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PLOS One logoLink to PLOS One
. 2021 Jun 11;16(6):e0252718. doi: 10.1371/journal.pone.0252718

Experiences with implementation of continuous positive airway pressure for neonates and infants in low-resource settings: A scoping review

Sara Dada 1,*, Henry Ashworth 1,2, Alina Sobitschka 1,3, Vanitha Raguveer 1,4, Rupam Sharma 1,5, Rebecca L Hamilton 6,7, Thomas Burke 1,2,8,9
Editor: Jacqueline J Ho10
PMCID: PMC8195417  PMID: 34115776

Abstract

Background

Continuous positive airway pressure (CPAP) is the gold standard of care in providing non-invasive positive pressure support to neonates in respiratory distress in high-resource settings. While safety has been demonstrated in low-resource settings, there is a lack of knowledge on the barriers and facilitators to proper implementation.

Objective

To identify and describe the barriers, facilitators, and priorities for future implementation of CPAP for neonates and infants in low-resource settings.

Methods

A systematic search (database inception to March 6, 2020) was performed on MEDLINE, Embase, Web of Science, CINAHL, Global Health, and the WHO Global Index Medicus using PRISMA-ScR guidelines. Original research articles pertaining to implementation of CPAP devices in low-resource settings, provider or parent perspectives and experiences with CPAP, cost-benefit analyses, and cost-effectiveness studies were included. Inductive content analysis was conducted.

Findings

1385 article were screened and 54 studies across 19 countries met inclusion criteria. Six major themes emerged: device attributes, patient experiences, parent experiences, provider experiences, barriers, and facilitators. Nasal trauma was the most commonly reported complication. Barriers included unreliable electricity and lack of bioengineering support. Facilitators included training, mentorship and empowerment of healthcare providers. Device design, supply chain infrastructure, and training models were imperative to the adoption and sustainability of CPAP.

Conclusion

Sustainable implementation of CPAP in low resource settings requires easy-to-use devices, ready access to consumables, and holistic, user-driven training. Further research is necessary on standardizing metrics, interventions that support optimal provider performance, and conditions needed for successful long-term health system integration.

Introduction

The World Health Organization has declared the reduction of neonatal mortality a global priority [1]. Each year, two and a half million infants die in their first month of life and the majority of these deaths occur in low resource settings [2]. While considerable progress has been made over the last few decades, respiratory distress syndrome (RDS) remains a leading cause of neonatal mortality worldwide [14]. RDS usually develops in the first 24 hours after birth in premature newborns due to a lack of surfactant within the lungs, and often requires positive pressure ventilation for treatment [5]. Continuous positive airway pressure (CPAP) is considered to be the gold standard, treatment for preterm neonates experiencing RDS and is recommended by WHO [69].

Forms of CPAP can vary across a number of factors including the patient interface, sophistication, and how they generate pressure. Bubble continuous positive airway pressure (bCPAP) is a common mode of CPAP delivery for newborns that uses a bubbler instead of a ventilator to generate pressure [68]. Since bCPAP systems are considered at least as efficacious and are considerably lower cost than ventilator-derived CPAP devices, they may have significant potential to improve access to non-invasive ventilation in low-resource regions worldwide [7, 10, 11]. While reviews of all forms of CPAP [12, 13] have described the efficacy of the treatment, there has been a specific focus on bCPAP therapies suggesting that bCPAP may be safe and effective in low and middle income countries (LMICs) [1416]. These reviews called for further research on effectiveness and sustainability of bCPAP therapy in low-resource settings [1316]. A recent systematic review on barriers and facilitators to implementation of neonatal bCPAP among health facilities in sub-Saharan Africa found that staffing ratios, provider knowledge, and device maintenance were crucial to the success of the intervention [17]. However, more information is needed to understand optimization and guide further implementation of all forms of CPAP, including bCPAP, across low-resource settings. Consideration of implementation factors such as successful CPAP device attributes, provider and parent acceptance, and systems uptake must be better understood. Additionally, a broader picture that considers qualitative factors is needed to understand how to create lasting sustainable uptake of CPAP. To explore these factors the following research question was formulated: What are identified barriers, facilitators, and priorities for future implementation of CPAP for neonates and infants in low-resource settings? To answer this more qualitative and nuanced question, a scoping review was chosen to broadly map knowledge gaps and evidence [18].

Methods

Search strategy

The scoping review framework was adopted in order to present an overview of all the evidence relating to experiences with CPAP implementation [19]. A scoping review protocol was developed according to the Joanna Briggs Reviewer’s manual [20] and this review is reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) checklist (S1 File) [21]. The final protocol was registered on Open Science Framework (https://osf.io/qwvgs/). The search query (S2 File) was run on six databases (MEDLINE, Embase, Web of Science, CINAHL, Global Health, and the WHO Global Index Medicus) from database inception to March 6th, 2020.

Selection of studies

Search results were uploaded to an online program (Covidence, Veritas Health Information, Melbourne, Australia) to allow for collaborative screening by multiple authors. Four reviewers (SD, RS, HA, AS) independently screened a sample of ten titles and abstracts and agreed on criteria for inclusion and exclusion. Two blinded reviewers (SD, RS) independently screened all articles by title and abstract. Conflicts were resolved by an independent arbiter (RH). Two blinded reviewers (SD, RS) then screened articles by full text for potential eligibility. A final arbiter (RH) resolved conflicts of agreement on inclusion for the final dataset. Original peer-reviewed research articles of any study design on implementation of CPAP devices in low-resource settings as defined by the World Bank Classification at time of study, provider or caregiver perspectives and experiences with CPAP, and cost-benefit analyses or cost-effectiveness studies were included. Grey literature, reviews, and research articles that solely focused on safety and efficacy of CPAP were excluded.

Data extraction

Three reviewers (SD, HA, AS) independently extracted data from each study using the Covidence data extraction form. Extracted data included: study year; study type/method and setting; population; sample size and method; study objectives; characteristics of CPAP intervention or treatment; complications, barriers, and facilitators. Findings were coded into broad themes by two independent reviewers (SD, HA) using an inductive content analysis on NVivo 12 (QSR International, Melbourne, Australia). An inductive analysis was used in order to uncover patterns and themes in the experiences and perceptions of CPAP implementation [22, 23]. Once all studies were uploaded into NVivo, the two reviewers coded a sample of the studies until data saturation was reached. The individual codebooks were compared and discussed in order to create a final codebook which was then applied to the full dataset.

