Genetic and Biochemical Predictors of Neonatal Bronchopulmonary Dysplasia
Ontology highlight
ABSTRACT:
SUBMITTER: Abdellatif M
PROVIDER: S-EPMC9385253 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The objective of this study is to review the candidate gene and genome-wide association studies relevant to bronchopulmonary dysplasia, and to discuss the emerging understanding of the complexities involved in genetic predisposition to bronchopulmonary dysplasia and its outcomes. Genetic factors contribute much of the variance in risk for BPD. Studies to date evaluating single or a few candidate genes have not been successful in yielding results that are replicated in GWAS, perhaps due to more stringent p-value thresholds. GWAS studies have identified only a single gene (SPOCK2) at genome-wide significance in a European White and African cohort, which was not replicated in two North American studies. Pathway gene-set analysis in a North American cohort confirmed involvement of known pathways of lung development and repair (e.g., CD44 and phosphorus oxygen lyase activity) and indicated novel molecules and pathways (e.g., adenosine deaminase and targets of miR-219) involved in genetic predisposition to BPD. The genetic basis of severe BPD is different from that of mild/moderate BPD, and the variants/pathways associated with BPD vary by race/ethnicity. A pilot study of whole exome sequencing identified hundreds of genes of interest, and indicated the overall feasibility as well as complexity of this approach. Better phenotyping of BPD by severity and pathophysiology, and careful analysis of race/ethnicity is required to gain a better understanding of the genetic basis of BPD. Future translational studies are required for the identification of potential genetic predispositions (rare variants and dysregulated pathways) by next-generation sequencing methods in individual infants (personalized genomics).
| S-EPMC4644695 | biostudies-literature
Project description:Purpose of reviewBronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease in premature infants. Twin studies have shown strong heritability underlying this disease; however, the genetic architecture of BPD remains unclear.Recent findingsA number of studies employed different approaches to characterize the genetic aberrations associated with BPD, including candidate gene studies, genome-wide association studies, exome sequencing, integrative omics analysis, and pathway analysis. Candidate gene studies identified a number of genes potentially involved with the development of BPD, but the etiological contribution from each gene is not substantial. Copy number variation studies and three independent genome-wide association studies did not identify genetic variations significantly and consistently associated with BPD. A recent exome-sequencing study pointed to rare variants implicated in the disease. In this review, we summarize these studies' methodology and findings, and suggest future research directions to better understand the genetic underpinnings of this potentially life-long lung disease.SummaryGenetic factors play a significant role in the development of BPD. Recent studies suggested that rare variants in genes participating in lung development pathways could contribute to BPD susceptibility.
| S-EPMC4853271 | biostudies-literature
Project description:BackgroundThe association between the presence of common pathogens in the maternal cervicovaginal tract as well as neonatal gastric fluid and adverse outcomes in preterm newborns remains uncertain.MethodsCervicovaginal swabs were collected from 98 mothers, and gastric fluid specimens were obtained from 121 premature infants with gestational ages of ≤ 32 weeks within 24 h of birth. Thirteen pathogens were tested using suspension microarray. Neonatal outcomes were monitored until either death or discharge. RESULTS UREAPLASMA: was the predominant species identified in both maternal cervicovaginal swabs and neonatal gastric fluid. Preterm newborns with Ureaplasma in gastric fluid at birth exhibited a smaller gestational age (P < 0.001), a lower 1-min Apgar score (P = 0.01), an increased requirement for pulmonary surfactant (P = 0.029), and a higher incidence of bronchopulmonary dysplasia (BPD) (P = 0.02) compared to those who tested negative for Ureaplasma. Similarly, pregnant women with Ureaplasma colonization in the genital tract were more likely to deliver babies with a smaller gestational age (P = 0.002), a higher rate of tracheal intubation after birth (P = 0.013), a lower proportion of small for gestational age (SGA) infants (P = 0.018), and an increased occurrence of BPD (P = 0.048) than mothers without the agent. Furthermore, the presence of Ureaplasma in the gastric fluid of premature infants was identified as a risk factor for BPD, with an odds ratio (OR) of up to 6, alongside gestational age and SGA as independent predictors of BPD.ConclusionsThese findings suggest that antenatal exposure to Ureaplasma is correlated with the occurrence of BPD in premature infants, which has potential clinical implications.
| S-EPMC11921625 | biostudies-literature
Project description: Not available
| S-EPMC6938142 | biostudies-literature
Project description:ObjectiveTo evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants.Study designThis was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018.ResultsA 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).ConclusionOur findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.
| S-EPMC6917570 | biostudies-literature
Project description:Scientific and technological advances in perinatology and neonatology have led to an increased rate of survival and decreased incidences of various neonatal morbidities. However, the incidence of bronchopulmonary dysplasia has remained almost the same for years in very-low-birth-weight preterm infants. Although bronchopulmonary dysplasia is the leading cause of chronic respiratory morbidity in small preterms, no substantial improvement has been achieved in prevention and treatment strategies to date. Currently, postnatal very-low-dose corticosteroids, caffeine, and vitamin A seem to be the drugs of choice, and stem cell therapy appears to be the most promising treatment modality for the future. In this guideline, which was prepared by the Turkish Neonatal Society, recent evidence-based recommendations for the prevention and treatment of bronchopulmonary dysplasia are summarized.
