Bronchopulmonary Dysplasia Group Research Articles

Severe Bronchopulmonary Dysplasia Adversely Affects Brain Growth in Preterm Infants

Introduction: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental outcomes of preterm infants, but its effect on brain growth in preterm infants after the neonatal period is unknown. This study aimed to evaluate the effect of severe BPD on brain growth of preterm infants from term to 18 months of corrected age (CA). Methods: Sixty-three preterm infants (42 with severe BPD and 21 without severe BPD) who underwent magnetic resonance imaging at term equivalent age (TEA) and 18 months of CA were studied by using the Infant Brain Extraction and Analysis Toolbox (iBEAT). We measured segmented brain volumes and compared brain volume and brain growth velocity between the severe BPD group and the non-severe BPD group. Results: There was no significant difference in brain volumes at TEA between the groups. However, the brain volumes of the total brain and cerebral white matter in the severe BPD group were significantly smaller than those in the non-severe BPD group at 18 months of CA. The brain growth velocities from TEA to 18 months of CA in the total brain, cerebral cortex, and cerebral white matter in the severe BPD group were lower than those in the non-severe BPD group. Conclusion: Brain growth in preterm infants with severe BPD from TEA age to 18 months of CA is less than that in preterm infants without severe BPD.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC<lower limit of normal; odds ratio, 3.54) and high CT score (median difference, 2.54). School-aged children with severe BPD showed airflow limitations and structural abnormalities despite no subjective respiratory symptoms. These results suggest that patients with a history of prenatal oligohydramnios or prolonged mechanical ventilation require extended follow-up.

Incidence and Predictors of Bronchopulmonary Dysplasia Development and Severity Among Preterm Infants Born at 32 Weeks of Gestation or Less.

Background As the most common chronic lung disease (CLD) related to premature birth, bronchopulmonary dysplasia (BPD) is associated with long-term lung disease along with cardiovascular and neurodevelopmental disorders. However, data on the incidence and predictors of BPD in Qatar are lacking. Objectives In this study, we aimed to determine the incidence of BPD among infants born at ≤ 32 weeks gestational age (GA) at our neonatal unit, and identify risk factors for the development of BPD and moderate-severe BPD. Methods This was a retrospective observational cohort study conducted at a single site: a level-III neonatal intensive care unit (NICU) in Qatar. We included 1539 neonates born at ≤ 32 weeks of gestation with birth weights of ≤ 1500 grams who were admitted to the NICU between 2017 and 2020. Univariate and multivariate logistic regression analyses were performed to identify potential factors and predictors and their possible associations with the development of BPD and moderate-severe BPD. We also applied BPD classifications to determine the variability in the incidence of BPD in our cohort according to various definitions (2001 National Institute of Child Health and Human Development (NICHD) Diagnostic Criteria, 2016 Revisions of NICHD Criteria, and 2019 Neonatal Research Network Jensen Grading). Results A total of 451 infants (29.3%) had BPD (BPD group) while 1088 (70.7%) did not (non-BPD group), and the overall incidence of BPD was 29.3%. The most relevant risk factors associated with a higher risk of developing BPD identified in the multivariate logistic regression analysis were appropriate weight for gestational age (adjusted OR (aOR) 3.67, 95%CI 2.02-6.67, P < 0.001), presence of patent ductus arteriosus (PDA) (aOR 2.61, 95%CI 1.86-3.66, P < 0.001), late-onset sepsis (aOR 2.16; 95%CI 1.29-3.62; P = 0.003), and use of invasive ventilation (aOR 1.90; 95%CI 1.35-2.69; P < 0.001). The most relevant independent risk factors associated with a higher risk for developing moderate-severe BDP were postnatal steroids (aOR 7.12, 95%CI 3.77-13.44, P < 0.001), use of inhaled nitric oxide (aOR 3.65, 95%CI 1.48-9.01, P = 0.005), use of invasive ventilation (aOR 2.13, 95%CI 1.13-4.00, P = 0.019), late-onset sepsis (aOR 2.07, 95%CI 1.10-3.91, P = 0.025), and male sex (aOR 2.04, 95%CI 1.24-3.36, P = 0.005). The difference in the distribution of BPD severity across the three different definitions of NICHD was significant (P < 0.001). Conclusion The results of this study showed that the incidence of BPD remained high in infants born at ≤ 32 weeks of gestational age and birth weight <1500 g with appropriate weight for gestational age. The presence of PDA at birth or first echocardiography, late-onset sepsis, and use of invasive ventilation were significant risk factors for the incidence of BPD. The identification of risk factors will contribute to the implementation of lung-protective strategies for at-risk infants who may benefit from potential preventive therapy.

