Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

Can Red Blood Cell and Platelet Transfusions Have a Pathogenic Role in Bronchopulmonary Dysplasia?

OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Changes in Lung Function Among Infants Born Extremely Preterm over a 20-Year Period in the Post-Surfactant Era: A Retrospective Study.

Lung function was assessed at 8 years in 308 infants born extremely preterm between 1994 and 2013. Although lung function of those infants born at 22 through 25 weeks remained unchanged, those who were born at 26-27 weeks showed a significant improvement over the past 2 decades.

Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor Respiratory Function at 7-8 Years of Age.

OBJECTIVE: To clarify the relationships of 3 definitions of severity of bronchopulmonary dysplasia (BPD) with adverse neurodevelopmental and respiratory outcomes at early school-age. STUDY DESIGN: Participants comprised 218 consecutive survivors to 7-8 years of age born either <28 weeks' gestation or weighing <1000 g in Victoria, Australia, in 2005. BPD was classified as none, grade 1 (mild), grade 2 (moderate), or grade 3 (severe), using 2 commonly accepted definitions: 1) Jobe2001, and 2) Higgins2018, and our own 3) Victorian Infant Collaborative Study (VICS) 2005, adapted from Jensen2019. Outcomes included major neurodevelopmental disability, low IQ and academic achievement, poor motor function, and poor respiratory function as assessed by spirometry. Outcomes for children with each grade of BPD were compared with children with no BPD. RESULTS: Of the 218 survivors, 132 (61%) had BPD on Jobe2001 criteria, and 113 (52%) had BPD on both Higgins2018 and VICS2005 criteria. Grade 1 on any criteria was not associated with any adverse neurodevelopmental outcomes. Grade 1 on both Higgins2018 and VICS2005 was associated with reduced spirometry, grade 2 on both Higgins2018 and VICS2005, and grade 3 on all criteria were associated with increased risk for both adverse neurodevelopmental and respiratory outcomes. CONCLUSIONS: Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes.

Rates of bronchopulmonary dysplasia in very low birth weight neonates: a systematic review and meta-analysis.

IMPORTANCE: Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (< 32 weeks) neonates. DATA SOURCES: A search of MEDLINE from January 1990 until September 2019 using search terms related to BPD and prevalence was performed. STUDY SELECTION: Randomized controlled trials and observational studies evaluating rates of BPD in very low birth weight or very low gestational age infants were eligible. Included studies defined BPD as positive pressure ventilation or oxygen requirement at 28 days (BPD28) or at 36 weeks postmenstrual age (BPD36). DATA EXTRACTION AND SYNTHESIS: Two reviewers independently conducted all stages of the review. Random-effects meta-analysis was used to calculate the pooled prevalence. Subgroup analyses included gestational age group, birth weight group, setting, study period, continent, and gross domestic product. Sensitivity analyses were performed to reduce study heterogeneity. MAIN OUTCOMES AND MEASURES: Prevalence of BPD defined as BPD28, BPD36, and by subgroups. RESULTS: A total of 105 articles or databases and 780,936 patients were included in this review. The pooled prevalence was 35% (95% CI, 28-42%) for BPD28 (n = 26 datasets, 132,247 neonates), and 21% (95% CI, 19-24%) for BPD36 (n = 70 studies, 672,769 neonates). In subgroup meta-analyses, birth weight category, gestational age category, and continent were strong drivers of the pooled prevalence of BPD. CONCLUSIONS AND RELEVANCE: This study provides a global estimation of BPD prevalence in very low birth weight/low gestation neonates.

Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Expiratory airflow limitation in adults born extremely preterm: A systematic review and meta-analysis.

