Impact of prophylactic CPAP in the delivery room (DR-CPAP) on neonates <1500g in a low-resource setting: A feasibility trial

A birth that occurs before the start of the 37th week of pregnancy is termed a preterm birth. Complications of preterm births are the leading cause of under-five deaths worldwide. Inadequate lung development is a common and serious complication in preterm births, and is believed to be the leading cause of these preterm deaths. The highest risk of inadequate lung development is in infants born <1500g, termed very low birthweight (VLBW) infants. Unfortunately there are limited treatments available for inadequate lung development in low-resource settings. A number of studies have shown that simple and low-cost breathing support called bubble continuous positive airways pressure (bCPAP) can be safely and effectively implemented in low-resource settings. Indeed, we have shown a 44% reduction in preterm mortality in VLBW infants in our neonatal unit in Uganda following the implementation of bCPAP (Okello et al., 2019). Currently, there are no definitive studies and no consensus on the ideal time to start CPAP in preterms neonates in low-resource settings. In high-income countries (HICs), early CPAP has been shown to reduce the need for mechanical ventilation and artificial lung surfactant, neither of which are available in low-resources settings leaving the preterm neonates with no further options for treatment.

It is our belief, that early prophylactic CPAP in the delivery room in a low-resource setting is feasible, acceptable and safe and has the potential to reduce preterm mortality substantially. The feasibility of initiating CPAP in the delivery room has never been studied in a LIC. This pilot study is designed to determine the feasibility and acceptability of initiating CPAP in VLBW infants in the delivery room (DR-CPAP). It will also evaluate the safety of DR-CPAP in this setting through monitoring the number and nature of any adverse events. It will also determine the feasibility of randomizing VLBW infants within 15 minutes of birth to receive either DR-CPAP or to receive standard CPAP in the neonatal unit when clinically indicated. This pilot study will also evaluate the acceptability of using deferred consent in the delivery room for neonatal emergencies in this setting. Together these results will provide important data and knowledge to inform the design of a future larger multi-centre trial that will evaluate the impact of DR-CPAP on mortality and morbidity in VLBW infants.

Complications of prematurity are the leading cause of deaths in children under the age of five and the majority occur in low income countries. The predominant reason for these preterm deaths is respiratory distress syndrome (RDS). In high-income countries (HICs), the use of early CPAP, within 15 minutes of delivery, can reduce the need for mechanical ventilation and surfactant in the treatment of RDS. In low-resource settings, where access to mechanical ventilation or artificial surfactant is limited, when CPAP fails there are limited options for care.

We hypothesise that initiation of early prophylactic CPAP in the delivery room (DR-CPAP) will reduce the rate of CPAP failure and therefore the neonatal mortality rate in low-resource settings. This project will develop and test for feasibility, acceptability and safety a protocol for DR-CPAP, which if successful can later be tested for efficacy in a future trial. The feasibility of initiating CPAP in VLBW neonates within 15 minutes of delivery in this low-resource setting will be evaluated. The acceptability of administering CPAP in the delivery room will be assessed. The safety of DR-CPAP will be evaluated through adverse events. This project will ensure that deferred consent with prior assent is acceptable to both the mothers and the medical staff for a trial of neonatal emergency care. We will pilot low-cost third party randomisation and assess if neonates can randomised within 15 minutes of delivery to allow initiation of DR-CPAP within a suitable timeframe. This study will validate secondary outcomes for the future trial. The strong involvement of health leaders, medical staff, and mothers at all stages will ensure that if successful, the intervention will be both acceptable to the communities and more effectively scaled-up.

Together these findings will allow us to design a large and robust multi-centre unblinded randomised controlled trial to evaluate the impact of DR-CPAP on mortality in VLBW infants.

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