr.,
Department of Pediatrics, Children's Hospital, Milton S. Hershey Medical Center,
Pennsylvania State University College of Medicine
Christopher Cox, Department
of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University
Harry Frank, Departments
of Psychology and Earth & Resource Sciences, The University of Michigan-Flint,
United States
Michael Goodman, Department
of Epidemiology, Emory University, Rollins School of Public Health
Jean Harry, Laboratory of
Neurobiology, National Institute of Environmental Health Sciences, National
Institutes of Health, Department of Health and Human Services
Stephen R. Hooper, Clinical
Center for the Study of Development and Learning, University of North Carolina
School of Medicine
Roger Ladda, Milton S. Hershey
Medical Center, Pennsylvania State University College of Medicine
Judy S. LaKind, LaKind Associates,
LLC, Milton S. Hershey Medical Center, Pennsylvania State College of Medicine,
University of Maryland School of Medicine
Paul H. Lipkin, Division
of Neurology and Developmental Medicine, The Kennedy Krieger Institute, The
Johns Hopkins University School of Medicine
Lewis P. Lipsitt, Department
of Psychology, Brown University
Matthew N. Lorber, National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency
Gary Myers, Division of
Pediatric Neurology, University of Rochester Medical Center
Ann M. Mason, Research Foundation
for Health and Environmental Effects
Larry L. Needham, Division
of Environmental Health Laboratory Sciences, Centers for Disease Control and
Prevention,
Babasaheb Sonawane, National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency
Theodore D. Wachs, Department
of Psychological Sciences, Purdue University
Janice W. Yager, Environment Division, Electric Power Research Institute
Abstract
Neurodevelopmental disabilities affect 3–8% of the 4 million babies born each year in the U.S. alone, with known etiology for less than 25% of those disabilities. Numerous investigations have sought to determine the role of environmental exposures in the etiology of a variety of human neurodevelopmental disorders (e.g., learning disabilities, attention deficit-hyperactivity disorder, intellectual disabilities) that are manifested in childhood, adolescence, and young adulthood. A comprehensive critical examination and discussion of the various methodologies commonly used in investigations is needed. The Hershey Medical Center Technical Workshop: Optimizing the design and interpretation of epidemiologic studies for assessing neurodevelopmental effects from in utero chemical exposure provided such a forum for examining these methodologies. The objective of the Workshop was to develop scientific consensus on the key principles and considerations for optimizing the design and interpretation of epidemiologic studies of in utero exposure to environmental chemicals and subsequent neurodevelopmental effects. (The Panel recognized that the nervous system develops post-natally and that critical periods of exposure can span several developmental life stages.) Discussions from the Workshop Panel generated 17 summary points representing key tenets of work in this field. These points stressed the importance of:
• a well-defined, biologically plausible hypothesis as the foundation of in utero studies for assessing neurodevelopmental outcomes;
• understanding of the exposure to the environmental chemical(s) of interest, underlying mechanisms of toxicity, and anticipated outcomes;
• the use of a prospective, longitudinal cohort design that, when possible, runs for periods of 2–5 years, and possibly even longer, in an effort to assess functions at key developmental epochs;
• measuring potentially confounding variables at regular, fixed time intervals;
• including measures of specific cognitive and social–emotional domains along with non-cognitive competence in young children, as well as comprehensive measures of health;
• consistency of research design protocols across studies (i.e., tests, covariates, and analysis styles) in an effort to improve interstudy comparisons;
• emphasis on design features that minimize introduction of systematic error at all stages of investigation: participant selection, data collection and analysis, and interpretation of results; these would include (but not be limited to) reducing selection bias, using double-blind designs, and avoiding post hoc formulation of hypotheses;
• a priori data analysis strategies tied to hypotheses and the overall research design, particularly for methods used to characterize and address confounders in any neurodevelopmental study;
• actual quantitative measurements of exposure, even if indirect, rather than methods based on subject recall;
• careful examination of standard test batteries to ensure that the battery is tailored to the age group as well as what is known about the specific neurotoxic effects on the developing nervous system;
• establishment of a system for neurodevelopmental surveillance for tracking the outcomes from in utero exposure across early developmental time periods to determine whether central nervous system injuries may be lying silent until developmentally challenged;
• ongoing exploration of computerized measures that are culturally and linguistically sensitive, and span the age range from birth into the adolescent years;
• routine incorporation of narrative in manuscripts concerning the possibility of spurious (i.e., false positive and false negative) test results in all research reportage (this can be facilitated by detailed, transparent reporting of design, covariates, and analyses so that others can attempt to replicate the study);
• forthright, disciplined, and intellectually honest treatment of the extent to which results of any study are conclusive – that is, how generalizable the results of the study are in terms of the implications for the individual study participants, the community studied, and human health overall;
• confinement of reporting to the actual research questions, how they were tested, and what the study found, and avoiding, or at least keeping to a minimum, any opinions or speculation concerning public health implications;
• education of clinicians and policymakers to critically read scientific reports, and to interpret study findings and conclusions appropriately; and
• recognition by investigators of their ethical duty to report negative as well as positive findings, and the importance of neither minimizing nor exaggerating these findings.
