Moderate Bronchopulmonary Dysplasia Research Articles

Magnetic Resonance Imaging Assessment of Pulmonary Vascularity in Preterm Infants with Bronchopulmonary Dysplasia

Introduction: Pulmonary hypertension often complicates bronchopulmonary dysplasia (BPD) and infants with BPD plus pulmonary hypertension experience higher mortality rates. Current methods to evaluate pulmonary hypertension fail to evaluate the primary cause of this disease. We hypothesize that preterm infants with BPD experience altered pulmonary vascular growth and that magnetic resonance imaging (MRI) can be used to assess vascularity in BPD. Methods: In this observational cohort study, preterm infants with BPD (n = 33) and controls (n = 6) received a postnatal chest MRI that included a 2-dimensional time-of-flight acquisition. Semi-automatic segmentation was performed to measure vascularity parameters including vascular volume and density (vascular density = vascular volume/lung volume). Results: Vascular volume on MRI increases with post-menstrual age (877.2 mm3/week); however, the vascular density does not significantly change. Vascular volume is higher in infants with more severe BPD (p < 0.002), but vascular density did not significantly change when comparing mild, moderate, and severe BPD. Vascular density in infants with severe BPD requiring tracheostomy trended lower when compared to infants not requiring tracheostomy (0.18 mm3/mm3 vs. 0.27 mm3/mm3, p = 0.06). Vascular density increases with increasing days of inhaled nitric oxide (iNO) therapy in infants with severe BPD (0.02 mm3/mm3/week of iNO, rho = +0.56, p = 0.03). Conclusion: Neonatal MRI can be used to assess pulmonary vascularity in preterm infants with BPD. Infants with BPD experience altered vascular growth and while higher vascular volume is associated with more severe BPD, lower vascular density trends toward worse clinical outcomes. Vascular density increases with iNO therapy in severe BPD.

Bronchoscopic Evaluations in Preterm Infants with Moderate to Severe Bronchopulmonary Dysplasia

Purpose: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that primarily affects premature infants receiving mechanical ventilation and oxygen therapy. Severe BPD leads to long-term respiratory complications, including lung tissue damage, vascular abnormalities, and airway diseases. This study aimed to investigate bronchoscopy findings and characteristics in patients with moderate-to-severe BPD, and to investigate BPD-associated airway diseases.Methods: A retrospective study of preterm infants diagnosed with moderate-to-severe BPD who underwent bronchoscopic evaluation in the neonatal intensive care unit at Seoul National University Bundang Hospital between 2004 and December 2022 was conducted.Results: Nineteen patients with a mean gestational age of 28.0±1.6 weeks and mean birth weight of 960.5±271.0 g were included in the study. Among these 19 patients, 18 were diagnosed with severe BPD. Tracheobronchomalacia, laryngomalacia, and subglottic stenosis were observed in 63.2%, 52.6%, and 36.8% of patients, respectively. Tracheostomy was performed in nine of the 19 patients (47.4%); five were discharged without requiring tracheostomy following surgical or medical interventions.Conclusion: Tracheobronchomalacia, laryngomalacia, and subglottic stenosis were common in patients with moderate or severe BPD who underwent bronchoscopic evaluations, of which 50% required tracheostomy. Our study findings provide valuable insights into the pathophysiology of BPD-associated airway diseases and may inform future clinical management strategies for patients with BPD.

Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice.

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.

Quality Improvement Initiative Enhances Outpatient Pediatric Pulmonology Follow-up for Premature Infants with Bronchopulmonary Dysplasia

