Validation of a new Japanese classification for predicting severe bronchopulmonary dysplasia in preterm infants.

BackgroundThis study evaluated the effects of less invasive surfactant administration (LISA) and intubation-surfactant-extubation (InSurE) on bronchopulmonary dysplasia (BPD) in preterm infants with respiratory distress syndrome (RDS).MethodsNeonates with respiratory distress syndrome requiring surfactant, with gestational age < 32 weeks and birth weight < 1500 g admitted to our neonatal intensive care unit from January 2018 to December 2019, were retrospectively analyzed. LISA and InSurE were used independently. The incidence of BPD at 36 weeks postmenstrual age, pre-discharge mortality, and need for mechanical ventilation (MV) within 72 h of birth were compared between LISA and InSurE group. Secondary outcomes including necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization were analyzed.ResultsAmong the 148 included neonates, there were 46 and 102 infants in LISA group and InSurE group, respectively. There were no significant differences in BPD incidence, the severity of BPD at 36 weeks postmenstrual age, and the rate of MV within the first 72 h after birth between the two groups (P > 0.05, respectively). The incidences of necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization did not differ significantly between the two groups (P > 0.05, respectively).ConclusionsFor surfactant administration among preterm infants with respiratory distress syndrome, LISA did not decrease bronchopulmonary dysplasia and severity of BPD at 36 weeks postmenstrual age. The benefits of LISA would require further evaluations.

A comprehensive analysis of clinical variables for severe bronchopulmonary dysplasia in extremely preterm infants.

A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung disease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop proposed a severity-based definition of BPD for infants <32 weeks' gestational age (GA). Mild BPD was defined as a need for supplemental oxygen (O2) for > or =28 days but not at 36 weeks' postmenstrual age (PMA) or discharge, moderate BPD as O2 for > or =28 days plus treatment with <30% O2 at 36 weeks' PMA, and severe BPD as O2 for > or =28 days plus > or =30% O2 and/or positive pressure at 36 weeks' PMA. The objective of this study was to determine the predictive validity of the severity-based, consensus definition of BPD. Data from 4866 infants (birth weight < or =1000 g, GA <32 weeks, alive at 36 weeks' PMA) who were entered into the National Institute of Child Health and Human Development Neonatal Research Network Very Low Birth weight (VLBW) Infant Registry between January 1, 1995 and December 31, 1999, were linked to data from the Network Extremely Low Birth Weight (ELBW) Follow-up Program, in which surviving ELBW infants have a neurodevelopmental and health assessment at 18 to 22 months' corrected age. Linked VLBW Registry and Follow-up data were available for 3848 (79%) infants. Selected follow-up outcomes (use of pulmonary medications, rehospitalization for pulmonary causes, receipt of respiratory syncytial virus prophylaxis, and neurodevelopmental abnormalities) were compared among infants who were identified with BPD defined as O2 for 28 days (28 days definition), as O2 at 36 weeks' PMA (36 weeks' definition), and with the consensus definition of BPD. A total of 77% of the neonates met the 28-days definition, and 44% met the 36-weeks definition. Using the consensus BPD definition, 77% of the infants had BPD, similar to the cohort identified by the 28-days definition. A total of 46% of the infants met the moderate (30%) or severe (16%) consensus definition criteria, identifying a similar cohort of infants as the 36-weeks definition. Of infants who met the 28-days definition and 36-weeks definition and were seen at follow-up at 18 to 22 months' corrected age, 40% had been treated with pulmonary medications and 35% had been rehospitalized for pulmonary causes. In contrast, as the severity of BPD identified by the consensus definition worsened, the incidence of those outcomes and of selected adverse neurodevelopmental outcomes increased in the infants who were seen at follow-up. The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurodevelopmental outcomes in early infancy more accurately than other definitions.

Cochrane systematic reviews show that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have also been associated with an increased risk of neurodevelopmental impairment. It is unknown whether these beneficial and adverse effects are modulated by differences in corticosteroid treatment regimens. To assess the effects of different corticosteroid treatment regimens on mortality, pulmonary morbidity, and neurodevelopmental outcome in very low birth weight (VLBW) infants. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2) in the Cochrane Library (searched 21 March 2016), MEDLINE via PubMed (1966 to 21 March 2016), Embase (1980 to 21 March 2016), and CINAHL (1982 to 21 March 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials. Randomized controlled trials (RCTs) comparing two or more different treatment regimens of systemic postnatal corticosteroids in preterm infants at risk for BPD, as defined by the original trialists. Studies investigating one treatment regimen of systemic corticosteroids to a placebo or studies using inhalation corticosteroids were excluded. Two authors independently assessed eligibility and quality of trials and extracted data on study design, participant characteristics and the relevant outcomes. We asked the original investigators to verify if data extraction was correct and, if possible, to provide any missing data. The primary outcomes to be assessed were: mortality at 36 weeks' postmenstrual age (PMA) or at hospital discharge; BPD defined as oxygen dependency at 36 weeks' PMA; long-term neurodevelopmental sequelae, including cerebral palsy, measured by the Bayley Mental Developmental Index (MDI); and blindness or poor vision. Secondary outcomes were: duration of mechanical ventilation and failure to extubate at day 3 and 7 after initiating therapy; rescue treatment with corticosteroids outside the study period; and the incidence of hypertension, sepsis and hyperglycemia during hospitalizations. Data were analyzed using Review Manager 5 (RevMan 5). We used the GRADE approach to assess the quality of evidence. Fourteen studies were included in this review. Only RCTs investigating dexamethasone were identified. Eight studies enrolling a total of 303 participants investigated the cumulative dosage administered; three studies contrasted a high versus a moderate and five studies a moderate versus a low cumulative dexamethasone dose.Analysis of the studies investigating a moderate dexamethasone dose versus a high-dosage regimen showed an increased risk of BPD (typical risk ratio (RR) 1.50, 95% confidence interval (CI) 1.01 to 2.22; typical risk difference (RD) 0.26, 95% CI 0.03 to 0.49; number needed to treat for an additional harmful outcome (NNTH) 4, 95% CI 1.9 to 23.3; I² = 0%, 2 studies, 55 infants) as well as an increased risk of abnormal neurodevelopmental outcome (typical RR 8.33, 95% CI 1.63 to 42.48; RD 0.30, 95% CI 0.14 to 0.46; NNTH 4, 95% CI 2.2 to 7.3; I² = 68%, 2 studies, 74 infants) when using a moderate cumulative-dosage regimen. The composite outcomes of death or BPD and death or abnormal neurodevelopmental outcome showed similar results although the former only reached borderline significance.There were no differences in outcomes between a moderate- and a low-dosage regimen.Four other studies enrolling 762 infants investigated early initiation of dexamethasone therapy versus a moderately early or delayed initiation and showed no significant differences in the primary outcomes. The two RCTs investigating a continuous versus a pulse dexamethasone regimen showed an increased risk of the combined outcome death or BPD when using the pulse therapy. Finally, two trials investigating a standard regimen versus a participant-individualized course of dexamethasone showed no difference in the primary outcome and long-term neurodevelopmental outcomes.The quality of evidence for all comparisons discussed above was assessed as low or very low, because the validity of all comparisons is hampered by small samples of randomized infants, heterogeneity in study population and design, non-protocolized use of 'rescue' corticosteroids and lack of long-term neurodevelopmental data in most studies. Despite the fact that some studies reported a modulating effect of treatment regimens in favor of higher-dosage regimens on the incidence of BPD and neurodevelopmental impairment, recommendations on the optimal type of corticosteroid, the optimal dosage, or the optimal timing of initiation for the prevention of BPD in preterm infants cannot be made based on current level of evidence. A well-designed large RCT is urgently needed to establish the optimal systemic postnatal corticosteroid dosage regimen.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may play a role in this relationship. Objectives: To determine the association between prolonged episodes of intermittent hypoxemia and severe bronchopulmonary dysplasia. Methods: A post hoc analysis of extremely preterm infants in the Canadian Oxygen Trial who survived to 36 weeks' postmenstrual age was performed. Oxygen saturations <80% for ⩾1 minute and the proportion of time per day with hypoxemia were quantified using continuous pulse oximetry data that had been sampled every 10 seconds from within 24 hours of birth until 36 weeks' postmenstrual age. The study outcome was severe bronchopulmonary dysplasia as defined in the 2001 NIH Workshop Summary. Measurements and Main Results: Of 1,018 infants, 332 (32.6%) developed severe bronchopulmonary dysplasia. The median number of hypoxemic episodes ranged from 0.8/day (interquartile range, 0.2-1.1) to 60.2/day (interquartile range, 51.4-70.3) among the least and most affected 10% of infants. Compared with the lowest decile of exposure to hypoxemic episodes, the adjusted relative risk of severe bronchopulmonary dysplasia increased progressively from 1.72 (95% confidence interval, 1.55-1.90) at the 2nd decile to 20.40 (95% confidence interval, 12.88-32.32) at the 10th decile. Similar risk gradients were observed for time in hypoxemia. Significant differences in the rates of hypoxemia between infants with and without severe bronchopulmonary dysplasia emerged within the first week after birth. Conclusions: Prolonged intermittent hypoxemia beginning in the first week after birth was associated with an increased risk of developing severe bronchopulmonary dysplasia among extremely preterm infants. Clinical trial registered with www.isrctn.com (ISRCTN62491227) and www.clinicaltrials.gov (NCT00637169).

Background: Dexamethasone treatment started soon after birth is controversial. Objectives: To determine if postnatal dexamethasone treatment during the first week of life is beneficial in preventing bronchopulmonary dysplasia (BPD) in preterm infants. Methods: Randomised controlled trials of postnatal dexamethasone therapy started in the first week of life in infants at risk of BPD were sought using methods of the Cochrane Collaboration. Data regarding clinical outcomes including mortality, BPD, death or BPD, complications during the primary hospitalisation, and long-term outcome were abstracted and analysed using RevMan 5. Results: 20 randomised controlled trials enrolling a total of 2,860 participants were eligible for inclusion. Meta-analysis of these trials demonstrated significant benefits as regards earlier extubation and decreased risks of BPD at both 28 days’ and 36 weeks’ postmenstrual age (PMA), death or BPD at 28 days’ and 36 weeks’ PMA, patent ductus arteriosus and severe retinopathy of prematurity. Gastrointestinal bleeding and intestinal perforation were important adverse effects, and the risks of hyperglycaemia and hypertension were also increased. In the seven trials (921 infants) that reported late outcomes, cerebral palsy and the combined outcome of death or cerebral palsy were significantly more common in those treated with dexamethasone. Conclusions: The benefits of early dexamethasone treatment (≤7 days) to prevent BPD do not outweigh the known or potential adverse effects of this treatment, and it cannot be recommended for routine clinical practice.

Free oxygen radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. Superoxide dismutase (SOD) is a naturally occurring enzyme which provides a defense against such oxidant injury. Providing supplementary SOD has been tested in clinical trials to prevent BPD in preterm infants. To determine the efficacy and safety of SOD in the prevention and treatment of BPD on mortality and other complications of prematurity in infants at risk for, or having BPD. We searched CENTRAL, PubMed, Embase, and three trials registers on 22 September 2022 together with reference checking, citation searching and contact with study authors to identify additional studies. Randomized, quasi-randomized and cluster-randomized controlled trials (RCTs) where the participants were preterm infants who had developed, or were at risk of developing BPD, and who were randomly allocated to receive either SOD (in any form, by any route, any dose, anytime) or placebo, or no treatment. We used standard Cochrane methods. Our primary outcomes were BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality, mortality prior to discharge, and BPD or death at 36 weeks' postmenstrual age. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs) for the dichotomous outcomes. We used GRADE to assess certainty of evidence for each outcome. We included three RCTs (380 infants) on SOD administration in preterm infants at risk for BPD, and no studies in preterm infants with evolving BPD / early respiratory insufficiency. The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days (RR 1.09, 95% CI 0.94 to 1.26; RD 0.06, 95% CI -0.05 to 0.16, 1 study, 302 infants; I2 for RR and RD not applicable), BPD defined as oxygen at 36 weeks' postmenstrual age (RR 0.96, 95% CI 0.72 to 1.29; RD -0.01, 95% CI -0.11 to 0.09, 2 studies, 335 infants; I2 for RR and RD = 0%), neonatal mortality (RR 0.98, 95% CI 0.57 to 1.68; RD -0.00, 95% CI -0.08 to 0.07, 2 studies, 335 infants; I2 for RR and RD = 0%), and mortality prior to discharge (RR 1.20, 95% CI 0.53 to 2.71; RD 0.04, 95% CI -0.14 to 0.23, 2 studies, 78 infants; I2 for RR and RD = 0%). No studies reported BPD or death at 36 weeks' postmenstrual age. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage (RR 0.95, 95% CI 0.78 to 1.15; RD -0.03, 95% CI -0.15 to 0.08, 2 studies, 335 infants; I2for RR = 0%, I2 for RD = 8%), and severe retinopathy of prematurity (ROP) (RR 0.97, 95% CI 0.57 to 1.65; RD -0.01, 95% CI -0.10 to 0.09, 1 study, 244 infants; I2 for RR and RD not applicable). No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. Certainty of evidence was very low for all outcomes. We identified no ongoing trials. The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality and mortality prior to discharge compared to placebo. No studies reported BPD or death at 36 weeks' postmenstrual age and need for supplemental oxygen. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage and severe retinopathy of prematurity. No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. The effects of SOD in preterm infants has not been reported in any trial in the last few decades, considering that the most recent trial on SOD in preterm infants was conducted in 1997/1998, and no new studies are ongoing. In the light of the limited available evidence, new data from preclinical and observational studies are needed to justify the conduction of new RCTs. Observational studies might report how SOD is administered, including indication, dose and association with relevant outcomes such as mortality, BPD and long-term neurodevelopment.

