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      Exposure to adversity and inflammatory outcomes in mid and late childhood

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          Abstract

          Background

          We aimed to estimate the association between exposure to adversity and inflammatory markers in mid (4 years) and late (11–12 years) childhood, and whether effects differ by type and timing of exposure.

          Methods

          Data sources: Barwon Infant Study (BIS; N = 510 analyzed) and Longitudinal Study of Australian Children (LSAC; N = 1156 analyzed). Exposures: Adversity indicators assessed from 0 to 4 (BIS) and 0–11 years (LSAC): parent legal problems, mental illness and substance abuse, anger in parenting responses, separation/divorce, unsafe neighborhood, and family member death; a count of adversities; and, in LSAC only, early (0–3), middle (4–7), or later (10–11) initial exposure. Outcomes: Inflammation quantified by high sensitivity C-reactive protein (hsCRP, Log (ug/ml)) and glycoprotein acetyls (GlycA, Log (umol/L)). Analyses: Linear regression was used to estimate relative change in inflammatory markers, adjusted for sociodemographic characteristics, with exposure to adversity. Outcomes were log-transformed.

          Results

          Evidence of an association between adversity and hsCRP was weak and inconsistent (e.g., 3+ versus no adversity: BIS: 12% higher, 95%CI -49.4, 147.8; LSAC 4.6% lower, 95%CI: −36.6, 48.3). A small positive association between adversity and GlycA levels was observed at both 4 years (e.g., 3+ versus no adversity: 3.3% higher, 95%CI -3.0, 9.9) and 11–12 years (3.2% higher, 95%CI 0.8, 5.8). In LSAC, we did not find evidence that inflammatory outcomes differed by initial timing of adversity exposure.

          Conclusions

          Small positive associations between adversity and inflammation were consistently observed for GlycA, across two cohorts with differing ages. Further work is needed to understand mechanisms, clinical relevance, and to identify opportunities for early intervention.

          Highlights

          • Greater exposure to adversity was associated with small increases in inflammation as measured by GlycA at 4 and 11 years.

          • Associations differed by adversity type, but not by timing of initial exposure.

          • Further work is needed to understand the clinical relevance of these findings.

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          Most cited references42

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          Multiple imputation using chained equations: Issues and guidance for practice

          Multiple imputation by chained equations is a flexible and practical approach to handling missing data. We describe the principles of the method and show how to impute categorical and quantitative variables, including skewed variables. We give guidance on how to specify the imputation model and how many imputations are needed. We describe the practical analysis of multiply imputed data, including model building and model checking. We stress the limitations of the method and discuss the possible pitfalls. We illustrate the ideas using a data set in mental health, giving Stata code fragments. 2010 John Wiley & Sons, Ltd.
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            Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study.

            The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described. A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0-7) and risk factors for the leading causes of death in adult life. More than half of respondents reported at least one, and one-fourth reported > or = 2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P or = 50 sexual intercourse partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life. We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.
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              The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

              A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done.
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                Author and article information

                Contributors
                Journal
                Brain Behav Immun Health
                Brain Behav Immun Health
                Brain, Behavior, & Immunity - Health
                Elsevier
                2666-3546
                28 September 2020
                December 2020
                28 September 2020
                : 9
                : 100146
                Affiliations
                [k ]Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
                [l ]Murdoch Children's Research Institute, Melbourne, Australia
                [m ]Department of Paediatrics, The University of Melbourne, Melbourne, Australia
                [n ]Faculty of Health, School of Medicine, Deakin University, Australia
                [a ]Murdoch Children's Research Institute, Melbourne, Australia
                [b ]Department of Paediatrics, The University of Melbourne, Melbourne, Australia
                [c ]The Florey Institute of Neuroscience and Mental Health, Australia
                [d ]Melbourne School of Population and Global Health, The University of Melbourne, Australia
                [e ]University Hospital, Geelong, Barwon Health, Australia
                [f ]Faculty of Health, School of Medicine, Deakin University, Australia
                [g ]Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Queensland, Australia
                [h ]Global Adolescent Health Group, Burnet Institute, Australia
                [i ]Wardliparingga Aboriginal Research Unit, South Australian Health and Medical Research Institute, Australia
                [j ]ANU College of Arts & Social Sciences, Australian National University, Canberra, Australia
                [k ]Centre for Social and Emotional Development, School of Psychology, Deakin University, Burwood, Victoria
                Author notes
                []Corresponding author. The Australian National University, Canberra, ACT, 2600, Australia. naomi.priest@ 123456anu.edu.au
                Article
                S2666-3546(20)30111-3 100146
                10.1016/j.bbih.2020.100146
                8474172
                34589892
                df286842-4d71-4af5-af83-4f3746f0ae7c
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 August 2020
                : 16 September 2020
                Categories
                Full Length Article

                adversity,inflammation,multi-cohort,longitudinal
                adversity, inflammation, multi-cohort, longitudinal

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