Extreme preterm (EP) birth, denoting delivery before the onset of the third trimester, interrupts intrauterine development and causes significant early-life pulmonary trauma, thereby posing a lifelong risk to respiratory health. We conducted a systematic review and meta-analysis to investigate adult lung function following EP birth (gestational age <28 weeks); comparing forced expiratory volume in first second (FEV1), forced vital capacity (FVC), and FEV1/FVC to reference values. Subgroup differences were explored based on timing of birth relative to surfactant use (1991) and bronchopulmonary dysplasia (BPD) status. Systematic searches were performed in Medline, EMBASE, Web of Science and Cochrane Central. Quality assessments were carried out using a modified Newcastle-Ottawa Scale for cohort studies. Sixteen studies encompassing 1036 EP-born adults were included, with 14 studies (n = 787) reporting data as %predicted, and 11 (n = 879) as z-score (not mutually exclusive). Overall mean [95 % confidence interval (CI)] %FEV1 was 85.30 (82.51; 88.09), %FVC was 94.33 (91.74; 96.91), and FEV1/FVC was 79.54 (77.71 to 81.38), all three with high heterogeneity. Overall mean (95 %CI) zFEV1 was -1.05 (-1.21; -0.90) and zFVC was. -0.45 (-0.59; -0.31), both with moderate heterogeneity. Subgroup analyses revealed no difference in FEV1 before versus after widespread use of surfactant, but more impairments after neonatal BPD. This meta-analysis revealed significant airflow limitation in EP-born adults, mostly explained by those with neonatal BPD. FEV1 was more reduced than FVC, and FEV1/FVC was at the lower limit of normal. Although at a group level, most adult EP-born individuals do not meet COPD criteria, these findings are concerning.

Neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD) - A retrospective cohort study.

OBJECTIVE: To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Preterm infants < 29 weeks' gestation born 2007-2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks' postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18-42 months corrected age using the Bayley Scales of Infant Development, 3rd edition. RESULTS: 1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants. CONCLUSION: The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support.

Association between viral infection and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89-3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80-3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies.  Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known: • Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New: • Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age. • The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia.

Neurodevelopment at 24 months corrected age in extremely preterm infants treated with dexamethasone alternatives during the late postnatal period: a cohort study.

The administration of dexamethasone has been associated with suboptimal neurodevelopment. We aimed to compare the development of extremely premature infants treated or not with alternatives to dexamethasone: betamethasone, hydrocortisone hemisuccinate. This retrospective cohort study included infants born before 29 weeks of gestational age, treated or not with late (day ≥ 7) postnatal steroids (betamethasone, hydrocortisone hemisuccinate). The neurodevelopment outcome was evaluated at 24 months corrected age, after adjustment on comorbidities of extreme prematurity. In order to analyse their overall development, data about growth and respiratory outcomes were collected. Among the 192 infants included, 59 (30.7%) received postnatal steroids. Suboptimal neurodevelopment concerned 37/59 (62.7%) postnatal steroid-treated and 43/133 (38.1%; p = 0.002) untreated infants. However, in multivariable analysis, only severe neonatal morbidity (p = 0.007) and male gender (p = 0.027) were associated with suboptimal neurodevelopment outcome at 24 months.  Conclusions: Betamethasone or hydrocortisone hemisuccinate treatment was not an independent risk for suboptimal neurological development, growth and respiratory outcomes assessed at 24 months corrected age in extremely premature infants.  Registration number: The study was registered on the ClinicalTrials.gov register: NCT05055193. What is Known: • Late postnatal steroids are used to treat bronchopulmonary dysplasia • Meta-analyses warned against the neurological risk of dexamethasone use during neonatal period. Early or late hydrocortisone hemisuccinate has been evaluated in multiple studies, none of which have reported an adverse effect on neurodevelopment at least to 2 years. Data about the use of betamethasone are scarce. What is New: • The risk of suboptimal neurodevelopment was higher among extremely premature infants who received postnatal steroids when compared to those who did not. • Betamethasone and hydrocortisone hemisuccinate treatment was not an independent risk factor for suboptimal neurodevelopment at 24 months corrected age.

Pulmonary function and bronchopulmonary dysplasia classification: insights from the Spanish Registry.

In 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this observational study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36 weeks postmenstrual age (PMA). The study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7 years of age. Statistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36 weeks PMA. The study involved 143 patients with a median gestational age (GA) of 27.3 weeks (range 25.7-28.7) and a median weight of 880 g (range 740-1135). Abnormal spirometry results were observed in 39.2% (56) of the patients. Among patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36 weeks PMA exhibited an increased risk of abnormal spirometry results (OR 4.48; 95% CI 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10.65; 95% CI 2.06-54.98) and BPD type 2 (OR 6.76; 95% CI 1.09-42.06). No significant differences were found in the incidence of an obstructive pattern between BPD types.      Conclusion: The requirement of more than 30% oxygen at 36 weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function. What is Known: • Premature patients with bronchopulmonary dysplasia (BPD) may present abnormalities in pulmonary function tests during school age. However, the predictive accuracy of consensus BPD severity classification remains uncertain. What is New: • The requirement of more than 30% oxygen at 36 weeks postmenstrual age (PMA) indicates a potential risk of pulmonary function impairment in school-aged children with BPD. Additionally, a significant correlation has been observed between a restrictive-mixed pattern with exposure to mechanical ventilation and the development of severe forms of BPD.

Patent Ductus Arteriosus and Development of Bronchopulmonary Dysplasia-associated Pulmonary Hypertension.

Rationale: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). A patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. Objective: To determine whether the presence and duration of ductus arteriosus patency differs between extremely preterm infants with and without BPD-PH. Methods: We conducted a retrospective case-control study among preterm infants of gestational age 22 weeks, 0 days, to 28 weeks, 6 days, who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017 to 2020. Infants who were diagnosed with PH (cases) by echocardiography were compared with infants without PH (control subjects). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Logistic regression adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. Measurements and Main Results: A total of 138 infants developed BPD alone, and 82 infants developed BPD-PH. After adjustment for differing covariates between groups, both PDA (adjusted odds ratio, 4.29; 95% confidence interval, 1.89-9.77) and moderate to large PDA (adjusted odds ratio, 4.15; 95% confidence interval, 1.78-9.64) remained significantly related to BPD-PH at discharge. By probit analysis, each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (P < 0.001) and 0.45 (P < 0.001), respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both the presence of and a longer duration of ductus arteriosus patency were associated with the development of BPD-PH.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Risk factors associated with anemia of prematurity requiring red blood cell transfusion in very low birth weight infants: a retrospective study.

BACKGROUND: Anemia of prematurity (AOP) is prevalent among very low birth weight infants (VLBWIs). Red blood cell (RBC) transfusions, while necessary for managing AOP, have been linked to adverse neonatal outcomes. METHODS: This retrospective study analyzed the medical records of 98 VLBWIs (24-31 weeks gestation) admitted to the Chungbuk National University Hospital neonatal intensive care unit. Infants were categorized based on RBC transfusion status and birth weight (< 1000 g and 1000-1499 g). Clinical outcomes between the groups were compared. RESULTS: Of the 98 infants, 35 (35.7%) received RBC transfusions. The RBC transfusion group exhibited significantly higher incidence of bronchopulmonary dysplasia ([Formula: see text]moderate), prolonged invasive mechanical ventilation, intraventricular hemorrhage (grades 1-2), extended time to full enteral feeding, and extended total parenteral nutrition (TPN) compared to the non-RBC transfusion group. Birth weight was inversely correlated with the number of RBC transfusions (p = 0.004). The duration of invasive mechanical ventilation and TPN administration were positively associated with the number of RBC transfusions (p < 0.001 and p = 0.025, respectively). CONCLUSIONS: The RBC transfusion group experienced more comorbidities than the non-transfusion group. Birth weight, duration of invasive ventilation, and duration of TPN were associated with the number of RBC transfusions. Strategies to reduce the duration of invasive ventilation and early discontinuation of TPN may mitigate the need for RBC transfusions in AOP.

Sex differences in preterm respiratory morbidity: A recent whole-population study.

AIM: To determine whether there were differences between male and female infants in respiratory morbidity in a whole population of extremely preterm infants, including infants born below 24 weeks of gestation. METHODS: Retrospective whole-population study of all infants <28 weeks of gestation admitted to a neonatal unit in England from 2014 to 2019. Bronchopulmonary dysplasia (BPD) development was defined as any respiratory support at 36 weeks postmenstrual age. RESULTS: The 11 844 infants had a median (IQR) gestational age of 26.0 (24.9-27.1) weeks and a birth weight of 0.81 (0.67-0.96) kg. The duration of invasive ventilation was longer in male compared to female infants who were born at 24-27 completed weeks of gestation (p < 0.001), but not significantly different between male and female infants born at 22 and 23 weeks of gestation (p = 0.446). The incidence of BPD was higher in male compared to female infants born at 24-27 weeks of gestation (p < 0.001) but not different between male and female infants born at 22 and 23 weeks of gestation (p = 0.148). CONCLUSION: Respiratory morbidity was more pronounced in male compared to female extremely preterms, only in gestations 24-27 completed weeks. Male predominance was absent in infants born below 24 weeks of gestation.

Prediction of bronchopulmonary dysplasia by the chest radiographic thoracic area on day one in infants with exomphalos.

