Long-term lung function follow-up of preterm infants less than 32 weeks of gestational age.

BACKGROUND: Preterm infants, particularly those with bronchopulmonary dysplasia (BPD), are at risk of lung development problems. Over the last decades, lung protective strategies have been used, decreasing the risk of chronic lung disease. OBJECTIVE: To evaluate the pulmonary function test (PFT) of preterm infants born after the introduction of lung protective strategies and to assess perinatal determinants of impaired lung function in this population. METHODS: A prospective, observational, single-center study was conducted in the neonatal unit of a high-complexity hospital. The study included newborns with less than 32 weeks gestational age born between 2012 and 2014, who were followed up until they reach school age. For the main outcome, two groups were stablished: no BPD or grade 1 BPD (no BPD/1) and grade 2 or 3 BPD (BPD 2/3). RESULTS: Out of 327 patients, 116 were included. BPD was diagnosed in 49.1% (47), with 50.9% (29) classified as grade 1, 35.1% (20) as grade 2, and 14.0% (8) as grade 3. Mean age at PFT was 8.59 years (SD 0.90). Mean FEV1% was 95.36% (SD 13.21) and FEV1 z-score -0.36 (SD 1.12); FVC% 97.53% (SD 12.59) and FVC z-score -0.20 (SD 1.06); FEV1/FVC ratio 85.84% (SD 8.34) and z-score -0.24 (SD 1.34). When comparing patients with no BPD/1 and BPD 2/3, we observed differences in all pulmonary function parameters, which persisted after adjusting for gestational age. No differences in PFT were observed between patients without BPD and those with grade 1 BPD. Most patients (76.7%, 89) had normal spirometry pattern, with obstructive pattern observed in 12.9% (15), restrictive pattern in 9.5% (11), and mixed pattern in 0.9% (1) of patients. CONCLUSION: Preterm infants with BPD 2/3 showed a decrease in all pulmonary function parameters compared to preterm infants with no BPD/1; an effect that was independent of gestational age. Among patients with BPD who had an altered PFT pattern, the most common pattern was obstructive, followed by restrictive and then, mixed.

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.

Impact of catheterized ductal closure on renal and cerebral oximetry in premature neonates.

Percutaneous catheter-based closure is increasingly utilized in premature newborns. While near-infrared spectroscopy (NIRS) has been examined for assessment of interventional closure in surgical ligation, its application in percutaneous transcatheter closure remains unexplored. This study aims to assess cerebral and renal hemodynamic changes using NIRS during percutaneous closure compared to surgical closure in preterm infants. A prospective observational study enrolled preterm infants born at 32 weeks of gestation or less and diagnosed with hsPDA between January 2020 and December 2022. These infants received either surgical or catheter-based closure of the PDA. Cerebral and renal oxygen saturation was monitored using the INVOS 5100 device from 12 h before the intervention until 24 h after. Linear mixed-effects models were used to analyze time-dependent variables. Twenty-two patients were enrolled, with catheter-based closure performed in 16 cases and conventional surgery in 6 cases. Following ductal closure, a significant increase in renal and cerebral oximetry was observed alongside a decrease in renal and cerebral tissue oxygen extraction. These changes were particularly pronounced in the renal territory. No differences were detected between catheterization and surgical closure.   Conclusion: An improvement in cerebral and renal oximetry following hsPDA closure was observed. However, we did not identify differences in this pattern based on the type of interventional procedure for PDA, whether surgery or catheterization. What is Known: • The presence of a significant ductus is common in premature patients. Studies have shown that it affects cerebral and renal hemodynamics negatively, leading to decreased oximetry values in these areas. It has been reported that closure of the ductus, either pharmacologically or surgically, results in improved oximetry values. What is New: • This study assess the impact of percutaneous closure of ductus, revealing increased oximetry values in cerebral and renal territories without significant differences compared to surgical ligation. Notably, renal oximetry values showed a greater increase, underscoring the importance of multi-location monitoring.

