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Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants.

ABSTRACT: OBJECTIVE:To evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants. STUDY DESIGN:This was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018. RESULTS:A total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure (21.6%, P?=?0.001). After adjusting for covariates, the risk of BPD was associated independently with ibuprofen exposure (odds ratios (OR) 2.296, 95% confidence interval (CI): 1.166-4.522, p?=?0.016). Further analysis showed a trend towards higher risk of BPD in infants with successful patent ductus arteriosus (PDA) closure after ibuprofen treatment (32.3%) compared to non-treated infants (20.2%, p?=?0.162). CONCLUSION:Our findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.

SUBMITTER: Chen X

PROVIDER: S-EPMC6917570 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants.

Chen Xueyu X Qiu Xiaomei X Sun Panpan P Lin Yanqing Y Huang Zhifeng Z Yang Chuanzhong C Walther Frans J FJ

Journal of perinatology : official journal of the California Perinatal Association 20190807 1

<h4>Objective</h4>To evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants.<h4>Study design</h4>This was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018.<h4>Results</h4>A total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure ...[more]

PMID: 31391526

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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.

Dataset Information

Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants.

Publications

Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants.

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