Dr. Judy S. LaKind and Dr. Cheston M. Berlin, Jr.organized two workshops on environmental chemicals in human milk and biomonitoring. Information on these Workshops may be found below and at related links:
Technical Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States.
Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, 15-17 February 2002.
In 2002, the first Technical Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States was convened to develop state-of-the-science guidance on methodological aspects of studies involving human milk. The participants in the first Workshop (the Expert Panel) were experts in pediatrics, family medicine, nursing, lactation, human milk sampling, analytical chemistry, epidemiology, pharmacology, toxicology, nutrition, and risk evaluation and communication ( LaKind and Berlin, 2002). The Workshop was held at the Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine (15-17 February 2002). The Expert Panel described and defined the components of well-conducted human milk surveillance and research studies, including participant selection, sample collection and analysis techniques, questionnaire development, chemical selection, and data reporting and utilization ( LaKind and Berlin, 2002). These findings were published in a special issue of the Journal of Toxicology and Environmetnal Health (vol 65, no 22).
The Panel recommended that future surveillance and research utilize the study guidelines described by the Workshop. In addition, the Panel emphasized the importance of unique ethical issues in human milk research, including sharing of results with participants and the need to make special efforts to preserve and maintain breastfeeding (Berlin et al., 2002).
An important outcome of the Workshop was a series of recommendations for future surveillance and research, including the following (Berlin et al., 2002):
1. Determining levels of environmental chemicals found in human milk and infant formula, with special attention given to those women who may have increased exposures.
2. Identifying human biomarkers of exposure, susceptibility, and effects to predict potential health risks associated with specific environmental chemicals to breastfed and formula-fed infants, mothers, and families.
3. Developing methods to analyze the risks and benefits to infants and children exposed to environmental chemicals and endogenous chemicals via breastfeeding and/or formula feeding.
4. Creating an internet-based database for recording levels of environmental chemicals reported in human milk and infant formula in a standardized manner, with interpretation.
5. Developing strategies for the accurate dissemination of research findings, through education and other means, to health care providers (e.g., physicians, nurses, midwives, social workers) and the public.
Workshop support was
provided by the Brominated Flame Retardants Industry Panel, American Chemistry
Council; Department of Health and Human Services, Health Resources and Services
Administration; EPA Office of Children’s Health Protection and Office
of Research and Development; National Institute of Child Health and Human Development
National Institutes of Health; Nurses Leadership Council; Penn State University
College of Medicine; Research Foundation for Health and Environmental Effects;
and the Public Health Policy Advisory Board.
Second Technical Workshop on Human Milk Surveillance and Biomonitoring Research on Environmental Chemicals in the United States.
Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, 24-26 September 2004.