Effect of Donated Premature Milk in the Prevention of Bronchopulmonary Dysplasia.

INTRODUCTION: Breastfeeding is one of the strategies that has been shown to be effective in preventing severe forms of bronchopulmonary dysplasia (BPD). When mother's own milk (MOM) is not available, pasteurized donor milk (DM) is the best alternative. However, the evidence is inconclusive on the difference in the incidence of bronchopulmonary dysplasia (BPD) between patients fed MOM and those fed with DM. As standard DM is usually mature pooled milk donated by mothers who have delivered their babies at term, the potential benefits of preterm milk may be lost. MATERIALS AND METHODS: An observational, retrospective, single-center study was conducted in the neonatology department of a high-complexity hospital. The study included newborns <32 weeks of gestational age born between January 2020 and December 2022. When supplemental milk was needed, non-pooled preterm pasteurized donor milk (PDM) matched for gestational age and moment of lactation was used in this study, classifying preterm infants in two groups: mainly MOM (>50% of the milk) or mainly PDM (>50% of the milk). Two groups were established: those who received >50% MOM and those who received >50% PDM. They were also classified according to the diagnosis of DBP: one group included no BPD or grade 1 BPD (noBPD/1), while the other included grade 2 or 3 BPD (BPD 2-3). The objectives of this study were, firstly, to evaluate the incidence of BPD 2-3 among patients who predominantly received PDM versus MOM. Secondly, to analyze differences in the type of human milk received and its nutritional components, as well as to study the growth in patients with or without BPD. RESULTS: One hundred ninety-nine patients were included in the study. A comparison of noBPD/1 versus BPD 2-3 groups between those receiving mainly MOM versus PDM showed no significant differences (19% vs. 20%, p 0.95). PDM colostrum in BPD 2-3 compared to noBPD/1 was higher in protein content (2.24 g/100 mL (SD 0.37) vs. 2.02 g/100 mL (SD 0.29) p < 0.01), although the statistical significance decreased after adjustment for gestational age and birth weight z-score (OR 3.53 (0.86-14.51)). No differences were found in the macronutrients in the mature milk of patients feeding more than 50% PDM in both study groups. Growth of BPD 2-3 showed a greater decrease in the difference in z-scores for height at birth and at discharge compared to noBPD/1 (-1.64 vs. -0.43, p 0.03). CONCLUSIONS: The use of mainly MOM or PDM demonstrates a similar incidence of noBPD/1 or BPD 2-3. Non-pooled and matched by gestational age and time of lactation preterm donor milk can probably be an alternative when mother's own milk is not available, with a similar protective effect in the prevention of severe BPD.

A Survey of the Union of European Neonatal and Perinatal Societies on Neonatal Respiratory Care in Neonatal Intensive Care Units.

(1) Background: Our survey aimed to gather information on respiratory care in Neonatal Intensive Care Units (NICUs) in the European and Mediterranean region. (2) Methods: Cross-sectional electronic survey. An 89-item questionnaire focusing on the current modes, devices, and strategies employed in neonatal units in the domain of respiratory care was sent to directors/heads of 528 NICUs. The adherence to the "European consensus guidelines on the management of respiratory distress syndrome" was assessed for comparison. (3) Results: The response rate was 75% (397/528 units). In most Delivery Rooms (DRs), full resuscitation is given from 22 to 23 weeks gestational age. A T-piece device with facial masks or short binasal prongs are commonly used for respiratory stabilization. Initial FiO2 is set as per guidelines. Most units use heated humidified gases to prevent heat loss. SpO2 and ECG monitoring are largely performed. Surfactant in the DR is preferentially given through Intubation-Surfactant-Extubation (INSURE) or Less-Invasive-Surfactant-Administration (LISA) techniques. DR caffeine is widespread. In the NICUs, most of the non-invasive modes used are nasal CPAP and nasal intermittent positive-pressure ventilation. Volume-targeted, synchronized intermittent positive-pressure ventilation is the preferred invasive mode to treat acute respiratory distress. Pulmonary recruitment maneuvers are common approaches. During NICU stay, surfactant administration is primarily guided by FiO2 and SpO2/FiO2 ratio, and it is mostly performed through LISA or INSURE. Steroids are used to facilitate extubation and prevent bronchopulmonary dysplasia. (4) Conclusions: Overall, clinical practices are in line with the 2022 European Guidelines, but there are some divergences. These data will allow stakeholders to make comparisons and to identify opportunities for improvement.

Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.

High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. However, the possible impact of this new ventilation technique on cerebral hemodynamics is unknown. To evaluate the cerebral hemodynamics effect of HFOV combined with VG in an experimental animal model of neonatal respiratory distress syndrome (RDS) due to surfactant deficiency compared with HFOV and CMV+VG (control group). Eighteen newborn piglets were randomized, before and after the induction of RDS by bronchoalveolar lavage, into 3 mechanical ventilation groups: CMV, HFOV and HFOV with VG. Changes in cerebral oxygen transport and consumption and cerebral blood flow were analyzed by non-invasive regional cerebral oxygen saturation (CrSO2), jugular venous saturation (SjO2), the calculated cerebral oxygen extraction fraction (COEF), the calculated cerebral fractional tissue oxygen extraction (cFTOE) and direct measurement of carotid artery flow. To analyze the temporal evolution of these variables, a mixed-effects linear regression model was constructed. After randomization, the following statistically significant results were found in every group: a drop in carotid artery flow: at a rate of -1.7 mL/kg/min (95% CI: -2.5 to -0.81; p < 0.001), CrSO2: at a rate of -6.2% (95% CI: -7.9 to -4.4; p < 0.001) and SjO2: at a rate of -20% (95% CI: -26 to -15; p < 0.001), accompanied by an increase in COEF: at a rate of 20% (95% CI: 15 to 26; p < 0.001) and cFTOE: at a rate of 0.07 (95% CI: 0.05 to 0.08; p < 0.001) in all groups. No statistically significant differences were found between the HFOV groups. CONCLUSION: No differences were observed at cerebral hemodynamic between respiratory assistance in HFOV with and without VG, being the latter ventilatory strategy equally safe. WHAT IS KNOWN: • Preterm have a situation of fragility of cerebral perfusion wich means that any mechanical ventilation strategy can have a significant influence. High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. Several studies have compared CMV and HFOV and their effects at hemodynamic level. It is known that the use of high mean airway pressure in HFOV can cause an increase in pulmonary vascular resistance with a decrease in thoracic venous return. WHAT IS NEW: • The possible impact of VAFO + VG on cerebral hemodynamics is unknown. Due the lack of studies and the existing controversy, we have carried out this research project in an experimental animal model with the aim of evaluating the cerebral hemodynamic repercussion of the use of VG in HFOV compared to the classic strategy without VG.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Chylothorax in newborns after cardiac surgery: a rare complication?

