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      Prenatal Maternal Stress Associated with ADHD and Autistic Traits in early Childhood

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          Abstract

          Research suggests that offspring of mothers who experience high levels of stress during pregnancy are more likely to have problems in neurobehavioral development. There is preliminary evidence that prenatal maternal stress (PNMS) is a risk factor for both autism and attention deficit hyperactivity disorder (ADHD), however most studies do not control for confounding factors and no study has investigated PNMS as a risk factor for behaviors characteristic of these disorders in early childhood. A population cohort of 2900 pregnant women were recruited before their 18th week of pregnancy and investigated prospectively. Maternal experience of stressful life events was assessed during pregnancy. When offspring were age 2 years, mothers completed the child behavior checklist. Multiple regression showed that maternal stressful events during pregnancy significantly predicted ADHD behaviors in offspring, after controlling for autistic traits and other confounding variables, in both males ( p = 0.03) and females ( p = 0.01). Similarly, stressful events during pregnancy significantly predicted autistic traits in the offspring after controlling for ADHD behaviors and confounding variables, in males only ( p = 0.04). In conclusion, this study suggests that PNMS, in the form of typical stressful life events such as divorce or a residential move, show a small but significant association with both autistic traits and ADHD behaviors independently, in offspring at age 2 years, after controlling for multiple antenatal, obstetric, postnatal, and sociodemographic covariates. This finding supports future research using epigenetic, cross-fostering, and gene–environment interaction designs to identify the causal processes underlying this association.

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          Most cited references29

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          Effects of prenatal infection on brain development and behavior: a review of findings from animal models.

          Epidemiological studies with human populations indicate associations between maternal infection during pregnancy and increased risk in offspring for central nervous system (CNS) disorders including schizophrenia, autism and cerebral palsy. Since 2000, a large number of studies have used rodent models of systemic prenatal infection or prenatal immune activation to characterize changes in brain function and behavior caused by the prenatal insult. This review provides a comprehensive summary of these findings, and examines consistencies and trends across studies in an effort to provide a perspective on our current state of understanding from this body of work. Results from these animal modeling studies clearly indicate that prenatal immune activation can cause both acute and lasting changes in behavior and CNS structure and function in offspring. Across laboratories, studies vary with respect to the type, dose and timing of immunogen administration during gestation, species used, postnatal age examined and specific outcome measure quantified. This makes comparison across studies and assessment of replicability difficult. With regard to mechanisms, evidence for roles for several acute mediators of effects of prenatal immune activation has emerged, including circulating interleukin-6, increased placental cytokines and oxidative stress in the fetal brain. However, information required to describe the complete mechanistic pathway responsible for acute effects of prenatal immune activation on fetal brain is lacking, and no studies have yet addressed the issue of how acute prenatal exposure to an immunogen is transduced into a long-term CNS change in the postnatal animal. Directions for further research are discussed. Copyright 2010 Elsevier Inc. All rights reserved.
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            Empirically based assessment of the behavioral/emotional problems of 2- and 3- year-old children.

            The aim was to determine whether ratings of 2- and 3-year-olds could yield more differentiation among their behavioral/emotional problems than the internalizing-externalizing dichotomy found in previous studies. The 99-item Child Behavior Checklist for Ages 2-3 (CBCL/2-3) was designed to extend previously developed empirically based assessment procedures to 2-and 3-year-olds. Factor analyses of the CBCL/2-3 completed by parents of 398 2- and 3-year-olds yielded six syndromes having at least eight items loading greater than or equal to .30 and designated as Social Withdrawal, Depressed, Sleep Problems, Somatic Problems, Aggressive, and Destructive. Second-order analyses showed that the first two were related to a broad-band internalizing grouping, whereas the last two were related to a broad-band externalizing grouping. Scales for the six syndromes, two broad-band groupings, and total problem score were constructed from scores obtained by 273 children in a general population sample. Mean test-retest reliability r was .87, 1-year stability r was .69, 1-year predictive r with CBCL/4-16 scales at age 4 was .63, 2-year predictive r was .55, and 3-year predictive r was .49. Children referred for mental health services scored significantly higher than nonreferred children on all scales. A lack of significant r's with the Minnesota Child Development Inventory, Bayley, and McCarthy indicate that the CBCL/2-3 taps behavioral/emotional problems independently of the developmental variance tapped by these measures.
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              Physical and mental health outcomes of prenatal maternal stress in human and animal studies: a review of recent evidence.

              Prenatal maternal stress (PNMS) has been linked with adverse health outcomes in the offspring through experimental studies using animal models and epidemiological studies of human populations. The purpose of this review article is to establish a parallel between animal and human studies, while focusing on methodological issues and gaps in knowledge. The review examines the quality of recent evidence for prevailing PNMS theoretical models, namely the biopsychosocial model for adverse pregnancy outcomes and the fetal programming model for chronic diseases. The investigators used PubMed (2000-06) to identify recently published original articles in the English language literature. A total of 103 (60 human and 43 animal) studies were examined. Most human studies originated from developed countries, thus limiting generalisability to developing nations. Most animal studies were conducted on non-primates, rendering extrapolation of findings to pregnant women less straightforward. PNMS definition and measurement were heterogeneous across studies examining similar research questions, thus precluding the conduct of meta-analyses. In human studies, physical health outcomes were often restricted to birth complications while mental health outcomes included postnatal developmental disorders and psychiatric conditions in children, adolescents and adults. Diverse health outcomes were considered in animal studies, some being useful models for depression, schizophrenia or attention deficit hyperactivity disorder in human populations. The overall evidence is consistent with independent effects of PNMS on perinatal and postnatal outcomes. Intervention studies and large population-based cohort studies combining repeated multi-dimensional and standardised PNMS measurements with biomarkers of stress are needed to further understand PNMS aetiology and pathophysiology in human populations.
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                Author and article information

                Journal
                Front Psychol
                Front. Psychology
                Frontiers in Psychology
                Frontiers Research Foundation
                1664-1078
                16 October 2010
                19 January 2011
                2010
                : 1
                : 223
                Affiliations
                [1] 1simpleDepartment of Psychological Sciences, Centre for Brain and Cognitive Development, Birkbeck, University of London London, UK
                [2] 2simpleSchool of Women's and Infants’ Health, University of Western Australia Perth, WA, Australia
                [3] 3simpleTelethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia Perth, WA, Australia
                Author notes

                Edited by: Frederic Dick, University of California San Diego, USA

                Reviewed by: Frances Rice, University College London, UK; Angela Michelle Reiersen, Washington University School of Medicine, USA

                *Correspondence: Angelica Ronald, Department of Psychological Sciences, Centre for Brain and Cognitive Development, Birkbeck, Malet Street, London WC1E 7HX, UK. e-mail: a.ronald@ 123456bbk.ac.uk

                This article was submitted to Frontiers in Developmental Psychology, a specialty of Frontiers in Psychology.

                Article
                10.3389/fpsyg.2010.00223
                3153828
                21833278
                5debc4cc-c07e-4066-9f30-dd1b987c96d7
                Copyright © 2011 Ronald, Pennell and Whitehouse.

                This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 28 September 2010
                : 25 November 2010
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 43, Pages: 8, Words: 7114
                Categories
                Psychology
                Original Research

                Clinical Psychology & Psychiatry
                autism,stress,adhd,autistic traits,raine study,prenatal
                Clinical Psychology & Psychiatry
                autism, stress, adhd, autistic traits, raine study, prenatal

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