Impact of Changes in Early Respiratory Support Management on Respiratory Outcomes of Preterm Infants.

BACKGROUND: In the period immediately after birth, preterm infants are highly susceptible to lung injury. Ventilator-induced lung injury has been recognized as a major contributing factor for bronchopulmonary dysplasia (BPD) in preterm infants. Noninvasive respiratory support (NIRS) could decrease lung injury, and early respiratory support management might affect pulmonary outcomes. We conducted a study to evaluate the changes in early respiratory support management and their impact on respiratory outcome and complications of preterm infants in 3 different time periods over the last 13 years. METHODS: This study was a retrospective, single-center cohort study. We retrospectively reviewed the medical records of preterm infants < 32 weeks of gestational age born in our hospital from 2007-2020. The study period was divided into three 3-y discrete periods: 2007-2009 (period A), 2013-2015 (period B), and 2018-2020 (period C). Changes in early respiratory support management were assessed in the 3 periods. The outcomes measured included mortality, BPD, other major neonatal complications, initial respiratory support, and duration of mechanical ventilation. RESULTS: In all, 1,880 clinical records were assessed in our study, with 358 in period A, 825 in period B, and 697 in period C. The use of antenatal corticosteroids increased over time (56.1% in period A, 56.7% in period B, and 74.0% in period C (P < .001). The need for surfactant decreased from 65.6% in period A to 40.7% in period B and 45.9% in period C. Increased utilization of NIRS was associated with decreased invasive mechanical ventilation within 24 h after birth. NIRS only during the hospital stay increased from 22.9% in period A to 36.8% and 45.1% in the latter 2 periods (P < .001). Oxygen therapy duration decreased from 24.3 d in period A to 14.4 d in period B and 17.2 d in period C (P < .001). The overall incidence of BPD was 32.4% in the first period, 23.9% in the second period, and 25.4% in the third period (P < .001). The moderate-to-severe forms of BPD decreased from 12.8% in period A to 7.9% in period B and 7.6% in period C (P = .009). Other neonatal complications, such as pneumothorax, pulmonary hemorrhage, persistent pulmonary hypertension of the newborn, surgical necrotizing enterocolitis, intraventricular hemorrhage grade III/IV, and periventricular leukomalacia, were unchanged among the 3 periods. CONCLUSIONS: From 2007-2020, respiratory management was characterized by a marked reduction in invasive mechanical ventilation and an increase in the use of NIRS. Changes in early respiratory support management resulted in improved respiratory outcomes with a decrease in the overall incidence of BPD. It is likely that our aim to reduce lung injury by improving our respiratory management has contributed to a favorable outcome.

The Correlation Between Bronchopulmonary Dysplasia and Platelet Metabolism in Preterm Infants.

Background: Platelets play an important role in the formation of pulmonary blood vessels, and thrombocytopenia is common in patients with pulmonary diseases. However, a few studies have reported on the role of platelets in bronchopulmonary dysplasia. Objective: The objective of the study was to explore the relationship between platelet metabolism and bronchopulmonary dysplasia in premature infants. Methods: A prospective case-control study was performed in a cohort of premature infants (born with a gestational age <32 weeks and a birth weight <1,500 g) from June 1, 2017 to June 1, 2018. Subjects were stratified into two groups according to the diagnostic of bronchopulmonary dysplasia: with bronchopulmonary dysplasia (BPD group) and without bronchopulmonary dysplasia (control group). Platelet count, circulating megakaryocyte count (MK), platelet-activating markers (CD62P and CD63), and thrombopoietin (TPO) were recorded and compared in two groups 28 days after birth; then serial thrombopoietin levels and concomitant platelet counts were measured in infants with BPD. Results: A total of 252 premature infants were included in this study. Forty-eight premature infants developed BPD, 48 premature infants without BPD in the control group who were matched against the study infants for gestational age, birth weight, and admission diagnosis at the age of postnatal day 28. Compared with the controls, infants with BPD had significantly lower peripheral platelet count [BPD vs. controls: 180.3 (24.2) × 109/L vs. 345.6 (28.5) × 109/L, p = 0.001]. Circulating MK count in the BPD group was significantly more abundant than that in the control group [BPD vs. controls: 30.7 (4.5)/ml vs. 13.3 (2.6)/ml, p = 0.025]. The level of CD62p, CD63, and TPO in BPD group was significantly higher than the control group [29.7 (3.1%) vs. 14.5 (2.5%), 15.4 (2.0%) vs. 5.8 (1.7%), 301.4 (25.9) pg/ml vs. 120.4 (14.2) pg/ml, all p < 0.05]. Furthermore, the concentration of TPO was negatively correlated with platelet count in BPD group with thrombocytopenia. Conclusions: Our findings suggest that platelet metabolism is involved in the development of BPD in preterm infants. The possible mechanism might be through increased platelet activation and promoted TPO production by feedback.

Mesenchymal Stem Cells: Potential Therapeutic Prospect of Paracrine Pathways in Neonatal Infection.

