Left atrial strain in neonates with congenital diaphragmatic hernia and length of stay in pediatric intensive care unit.

Introduction: The role of cardiac left ventricle (LV) dysfunction in children with congenital diaphragmatic hernia (CDH) has gained increasing attention. The hernia allows abdominal mass to enter thorax and subsequently both dislocating and compressing the heart. The pressure on vessels and myocardium alters blood flow and may interfere with normal development of the LV. A dysfunctional LV is concerning and impacts the complex pathophysiology of CDH. Hence, assessing both the systolic and diastolic LV function in the newborn with CDH is important, and it may add value for medical treatment and prognostic factors as length of stay (LOS) in pediatric intensive care unit (PICU). LV strain is considered an early marker of systolic dysfunction used in the pediatric population. Left atrial (LA) strain is an echocardiographic marker of LV diastolic dysfunction used in the adult population. When filling pressure of the LV increases, the strain of the atrial wall is decreased. We hypothesized that reduced LA strain and LV strain are correlated with the LOS in the PICU of newborns with CDH. Methods: This retrospective observational cohort study included data of 55 children born with CDH between 2018 and 2020 and treated at Karolinska University Hospital, Sweden. Overall, 46 parents provided consent. Echocardiograms were performed in 35 children <72 h after birth. The LA reservoir strain (LASr), LV global longitudinal strain, LV dimensions, and direction of blood flow through the patent foramen ovale (PFO) were retrospectively assessed using the echocardiograms. Results: Children with LASr <33% (n = 27) had longer stays in the PICU than children with LA strain ≥33% (n = 8) (mean: 20.8 vs. 8.6 days; p < 0.002). The LASr was correlated with the LOS in the PICU (correlation coefficient: -0.378; p = 0.025). The LV dimension was correlated with the LOS (correlation coefficient: -0.546; p = 0.01). However, LV strain was not correlated to LOS. Conclusion: Newborns with CDH and a lower LASr (<33%) had longer stays in the PICU than children with LASr ≥33%. LASr is a feasible echocardiographic marker of diastolic LV dysfunction in newborns with CDH and may indicate the severity of the condition.

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

BACKGROUND: The 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 the system has been developed. The purpose of this study was to determine the feasibility of providing uninterrupted respiratory support with the simplified rPAP from birth up to 4 hours of life and to assess ease of use for skin-to skin stabilisation. METHODS: This was a non-randomised feasibility study conducted at Karolinska University Hospital, Sweden. Respiratory support with continuous positive airway pressure (CPAP) and positive pressure ventilation if needed was given with the simplified rPAP using heated humidified gases. Respiratory support was provided in the delivery room, during transportation and in the neonatal unit, for a maximum of 4 hours. RESULTS: 32 preterm infants with a mean (SD) gestational age of 33.4 weeks (±1.2) were included. Of 17 infants born vaginally, 13 were stabilised skin-to-skin. The remaining infants were stabilised on a resuscitation table. All infants received CPAP and nine received positive pressure ventilation. 31 infants received continued support during transport and after arrival in the neonatal unit. Minor interruptions in CPAP support occurred in all infants. The study did not reveal problems with usability of the system. CONCLUSION: It is feasible to stabilise preterm infants with the simplified respiratory support system both skin-to-skin and on a resuscitation table, and to provide continued respiratory support with the same system during transportation and in the neonatal unit. TRIAL REGISTRATION NUMBER: NCT04244890.

Nordic survey showed wide variation in discharge practices for very preterm infants.

AIM: We aimed to describe clinical practices and criteria for discharge of very preterm infants in Nordic neonatal units. METHODS: Medical directors of all 89 level-2 and level-3 units in Denmark, Finland, Iceland, Norway and Sweden were invited by e-mail to complete a web-based multiple-choice survey with the option to make additional free-text comments. RESULTS: We received responses from 83/89 units (93%). In all responding units, discharge readiness was based mainly on clinical assessment with varying criteria. In addition, 36% used formal tests of cardiorespiratory stability and 59% used criteria related to infant weight or growth. For discharge with feeding tube, parental ability to speak the national language or English was mandatory in 45% of units, with large variation among countries. Post-discharge home visits and video-consultations were provided by 59% and 51%, respectively. In 54% of units, parental preparation for discharge were not initiated until the last two weeks of hospital stay. CONCLUSION: Discharge readiness was based mainly on clinical assessment, with criteria varying among units despite similar population characteristics and care structures. This variation indicates a lack of evidence base and may unnecessarily delay discharge; further studies of this matter are needed. Earlier parental preparation and use of interpreters might facilitate earlier discharge.

Preterm birth in the Nordic countries-Capacity, management and outcome in neonatal care.

AIM: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. METHODS: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. RESULTS: Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. CONCLUSION: Management of very preterm infants exhibited significant regional variations in the Nordic countries.

Respiratory outcomes after delivery room stabilisation with a new respiratory support system using nasal prongs.

AIM: To study if stabilisation using a new respiratory support system with nasal prongs compared to T-piece with a face mask is associated with less need for mechanical ventilation and bronchopulmonary dysplasia. METHODS: A single-centre follow-up study of neonates born <28 weeks gestation at Karolinska University Hospital, Stockholm included in the multicentre Comparison of Respiratory Support after Delivery (CORSAD) trial and randomised to initial respiratory support with the new system versus T-piece. Data on respiratory support, neonatal morbidities and mortality were collected up to 36 weeks post-menstrual age. RESULTS: Ninety-four infants, 51 female, with a median (range) gestational age of 25 + 2 (23 + 0, 27 + 6) weeks and days, were included. Significantly fewer infants in the new system group received mechanical ventilation during the first 72 h, 24 (52.2%) compared with 35 (72.9%) (p = 0.034) and during the first 7 days, 29 (63.0%) compared with 39 (81.3%) (p = 0.045) in the T-piece group. At 36 weeks post-menstrual age, 13 (28.3%) in the new system and 13 (27.1%) in the T-piece group were diagnosed with bronchopulmonary dysplasia. CONCLUSION: Stabilisation with the new system was associated with less need for mechanical ventilation during the first week of life. No significant difference was seen in the outcome of bronchopulmonary dysplasia.

Transition of Extremely Preterm Infants from Birth to Stable Breathing: A Secondary Analysis of the CORSAD Trial.

OBJECTIVE: Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period. METHODS: This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups. RESULTS: Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD -16.5, 95% CI [-31.7 to -1.1], p 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD -15.6, 95% CI [-30.7 to -0.8], p 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups. CONCLUSION: In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation.

First week of life respiratory management and pulmonary ventilation/perfusion matching in infants with bronchopulmonary dysplasia: a retrospective observational study.

OBJECTIVE: To investigate the association between early neonatal respiratory management in infants with bronchopulmonary dysplasia (BPD) and the degree of pulmonary ventilation perfusion-matching (V/Q) at term. METHODS: 30 preterm infants with a diagnosis of BPD who were initially treated with either controlled mechanical ventilation/continuous positive airway pressure (CMV/CPAP) (n = 14) or high-frequency oscillatory ventilation (HFOV) using a high lung-volume strategy (n = 16) were retrospectively included in this study. All infants underwent pulmonary V/Q single photon emission computed tomography at a median postmenstrual age of 37 weeks. RESULTS: Infants treated with HFOV had significantly larger proportion of the lung with matched V/Q as compared to infants treated with CMV/CPAP, median (interquartile range) 60.4% (55.5-66.0%) and 45.8% (37.8-53.1%) respectively (p = 0.01). CONCLUSIONS: In infants who needed mechanical ventilation the first week of life and later developed BPD an association was observed between treatment with a HFOV and better pulmonary V/Q matching at near-term age.

Patterns of Respiratory Support by Gestational Age in Very Preterm Infants.