OBJECTIVES: To determine if infants with exomphalos had abnormal antenatal lung growth as indicated by lower chest radiographic thoracic areas (CRTA) on day one compared to controls and whether the CRTA could predict the development of bronchopulmonary dysplasia (BPD). METHODS: Infants with exomphalos cared for between January 2004 and January 2023 were included. The controls were term, newborn infants ventilated for absent respiratory drive at birth, without lung disease and had no supplemental oxygen requirement by 6 h of age. The radiographs were imported as digital image files by Sectra PACS software (Sectra AB, Linköping, Sweden). Free-hand tracing of the perimeter of the thoracic area was undertaken and the CRTA calculated by the software. RESULTS: Sixty-four infants with exomphalos and 130 controls were included. Infants with exomphalos had a lower median (IQR) CRTA (1,983 [1,657-2,471] mm2) compared to controls (2,547 [2,153-2,932] mm2, p<0.001). Following multivariable regression analysis, infants with exomphalos had lower CRTAs compared to controls (p=0.001) after adjusting for differences in gestational age and male sex. In the exomphalos group, the CRTAs were lower in those who developed BPD (n=14, 1,530 [1,307-1,941] mm2) compared to those who did not (2,168 [1,865-2,672], p<0.001). Following multivariable regression analysis, the CRTA was associated with BPD development (p=0.021) after adjusting for male sex and gestational age. CONCLUSIONS: Lower CRTAs on day one in the exomphalos infants compared to the controls predicted BPD development.

Impact of Congenital Heart Disease on the Outcomes of Very Low Birth Weight Infants.

OBJECTIVE: This study aimed to investigate the association of congenital heart disease (CHD) with morbidity and mortality of very low birth weight (VLBW) infants. STUDY DESIGN: This matched case-control study included VLBW infants born at a single institution between 2001 and 2015. The primary outcome was mortality. Secondary outcomes included necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity, and intraventricular hemorrhage. These outcomes were assessed by comparing VLBW-CHDs with control VLBW infants matched by gestational age within a week, birth weight within 500 g, sex, and birth date within a year using conditional logistic regression. Multivariable logistic regression analyzed differences in outcomes in the VLBW-CHD group between two birth periods (2001-2008 and 2009-2015) to account for changes in practice. RESULTS: In a cohort of 44 CHD infants matched with 88 controls, the mortality rate was 27% in infants with CHD and 1% in controls (p < 0.0001). The VLBW-CHDs had increased BPD; (odds ratio [OR]: 7.70, 95% confidence interval [CI]: 1.96-30.29) and sepsis (OR: 10.59, 95% CI: 2.99-37.57) compared with the control VLBWs. When adjusted for preoperative ventilator use, the VLBW-CHDs still had significantly higher odds of BPD (OR: 6.97, 95% CI: 1.73-28.04). VLBW-CHDs also had significantly higher odds of both presumed and culture-positive sepsis as well as late-onset sepsis than their matched controls. There were no significant differences in outcomes between the two birth periods. CONCLUSION: VLBW-CHDs showed higher odds of BPD, sepsis, and mortality than VLBW infants without CHD. Future research should focus on the increased mortality and specific complications encountered by VLBW infants with CHD and implement targeted strategies to address these risks. KEY POINTS: · Incidence of CHD is higher in preterm infants than in term infants but the incidence of their morbidities is not well described.. · VLBW infants with CHD have higher odds of mortality, bronchopulmonary dysplasia, and sepsis.. · Future research is needed to implement targeted preventive responses..

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OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

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OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

Molecular mechanisms of cell death in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) in neonates is the most common pulmonary disease that causes neonatal mortality, has complex pathogenesis, and lacks effective treatment. It is associated with chronic obstructive pulmonary disease, pulmonary hypertension, and right ventricular hypertrophy. The occurrence and development of BPD involve various factors, of which premature birth is the most crucial reason for BPD. Under the premise of abnormal lung structure and functional product, newborns are susceptible to damage to oxides, free radicals, hypoxia, infections and so on. The most influential is oxidative stress, which induces cell death in different ways when the oxidative stress balance in the body is disrupted. Increasing evidence has shown that programmed cell death (PCD), including apoptosis, necrosis, autophagy, and ferroptosis, plays a significant role in the molecular and biological mechanisms of BPD and the further development of the disease. Understanding the mode of PCD and its signaling pathways can provide new therapeutic approaches and targets for the clinical treatment of BPD. This review elucidates the mechanism of BPD, focusing on the multiple types of PCD in BPD and their molecular mechanisms, which are mainly based on experimental results obtained in rodents.