Introduction: Bronchopulmonary dysplasia (BPD) is a chronic lung disorder affecting many premature infants. Infants with BPD have higher hospital readmission rates due to respiratory-related morbidity. We aimed to increase the rates of outpatient pulmonary follow-up and attendance of premature babies with moderate and severe BPD to above 85% within 6 months. Methods: We conducted a quality improvement project at Yale New Haven Children’s Hospital. Key interventions included developing a BPD clinical pathway integrated into the electronic medical record to assist providers in correctly classifying BPD severity, assigning the appropriate International Classification of Diseases, 10th Revision code (P27.1), and providing standardized treatment options. The outcome measures included correct diagnosis and classification of BPD, the percentage of patients with BPD scheduled for pediatric pulmonology appointments within 45 days, and the percentage attending those appointments. Results: There were 226 patients in our study, including 85 in the baseline period. Correct diagnosis of BPD increased from 49% to 95%, the percentage of scheduled appointments increased from 71.9% to 100%, and the percentage of appointments attended increased from 55.6% to 87.1%. Conclusions: Our quality improvement initiative improved the accuracy of diagnosis, severity classification, and outpatient pulmonary follow-up of children with moderate and 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.

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks' gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

Patent Ductus Arteriosus and Lung Magnetic Resonance Imaging Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension.

Rationale: Hemodynamically significant patent ductus arteriosus (hsPDA) in premature infants has been associated with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). However, these associations remain incompletely understood. Objectives: To assess the associations between hsPDA duration and clinical outcomes, PH, and phenotypic differences on lung magnetic resonance imaging (MRI). Methods: In this retrospective cohort study, we identified all infants with BPD at <32 weeks' gestation who also underwent research lung MRI at <48 weeks' postmenstrual age (PMA) from 2014 to 2022. Clinical echocardiograms were reviewed for hsPDA and categorized as no hsPDA, hsPDA 1-60 days, and hsPDA >60 days. Outcome variables included BPD severity, PH at 36 weeks' PMA, PH after 36 weeks' PMA in the absence of shunt (PH-pulmonary vascular disease [PVD]), tracheostomy or death, and lung phenotype by MRI via modified Ochiai score, indexed total lung volume, and whole-lung hyperdensity. Logistic regression and ANOVA were used. Measurements and Main Results: In total, 133 infants born at 26.2 ± 1.9 weeks, weighing 776 ± 276 g, were reviewed (47 with no hsPDA, 44 with hsPDA 1-60 days, and 42 with hsPDA >60 d). hsPDA duration > 60 days was associated with BPD severity (P < 0.01), PH at 36 weeks' PMA (adjusted odds ratio [aOR], 9.7 [95% confidence interval (CI), 3.3-28.4]), PH-PVD (aOR, 6.5 [95% CI, 2.3-18.3]), and tracheostomy or death (aOR, 3.0 [95% CI, 1.0-8.8]). Duration of hsPDA > 60 days was associated with higher Ochiai score (P = 0.03) and indexed total lung volume (P = 0.01) but not whole-lung hyperdensity (P = 0.91). Conclusions: In infants with moderate or severe BPD, prolonged exposure to hsPDA is associated with BPD severity, PH-PVD, and increased parenchymal lung disease by MRI.

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

BackgroundNeonatal 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.MethodsWe 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 < 30 weeks 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 < 30 weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures.ResultsWe 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 90 days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury.ConclusionThe 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.Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Factors affecting length of stay according to bronchopulmonary dysplasia severity: a nationwide cohort study in Korea

BackgroundLonger hospitalizations for preterm infants with bronchopulmonary dysplasia (BPD) delay developmental outcomes, increase the risk for hospital-acquired complications, and exert a substantial socioeconomic burden. This study aimed to identify factors associated with an extended length of stay (LOS) at different levels of severity of BPD.MethodsA cohort study was conducted using the Korean Neonatal Network registry of very low birth weight infants with BPD between 2013 and 2017 through retrospective analysis.ResultsA total of 4263 infants were diagnosed with BPD. For mild BPD, infants requiring surgical treatment for patent ductus arteriosus needed a longer LOS [eadjusted β coefficients (adj β) 1.041; 95% confidence interval (CI): 0.01–0.08] and hydrocephalus (eadj β 1.094; 95% CI 0.01–0.17). In moderate BPD, infants administered steroids or with intraventricular hemorrhage required a longer LOS (eadj β 1.041; 95% CI 0.00–0.07 and eadj β 1.271; 95% CI 0.11–0.38, respectively). In severe BPD, infants with comorbidities required a longer LOS: pulmonary hypertension (eadj β 1.174; 95% CI 0.09–0.23), administrated steroid for BPD (eadj β 1.116; 95% CI 0.07–0.14), sepsis (eadj β 1.062; 95% CI 0.01–0.11), patent ductus arteriosus requiring surgical ligation (eadj β 1.041; 95% CI 0.00–0.08), and intraventricular hemorrhage (eadj β 1.016; 95% CI 0.05–0.26). Additionally, the higher the clinical risk index score, the longer the LOS needed for infants in all groups.ConclusionsThe factors affecting LOS differed according to the severity of BPD. Individualized approaches to reducing LOS may be devised using knowledge of the various risk factors affecting LOS by BPD severity.Graphical