The aim of this study was to analyze patients diagnosed with chylothorax after congenital heart disease surgery among a cohort of neonatal patients, comparing the evolution, complications, and prognosis after surgery of patients who were and were not diagnosed with chylothorax, and to analyze possible risk factors that may predict the appearance of chylothorax in this population. Retrospective and observational study included all neonates (less than 30 days since birth) who underwent congenital heart disease surgery in a level III neonatal intensive care department. We included infants born between January 2014 and December 2019. We excluded those infants who were born before 34 weeks of gestational age or whose birth weight was less than 1800 g. We also excluded catheter lab procedures and patent ductus arteriosus closure surgeries. Included patients were divided into two groups depending on whether they were diagnosed with chylothorax or not after surgery, and both groups were compared in terms of perinatal-obstetrical information, surgical data, and NICU course after surgery. We included 149 neonates with congenital heart disease surgery. Thirty-one patients (20.8%) developed chylothorax, and in ten patients (32.3%), it was considered large volume chylothorax. Regarding the evolution of these patients, 22 infants responded to general dietetic measures, a catheter procedure was performed in 9, and 5 of them finally required pleurodesis. Cardiopulmonary bypass, median sternotomy, and delayed sternal closure were the surgical variables associated with higher risks of chylothorax. Patients with chylothorax had a longer duration of inotropic support and mechanical ventilation and took longer to reach full enteral feeds. As complications, they had higher rates of cholestasis, catheter-related sepsis, and venous thrombosis. Although there were no differences in neonatal mortality, patients with chylothorax had a higher rate of mortality after the neonatal period. In a multiple linear regression model, thrombosis and cardiopulmonary bypass multiplied by 10.0 and 5.1, respectively, the risk of chylothorax and have an umbilical vein catheter decreases risk. CONCLUSION: We have found a high incidence of chylothorax after neonatal cardiac surgery, which prolongs the average stay and causes significant morbidity and mortality. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during the neonatal period. WHAT IS KNOWN: • Acquired chylothorax in the neonatal period usually appears as a complication of congenital heart disease surgery, being the incidence quite variable among the different patient series (2.5-16.8%). The appearance of chylothorax as a complication of a cardiac surgery increases both mortality and morbidity in these patients, which makes it a quality improvement target in the postsurgical management of this population. WHAT IS NEW: •Most of the published studies include pediatric patients of all ages, from newborns to teenagers, and there is a lack of studies focusing on neonatal populations. The main strength of our study is that it reports, to the best of our knowledge, one of the largest series of neonatal patients receiving surgery for congenital heart disease in the first 30 days after birth. We have found a high incidence of chylothorax after cardiac surgery during the neonatal period compared to other studies. We suggested that chylothorax could be an underestimated complication of congenital heart disease surgery during this period of life.

Lung protection strategy with high-frequency oscillatory ventilation improves respiratory outcomes at two years in preterm respiratory distress syndrome: a before and after, quality improvement study.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) remains one of the major challenges of extreme prematurity. High-frequency oscillatory ventilation (HFOV) with volume guarantee (HFOV-VG) can be used as an early-rescue ventilation to protect developing lungs. However, the studies exploring the impact of this ventilatory strategy on neonatal respiratory morbidity are very limited. This study aimed at documenting the improvement in respiratory outcomes in mechanically ventilated preterm newborns, after the implementation of a new mechanical ventilation respiratory bundle. METHODS: A prospective, quality improvement study was conducted between January 2012 and December 2018 in a third level NICU in Madrid, Spain. Infants born <32 weeks of gestation with severe respiratory distress syndrome (RDS) and requiring invasive mechanical ventilation were included. The intervention consisted of a new ventilation respiratory care bundle, with HFOV as early rescue therapy using low high-frequency tidal volumes (Vthf) and higher frequencies (15-20 Hz). Criteria for HFOV start were impaired oxygenation or ventilation on conventional ventilation, or peak inspiratory pressures >15 cmH2O. Two cohorts of mechanically ventilated patients were compared, cohort 1 (2012-2013, baseline period) and cohort 2 (2016-2018, after implementation of the new bundle). Clinical outcomes at 36 weeks and 2 years of postmenstrual age were compared between the groups. RESULTS: A total of 216 patients were included, the median gestational age was 26 weeks (IQR 25-28) and median birth weight was 895 g (IQR 720-1160). There were no significant differences in survival between the groups, but patients with the protective ventilation strategy (cohort 2) had higher survival without BPD 2-3 (OR 2.93, 95%CI 1.41-6.05). At 2 years of postmenstrual age, patients in cohort 2 also had a higher survival free of baseline respiratory treatment and hospital respiratory admissions than the control group (adjusted OR 2.33, 95%CI 1.10-4.93, p=.03). The results did not suggest significant differences in neurologic development. CONCLUSIONS: In extreme premature related severe respiratory failure, the use of a lung protective HFOV-VG strategy was proven to be a useful quality improvement intervention in our unit, leading to better pulmonary outcomes at 36 weeks and additional improved respiratory prognosis at two years of age.

Less Invasive Surfactant Administration: A Review of Current Evidence of Clinical Outcomes With Beractant.

Evidence supporting clinical recommendations or approval for less invasive surfactant administration (LISA) has primarily examined heterogeneous or small-volume (e.g., 1.25-2.5 mL/kg) animal-derived surfactant regimens. To address the evidence gap for larger-volume (e.g., 4-5 mL/kg) animal-derived surfactants, the aim of this review was to evaluate and summarize LISA literature for widely used larger-volume beractant. Surfactant treatment and the LISA technique were initially summarized. The available literature on beractant with LISA was thoroughly assessed and reviewed, including a recent systematic analysis, studies from regions where access or preferences may influence reliance on larger-volume surfactants, and investigations of short- and long-term outcomes. The available literature indicated improved short-term outcomes, including less need for mechanical ventilation, death, or bronchopulmonary dysplasia, and no negative long-term developmental outcomes when beractant was administered via LISA compared with older, more invasive techniques. The rates of short-term outcomes were similar to those previously observed in examinations of LISA with small-volume surfactants, including in populations reflecting very preterm infants. As uptake of LISA is expected to increase, future research directions for larger-volume surfactants include cost-effectiveness evaluations and robust examinations of repeat dosing and surfactant reflux to further inform clinical practice. This review provides a detailed assessment of the literature describing surfactant and LISA, with a focus on studies of beractant. Collectively, the available evidence supports the use of beractant with LISA based both on short-term and long-term outcomes relative to more invasive techniques and comparability of outcomes with small-volume surfactants and may be valuable in guiding clinical decision-making.

Lung recruitment in neonatal high-frequency oscillatory ventilation with volume-guarantee.

BACKGROUND AND OBJECTIVES: The optimal lung volume strategy during high-frequency oscillatory ventilation (HFOV) is reached by performing recruitment maneuvers, usually guided by the response in oxygenation. In animal models, secondary spontaneous change in oscillation pressure amplitude (ΔPhf) associated with a progressive increase in mean airway pressure during HFOV combined with volume guarantee (HFOV-VG) identifies optimal lung recruitment. The aim of this study was to describe recruitment maneuvers in HFOV-VG and analyze whether changes in ΔPhf might be an early predictor for lung recruitment in newborn infants with severe respiratory failure. DESIGN AND METHODS: The prospective observational study was done in a tertiary-level neonatology department. Changes in ΔPhf were analyzed during standardized lung recruitment after initiating early rescue HFOV-VG in preterm infants with severe respiratory failure. RESULTS: Twenty-seven patients were included, with a median gestational age of 24 weeks (interquartile range [IQR]: 23-25). Recruitment maneuvers were performed, median baseline mean airway pressure (mPaw) was 11 cm H2 O (IQR: 10-13), median critical lung opening mPaw during recruitment was 14 cm H2 O (IRQ: 12-16), and median optimal mPaw was 12 cm H2 O (IQR: 10-14, p < 0.01). Recruitment maneuvers were associated with an improvement in oxygenation (FiO2 : 65.0 vs. 45.0, p < 0.01, SpO2/FiO2 ratio: 117 vs. 217, p < 0.01). ΔPhf decreased significantly after lung recruitment (mean amplitude: 23.0 vs. 16.0, p < 0.01). CONCLUSION: In preterm infants with severe respiratory failure, the lung recruitment process can be effectively guided by ΔPhf on HFOV-VG.

Nasal Intermittent Positive Pressure Ventilation and Bronchopulmonary Dysplasia Among Very Preterm Infants Never Intubated During the First Neonatal Admission: A Multicenter Cohort Study.

