The compromised intra-uterine environment: Implications for future lung health

1. Epidemiological studies of infants, children and adults indicate that pr enatal compromises that restrict fetal growth and cause low birthweight inc rease the risk of respiratory deficiencies after birth. 2. It is apparent that the lung has a limited ability to recover from early developmental compromises and that altered development can permanently imp air lung architecture. 3. Lung development in utero can be adversely affected by factors associate d with fetal growth restriction, namely fetal hypoxaemia, reduced substrate supply and hypercortisolaemia. 4. We have conducted a series of studies of respiratory development in chro nically catheterized ovine fetuses and postnatal lambs in which growth rest riction was induced during late gestation by embolizing the umbilico-placen tal vascular bed, a technique that replicates key aspects of human placenta l insufficiency. 5. During late gestation, restricting the growth of the ovine fetus did not alter lung weight or lung liquid secretion or volume when each factor was related to bodyweight, but it did lead to increased lung DNA concentrations and an increased thickness of the air-blood barrier. Expression of pulmona ry surfactant proteins A, B and C were not altered and, hence, it was unlik ely that surfactant protein synthesis had been impaired by growth restricti on. 6. When growth restriction continued to term, lambs were born with a low bi rthweight and remained small compared with controls for 8 weeks after birth . Low-birthweight lambs were mildy hypoxaemic and compliances of their lung s and chest wall were, respectively, decreased and increased relative to co ntrols. Pulmonary surfactant proteins A, B and C were not deficient, indica ting that decreased lung compliance most likely had a structural basis. 7. Morphometric analysis of lungs at 8 weeks after birth indicated that low -birthweight lambs had increased alveolar wall thicknesses, less 'air-space ' and thicker blood-air barriers. These properties would be expected to res trict pulmonary gas exchange and decrease pulmonary compliance. 8. We conclude that growth restriction during early development can have la sting adverse effects on the lungs and chest wall and that these may be suf ficient to affect respiratory function throughout later life as well as adv ancing ageing of the lungs.