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

Abstract

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.

The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development

“…Despite increased cortisol concentrations, 1 wk of SUAL-induced IUGR alone did not alter fetal lung morphology. This is supported by a previous study in sheep in which umbilicoplacental embolization was used to induce IUGR (10). Following 20 d of umbilicoplacental embolization, tissue density and alveolar size and number were unaffected.…”

“…Following 20 d of umbilicoplacental embolization, tissue density and alveolar size and number were unaffected. However when these animals were studied postnatally, tissue density was increased at 8 wk of age whereas at 2 years of age the IUGR lung had fewer, larger alveoli (10,11). This suggests that while no structural changes are present in fetal tissue, experimental IUGR may induce morphological changes later in life.…”

“…In experimental studies, structural changes in the IUGR fetal lung have been reported that may underlie impaired lung function. For example, studies in sheep have found that IUGR results in fewer, larger alveoli with thicker alveolar septa, and therefore impaired blood-gas exchange, which persists into adulthood (10,11). Functionally, these structural lung effects in IUGR sheep are reflected by reduced lung compliance and increased chest wall compliance in sheep-changes that may compromise respiratory function (12).…”

Influence of Intrauterine Growth Restriction on Airway Development in Fetal and Postnatal Sheep

“…Thus, the degree of structural recovery may have been greater than that observed by comparing airways of 140-d-old fetuses and 8-wk-old animals. Although there were no differences between treatment groups in airway morphometry at 8 wk, our other studies in lambs subjected to IUGR have shown that persistent changes were present in aspects of lung function (13) and alveolar structure (12). It is possible that such alterations could account for some of the detrimental effects of IUGR on respiratory function reported in epidemiologic studies.…”

“…Despite evidence that restriction of fetal growth impacts upon lung development (12,13), there have been few studies on the effects of growth restriction on airway development. One study examined the tracheal structure of fetal sheep after restriction of fetal growth induced by the restriction of placental growth (14).…”