Introduction: While non-invasive positive-pressure ventilation (NIPPV) is increasingly used as a mode of respiratory support for preterm infants, it remains unclear whether this technique translates into improved respiratory outcomes. We assessed the association between NIPPV use and bronchopulmonary dysplasia (BPD)-free survival in never intubated very preterm infants. Methods: This multicenter cohort study analyzed data from the Spanish Neonatal Network SEN1500 corresponding to preterm infants born at <32 weeks gestational age and <1,500 g and not intubated during first admission. The exposure of interest was use of NIPPV at any time and the main study outcome was survival without moderate-to-severe BPD. Analyses were performed both by patients and by units. Primary and secondary outcomes were compared using multilevel logistic-regression models. The standardized observed-to-expected (O/E) ratio was calculated to classify units by NIPPV utilization and outcome rates were compared among groups. Results: Of the 6,735 infants included, 1,776 (26.4%) received NIPPV during admission and 6,441 (95.6%) survived without moderate-to-severe BPD. After adjusting for confounding variables, NIPPV was not associated with survival without moderate-to-severe BPD (OR 0.84; 95%CI 0.62-1.14). A higher incidence of moderate-to-severe BPD-free survival was observed in high- vs. very low-utilization units, but no consistent association was observed between O/E ratio and either primary or secondary outcomes. Conclusion: NIPPV use did not appear to decisively influence the incidence of survival without moderate-to-severe BPD in patients managed exclusively with non-invasive ventilation.

Antenatal corticosteroids and the influence of sex on morbidity and mortality of preterm infants.

OBJECTIVE: To study the associated effect of a complete course of antenatal corticosteroids (ACSs) on mortality and morbidity rates among preterm infants in our population. STUDY DESIGN: Observational prospective study of infants born at less than 32 weeks' gestation and admitted to our Neonatal Care Unit between January 2012 and December 2018. We analyzed mortality at discharge and respiratory and neurological morbidity, both during hospitalization and at 24 months' postmenstrual age. RESULTS: The study included a total of 710 patients with a median gestational age of 28.5 weeks (IQR 26.4-30.5) and mean weight of 1.090 g (IQR 800-1.391). Of which, 62.4% received a complete course of antenatal steroids. Given the differences observed in the baseline characteristics of patients who either did or did not receive a full course of antenatal steroids, a propensity score covariate adjustment was performed for all estimations. The effect of ACS therapy differs depending on sex with a positive effect on acute respiratory morbidity and mortality in male patients of less than 29 weeks' gestation. In female infants, there is no significant beneficial association between ACS therapy and mortality or any of the morbidities studied. CONCLUSION: In our population of preterm infants, treatment with antenatal steroids is associated with a different effect depending on sex. Antenatal steroids therapy associated with a positive effect in male patients with a gestational age of less than 29 weeks.

Risk factors and bronchopulmonary dysplasia severity: data from the Spanish Bronchopulmonary Dysplasia Research Network.

GEIDIS is a national-based research-net registry of patients with bronchopulmonary dysplasia (BPD) from public and private Spanish hospitals. It was created to provide data on the clinical characterization and follow-up of infants with BPD until adulthood. The purpose of this observational study was to analyze the characteristics and the impact of perinatal risk factors on BPD severity. The study included 1755 preterm patients diagnosed with BPD. Of the total sample, 90.6% (n = 1591) were less than 30 weeks of gestation. The median gestational age was 27.1 weeks (25.8-28.5) and median birth weight 885 g (740-1,070 g). A total of 52.5% (n = 922) were classified as mild (type 1), 25.3% (n = 444) were moderate (type 2), and 22.2% (n = 389) were severe BPD (type 3). In patients born at under 30 weeks' gestation, most pre-and postnatal risk factors for type 2/3 BPD were associated with the length of exposure to mechanical ventilation (MV). Independent prenatal risk factors were male gender, oligohydramnios, and intrauterine growth restriction. Postnatal risk factors included the need for FiO2 of > 0.30 in the delivery room, nosocomial pneumonia, and the length of exposure to MV. Conclusion: In this national-based research-net registry of BPD patients, the length of MV is the most important risk factor associated with type 2/3 BPD. Among type 3 BPD patients, those who required an FiO2 > .30 at 36 weeks' postmenstrual age had a higher morbidity, during hospitalization and at discharge, compared to those with nasal positive pressure but FiO2 < .30. What is Known: • BPD is a highly complex multifactorial disease associated with preterm birth. What is New: • The length of exposure to mechanical ventilation is the most important postnatal risk factor associated to bronchopulmonary severity which modulate the effect of most pre and postnatal risk factors. • Among patients with BPD, the requirement for FiO2 >.30% at 36 weeks of postmenstrual age is associated with greater morbidity during hospitalization and at discharge.

