title: Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence.
abstract: Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans.
authors.affiliation: 1] Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] NIHR Southampton Respiratory Biomedical Research Unit [3].
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Pike
authors.affiliation: 1] Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [3].
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Davis
authors.affiliation: Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Collins
authors.affiliation: 1] Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] NIHR Southampton Respiratory Biomedical Research Unit.
authors.forename: Jane S A
authors.initials: JS
authors.lastname: Lucas
authors.affiliation: 1] Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Inskip
authors.affiliation: Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wilson
authors.affiliation: Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
authors.forename: Elin R
authors.initials: ER
authors.lastname: Thomas
authors.affiliation: Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
authors.forename: Harris A
authors.initials: HA
authors.lastname: Wain
authors.affiliation: Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
authors.forename: Piia H M
authors.initials: PH
authors.lastname: Keskiväli-Bond
authors.affiliation: 1] Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK [3] Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: 1] Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK [3] Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Godfrey
authors.affiliation: Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Torrens
authors.affiliation: 1] Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [3] NIHR Southampton Respiratory Biomedical Research Unit [4].
authors.forename: Graham
authors.initials: G
authors.lastname: Roberts
authors.affiliation: 1] Clinical and Experimental Sciences Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [2] Human Developmental and Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, UK [3].
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D018753:Diet, Protein-Restricted; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
chemical_list: D016085:Bronchoconstrictor Agents
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