Since the time of the first Workshop, there has been interest at both the federal and state levels, as well as by advocacy organizations, in developing human milk biomonitoring programs. Given the enormous expense associated with human milk biomonitoring, the potential for negatively impacting breastfeeding rates by conducting these studies, and in order to avoid the initiation of biomonitoring programs with ambiguous goals, it is critical that human milk studies be driven by carefully thought-out hypotheses, and conducted in a manner that adequately addresses these hypotheses. Due to the heightened interest in human milk biomonitoring in the US, this is a propitious time to discuss the overarching issue of implementation of human milk studies in the US in order and to clearly define the goals of milk biomonitoring programs. Therefore, we convened the Second Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States. The guidance arising from this Workshop can be used to guide the development of biomonitoring components of such large-scale research programs as the National Children’s Study, as well as agency- and state-specific biomonitoring programs. In addition, the guidance can be considered by individual investigators seeking to include milk biomonitoring in their site-specific studies of human health and exposure. Manuscripts have been published in the Journal of Toxicology and Environmental Health, Volume 68, Number 20, 2005.
LaKind, J.S., Berlin, C.M.
Jr., and Bates, M.N. 2005. Overview: Technical Workshop on Human Milk Surveillance
and Biomonitoring for Environmental Chemicals in The United States. Journal
of Toxicology and Environmental Health 68(20):1683-1690.
Fenton, S.E., Condon, M., Ettinger, A., Mason, A., McDiarmid, M, Qian, Z., Selevan, S.G., LaKind, J.S. 2005. Collection and use of exposure data from human milk biomonitoring in the Unites States. Journal of Toxicology and Environmental Health 68(20):1691-1712.
LaKind, J.S., Brent, R.L., Dourson, M.L., Kacew, S., Koren, G., Sonawane, B., Tarzian, A.J., Uhl, K. 2005. Human milk biomonitoring data: interpretation and risk assessment issues. Journal of Toxicology and Environmental Health 68(20):1713-1770.
Wang, R.Y., Bates, M.N., Goldstein, D.A., Haynes, S.G., Hench, K.D., Lawrence, R.A., Paul, I.M., Quan, Z. 2005. Human milk research for answering questions about human health. Journal of Toxicology and Environmental Health 68(20):1771-1802.
Berlin, C.M., Jr, Crase, B.L., Fürst, P., Moy, G., Needham, L.L., Pugh, L., Tully, M.R., LaKind, J.S. 2005. Methodologic considerations for improving and facilitating human milk research. Journal of Toxicology and Environmental Health 68(20):1803-1824.
Berlin, C.M. Jr., LaKind, J.S., Fenton, S.E., Wang, R.Y., Bates, M.N., Brent, R.L., Condon, M., Crase, B.L. , Dourson, M.L., Ettinger, A.S., Foos, B., Fürst, P., Giacoia, G.P., Goldstein, D.A., Haynes, S.G., Hench, K.D., Kacew, S., Koren, G. , Lawrence, , R.A., Mason, A., McDiarmid, M.A., Moy, G., Needham, L.L., Paul, I.M., Pugh, L.C., Qian, Z., Salamone, L., Selevan, S.G., Sonawane, B., Tarzian, A.J., Tully, M.R., Uhl, K. 2005. Conclusions and recommendations of the Expert Panel: Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States. Journal of Toxicology and Environmental Health 68(20):1825-1831.
Participants:
Michael N. Bates, Ph.D.
School of Public Health, Division of Environmental Health Sciences
University of California, Berkeley
Cheston M. Berlin, Jr.,
MD
Department of Pediatrics, Children’s Hospital
Milton S. Hershey Medical Center
Pennsylvania State University College of Medicine
Robert L. Brent , MD, PhD,
FAAP
Distinguished Professor of Pediatrics, Louis and Bess Stein Professor of Pediatrics,
Radiology and Anatomy, at the Jefferson Medical College of Thomas Jefferson
University and Head of the Laboratory of Clinical and Environmental Teratology,
A I duPont Hospital for Children
Marian Condon RN, MS
Research Nurse, Antineoplastic Drug Exposure Project
University of Maryland School of Medicine
Betty L. Crase, IBCLC
Manager, Breastfeeding Initiatives American Academy of Pediatrics Division of
Community Health Services
Breastfeeding Promotion in Physicians' Office Practices Program
Section on Breastfeeding, American Academy of Pediatrics
Michael L. Dourson, Ph.D.,
DABT
Toxicology Excellence for Risk Assessment
Adrienne S. Ettinger, Sc.D.,
M.P.H.
Assistant Professor
Johns Hopkins Bloomberg School of Public Health
Suzanne E. Fenton, Ph.D.