Blood pressure in preterm infants with bronchopulmonary dysplasia in the first three months of life.

Neonatal hypertension is common in preterm infants with bronchopulmonary dysplasia (BPD). Our study aimed to examine blood pressure variation in the first three months of life in preterm BPD patients. We conducted a retrospective, single-centre study at the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We collected blood pressure data from 26 preterm infants (born at < 30weeks gestation) with moderate or severe BPD over three years (2019-2021). We calculated the BPD group's daily average blood pressure values and used previously defined normal blood pressure values from a preterm patient group born at < 30weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures. We found a statistically significant correlation between the blood pressure values of the BPD patient group and the reference data. The difference between the blood pressure curve of the group with BPD and that of the reference group was also statistically significant. We also analysed individual patients' daily average blood pressure values and found that 11 patients (42%) had hypertensive blood pressure values for three or more days within the first 90days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury. The blood pressure of the BPD group not only correlated with but also significantly differed from the reference data. Hypertension lasting three or more days occurred more frequently in patients with acute kidney injury accompanied by BPD.

Effect and mechanism of transient receptor potential canonical channel 3 on hyperoxic lung injury in neonatal rats

AbstractThe aim of this study is to research the expression of the transient receptor potential canonical channel 3 (TRPC3) in a neonatal hyperoxic lung injury model of bronchopulmonary dysplasia (BPD), and to further investigate the role of the TRPC3/nuclear factor‐κB (NF‐κB) signaling pathway in hyperoxia‐induced BPD by a TRPC3 agonist (GSK1702934A). The hyperoxic lung injury model of BPD was established in Sprague–Dawley neonatal rats. Hematoxylin and eosin (HE) staining and radial alveolar count (RAC) values showed that the hyperoxic lung injury model of BPD was successfully established in the neonatal rats, and pulmonary edema was found in the neonatal rats with BPD. The results of reference transcriptome sequencing, Quantitative real‐time PCR (qPCR), and western blot showed lower pulmonary expression of TRPC3 in the BPD group than in the control group. Immunofluorescence showed predominant expression of TRPC3 in airways and pulmonary vessels, and the fluorescence intensity of the BPD group was lower than that of the control group. Lung dry‐to‐wet weight ratio, HE staining, and RAC value showed that the lung histomorphology significantly improved in the BPD + TRPC3 agonist group compared with the BPD group on day 14 but did not revert to the level of the control group. According to qPCR results, compared with the control group, the expression of NF‐κB1 decreased and the expression of NF‐κBiz increased in the BPD group, whereas the expression of NF‐κBiz decreased in the BPD + TRPC3 agonist group. Therefore, we draw the conclusion that TRPC3 may activate NF‐κB by inhibiting NF‐κBiz to promote cell proliferation and lung growth and development.

[A retrospective cohort study on the correlation between early energy management and bronchopulmonary dysplasia in premature infants].

