Atrial septal defect closure is associated with improved clinical status in patients ≤ 10 kg with bronchopulmonary dysplasia

Abstract

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post-ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD-ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD-ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre- to 8 weeks post-intervention, and pre- and post-intervention score slopes were created. These slopes were compared using mixed regression modeling with an interaction term. There was a significant difference in pre- versus post-intervention slope with the most score drop the first week post-intervention (-2.1 + /- 0.8, p = 0.014). The mean score also dropped through weeks 2 (slope -0.8 + /- 0.8, p = 0.013) and 4 (slope -1.0 + /- 0.5, p = 0.001) post-intervention. There was a significant difference in pre- and post-intervention slopes for diuretics (p = 0.018) and the combined score of respiratory support, FiO₂ need, and respiratory symptoms (p = 0.018). This study demonstrated significant improvement in BPD-ASD score, diuretic need, and respiratory status after ASD closure in BPD-ASD patients ≤ 10 kg that was outside of the natural course of BPD. Our study was limited by its small, single-center, retrospective nature. Future studies should be performed in a larger multicenter population to both validate the scoring system and compare to non-intervention infants.

Keywords: neonatal lung disease & BPD; pediatrics; pulmonary hypertension.

Figure 1

(a) Spaghetti plot showing each individual bronchopulmonary dysplasia (BPD)‐atrial septal defect (ASD) score over time with time “0” marking the intervention, and scores 8 weeks before and 8 weeks after the intervention. (b) A simplified graph, with the only breakpoint at intervention, to allow the analysis of aggregate slopes with 95% confidence limits (regression lines) before and after intervention. This shows that while the pre‐intervention slope was no different than 0, the score post‐intervention was significantly decreasing, and the pre‐ and post‐intervention slopes were significantly different than each other. (c) Graph with slopes and 95% confidence limits before and after intervention, with additional division of time periods post‐intervention to evaluate the speed of change in relationship to intervention timing. Before intervention, the BPD‐ASD score was stable with no change over time. The week after the intervention the score drops an average of 2.2 ± 0.8 points, which is a significant slope change (p = 0.014). The mean score continues to significantly drop through weeks 2 and 4 post‐intervention. After week 4, there is no longer a significant drop in score. *p < 0.05.

Figure 2

Stacked area graphs for each subcomponent of the bronchopulmonary dysplasia (BPD)‐atrial septal defect (ASD) score, showing by shade the proportion of subjects with each subcomponent score. (a) The proportion of patients with high diuretic scores decreases after the intervention. (b) Respiratory score, which is a combination score consisting of the FiO₂ need, respiratory support, and respiratory symptoms scores. After the intervention, the majority of the patients had a lower score than before the intervention. (c) Growth score, showing no difference in improvement of growth pre‐ and post‐intervention. (d) Estimated right ventricular (RV) pressure, which shows that after the intervention the majority of patients ultimately had a normal RV pressure.

Figure 3

Regression analysis with 95% interval lines fit for each subcomponent of the bronchopulmonary dysplasia (BPD)‐atrial septal defect (ASD) scoring system was performed with the only breakpoint at the time of intervention. (a) The pre‐intervention diuretic score was not significantly different than a slope of 0. The post‐intervention diuretic score slope was significantly different than a slope of 0 (decreasing) and the post‐intervention score slope was significantly different than the pre‐intervention diuretic score slope (p = 0.018). (b) Respiratory score consisted of the total points assigned for FiO₂ need, respiratory symptoms, and respiratory support. The pre‐intervention respiratory score slope was not significantly different than 0. The post‐intervention respiratory score slope was significantly different than 0 (decreasing) and the post‐intervention score slope was significantly different than the pre‐intervention respiratory score slope. (c) The growth score slope was significantly different than 0 (decreasing) for both pre‐ and post‐intervention and there was no significant difference between slope 1 and slope 2. (d) The pre‐intervention estimated RV pressure score slope was no different than 0, but the post‐intervention estimated RV pressure score was significantly different than 0, indicating a significant decrease in estimated RV pressure score. However, there was no difference between pre‐ and post‐intervention slopes. *p ≤ 0.05.