Restricted fetal growth and lung development: a morphometric analysis of pulmonary structure

Intrauterine growth restriction (IUGR) in humans increases the risk of lung disease and impaired function suggesting that adverse intra-uterine conditions can alter lung development. We hypothesized that placental restriction (PR) of fetal growth would alter lung structure in late gestation. PR involved removal of implantation sites in pre-pregnant ewes. Normal (n = 7) and PR (n = 11) fetuses were delivered at day 140 gestation. Lungs were fixed by tracheal infusion, processed and analyzed by morphometry. PR reduced ponderal index (PI) of lambs by 13%, increased lung volume:body weight (BW) (19%), and decreased the proportion of lung volume that comprised parenchyma from 86.5(2.6)% to 76.7(2.1)% with no change in absolute volume of non-parenchyma. Within the parenchyma, PR increased the proportion comprising airspace from 42.0(2.2)% to 55.5(1.7)% with smaller (-13%) more dense (18%) airsacs/alveoli present. The overall effect was a reduction in total gas-exchange surface density (-10%). Lung wet-weight and volume, parenchymal volume, gas-exchange tissue, and airspace volumes and gas-exchange surface area correlated positively with BW and crown-rump length (CRL) for all animals. The relative lung weight and volume correlated negatively with BW, CRL, and lung weight:BW with PI. Lung weight, lung volume, parenchymal volume, airspace perimeter, percent of parenchymal gas-exchange tissue, gas-exchange surface density, and area correlated positively with PI. The results indicate increased sparing of lung growth but with increasing structural changes, predominantly within lung parenchyma, with increasing growth restriction. Structural alterations associated with PR and poor fetal growth may be important in the pathogenesis of impaired lung function associated with IUGR.