Research Biologist, Endocrinology Branch
Reproductive Toxicology Division
NHEERL
US Environmental Protection Agency
Brenda Foos
Office of Children's Health Protection
US Environmental Protection Agency
Peter Fürst, Ph.D.
Chemical and Veterinary Control Laboratory
George P. Giacoia, MD
Pediatric Pharmacology Research Unit Network
National Institute of Child Health and Human Development
National Institutes of Health
Daniel A. Goldstein, MD
Product Coordinator
Monsanto Company
Suzanne G. Haynes, Ph.D.
Senior Science Advisor
Office on Women’s Health
Department of Health and Human Services
Karen D. Hench, RN, MS
Captain, U.S. Public Health Service, Perinatal Health Specialist
Division of Perinatal Systems and Women's Health
Maternal and Child Health Bureau
Health Resources and Services Administration
Sam Kacew, Ph.D.
Editor-in-Chief, Journal of Toxicology and Environmental Health
Professor, Department of Pharmacology
University of Ottawa
Gideon Koren, M.D., F.A.C.M.T.
FRCP(C)
Professor, Developmental Pharmacology and Toxicology
Hospital For Sick Children
Clinical Pharmacology Department
Judy S. LaKind, Ph.D.
President, LaKind Associates, LLC
Adjunct Associate Professor
Department of Pediatrics, Children’s Hospital
Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine
Ruth A. Lawrence, MD
Professor of Pediatrics, Obstetrics & Gynecology
Director, Newborn Nursery, Children's Hospital at Strong
Director, Breastfeeding and Human Lactation Study Center
University of Rochester
Carol Ley, MD
Medical Director
3M Medical Department
Kathryn R. Mahaffey, Ph.D.
Director of the Division of Exposure Assessment, Coordination and Policy
Office of Science Coordination and Policy of OPPTS
US Environmental Protection Agency
Ann Mason
Managing Director
Research Foundation for Health and Environmental Effects
Melissa A. McDiarmid MD,
MPH, DABT
Professor of Medicine and Director,
University of Maryland Occupational Health Program
Gerald Moy, Ph.D.
GEMS/Food Coordinator
World Health Organization
Larry L. Needham, Ph.D.
Chief, National Center of Environmental Health
Division of Environmental Health Laboratory Sciences
Centers for Disease Control and Prevention
Ian M. Paul, MD
Department of Pediatrics, Children’s Hospital
Milton S. Hershey Medical Center
Pennsylvania State University College of Medicine
Linda Pugh PhD, RNC, FAAN
Associate Professor
Director, Baccalaureate Program
Johns Hopkins University School of Nursing
Zhengmin Qian, M.D., Ph.D.
Assistant Professor
Milton S. Hershey Medical Center
Pennsylvania State College of Medicine
Health Evaluation Sciences
Lee Salamone
Director, Public Health and Science Policy Issue Group
American Chemistry Council
Sherry Selevan, Ph.D.
Reproductive Epidemiologist
National Center for Environmental Assessment
Office of Research and Development
US Environmental Protection Agency
Bob Sonawane, Ph.D.
Chief, Effects Identification and Characterization Group
National Center for Environmental Assessment
US Environmental Protection Agency
Anita J. Tarzian, Ph.D.
Ethics and Research Consultant
Adjunct faculty, University of Maryland, Baltimore, School of Nursing
Mary Rose Tully, MPH, IBCLC
Human Milk Banking Association of North America
Director of Lactation Services
N.C. Women’s Hospital
UNC Health Care
Kathleen Uhl, MD
Medical Team Leader
US Food & Drug Administration
Center for Drug Evaluation & Research
Office of New Drugs
Pregnancy Labeling Team
Richard Wang, DO
Senior Medical Officer
Organic Analytical Toxicology Branch
Division of Laboratory Sciences, National Center for Environmental Health
Centers for Disease Control and Prevention
Workshop support was provided by: The American Chemistry Council; the Centers for Disease Control and Prevention; the Department of Health and Human Services, Health Resources and Services Administration; Health Canada; 3M; Pennsylvania State University College of Medicine; the Research Foundation for Health and Environmental Effects; and the U.S. Environmental Protection Agency, Office of Children’s Health.