Objective: To investigate the correlation between early energy supplement and bronchopulmonary dysplasia (BPD) in very preterm and very low birth weight infants. Methods: A retrospective cohort study design was used. A total of 939 preterm infants who were admitted to the Department of Neonatology of the West China Second Hospital of Sichuan University within 24 h after birth from January 2019 to December 2021 were enrolled in the study. They were born with a gestational age of <32 weeks and (or) a birth weight of <1 500 g. Of them, 250 preterm infants who developed BPD were enrolled in the BPD group, and each of them was matched to a preterm infant who did not develop BPD (matched for gestational age and birth weight) in the order of priority after calculating propensity score. Their total energy, enteral energy, parenteral energy, total fluid intake and energy per unit of fluid per week were collected within the first 2 weeks of life. The independent sample t-test or Mann Whitney U test was used for continuous variables, and the χ2 test for between-group comparisons of categorical variables. Univariate and multivariate Logistic regression analyses were used to explore the association between total energy and total fluid and BPD incidence, respectively. The dose-response relationship between parenteral energy and BPD was investigated by a generalized additive model, and the threshold effect of parenteral energy on BPD used a two-piecewise linear regression model. Results: The gestational age was (28.4±1.9) weeks in the BPD group and (29.5±1.3) weeks in the control group; the birth weight was (1 107±258) g in the BPD group and (1 324±261) g in the control group; and there were 140 males (56.0%) and 131 males (52.4%) in each group, respectively. An increase in energy per unit of fluid in the second week of life was associated with a reduced risk of BPD (OR=0.32, 95%CI 0.12-0.84, P=0.021), and an increase in total energy in the second week of life was also associated with a reduced risk of BPD, with total energy of >418-502 kJ/(kg·d) was significantly lower than when total energy was ≤334 kJ/(kg·d) (OR=0.15, 95%CI 0.03-0.85, P=0.033). There was no association between the average total fluid intake and BPD incidence (both P>0.05) in the first and second week. The increase in the proportion of parenteral energy to total energy in the second week of life was associated with an increased incidence of BPD (OR=8.45, 95%CI 2.14-33.32, P=0.003); specifically, the risk of BPD significantly increased when the parenteral energy was ≥305 kJ/(kg·d) (OR=1.02, 95%CI 1.01-1.03, P=0.003). Conclusions: Maintaining a high total energy supply in the early postnatal period in preterm infants may reduce the risk of BPD, but continued reliance on high parenteral energy to meet total energy requirements increases the risk of BPD, so enteral feeds should be initiated as early as possible and maximized as tolerated.

Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia.

N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of bronchopulmonary dysplasia (BPD) remains poorly characterized. Thus, the purpose of this investigation was to evaluate the effects of m6A RNA methylation regulators on the development of BPD. BPD-related transcriptome data were downloaded from the GEO database. Differentially expressed m6A methylation regulators between BPD and control group were identified. Consensus clustering was conducted for the classification of BPD and association between clusters and BPD phenotypes were explored. Analysis of differentially expressed genes (DEGs) and immune-related DEGs was performed. The GSEA, GO and KEGG analyses were used to interpret the functional enrichments. The composition of immune cell subtypes in BPD subsets was predicted by CIBERSORT analysis. Compared with the control group, expression of most m6A regulators showed significant alteration, especially for IGF2BP1/2/3. BPD was classified into 2 subsets, and cluster 1 was correlated with severe BPD. Furthermore, the results of functional enrichment analyses showed a disturbed immune-related signaling pathway. Based on CIBERSORT analysis, we found that the proportion of immune cell subsets changed between cluster 1 and cluster 2. Our study revealed the implication of m6A methylation regulators in the development of BPD, which might provide a novel insight for the diagnosis and treatment of BPD.

Sex-Based Differences in the Sonographic Characterization of Diaphragm Thickness in Preterm Infants With Bronchopulmonary Dysplasia at Term Corrected Age: A Secondary Analysis of a Prospective Study.

To determine the sex-specific diaphragm thickness in infants with bronchopulmonary dysplasia (BPD) as well as in healthy term and near-term infants. We performed a secondary analysis of an observational study to compare the sonographic diaphragm thickness at end expiration (DTexp ) in female and male infants. The study included infants with BPD and healthy near-term and term infants. To account for differences in anthropometric measurements, we calculated the DTexp as a ratio of body surface area (BSA). Statistical analysis was performed using R statistical software. Of the 111 infants included, 54 (48.6%) were female. There were no significant differences in mean (SD) birth gestation [26.2 (2.1) vs 26.3 (2.1) weeks] and mean study age [38.0 (2.0) vs 37.4 (1.1) weeks] of male vs female infants with BPD. The mean (SD) DTexp [1.5 (0.4) mm vs 1.2 (0.3) mm, P = .02] and DTexp /BSA [8.3 (2.3) mm/m2 vs 6.7 (1.6) mm/m2 , P < .01] were significantly thicker in female than male infants with BPD. In contrast, there were no significant differences in DTexp between sexes [1.5 (0.4) mm vs 1.5 (0.3) mm, P = .89] within the healthy control group. Moreover, there were no differences in inspiratory diaphragm thickness, diaphragm thickness fraction, or excursion between males and females in the BPD or healthy groups. Male infants with BPD exhibit thinner diaphragm thickness compared with female infants. Its implication on higher rates of BPD in preterm males is unclear, but this finding highlights the need for further investigation.

The serum thioredoxin-1 levels are not associated with bronchopulmonary dysplasia and retinopathy of prematurity.

We hypothesized that the serum TRX-1 in extremely preterm infants (EPIs) after birth was associated with the development of severe bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). This single-centered retrospective study enrolled EPIs treated at our institution. Serum TRX-1 concentrations of the residual samples taken on admission, day 10-20 of life, and 36-40 weeks of postmenstrual age (PMA) were measured with an enzyme-linked immunosorbent assay. The serum TRX-1 levels on admission were not different between the severe BPD (n = 46) and non-severe BPD groups (n = 67): [median (interquartile range) 147 (73.0-231) vs. 164 (80.5-248) ng/mL] (P = 0.57). These had no significant difference between the severe ROP (n = 47) and non-severe ROP groups (n = 66): [164 (71.3-237) vs. 150 (80.9-250) ng/mL] (P = 0.93). The TRX-1 levels at 10-20 days of life and 36-40 weeks of PMA also had no association with the development of severe BPD and ROP. The serum TRX-1 levels after birth are not predictive of severe BPD and ROP. Serum thioredoxin-1 levels in extremely preterm infants on the day of birth are lower than those in term or near-term infants hospitalized for transient tachypnea of the newborn. In extremely preterm infants, the serum thioredoxin-1 levels on the day of birth, at 10-20 days of life, and at postmenstrual age of 36-40 weeks were not associated with severe bronchopulmonary dysplasia and retinopathy of prematurity. The thioredoxin system is under development in extremely preterm infants; however, the serum thioredoxin-1 level is not predictive for severe bronchopulmonary dysplasia and retinopathy of prematurity.

Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants

ObjectiveAs the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates.Materials and methodsThe study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC).ResultsAmong the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96.ConclusionA predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes.

Plasma KL-6 as a Potential Biomarker for Bronchopulmonary Dysplasia in Preterm Infants.

KL-6 is a biomarker of interstitial lung injury and increases during repair. Our aim was to determine the predictive value of plasma KL-6 for the development of bronchopulmonary dysplasia (BPD) in preterm infants. Ninety-five extremely preterm infants (EPIs), born at <28 gestational age (GA), were divided into two main BPD groups as follows: the moderate/severe and the no/mild group. KL-6 was analyzed on days 7 and 14. Binary logistic regression analyses and ROC curve analyses were performed. Infants <26 + 0 weeks' GA have higher mean KL-6 than infants >25 + 6 weeks' GA on 7 and 14 days (335 vs. 286 U/ml and 378 vs. 260 U/ml; p = 0.005 and 0.018, respectively). In the binary regression model at KL-6 day 7, three of the prognostic factors remained significant-mechanical ventilation OR: 10.38 (95% CI: 3.57-30.14), PDA OR: 6.39 (95% CI: 0.87-46.74), and KL-6 OR: 4.98 (95% CI: 1.54-16.08). The AUC was 0.86 with a sensitivity and specificity of 79% at a cutoff value ≥0.34. In the binary regression model at KL-6 day 14, six of the prognostic factors were significant-PDA OR: 23.34 (95% CI: 2.14-254.24), KL-6 OR: 13.59 (95% CI: 3.19-57.96), GA OR: 4.58 (95% CI: 1.16-18.06), mechanical ventilation OR: 4.45 (95% CI: 1.23-16.16), antenatal steroids OR: 0.19 (95% CI: 0.04-0.95), and gender (female OR: 0.30 (95% CI 0.08-1.12)). The AUC was 0.91, and the sensitivity and accuracy for a cutoff ≥0.37 were 89% and 85%, respectively. KL-6 could be a useful screening biomarker for early detection of infants at increased risk for developing BPD.

Predictive and Diagnostic Values of Systemic Inflammatory Indices in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants, and there is a lag in the diagnosis of BPD. Inflammation is a vital pathogenic factor for BPD; we aim to evaluate the predictive and diagnostic values of systemic inflammatory indices in BPD. Between 1 January 2019 and 31 May 2023, the clinical data of 122 premature infants with a gestational age of <32 weeks in the Department of Neonatology, the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, were retrospectively collected and classified into non-BPD (n = 72) and BPD (n = 50) groups based on the National Institute of Child Health and Human Development 2018 criteria. To compare the general characteristics of each group, we identified the independent risk variables for BPD using multivariate logistic regression analysis, compared the systemic inflammatory indices at birth, 72 h, 1 week, 2 weeks, and 36 weeks postmenstrual age (PMA), and constructed the receiver operating characteristic curves of neutrophil-to-lymphocyte ratio (NLR) diagnosis of BPD at different time points. ① The independent risk factors for BPD in preterm infants were birth weight, small for gestational age, and days of oxygen therapy (all p < 0.05). ② At 72 h and 1 week after birth, the serum NLR of the BPD group was higher than for the non-BPD group (p < 0.05). Furthermore, the neutrophil count (N), NLR, monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index, systemic inflammation response index (SIRI), and pan-immune-inflammation value of infants with BPD were higher than the non-BPD group at 3 weeks after birth (p < 0.05). Moreover, at 36 weeks of PMA, the serum N, NLR, MLR, and SIRI of BPD infants were higher than those of non-BPD infants (p < 0.05). ③ The NLR of infants with and without BPD gradually increased after birth, reaching a peak at 72 h and 1 week, respectively. At 3 weeks postnatal, the NLR had the highest predictive power for BPD, with an area under the curve (AUC) of 0.717 (p < 0.001); the sensitivity was 56% and specificity was 86.1%. In addition, the NLR at 36 weeks of PMA exhibited some diagnostic value for BPD. The AUC was 0.693 (p < 0.001), the sensitivity was 54%, and specificity was 83.3%. At 3 weeks after birth and 36 weeks of PMA, some systemic inflammation indices (like N, NLR, SIRI) of preterm infants with BPD have specific predictive and diagnostic values; these indices may help the management of high-risk preterm infants with BPD.

Evidence of abnormality in glutathione metabolism in the airways of preterm born children with a history of bronchopulmonary dysplasia

Preterm-born children are at risk of long-term pulmonary deficits, including those who developed bronchopulmonary dysplasia (BPD) in infancy, however the underlying mechanisms remain poorly understood. We characterised the exhaled breath condensate (EBC) metabolome from preterm-born children, both with and without BPD. Following spirometry, EBC from children aged 7–12 years, from the Respiratory Health Outcomes in Neonates study, were analysed using Time-of-Flight Mass Spectrometry. Metabolite Set Enrichment Analysis (MSEA) linked significantly altered metabolites to biological processes. Linear regression models examined relationships between metabolites of interest and participant demographics. EBC was analysed from 214 children, 144 were born preterm, including 34 with BPD. 235 metabolites were detected, with 38 above the detection limit in every sample. Alanine and pyroglutamic acid were significantly reduced in the BPD group when compared to preterm controls. MSEA demonstrated a reduction in glutathione metabolism. Reduced quantities of alanine, ornithine and urea in the BPD group were linked with alteration of the urea cycle. Linear regression revealed significant associations with BPD when other characteristics were considered, but not with current lung function parameters. In this exploratory study of the airway metabolome, preterm-born children with a history of BPD had changes consistent with reduced antioxidant mechanisms suggesting oxidative stress.

Association of early and current life factors with telomere length in preterm-born children

Background Telomeres shorten after each cell division. Since preterm-born babies are delivered early and often suffer from inflammatory conditions such as bronchopulmonary dysplasia (BPD), their telomere length may be altered. Objectives We assessed associations of early and current life factors with telomere length in saliva samples obtained from 7–12-year-old children born at ≤34 weeks’ gestation and term-born controls. Study design Relative telomere length was measured by qPCR on extracted DNA. Groups were compared using independent t-tests or ANOVA with post-hoc correction. Linear regression analysis was also used. Results 534 children had satisfactory telomere data including 383 who were preterm-born (mean (SD) birthweight 1732g (558g), gestation 31.1 (2.6) weeks) and 151 term-born (3464g (510g); 39.8 (1.3) weeks). Telomere length was longer in children who had intrauterine growth restriction (IUGR) at birth: mean (SD): 464.6 (166.3) vs. 418.6 (110.7) in the no-IUGR group; in females: 440.2 (130.1) vs. 405.7 (101.5) in males; and in the least deprived group (397.8 (95.0) vs. 437.6 (121.9) most vs least deprivation quintile). Differences were most notable in females with IUGR. However, telomere length was not different between the preterm and term groups; the BPD and no BPD groups nor was it related to lung function or cardiovascular measurements. In multivariable regression analyses, telomere length was associated with sex, IUGR and deprivation with the greatest difference observed in females with IUGR. Conclusions Telomere length was associated with sex, IUGR and deprivation, especially in females with IUGR, but not with prematurity, BPD, lung function or cardiovascular measurements.

