Quantitative Lung Ultrasonography to Guide Surfactant Therapy in Neonates Born Late Preterm and Later.

Importance: Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population. Objective: To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates. Design, Setting, and Participants: This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled. Exposure: Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making. Main Outcomes and Measures: The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed. Results: A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted ß, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted ß, 0.2; 95% CI, 0.1-0.3; P < .001). Conclusions and Relevance: In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.

Efficacy and safety of different inhaled corticosteroids for bronchopulmonary dysplasia prevention in preterm infants: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants. METHOD: Electronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed. RESULTS: Overall, budesonide was significantly associated with a reduction in BPD at 36 weeks' postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks' postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks' postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments. CONCLUSION: These findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.

Surfactant administration methods for premature newborns: LISA vs. INSURE comparative analysis.

INTRODUCTION: Respiratory Distress Syndrome (RDS) is the most common respiratory disorder among premature infants. The use of surfactant has significantly reduced respiratory complications and mortality. There are two conventional methods for administering surfactant: Intubate-Surfactant-Extubate (INSURE) and Less Invasive Surfactant Administration (LISA). This study aims to compare the effects of surfactant administration using these two methods on the treatment outcomes of premature newborns. MATERIALS AND METHODS: In this retrospective cohort study, we included 100 premature newborns with RDS and spontaneous breathing who were admitted to the Neonatal Intensive Care Unit of Besat Hospital in Sanandaj city in 2021. Exclusion criteria comprised congenital anomalies and the needing for intubation for resuscitation at birth. The outcomes of epmericaly trated with two methods were compared: the LISA (50 neonates) and the INSURE (50 neonates). Our interesting outcomes were needing for mechanical ventilation, duration of ventilation, pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia. Finally, we entered the data into STATA-14 statistical software and analyzed it using chi-square and t-tests. RESULTS: In this study, 69% of the neonates were boys. The LISA group exhibited significantly lower rates of need for mechanical ventilation (P = 0.003) and ventilation duration (P < 0.001) compared to the INSURE group. Conversely, there were no significant differences between the two groups (P > 0.05) in terms of pneumothorax, pulmonary hemorrhage, severe retinopathy, CPAP duration, and bronchopulmonary dysplasia rates. CONCLUSION: The results of this study suggest that the LISA method is a safe and non-invasive approach for surfactant administration. Notably, it resulted in a reduced need for mechanical ventilation and decreased ventilation duration compared to the INSURE method.

Exogenous surfactant for lung contusion causing ARDS: A systematic review of clinical and experimental reports.

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.

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OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

The current clinical landscape of neonatal respiratory failure in Jiangsu Province of China: patient demographics, NICU treatment interventions, and patient outcomes.

INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.

Evaluation of a respiratory care protocol including less invasive surfactant administration in preterm infants.

BACKGROUND: Respiratory care protocol including less invasive ssurfactant administration (LISA) in ≤29 weeks' gestational age (GA) infants introduced in October 2018. METHODS: Retrospective study of infants admitted on continuous positive airway pressure (CPAP) October 2018 to December 2021. Maternal and neonatal variables were compared between infants managed on CPAP with and without LISA. Infants who received LISA and subsequently required mechanical ventilation (MV) within 72 h of life (HOL) [LISA failure (LF)] were compared with those who required no MV [LISA success (LS)]. RESULTS: 249 infants were admitted on CPAP, 5 were intubated prior to LISA, 143 required LISA and 101 remained on CPAP without surfactant. Of those receiving LISA, 108 were LS and 35 were LF. Compared to LS, LF infants were of lower GA and birth weight, required higher fractional inspired oxygen (FiO2), and CPAP level at birth, admission, one HOL, and an hour after LISA. Moreover, LF infants had higher mortality and morbidity. Together GA ≤ 25 weeks' and FiO2 ≥ 0.3 an hour after LISA best predicted LF. CONCLUSIONS: Over 80% of infants admitted on CPAP avoided MV within 72 HOL. Early predictors of LF provide targets for future interventions to decrease need for MV in preterm infants. IMPACT: Less invasive surfactant administration (LISA) decreases the need for mechanical ventilation (MV) and improves outcomes. However, some infants require MV within 72 h of life (HOL) despite LISA (LISA failure). Over 80% of ≤29 weeks' gestational age (GA) infants can be successfully managed on CPAP with or without surfactant in the first 72 HOL. A combination of factors including ≤25 weeks' GA and fraction of inspired oxygen ≥0.3 an hour after LISA predict LISA failure. Evaluation of a noninvasive respiratory support strategy including LISA provides targets for intervention to decrease need for MV in preterm infants.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.

