Oligohydramnios-Induced Lung Hypoplasia: The Influence of Timing and Duration in Gestation

Abstract
We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45,δ of −0.047 mg, p = 0.004; period B, days 45 to 50, δ of −0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, δ of —0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, δ of −0.072 mg, p = 0.001; period E, days 45 to 55, 5 of −0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level). A two-way analysis of variance indicated that the magnitude of the changes was related to both the time of onset and the duration of oligohydramnios. We conclude that even a short period of oligohydramnios interferes with lung development, and that the extent of this interference depends to a large extent on the time of onset and to a lesser extent on the duration of oligohydramnios. Irrespective of duration, the greatest effects were observed during the canalicular stage of lung development.