Single-Course Antenatal Betamethasone Alters Lung Morphometry in Late Preterm Lambs.
Sushma Krishna MD1, Shetal I. Shah MD1, Sylvia Gugino MA2, Satyan Lakshminrusimha MD2
- Department of Pediatrics, Division of Neonatology, Stony Brook Long Island Children’s Hospital
- Department of Pediatrics, Division of Neonatology, State University of New York at Buffalo
Background: Late preterm infants (34 0/7-36 6/7 weeks) exhibit significant rates of respiratory distress syndrome, but the use of antenatal steroids at these gestations has not been fully evaluated. The purpose of this study is to determine the effect of antenatal betamethasone on lung histology in the late preterm fetal lamb.
Methods: Time-dated pregnant ewes were injected with betamethasone (15mg/day) or placebo on day of life (DOL) 132 & 133 (term -147 days) (N=12 each). C-section was performed on DOL 134. Lungs from 6 lambs from each group were harvested prior to first breath. Six remaining lambs were ventilated for 6 hours. Harvested lungs were fixed-inflated and morphometric assessments were performed blind on 7mm cross sections stained with Hematoxylin-eosin. A linear 56-point-counting grid was superimposed onto each digitized image. Air space, alveolar tissue, parenchyma, air-tissue intercepts, sampled radial alveolar count, number of alveoli-per-linear field, and mean alveolar width were counted. Alveolar density and total alveolar surface area were calculated. Full-term, day-old newborn lambs were studied for comparison. One-way ANOVA testing with Bonferroni correction was used in analysis.
Results: Both full-term and steroid-treated lambs exhibited lower radial alveolar counts and decreased alveoli-per-linear field measurements compared to control (p<0.001, p<0.01 respectively). Mean alveolar width was increased in steroid-treated animals compared to controls (p<0.05) but reduced as compared to full term sheep (p<0.001). Total alveolar surface area was significantly increased in the full term sheep compared to either the control or steroid-treated groups (p<0.001 for both). No differences in the percentage of air space, parenchyma, vascularity, air space/parenchyma ratio, alveolar density or alveolar surface area were observed.
Conclusions: Exposure to antenatal betamethasone in the late-preterm period increases the size, but reduces the number of alveoli, resulting in the same percentage of air space and unchanged alveolar surface area. We speculate the improvement in short-term lung function seen in steroid-treated animals is not associated with major structural changes in the lung.