Gm15886-Hipk1 Signaling Pathway Plays Important Roles in the Pathogenesis of Bronchopulmonary Dysplasia Mice

Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in the respiratory system of premature infants. Gm15886, as a lncRNA, is highly expressed in lung tissue of BPD newborn mice. Aims: This study aimed to clarify the roles of the Gm15886 gene in the pathogenesis of BPD mice by determining the expression of Gm15886 and Hipk1 in lung tissues. Methods: Sequence and localization of the Gm15886 gene and the related information of its adjacent genes were obtained using the UCSC browsing tool. The targeting gene of the Gm15886 was predicted using the Ensemble database and double luciferase assay. Neonatal C57BL/6J mice were exposed to 95% hyperoxia for 7 days to generate the hyperoxia-induced BPD mouse model. RT-PCR assay was used to detect Gm15886, Hipk1, and VEGF gene transcriptions in lung tissues in the development process of BPD (0, 3, 5, and 7 days). The pathological changes in lung tissues and Hipk1/VEGF gene transcription in lung tissues were detected in the Gm15886 gene silenced BPD mice. Results: Gm15886 gene transcription in lung tissues was significantly increased in mice of the hyperoxia model group compared to that in the air control group (p&lt;0.05). Gm15886 gene could completely bind and interact with the base sequence within the second exon of the Hipk1 gene. Hipk1 was a targeting gene for Gm15886. Gene transcription and expression of Hipk1 were remarkably enhanced in mice of the hyperoxia model group compared to that in the air control group (p&lt;0.05). The silencing of the Gm15886 gene improved alveolar morphology and markedly downregulated Hipk1 and upregulated VEGF gene transcription compared to those in the Blank vector BPD group (p&lt;0.05). Conclusions: Gm15886-Hipk1 signaling pathway plays a critical role in the pathogenesis of BPD through modulating Hipk1 and VEGF gene transcription. This study might provide a theoretical basis for the treatment of BPD.

Clinical characteristics of bronchopulmonary dysplasia in very preterm infants.