Synthesis of results

Studies were grouped by intervention. Broad categories were developed from extracted data related to experiences with implementation of CPAP treatments and results were synthesized across articles. Due to the high variation in study designs and in order to capture and present all of the existing data, studies were not excluded based on quality; and therefore, critical appraisals were not conducted.

Results

Overview of included studies

Of the 1385 identified studies, 54 were included in the final analysis (Fig 1PRISMA chart) [24]. Included studies are summarized in Table 1. Reasons for exclusion during full-text screening were: incorrect population, unrelated intervention, inappropriate setting, not about experiences with implementation, not original research, unavailable or incorrect reference. No studies were excluded based on language (six non-English papers were translated using Google Translate). Findings were coded into six main categories: device attributes, patient experiences, provider experiences, parent experiences, barriers, and facilitators (Inter-rater reliability kappa score 0.91).

Fig 1. PRISMA chart.

Fig 1

Adapted from Moher D, Liberati A, Tetzlaff, J, Altman DG, The PRISMA GROUP (2009) Studies included in synthesis (n = 54). From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097 For more information, visit www.prisma-statement.org.

Table 1. Summary table of included studies.

Study Country Specific Intervention Design Study participants Number of participants Facility Type
CPAP
Abdulkadir 2013 [81] Nigeria bCPAP Case Study Neonates 1 Teaching Hospital
Abdulkadir 2015 [82] Nigeria Nasal bCPAP (Improvised) Descriptive Observational Neonates 20 Teaching Hospital
Al-Lawama 2019 [62] Jordan Nasal bCPAP (Fisher & Paykel) Prospective Observational Neonates 143 Tertiary Care Hospital
Amadi 2019 [25] Nigeria Polite bCPAP Prospective Cohort Neonates 57 Tertiary Care Hospital
bCPAP (Improvised)
Antunes 2010 [55] Brazil Questionnaire Descriptive Observational Nurses 11 Tertiary Care Hospital
Atreya 2018 [26] India bCPAP (Fisher & Paykel) Qualitative Interviews Healthcare providers 14 Tertiary Care Hospital
Audu 2014 [27] Nigeria bCPAP (Improvised) Descriptive Observational Neonates and infants 48 Tertiary Care Hospital
Bahman-Bijari 2011 [30] Iran bCPAP (Fisher & Paykel) Randomized Controlled Trial Preterm neonates 50 Tertiary Care Hospital
vCPAP (Bear Medical Systems)
Bassiouny 1994 [47] Oman Nasal bCPAP (Beneveniste’s pediatric gas jet) Retrospective Descriptive Neonates 44 Teaching Hospital
Boo 2016 [72] Malaysia EnCPAP Retrospective Cohort Hospital facilities 34 Not Specified
EnCPAP VLBW Neonates 2836
Carns 2019 [42] Malawi CPAP (Pumani) Descriptive Observational Neonates 2850 District Hospital
Chen 2014 [28] Malawi bCPAP (Pumani) Cost-Effectiveness Analysis Neonates 87 Not Specified
Nasal oxygen
Crehan 2018 [64] Malawi bCPAP TRY algorithm (Pumani) Descriptive Observational Infants 57 District Hospital
Daga 2014 [29] India nCPAP (Improvised) Retrospective Cohort Neonates 140 Teaching Hospital
Dai 2020 [83] China nCPAP (CareFusion Infant Flow System) Prospective Observational Neonates 429 Tertiary Care Hospital
deSiqueira 2014 [84] Brazil CPAP Survey Nurses 20 Teaching Hospital
Dewez 2018 [34] India CPAP Qualitative Interviews Healthcare providers 69 District Hospitals and Medical Colleges
Dewez 2020 [38] India CPAP (Improvised) Cross-sectional Cluster Hospital facilities 694 Government Hospital
CPAP (Commercial)
Garcia Reza 2018 [39] Mexico nCPAP Descriptive Observational Nurses 25 Tertiary Care Hospital
Ghorbani 2013 [59] Iran nCPAP Cross-Over Cohort Preterm neonates 44 Teaching Hospital
Gondwe 2017 [61] Malawi bCPAP (Pumani) Qualitative Interviews Caregivers 12 Tertiary Care Hospital
Guedes 2019 [65] Brazil nCPAP Qualitative Interviews Nurses 30 Teaching Hospital
Hendriks 2014 [31] South Africa nCPAP (Fisher & Paykel) Retrospective Descriptive Neonates 128 Rural District Hospital
Hundalani 2015 [66] Malawi bCPAP TRY algorithm (Pumani) Prospective Cohort Neonates 325 Tertiary Care Hospital
bCPAP early algorithm (Pumani)
Oxygen only
Jardine 2015 [44] South Africa bCPAP (Fisher & Paykel) Retrospective Descriptive Neonates 711 Tertiary Care Hospital
Khan 2017 [45] India CPAP (Fisher & Paykel) Randomized Controlled Trial Preterm neonates 170 Tertiary Care Hospital
CPAP (Phoenix Medical)
Koyamaibole 2006 [35] Fiji bCPAP (Fisher & Paykel) Retrospective Cohort Neonates 1152 Tertiary Care Hospital
Myhre 2016 [69] Kenya bCPAP (Improvised) Retrospective Descriptive Preterm neonates 118 Rural Tertiary Care Hospital
Nahimana 2015 [70] Rwanda bCPAP (Pumani) Retrospective Cohort Preterm VLBW Neonates 135 Rural District Hospital
Nyondo-Mipando 2020 [49] Malawi bCPAP Qualitative Interviews Healthcare providers 46 Secondary and Tertiary Care Hospitals
Okonkwo 2016 [71] Nigeria bCPAP Survey healthcare providers 237 Tertiary Care Hospital
Osman 2014 [58] Egypt nCPAP Prospective Cohort Preterm infants 60 Tertiary Care Hospital
High flow nasal canula
Sessions 2019 [33] Malawi bCPAP Observational: Time Motion Study 12 Rural District Hospital
Silva 2010 [37] Brazil Questionnaire Qualitative Interviews Nurses and nursing technicians 30 Tertiary Care Hospital
Tagare 2010 [7] India bCPAP (Fisher & Paykel) Randomized Controlled Trial Preterm neonates 30 Tertiary Care Hospital
vCPAP (Bear Medical Systems)
Van den Heuvel 2011 [41] Malawi bCPAP (Improvised) Prospective Cohort Neonates 5 Tertiary Care Hospital
CPAP & Training
Ntigurirwa 2017 [67] Rwanda Neonatal training program (427 days) Retrospective Descriptive Hospital facilities 4 Teaching and District Hospitals
bCPAP (Fisher & Paykel) Infants 365
Olayo 2019 [43] Kenya bCPAP training (2 days) Prospective Cohort Healthcare providers 79 Level 4 and Level 5 Hospitals
bCPAP (Devilbiss IntelliPAP) Neonates and infants 1111
Chen 2017 [63] Taiwan Mobile Cart Training Pre-Post Intervention Healthcare providers 59 Tertiary Care Hospital
bCPAP (Infant Star v Drager) Infants 113
McAdams 2015 [36] Uganda RSS Scoring Training Descriptive Observational Healthcare providers 19 Rural Tertiary Care Hospital
bCPAP (Improvised) Neonates 21
Training
Asibon 2019 [68] Malawi Peer mentorship and training program Pre-Post Intervention Nurses 113 Secondary and Tertiary Care Hospitals
Tiryaki 2016 [73] Turkey bCPAP Lecture Pre-Post Intervention Nurses 36 University, State and Private Hospitals
Wilson 2014 [32] Ghana 1st generation international trainers Descriptive Observational Healthcare providers 28 District Hospital
2nd generation local trainers
Patient Interface
Bashir 2019 [53] India CPAP nasal mask (Fisher & Paykel) Randomized Controlled Trial Preterm neonates 175 Tertiary Care Hospital
CPAP nasal prongs (Fisher & Paykel)
CPAP rotating group—prongs and mask (Fisher & Paykel)
Bonfim 2014 [48] Brazil New nasal prongs Prospective Cohort Infants with GA < 37 weeks 70 Tertiary Care Hospital
Reused nasal prongs
Goel 2015 [52] India bCPAP prongs (Fisher & Paykel) Randomized Controlled Trial Preterm neonates 118 Tertiary Care Hospital
bCPAP mask (Fisher & Paykel)
Singh 2017 [46] India nCPAP nasal mask Randomized Controlled Trial Neonates 75 Tertiary Care Hospital
nCPAP nasal prongs
Yong 2005 [40] Malaysia bCPAP nasal prongs Randomized Controlled Trial VLBW infants 89 Tertiary Care Hospital
bCPAP nasal mask
Nasal Protection
Nunes 2012 [57] Brazil Nasal protection Case Study VLBW neonates 1 Tertiary Care Hospital
Xiaoyan 2013 [50] China Hydrocolloid Randomized Controlled Trial Neonates 500 Not Specified
Rhinobyon
Xie 2014 [51] China Hydrocolloid Dressing (Hamilton Medical) Randomized Controlled Trial Preterm neonates 65 Tertiary Care Hospital
Paraffin Oil
Body Position
Brunherotti 2015 [60] Brazil Body position Cross-Over Cohort Preterm neonates 16 Tertiary Care Hospital
Jabraeili 2018 [56] Iran Fetal Position nCPAP Cross-Over Cohort Preterm neonates 50 Tertiary Care Hospital
Supine Position nCPAP
Prone Position nCPAP
Pain
Antunes 2013 [54] Brazil Non-nutritive sucking Randomized controlled trial Preterm infants 20 Government Hospital