Temporal trends in respiratory care and bronchopulmonary dysplasia in very preterm infants over a 10-year period in Spain.

OBJECTIVE: To evaluate trends in respiratory care practices and bronchopulmonary dysplasia (BPD) among very preterm infants born in Spain between 2010 and 2019. STUDY DESIGN: This was a retrospective cohort study of data obtained from a national population-based database (SEN1500 network). Changes in respiratory care and BPD-free survival of infants with gestational age (GA) of 230-316 weeks and <1500 g were assessed over two 5-year periods. Temporal trends were examined by joinpoint and Poisson regression models and expressed as the annual per cent change and adjusted relative risk (RR) for the change per year. RESULTS: A total of 17 952 infants were included. In the second period, infants were less frequently intubated in the delivery room and during neonatal intensive care unit stay. This corresponded with an increase in use of non-invasive ventilation techniques. There were no significant differences between the periods in BPD-free survival or survival without moderate-to-severe BPD. After adjusting for covariates, the RR for the change per year was significant for the following variables: never intubated (RR 1.03, 95% CI 1.02 to 1.04); intubation in the delivery room (RR 0.98, 95% CI 0.97 to 0.99); use of nasal intermittent positive pressure ventilation (RR 1.08, 95% CI 1.05 to 1.11); and BPD-free survival (only in the group with the lowest GA; RR 0.98, 95% CI 0.97 to 0.99). CONCLUSION: Our findings reveal significant changes in respiratory care practices between 2009 and 2019. Despite an increase in use of non-invasive respiratory strategies, BPD-free survival did not improve and even worsened in the group with the lowest GA (230-256).

Target volume-guarantee in high-frequency oscillatory ventilation for preterm respiratory distress syndrome: Low volumes and high frequencies lead to adequate ventilation.

BACKGROUND AND OBJECTIVES: Respiratory distress syndrome (RDS) and ventilation-induced lung injury lead to significant morbidity in preterm infants. High-frequency oscillatory ventilation with volume-guarantee (HFOV-VG) has been used as a rescue therapy and might lead to lower rates of death and bronchopulmonary dysplasia, especially when using low tidal volumes and high frequencies. The aim of the study was to define HFOV-VG parameters leading to adequate ventilation in the first 72 h of preterm RDS using a low volume and high-frequency strategy. DESIGN AND METHODS: Retrospective cohort study in a tertiary-level neonatology unit. Infants <32 weeks with severe respiratory insufficiency needing HFOV-VG were included. Patients were ventilated following a standard mechanical ventilation aiming for low tidal volumes and high frequencies. Clinical data, perinatal characteristics and high-frequency parameters corresponding with adequate ventilation were recorded. RESULTS: 116 patients were included. Median gestational age was 25 weeks (interquartile range [IQR] = 24-27), median birth weight 724 g (IQR = 600-900 g). HFOV-VG was started at 2 h, median high-frequency tidal volume was 1.63 ml/kg (IQR = 1.44-1.84) and median frequency was 16 Hz (IQR = 15-18). Weight-adjusted tidal volumes did not depend on gestational age, antenatal corticosteroids nor chorioamnionitis, and were inversely correlated with frequencies (R 2 = -0.10, p = .001). CONCLUSION: HFOV-VG can reach adequate ventilation at high frequencies when using adequate volumes, providing a feasible ventilation strategy that might be of help in preterm infants with RDS.

Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial.

