title: Prenatal Stress, Prematurity, and Asthma.
abstract: Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health.
authors.affiliation: Fellow, Division of Newborn Medicine.
authors.forename: Brock
authors.initials: B
authors.lastname: Medsker
authors.affiliation: Assistant Professor of Pediatrics, Division of Pulmonary Medicine, Allergy and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC.
authors.forename: Erick
authors.initials: E
authors.lastname: Forno
authors.affiliation: Associate Professor of Obstetrics, Gynecology and Reproductive Sciences, and Chief, Division of Maternal-Fetal Medicine, Magee Women's Hospital, Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA.
authors.forename: Hyagriv
authors.initials: H
authors.lastname: Simhan
authors.affiliation: Niels K. Jerne Professor of Pediatrics and Chief, Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Celedón
mesh_terms: D001249:Asthma / Q000209:etiology* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D010913:Pituitary-Adrenal System; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology*
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid