Evaluation of Moderate-Course Hydrocortisone for the Prevention of Bronchopulmonary Dysplasia in Premature Infants: A Pilot Study.

To systematically evaluate the predictive value of platelet (PLT) parameters for bronchopulmonary dysplasia (BPD) in preterm infants. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for studies on PLT parameters predicting BPD in preterm infants from inception to December 2023. The Newcastle-Ottawa Scale was adopted to judge the article's quality. RevMan 5.4 was utilized for Meta-analysis, and Stata/SE 15.1 was applied for sensitivity analysis and Egger regression test. Ten studies were included, including 1637 preterm infants, of which 540 were diagnosed with BPD. Meta-analysis showed that PLTs (SMD = -0.98, 95% CI [-1.57, -0.38], P = .001), mean platelet volume (MPV) (SMD = 0.67, 95% CI [0.19, 1.15], P = .006), and PMI (SMD = -0.47, 95% CI [-0.65, -0.28], P < .00001) could assist in predicting BPD in preterm infants. Subgroup analyses showed that PLT parameters 3 days after birth had better predictive performance for BPD in preterm infants. Sensitivity analysis implied no significant change in the results after excluding the studies 1 by 1, suggesting robust results of meta-analysis. There was a significant publication bias in the enrolled studies (P < .001). PLT, MPV, and PMI have a predictive value for BPD in preterm infants.

To systematically evaluate the incidence and risk factors of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants. Cohort and case-control studies on the incidence and risk factors of PH complicating BPD (hereinafter referred to as BPD-PH) in preterm infants, published from database inception to July 2024, were retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP Database, Chinese Biomedical Literature Database, PubMed, Web of Science, Embase, MEDLINE, and Cochrane Library. Meta analysis was performed using Stata 15.0 software. A total of 15 studies involving 4 561 preterm infants were included. Meta analysis results showed that the overall incidence of BPD-PH in preterm infants was 20.1% (95%CI: 16.1%-24.0%). Hemodynamically significant patent ductus arteriosus (OR=3.43), mechanical ventilation duration (OR=1.05), small for gestational age (SGA) (OR=7.30), severe BPD (OR=13.25), patent ductus arteriosus requiring surgical ligation (OR=6.03), oligohydramnios (OR=7.24), ventilator-associated pneumonia (OR=3.97), and respiratory distress syndrome (OR=2.70) were identified as risk factors for BPD-PH in preterm infants (P<0.05). The overall incidence of BPD-PH in preterm infants is relatively high. Hemodynamically significant patent ductus arteriosus, mechanical ventilation duration, SGA, severe BPD, patent ductus arteriosus requiring surgical ligation, oligohydramnios, ventilator-associated pneumonia, and respiratory distress syndrome can increase the risk of PH in preterm infants with BPD, and clinical monitoring should prioritize BPD infants with these high-risk factors.

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

Azithromycin has anti-Ureaplasma and anti-inflammatory properties that might help reduce lung injury in preterm infants. To test the efficacy and safety of prophylactic or therapeutic azithromycin in preventing bronchopulmonary dysplasia (BPD) in preterm infants with unknown or proven Ureaplasma status. We searched PubMed, Web of Science, and Cochrane Library until 13 September 2020. Two authors independently assessed the eligibility, risk of bias, and extracted the data. We performed a random-effects model meta-analysis to yield pooled relative risk (RR) or mean difference (MD) with 95% confidence interval (CI). We used the Cochrane GRADE methodology for summarizing the results. We included five randomized clinical trials. The meta-analysis revealed no significant differences in BPD (RR, 0.92; 95% CI,0.71, 1.19; low-quality evidence), death (RR,0.75; 95% CI, 0.52, 1.10; low-quality evidence), and BPD or death (RR, 0.90; 95% CI, 0.74, 1.10; low-quality evidence). However, a significantly lower BPD or death (RR, 0.83; 95% CI, 0.70, 0.99) and a trend towardlower BPD (RR, 0.83; 95% CI, 0.66, 1.03) with azithromycin therapy was noted in Ureoplasma positive neonates. No differences in secondary outcomes were noted, except for significantly lower supplemental oxygen days with azithromycin (MD, -6.06; 95% CI, -7.40, -4.72; moderate-quality evidence). The test for subgroup differences between short (<7 days) and long (>7 days) course of azithromycin were nonsignificant for all the outcomes. Low-quality evidence suggests azithromycin therapy reduces BPD or death in preterm infants with positive Ureoplasma, but not in all 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.

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.

Background: This study examines the relationship between feeding methods during the first 2 weeks post-birth-mother's own milk (MOM), donor human milk (DHM), and formula-and the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. Materials and Methods: A retrospective cohort study was conducted on preterm infants (<32 weeks gestation or <1,500 g birth weight) admitted to Fujian Maternal and Child Health Hospital from March 2023 to February 2024. Infants were grouped by primary feeding method within the first 2 weeks after birth, defined as MOM, DHM, or formula contributing to ≥50% of total feeding. The primary outcome was BPD incidence; the secondary outcome included necrotizing enterocolitis (NEC) stage II or higher, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and sepsis. Results: BPD incidence was lower in the MOM and DHM groups compared with formula (22%, 16% vs. 35%; p = 0.03). Adjusted odds ratios for BPD were 3.35 (95% CI 1.43, 7.85) in the formula group versus MOM and 6.48 (95% CI 1.47, 28.57) versus DHM, with no significant difference between MOM and DHM. NEC incidence was also lower in MOM and DHM groups (7.15%, 9.38% vs. 20.21%; p = 0.016). No significant differences were observed in ROP, PVL, or sepsis rates. Conclusions: MOM and DHM reduce the risk of BPD and NEC in preterm infants, with DHM being as safe as MOM.

To determine whether angiopoietin-1 and endostatin levels in the cord blood could predict the subsequent development of bronchopulmonary dysplasia (BPD) in preterm infants. A total of 102 preterm (gestational age ≤ 32 weeks) infants (28 infants developed BPD and 74 had no BPD) were enrolled in the study. Cord plasma levels of angiopoietin-1 and endostatin were measured by enzyme-linked immunosorbent assay. Preterm infants who subsequently developed BPD had significantly lower cord plasma levels of angiopoietin-1 than those who did not (p < 0.001). Our results showed that cord plasma levels of endostatin were significantly higher in infants with BPD than in those without (p < 0.001). In infants with BPD, angiopoietin-1 levels in cord plasma correlated negatively with endostatin (r = -0.48; p = 0.008). In preterm infants, low-angiopoietin-1 and high-endostatin levels in cord plasma at birth predict the subsequent development of BPD.

To investigate the risk factors for moderate/severe bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age of <32 weeks. A retrospective analysis was performed on the medical data of preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥28 days who were admitted to the neonatal intensive care unit (NICU) of 17 institutions of Jiangsu Neonatal Perinatal Cooperation Network from January 1, 2019 to December 31, 2020 and were diagnosed with BPD. The preterm infants were grouped according to gestational age and severity of BPD. A multivariate logistic regression analysis was used to investigate the risk factors for moderate/severe BPD in various gestational age groups. During the two-year period, a total of 2 603 preterm infants with a gestational age of <32 weeks were admitted to the NICU of the 17 institutions, among whom 961 were diagnosed with BPD, and the incidence rates of BPD and moderate/severe BPD were 36.92% (961/2 603) and 8.64% (225/2 603), respectively. The incidence rate of moderate/severe BPD was 56.5% (26/46) in preterm infants with a gestational age of 24+0-25+6 weeks, 31.0% (66/213) in those with a gestational age of 26+0-27+6 weeks, 16.9% (75/445) in those with a gestational age of 28+0-29+6 weeks, and 22.6% (58/257) in those with a gestational age of 30+0-31+6 weeks. The multivariate logistic regression analysis showed that there were different risk factors for moderate/severe BPD in preterm infants with different gestational ages: patent ductus arteriosus requiring treatment as risk factors in preterm infants with a gestational age of 24+0-25+6 weeks; premature rupture of membranes ≥18 hours, positive pressure ventilation for resuscitation, clinical sepsis, and duration of mechanical ventilation ≥14 days as risk factors in preterm infants with a gestational age of 26+0-27+6 weeks; duration of mechanical ventilation ≥14 days, neonatal pneumonia, and patent ductus arteriosus requiring treatment as risk factors in preterm infants with a gestational age of 28+0-29+6 weeks; positive pressure ventilation for resuscitation, neonatal pneumonia, and anemia of prematurity as risk factors in preterm infants with a gestational age of 30+0-31+6 weeks (P<0.05). The development of moderate/severe BPD is multifactorial in preterm infants with a gestational age of <32 weeks, and there are different risk factors in different gestational age groups. Targeted preventive measures for preterm infants of different gestational ages may be useful to reduce the severity of BPD.

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.

The effect of early dexamethasone administration on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome

BackgroundVitamin D deficiency is associated with asthma and reactive airway disease in childhood but its potential contribution to bronchopulmonary dysplasia (BPD) in preterm infants is unknown. Preterm infants have lower levels of 25-hydroxyvitamin D (25[OH]D) at birth and are at risk for nutritional deficiencies after birth.ObjectiveTo evaluate the association of 25(OH) D concentrations at birth and at 36 weeks corrected gestational age with BPD in preterm infants born prior to 29 completed weeks of gestation.MethodsWe collected umbilical cord blood samples from 44 preterm infants (gestational age <29 weeks) delivered at Brigham and Women's Hospital in Boston. In addition, with parental consent we collected venous samples at 36 weeks corrected age from 20 preterm infants born before 29 weeks gestation (including 6 infants with previously collected cord blood). Samples were frozen at -80°C until subsequent measurement of 25(OH) D levels by chemiluminescence. We used multivariable logistic models to adjust for gestational age and considered other confounding variables including maternal race, age, mode of delivery and infant sex.ResultsAmong 44 infants, 41 (93.2%) survived and 3 (6.8%) died before 36 weeks corrected age. Median 25(OH) D levels at birth were 30.4 ng/ml in preterm infants who subsequently died or developed BPD and 33.8 ng/ml in infants who survived without BPD (p=0.6). Median 25(OH) D levels at corrected age of 36 weeks were 59.0 ng/ml among survivors without BPD and 64.2 ng/ml among survivors with BPD (p=0.9). Neither cord blood nor 36 week corrected 25(OH) D levels were associated with odds of death or BPD (adjusted OR 1.00, 95% CI: 0.73-1.37, OR 0.93, 95% CI: 0.61-1.43 respectively).ConclusionAmong this population of extremely preterm infants neither cord blood nor the 36 week corrected age 25(OH) D levels were associated with development of BPD. Notably, at the current level of supplementation, all extremely preterm infants in our cohort had achieved 25(OH) D levels >30 ng/ml by 36 weeks corrected age, which is thought to represent sufficiency in adult and pediatric populations.

Aim: We tested whether interleukin‐6 (IL‐6) in tracheal aspirate (TA) at birth, as a marker of fetal pulmonary inflammation, can be a predictor of bronchopulmonary dysplasia (BPD) in preterm infants. Methods: A total of 75 preterm (≤32 wk) infants who were intubated in the delivery room were prospectively enrolled. Multivariate logistic regression analysis was done to determine whether IL‐6 in TA at birth is an independent risk factor for BPD, and a receiver‐operating characteristic curve was constructed to determine the accuracy of IL‐6 in TA for predicting the risk of BPD. Results: IL‐6 in TA at birth was an independent risk factor for BPD. Fetal pulmonary inflammation defined as IL‐6 in TA at birth ≥316 pg/ml together with patent ductus arteriosus (PDA) additively predicted the risk of BPD. The sensitivity, specificity, and positive and negative predictive values of fetal pulmonary inflammation for the identification of BPD were 73%, 71%, 58% and 83%, respectively. Conclusion: IL‐6 in TA at birth can be used as a predictor of BPD in combination with the presence of PDA.

This research will explore non-linear relationship between vitamin D status on admission and bronchopulmonary dysplasia (BPD) in preterm infants. Data were retrospectively collected on preterm infants ≤32 weeks gestation and ≥28 weeks gestation hospitalized in our hospital between Jan. 2019 and Jul. 2022, which were classified into BPD and non-BPD groups according to BPD diagnostic criteria. Independent influences between the two groups were staged using comparison of differences between groups, univariate analysis, multivariate analysis, smoothed curve fitting, and threshold effect staging. 255 preterm infants were enrolled in this research, including 135 males and 120 females, with a mean gestational age of 30.59 ± 0.86 weeks. Vitamin D status on admission was an independent protective factor for BPD in preterm infants, with a 6% reduction in the probability of BPD for every 1 ng/ml increase in vitamin D status on admission (p = 0.036). There was also a non-linear relationship, with each 1 ng/ml increase in vitamin D status on admission being associated with an 87% reduction in the incidence of BPD when vitamin D status was <12.82 ng/ml (p = 0.010). Vitamin D status on admission and BPD are non-linearly in preterm infants at 28-32 weeks gestation. Analyzing the relationship between vitamin D status on admission and BPD. A nonlinear relationship and turning point between vitamin D status on admission and BPD was derived by curve fitting and threshold effect. We provide a new reference point for vitamin D supplementation for the prevention of neonatal BPD and to avoid ineffective overmedication.

To analyze the impact of placental histological findings on the development of bronchopulmonary dysplasia (BPD) in preterm infants, this prospective, observational, single-center study included infants born before 32 weeks of gestation between 2012 and 2023. Perinatal variables were collected and correlated with mortality at hospital discharge and the diagnosis of grade 2–3 BPD at 36 weeks postmenstrual age (PMA). Placental histology was categorized into three groups: inflammatory pathology, vascular malperfusion, and no pathology. A total of 1128 preterm infants were enrolled, with placental histology results available for 899 cases. Inflammatory placental pathology was associated with a lower gestational age (GA) at birth (− 1.4 weeks, 95% CI − 1.74 to − 1.11). The increased mortality linked to placental inflammation was no longer significant after adjusting for GA. In preterm infants born at 27 weeks’ GA or later, the effect of vascular malperfusion on BPD showed sexual dimorphism. In males, placental malperfusion was associated with a 2.25-fold increased risk of developing BPD (95% CI 1.10 to 4.57), independent of GA and exposure to mechanical ventilation. No significant differences were observed in females born at 27 weeks or later. Conclusions: The impact of placental histological abnormalities on BPD development is influenced by gestational age and sex. While placental inflammation increases mortality by triggering extremely preterm birth, it does not appear to increase respiratory morbidity compared to cases with normal placental histology at similar GAs. In males, however, placental malperfusion appears to affect lung development and contributes to BPD independently of GA and exposure to mechanical ventilation.What is Known:• Bronchopulmonary dysplasia (BPD) is a common respiratory complication among preterm infants, strongly influenced by prenatal events.• The placenta plays a crucial role in fetal lung development, and its analysis provides objective insight into antenatal conditions.What is New:• Placental malperfusion affects lung development in a sex-specific manner, with male infants born at or after 27 weeks of gestation being more specifically affected and showing a higher susceptibility to BPD, independent of gestational age or mechanical ventilation.• These findings highlight the importance of considering sex differences in BPD pathophysiology and the role of placental pathology.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-025-06016-9.