With the development of perinatal and neonatal intensive care medicine, the survival rate of very premature infants increases year by year. However, the incidence of bronchopulmonary dysplasia (BPD) increases year by year, which seriously affects the survival prognosis of very premature infants. How to prevent and treat BPD effectively has become the focus of neonatologists. This study aims to provide ideas for the prevention and treatment of BPD in very preterm infants via analyzing the clinical characteristics of BPD. A total of 472 cases of very premature infants admitted to the Divison of Neonatology, Department of Pediatrics at the Second Xiangya Hospital of Central South University were retrospectively selected and assigned into a BPD group (n=147) and a non-BPD group (n=325) according to the diagnosis of BPD. Clinical data of each group were collected to find out the clinical characteristics of BPD in very preterm infants. Basic information, maternal pregnancy data, laboratory findings, nutritional support, respiratory support patterns and duration, and systemic complications were included. Compared with the non-BPD group, gestational age, birth weight, head circumference and body length in the BPD group were lower, the Apgar score in 1st min and 5th min and average body weight growth rate were lower (all P<0.05); the ratios of male, very low birth weight (VLBW), and extremely low birth weight (ELBW) in the BPD group were higher than those in the non-BPD group (all P<0.5); the incidence of maternal cervical insufficiency and the rate of using embryo transfer technology in the BPD group were higher than those in the non-BPD group, and the rate of using prenatal hormone in the BPD group was lower than that in the non-BPD group (all P<0.05). The positive rate of sputum culture in the BPD group was higher than that in the non-BPD group (P<0.05), and the white blood cell count, neutrophil ratio, and procalcitonin in the BPD group were higher than those in the non-BPD group (all P<0.05). The period of fasting, minimal feeding, total parenteral nutrition (TPN), and partial parenteral nutrition (PPN) in the BPD group were longer than those in the non-BPD group (all P<0.05). The duration of nasal catheter oxygen inhalation and mechanical ventilation in the BPD group was longer than that in the non-BPD group, and the rates of mechanical ventilation at Day 1, 3, 7, 14, 21 and 28 after birth were higher than those in the non-BPD group (all P<0.05). The incidence of respiratory distress syndrome, apnea of prematurity, respiratory failure, pneumonia, pulmonary hemorrhage, pleural effusion, persistent pulmonary hypertension, hemodynamic patent ductus arteriosus, cytomegalovirus infection, neonatal necrotic enterocolitis, cholestasis, anemia, abnormal blood system, hypothyroidism, retinopathy of prematurity, and internal environment disorders in the BPD group were significantly higher than those in non-BPD group (all P<0.05). There are significant differences between very premature infants with BPD and those without BPD in general information, maternal history, inflammatory indicators, nutritional support, respiratory support, comorbidities and complication rates. To ensure normal fetal development, reducing the inflammatory reaction of very premature infants, establishing enteral nutrition as early as possible, shortening the time of mechanical ventilation, and reducing the occurrence of complications are beneficial to decrease the incidence of BPD in very premature infants and improve the long-term prognosis of BPD.

Risk factors for bronchopulmonary dysplasia infants with respiratory score greater than four: a multi-center, prospective, longitudinal cohort study in China

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity involving both pre- and post-natal factors. A large, prospective, longitudinal cohort study was conducted to determine whether inflammation-related factors are associated with an increased risk of BPD in preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and respiratory score > 4. The study included infants from 25 participating hospitals in China between March 1, 2020 and March 31, 2022. The primary outcomes were BPD and severity of BPD at 36 weeks post-menstrual age. A total of 1362 preterm infants were enrolled in the study. After exclusion criteria, the remaining 1088 infants were included in this analysis, of whom, 588 (54.0%) infants were in the BPD group and 500 (46.0%) were in the non-BPD group. In the BPD III model, the following six factors were identified: birth weight (OR 0.175, 95% CI 0.060–0.512; p = 0.001), surfactant treatment (OR 8.052, 95% CI 2.658–24.399; p < 0.001), mean airway pressure (MAP) ≥ 12 cm H2O (OR 3.338, 95% CI 1.656–6.728; p = 0.001), late-onset sepsis (LOS) (OR 2.911, 95% CI 1.514–5.599; p = 0.001), ventilator-associated pneumonia (VAP) (OR 18.236, 95% CI 4.700–70.756; p < 0.001) and necrotizing enterocolitis (NEC) (OR 2.725, 95% CI 1.182–6.281; p = 0.019). Premature infants remained at high risk of BPD and with regional variation. We found that post-natal inflammation-related risk factors were associated with an increased risk of severe BPD, including LOS, VAP, NEC, MAP ≥ 12 cm H2O and use of surfactant.

Microbial signatures in amniotic fluid at preterm birth and association with bronchopulmonary dysplasia