[Efficacy and safety of inhalation of pulmonary surfactant using vibrating mesh nebulizers combined with nasal continuous positive airway pressure in the treatment of neonatal respiratory distress syndrome].

OBJECTIVE: To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS). METHODS: A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. RESULTS: A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO2/FiO2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO2/FiO2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO2/FiO2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found (P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. CONCLUSIONS: Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO2/FiO2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.

Can surfactants affect mortality and morbidity in term infants with respiratory failure?

BACKGROUND: We aimed to discuss term infants who are given surfactant due to respiratory disorder according to the underlying etiology, the dose of surfactant administration, and the need for repeated surfactant administration. METHODS: In this retrospective study infants hospitalized in the 4th level neonatal intensive care unit during January 2019 and December 2021 and administered surfactant due to respiratory distress were included. Term infants given surfactant due to respiratory failure were included in the study through the data recording system. The number of surfactant doses, indications for administration, mortality, duration of hospitalization, intubation time, and inotrope use were recorded in the infants included in the study. RESULTS: : During the two-year period, 1250 infants were hospitalized in our neonatal intensive care unit. Of those, 56 infants received surfactant replacement therapy for severe respiratory failure. There were 30 infants with pneumonia, 4 infants with meconium aspiration syndrome (MAS), and 22 infants with transient tachypnea of the newborn (TTN). It was seen that single-dose administration was higher in patients with TTN (p = 0.01), while multiple-dose surfactant administration was more common in patients with MAS, resulting in a statistical difference (p = 0.02). Mortality was lower, especially in cases given early surfactant administration and this situation was statistically significant (p < 0.001). Duration of intubation was 5.05 ± 4.7 days in early surfactant administration group and 8.0 ± 6.1 days in late surfactant administration group. This difference was statistically significant (p = 0.04). While early surfactant application was statistically higher in the TTN group (p = 0.007), late surfactant application was statistically higher in the pneumonia group (p = 0.001). DISCUSSION: Despite the difference on administration time and repeat dose interval due to etiology, surfactant treatment is improving the respiratory distress of term infants.

Video-based reflection on neonatal interventions during COVID-19 using eye-tracking glasses: an observational study.

OBJECTIVE: The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal interventions during the COVID-19 pandemic. DESIGN: Observational prospective single-centre study. SETTING: Neonatal intensive care unit at the Leiden University Medical Center. PARTICIPANTS: All local neonatal healthcare providers. INTERVENTION: There were two groups of participants: proceduralists, who wore eye-tracking glasses during procedures, and observers who later watched the procedures as part of a video-based reflection. MAIN OUTCOME MEASURES: The primary outcome was the feasibility of, and the proceduralists and observers' experience with, the point-of-view eye-tracking videos as an additional tool for bedside teaching and video-based reflection. RESULTS: We conducted 12 point-of-view recordings on 10 different patients (median gestational age of 30.9±3.5 weeks and weight of 1764 g) undergoing neonatal intubation (n=5), minimally invasive surfactant therapy (n=5) and umbilical line insertion (n=2). We conducted nine video-based observations with a total of 88 observers. The use of point-of-view recordings was perceived as feasible. Observers further reported the point-of-view recordings to be an educational benefit for them and a potentially instructional tool during COVID-19. CONCLUSION: We proved the practicability of eye-tracking glasses for point-of-view recordings of neonatal procedures and videos for observation, educational sessions and logistics considerations, especially with the COVID-19 pandemic distancing measures reducing bedside teaching opportunities.

Trial of aerosolised surfactant for preterm infants with respiratory distress syndrome.

