title: Increased Bronchial Hyperresponsiveness and Higher Asymmetric Dimethylarginine Levels after Fetal Growth Restriction.
abstract: Bronchial hyperresponsiveness (BHR), a feature of asthma, is observed in preterm-born children and has been linked to intrauterine growth restriction. BHR is mediated via airway smooth muscle tone and is modulated by the autonomic nervous system, nitric oxide, and airway inflammation. Interactions among these factors are insufficiently understood. Methacholine-induced BHR (Met-BHR), fractional exhaled NO, and systemic soluble markers of nitric oxide metabolism and inflammation were determined in a population-based sample of 57 eleven-year-old children born extremely preterm (gestational age [GA] < 28 wk) or with extremely low birth weight (<1,000 g), and in a matched normal-birth weight term-born control group (n = 54). Bronchopulmonary dysplasia (BPD) was defined as the need for oxygen treatment at a GA of 36 weeks. In preterm-born children, birth weight below the 10th percentile for GA was associated with increased Met-BHR and higher plasma levels of asymmetric dimethylarginine (ADMA), with an increased odds ratio for being in the upper tertile of Met-BHR (11.8; 95% confidence interval, 3.3-42.4) and of ADMA (5.2; 95% confidence interval, 1.3-20.3). Met-BHR was correlated to ADMA level (r = 0.27, P = 0.007). There were no significant differences in Met-BHR, fractional exhaled NO, or z-FEV1according to BPD status. No associations with systemic soluble markers of inflammation were observed for Met-BHR, birth, or BPD status. Intrauterine growth restriction in preterm-born children was associated with substantially increased Met-BHR and higher ADMA levels, suggesting altered nitric oxide regulation. These findings contribute to the understanding of the consequences from an adverse fetal environment; they should also be tested in term-born children.
authors: 1 Laboratory of Clinical Biochemistry, and.
authors: Anne-Lise
authors: AL
authors: Bjørke-Monsen
authors: 2 Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors: Maria
authors: M
authors: Vollsæter
authors: 1 Laboratory of Clinical Biochemistry, and.|3 Bevital A/S, Bergen, Norway.
authors: Per M
authors: PM
authors: Ueland
authors: 4 Department of Clinical Science, University of Bergen, Bergen, Norway; and.
authors: Trond
authors: T
authors: Markestad
authors: 4 Department of Clinical Science, University of Bergen, Bergen, Norway; and.|5 Department of Pediatrics, Stavanger University Hospital, Stavanger, Norway.
authors: Knut
authors: K
authors: Øymar
authors: 2 Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.|4 Department of Clinical Science, University of Bergen, Bergen, Norway; and.
authors: Thomas
authors: T
authors: Halvorsen
mesh_terms: D000886:Anthropometry; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000097:blood* / Q000503:physiopathology; D002648:Child; D003710:Demography; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D047928:Premature Birth; D012129:Respiratory Function Tests; D012995:Solubility
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D016210:Methacholine Chloride; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: asymmetric dimethylarginine; bronchial hyperresponsiveness; intrauterine growth restriction; methacholine; nitric oxide