INTRODUCTION: A detailed understanding of respiratory support patterns in preterm infants is lacking. The aim was to explore and visualize this practice in Sweden. METHODS: Preterm infants with gestational ages of 22-31 weeks, admitted to neonatal units reporting daily to the Swedish Neonatal Quality Register and discharged alive in November 2015-April 2022, were included in this descriptive cohort study. Proportions receiving mechanical ventilation, noninvasive support, or supplemental oxygen were calculated and graphically displayed for each gestational week and postnatal day (range 0-97) up to hospital discharge or 36 weeks of postmenstrual age. RESULTS: Respiratory support in 148,515 days of care (3,368 infants; 54% males; median [interquartile range] birthweight = 1,215 [900-1,525] g) was evaluated. Trajectories showed distinct nonlinear patterns for each category of respiratory support, but differences in respiratory support over the gestational age range were linear: the proportion of infants on mechanical ventilation decreased by -11.7 to -7.3% (variability in estimates related to the postnatal day chosen for regression analysis) for each week higher gestational age (r = -0.99 to -0.87, p ≤ 0.001). The corresponding proportions of infants with supplemental oxygen decreased by -12.4% to -4.5% for each week higher gestational age (r = -0.98 to -0.94, p < 0.001). At 36 weeks of postmenstrual age, dependencies on mechanical ventilation, noninvasive support, and supplemental oxygen varied from 3%, 84%, and 94% at 22 weeks to 0%, 3%, and 5% at 31 weeks of gestational age, respectively. CONCLUSIONS: Respiratory support patterns in very preterm infants follow nonlinear, gestational age-specific postnatal trajectories in a dose-response-related fashion.

Do newborn infants exhale through the CPAP system? Secondary analysis of a randomised cross-over trial.

BACKGROUND: During nasal continuous positive airway pressure (nCPAP) treatment in neonates, leakage is inevitable and can lead to reduced distending pressure in the lungs of the infant. In current practice, neither leakage nor expiratory flow is measured, which makes it difficult to assess if exhalation is through the device or entirely through leakages. OBJECTIVE: To examine if infants treated with nCPAP exhale through the CPAP system. DESIGN AND SETTING: Secondary data analyses from the ToNIL trial on leakages during nCPAP treatment. We retrospectively examined respiratory curves for the 50 infants included in the trial, using NI LabVIEW 2015. Each infant was measured with both prongs and nasal masks. A flow recording was classified as exhalation through the system if more than 50% of all expirations showed reverse flow, each for a minimum duration of 0.1 s. PATIENTS: 50 infants were included, born with a mean gestational age (GA) of 34 weeks, median birth weight of 1948 g and mean age at measurement 6.5 days. Inclusion criteria were CPAP treatment and a postmenstrual age (PMA) of 28-42 weeks. RESULTS: In our measurements, 32/50 infants exhaled through the CPAP system in at least one recording with either nasal mask or prongs. Leakages exceeding 0.3 L/min were seen in 97/100 recordings. CONCLUSIONS: During nCPAP treatment, infants can exhale through the CPAP system and leakage was common. Measuring expiratory flows and leakages in clinical settings could be valuable in optimising CPAP treatment of infants. TRIAL REGISTRATION NUMBER: NCT03586856.

Development and Validation of a Mortality Prediction Model in Extremely Low Gestational Age Neonates.

INTRODUCTION: Understanding factors that associate with neonatal death may lead to strategies or interventions that can aid clinicians and inform families. OBJECTIVE: The aim of the study was to develop an early prediction model of neonatal death in extremely low gestational age (ELGA, <28 weeks) neonates. METHODS: A predictive cohort study of ELGA neonates was derived from the Swedish Neonatal Quality Register between the years 2011 to May 2021. The goal was to use readily available clinical variables, collected within the first hour of birth, to predict in-hospital death. Data were split into a train cohort (80%) to build the model and tested in 20% of randomly selected neonates. Model performance was assessed via area under the receiver operating characteristic curve (AUC) and compared to validated mortality prediction models and an external cohort of neonates. RESULTS: Among 3,752 live-born extremely preterm infants (46% girls), in-hospital mortality was 18% (n = 685). The median gestational age and birth weight were 25.0 weeks (interquartile range [IQR] 24.0, 27.0) and 780 g (IQR 620, 940), respectively. The proposed model consisted of three variables: birth weight (grams), Apgar score at 5 min of age, and gestational age (weeks). The BAG model had an AUC of 76.9% with a 95% confidence interval (CI) (72.6%, 81.3%), while birth weight and gestational age had an AUC of 73.1% (95% CI: 68.4%,77.9%) and 71.3% (66.3%, 76.2%). In the validation cohort, the BAG model had an AUC of 68.9%. CONCLUSION: The BAG model is a new mortality prediction model in ELGA neonates that was developed using readily available information.