| S-EPMC6568289 | biostudies-literature
Project description:Objective: To assess the longitudinal metabolic patterns during the evolution of bronchopulmonary dysplasia (BPD) development. Methods: A case-control dataset of preterm infants (<32-week gestation) was obtained from a multicenter database, including 355 BPD cases and 395 controls. A total of 72 amino acid (AA) and acylcarnitine (AC) variables, along with infants' calorie intake and growth outcomes, were measured on day of life 1, 7, 28, and 42. Logistic regression, clustering methods, and random forest statistical modeling were utilized to identify metabolic variables significantly associated with BPD development and to investigate their longitudinal patterns that are associated with BPD development. Results: A panel of 27 metabolic variables were observed to be longitudinally associated with BPD development. The involved metabolites increased from 1 predominant different AC by day 7 to 19 associated AA and AC compounds by day 28 and 16 metabolic features by day 42. Citrulline, alanine, glutamate, tyrosine, propionylcarnitine, free carnitine, acetylcarnitine, hydroxybutyrylcarnitine, and most median-chain ACs (C5:C10) were the most associated metabolites down-regulated in BPD babies over the early days of life, whereas phenylalanine, methionine, and hydroxypalmitoylcarnitine were observed to be up-regulated in BPD babies. Most calorie intake and growth outcomes revealed similar longitudinal patterns between BPD cases and controls over the first 6 weeks of life, after gestational adjustment. When combining with birth weight, the derived metabolic-based discriminative model observed some differences between those with and without BPD development, with c-statistics of 0.869 and 0.841 at day 7 and 28 of life on the test data. Conclusions: The metabolic panel we describe identified some metabolic differences in the blood associated with BPD pathogenesis. Further work is needed to determine whether these compounds could facilitate the monitoring and/or investigation of early-life metabolic status in the lung and other tissues for the prevention and management of BPD.
| S-EPMC9459725 | biostudies-literature
Project description:ObjectiveThis study was designed to investigate the predictors of bronchopulmonary dysplasia in neonates with respiratory distress syndrome.MethodsThis was a single-center retrospective cohort study conducted between 1 January 2015 and 31 December 2020. A total of 625 neonates with respiratory distress syndrome (RDS) were enrolled. Demographic data, clinical presentations, complications and related treatment information were collected and analyzed. We used bivariate and multivariate logistic-regression analyses to determine significant predictors of bronchopulmonary dysplasia (BPD) in RDS neonates.ResultsIn these 625 neonates, 102 (16.3%) of them developed BPD. Bivariate analysis and multivariate logistic-regression analyses revealed that birthweight, gestational age under 32 weeks, duration of oxygen therapy over 10 days, asphyxia, patent ductus arteriosus, transfusion of red blood cells (packed red blood cells) and surfactant use were significantly associated with the development of BPD.ConclusionBirthweight, gestational age <32 weeks, total duration of oxygen therapy >10 days, asphyxia, patent ductus arteriosus, need for red blood cell infusion, and the use of pulmonary surfactant were important predictors of BPD in neonates with RDS.
| S-EPMC9122647 | biostudies-literature
Project description:Disrupted neonatal lung angiogenesis and alveologenesis often give rise to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. Hyperoxia-induced pulmonary vascular and alveolar damage in premature infants is one of the most common and frequent factors contributing to BPD. The purpose of the present study was to explore the key molecules and the underlying mechanisms in hyperoxia-induced lung injury in neonatal mice and to provide a new strategy for the treatment of BPD. In this work, we reported that hyperoxia decreased the proportion of endothelial cells (ECs) in the lungs of neonatal mice. In hyperoxic lung ECs of neonatal mice, we detected upregulated fibroblast growth factor receptor 1 (FGFR1) expression, accompanied by upregulation of the classic downstream signaling pathway of activated FGFR1, including the ERK/MAPK signaling pathway and PI3K-Akt signaling pathway. Specific deletion of Fgfr1 in the ECs of neonatal mice protected the lungs from hyperoxia-induced lung injury, with improved angiogenesis, alveologenesis and respiratory metrics. Intriguingly, the increased Fgfr1 expression was mainly attributed to aerosol capillary endothelial (aCap) cells rather than general capillary endothelial (gCap) cells. Deletion of endothelial Fgfr1 increased the expression of gCap cell markers but decreased the expression of aCap cell markers. Additionally, inhibition of FGFR1 by an FGFR1 inhibitor improved alveologenesis and respiratory metrics. In summary, this study suggests that in neonatal mice, hyperoxia increases the expression of endothelial FGFR1 in lung ECs and that deficiency of endothelial Fgfr1 can ameliorate hyperoxia-induced BPD. These data suggest that FGFR1 may be a potential therapeutic target for BPD, which will provide a new strategy for the prevention and treatment of BPD.
| S-EPMC9716472 | biostudies-literature
Project description:BackgroundBradycardia and oxygen desaturation episodes are common among preterm very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU), and their association with adverse outcomes such as bronchopulmonary dysplasia (BPD) is unclear.MethodsFor 502 VLBW infants we quantified bradycardias (HR < 100 for ≥ 4 s) and desaturations (SpO2 < 80% for ≥ 10 s), combined bradycardia and desaturation (BD) events, and percent time in events in the first 4 weeks after birth (32 infant-years of data). We tested logistic regression models of clinical risks (including a respiratory acuity score incorporating FiO2 and level of respiratory support) to estimate the risks of BPD or death and secondary outcomes. We then tested the additive value of the bradycardia and desaturation metrics for outcomes prediction.ResultsBPD occurred in 187 infants (37%). The clinical risk model had ROC area for BPD of 0.874. Measures of desaturation, but not bradycardia, significantly added to the predictive model. Desaturation metrics also added to clinical risks for prediction of severe intraventricular hemorrhage, retinopathy of prematurity and prolonged length of stay in the NICU.ConclusionsOxygen desaturations in the first month of the NICU course are associated with risk of BPD and other morbidities in VLBW infants.
| S-EPMC6488465 | biostudies-literature