OBJECTIVES: Most studies of inhaled nitric oxide (iNO) for prevention of bronchopulmonary dysplasia (BPD) in premature infants have focused on short-term mortality and morbidity. Our aim was to determine the long-term effects of iNO. METHODS: A 7-year follow-up was undertaken of infants entered into a multicenter, double-blind, randomized, placebo-controlled trial of iNO for prevention of BPD in premature infants born between 24 and 28 weeks plus six days of gestation. At 7 years, survival and hospital admissions since the 2-year follow-up, home oxygen therapy in the past year, therapies used in the previous month and growth assessments were determined. Questionnaires were used to compare general health, well-being, and quality of life. RESULTS: A total of 305 children were assessed. No deaths were reported. Rates of hospitalization for respiratory problems (6.6 vs. 10.5%, iNO and placebo group, respectively) and use of respiratory medications (6.6 vs. 9.2%) were similar. Two patients who received iNO and one who received placebo had received home oxygen therapy. There were no significant differences in any questionnaire-documented health outcomes. CONCLUSIONS: iNO for prevention of BPD in very premature infants with respiratory distress did not result in long-term benefits or adverse long-term sequelae. In the light of current evidence, routine use of iNO cannot be recommended for prevention of BPD in preterm infants.

Effect of a new respiratory care bundle on bronchopulmonary dysplasia in preterm neonates.

The development of devices that can fix the tidal volume in high-frequency oscillatory ventilation (HFOV) has allowed for a significant improvement in the management of HFOV. At our institution, this had led to the earlier use of HFOV and promoted a change in the treatment strategy involving the use of higher frequencies (above 15 Hz) and lower high-frequency tidal volumes (VThf). The purpose of this observational study was to assess how survival without bronchopulmonary dysplasia grades 2 and 3 (SF-BPD) is influenced by these modifications in the respiratory strategy applied to preterm infants (gestational age < 32 weeks at birth) who required mechanical ventilation (MV) in the first 3 days of life. We compared a baseline period (2012-2013) against a period in which this strategy had been fully implemented (2016-2017). A total of 182 patients were exposed to MV in the first 3 days of life being a higher proportion on HFOV at day 3 in the second period 79.5% (n 35) in 2016-2017 vs 55.4% (n 31) in 2012-2013. After adjusting for perinatal risk factors, the second period is associated with an increased rate of SF-BPD (OR 2.28; CI 95% 1.072-4.878); this effect is more evident in neonates born at a gestational age of less than 29 weeks (OR 4.87; 95% CI 1.9-12.48).Conclusions : The early use of HFOV combined with the use of higher frequencies and very low VT was associated with an increase in the study population's SF-BPD. What is Known: • High-frequency ventilation with volume guarantee improve ventilation stability and has been shown to reduce lung damage in animal models. What is New: • The strategy of an earlier use of high-frequency oscillatory ventilation combined with the use of higher frequencies and lower tidal volume is associated to an increase in survival without bronchopulmonary dysplasia in our population of preterm infants.

Beractant and poractant alfa in premature neonates with respiratory distress syndrome: a systematic review of real-world evidence studies and randomized controlled trials.

Findings from previous meta-analyses of randomized clinical trials (RCTs) in premature infants with respiratory distress syndrome (RDS) varied as to whether clinical outcomes differed by type of animal-derived pulmonary surfactant; real-world evidence (RWE) was excluded. We extracted study characteristics and outcomes from full-text articles from a systematic search for studies that compared beractant with poractant alfa for RDS in preterm infants. RWE data were tabulated; RCT data were subjected to meta-analyses. Designs, patient characteristics, and follow-up durations varied widely among studies (4 RWE, 15 RCT). RWE studies with adjusted odds ratios (ORs) found no statistically significant between-treatment differences in outcomes. In RCT meta-analyses, no statistically significant between-treatment differences were observed for death (OR [95% confidence interval], 1.35 [0.98-1.86]), bronchopulmonary dysplasia (1.25 [0.96-1.62]), pneumothorax (1.21 [0.72-2.05]), and air leak syndrome (2.28 [0.82-6.39]). Collectively, outcomes were similar with beractant and poractant alfa in RWE studies and pooled RCTs.