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.

Clinical assessment of the severity of bronchopulmonary dysplasia in children born prematurely

Bronchopulmonary dysplasia (BPD) – chronic lung disease, which evolves with broncho-obstructive syndrome, signs of respiratory failure, pulmonary fibrosis. Aim. Analytical case-control study included 41 children with BPD and 40 preterm children without BPD, who were clinically evaluated. Methods. Evaluation of clinical respiratory syndromes and degree of severity of bronchopulmonary dysplasia in premature infants. Results. The study demonstrated that the O2 saturation determined by pulse oximetry in premature children with BPD is reduced - 94.5±0.4%, compared to the O2 saturation of premature children without BPD (97.85±0.14%), which is significantly higher (F stat = 66.7, T stat = 8.17, p&lt;0.0001). Children with mild grade BPD present intercostal retractions in 22.2%: 95%CI 2.8-60, in moderate grade BPD – 52.6%: 95%CI 28.9-75.6 and in severe grade DBP all the children had chest retractions. Depending on the degrees of severity, children with mild BPD present intercostal retractions in 22.2%, in moderate BPD – 73.7% and in severe BPD all children had intercostal retractions. Costal retractions, which is an indicator of respiratory insufficiency, was found in all preterm infants with severe BPD, in 52.6%: 95%CI 28.9-75.6 preterm infants with moderate BPD. Premature children with mild BPD did not present costal retractions at the stage of diagnosis confirmation (χ2 = 15.3; p&lt;0.001). Conclusions. According to the study, bronchopulmonary dysplasia in children born prematurely is manifested by signs of respiratory insufficiency - accelerated breathing, intercostal and thoracic retractions, low values of O2 saturation. The severity of signs of respiratory impairment is dependent on the degree of bronchopulmonary dysplasia, having a clinical expression through different forms of thoracic retractions.

Family Integrated Care Shortens the Duration of Home Oxygen Therapy in Infants With Bronchopulmonary Dysplasia.

There have been few reports on whether family integrated care (FIC) can help premature infants with moderate to severe bronchopulmonary dysplasia (BPD) to shorten the duration of home oxygen therapy (HOT). To investigate the effect of FIC on the duration of HOT in premature infants with moderate to severe BPD. The subjects were retrospectively selected from premature infants with moderate to severe BPD in our center between June 2019 and December 2021. Patients were divided into the FIC group (n = 47) and the non-FIC group (n = 34). For univariate analysis, t test, Mann-Whitney U test, Pearson χ 2 test, or Fisher exact test was performed to explore the differences between the 2 groups. For multivariate analysis, simple and multiple linear regression was conducted to explore the effect of FIC on the duration of HOT. (1) The duration of HOT and length of stay after grouping were significantly shorter in the FIC group than in the non-FIC group ( P < .05). (2) The results of linear regression further revealed that FIC could significantly shorten the duration of HOT (simple linear regression, FIC [A] B : -12.709, 95% confidence interval (CI): -21.665 to -3.753; multiple linear regression, FIC [B] B : -11.419, 95% CI: -18.055 to -4.783). FIC improved the optimal target oxygen saturation ratio before discharge and shortened the duration of HOT in premature infants with moderate and severe BPD. FIC should be promoted in China's neonatal intensive care units, though it puts forward new requirements for nursing education and training.