Description of included studies

The 54 included studies were conducted in 19 countries over five regions: Africa (n = 23), Asia (n = 15), Central & South America (n = 9), Middle East (n = 6), and Oceania (n = 11). Studies ranged from analysis of CPAP treatments (n = 34), training processes (n = 7), patient interfaces (n = 5), nasal protection (n = 3), body positions (n = 2), pain relief (n = 1), and general knowledge or perception surveys (n = 2). Most included studies were randomized controlled trials (n = 10), followed by observational (n = 8) and prospective cohort (n = 6) studies. The most common study populations were term and preterm neonates (n = 18), followed by only preterm neonates (n = 11), and healthcare providers (n = 15). Four studies described their sample population with the general term “infants,” which refers to ages 1–12 months, so unless specifically mentioned, the following findings refer to preterm and term neonates, defined as under one month of age.

Device attributes

Fourteen different CPAP devices were described across the included studies, including Fisher & Paykel (n = 14), Pumani (n = 8) and locally-made or improvised devices (n = 9). CPAP devices varied in price, features, and patient interfaces.

Price was one of the most common themes overall. Five studies emphasized that affordability and cost-effectiveness of different CPAP devices encouraged implementation [2529] while five studies cited that if a CPAP device was expensive, cost was a barrier to implementation [2527, 30, 31]. Commercial CPAP devices were noted to have other challenges. For example, one study reported that nurses found certain CPAP systems “cumbersome [to set up], particularly securing the tubing to the headdress” [32]. Sessions et al. measured the length of time healthcare providers (HCPs) spent initiating and monitoring treatment with Fisher & Paykel bCPAP devices and reported it took 12.45 additional minutes to set up and adjust bCPAP equipment compared to the application of standard nasal oxygen [33]. A major focus of most bCPAP devices is to blend pure oxygen with air in order to decrease risk of potential complications from high concentrations of oxygen such as retinopathy of prematurity. However, this complex process is not possible in improvised CPAP devices, and was reported as an important challenge [27].

Important characteristics of various CPAP devices described across the studies included ease of use [2527, 29, 34, 35] and effectiveness [26, 28, 30, 32, 34, 35]. Ease of use referred to experiences around simple set ups or low maintenance CPAP devices, while effectiveness related to a device’s overall ability to provide quality care. Factors such as “simplicity” 27] of a CPAP device and “the feedback provided with use of bCPAP, in terms of bubbling of the water column and wiggling of the chest wall” 26] were cited examples of ease of use. An additional identified device benefit was the potential for certain CPAP devices to be transportable, which could enable use in critical pre-hospital and transit settings [25].

Patient experience

Twenty-seven studies examined CPAP-related complications and comfort. The most common reported complications were related to nasal irritation [36, 37], nasal lesions [3840] and abrasions [41] as well as nasal trauma or injuries such as nasal bleeds or hyperemia [40, 42, 43], and nasal septal necrosis [37, 4446]. Low patient birthweights, low gestational ages [46, 47], and longer treatment times [40, 48, 49] were associated with increased nasal trauma. A number of studies also reported on techniques to reduce nasal trauma through application of protective dressings and use of various patient-device interfaces. In two studies, hydrocolloid dressings, a soft gel-based dressing, effectively reduced nasal injuries [50, 51]. Two of the four studies that compared nasal prongs to nasal masks concluded nasal masks were associated with statistically significant lower incidences of nasal injuries [(36% vs 58%] [52] (33% vs 92%) [53]].