Respiratory support of infants born at 22-24 weeks of gestational age.

Lung immaturity and acute respiratory failure are the major problems in the care of extremely preterm infants. Most infants with gestational age (GA) 22-24 weeks will need mechanical ventilation and many will depend on some type of respiratory support, invasive and non-invasive for extended periods. There is ongoing gap in knowledge regarding optimal respiratory support and applying strategies that are effective in more mature populations is not easy or even suitable because lung maturation differs in smaller infants. Better strategies on how to avoid lung damage and to promote growth and development of the immature lung are warranted since increased survival is accompanied by increasing rates of bronchopulmonary dysplasia and concerns over long-standing reductions in lung function. This review focuses on some aspects of respiratory care of infants born at 22-24 weeks of GA.

Comparison of Respiratory Support After Delivery in Infants Born Before 28 Weeks' Gestational Age: The CORSAD Randomized Clinical Trial.

Importance: Establishing stable breathing is a key event for preterm infants after birth. Delivery of pressure-stable continuous positive airway pressure and avoiding face mask use could be of importance in the delivery room. Objective: To determine whether using a new respiratory support system with low imposed work of breathing and short binasal prongs decreases delivery room intubations or death compared with a standard T-piece system with a face mask. Design, Setting, and Participants: In this unblinded randomized clinical trial, mothers threatening preterm delivery before week 28 of gestation were screened. A total of 365 mothers were enrolled, and 250 infants were randomized before birth and 246 liveborn infants were treated. The trial was conducted in 7 neonatal intensive care units in 5 European countries from March 2016 to May 2020. The follow-up period was 72 hours after intervention. Interventions: Infants were randomized to either the new respiratory support system with short binasal prongs (n = 124 infants) or the standard T-piece system with face mask (n = 122 infants). The intervention was providing continuous positive airway pressure for 10 to 30 minutes and positive pressure ventilation, if needed, with the randomized system. Main Outcomes and Measures: The primary outcome was delivery room intubation or death within 30 minutes of birth. Secondary outcomes included respiratory and safety variables. Results: Of 246 liveborn infants treated, the mean (SD) gestational age was 25.9 (1.3) weeks, and 127 (51.6%) were female. A total of 41 infants (33.1%) receiving the new respiratory support system were intubated or died in the delivery room compared with 55 infants (45.1%) receiving standard care. The adjusted odds ratio was statistically significant after adjusting for stratification variables (adjusted odds ratio, 0.53; 95% CI, 0.30-0.94; P = .03). No significant differences were seen in secondary outcomes or safety variables. Conclusions and Relevance: In this study, using the new respiratory support system reduced delivery room intubation in extremely preterm infants. Stabilizing preterm infants with a system that has low imposed work of breathing and binasal prongs as interface is safe and feasible. Trial Registration: ClinicalTrials.gov Identifier: NCT02563717.

Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants with, or at Risk of, Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To investigate the efficacy and safety of sildenafil added to inhaled nitric oxide (iNO) for newborn infants with persistent pulmonary hypertension of newborn (PPHN) or hypoxic respiratory failure (HRF) at risk of PPHN. STUDY DESIGN: Part A of a multinational, randomized, double-blind, placebo-controlled trial. Infants ≤96 hours' old, >34 weeks of gestation, receiving iNO (10-20 ppm on ≥50% FiO2) for PPHN or HRF at risk of PPHN, and oxygen index >15 to <60, were randomized (1:1) to intravenous (IV) sildenafil (loading: 0.1 mg/kg, over 30 minutes; maintenance: 0.03 mg/kg/h) or placebo, for up to 14 days. Coprimary end points were treatment failure rate (day 14/discharge) and time on iNO without treatment failure. Secondary end points included time on ventilation and oxygenation measures. RESULTS: Of 87 infants screened, 29 were randomized to IV sildenafil and 30 to placebo; 13 discontinued treatment (sildenafil, n = 6; placebo: n = 7), including 3 deaths (sildenafil: n = 2; placebo: n = 1). Treatment failure rates did not differ with sildenafil (27.6%) vs placebo (20.0%; P = .4935). Mean time on iNO was not different with sildenafil (4.1 days) vs placebo (4.1 days; P = .9850). No differences were noted in secondary end points. Most common adverse events (AEs) with sildenafil (≥10% infants) were hypotension (n = 8/29), hypokalemia (n = 7/29), anemia, drug withdrawal syndrome (n = 4/29, each), and bradycardia (n = 3/29). One serious AE (hypotension) was considered treatment-related. CONCLUSIONS: IV sildenafil added to iNO was not superior to placebo in infants with PPHN or HRF at risk of PPHN. A review of AEs did not identify any pattern of events indicative of a safety concern with IV sildenafil. Infants will have developmental follow-up (Part B). TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01720524.

Interface leakage during neonatal CPAP treatment: a randomised, cross-over trial.

OBJECTIVE: To determine leakage for two neonatal continuous positive airway pressure (CPAP) interfaces and evaluate leak-corrective manoeuvres. DESIGN: The ToNIL (Trial of NCPAP Interface Leakage) study was a randomised, clinical, cross-over trial with data collection between August 2018 and October 2019. The primary outcome was blinded to the treating staff. SETTING: One secondary, 8-bed neonatal intensive care unit (NICU) and three larger (>15 beds), academic NICU referral centres. PATIENTS: Newborn infants with CPAP were screened (n=73), and those with stable spontaneous breathing, low oxygen requirement, postmenstrual age (PMA) over 28 weeks and no comorbidities were eligible. In total, 50 infants were included (median PMA 33 completed weeks). INTERVENTIONS: Leakage was measured for both prongs and nasal mask, before and after leak-corrective manoeuvres. Interface application was performed in a randomised order by a nurse, blinded to the measured leakage. MAIN OUTCOME MEASURES: 30 s average leakage, measured in litres per minute (LPM). RESULTS: Analyses showed a significantly lower leakage (mean difference 0.86 LPM, 95% CI 0.07 to 1.65) with prongs (median 2.01 LPM, IQR 1.00-2.80) than nasal mask (median 2.45 LPM, IQR 0.99-5.11). Leak-corrective manoeuvres reduced leakage significantly for both prongs (median 1.22 LPM, IQR 0.54-1.87) and nasal mask (median 2.35 LPM, IQR 0.76-4.75). CONCLUSIONS: Large leakages were common for both interfaces, less with prongs. Simple care manoeuvres reduced leakage for both interfaces. This is the first report of absolute leakage for nasal interfaces and should encourage further studies on leakage during CPAP treatment.

Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial.

Lactobacillus reuteri DSM 17938 supplementation reduces morbidities in very low birth weight infants (<1500 g), while the effect on extremely low birth weight infants (ELBW, <1000 g) is still questioned. In a randomised placebo-controlled trial (ClinicalTrials.gov ID NCT01603368), head growth, but not feeding tolerance or morbidities, improved in L. reuteri-supplemented preterm ELBW infants. Here, we investigate colonisation with the probiotic strain in preterm ELBW infants who received L. reuteri DSM 17938 or a placebo from birth to postmenstrual week (PMW) 36. Quantitative PCR was used on 582 faecal DNA samples collected from 132 ELBW infants at one, two, three, and four weeks, at PMW 36, and at two years of age. Human milk oligosaccharides were measured in 31 milk samples at two weeks postpartum. At least 86% of the ELBW infants in the L. reuteri group were colonised with the probiotic strain during the neonatal period, despite low gestational age, high antibiotic pressure, and independent of infant feeding mode. Higher concentrations of lacto-N-tetraose, sialyl-lacto-N-neotetraose c, and 6'-sialyllactose in mother's milk weakly correlated with lower L. reuteri abundance. Within the L. reuteri group, higher L. reuteri abundance weakly correlated with a shorter time to reach full enteral feeding. Female sex and L. reuteri colonisation improved head growth from birth to four weeks of age. In conclusion, L. reuteri DSM 17938 supplementation leads to successful colonisation in ELBW infants.