Background: The natural history and optimal management of a patent ductus arteriosus (PDA) among infants with established severe bronchopulmonary dysplasia (sBPD) remains uncertain. Objectives: To describe the characteristics of PDA present at ≥36 weeks’ postmenstrual age (PMA) and the effects of late surgical PDA closure in a referral cohort of very preterm infants with sBPD. Study Design: This retrospective cohort study was performed in a tertiary neonatal intensive care unit. Study infants were born at <32 weeks’ gestation between 2010 and 2016, diagnosed with sBPD, and had an echocardiographic PDA at ≥36 weeks’ PMA. We reviewed echocardiograms performed closest to 3 time points (≥36 weeks’ PMA, hospital discharge, and 1 year of age) and assessed clinical outcomes among infants with versus without late PDA treatment. Results: Among 329 infants with sBPD, 59 had a PDA at ≥36 weeks’ PMA. Most PDAs were small (n = 33) and shunted left to right (n = 53). The PDA closed spontaneously prior to discharge in 5 of 21 infants who did not undergo surgical closure and decreased in size in 3. The PDA spontaneously closed by 1 year of age in 6 out of 12 infants with an open duct at discharge. PDA surgery (n = 23) at ≥36 weeks’ PMA was not associated with increased risk for the composite outcome of tracheostomy, systemic vasodilator at discharge, or death after adjusting for potential confounders (OR 3.2, 95% CI 0.81–13.0). Conclusions: The majority of conservatively treated late PDAs closed spontaneously or decreased in size.PDA surgery was not associated with severe adverse clinical outcomes.

Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth. Red blood cell distribution width (RDW), a measure of the variation of red blood cell size, could reflect oxidative stress and chronic inflammation in many diseases such as cardiovascular, pulmonary, and other diseases. The objectives of the present study were to evaluate perinatal factors affecting RDW and to validate whether RDW could be a potential biomarker for BPD. A total of 176 preterm infants born at < 30 weeks were included in this study. They were categorized into BPD (n = 85) and non-BPD (n = 91) infants. RDW at birth and 14 days and 28 days of life (DOL 14, DOL 28) were measured. Clinical data were obtained from all subjects at Fukushima Medical University (Fukushima, Japan). The mean RDW at birth, DOL 14 and DOL 28 were 16.1%, 18.6%, 20.1%, respectively. Small for gestational age (SGA), chorioamnionitis (CAM), hypertensive disorders of pregnancy (HDP), gestational age and birth weight were significantly associated with RDW at birth. SGA, BPD and red blood cell (RBC) transfusion before DOL 14 were associated with RDW at DOL 14. BPD and RBC transfusion before DOL 14 were associated with RDW at DOL 28. Compared with non-BPD infants, mean RDW at DOL 14 (21.1% vs. 17.6%, P < 0.001) and DOL 28 (22.2% vs. 18.2%, P < 0.001) were significantly higher in BPD infants. Multivariate analysis revealed that RDW at DOL 28 was significantly higher in BPD infants (P = 0.001, odds ratio 1.63; 95% CI 1.22–2.19). Receiver operating characteristic analysis for RDW at DOL 28 in infants with and without BPD yielded an area under the curve of 0.87 (95% CI 0.78–0.91, P < 0.001). RDW at DOL 28 with mild BPD (18.1% vs. 21.3%, P < 0.001), moderate BPD (18.1% vs. 21.2%, P < 0.001), and severe BPD (18.1% vs. 24.0%, P < 0.001) were significantly higher than those with non-BPD, respectively. Furthermore, there are significant differences of RDW at DOL 28 among mild, moderate, and severe BPD. In summary, we conclude that RDW at DOL 28 could serve as a biomarker for predicting BPD and its severity. The mechanism by which RDW at DOL 28 is associated with the pathogenesis of BPD needs further elucidation.