Seven studies described pain or discomfort experienced by a patient on CPAP treatment [37, 45, 5458]. These studies noted different levels of reported pain (assessed using validated pain assessment tools) based on device type and patient position. Khan et al. found that neonates in a local low-cost CPAP (J-CPAP) group had significantly lower average Neonatal-Pain Agitation and Sedation Scores (N-PASS) than those in a Fisher & Paykel bCPAP group [45]. Osman et al. reported higher pain scores in an nCPAP group compared to high flow nasal cannula [58]. Jabraeli et al. compared pain scores across supine, prone, and facilitated tucking (fetal) positions with nCPAP and described that the lowest pain scores were recorded when the neonate was in a fetal position [56]. Two additional studies found that when neonates received CPAP in a prone position, heart rates and respiratory rates were lower [59], but there were higher rates of nasal prong displacement (56% required repositioning) [60].

Parent experience

Four studies reported on parents’ experience when their newborns underwent CPAP treatment [33, 49, 50, 61]. These studies emphasized that communication between HCPs and parents is important. Parents should be taught about CPAP and engaged in their neonate’s care [61]. Two studies described parents’ fears related to CPAP treatment [49, 61]. Nyondo-Mipando et al. stated: “Study participants reported that caregivers sometimes had fears that the many tubes interfered with breathing and that oxygen therapy was associated with death–a perception that may have been influenced by the lack of clear, effective communication between providers and caregivers” [49]. These two studies also reported on parent interactions with their babies while on CPAP treatment. Participation in their infant’s care, such as checking for bubbling in the device, was associated with decreased anxiety and worry [49, 61].

Provider experience

Multiple studies discussed providers’ knowledge of CPAP, device assembly, and patient selection for CPAP treatment. HCPs were more confident in their ability to use CPAP when the devices were simple and accompanied by quality training [26, 32, 34]. Several studies described nurses’ perceptions with CPAP treatment [26, 34, 35, 41, 43, 62]. Dewez et al. highlighted “most nurses felt that trained nurses could initiate CPAPindependently’” [34] and Atreya et al. stated that a CPAP device provided “neonatal nurses with more autonomy” [26]. In settings with limited medical personnel, this allowed nurses to play an important role in patient care [34].

Six studies described providers’ experiences with setting up CPAP devices and initiation of CPAP treatment [33, 39, 6366]. Nasal prong dislodgment and the need to re-adjust the patient-device interface were common technical challenges during treatment for neonates and infants [7, 45, 67]. Ntigurirwa et al. described these challenges were difficult to address, “when the nurse to patient ratio is so much lower” [67]. Additionally, Sessions et al. reported that health workers “spent an average of 34.71 min longer per patient, initiating bCPAP compared to low-flow oxygen[and] performed, on average, 26.40 more unique tasks” [33]. Chen et al. addressed this issue by demonstrating that both preparation and application time decreased significantly after staff were trained on a specific CPAP set up protocol [63].

Barriers

The primary barriers to CPAP implementation were a lack of HCPs and insufficient facility resources. HCP turnover and scarcity were often cited as limitations to effective training and quality patient monitoring [26, 32, 34, 41, 42, 44, 49, 65, 6770]. Nahimana et al. suggested that gaps in “correct identification and initiation of eligible infantsmight be a result of turnover of nurses and doctors” [70]. A lack of knowledge on how and when to initiate CPAP treatment was another commonly described barrier [26, 34, 37, 41, 49, 63, 70]. One study reported that a lack of device familiarity led to hesitation in use [41]. A lack of familiarity with CPAP may be associated with insufficient staff training [32, 49, 63, 64, 68, 71]. Two studies reported on nurses’ hesitation because they were “afraid of harming neonates because of the need to reuse consumables” [34] or due to “fear that the clinician would question their decision” [49] to initiate CPAP treatment. Other barriers to use of CPAP included lack of institutional buy-in [34, 41] and low staff motivation [67].

Facility resource constraints included lack of uninterrupted electricity, compressed air, oxygen blenders, specific CPAP protocols [72], and computers for record keeping [65]. Reliable electricity was the most frequently described facility infrastructure barrier that affected both patient care [34, 42, 49] and training [68]. In some instances, facility backup generators were not reliable during power outages [49]. Equipment shortages at medical facilities and in supply chains were the most commonly noted of all physical barriers [27, 32, 34, 49, 71, 72]. Amadi et al. identified “the high cost of devices, consumables and maintenance as limitations to the use of commercial CPAP systems” [25]. Four studies described it is critical that CPAP replacement parts are available in local supply chains [25, 27, 32, 42]. One study reported that facilities lacked CPAP devices because there were “not enough machines or many machines were broken” [34]. To address these challenges, Carns et al. described that “spare parts should be easily sourced, and consumables should not be costly” [42].

Facilitators

Quality training and mentorship were the most commonly described facilitators for successful CPAP implementation [32, 35, 36, 4143, 49, 63, 6771, 73]. Four papers reported that refresher trainings improve CPAP use [32, 49, 68, 70]. Carns et al. described that follow-up “mentoring visits have ensured continued use of CPAP” [42] and Ntigurirwa et al. stated, “through regular, short visits, intensive training can be delivered and problems dealt withbut avoids the potential risk of trainers taking over the clinical care of the babies from local staff” [67]. While some studies reported that CPAP training increases provider knowledge and awareness [42, 63, 73], the most effective approach to training that enables long-term CPAP implementation is not well understood. Wilson et al. implemented a train-the-trainer model where American providers trained Ghanaian nurses, who then trained their colleagues; the latter of whom scored significantly lower on both knowledge and skills testing [32].

Another facilitator described by six studies was the use of an algorithm to guide optimal selection and treatment of patients [36, 44, 49, 64, 66, 70]. Clinical decision algorithms, such as the TRY algorithm were described as easy to teach and integrate [36] to improve infant and neonate treatment [64, 66]. According to Crehan et al, “the TRY-CPAP algorithm was helpful in guiding healthcare workers in the safe and appropriate application of low-cost bubble CPAP in a district hospital setting where usually physicians are absent and care is nurse-led” [64]. Additionally, some studies reported on the need for training on bioengineering support for CPAP devices [36, 42]. Finally, two studies identified buy-in from Ministries of Health and policymakers as critical facilitators to successful implementation [26, 42].