OBJECTIVE: To evaluate the safety of an aerosolised surfactant, SF-RI 1, administered via nasal continuous positive airway pressure (nCPAP) and a prototype breath synchronisation device (AeroFact), to preterm infants with respiratory distress syndrome (RDS). DESIGN: Multicentre, open-label, dose-escalation study with historical controls. SETTING: Newborn intensive care units at Mater Mothers' Hospital, Brisbane, and Royal Hospital for Women, Sydney, Australia. PATIENTS: Infants 26 weeks through 30 weeks gestation who required nCPAP 6-8 cmH2O and fraction of inspired oxygen (FiO2) <0.30 at <2 hours of age. INTERVENTIONS: In part 1, infants received a single dose of 216 mg/kg of aerosolised surfactant. In part 2, infants could receive up to four doses of aerosolised surfactant. Three historical control infants were matched for each enrolled infant. MAIN OUTCOME MEASURES: Treatment failure was defined as Respiratory Severity Score (FiO2×cmH2O nCPAP) >2.4, nCPAP >8 cmH2O, arterial carbon dioxide >65 mm Hg, pH <7.20 or three severe apnoeas within 6 hours during the first 72 hours of life. Other outcomes included tolerance of the AeroFact treatment and complications of prematurity. RESULTS: 10 infants were enrolled in part 1 and 21 in part 2 and were compared with 93 historical controls. No safety issues were identified. In part 2, 6 of 21 (29%) AeroFact-treated infants compared with 30 of 63 (48%) control infants met failure criteria. Kaplan-Meier analysis of patients in part 2 showed a trend towards decreased rate of study failure in the AeroFact-treated infants compared with historical controls (p=0.10). CONCLUSION: The AeroFact system can safely deliver aerosolised surfactant to preterm infants with RDS who are on nCPAP. TRIAL REGISTRATION NUMBER: ACTRN12617001458325.

Catheter insertion depths in less-invasive surfactant administration.

INTRODUCTION: Less-invasive surfactant administration (LISA) under continuous positive airway pressure is increasingly used for the treatment of neonatal respiratory distress. Different procedures are described, but data on the optimal catheter insertion depth are sparse. OBJECTIVE: To generate data for recommending an optimal catheter insertion depth in LISA. METHODS: We examined 112 anterior-posterior chest X-rays from intubated infants and determined the carina's vertebral projection, whenever possible. After that, distances between the middle of cervical vertebra 4 (C4) and thoracic vertebra 2 and the middle of C4 to thoracic vertebra 3, respectively, were measured. Results were plotted against infant's weight. RESULTS: A weight-based chart and recommendations for the optimal intratracheal catheter position in infants with a body weight between 350 and 4000 g were created. CONCLUSIONS: Generated data offer standardisation and may thus help to find a balance between risk of surfactant reflux and unilateral surfactant administration.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial.

BACKGROUND: Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy. OBJECTIVES: To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant. METHODS: We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27+0 and 34+6 weeks' gestation, presenting respiratory distress after birth. EXCLUSION CRITERIA: endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH2O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results. RESULTS: We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH2O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH2O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH2O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support. CONCLUSION: Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.

Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis.

CONTEXT: Surfactant nebulization (SN) may offer a safe alternative for surfactant administration in respiratory distress syndrome of preterm infants. OBJECTIVE: To evaluate the efficacy of SN for the prevention of early intubation. DATA SOURCES: Medline, Embase, The Cochrane Library, clinicaltrials.gov, published abstracts, and references of relevant articles were searched through March 23, 2021. STUDY SELECTION: Randomized clinical trials of preterm infants <37 weeks' gestation comparing SN with noninvasive respiratory support or intratracheal surfactant application. DATA EXTRACTION: Two reviewers extracted data and assessed risk of bias from included studies separately and blinded. Data were pooled by using a fixed-effects model. Subgroups (gestational age, type of nebulizer, surfactant type, and dosage) were evaluated. Primary outcome was intubation rate at 72 hours after birth. RESULTS: Nine studies recruiting 1095 infants met inclusion criteria. SN compared with standard care significantly reduced intubation rate at 72 hours after birth (226 of 565 infants [40.0%] vs 231 of 434 infants [53.2%]; risk ratio [RR]: 0.73, 95% confidence interval [CI]: 0.63-0.84; number needed to treat: 8; 95% CI: 5-14]). Prespecified subgroup analysis identified important heterogeneity: SN was most effective in infants ≥28 weeks' gestation (RR: 0.70, 95% CI: 0.60-0.82), with a pneumatically driven nebulizer (RR: 0.52, 95% CI: 0.40-0.68) and in infants receiving ≥200 mg/kg and animal-derived surfactant (RR: 0.63, 95% CI: 0.52-0.75). No differences in neonatal morbidities or mortality were identified. LIMITATIONS: Quality of evidence was low owing to risk of bias and imprecision. CONCLUSIONS: SN reduced the intubation rate in preterm infants with a higher efficacy for specific subgroups. There was no difference in relevant neonatal morbidities or mortality.

