Complications of prematurity are the leading cause of deaths in children under the age of five.(1) In fact in 2015, complications from preterm birth led to the death of 1.055 million neonates worldwide, with the majority occurring in low- and middle-income countries (LMICs) like Uganda.(1) The predominant reason for these preterm deaths was RDS, with more than 50% of neonates born before 30 weeks of gestation developing RDS.(2, 3) In HICs, continuous positive airway pressure (CPAP) has been shown to reduce preterm mortality by 48%, reduce the need for mechanical ventilation by 50% and reduce chronic lung disease.(4) CPAP is now the standard of care for RDS in HICs, with the option of mechanical ventilation and artificial surfactant if required.(5) However, in LICs, ventilation, surfactant and CPAP are rarely accessible or affordable leaving limited treatment options for preterm neonates with RDS.
In Uganda, the Neonatal Mortality Rate has not changed over 2 decades, remaining high at 28/1000 live births and the leading cause of these deaths is complications of prematurity.(6) The UN Sustainable Development Goals seek to reduce global neonatal mortality to 12 deaths per 1000 live births by 2030.(7) For this to be achieved, mortality from preterm complications must be drastically reduced. Dedicated and resource-appropriate neonatal care that appropriately addresses the challenges of healthcare provision in LICs is needed to help meet this goal. Low-cost bCPAP for preterm infants was listed by the World Health Organization in 2012 as an area in need of implementation.(8)
Attempts at improvised CPAP are often made in LICs but this can be risky.(9) Due to their simplicity and affordability, low-cost bCPAP devices have been introduced in many neonatal units in LMICs.(10) However, 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.(11-14) In LICs, three observational studies in hospitals without access to mechanical ventilation or artificial surfactant, have documented the use of bCPAP.(15-17)
Our study is the first observational study in a LIC to determine the outcome of neonates <1500g during two distinct periods, before and after the use of bCPAP,
The study was conducted in MRRH, a government hospital in eastern Uganda that serves a population of 4.5 million people. Since 11 May 2015, MRRH has had a dedicated NNU that admits over 2000 neonates a year including around 140 VLBW infants.(18) Neonates are admitted directly from the labour ward, referred from surrounding health facilities and, due to a high rate of home deliveries, some neonates are brought directly from home.(6) The MRRH-NNU is staffed by one full-time neonatal doctor, two neonatal clinicians, 6 specially trained neonatal nurses and a rotating intern. The ward has an average of 35 neonates admitted at any one time and 24-hour nursing care is provided by a single neonatal specialist nurse in 8-hourly shifts.
Standard of care
In MRRH-NNU, treatment with intravenous fluids, intravenous antibiotics, anticonvulsants, aminophylline, multivitamins and iron supplements is possible.(18) All VLBW infants are started on broad-spectrum antibiotics, aminophylline and dextrose 10% infusion on day 1. Almost all preterms are fed exclusively with expressed human breastmilk. Feeding is commenced at 25ml/kg/day and advanced by 25ml/kg/day as tolerated either by nasogastric tube or spoon feeding until 150ml/kg/day is achieved. Thermoregulation is achieved using kangaroo care. MRRH-NNU does not routinely have access to echocardiography, blood gas analysis, c-reactive protein, blood cultures, blood pressure monitoring or portable chest x-ray. Mechanical ventilation and surfactant are not available.
Oxygen saturations are checked on admission and once daily on the ward round. Controlled free-flow nasal oxygen can be given from 0.1 – 1.5l/min. On 12th July 2016, bCPAP was introduced in MRRH-NNU. The bCPAP devices (Diamedica UK Ltd, Bratton Fleming, UK) are designed for low-resource settings and can provide a distending pressure of up to 10cmH2O and a fraction of inspired oxygen (FiO2) between 0.21-0.95.(19) The devices have an integrated oxygen concentrator, so cylinders are not required. Treatment was delivered using nasal prongs (RAM Cannula, Neotech) and a selection of sizes were available to ensure a suitable fit for each neonate. Laboratory testing by Diamedica showed that, if the water in the bubble bottle was at the correct level, the pressure setting on the bubble bottle was reflected at the RAM cannula (±1cmH2O) irrespective of the cannula size used.
Given the diagnostic limitations described above, RDS was a clinical diagnosis defined by signs of respiratory distress in a VLBW or preterm neonate. Indications to initiate bCPAP for RDS in MRRH-NNU included the presence of any of the following: severe subcostal recession, sternal recession, grunting, recurrent apnoea, hypoxia not responding to oxygen therapy. We were unable to exclude concurrent pneumonia or cardiac disease. At admission, all VLBW neonates are routinely given antibiotics for possible sepsis and aminophylline prophylaxis for apnoea of prematurity. The bCPAP was applied to any VLBW neonate with a clinical diagnosis of RDS if a device was available. treating up to five neonates at one time. If a bCPAP device was not available the neonate continued on oxygen therapy alone as needed.
The bCPAP could be initiated by any member of staff including the nurses, therefore the MRRH-NNU bCPAP guideline was suitably simple. Every nurse working in the neonatal unit attended the Newborn Care Training Course, which included a 2-hour module on the recognition and treatment of respiratory illness in neonates.(18) Each nurse was also given one-on-one bedside training from a senior member of the team in the recognition of respiratory distress, how to correctly set-up the bCPAP and how to select and apply the correct interface. The distending pressure was initiated at 5cmH2O and adjusted between 2-8cmH2O depending on the level of respiratory distress observed. The FiO2 was initiated at 0.58 and could be adjusted from 0.21-0.95 to achieve oxygen saturations of 90-93% in the preterm neonates.(20)
bCPAP is a particular method of CPAP delivery that does not feature any sensors or closed loop feedback to control the pressure. Therefore, in any patient care using bCPAP, clinicians rely on clinical signs and titrate the pressure and the FiO2 depending on the needs of the patient. In this study, neonates on bCPAP settings were assessed 1-2 times a day by the neonatal doctor or neonatal clinician. The FiO2 was adjusted to maintain the oxygen saturations 90-93%. The pressure was adjusted between 2-8 cmH2O based on the level of respiratory distress evident on clinical examination. When no respiratory distress was present the pressure was reduced by 1-2 cmH2O and the clinical response observed. When respiratory distress and/or apneas were no longer present when using a pressure of 2 cmH2O, the neonate was weaned off bCPAP. This was done for increasing durations of time from 30 minutes up to 2 hours daily. These periods were supported by oxygen therapy if required. Once the neonate was comfortable without bCPAP for a 2 hour period it was discontinued.