Discussion

This scoping review examined the literature to identify challenges and priorities of CPAP implementation in low-resource settings. Potential priorities for successful CPAP implementation included ease of CPAP device operation [2527, 29, 34, 35], low cost [2527, 30, 31], and reliable supply chain for consumables [25, 27, 32, 42]. Common barriers of CPAP implementation included unreliable electricity [34, 42, 49, 68], insufficient CPAP devices and supporting equipment such as pulse oximeters [27, 32, 34, 49, 71, 72], and lack of bioengineering for CPAP device maintenance and repair [32, 34]. Quality training and mentorship that empowered providers facilitated successful CPAP implementation [32, 35, 36, 4143, 49, 63, 6771, 73].

A major finding from this review was that it is essential that CPAP devices are easy to assemble, use, maintain, and have simple bioengineering support [33, 39]. Evidence has shown how devices designed in high resource settings are not sustainable as once they break, there is no bioengineering support to fix them [74, 75]. While CPAP devices have traditionally been designed in high resource settings, the unique contexts of low resource regions need to be considered when implementing CPAP across these settings. For example, the polite bCPAP device was specifically designed after surveying Nigerian HCPs on their preferences. Affordability, transportability, and simplicity were the most essential characteristics [25]. The essential takeaway here is that a device’s success is dependent on the users and their settings and therefore it is imperative to involve the target audience in the design and implementation process. Such a human-centered design approach has a greater potential to create sustainable, context-based solutions [76]. Incorporating human-centered design facilitates local ownership of CPAP devices and programs by creating a system that may be more appropriate and sustainable [77].

In addition to engineering devices to match their settings, the sustainability of their consumables must also be considered [74]. It is well understood with any device that without available consumables devices will be unusable and only generate waste. That is why it is essential future interventions go beyond facility introduction of CPAP devices to comprehensive integration into health systems in order to ensure sustainability and scale. This includes engaging local manufactures and supply chains. Another solution includes understanding what components could be safely cleaned as reused. Two studies in this review did so for nasal prongs [48, 78], but there is a need to determine safe and standardized reprocessing procedures that are feasible across facilities with different levels of resources. These factors should also be considered in the initial design of devices as mentioned above [76].

Quality training and mentorship were identified as vital facilitators of successful CPAP implementation [17]. Providers must feel confident, empowered, and knowledgeable about CPAP to support and encourage long-term implementation. There is a need for more evidence on different models of training and mentorship, especially taking into account limitations on staff availability. The findings from this review suggest that training models should be integrated into the flow of work with interval in-service training and simulation. As with device design, the development and implementation of training materials should be co-created with local healthcare provider leaders in the settings where they will be used. This will not only foster engagement, but also further adapt education and use to the particular setting in which it will be used [79].

Limitations

A limitation of this review was the significant variation in study design across the included studies. By setting out to capture a wide range of experiences, we incorporated studies with varied interventions and outcomes. For example, the subset of papers on complications and interventions associated with nasal injury were challenging to compare with studies that reported on the effectiveness of different CPAP devices.

Conclusion

Inconsistent parameters and outcomes between studies to-date have prevented meta-analyses [1316]. The study designs, interventions, and objectives in our included studies were also remarkably diverse. Each of the studies in this review addressed an aspect of CPAP implementation that is important to consider when planning for long-term integration of this treatment. While implementation factors are often addressed separately from efficacy and safety in high-resource settings [80], the breadth of experiences described in this review indicates how these measures must be considered concurrently in low-resource settings. Future effectiveness studies should consider not only the short and medium term population outcomes, but also factors that influence sustained integration of CPAP into health systems. A standardized set of implementation outcomes for future research–common barriers and facilitators to study–could allow for improved data synthesis and guidance on optimal care and future research questions.

Successful implementation and integration of CPAP devices across health systems in low-resource settings require appropriate devices, reliable supply chains to replace consumables, and innovative training models that engage users. Each of these elements have one key connection: they each require a deeper engagement of healthcare workers and health systems using these devices. From start to finish CPAP design and implementation should be driven by the final users and the system in which they operate. Combined, it is the hope that these efforts can empower and promote device use, rather than perpetuate potentially unsustainable implementation processes for CPAP use in low-resource settings.

Supporting information

S1 File. PRISMA-ScR checklist.

(DOCX)

S2 File. Database search queries.

(DOCX)

Acknowledgments

The authors would like to acknowledge Harvard Countway Library for the review services provided by Paul Bain in reviewing and running the search query across databases and importing the citations into Covidence.

Data Availability

All relevant data are within the manuscript and its Supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Jacqueline J Ho

2 Mar 2021

PONE-D-20-36892

Experiences with implementation of continuous positive airway pressure for newborns and infants in resource-poor settings: a scoping review

PLOS ONE

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The review is interesting, though there are some concerns regarding methodology and reporting. Overall, please review the PRISMA checklist in detail to make sure all points are covered as it is currently insufficiently reported. There is currently some ambiguity between bubble CPAP and CPAP and the manuscript could be strengthened by more clarity on type. There are some recommendations on how the results section could be tightened as currently there is overlap between the different sub-sections. Furthermore, the unique contribution to the literature and implications for policy and practice can be made more explicit and addition of a conclusion section is strongly recommended as the manuscript currently ends very abruptly. Below are detailed comments that I believe will strengthen the paper.

Abstract

1. Missing why CPAP is of relevance to resource-poor settings. Please start with a line or two of background.

2. Please define acronyms the first time they are mentioned, such as CPAP in line 47.

3. Please clarify what is meant by "original research articles and case studies" - case studies would be original research. Do the authors mean both interventions and observational studies?

4. As the authors note that they have used the PRISMA checklist, more information is needed in the abstract. Please see point 2 of the PRISMA checklist: "Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

Introduction and methods

5. Reference needed for "each year, two and a half million infants die in their first month of life" line 75

6. As a background, more information is needed on respiratory distress syndrome and why it is important particularly to consider for preterm neonates, since it is mentioned that CPAP is recommended in WHO guidelines for preterm infants. Please also quantify "leading cause".

7. The introduction jumps between CPAP and bubble CPAP and it is not completely clear to the reader on what is the focus of the current review. Please clarify the scope of the review (CPAP in general, bubble CPAP because it is more used in LMIC settings?) and the uniqueness of the current review from the previous reviews (i.e. is the current review an expansion of the systematic review of implementation factors for bubble CPAP in sub-Saharan Africa or was it a wider search for all studies of CPAP, not just bubble CPAP?). Why is this review needed?

