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      Early-Life Adversity Due to Bereavement and Inflammatory Diseases in the Next Generation: A Population Study in Transgenerational Stress Exposure

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          Abstract

          Emerging evidence suggests that trauma experienced in childhood has negative transgenerational implications for offspring mental and physical health. We aimed to investigate whether early-life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included 3 generations of Swedish families with a base population of 453,516 children (generation 3) born in 2001–2012. Exposure was defined as the middle generation’s (generation 2) experiencing bereavement in childhood due to the death of a parent (generation 1). Outcomes in generation 3 included 2 diagnoses of inflammatory diseases, including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways, including investigation of mediation by generation 2 mood disorders and socioeconomic status (SES). We found that early-life bereavement experienced by women was associated with early-onset offspring asthma (hazard ratio = 1.15, 95% confidence interval: 1.08, 1.23); mediation analysis revealed that 28%–33% of the association may be mediated by SES and 9%–20% by mood disorders. Early-life bereavement experienced by men was associated with autoimmune diseases in offspring (hazard ratio = 1.31, 95% confidence interval: 1.06, 1.62), with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk of inflammatory diseases which is partly mediated by mood disorders and SES.

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          Most cited references44

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          Sensitivity Analysis in Observational Research: Introducing the E-Value.

          Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
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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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              Effect of in utero and early-life conditions on adult health and disease.

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                Author and article information

                Journal
                Am J Epidemiol
                Am J Epidemiol
                aje
                American Journal of Epidemiology
                Oxford University Press
                0002-9262
                1476-6256
                January 2022
                22 September 2021
                22 September 2021
                : 191
                : 1
                : 38-48
                Author notes
                Correspondence to Dr. Bronwyn K. Brew, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 12a Nobels vag, Solna, 171 77, Stockholm, Sweden (e-mail: bronwyn.haasdyk.brew@ 123456ki.se ).
                Article
                kwab236
                10.1093/aje/kwab236
                8751780
                34550338
                ff812486-229f-4817-afff-6956d5b6b244
                © The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 25 July 2020
                : 25 August 2021
                : 17 September 2021
                Page count
                Pages: 11
                Categories
                AcademicSubjects/MED00860
                Original Contribution

                Public health
                adverse childhood experiences,allergy,asthma,bereavement,inflammatory disease,transgenerational stress

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