To our knowledge, this is the first retrospective study comparing a pre- and post-bCPAP era in a LIC. The survival of VLBW neonates at MRRH-NNU was significantly improved by the introduction of bCPAP for the treatment of RDS. This supports data from similar studies in MICs [11,12,13,14, 22, 23].
A critical analysis of this study’s limitations is vital. Firstly, we only evaluated a small number of VLBW neonates; this can be explained because we were a single center and were limited by the timings; the creation of the NNU, the introduction of bCPAP and further improvements to the NNU. Secondly, no accurate gestational data was available since none of the mothers had had a dating scan and the dates of the last normal menstrual period were often not known. The outcomes in this study can only be interpreted compared to birth weight. This may however provide a more pragmatic approach to clinicians working in similar low-resource settings, where even postnatal gestational age assessment can be challenging. It was not possible to ensure that all other variables remained constant during the two periods, however to our knowledge there were no changes in practice in MRRH labour ward during this time. In addition, no other equipment was introduced to the NNU apart from the bCPAP during the study. There were no changes in neonatal protocols, medications or training. Neonatal nursing staff in the NNU did change over during this period, although no additional staff were added. All neonatal nurses received the same neonatal training on commencing work in the NNU.
Resource limitations and the retrospective nature of the study means that there is limited data on adverse effects or complications of bCPAP. Future studies need to consider the incidence of nasal septum injury and pneumothorax. Our NNU chose to use binasal prongs to deliver bCPAP, due to their simplicity and availability of various sized prongs. It is possible that alternative interfaces may improve the delivery and the safety in similar settings.
It was not uncommon to have more neonates that required bCPAP than the five machines that were available. Unfortunately, data on these numbers were not available, therefore it is likely that the impact on mortality would be have been greater if more bCPAP machines were available. There is also a possibility that in practice staff tended to treat neonates with more severe RDS with bCPAP and those with less severe RDS with nasal oxygen. To account for this potential bias we compared the outcome of neonates who received bCPAP versus those who received only oxygen therapy in the post-bCPAP period. There was still a trend towards a lower mortality rate for those receiving bCPAP (13/56, 23.2%) than those neonates receiving oxygen alone (38/112, 33.9%, P = 0.22).
Failure of bCPAP can include death, pneumothorax, severe intraventricular hemorrhage and bronchopulmonary dysplasia. This study was not able to provide data regarding the risk factors, however previous studies have identified the FiO2, lower antenatal steroid exposure, birthweight, gestational age, apnoea, late initiation of CPAP, as significant predictors of CPAP failure [24,25,26]. These factors and indicators of failure need to be considered in future prospective studies of bCPAP.
bCPAP in LMICs
Although there have been no randomized trials conducted in LMICs investigating the efficacy of bCPAP. Six observational studies from middle-income countries have compared outcomes of preterms in a pre- and post-CPAP periods [11,12,13,14]. Implementation of home-made bCPAP in India reduced mortality from 10.7 to 2.4% . In another study in India, introduction of CPAP reduced up-transfers from 74 to 37% . Findings were similar in South Africa, with up-transfers reduced from 16.7 to 5.1% . In Kenya, the survival-to-discharge rate was increased from 61 to 85% after bubble CPAP was implemented . A small retrospective study of VLBW neonates in Brazil showed the introduction of underwater bCPAP reduced the need for resuscitation, surfactant and mechanical ventilation in < 1500 g neonates . In a large neonatal unit in Nicaragua, a new strategy to promote the systematic use of bCPAP significantly reduced the rate of intubation and mortality . A small prospective observational study from India, that was able to monitor the safety of bCPAP with pulse oximetry, radiologically and with blood gases, found bCPAP to be safe .
In LICs, three observational studies in hospitals without access to mechanical ventilation or artificial surfactant, have documented the use of bCPAP [15,16,17]. In a dedicated physician-led neonatal ward in Malawi, implementation of a commercial low-cost bubble CPAP device for treatment of severe respiratory distress in neonates > 1000 g showed a 27% improvement in neonatal survival . The study from Uganda, in a dedicated physician-led neonatal unit, and the study from Rwanda, in three rural district hospitals providing basic neonatal care, had no comparison groups and thus could only conclude that bCPAP was feasible for low-resource settings [15, 16]. The Rwandan study did observe a trend towards improved outcome of VLBW infants using bCPAP however they still reported low survival rates of VLBW infants treated with CPAP of 42%.
Despite the limitations of this study, it is clear that in a low-resource setting where blood gas analysis, x-rays, mechanical ventilation and surfactant administration are not routinetly available, bCPAP is an effective intervention for VLBW neonates with RDS. Not only is bCPAP low-cost, it also avoids the need for intubation and is simple to assemble and easy to apply. Given this simplicity, it is feasible to introduce bCPAP into a NNU that is mainly staffed by nurses and clinical officers, as was shown in South Africa . This study suggests that with adequate training and supervision, low-cost bCPAP can have a dramatic impact on preterm mortality in such as setting. In fact, given the limited number of bCPAP machines, the reported reduction in mortality may actually be an underestimate.
Future research should focus on identifying which neonates benefit most from bCPAP and improving the data on the safety and complications of bCPAP. We must also establish the optimal time to initiate and discontinue bCPAP for these neonates and indeed whether prophylactic bCPAP in such settings with limited intensive care has benefit . Data regarding the predictors of bCPAP failure would help identify those neonates that would benefit from intensive care if available. Lastly a minimum level of training and senior support for the safe and effective use of bCPAP needs to be established.