8. If the focus is on CPAP in general, please provide some background literature review on the implementation of CPAP in resource-limited settings. Currently, the background is focused on bubble CPAP. Is there no examples of other forms of CPAP implemented in LMIC settings? Though I am doubtful that there are no other forms of CPAP implemented, if this is truly the case, this should definitely be added to the background.

9. In line 88, note that the review was on neonatal bubble CPAP, not CPAP in general.

10. The objectives of the review are currently poorly defined. Is the intervention CPAP or bubble CPAP? From the title and introduction, the review appears limited to neonates but this is not stated in the research question. How is newborn defined? How is resource-poor setting defined? Types of studies included?

11. Please explain the scoping review framework further in the methods. It is unclear what this entails and how this is different from a systematic review framework. There is currently no description on why a scoping review methodology was chosen and what makes it unique from a systematic review.

12. Any changes between the protocol and implementation of the review?

13. The eligibility criteria is missing (though reported as completed under item 6 of the PRISMA checklist). Seems like this is in the protocol but more information needs to be added to the manuscript.

14. As stated in item 11 of the PRISMA checklist, please elaborate more on how the reviewer team defined barriers and facilitators. The research question states that it is examining identified "barriers, facilitators, challenges and priorities" (line 95-96). How is barriers different from challenges? What is meant by priorities? Who's priorities?

15. Please describe grounded theory with references, how it was used in this review and provide a coding tree as a supplementary file.

16. Regarding critical appraisals, it states in the protocol that "Included studies will be assessed for risk of bias/quality assessment according to Joanna Briggs Institute (JBI) Critical Appraisal Tool checklists". However in line 132-133, it states that critical appraisals were not conducted. Please clarify this discrepancy and state the justification for amending the protocol if necessary.

Results

17. How many non-English studies were translated? Please add details about the translation process in the methods - was is translated within the reviewer team? Contracted to a professional translator? Google translated?

18. Were the six main categories of coding determined apriori? If so, please revisit grounded theory approach, which is an inductive approach. Is the kappa score regarding the six main categories or the sub-categories? If for the former, what is the kappa for the sub-categories. What was the analysis methodology in developing the sub-categories? More details of this process is needed in the methods.

19. These six main categories should also be added to the abstract. If apriori, then in the methods. If emerged from the data, then in the results.

20. Please define CPAP devices - were they all bubble CPAP devices or other forms of CPAP?

21. For cost effectiveness vs high cost, did it matter between different types of CPAP devices?

22. Please elaborate on why the inability to blend oxygen was reported to be a challenge, particularly to those unfamiliar to respiratory support systems.

23. Easy of use is further elaborated but more detail on what is found for "effectiveness" is needed. Lines 171-6.

24. Please explain what is hydrocolloid dressings? Line 185-6.

25. Please provide more details on why lower birthweight and lower gestational age was associated with increased nasal trauma - is it because nasal prongs were inappropriately sized for small infants. If so, this should be added to the device attributes subsection.

26. The six main categories should be condensed as the first four discuss aspects of CPAP use with barriers and facilitators described. The final two sections on barriers and facilitators should be reworked into the first four categories. Currently, there is overlap and some repetition.

Discussion

27. Table 2 should be reported as part of the results, not the discussion.

28. Regarding "challenges and priorities" (line 284), it is unclear how challenges are different from barriers (see comment 14. Additionally, the results currently do not report priorities. More clarity overall and reporting in the results is required around priority setting.

29. Line 291-292 "lack of bioengineering for CPAP device maintenance and repair" - please rephrase as it is unclear what is meant by bioengineering. Do the authors mean a locally available bioengineering department or that devices need bioengineering development to reduce maintenance and repair needs. If the latter, please discuss some of the innovative systems like Pumani which have aimed to address these concerns.

30. Line 296 regarding devices are easy to assemble, use and maintain: please highlight here that there are different forms of CPAP devices covered in review. Only the Nigerian version was described but this is a form of bubble CPAP. What about different forms of CPAP overall?

31. Are there any policy implications or recommendations?

32. Line 337-339 regarding the current COVID-19 pandemic reads disjointed from the rest of the manuscript and requires further elaboration on what is meant by a it and a "holistic lens".

33. Line 339-340 is a really important point that needs to be made more explicit. Current impact on neonatal survival is still not adequately determined. What do the authors mean by "true impact"?

Conclusion

34. The manuscript would benefit from a conclusion section as it appears missing right now. What is the take home messages and linkages to the bigger picture of neonatal health that the authors would like to conclude after doing their review? Note that this is item 21 in the PRISMA checklist, which is currently inadequately completed.

Reviewer #2: This is a nice scoping review, the primary aim of which is to provide an overview of the available research evidence without producing a summary answer to a "discrete research question", and instead, focusses on a broad research question (well-defined here) . In that regard, the manuscript fits all the requirements necessary for a successful scoping review. In that regard, there is not much statistical analysis to conduct, other than efficient data summarization. I do have some minor comments:

(a) Page 8, line 150: I do not understand how one can have "n = 10" RCTs, when the total number of studies is 54. Is it 40 (unless, the total can't be 54), or I am mistaken?

(b) Page 8, lines 151-153: Same here; the study populations mentioned do not add to 54.

Reviewer #3: - The authors state that they used a scoping review framework referring to the PRISMA checklist. The PRISMA checklist, however, is a framework for reporting the results of a scoping review. It remains unclear which framework the authors used for conducting the scoping review and which considerations determined their decisions. How did the authors deal with critique and recommendations by other scholars, such as Levac and colleagues? This is also not described in the research protocol referred to in the methods section.

- The authors state that they conducted a systematic search. It remains unclear which quality standards/recommendations were applied for conducting the search. A reference to/description of the used framework is missing.

- The authors did not search Pubmed. Why? Pubmed has a broader scope compared to Medline, for example including ahead of print citations.

- The authors state in the review protocol that included studies were supposed to be assessed for risk of bias/quality assessment. However, they decided not to exclude studies based on quality assessment. On page 7 of the manuscript, the authors state that “due to standard scoping review guidelines and variations in study designs, critical appraisals were not conducted” (here, again, it remains unclear which framework the authors used for conducting the scoping review). However, I don’t believe this is not a valid reason to not conduct critical appraisal – just because it does not conventional for scoping reviews. The authors could have decided to use a different method. The question is whether they believe critical appraisal is necessary, and if not, why.

