Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep

OBJECTIVE: The aim of this study was to determine the effects of intrauterine growth restriction on fetal lung liquid and lung development. STUDY DESIGN: Intrauterine growth restriction was induced in 7 fetal sheep from 120 to 140 days' gestation (term, approximately 147 days' gestation) by umbilicoplacental embolization. We used 6 control fetuses. Volumes and production rates of fetal lung liquid were measured, and lungs were removed post mortem (140 days' gestation) for analysis of concentrations of deoxyribonucleic acid, protein, and messenger ribonucleic acid for surfactant proteins A, B, and C. RESULTS: Umbilicoplacental embolization induced fetal hypoxemia, hypoglycemia, and intrauterine growth restriction. At 140 days' gestation lung weight was reduced by 34%, and the fetal lung liquid production rate (15.9 +/- 1.8 mL/h for intrauterine growth restriction vs 24.8 +/- 3.9 mL/h for control) and volume (110.9 +/- 16.3 mt for intrauterine growth restriction vs 178.1 +/- 11.9 mt for control) were reduced in the intrauterine growth restriction group. After adjustment for body weight, however, values were not different from those in the control group. Pulmonary deoxyribonucleic acid and plasma cortisol concentrations were elevated by intrauterine growth restriction, but levels of messenger ribonucleic acid for surfactant proteins were unchanged. CONCLUSION: In intrauterine growth restriction, lung liquid and lung growth were proportionate to body weight, and surfactant protein expression was unaffected. Alterations in lung deoxyribonucleic acid concentrations suggest that the lungs may be structurally immature.