Montelukast Sodium to Prevent and Treat Bronchopulmonary Dysplasia in Very Preterm Infants: A Quasi-Randomized Controlled Trial.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, p = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, p = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.

Effect of different courses and durations of invasive mechanical ventilation on respiratory outcomes in very low birth weight infants

This multicenter retrospective study was conducted to explore the effects of different courses and durations of invasive mechanical ventilation (MV) on the respiratory outcomes of very low birth weight infants (VLBWI) in China. The population for this study consisted of infants with birth weight less than 1500 g needing at least 1 course of invasive MV and admitted to the neonatal intensive care units affiliated with the Chinese Neonatal Network within 6 h of life from January 1st, 2019 to December 31st, 2020. Univariate and multivariate logistic regression analyses were performed to evaluate associations between invasive MV and respiratory outcomes. Adjusted odds ratios (ORs) were computed with the effects of potential confounders. (1) Among the 3183 VLBWs with a history of at least one course of invasive MV, 3155 (99.1%) met inclusion criteria and were assessed for the primary outcome. Most infants received one course (76.8%) and a shorter duration of invasive MV (62.16% with ventilation for 7 days or less). (2) In terms of the incidence of all bronchopulmonary dysplasia (BPD) (mild, moderate, and severe BPD), there were no significant differences between different invasive MV courses [For 2 courses, adjusted OR = 1.11 (0.88, 1.39); For 3 courses or more, adjusted OR = 1.07 (0.72, 1.60)]. But, with the duration of invasive MV prolonging, the OR of BPD increased [8–21 days, adjusted OR = 1.98 (1.59, 2.45); 22–35 days, adjusted OR = 4.37 (3.17, 6.03); ≥ 36 days, adjusted OR = 18.44 (10.98, 30.99)]. Concerning severe BPD, the OR increased not only with the course of invasive MV but also with the duration of invasive MV [For 2 courses, adjusted OR = 2.17 (1.07, 4.40); For 3 courses or more, adjusted OR = 2.59 (1.02, 6.61). 8–21 days, adjusted OR = 8.42 (3.22, 22.01); 22–35 days, adjusted OR = 27.82 (9.08, 85.22); ≥ 36 days, adjusted OR = 616.45 (195.79, > 999.999)]. (3) When the interaction effect between invasive MV duration and invasive MV course was considered, it was found that there were no interactive effects in BPD and severe BPD. Greater than or equal to three courses would increase the chance of severe BPD, death, and the requirement of home oxygen therapy. Compared with distinct courses of invasive MV, a longer duration of invasive MV (> 7 days) has a greater effect on the risk of BPD, severe BPD, death, and the requirement of home oxygen therapy.

Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia

Introduction: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). Methods: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks’ postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. Results: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57–0.95; aOR 0.70, 95% CI 0.54–0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09–9.61; aOR 5.44, 95% CI 1.62–18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11–5.57). Conclusion: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.

Role of birthweight discordance in preterm twins' outcomes in the Korean neonatal network.

Twin pregnancies can be complicated by birthweight (BW) discordance. We analyzed the impact of BW discordance on clinical outcomes of very-low-birthweight (VLBW) twins. The study population was preterm infants in the Korean Neonatal Network registry. Multivariate logistic regression analyses were used to determine the contribution of BW discordance on respiratory morbidities and mortality of VLBW infants. Also, we assessed the effect of small for gestational age (SGA) on morbidity and mortality in discordant twins (DTs) and compared separately the clinical outcomes of smaller and larger DTs with different singletons matched for perinatal factors including BW percentile. A total of 935 twin pairs [1548 concordant twins (CTs) and 322 DTs] were included. BW discordance was associated with increased odds of moderate bronchopulmonary dysplasia, mortality, and composite outcomes. Compared with the CTs, the smaller, but not larger, DTs had greater odds of morbidities and mortality. DTs had higher odds of adverse neonatal outcome when combined with SGA. Meanwhile, DTs had morbidities and mortality similar to singletons matched for BW percentile. BW discordance in VLBW twins adversely affects neonatal mortality or respiratory morbidity which is predominant in smaller DTs. The impact of BW discordance could be increased through SGA.

