title: Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs.
abstract: Intrauterine growth restriction (IUGR) and preterm birth are frequent comorbidities and, combined, increase the risk of adverse respiratory outcomes compared with that in appropriately grown (AG) infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared with AG infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements, and/or increased ventilation-induced lung injury. IUGR was surgically induced in preterm fetal sheep (0.7 gestation) by ligation of a single umbilical artery. Four weeks later, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Ventilator requirements, lung inflammation, early markers of lung injury, and morphological changes in lung parenchymal and vascular structure and surfactant composition were analyzed. IUGR preterm lambs weighed 30% less than AG preterm lambs, with increased brain-to-body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared with AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth and had significant, but similar, increases in proinflammatory cytokine expression, lung injury markers, gene expression, and surfactant phosphatidylcholine species compared with unventilated controls. IUGR does not induce pulmonary structural changes in our model. Furthermore, IUGR and AG preterm lambs have similar ventilator requirements in the immediate postnatal period. This study suggests that increased morbidity and mortality in IUGR infants is not due to altered lung tissue or vascular structure, or to an altered response to early ventilation.
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia; beth.allison@hudson.org.au.
authors.forename: Beth J
authors.identifier: http://orcid.org/0000-0002-1060-513X
authors.initials: BJ
authors.lastname: Allison
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia;
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Hooper
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia;
authors.forename: Elise
authors.initials: E
authors.lastname: Coia
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia;
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Zahra
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia;
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Monash Newborn, Monash Medical Centre, and Department of Pediatrics, Monash University, Melbourne, Victoria, Australia;
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Monash Newborn, Monash Medical Centre, and Department of Pediatrics, Monash University, Melbourne, Victoria, Australia;
authors.forename: Arvind
authors.initials: A
authors.lastname: Sehgal
authors.affiliation: Department of Neonatology, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia;
authors.forename: Martin
authors.initials: M
authors.lastname: Kluckow
authors.affiliation: Centre for Neonatal Research and Education, The University of Western Australia, Western Australia, Australia; and.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Gill
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Foula
authors.initials: F
authors.lastname: Sozo
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia;
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Miller
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia;
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005865:Gestational Age; D008168:Lung / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism*; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012121:Respiration, Artificial / Q000009:adverse effects; D012756:Sheep; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism*
chemical_list: D011663:Pulmonary Surfactants
keywords: IUGR; SGA; lung inflammation; lung injury