Decreasing Continuous Positive Airway Pressure Failure in Preterm Infants.

BACKGROUND AND OBJECTIVES: Many preterm infants stabilized on continuous positive airway pressure (CPAP) at birth require mechanical ventilation (MV) during the first 72 hours of life, which is defined as CPAP failure. Our objective was to decrease CPAP failure in infants ≤29 weeks' gestational age (GA). METHODS: A quality improvement bundle named OPTISURF was implemented for infants ≤29 weeks' GA admitted on CPAP, consisting of stepwise escalation of CPAP and less invasive surfactant administration guided by fractional inspired oxygen concentration ≥0.3. The CPAP failure rate was tracked by using control charts. We compared practice and outcomes of a pre-OPTISURF cohort (January 2017 to September 2018) to a post-OPTISURF cohort (October 2018 to December 2019). RESULTS: Of the 216 infants ≤29 weeks' GA admitted to NICU on CPAP, 125 infants belonged to the pre-OPTISURF cohort (OSC) and 91 to the post-OSC. Compared with the pre-OSC, a higher proportion of infants in the post-OSC received CPAP 7 cm H2O within 4 hours of life (7% vs 32%; P < .01). The post-OSC also had lower rates of CPAP failure (54% vs 11%; P < .01), pneumothoraces (8% vs 1%; P < .03), need for MV (58% vs 31%; P < .01), and patent ductus arteriosus treatment (21% vs 9%; P = .02). Additionally, in a subgroup analysis, CPAP failure was lower in the post-OSC among infants 23 to 26 weeks (79% vs 27%; P < .01) and 27 to 29 weeks' GA (46% vs 3%; P < .01). CONCLUSIONS: Implementation of a quality improvement bundle including CPAP optimization and less invasive surfactant administration decreased CPAP failure and need for MV in preterm infants.

The possible effect of pentoxifylline on development and severity of retinopathy of prematurity.

BACKGROUND AND AIM: Retinopathy of prematurity (ROP) is the major ocular problem of preterm infants that occurs with abnormal proliferation of immature retinal vessels. Although pentoxifylline (PTX) was reported to inhibit vasculogenesis and neovascularization in experimental studies, there is no clinical data about the effects of PTX treatment on the development and severity of ROP. This clinical study aimed to investigate the possible effects of PTX on the development of ROP. MATERIALS AND METHODS: A single-centre retrospective study was conducted including preterm infants who were hospitalised in the neonatal intensive care unit between 2015-2017 years. Infants were divided into two groups in terms of PTX administration for adjuvant therapy, as PTX and non-PTX groups. RESULTS: A total of 211 infants were included in the study [gestational age 29 (27-31) weeks, birth weight 1140 (960-1340) g]. From these, 97 infants (46%) were given PTX treatment. The two groups were similar in terms of demographic data and baseline clinical characteristics. Any stage of ROP was detected in 47.4% of infants in the PTX group, which was significantly higher than those in the non-PTX group (27.2%) (p = 0.002). The incidence of advanced-stage ROP in the PTX group (10.3%) was also higher than in the non-PTX group (2.6%) (p = 0.021). Repeated usage of PTX was not found to be related to the development of ROP (p = 0.059). The time of PTX administration was similar between the ROP and no-ROP groups (median; one vs one week, p = 0.825). Surfactant therapy, duration of hospital stay, and PTX treatment were found as significant risk factors for ROP in the logistic regression analysis. CONCLUSIONS: In contrast to the experimental studies and also promising results of PTX treatment in some neonatal morbidities, it may be associated with increased incidence and stage of ROP.