Respiratory Support In Preterm Infants Research Articles

Skin-to-skin stabilisation and uninterrupted respiratory support for preterm infants after birth: feasibility of a new and simplified rPAP system

BackgroundThe rPAP respiratory support system, used for delivery room stabilisation with nasal prongs, has been shown to reduce the need for intubation in extremely preterm infants. A simplified version of...

Moving on from clinical animal-derived surfactants to peptide-based synthetic pulmonary surfactant.

Research on lung surfactant has exerted a great impact on newborn respiratory care and significantly improved survival and outcome of preterm infants with respiratory distress syndrome (RDS) due to surfactant deficiency because of lung immaturity. Current clinical, animal-derived, surfactants are among the most widely tested compounds in neonatology However, limited availability, high production costs, and ethical concerns about using animal-derived products constitute important limitations in their universal application. Synthetic lung surfactant offers a promising alternative to animal-derived surfactant by providing improved consistency, quality and purity, availability and scalability, ease of production and lower costs, acceptance, and safety for the treatment of neonatal RDS and other lung conditions. Third-generation synthetic surfactants built around surfactant protein B (SP-B) and C (SP-C) peptide mimics stand at the forefront of innovation in neonatal pulmonary medicine, while nasal continuous positive airway pressure (nCPAP) has become the standard non-invasive respiratory support for preterm infants. nCPAP can prevent the risk of chronic lung disease (bronchopulmonary dysplasia) and reduce lung injury by avoiding intubation and mechanical ventilation, is a relatively simple technique and can be initiated safely and effectively in the delivery room. Combining nCPAP with noninvasive, preferably aerosol, delivery of synthetic lung surfactant promises to improve respiratory outcomes for preterm infants, especially in low-and-middle income countries.

The effect of NHFOV on hemodynamics in mild and moderately preterm neonates: a randomized clinical trial

The aim of this study is to study cardio-respiratory effects of nasal high-frequency oscillatory ventilation (NHFOV) vs. NCPAP as an initial mode of ventilation in moderate-late-preterm infants. A randomized controlled trial was conducted in NICU of Alexandria University Maternity Hospital (AUMH). One-hundred late-moderate-preterm infants were randomly assigned to either NHFOV-group (n = 50) or NCPAP-group (n = 50). For both groups, functional echocardiography was performed in the first 24 h to detect hemodynamic changes and respiratory outcome was monitored throughout the hospital stay. The main outcomes were hemodynamic measurements and myocardial function using functional echocardiography of those infants along with the respiratory outcome and complications. Kaplan–Meier survival plot was used representing time course of NCPAP and NHFOV failure. Left ventricular output values were not significantly different in both groups with median 202 ml/kg /min and IQR (176–275) in NCPAP-group and 226 ml/kg/min with IQR (181–286) in NHFOV group. Nevertheless, ejection fraction and fractional shortening were significantly higher in NHFOV-group with P 0.001. The time to weaning, the time to reach 30%-FIO2, the need for invasive ventilation, oxygen support duration, and maximal-FIO2 were significantly more in NCAPAP group. Conclusion: NHFOV is an effective and promising tool of non-invasive-ventilation which can be used as a primary modality of respiratory support in preterm infants with variable forms of respiratory distress syndrome without causing detrimental effect on hemodynamics or significant respiratory complications. Trial registration: NCT05706428 (registered on January 21, 2023).What is Known:• NHFOV might be beneficial as a secondary mode of ventilation and might have an impact on hemodynamics.What is New:• NHFOV can be used as an initial mode of ventilation with CDP beyond the reported pressure limits of CPAP without causing neither CO2 retention nor adverse hemodynamic consequences.