To study the influencing factors for the development and severity of bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g. A retrospective analysis was performed on the medical data of preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g who were admitted to Women and Children's Hospital Affiliated to Xiamen University from January 1, 2017 to December 31, 2021. According to oxygen dependence on day 28 after birth, they were divided into two groups: BPD (n=218) and non-BPD (n=142). According to disease severity based on oxygen concentration required at the corrected age of 36 weeks or at discharge, the infants with BPD were divided into two groups: mild BPD (n=154) and moderate/severe BPD (n=64). Indices such as perinatal data and nutritional status were compared between groups. The multivariate logistic regression analysis was used to determine the influencing factors for BPD and its severity. The incidence rate and severity of BPD increased with the reduction in gestational age and birth weight (P<0.05). The multivariate logistic regression analysis showed that a long duration of invasive mechanical ventilation (OR=1.320, P<0.05), hemodynamically significant patent ductus arteriosus (OR=2.032, P<0.05), and a prolonged time to reach oral calorie goal of 110 kcal/(kg·d) (OR=1.041, P<0.05) were risk factors for BPD, while an older gestational age was a protective factor against BPD (OR=0.535, P<0.05). Early-onset sepsis (OR=2.524, P<0.05) and a prolonged time to reach oral calorie goal of 110 kcal/(kg·d) (OR=1.029, P<0.05) were risk factors for moderate/severe BPD, while a high mean weight growth velocity was a protective factor against moderate/severe BPD (OR=0.906, P<0.05). The incidence rate and severity of BPD in preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g can be reduced by shortening the duration of invasive mechanical ventilation, giving early treatment of early-onset sepsis and hemodynamically significant patent ductus arteriosus, adopting active enteral nutritional strategies, and increasing mean weight growth velocity.

BackgroundLess invasive surfactant administration (LISA) is a way of giving surfactant without endotracheal intubation and has shown to be promising in reducing the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, the mechanism underlying its beneficial effect and variations in the technique of administration may prevent its widespread use. This trial aims to evaluate the effects of two methods of surfactant administration, LISA or endotracheal surfactant administration followed by low peak pressure (LPPSA) ventilation, in preterm infants with respiratory distress syndrome (RDS).MethodsThe LISA Or Low Peak Pressure trial is to be conducted in 14 tertiary neonatal intensive care units in China. A total of 600 preterm infants born with gestational age between 250/7 and 316/7 weeks and with a primary diagnosis of RDS will be involved in the study. Infants will be randomized to the LISA or LPPSA group when surfactant therapy is indicated. Primary outcomes include mortality, severity of bronchopulmonary dysplasia at 36 weeks of postmenstrual age (PMA), and mechanical ventilation (MV) in the first 72 h of life. Secondary outcomes include the days of MV, duration of all sorts of non-invasive respiratory support, fraction of inspired oxygen, oxygen saturation before and after surfactant administration, and time required to perform the procedure for surfactant administration. The incidence of comorbidities, including retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), hemodynamically significant patent ductus arteriosus (hsPDA), pneumothorax, and massive pulmonary hemorrhage within 48 h of surfactant administration, and the failure rates of each technique will be determined.DiscussionData from recent systematic review and meta-analysis have suggested a possible improvement in outcomes of preterm infants with RDS by the LISA technique. However, robust evidence is lacking. Why LISA plays a potential role in reducing respiratory morbidity, mainly BPD in preterm infants, remains unclear. The possible explanations are the active and uninterrupted delivery of continuous positive airway pressure during the LISA procedure and the avoidance of complications caused by intubation and relatively high pressure/volume ventilation following surfactant administration. We hypothesized that LISA’s effectiveness lies mainly in avoiding relatively high-pressure positive ventilation immediately following surfactant administration. Thus, this multicenter randomized controlled trial will focus on issues of endotracheal intubation and the pressure/volume used during conventional surfactant administration. The effectiveness, safety and comorbidities of preterm infants following LISA or LPPSA will be evaluated.Trial registrationChinese Clinical Trial Registry: ChiCTR1900020970. Registered on 23 January 2019.