- The authors state that they used a grounded theory approach for the data extraction. It remains unclear which framework the authors used. Grounded theory approach is used to develop new theory from data. However, this is not what the authors have done. They merely conducted a descriptive analysis.

- They research question is limited to the use of CPAP in resource poor setting. What did the authors do with studies in the search result concerning high-resource countries, and why?

- The use/experiences/implementation of CPAP directly after birth is very different from for example 8 months post partum. This difference is not addressed in the result section. I wonder whether the authors paid attention to the relation between age and the use/experiences/implementation.

- In the discussion section, the authors make a few recommendations, for example regarding the availability of consumables. However, they do not address why consumables are not available and what the steps are to making consumable available in in low-resource setting. How is this discussed amongst scholars and in public debate? The analysis remains rather superficial and misses depth in terms of, for example, critically discussing the results in relation to the contemporary body of knowledge, ethics and equity.

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Reviewer #1: Yes: Mai-Lei Woo Kinshella

Reviewer #2: No

Reviewer #3: Yes: Bahareh Goodarzi, Department of Midwifery Science, AVAG, Amsterdam Public Health Research Institute, Amsterdam UMC,

Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

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PLoS One. 2021 Jun 11;16(6):e0252718. doi: 10.1371/journal.pone.0252718.r002

Author response to Decision Letter 0


12 Apr 2021

Dear Editorial Team,

Thank you for sharing the below reviewer comments on our manuscript entitled “Experiences with implementation of continuous positive airway pressure for neonates and infants in resource-poor settings: a scoping review.”

We appreciate the opportunity to strengthen our manuscript based on the constructive feedback of the reviewers. To date, the majority of systematic reviews about CPAP in low and middle-income settings focus on the safety and efficacy of treatment. This scoping review aims to fill a gap in the literature by summarizing additional contextual factors that influence implementation. We believe that identifying and addressing these factors are imperative to implementing long-term and sustainable CPAP programs in low-resource settings. In particular, the COVID-19 pandemic has highlighted an increased interest toward developing and strengthening available oxygen therapy and ventilation delivery systems. This scoping review aims to better understand lessons learned and opportunities for improvement in the implementation of CPAP therapy for newborns in respiratory distress.

After incorporating these constructive comments from the reviewers, we believe this article could be a valuable contribution to PLOS One and its publication could add to current discussions and approaches to the implementation of oxygen therapy and ventilation delivery systems in response to the COVID-19 pandemic. Finally, we would like to thank the reviewers for their incredibly helpful comments and feedback that we believe have strengthened the manuscript.

Please see our responses to the reviewers’ comments below.

Thank you again for your time and consideration.

Regards,

Sara Dada, MSc

Corresponding Author

Reviewer #1

The review is interesting, though there are some concerns regarding methodology and reporting. Overall, please review the PRISMA checklist in detail to make sure all points are covered as it is currently insufficiently reported. There is currently some ambiguity between bubble CPAP and CPAP and the manuscript could be strengthened by more clarity on type. There are some recommendations on how the results section could be tightened as currently there is overlap between the different sub-sections. Furthermore, the unique contribution to the literature and implications for policy and practice can be made more explicit and addition of a conclusion section is strongly recommended as the manuscript currently ends very abruptly. Below are detailed comments that I believe will strengthen the paper.

Abstract:

1. Missing why CPAP is of relevant to resource-poor settings. Please start with a line or two of background.

RESPONSE: We agree that the abstract is strengthened with more information regarding the context and background prior to stating the objective. We have incorporated this (page 2, lines 26-29).

2. Please define acronyms the first time they are mentioned, such as CPAP in line 47.

RESPONSE: This has been adjusted (page 2, line 26).

3. Please clarify what is meant by "original research articles and case studies" - case studies would be original research. Do the authors mean both interventions and observational studies?

RESPONSE: We have omitted “case studies” as it is redundant as the reviewer has described. Any original research articles were considered eligible for inclusion (page 2, line 36).

4. As the authors note that they have used the PRISMA checklist, more information is needed in the abstract. Please see point 2 of the PRISMA checklist: "Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

RESPONSE: Thank you to the reviewer for highlighting this oversight. We have incorporated a ‘background’ section in the Abstract to address this comment as well as comment #1 (page 2, lines 26-29; lines 38-39).

Introduction and Methods:

5. Reference needed for "each year, two and a half million infants die in their first month of life" line 75

RESPONSE: The reference for this sentence and the following were the same so this has now been addressed appropriately (page 4, lines 69-70).

6. As a background, more information is needed on respiratory distress syndrome and why it is important particularly to consider for preterm neonates, since it is mentioned that CPAP is recommended in WHO guidelines for preterm infants. Please also quantify "leading cause."

RESPONSE: We appreciate the reviewers comment to provide additional information on respiratory distress syndrome. We have added this detail in the background on RDS (page 4, lines 72-76)

7. The introduction jumps between CPAP and bubble CPAP and it is not completely clear to the reader on what is the focus of the current review. Please clarify the scope of the review (CPAP in general, bubble CPAP because it is more used in LMIC settings?) and the uniqueness of the current review from the previous reviews (i.e. is the current review an expansion of the systematic review of implementation factors for bubble CPAP in sub-Saharan Africa or was it a wider search for all studies of CPAP, not just bubble CPAP?). Why is this review needed?

RESPONSE: This review focused on implementation of CPAP in general, but we focus on bCPAP overall due to the advantages described in the introduction (such as the lower cost) and provide additional information in the introduction on bCPAP as it is more often used in LMIC settings. We have clarified this in the introduction by describing that there are different forms of CPAP (page 4, lines 78-79) as well as clarified what this review contributes to the growing discussion (page 5, line 96-101).

8. If the focus is on CPAP in general, please provide some background literature review on the implementation of CPAP in resource- limited settings. Currently, the background is focused on bubble CPAP. Is there no examples of other forms of CPAP implemented in LMIC settings* Though I am doubtful that there are no other forms of CPAP implemented, if this is truly the case, this should definitely be added to the background.

RESPONSE: We appreciate this comment as with comment #7 in order to provide further specificity and clarity to the scope of this review. We have added more introductory information describing how CPAPs are differentiated (page 4, lines 78-81) and added additional citations for the efficacy for CPAP in general (page 4, lines 84-85)

9. In line 88, note that the review was on neonatal bubble CPAP, not CPAP in general.

RESPONSE: This has been clarified to specify “neonatal bubble CPAP” (page 4, line 88).

