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The Utility of Comprehensive Metabolic Panel Tests for the Prediction of Bronchopulmonary Dysplasia in Extremely Premature Infants.

ABSTRACT: Background:Comprehensive metabolic panel tests (CMP) are routinely performed in extremely premature infants within the first days of life. The association between the parameters of first postnatal CMP and the risk of bronchopulmonary dysplasia (BPD) remains elusive. Methods:A retrospective analysis was performed to evaluate the correlation between the parameters of first postnatal CMP and the risk of BPD in a cohort of extremely premature infants (born with a gestational age less than 28 weeks or a birth weight less than 1000 grams) at the neonatal intensive care unit, Shenzhen Maternity and Child Healthcare Hospital, from January 2016 to October 2018. A multivariant regression model was built to assess the association of the first postnatal CMP with the development of BPD. Results:A total of 256 extremely premature infants were included in this study. BPD developed in 76 (29.7%) infants. The first CMP in these infants was performed at 5 to 8 days after birth. The levels of blood urea nitrogen (BUN) and magnesium were significantly higher in infants with BPD compared to infants with no BPD (10.2 versus 7.5 mmol/L, P < 0.001 and 0.9 versus 0.8 U/L, P = 0.001, respectively) whereas the level of alkaline phosphatase (ALP) and total protein was significantly lower in infants with BPD (215.5 versus 310.0 U/L, P = 0.002 and 41.2 versus 42.9 g/L, P = 0.037, respectively). Multiple analysis showed that a higher level of BUN (>8.18 mmol/L) was independently associated with BPD (OR 3.261, 95% CI 1.779-5.978). Conclusion:Our findings indicate that a higher postnatal BUN level (>8.18 mmol/L) may be a predictor for the development of BPD in extremely premature infants.

SUBMITTER: Chen X

PROVIDER: S-EPMC6854975 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls. Similarly, bronchoalveolar lavage fluid from hyperoxia-exposed mice (an animal model of BPD) and supernatants from hyperoxia-exposed human bronchial epithelial cells (in vitro model of BPD) had increased exosomes compared with air controls. Next, in a prospective cohort study of tracheal aspirates obtained at birth from extremely preterm infants, utilizing independent discovery and validation cohorts, we identified unbiased exosomal miRNA signatures predictive of severe BPD. The strongest signal of reduced miR-876-3p in BPD-susceptible compared with BPD-resistant infants was confirmed in the animal model and in vitro models of BPD. In addition, based on our recent discovery of increased Proteobacteria in the airway microbiome being associated with BPD, we developed potentially novel in vivo and in vitro models for BPD combining Proteobacterial LPS and hyperoxia exposure. Addition of LPS led to a larger reduction in exosomal miR 876-3p in both hyperoxia and normoxia compared with hyperoxia alone, thus indicating a potential mechanism by which alterations in microbiota can suppress miR 876-3p. Gain of function of miR 876-3p improved the alveolar architecture in the in vivo BPD model, demonstrating a causal link between miR 876-3p and BPD. In summary, we provide evidence for the strong predictive biomarker potential of miR 876-3p in severe BPD. We also provide insights on the pathogenesis of neonatal lung disease, as modulated by hyperoxia and microbial product-induced changes in exosomal miRNA 876-3p, which could be targeted for future therapeutic development.

Project description:Background: Infants born extremely preterm are at high risk of developing bronchopulmonary dysplasia (BPD). This study aimed to assess the incremental health care burden of BPD and associated comorbidities among extremely preterm infants in the United States. Methods: Health service claims in the Premier Perspective database were retrospectively analyzed for infants born at ?28 weeks gestation who were admitted to neonatal intensive care during birth hospitalization and survived to a postmenstrual age of ?36 weeks. Gestational age (GA) at birth and BPD status of infants was determined based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes recorded in the database. Results: Of the 12,017 infants included, 4,904 (40.8%) had BPD. BPD increased with decreasing GA: 67.4% of infants born at <24 weeks GA had BPD vs. 28.7% of those born at 27-28 weeks. Infants with BPD had significantly longer hospital stays following birth than those without (mean [standard deviation (SD)] 102 [34] vs. 83 [24] days, respectively, P < 0.001), and incurred higher total charges (mean [SD] $799,499 [$535,528] vs. $588,949 [$377,137], respectively, P < 0.001). Mean total charges incurred during index hospitalization decreased as GA at birth increased, with GA having a bigger effect than presence or absence of BPD. During their first year, infants with BPD had a higher in-hospital late mortality rate than those without (1.9 vs. 0.6%), and were more likely to have two or more hospital encounters following birth hospitalization (58.0 vs. 48.2%). Among infants who had two or more encounters after discharge, those with BPD experienced a higher percentage of pulmonary symptoms than those without (46.3 vs. 38.9%). Comparison with infants who did not have BPD, retinopathy of prematurity, or intraventricular hemorrhage showed that BPD is the main complication contributing to increased length of stay, costs, in-hospital mortality, and additional health care encounters. Conclusion: BPD is a key contributor to the large health care burden associated with extremely preterm birth. However, GA at birth has a bigger effect on health care costs for extremely preterm infants than the presence of BPD.

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The Utility of Comprehensive Metabolic Panel Tests for the Prediction of Bronchopulmonary Dysplasia in Extremely Premature Infants.

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