A multicentre neonatal interventional randomised controlled trial of nebulized surfactant for preterm infants with respiratory distress: Neo-INSPIRe trial protocol.

INTRODUCTION: Respiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce. Recent trials from high-resourced countries utilising aerosolized surfactant have had a low quality of evidence and varying outcomes. METHODS AND ANALYSIS: The Neo-INSPIRe trial is an unblinded, multicentre, randomised trial of a novel aerosolized surfactant drug/device combination. Inclusion criteria include preterm infants of 27-34+6 weeks' gestational age who weigh 900-1999g and who require CPAP with a fraction of inspired oxygen (FiO2) of 0.25-0.35 in the first 2-24 h of age. Infants are randomised 1:1 to control (CPAP alone) or intervention (CPAP with aerosolized surfactant). The primary outcome is the need for intratracheal bolus surfactant instillation within 72 h of age. Secondary outcomes include the incidence of reaching failure criteria (persistent FiO2 of > 0.40, severe apnoea or severe work of breathing), the need for and duration of ventilation and respiratory support, bronchopulmonary dysplasia and selected co-morbidities of prematurity. Assuming a 40% relative risk reduction to reduce the proportion of infants requiring intratracheal bolus surfactant from 45 to 27%, the study will aim to enrol 232 infants for the study to have a power of 80% to detect a significant difference with a type 1 error of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been granted by the relevant human research ethics committees at University of Cape Town (HREC 681/2022), University of the Witwatersrand HREC (221112) and Stellenbosch University (M23/02/004). TRIAL REGISTRATION: PACTR202307490670785.

Respiratory Interventions for Preterm Infants in LMICs: A Prospective Study From Cape Town, South Africa.

Background: Preterm birth is a global public health issue and complications of preterm birth result in the death of approximately 1 million infants each year, 99% of which are in low-and-middle income countries (LMIC). Although respiratory interventions such as continuous positive airway pressure (CPAP) and surfactant have been shown to improve the outcomes of preterm infants with respiratory distress, they are not readily available in low-resourced areas. The aim of this study was to report the respiratory support needs and outcomes of preterm infants in a low-resourced setting, and to estimate the impact of a lack of access to these interventions on neonatal mortality. Methods: We conducted a six-month prospective observational study on preterm infants <1,801 g admitted at Groote Schuur Hospital and Mowbray Maternity Hospital neonatal units in Cape Town, South Africa. We extrapolated results from the study to model the potential outcomes of these infants in the absence of these interventions. Results: Five hundred and fifty-two infants (552) <1,801 g were admitted. Three hundred (54.3%) infants received CPAP, and this was the initial respiratory intervention for most cases of respiratory distress syndrome. Surfactant was given to 100 (18.1%) infants and a less invasive method was the most common method of administration. Invasive mechanical ventilation was offered to 105 (19%) infants, of which only 57 (54.2%) survived until discharge from hospital. The overall mortality of the cohort was 14.1% and the hypothetical removal of invasive mechanical ventilation, surfactant and CPAP would result in an additional 157 deaths and increase the overall mortality to 42.5%. A lack of CPAP availability would have the largest impact on mortality and result in the largest number of additional deaths (109). Conclusion: This study highlights the effect that access to key respiratory interventions has on preterm outcomes in LMICs. CPAP has the largest impact on neonatal mortality and improving its coverage should be the primary goal for low-resourced areas to save newborn lives.