Infection is the leading cause of admission and mortality in neonatal intensive care units. Immature immune function and antibiotic resistance make the treatment more difficult. However, there is no effective prevention for it. Recently, more and more researches are focusing on stem cell therapy, especially mesenchymal stem cells (MSCs); their potential paracrine effect confer MSCs with a major advantage to treat the immune and inflammatory disorders associated with neonatal infection. In this review, we summarize the basal properties and preclinical evidence of MSCs and explore the potential mechanisms of paracrine factors of MSCs for neonatal infection.

Cord Blood Levels of Angiopoietin-Like 7 (ANGPTL7) in Preterm Infants.

OBJECTIVE: ANGPTL7 is a member of the angiogenin-like protein family. Compared to other members, ANGPTL7 is the least known. Recent studies have explored the relationship between ANGPTL7 and multiple pathological processes and diseases. However, there is no research about ANGPTL7 in neonates. This study was designed to investigate the concentration of ANGPTL7 in cord blood of preterm infants. METHOD: Singleton infants born in November 2017 to June 2019 in the study hospital were enrolled in the study. Maternal and neonatal clinical data were collected. ANGPTL7 levels in cord blood and serum on the third day after birth were measured by an enzyme-linked immunosorbent assay. RESULT: A total of 182 infants were enrolled in this study. Patients were categorized into two groups by gestational age (102 preterm, 80 full-term). ANGPTL7 levels in preterm infants were significantly higher than that in full-term babies (t = 15.4, P < 0.001). In multiple line regression analysis, ANGPTL7 levels independently correlated with gestational age (ß = -0.556, P < 0.001). There is also no correlation between preterm outcomes and ANGPTL7 levels. Cord blood levels of ANGPTL7 were significantly higher than those in serum on the third day after birth (t = 13.88, P < 0.001). CONCLUSION: Cord blood ANGPTL7 levels are higher in preterm infants than full-term babies. The levels are independently influenced by gestational ages and attenuated significantly after birth. The underlying mechanism needs to be further studied.

[Expression of ubiquitin-specific protease 7 in lung tissue of preterm rats after hyperoxia exposure].

OBJECTIVE: To study the expression and significance of ubiquitin-specific protease 7 (USP7) and the key factors of the Wnt signaling pathway in the lung tissue of preterm rats after hyperoxia exposure. METHODS: A total of 180 preterm neonatal Wistar rats were randomly divided into an air control group, an air intervention group, a hyperoxia control group, and a hyperoxia intervention group, with 45 rats in each group. Lung injury was induced by hyperoxia exposure in the hyperoxia groups. The preterm rats in the intervention groups were given intraperitoneal injection of the USP7 specific inhibitor P5091 (5 mg/kg) every day. The animals were sacrificed on days 3, 5, and 9 of the experiment to collect lung tissue specimens. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. RT-PCR and Western blot were used to measure the mRNA and protein expression levels of USP7 and the key factors of the Wnt signaling pathway ß-catenin and α-smooth muscle actin (α-SMA) in lung tissue. RESULTS: The air groups had normal morphology and structure of lung tissue; on days 3 and 5, the hyperoxia control group showed obvious alveolar compression and disordered structure, with obvious inflammatory cells, erythrocyte diapedesis, and interstitial edema. On day 9, the hyperoxia control group showed alveolar structural disorder and obvious thickening of the alveolar septa. Compared with the hyperoxia control group at the corresponding time points, the hyperoxia intervention group had significantly alleviated disordered structure, inflammatory cell infiltration, and bleeding in lung tissue. At each time point, the hyperoxia groups had a significantly lower radial alveolar count (RAC) than the corresponding air groups (P < 0.05), and the hyperoxia intervention group had a significantly higher RAC than the hyperoxia control group (P < 0.05). On days 3, 5, and 9 of the experiment, the hyperoxia groups had significantly higher mRNA expression of USP7 and ß-catenin and protein expression of USP7, ß-catenin, and α-SMA than the corresponding air groups (P < 0.05). Compared with the hyperoxia control group, the hyperoxia intervention group had significant reductions in the mRNA expression of ß-catenin and the protein expression of ß-catenin and α-SMA (P < 0.05), while there were no significant differences in the mRNA and protein expression of USP7 between the hyperoxia intervention and hyperoxia control groups (P > 0.05). There were no significant differences in the mRNA expression of USP7 and ß-catenin and the protein expression of USP7, ß-catenin, and α-SMA between the air intervention and air control groups (P > 0.05). CONCLUSIONS: Hyperoxia exposure can activate the Wnt/ß-catenin signaling pathway, and USP7 may participate in hyperoxic lung injury through the Wnt/ß-catenin signaling pathway. The USP7 specific inhibitor P5091 may accelerate the degradation of ß-catenin by enhancing its ubiquitination, reduce lung epithelial-mesenchymal transition, and thus exert a certain protective effect against hyperoxic lung injury.