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      Principles and Practices of Neurodevelopmental Assessment in Children: Lessons Learned from the Centers for Children’s Environmental Health and Disease Prevention Research


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          Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children’s Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study’s concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children’s Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene–environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children’s Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand.

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          Most cited references69

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          Measurement of Temperament in Infancy

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            The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report.

            To determine whether the effects of low-level lead exposure persist, we reexamined 132 of 270 young adults who had initially been studied as primary school-children in 1975 through 1978. In the earlier study, neurobehavioral functioning was found to be inversely related to dentin lead levels. As compared with those we restudied, the other 138 subjects had had somewhat higher lead levels on earlier analysis, as well as significantly lower IQ scores and poorer teachers' ratings of classroom behavior. When the 132 subjects were reexamined in 1988, impairment in neurobehavioral function was still found to be related to the lead content of teeth shed at the ages of six and seven. The young people with dentin lead levels greater than 20 ppm had a markedly higher risk of dropping out of high school (adjusted odds ratio, 7.4; 95 percent confidence interval, 1.4 to 40.7) and of having a reading disability (odds ratio, 5.8; 95 percent confidence interval, 1.7 to 19.7) as compared with those with dentin lead levels less than 10 ppm. Higher lead levels in childhood were also significantly associated with lower class standing in high school, increased absenteeism, lower vocabulary and grammatical-reasoning scores, poorer hand-eye coordination, longer reaction times, and slower finger tapping. No significant associations were found with the results of 10 other tests of neurobehavioral functioning. Lead levels were inversely related to self-reports of minor delinquent activity. We conclude that exposure to lead in childhood is associated with deficits in central nervous system functioning that persist into young adulthood.
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              New Ballard Score, expanded to include extremely premature infants.

              The Ballard Maturational Score was refined and expanded to achieve greater accuracy and to include extremely premature neonates. To test validity, accuracy, interrater reliability, and optimal postnatal age at examination, the resulting New Ballard Score (NBS) was assessed for 578 newly born infants and the results were analyzed. Gestational ages ranged from 20 to 44 weeks and postnatal ages at examination ranged from birth to 96 hours. In 530 infants, gestational age by last menstrual period was confirmed by agreement within 2 weeks with gestational age by prenatal ultrasonography (C-GLMP). For these infants, correlation between gestational age by NBS and C-GLMP was 0.97. Mean differences between gestational age by NBS and C-GLMP were 0.32 +/- 1.58 weeks and 0.15 +/- 1.46 weeks among the extremely premature infants (less than 26 weeks) and among the total population, respectively. Correlations between the individual criteria and C-GLMP ranged from 0.72 to 0.82. Interrater reliability of NBS, as determined by correlation between raters who rated the same subgroup of infants, ws 0.95. For infants less than 26 weeks of gestational age, the greatest validity (97% within 2 weeks of C-GLMP) was seen when the examination was performed before 12 hours of postnatal age. For infants at least 26 weeks of gestational age, percentages of agreement with C-GLMP remained constant, averaging 92% for all postnatal age categories up to 96 hours. The NBS is a valid and accurate gestational assessment tool for extremely premature infants and remains valid for the entire newborn infant population.

                Author and article information

                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                October 2005
                24 June 2005
                : 113
                : 10
                : 1437-1446
                [1 ]University of Cincinnati College of Medicine, Division of Epidemiology and Biostatistics, Department of Environmental Health, and the Cincinnati Children’s Environmental Health Center, Cincinnati, Ohio, USA
                [2 ]Center for Children’s Environmental Health Research, School of Public Health, University of California at Berkeley, California, USA
                [3 ]The Friends Children’s Environmental Health Center, University of Illinois, Urbana-Champaign, Illinois, USA
                [4 ]Children’s Environmental Health Center, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
                [5 ]Columbia Center for Children’s Environmental Health, Columbia University, New York, New York, USA
                [6 ]Pediatric Neuropsychology Group, Berkeley, California, USA
                [7 ]Department of Family Health Care Nursing, School of Nursing, University of California, San Francisco, California, USA
                [8 ]Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, New York, USA
                [9 ]Department of Molecular Biosciences, and
                [10 ]Department of Neurological Surgery, University of California at Davis, Davis, California, USA
                Author notes
                Address correspondence to K.N. Dietrich, University of Cincinnati College of Medicine, Department of Environmental Health, Division of Epidemiology and Biostatistics, 3223 Eden Ave., Cincinnati, Ohio 45267-0056. Telephone: (513) 558-0531. Fax: (513) 558-4838. E-mail: Kim.Dietrich@uc.edu

                The authors declare they have no competing financial interests.

                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.

                Public health
                behavior,study design,neurotoxicology,national children’s study,development
                Public health
                behavior, study design, neurotoxicology, national children’s study, development


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