BackgroundMicrobiome dysbiosis can have long-lasting effects on our health and induce the development of various diseases. Bronchopulmonary dysplasia (BPD) is a multifactorial disease with pre- and postnatal origins including intra-amniotic infection as main risk factor. Recently, postnatal pathologic lung microbiota colonization was associated with BPD. The objectives of this prospective observational cohort study were to describe differences in bacterial signatures in the amniotic fluid (AF) of intact pregnancies without clinical signs or risk of preterm delivery and AF samples obtained during preterm deliveries and their variations between different BPD disease severity stages.MethodsAF samples were collected under sterile conditions during fetal intervention from intact pregnancies (n = 17) or immediately before preterm delivery < 32 weeks (n = 126). Metabarcoding based approaches were used for the molecular assessment of bacterial 16S rRNA genes to describe bacterial community structure.ResultsThe absolute amount of 16S rRNA genes was significantly increased in AF of preterm deliveries and detailed profiling revealed a reduced alpha diversity and a significant change in beta diversity with a reduced relative abundance of 16S rRNA genes indicative for Lactobacillus and Acetobacter while Fusobacterium, Pseudomonas, Ureaplasma and Staphylococcus 16S rRNA gene prevailed. Although classification of BPD by disease severity revealed equivalent absolute 16S rRNA gene abundance and alpha and beta diversity in no, mild and moderate/severe BPD groups, for some 16S rRNA genes differences were observed in AF samples. Bacterial signatures of infants with moderate/severe BPD showed predominance of 16S rRNA genes belonging to the Escherichia-Shigella cluster while Ureaplasma and Enterococcus species were enriched in AF samples of infants with mild BPD.ConclusionsOur study identified distinct and diverse intrauterine 16S rRNA gene patterns in preterm infants immediately before birth, differing from the 16S rRNA gene signature of intact pregnancies. The distinct 16S rRNA gene signatures at birth derive from bacteria with varying pathogenicity to the immature lung and are suited to identify preterm infants at risk. Our results emphasize the prenatal impact to the origins of BPD.

The value of hematocrit for predicting bronchopulmonary dysplasia in very low birth weight preterm infants.

To determine hematocrit (HCT) and to identify independent risk factors for predicting bronchopulmonary dysplasia (BPD) in preterm infants with very low birth weight (VLBW) infants. This retrospective study included 296 premature infants with VLBW in the neonatal intensive care unit of the First Affiliated Hospital of the University of Science and Technology of China between January 2015 and December 2019. Maternal pregnant information and clinical information as well as hematological parameters of preterm babies were collected and compared. Then the maximum area under the curve of receiver operating characteristic curve was developed to estimate the predictive indicator in the blood. Finally, differential variables together with the predictive index were screened for multiple logistic regression analysis to determine independent prognostic factors for BPD. Infants were divided into a BPD group (134 cases) and a non-BPD group (162 cases). The area under the curve of HCT at postnatal 1 week was 0.737 with the sensitivity of 52.30 % and the specificity of 86.00%. Birth weight (BW) <1.12 kg, gestational age <28.4 weeks, newborn respiratory distress syndrome, mechanical ventilation ≥ 7 days, ventilation associated pneumonia, patent arterial duct, PaO2/FiO2 <300 mm Hg and HCT <0.455 at postnatal 1 week were risk factors for BPD of VLBW infants. HCT levels below 0.455 at 1 week after birth serve as a valuable indicator for the potential development of BPD.

Association between plasma lysophosphatidic acid levels and bronchopulmonary dysplasia in extremely preterm infants: A prospective study.

Lysophosphatidic acid (LPA) is implicated in bronchopulmonary dysplasia (BPD) pathogenesis, but clinical evidence is lacking. This study aimed to investigate LPA levels in preterm infants with and without BPD and explore LPA as a biomarker for predicting BPD occurrence. Premature infants with a gestational age of <28 weeks or a birth weight of <1000 g were enrolled. Blood samples were collected at postnatal day (PD) 7, 28, and postmenstrual age (PMA) 36 weeks, and plasma LPA levels were measured using a commercial ELISA kit. Receiver operating characteristic curve (ROC) curve analysis determined the PD 28 cutoff for LPA, and multivariable regression analyzed LPA's independent contribution to BPD and exploratory outcomes. Among the 91 infants enrolled in this study, 35 were classified into the non-BPD group and 56 into the BPD group. Infants with BPD had higher plasma LPA levels at PD 28 (6.467 vs. 4.226 μg/mL, p = 0.034) and PMA 36 weeks (2.330 vs. 1.636 μg/mL, p = 0.001). PD 28 LPA level of 6.132 μg/mL was the cutoff for predicting BPD development. Higher PD 28 LPA levels (≥6.132 μg/mL) independently associated with BPD occurrence (OR 3.307, 95% CI 1.032-10.597, p = 0.044). Higher LPA levels correlated with longer oxygen therapy durations [regression coefficients (β) 0.147, 95% CI 0.643-16.133, p = .034]. Infants with BPD had higher plasma LPA levels at PD 28 and PMA 36 weeks. Higher PD 28 LPA levels independently associated with an increased BPD risk.