Non-invasive versus invasive respiratory support in preterm infants

Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support management strategies are available for these infants, separable into non-invasive and invasive forms of respiratory support. Here we review the history and evolution of respiratory care for the preterm infant and then examine evidence that has emerged to support a non-invasive approach to respiratory management where able. Continuous positive airway pressure (CPAP) is the non-invasive respiratory support mode currently with the most evidence for benefit. CPAP can be delivered safely and effectively and can commence in the delivery room. Particularly in early life, time spent on non-invasive respiratory support, avoiding intubation and mechanical ventilation, affords benefit for the preterm infant by virtue of a lessening of lung injury and hence a reduction in incidence of bronchopulmonary dysplasia. In recent years, enthusiasm for application of non-invasive support has been further bolstered by new techniques for administration of exogenous surfactant. Methods of less invasive surfactant delivery, in particular with a thin catheter, have allowed neonatologists to administer surfactant without resort to endotracheal intubation. The benefits of this approach appear to be sustained, even in those infants subsequently requiring mechanical ventilation. This cements the notion that any reduction in exposure to mechanical ventilation leads to alleviation of injury to the vulnerable preterm lung, with a long-lasting effect. Despite the clear advantages of non-invasive respiratory support, there will continue to be a role for intubation and mechanical ventilation in some preterm infants, particularly for those born <25 weeks’ gestation. It is currently unclear what role early non-invasive support has in this special population, with more studies required.

Nasal continuous positive airway pressure practices in preterm infants: A survey of neonatal providers.

The standard of care for respiratory support of preterm infants is nasal continuous positive airway pressure (CPAP), yet practices are not standardized. Our aim was to survey CPAP practices in infants < 32 weeks gestation among the American Academy of Pediatrics Neonatal-Perinatal section. A US, web-based survey inquired about the initiation, management, and discontinuation of CPAP, and chinstrap use and oral feedings on CPAP. 857 providers consented. Regarding criteria to discontinue/wean CPAP: 69% use specific respiratory stability criteria; 22% a specific post-menstrual age; 8% responded other. 64% did not have guidelines for CPAP discontinuation; 54% did not have guidelines for CPAP initiation. 66% believe chinstraps improve CPAP efficacy; however, 11% routinely apply a chinstrap. 22% allow oral feeds on CPAP in certain circumstances. There are meaningful variabilities in CPAP practices among neonatal providers across the US. Given the potential long-term implications this can have on the growth and development of the preterm lung, further evidence-based research is needed in relation to respiratory outcomes to optimize and standardize CPAP strategies.

The vocal cords are predominantly closed in preterm infants

AimStudies in animals have shown that vocal cords (VCs) close during apnoea before and after birth, thereby impairing the effect of non-invasive ventilation. We tested the feasibility of visualising VCs using ultrasonography (US) and investigated the position and movement of the VCs during non-invasive respiratory support of preterm infants at birth. MethodsIn an observational study, VCs were visualised using US in infants <30 weeks gestation during both stabilisation after birth and at one hour after birth. Respiratory efforts were simultaneously recorded. The percentage of time the VCs were closed in the first ten minutes was determined from videoframes acquired at 15 Hz and compared with respiratory flow patterns measured using a respiratory function monitor. ResultsUS of the VCs could be performed in 20/20 infants included (median (IQR) gestational age 27+6 (27+1–28+6) weeks) without interfering with stabilisation, of whom 60% (12/20) were initially breathing and 40% (8/20) were apnoeic at birth. In breathing infants, the VCs closed between breaths and during breath holds, which accounted for 57% (49–66) of the time. In apnoeic infants receiving positive pressure ventilation, the VCs were closed for 93% (81–99) of the time. US at one hour after birth could be performed in 14/20 infants, VCs were closed between breaths and during breath holds, accounting for 46% (27–52) of the time. ConclusionVisualising VCs in preterm infants at birth using US is feasible. The VCs were closed during apnoea, in between breaths and during breath holds, impairing the effect of ventilation given.

Nasal high flow therapy for primary respiratory support in preterm infants.

Nasal high flow therapy for primary respiratory support in preterm infants.

Effects of caffeine on diaphragmatic activity in preterm infants.

Caffeine is the first-choice drug for the treatment for apnea of prematurity (AOP) in preterm infants and it has been reported that it improves the diaphragm activity. The aim of this study was to evaluate by ultrasound possible changes in diaphragm contractility and motility induced by caffeine. We studied 26 preterm infants with gestational age ≤34 weeks treated with caffeine for the prevention or treatment of AOP. Diaphragmatic ultrasound was performed 15 min (T0 ) before and 60 min (T60 ) after the loading (20 mg/kg) or maintenance (5 mg/kg) dose of caffeine. Diaphragmatic excursion (DE) and thickness at the end of inspiration (DT-in) and expiration (DT-ex), as well as peak velocity of the excursion at the end of inspiration (DT-in) and expiration (DT-ex) increased after administration of both loading and maintenance dose of caffeine. Ultrasounds confirmed that caffeine improves the activity of diaphragm in preterm infants improving its thickness, amplitude of excursions, and contraction velocity. These results are consistent with the effectiveness of caffeine in treating AOP and decreasing the risk of failure of noninvasive respiratory support in preterm infants with respiratory distress syndrome (RDS).

Biphasic non-invasive lung ventilation in the neonatal intensive care unit: the choice of tactics for starting respiratory support in preterm infants

The article deals with modern clinical and pathogenetic features of the variants of the respiratory pattern of non-invasive lung ventilation with two phases of airway pressure in the neonatal intensive care unit. The epidemiology, pathogenesis and assessment of the severity of the clinical picture of the neonatal respiratory distress syndrome are presented. The anatomical and physiological features of cardiorespiratory adaptation and targeted indicators of complex monitoring of the vital functions of the body of premature babies during the initiation of the starting two-phase non-invasive ventilation of the lungs are discussed. Early predictors of failure and criteria for optimizing the clinical efficacy of initial biphasic non-invasive ventilation in children with extremely low birth weight are considered. The clinical and prognostic role and features of perinatal screening were assessed when choosing the tactics of starting respiratory support in premature infants in the neonatal intensive care unit.

A physiological approach to applying CPAP in the preterm infant.

Nasal continuous positive airway pressure (CPAP) is increasingly used for respiratory support in preterm infants with respiratory distress syndrome at birth and after extubation from mechanical ventilation. Controversies with CPAP use still exists due to non-uniformity of devices and interfaces used, equivalence of testing conditions for different CPAP systems, differences in study designs, and short study periods that may be insufficient to detect important and relevant clinical outcomes. Compared with ventilator-derived constant-pressure flow-opposition CPAP, variable fluidic flow-opposition CPAP systems may be advantageous and offer some clinical benefits. The distinction between constant-flow fluid-sealed bubble CPAP and variable-flow fluidic flow-opposition systems is less clear. Appropriately designed randomized clinical trials that separately address the controversies with CPAP use in various clinical settings, are necessary to determine which CPAP system results in best outcomes.

Efficacy of noninvasive high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation as post-extubation respiratory support in preterm infants: a Meta analysis

To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants. China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05). Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.

Machine learning to predict late respiratory support in preterm infants: a retrospective cohort study

Bronchopulmonary dysplasia (BPD) has been a critical morbidity in preterm infants. To improve our definition and prediction of BPD is challenging yet indispensable. We aimed to apply machine learning (ML) to investigate effective models by using the recently-proposed and data-driven definition to predict late respiratory support modalities at 36 weeks’ post menstrual age (PMA). We collected data on very-low-birth-weight infants born between 2016 and 2019 from the Taiwan Neonatal Network database. Twenty-four attributes associated with their early life and seven ML algorithms were used in our analysis. The target outcomes were overall mortality, death before 36 weeks’ PMA, and severity of BPD under the new definition, which served as a proxy for respiratory support modalities. Of the 4103 infants initially considered, 3200 were deemed eligible. The logistic regression algorithm yielded the highest area under the receiver operating characteristic curve (AUROC). After attribute selection, the AUROC of the simplified models remain favorable (e.g., 0.801 when predicting no BPD, 0.850 when predicting grade 3 BPD or death before 36 weeks’ PMA, and 0.881 when predicting overall mortality). By using ML, we developed models to predict late respiratory support. Estimators were developed for clinical application after being simplified through attribute selection.

High-flow nasal cannula versus continuous positive airway pressure in primary respiratory support for preterm infants: Asystematic review and meta-analysis.