Morbidity and Mortality of Very-Low-Birthweight Twin Infants according to Their Sex and the Sex of the Co-Twin: A Retrospective Cohort Study

Introduction: The concept of male disadvantage regarding the prognosis of premature newborns was introduced more than half a century ago, and it has been corroborated over time. However, the influence of the sex of one twin on the outcomes of the other has yielded contradictory results. Objective: The aim of the study was to determine if, in twin pregnancies of VLBW infants, the outcomes of one twin are modified by the sex of the co-twin. Methods: A multicentre retrospective study of a cohort of infants admitted to the collaborating units of the Spanish SEN1500 neonatal network was conducted. Liveborn VLBW twin infants, from 23+0 to 31+6 weeks of gestational age (GA), admitted from 2011 to 2020 were included. Outborn patients, infants with major congenital anomalies, and cases with only one twin admitted were excluded. The main outcomes were survival until first hospital discharge, survival without moderate or severe bronchopulmonary dysplasia (BPD), survival without major brain damage (MBD), and survival without major morbidity. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated. Results: 2,111 twin pairs were included. Male infants exhibited worse outcomes than females (IRR; 95% CI) regarding survival (0.96; 0.94, 0.98), survival without moderate or severe BPD (0.89; 0.86, 0.93), survival without MBD (0.94; 0.91, 0.97), and survival without major morbidity (0.87; 0.81, 0.93). Differences disappeared when the co-twin was a female infant: survival (1.00; 0.97, 1.03), survival without moderate or severe BPD (0.96; 0.91, 1.01), survival without MBD (0.99; 0.95, 1.04), and survival without major morbidity (0.94; 0.85, 1.03). Results for female infants did not change significantly with co-twin sex. Conclusions: Among VLBW twins from 23+0 to 31+6 weeks of GA, male infants have higher risk of morbidity and mortality overall. In cases of pregnancies with different-sex foetuses, males seem to improve their results, while these do not change for females. The underlying mechanism of this influence deserves further investigation.

Bronchopulmonary Dysplasia: A Five-Year Retrospective Cohort Study on Differences in Clinical Characteristics and Morbidities According to Severity Grading.

Bronchopulmonary dysplasia (BPD) is the most common complication associated with extreme prematurity. Although several criteria defining severity were developed over time, there are a few studies describing the differences in BPD phenotype and neonatal morbidities and complications between severity groups. We aimed to describe these differences in BPD patients of a neonatal intensive care unit (NICU). We conducted an observational retrospective cohort study through a medical record review over a five-year period. Participants were newborns admitted to an NICU who were diagnosed with BPD. We performed a descriptive statistical analysis of gestational complications and the use of antenatal corticosteroid therapy, birth-related data, and complications throughout the NICU stay, as well as the respiratory support used. We also compared different severity groups across these variables. The patients were divided into severe and non-severe BPD using the severity criteria of the 2001 NICHD/NHLBI/ORD consensus workshop. A total of 101 newborns with BPD participated in the study and 73 had data on BPD severity. The median gestational age was 27 weeks, ranging from 23 to 32 weeks. Of these 73 newborns, 36 had mild BPD (49.3%), 10 had moderate BPD (13.7%), and 27 had severe BPD (37.0%). When comparing severe and non-severe BPD, we found that extreme prematurity, extremely low birth weight, and small size for gestational age were more frequent in the severe BPD group (p-value=0.012, p-value<0.001, and p-value=0.012, respectively). Infants with severe BPD had a longer duration of invasive ventilation than those with mild or moderate BPD (p-value<0.001). Late sepsis, necrotizing enterocolitis, severe brain injury, and retinopathy of prematurity were more frequent in severe BPD (p-value=0.017, p-value=0.045, p-value=0.033, p-value=0.003, respectively). Previously published evidence describing causal links between BPD development and comorbidities exists but data on their impact on BPD severity are scarce. In our study, severe BPD seemed to be associated with a higher frequency of comorbidities and complications. Further studies are needed to ascertain the impact of each morbidity on the severity of BPD and if measures to prevent them could lead to potentially milder BPD disease.

