A randomised trial of prophylactic oropharyngeal surfactant for preterm infants

Background: Preterm infants are at high risk of developing respiratory distress syndrome (RDS). Endotracheal surfactant is effective in preventing and treating RDS; however, intubation is invasive and associated with adverse effects. Half of infants born <29 weeks’ gestation initially managed with continuous positive airway pressure (CPAP) are ultimately intubated for surfactant. Administration of surfactant into the pharynx has been reported in preterm animals and humans and may be effective. Objective: We wished to determine whether giving oropharyngeal surfactant at birth reduces the rate of endotracheal intubation for respiratory failure in preterm infants within 120 hours. Design/Methods: Infants born before 29 weeks’ gestation who were free of major anomalies were enrolled to this unblinded study at 9 centres in 6 European countries. They were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. The primary outcome was intubation within 120 hours of birth, either for bradycardia and/or apnoea despite respiratory support in the delivery room, or for pre-specified respiratory failure criteria in the neonatal intensive care unit. Secondary outcomes included incidence of mechanical ventilation, chronic lung disease, and death before hospital discharge. Results: A total of 251 infants were included in the study; 126 infants were assigned to oropharyngeal surfactant and 125 infants to control. The groups were well matched at study entry (table 1); their mean (SD) gestational age was 26 (2) vs 26 (2) weeks, and their mean (SD) birth weight was 874 (261) vs 851 (253) g respectively. There was no difference between groups in the rate of intubation at 120 hours [79/126 (63) vs 81/125 (65) %, p=0.793] (table 2). There were no differences between the groups in the rate or duration of mechanical ventilation; the rates of bronchopulmonary dysplasia, chronic lung disease, or postnatal steroid use; or in the rate of death before hospital discharge. Conclusion(s): Administration of surfactant into the oropharynx immediately after birth in addition to CPAP compared to CPAP alone did not reduce the rate of intubation amongst infants born before 29 weeks’ gestation in the first 5 days of life

Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial

Importance - Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative. Objective - To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure. Design, Setting, and Participants - This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023. Intervention - Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA). Main Outcomes and Measures - The primary outcome was intubation in the delivery room for bradycardia and/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment. Results - Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P = .04). Conclusions and Relevance - This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks’ GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used

Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia

Peer reviewe

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome

Objective CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of two human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy. Design Multicentre cohort study. Patients Forty infants from 27+0 to 33+6 weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO2) ≥0.35 were treated with a single dose of CHF5633 within 48 hours after birth. The first 20 received 100 mg/kg and the second 20 received 200 mg/kg. Outcome measures Adverse events (AEs) and adverse drug reactions (ADRs) were monitored with complications of prematurity considered AEs if occurring after dosing. Systemic absorption and immunogenicity were assessed. Efficacy was assessed by change in FiO2 after dosing and need for poractant-alfa rescue. Results Rapid and sustained improvements in FiO2 were observed in 39 (98%) infants. One responded neither to CHF5633 nor two poractant-alfa doses. A total of 79 AEs were experienced by 19 infants in the 100 mg/kg cohort and 53 AEs by 20 infants in the 200 mg/kg cohort. Most AEs were expected complications of prematurity. Two unrelated serious AEs occurred in the second cohort. One infant died of necrotising enterocolitis and another developed viral bronchiolitis after discharge. The single ADR was an episode of transient endotracheal tube obstruction following a 200 mg/kg dose. Neither systemic absorption, nor antibody development to either peptide was detected. Conclusions Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome: two-year outcomes

Objective: To assess at 24 months corrected age (CA) the neurological, respiratory, and general health status of children born prematurely from 27 +0 to 33 +6 weeks’ gestation who were treated in a first-in-human study with a new fully synthetic surfactant (CHF5633) enriched with SP-B and SP-C proteins.  Outcome measures: Children were assessed using Bayley Scales of Infant Development (BSID), with a score below normal defined as BSID-II Mental Development Index score <70, or BSID-III cognitive composite score <85. In addition, a health status questionnaire was used to check for functional disability including respiratory problems and related treatments, sensory and neurodevelopment assessments, communication skills as well as the number of hospitalizations.  Results: 35 of 39 survivors had a neurodevelopmental assessment, 24 infants being evaluated by Bayley’s Scales and 11 by health status questionnaires only. 23 children had scores within normal limits and one had BSID-III <85. The remaining 11 were judged clinically to have normal development. Health status questionnaires detected only issues that would normally be expected in preterm-born children.  Conclusions: This assessment offers reassurance that treatment with CHF5633 surfactant was not associated with adverse neurodevelopmental, respiratory, or health outcomes by two years corrected age

Early inhaled budesonide for the prevention of bronchopulmonary dysplasia

BACKGROUND Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. METHODS We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. RESULTS A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P = 0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P = 0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P = 0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P = 0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P = 0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. CONCLUSIONS Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality

Mortalita a morbidita extremne nezraleho novorozence a moznosti jejich ovlivneni.

Text also in EnglishAvailable from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Efficacy of FiO2 Increase During the Initial Resuscitation of Premature Infants < 29 Weeks: An Observational Study

To evaluate the heart rate (HR) and oxygen saturation (SpO2) at 15-second intervals within 60 seconds after incremental increases of fractional inspired oxygen (FiO2) during resuscitation of infants younger than 29 weeks requiring two different forms of ventilatory support. Study design: Retrospective observational study. Methods: Forty-three infants were stabilized, 14 by continuous positive airway pressure exclusively (CPAP group), and 29 by positive pressure ventilation (PPV group). Both groups received ventilatory support in a special bed with two cameras enabling the evaluation of all interventions including HR, SpO2, FiO2, positive inflation pressure, and positive end-expiratory pressure values. FiO2 was commenced at 0.30 and titrated in 0.1–0.2 increments every 30–60 seconds. The relationships between the incremental increases of FiO2 and related SpO2 and HR changes were evaluated. Results: Although there was an inverse correlation between initial FiO2 and SpO2 in both groups, a significant positive correlation between the incremental increase of FiO2 and SpO2 changes after 30 seconds was found only in the CPAP group. Only higher initial levels of FiO2 had a positive effect on the improvement in SpO2 in the PPV group. Conclusion: The efficacy of FiO2 titration in 0.1–0.2 increments may be attenuated and delayed in extremely preterm infants required PPV during the first 6 minutes of life