Evidence establishing a link between prenatal and early-life stress and asthma development

Purpose of review The objective of this review is to provide an update on our evolving understanding of the effects of stress in pregnancy and during early development on the onset of asthma-related phenotypes across childhood, adolescence, and into early adulthood. Recent findings Accumulating evidence over the past 2 decades has established that prenatal and early-life psychological stress and stress correlates (e.g., maternal anxiety or depression) increase the risk for childhood respiratory disorders. Recent systematic reviews and meta-analyses including numerous prospective epidemiological and case–control studies substantiate a significant effect of prenatal stress and stress in early childhood on the development of wheeze, asthma, and other atopic-related disorders (eczema and allergic rhinitis), with many studies showing an exposure–response relationship. Offspring of both sexes are susceptible to perinatal stress, but effects differ. The impact of stress on child wheeze/asthma can also be modified by exposure timing. Moreover, coexposure to prenatal stress can enhance the effect of chemical stressors, such as prenatal traffic-related air pollution, on childhood respiratory disease risk. Understanding complex interactions among exposure dose, timing, child sex, and concurrent environmental exposures promises to more fully characterize stress effects and identify susceptible subgroups. Although the link between perinatal stress and childhood asthma-related phenotypes is now well established, pathways by which stress predisposes children to chronic respiratory disorders are not as well delineated. Mechanisms central to the pathophysiology of wheeze/asthma and lung growth and development overlap and involve a cascade of events that include disrupted immune, neuroendocrine, and autonomic function as well as oxidative stress. Altered homeostatic functioning of these integrated systems during development can enhance vulnerability to asthma and altered lung development. Summary Mechanistic studies that more comprehensively assess biomarkers reflecting alterations across interrelated stress response systems and associated regulatory processes, in both pregnant women and young children, could be highly informative. Leveraging high-throughput systems-wide technologies to include epigenomics (e.g., DNA methylation, microRNAs), transcriptomics, and microbiomics as well as integrated multiomics are needed to advance this field of science. Understanding stress-induced physiological changes occurring during vulnerable life periods that contribute to chronic respiratory disease risk could lead to the development of preventive strategies and novel therapeutic interventions. Correspondence to Rosalind J. Wright, MD, MPH, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1198, New York, NY 10029, USA. Tel: +1 212 241 5287; fax: +1 212 289 8569; e-mail: rosalind.wright@mssm.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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