Related Experiment Video
Updated: Mar 29, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs
Beth J Allison1, Stuart B Hooper2, Elise Coia3
1The 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.
Insights
Intrauterine growth restriction (IUGR) does not alter lung structure or response to ventilation in preterm lambs. This suggests other factors contribute to increased respiratory issues in IUGR infants.
Area of Science:
- Neonatal Physiology
- Fetal Development
- Respiratory Medicine
Background:
- Intrauterine growth restriction (IUGR) and preterm birth are linked to increased respiratory morbidity.
- Potential causes include altered fetal lung development, inflammation, or ventilation injury.
- Understanding these factors is crucial for improving outcomes in affected infants.
Purpose of the Study:
- To investigate whether IUGR impacts fetal lung development and alters the response to early postnatal ventilation.
- To compare lung inflammation, injury markers, and structural changes in IUGR versus appropriately grown (AG) preterm lambs.
- To assess ventilator requirements and physiological responses in IUGR preterm lambs.
Main Methods:
- Surgically induced IUGR in preterm sheep (0.7 gestation) via umbilical artery ligation.
- Preterm lambs were studied at delivery or after 2 hours of ventilation.
- Analyses included lung inflammation, injury markers, gene expression, surfactant composition, and lung morphology.
Main Results:
- IUGR lambs exhibited reduced body weight and increased brain-to-body weight ratio (brain sparing).
- No significant differences in lung inflammation, injury, or structural changes were found between IUGR and AG lambs.
- Both groups showed similar oxygenation, respiratory needs, and inflammatory responses post-ventilation.
Conclusions:
- IUGR does not induce pulmonary structural changes or alter the immediate response to ventilation in this ovine model.
- The increased respiratory morbidity in IUGR infants is likely not due to altered lung tissue or vascular structure.
- Further research is needed to identify the specific mechanisms driving respiratory complications in IUGR.
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.
