Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

Intrauterine growth restriction (IUGR) and preterm birth are frequent co-morbidities and, combined, increase the risk of adverse respiratory outcomes compared to that in appropriately grown infants. Potential underlying reasons for this increased respiratory morbidity in IUGR infants compared to appropriately grown infants include altered fetal lung development, fetal lung inflammation, increased respiratory requirements and/or increased ventilation induced lung injury Methods: 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 hours 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. RESULTS: IUGR preterm lambs weighed 30 less than appropriately grown (AG) preterm lambs, with increased brain:body weight ratio, indicating brain sparing. IUGR did not induce lung inflammation or injury or alter lung parenchymal and vascular structure compared to AG fetuses. IUGR and AG lambs had similar oxygenation and respiratory requirements after birth, and had significant, but similar, increases in pro-inflammatory cytokine expression, lung injury markers gene expression and surfactant phosphatidylcholine species compared to unventilated controls. CONCLUSION: 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.