Abstract
Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants. The soluble receptor for advanced glycation end products (sRAGE) is implicated in the development of various pulmonary diseases. The objectives of the current study were to investigate perinatal factors associated with serum sRAGE levels at birth and to establish whether serum sRAGE could be a biomarker for BPD. This retrospective single-center study was conducted at Fukushima Medical University Hospital's Department of Pediatrics Neonatal Intensive Care Unit from April 2014 to September 2020. Mechanically ventilated or oxygenated neonates born at <32 weeks gestational age and healthy control neonates were included in this study. Serum sRAGE levels in cord blood were measured using an enzyme-linked immunosorbent assay. Eighty-four preterm infants born at <32 weeks and 40 healthy infants were identified. The 84 born at <32 weeks were categorized as BPD (n = 34) or non-BPD (n = 50) neonates. The median gestational age (GA) and birthweight (BW) were significantly lower in BPD vs. non-BPD neonates (24.4 vs. 27.6 weeks, P < 0.001, 634 vs. 952 g, P < 0.001, respectively). Serum sRAGE at birth in all 124 preterm and term infants significantly correlated with BW (r = 0.417, P < 0.0001) and GA (r = 0.415, P < 0.0001). Among those born at <32 weeks, median serum sRAGE levels at birth were significantly lower in infants with BPD than without (1,726 vs. 2,797 pg/mL, P = 0.0005). Receiver operating characteristic analysis for sRAGE levels at birth in infants with and without BPD revealed that the area under the curve was 0.724 (95% confidence interval 0.714–0.834, P = 0.001). However, serum RAGE levels were not associated with severity of BPD. Serum sRAGE levels at birth were significantly correlated with BW and GA. Furthermore, serum sRAGE levels at birth could serve as a biomarker for predicting BPD, but not its severity.
Highlights
Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants, with long-term respiratory and neurodevelopmental consequences (1, 2)
Multivariate analysis showed that gestational age (GA) and BW were significantly correlated with serum Soluble receptor for advanced glycation end-products (RAGE) (sRAGE) levels at birth
To the best of our knowledge, this is the first study to reveal that lower serum sRAGE levels at birth among those born at
Summary
Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants, with long-term respiratory and neurodevelopmental consequences (1, 2). A key pathophysiological feature of infants affected with BPD is characterized by perturbations to lung structure including reduced alveolar number, thickened septa, and malformed pulmonary circulation (4). Such structural alterations are accompanied by characteristic inflammatory changes and extensive remodeling of the extracellular matrix (ECM) (4). Soluble RAGE (sRAGE), without transmembrane or cytoplasmic domains, can act as a decoy receptor for RAGE ligands, thereby attenuating RAGE-mediated inflammation (9). SRAGE levels were significantly reduced in premature infants with maternal inflammation (14). Benjamin et al reported that total sRAGE levels were reduced in the airways of preterm infants at risk for developing BPD (15). There are no reports correlating perinatal factors with serum sRAGE at birth in any large cohort
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