Application of lung ultrasound in monitoring bronchopulmonary dysplasia and pulmonary arterial pressure in preterm infants.

The aim of this study was to evaluate the application value of lung ultrasound in monitoring bronchopulmonary dysplasia (BPD) and pulmonary artery pressure in premature infants. A total of 98 preterm infants diagnosed with BPD in the Fourth Hospital in Shijiazhuang were recruited, and their disease severity was classified as mild (n=32), moderate (n=33), or severe BPD (n=33) based on gestational age and oxygen concentration. Lung ultrasonography of the children was performed. The correlation between lung ventilation scores and disease severity was statistically analyzed, and the discrete optimization results were documented. The pulmonary hypertension indexes of the three groups of children were compared. Aberrant alterations of the pleural line were observed in all included children, and the B-line rose as the disease progressed. The duration of invasive ventilation, medication, and hospital stay increased with disease exacerbation (p<0.05). The three groups significantly differed in terms of ultrasound pulmonary ventilation scores and clinical severity (p<0.05). Only mild BDP was identified by lung ultrasound on the first day of birth (T1), and severe BDP was detectable during the first and second week (T2-T3) as well as the third and fourth week (T4-T5). Severe BPD was associated with significantly higher levels of pulmonary hypertension indices vs. mild and moderate BPD (p<0.05). Pulmonary ultrasonography demonstrates great potential to predict pulmonary hypertension in children and assesses the disease severity. Pulmonary ultrasound allows for dynamical real-time observation of the pulmonary lesions in children with pulmonary hypertension, thereby revealing the severity of pulmonary hypertension in premature children.

Two-stage learning-based prediction of bronchopulmonary dysplasia in very low birth weight infants: a nationwide cohort study.

The aim of this study is to develop an enhanced machine learning-based prediction models for bronchopulmonary dysplasia (BPD) and its severity through a two-stage approach integrated with the duration of respiratory support (RSd) using prenatal and early postnatal variables from a nationwide very low birth weight (VLBW) infant cohort. We included 16,384 VLBW infants admitted to the neonatal intensive care unit (NICU) of the Korean Neonatal Network (KNN), a nationwide VLBW infant registry (2013-2020). Overall, 45 prenatal and early perinatal clinical variables were selected. A multilayer perceptron (MLP)-based network analysis, which was recently introduced to predict diseases in preterm infants, was used for modeling and a stepwise approach. Additionally, we applied a complementary MLP network and established new BPD prediction models (PMbpd). The performances of the models were compared using the area under the receiver operating characteristic curve (AUROC) values. The Shapley method was used to determine the contribution of each variable. We included 11,177 VLBW infants (3,724 without BPD (BPD 0), 3,383 with mild BPD (BPD 1), 1,375 with moderate BPD (BPD 2), and 2,695 with severe BPD (BPD 3) cases). Compared to conventional machine learning (ML) models, our PMbpd and two-stage PMbpd with RSd (TS-PMbpd) model outperformed both binary (0 vs. 1,2,3; 0,1 vs. 2,3; 0,1,2 vs. 3) and each severity (0 vs. 1 vs. 2 vs. 3) prediction (AUROC = 0.895 and 0.897, 0.824 and 0.825, 0.828 and 0.823, 0.783, and 0.786, respectively). GA, birth weight, and patent ductus arteriosus (PDA) treatment were significant variables for the occurrence of BPD. Birth weight, low blood pressure, and intraventricular hemorrhage were significant for BPD ≥2, birth weight, low blood pressure, and PDA ligation for BPD ≥3. GA, birth weight, and pulmonary hypertension were the principal variables that predicted BPD severity in VLBW infants. We developed a new two-stage ML model reflecting crucial BPD indicators (RSd) and found significant clinical variables for the early prediction of BPD and its severity with high predictive accuracy. Our model can be used as an adjunctive predictive model in the practical NICU field.