Respiratory support is crucial for the survival of preterm infants, and High-flow Nasal Cannula Oxygen Therapy (HFNC) and Continuous Positive Airway Pressure (CPAP) are commonly used for neonatal respiratory support. This meta-analysis aimed to compare the effects of HFNC and CPAP in primary respiratory support for preterm infants, to provide evidence-based support for clinical practice. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, VIP, WANFANG and SinoMed were searched for eligible studies. The primary outcomes included the incidence of treatment failure and the application of mechanical ventilation. A total of 27 eligible studies with 3,351 participants were included. There was no significant difference in the incidence of respiratory support failure [RR = 1.17, 95%CI (0.88-1.56)] and the application of mechanical ventilation [RR = 1.00, 95%CI (0.84-1.19)] between HFNC group and CPAP group. HFNC resulted in lower rate of air leaks [RR = 0.65, 95%CI (0.46-0.92)], nasal trauma [RR = 0.36, 95%CI (0.29-0.45)] and abdominal distension [RR = 0.39, 95%CI (0.27-0.58)], and later time of mechanical ventilation initiating [SMD = 0.60, 95%CI (0.21-0.99)], less duration of oxygen therapy [SMD = -0.35, 95%CI (-0.68 to -0.02)] and earlier enteral feeding [SMD = -0.54, 95%CI (-0.95 to -0.13)]. Alternative non-invasive respiratory support after initial treatment failure resulted in no difference in the application of mechanical ventilation between the two groups [RR = 0.99, 95%CI (0.52-1.88)]. HFNC might be more effective and safer in primary respiratory support for preterm infants. Using CPAP as a remedy for the treatment failure of HFNC could not avoid intubation. For premature infants with the gestational age <28 weeks, HFNC as primary respiratory support still needs to be further elucidated. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022313479, identifier: CRD42022313479.

Clinical significance of dynamics between oxidative stress levels during mechanical lung ventilation in premature infants with persistent pulmonary hypertension

The aim of this study was to determine the clinical significance of the levels and dynamics of the urinary 8-hydroxy-2-deoxyguanosine, degree of pulmonary hypertension on choosing the duration and form of respiratory support in premature infants with respiratory distress syndrome in combination with perinatal asphyxia.&#x0D; Materials and methods. The levels of the urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), ng/ml were determined by enzyme immunoassay (ELISA) method and the degree of pulmonary hypertension (PH) - by echocardiography in 60 premature new-borns at 26-32 weeks of gestation on the 1st and the 3rd–5th days of life. A comparative analysis of indicators was carried out in 2 groups: I – 32 children with respiratory distress syndrome (RDS); II – 28 children with RDS combined with perinatal asphyxia. All infants received a respiratory support, depending on the clinical condition, blood gas analyses, and the chest X-ray.&#x0D; Results. The level and dynamics of the urinary 8-OHdG correlated to degree of PH, form, and duration of respiratory support. Children of the group II on the 1st day of life had echocardiogram indicators of mild PH and indicators of the urinary 8-OHdG 2.27±0.39 ng/ml; by 3rd–5th days of life – level of the urinary 8-OHdG increased to 4.10±0.42 ng/ml and the level of PH – to moderate, required 76.2 % longer respiratory support compared to children of the group I.&#x0D; Conclusions. Prematurely born infants with RDS in combination with perinatal asphyxia have a higher oxidative stress (OS) levels and more significant pulmonary hypertension, which requires a longer respiratory support by 76.2 % and more often use of high frequency oscillatory ventilation (HFOV) by 9.3 %

The long-term outcomes of preterm infants receiving non-invasive high-frequency oscillatory ventilation.

ObjectiveTo investigate the clinical outcomes of preterm infants who received non-invasive high-frequency oscillatory ventilation following extubation in a neonatal intensive care unit.MethodsInfants born between 25 and 34 weeks of gestation with a birth weight of <1,500 g, who were admitted into the neonatal intensive care unit of Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, China, requiring mechanical ventilation on admission were randomized to the non-invasive high-frequency ventilation group, nasal intermittent positive pressure ventilation group, or nasal continuous positive airway pressure group following extubation. Their respiratory and neurodevelopmental outcomes were assessed at 12 and 24 months of corrected age.ResultsAmong 149 preterm infants who underwent randomization, 139 completed their treatment in the neonatal intensive care unit (45, 47, 47 in the non-invasive high-frequency ventilation group, nasal intermittent positive pressure ventilation group, or nasal continuous positive airway pressure group, respectively), 113 were assessed at 12-month corrected age, and 110 of 113 were assessed again at 24-month corrected age. There were no differences in the number of times bronchitis, pneumonia, wheezing episodes, and re-hospitalization rates appeared due to respiratory diseases among the three groups (P > 0.05); the pulmonary function tests at 12-month corrected age showed respiratory rate, tidal volume, inspiratory time/expiratory time, time to peak expiratory flow/expiratory time, volume at peak expiratory flow/expiratory volume, expiratory flow at 25, 50, and 75% tidal volume were all similar among infants from the 3 groups (P > 0.05). There were no differences in the rates of neurodevelopmental impairment among the three groups at 24-month corrected age (P > 0.05).ConclusionAs post-extubation respiratory support in preterm infants, non-invasive high-frequency ventilation did not increase the rates of long-term respiratory morbidities and neurodevelopmental impairment compared with nasal intermittent positive pressure ventilation and nasal continuous positive airway pressure.

