Pulmonary function and structure following mild preterm birth in lambs

Abstract

Our objective was to determine whether postnatal respiratory function, lung growth, and lung structure are affected by preterm birth which did not require neonatal respiratory support. Two groups of preterm (P) lambs were delivered 2 weeks before term, at 133 days of gestational age (GA). Tissue was collected at term equivalent age (TEA, 147 days GA) in one P group and at 6 weeks post-TEA in the other. Tissue was also collected from control (C) lambs soon after term birth (TEA) and at 6 weeks post-TEA. Lung function was assessed at TEA and 6 weeks post-TEA. Respiratory system compliance (Crs/kg BWT) was not different between P and C groups at TEA, but was higher (P = 0.02) in P lambs at 6 weeks post-TEA. Pulmonary resistance was 62% higher in P lambs than controls (P = 0.07) at TEA, and remained higher at 6 weeks post-TEA. Lung weights (wet and dry) were greater (P < 0.05) in preterm animals at both ages; when adjusted for body weight, only dry lung weight remained higher at 6 weeks post-TEA. Alveoli were more numerous (P = 0.05) and smaller (P = 0.05) in preterm lambs compared to controls at both ages. Alveolar septa were 33% thicker and the blood-air barrier was 26% thicker in P lambs than in controls at TEA, and remained thicker at 6 weeks post-TEA. In P lambs, the airway epithelium was thicker at TEA and 6 weeks post-TEA. At TEA, pulmonary tropoelastin expression was 27% lower in P lambs. At 6 weeks post-TEA, dry lung weight and lung protein content were approximately 50% greater in preterm lambs than in controls (P < 0.05), whereas lung DNA, elastin, and collagen contents were similar in the two groups. We conclude that mild preterm birth per se leads to both transient and persistent changes in lung development. Persistent increases in lung protein content and in the thickness of the airway epithelium, and a greater number of smaller alveolar, may alter later lung function.