Compromised Respiratory Function in Postnatal Lambs after Placental Insufficiency and Intrauterine Growth Restriction

Abstract

Epidemiologic studies have shown persistent effects of low birth weight on respiratory function and lung health, but underlying mechanisms are not understood. Our aim was to determine the effects of intrauterine growth restriction (IUGR), a major cause of low birth weight, on postnatal respiratory function. IUGR was induced by umbilico-placental embolization during late gestation in chronically catheterized sheep. Umbilicoplacental embolization was performed between 120 d of gestation and term (~146 d) during which fetuses were hypoxemic and hypoglycemic relative to controls. Umbilico-placental embolization led to a 48% reduction in birth weight compared with controls, and throughout the postnatal study period IUGR lambs (n ϭ 8) remained lighter than controls (n ϭ 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 IUGR lambs, relative to controls, O 2 consumption (mL/min/kg) and minute ventilation (mL/kg) were increased and pulmonary diffusing capacity (adjusted for functional residual capacity) was decreased. Functional residual capacity, measured by helium dilution, and total lung capacity (measured at 30 cm H 2 O) were smaller in IUGR lambs than in controls. When adjusted for functional residual capacity, static lung compliance was reduced and chest wall compliance was increased in IUGR lambs. Restricted fetal growth, resulting in low birth weight, has been associated with altered lung development and impaired respiratory function after birth. Recent studies of neonates and infants who have been growth restricted in utero indicate that they have an increased risk of mortality and morbidity (1), including respiratory distress (2, 3). Respiratory compromise may persist during postnatal development as it has been shown that children with evidence of growth restriction in utero have reduced forced expiratory flow rates (4, 5) indicative of impaired airway function. In addition, adults who were of low birth weight and, therefore, likely to have been growth restricted in utero, have reduced expiratory flow rates and an increased risk of respiratory morbidity and mortality (6, 7). Thus, a number of epidemiologic studies suggest that pulmonary gas exchange and airway function after birth may be affected by IUGR.Placental insufficiency and IUGR are common causes of low birth weight, and are associated with pregnancy-induced hypertension, maternal tobacco smoking, and placental pathology (8, 9). Fetuses identified as being growth restricted have been found to be hypoxemic, hypoglycemic, and to have elevated

Effect of Lung Hypoplasia on Birth-Related Changes in the Pulmonary Circulation in Sheep

“…After 3-5 d of fixation (for future histologic analysis), the right LV was determined using the Cavalieri method (22). Pulmonary DNA and soluble protein concentrations in lung tissue were determined using established fluorometric DNA and colorimetric protein assays (23).…”

Effect of Nω-Nitro-l-Arginine Methyl Ester–Induced Intrauterine Growth Restriction on Postnatal Lung Growth in Rats

“…uteroplacental embolization in pregnant ewes, caused impairments in bronchial growth (27) at birth and significantly reduced functional residual capacity, total lung capacity at 30 cm H 2 O, diffusing capacity of the lung for carbon monoxide, and compliance of the respiratory system from birth to 8 wk of postnatal age in lambs (28). Moreover, gas exchange surface area, oxygen uptake, and body weight are strongly correlated in mammals (29).…”

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

“…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).…”