Current Controversies and Advances in Non-invasive Respiratory Support for Preterm Infants

Current Controversies and Advances in Non-invasive Respiratory Support for Preterm Infants

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

IntroductionWhile 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.MethodsThis 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.ResultsOf 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.ConclusionNIPPV use did not appear to decisively influence the incidence of survival without moderate-to-severe BPD in patients managed exclusively with non-invasive ventilation.

Human bone marrow-derived mesenchymal stem cells rescue neonatal CPAP-induced airway hyperreactivity

Continuous positive airway pressure (CPAP) is a primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. The therapeutic benefits of mesenchymal stem cells (MSCs) have been demonstrated in a variety of animal models and several clinical trials are currently underway to assess their safety profiles in the setting of prematurity and bronchopulmonary dysplasia (BPD). In the present study, using a mouse model of neonatal CPAP, we investigated whether conditioned medium harvested from cultures of human bone-marrow derived mesenchymal stem cells (hMSC) could rescue the CPAP-induced AHR, based upon previous observations of their anti-AHR properties. Newborn mice (male and female) were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for the first 7 postnatal days. At postnatal day 21 (two weeks after CPAP ended), lungs were removed, precision-cut lung slices were sectioned and incubated for 48 h in vitro in conditioned medium collected from cultures of three different hMSC donors. As expected, CPAP resulted in AHR to methacholine compared to untreated control mice. hMSC conditioned medium from the cultures of all three donors completely reversed AHR. These data reveal potential therapeutic benefits of hMSC therapy, which may be capable of rescuing the long-term adverse effects of neonatal CPAP on human airway function.

Noninvasive Ventilation and Exogenous Surfactant in Times of Ever Decreasing Gestational Age: How Do We Make the Most of These Tools?

Noninvasive Ventilation and Exogenous Surfactant in Times of Ever Decreasing Gestational Age: How Do We Make the Most of These Tools?

A New Approach of Several Minimally Invasive Procedures for Improvement of the Outcome in Preterm Infants

BACKGROUND: Based on the last update of European Consensus Guidelines on Management of Respiratory Distress Syndrome, the following study is new for our clinic approach for minimally invasive respiratory support in preterm infants. AIM: The aim is to find out if the implementation of several minimally invasive procedures leads to a reduction of the frequency and severity of chronic complications and improved outcomes in extremely premature infants. MATERIALS AND METHODS: Infants are below 30 gestational weeks, divided into two groups – therapeutic – 37 infants on standardized early respiratory management protocol which includes: High-flow continuous positive airway pressure (20l/min ≥ 15 PEEP) in the delivery room, support of spontaneous breathing and non-invasive mechanical ventilation, avoidance of hypothermia and LISA shortly after birth, and control group – 46 infants that received standard respiratory support (positive pressure ventilation – invasive and non-invasive in the delivery room, most infants ≤ 27 weeks gestational age were intubated and received early surfactant, extubation “when being ready” – usually after few days). RESULTS: The duration of mechanical ventilation, oxygen therapy, and hospital stay is shorter in the therapeutic group (p &lt; 0.05). Severe bronchopulmonary dysplasia is not found in the interventional group, 26% of the patients in the control group have severe form of the disease (p = 0.001). Severe intraventricular hemorrhages are found in 11% of the infants in the therapeutic group and 28% in the control group (p = 0.06). CONCLUSION: Due to the changed protocol, we report increased survival of ELBW infants without severe chronic complications. The acute pulmonary injury, acquired in the perinatal period, is directly connected with the development of BPD. For this reason, all the changes that we introduced in our clinic (heat management, support of spontaneous breathing, “open up” lungs – high flow PEEP/CPAP, and LISA during spontaneous breathing) contribute to the lower frequency of severe chronic complications and high percentage of ELBW infants, who do not develop severe BPD.