Pulmonary vasculature development in congenital diaphragmatic hernia: a novel automated quantitative imaging analysis.

PURPOSE: Impaired fetal lung vasculature determines the degree of pulmonary hypertension in the congenital diaphragmatic hernia (CDH). This study aims to demonstrate the morphometric measurements that differ in pulmonary vessels of fetuses with CDH. METHODS: Nitrofen-induced CDH Sprague-Dawley rat fetuses were scanned with microcomputed tomography. The analysis of the pulmonary vascular tree was performed with artificial intelligence. RESULTS: The number of segments in CDH was significantly lower than that in the control group on the left (U = 2.5, p = 0.004) and right (U = 0, p = 0.001) sides for order 1(O1), whereas there was a significant difference only on the right side for O2 and O3. The pooled element numbers in the control group obeyed Horton's law (R2 = 0.996 left and R2 = 0.811 right lungs), while the CDH group broke it. Connectivity matrices showed that the average number of elements of O1 springing from elements of O1 on the left side and the number of elements of O1 springing from elements of O3 on the right side were significantly lower in CDH samples. CONCLUSION: According to these findings, CDH not only reduced the amount of small order elements, but also destroyed the fractal structure of the pulmonary arterial trees.

The Survivorship Bias in Congenital Diaphragmatic Hernia.

Current literature for congenital diaphragmatic hernia (CDH) focuses on the comparison of the overall mortality in CDH patients. Only a few studies concentrate on analyzing the unstable patients who could not achieve surgical repair, as well as those who could but did not survive after. Hence, this study aimed to analyze the effects of various parameters on the timing of death. A retrospective analysis was performed by using the data of all CDH patients from 2003 to 2016 at a single tertiary center. Patients who were diagnosed with left-sided CDH and expired were included in the study regardless of the cause. Of the 66 expired patients, 5 were excluded due to right-sided CDH. The study population constituted a total of 61 patients, of which 31 patients expired prior to CDH repair, and 30 patients expired at different times after CDH repair. Multinomial regression analysis identified that the ECMO need (B = 20.257, p = 0.000, OR: 62.756, 95% CI 10.600-371.384) and O/E LHR (B = 20.376, p = 0.000, OR: 70.663, 95% CI 48.716-102.415) values were the independent predictors that influenced mortality in this cohort. Prenatal pulmonary measurements are the major predictors determining the severity of the disease in patients with CDH.

Reversible Fetal Tracheal Occlusion in Mice: A Novel Minimal Invasive Technique.

BACKGROUND: There is a certain need for reversible, cheap, and reproducible animal models for understanding the impact of tracheal occlusion (TO) in the congenital diaphragmatic hernia and pathophysiology. We aimed to present an easy, reversible, and minimally invasive murine TO model with optimized time points for introduction and removal of TO. METHODS: Time-mated C57BL/6 mice underwent laparotomy at embryonic day 16.5 (E16.5) with transuterine TO performed on two fetuses in each uterine horn. In the TO group, the fetuses were harvested at E18.5 without suture removal; the suture was released at E17.5 in the TO-R group, and all fetuses were harvested at E18.5. The lungs of the fetuses were compared by morphometric and histologic analysis. RESULTS: Successful TO was confirmed in 34 of 37 fetuses. Twenty-nine of them survived to E18.5 (90.6%), six of the fetuses had a spontaneous vaginal delivery. Fetal weights were comparable, but there was significant difference in lung weights and lung-to-body weight ratios (0.020 ± 0.006 [control] versus 0.026 ± 0.002 [TO] versus 0.023 ± 0.005 [TO-R]; P = 0.013). DNA/protein and DNA/lung weight ratios were elevated, whereas protein/lung weight ratio was lower in TO compared with the control group. CONCLUSIONS: Reversal of fetal transuterine TO at E17.5, which was put at E16.5 in mice, is feasible with comparable outcomes to other current animal models with certain advantages and potential to translate the studies to the human.