Flows and function of the Infant Flow neonatal continuous positive airway pressure device investigated with computational fluid dynamics.

AIM: The first dedicated neonatal continuous positive airway pressure (CPAP) device using variable flow was the Infant Flow. The system was pressure stable with a low resistance to breathing. The aim of this study was to describe the flow and function of the Infant Flow geometry using simulated breathing and computational fluid dynamics. METHOD: The original Infant Flow geometry was used with simulated term infant breathing at three levels of CPAP. The large eddy simulation methodology was applied in combination with the WALE sub-grid scale model. RESULTS: The simulation fully resolved the flow phenomena in the Infant Flow geometry. The main flow feature during inspiration was support by gas entrainment and mixing. During expiration, the jet deflected towards the outlet with unstable impingement of the jet at the opposing edge. CONCLUSION: The proposed mechanism has previously been based on theoretical reasoning, and our results present the first detailed description of the Infant Flow. The pressure stability was based on a jet supporting inspiration by gas entrainment and then being deflected during exhalation. This confirmed previously assumed principles of function and flows within the geometry and provided a base for further developments.

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.

COVID-19: minimising contaminated aerosol spreading during CPAP treatment.

BACKGROUND: The COVID-19 pandemic has raised concern for healthcare workers getting infected via aerosol from non-invasive respiratory support of infants. Attaching filters that remove viral particles in air from the expiratory limb of continuous positive airway pressure (CPAP) devices should theoretically decrease the risk. However, adding filters to the expiratory limb could add to expiratory resistance and thereby increase the imposed work of breathing (WOB). OBJECTIVE: To evaluate the effects on imposed WOB when attaching filters to the expiratory limb of CPAP devices. METHODS: Two filters were tested on three CPAP systems at two levels of CPAP in a mechanical lung model. Main outcome was imposed WOB. RESULTS: There was a minor increase in imposed WOB when attaching the filters. The differences between the two filters were small. CONCLUSION: To minimise contaminated aerosol generation during CPAP treatment, filters can be attached to expiratory tubing with only a minimal increase in imposed WOB in a non-humidified environment. Care has to be taken to avoid filter obstruction and replace filters as recommended.

Basic principles of neonatal bubble CPAP: effects on CPAP delivery and imposed work of breathing when altering the original design.

BACKGROUND: The original bubble continuous positive airway pressure (bCPAP) design has wide-bore tubing and a low-resistance interface. This creates a stable airway pressure that is reflected by the submersion depth of the expiratory tubing. Several systems with alterations to the original bCPAP design are now available. Most of these are aimed for use in low-income and middle-income countries and have not been compared with the original design. OBJECTIVE: We identified three major alterations to the original bCPAP design: (1) resistance of nasal interface, (2) volume of dead space and (3) diameter of expiratory tubing. Our aim was to study the effect of these alterations on CPAP delivery and work of breathing in a mechanical lung model. Dead space should always be avoided and was not further tested. METHODS: The effect of nasal interface resistance and expiratory tubing diameter was evaluated with simulated breathing in a mechanical lung model without interface leakage. The main outcome was delivered CPAP and imposed work of breathing. RESULTS: High-resistance interfaces and narrow expiratory tubing increased the work of breathing. Additionally, narrow expiratory tubing resulted in higher CPAP levels than indicated by the submersion depth. CONCLUSION: Our study shows the significant effect on CPAP delivery and imposed work of breathing when using high-resistance interfaces and narrow expiratory tubing in bCPAP systems. New systems should include low-resistance interfaces and wide-bore tubing and be compared with the original bCPAP. Referring to all systems that bubble as bCPAP is misleading and potentially hazardous.