Effects of fetal growth restriction on lung development before and after birth: a morphometric analysis

Our aim was to determine the effects of fetal growth restriction (FGR) during late gestation on the structure of the lungs in the fetus near term and at 8 weeks after birth. The studies were performed using two groups of pregnant sheep and their offspring. In both groups, FGR was induced by umbilico-placental embolisation (UPE); for fetal studies, UPE was performed from 120 days of gestation until 140 days (term, approximately 146 days), when fetuses were killed for tissue analysis. For postnatal studies, UPE continued from 120 days until delivery at term; postnatal lambs were killed at 8 weeks after birth for tissue analysis. UPE led to a thicker pulmonary blood-air barrier at 140 days of gestation and this difference, which was due to a thickened basement membrane, was still present at 8 weeks after birth. At 8 weeks, we also observed a smaller number of alveoli per respiratory unit, thicker interalveolar septa, and a greater volume density of lung tissue in FGR lambs compared to controls. These changes would be expected to impair gas exchange and alter the mechanical properties of the lungs. Our data show that structural alterations in the lungs induced by placental insufficiency were more evident at 8 weeks of postnatal age than near term, indicating that the effects of FGR on the lung may become more serious with age and may affect respiratory health later in life.