Compromised respiratory function in postnatal lambs after placental insufficiency and intrauterine growth restriction

Epidemiologic studies have shown persistent effects of low birth weight on respiratory function and lung health, but underlying mechanisms are not und erstood. Our aim was to determine the effects of intrauterine growth restri ction (IUGR), a major cause of low birth weight, on postnatal respiratory f unction. IUGR was induced by umbilico-placental embolization during late ge station in chronically catheterized sheep. Umbilico-placental embolization was performed between 120 d of gestation and term (similar to 146 d) during which fetuses were hypoxemic and hypoglycemic relative to controls. Umbili co-placental embolization led to a 48% reduction in birth weight compared w ith controls, and throughout the postnatal study period IUGR lambs (n = 8) remained lighter than controls (n = 8). Respiratory function was repeatedly studied in lambs for 8 wk after birth; during this period, IUGR lambs were mildly hypoxemic and tended to be hypercapnic compared with controls. In I UGR lambs, relative to controls, O-2 consumption (mL/min/kg) and minute ven tilation (mL/kg) were increased and pulmonary diffusing capacity (adjusted for functional residual capacity) was decreased. Functional residual capaci ty, measured by helium dilution, and total lung capacity (measured at 30 cm H2O) Were smaller in IUGR lambs than in controls. When adjusted for functi onal residual capacity, static lung compliance was reduced and chest wall c ompliance was increased in IUGR lambs. At 8 wk, pulmonary DNA and protein c oncentrations were decreased in IUGR lambs relative to controls. We conclud e that restriction of fetal growth by placental insufficiency induces alter ations in the lungs and chest wall that result in persistent impairments in respiratory function during early postnatal life.