Association of increased cord blood soluble endoglin with the development of bronchopulmonary dysplasia in preterm infants with maternal preeclampsia.

To investigate the risk factors for bronchopulmonary dysplasia (BPD) in preterm infants, and to establish a risk prediction model. A total of 120 preterm infants who were admitted to the neonatal intensive care unit of Shanghai Children's Hospital from January to December 2022 were included. According to the diagnostic criteria for BPD released by the National Institute of Child Health and Human Development in 2018, they were divided into a non-BPD group (84 infants) and a BPD group (36 infants). The clinical data of the infants and their mothers were compared between the two groups. The univariate analysis and the stepwise multivariate regression analysis were used to identify the risk factors for BPD and establish a risk prediction model. The results showed that a gestational age of <28 weeks, duration of noninvasive respiratory support, comorbidity with infectious pneumonia, and chorioamnionitis in the mother were independent risk factors for BPD in preterm infants (P<0.05). A nomogram model for predicting the development of BPD was established based on the risk factors, with an area under the receiver operating characteristic curve of 0.93, and the calibration curve of this nomogram had a slope of about 1. The goodness-of-fit test indicated the model fitted well (χ2=8.287, P=0.406). A gestational age of <28 weeks, duration of noninvasive respiratory support, comorbidity with infectious pneumonia, and chorioamnionitis in the mother are independent risk factors for BPD in preterm infants.

Objective: To study the association between Sirtuin1 (Sirt1), a class III histone deacetylator, in tracheal aspirate (TA) leukocytes and the development of bronchopulmonary dysplasia (BPD) in premature infants and modulation of Sirt1 with dexamethasone (Dex) use. Design/methods: Serial TA samples were collected on days 1, 3, 5 and 7 from ventilated premature neonates. Sirt1 was localized by immunocytochemistry and quantified on a scale of 0–4 by blinded observers. BPD was defined as the need of supplemental oxygen at 36 weeks postmenstrual age (PMA). Results: A total of 130 TA samples were collected from 51 infants (mean ± SD: GA 25.5 ± 1.4 w, BW 762 ± 174 g). Eleven infants survived without BPD and 40 infants died before 36 weeks PMA or developed BPD. Sirt1 was localized in the cytoplasm and nuclei of mononuclear (MONO) as well as polymorphonuclear cells. Sirt1 was significantly more localized in the nuclei of MONO cells in infants without BPD compared to infants who developed BPD or died before 36 weeks PMA. Twenty six infants received Dex. There was no significant change in Sirt1 localization with steroid therapy. Conclusions: Lower Sirt1 in TA leukocytes is associated with the development of BPD or death in premature infants. Dex use had no effect on Sirt1.

Bronchopulmonary dysplasia (BPD) is a major morbidity in preterm infants, necessitating early risk assessment to guide interventions. The present study aimed to develop and internally validate a clinical prediction model for BPD. A total 120 preterm infants (<32 gestation weeks) admitted to a neonatal intensive care unit from January 2020 to December 2022 were retrospectively analyzed. Infants were retrospectively classified into BPD (n=34) and non-BPD (n=86) groups based on the 2018 National Institute of Child Health and Human Development criteria. Clinical variables, including maternal, neonatal, respiratory and comorbid factors, were assessed. Univariate and multivariate logistic regression identified independent predictors, which were used to construct a nomogram. Model performance was evaluated using the area under the curve (AUC) of a receiver operating characteristic curve, a calibration curve and Hosmer-Lemeshow test. Internal validation was performed via bootstrapping. The results demonstrated that gestational age, birth weight, sepsis, patent ductus arteriosus and intraventricular hemorrhage were independent predictors of BPD. The model demonstrated good discrimination (AUC=0.918; 95% confidence interval, 0.866-0.971) and good calibration. The nomogram enabled individualized risk estimation, and internal validation confirmed model robustness. In conclusion, the proposed nomogram demonstrated strong discriminative power and clinical applicability for early BPD risk assessment. Future multicenter validation will help extend its generalizability across diverse neonatal populations.