10. The objectives of the review are currently poorly defined. Is the intervention CPAP or bubble CPAP? From the title and introduction, the review appears limited to neonates but this is not stated in the research question. How is newborn defined? How is resource-poor setting defined? Types of studies included?

RESPONSE: We appreciate the call to further clarify our stated objectives. Per comments #7 and #8, we have further clarified that we reviewed CPAP in general, and that specific focus was given to bCPAP as it is often in low-resource settings and appeared in a majority of our results. We have clarified the question to include the patient population that CPAP would be serving (this is consistent with our protocol). The inclusion/exclusion criteria are described in the methods (page 6, lines 140-145). We originally used the term “newborn” to be a less technical term, but because the included literature and rest of the text use the term “neonate” we have changed this to be consistent. This is defined in the results (page 8, lines 195-197). We have also altered the terminology to refer instead to “low-resource” settings as it is more recognizable. We used the World Bank classifications to determine countries that fit this criterion (page 6, lines 142).

11. Please explain the scoping review framework further in the methods. It is unclear what this entails and how this is different from a systematic review framework. There is currently no description on why a scoping review methodology was chosen and what makes it unique from a systematic review.

RESPONSE: We have specified the scoping review framework and methodology more clearly in the Methods section as well as the reasoning for conducting a scoping review – to be broader and more inclusive in providing an overview of all the evidence (page 5, lines 109-113). Because we did not have predetermined outcomes that we were looking for and wanted to capture all experiences relating to implementation, a scoping review was more appropriate than a systematic review for this study.

12. Any changes between the protocol and implementation of the review?

RESPONSE: Thank you to the reviewer for bringing this to our attention. The final updated version of the protocol that was used for the review was not properly uploaded to the registration portal (OSF) – this has now been addressed and the publicly available protocol is the version that was used to guide the implementation of the review. The main changes were largely language edits and the decision to not include critical appraisals.

13. The eligibility criteria is missing (though reported as completed under item 6 of the PRISMA checklist). Seems like this is in the protocol but more information needs to be added to the manuscript.

RESPONSE: The eligibility criteria is currently described in the methodology selection of studies (pages 6, lines 140-145).

14. As stated in item 11 of the PRISMA checklist, please elaborate more on how the reviewer team defined barriers and facilitators. The research question states that it is examining identified "barriers, facilitators, challenges and priorities" (line 95-96). How is barriers different from challenges? What is meant by priorities? Who's priorities?

RESPONSE: As described in the methods section, an inductive content analysis was conducted. We did not define the barriers and facilitators a priori and coded experiences that the primary studies described as barriers and facilitators into these categories. Additional challenges and potential priorities emerged in the analysis and are described in the discussion as areas future research/implementation work must consider. We have clarified the objectives and question of the study to reflect this (page 2, lines 31-32; page 5, lines 101-105)

15. Please describe grounded theory with references, how it was used in this review and provide a coding tree as a supplementary file.

RESPONSE: Thank you to the reviewer for bringing this up. Upon further reflection, we have instead described this as an inductive analytical approach because we are not presenting a potential theory as some interpretations of “grounded theory” call for. We have updated this in the methodology and have included relevant references (pages 6-7, lines 151-161).

16. Regarding critical appraisals, it states in the protocol that "Included studies will be assessed for risk of bias/quality assessment according to Joanna Briggs Institute (JBI) Critical Appraisal Tool checklists". However in line 132- 133, it states that critical appraisals were not conducted. Please clarify this discrepancy and state the justification for amending the protocol if necessary.

RESPONSE: As referenced in the response to Comment #12, we have uploaded the updated final version of the review to the registration portal (OSF). We have also added further explanation as to why we did not conduct critical appraisals (page 7, lines 166-168).

Results:

17. How many non-English studies were translated? Please add details about the translation process in the methods - was it translated within the reviewer team? Contracted to a professional translator* Google translated?

RESPONSE: This has been clarified (page 7, lines 176-177). We used a Google Translate script to translate the six non-English papers (1 Korean, 1 Spanish, 4 Portuguese) and had a native Portuguese speaker cross-check the Portuguese translations.

18. Were the six main categories of coding determined a priori? If so, please revisit grounded theory approach, which is an inductive approach. Is the kappa score regarding the six main categories or the sub-categories? If for the former, what is the kappa for the sub-categories. What was the analysis methodology in developing the sub-categories? More details of this process is needed in the methods.

RESPONSE: The categories were not determined a priori which is why we describe this as an inductive content analysis. The kappa score was for all of the nodes that were coded (categories + subcategories). We had three reviewers independently extract the data from all of the studies (each study was extracted twice and then check by the third). All studies were then uploaded into NVivo and two reviewers coded a sample of the studies and then compared and discussed their codebooks to create a final codebook (categories + subcategories) which was then applied to the full dataset. We have incorporated additional explanation into the methods section (pages 6-7, lines 152-161).

19. These six main categories should also be added to the abstract. If a priori, then in the methods. If emerged from the data, then in the results.

RESPONSE: The six main categories are described in the Abstract under findings (page 2, lines 41-43).

20. Please define CPAP devices - were they all bubble CPAP devices or other forms of CPAP?

RESPONSE: The CPAP devices used in each study are described in the summary table. One of the major challenges we came across was the varying terminology used by different studies – some specified “bubble CPAP” while others used the term “nasal CPAP” even for devices that are known bCPAP systems. We did not want to alter anything that was described in the studies and so we report them verbatim.

21. For cost effectiveness vs high cost, did it matter between different types of CPAP devices?

RESPONSE: Overall, cost was described as a barrier and included studies did not provide enough information to determine if or how this differed between the types of devices. We thank the reviewer for pointing out the need to clarify and have done so (page 8, lines 204-206).

22. Please elaborate on why the inability to blend oxygen was reported to be a challenge, particularly to those unfamiliar to respiratory support systems.

RESPONSE: We thank the reviewer for asking to clarify this nuance for readers less familiar with the topic. We have added language explaining the background and difficulty with improvised devices (page 9, lines 214-217).

23. Ease of use is further elaborated but more detail on what is found for "effectiveness" is needed. Lines 171-6.

RESPONSE: We have provided further clarification on the difference between ease of use and effectiveness throughout the noted paragraph (page 9, lines 221-223).

24. Please explain what is hydrocolloid dressings? Line 185- 6.

RESPONSE: We have added further description by describing the material used in hydrocolloid dressings (page 10, lines 244-245).

25. Please provide more details on why lower birthweight and lower gestational age was associated with increased nasal trauma - is it because nasal prongs were inappropriately sized for small infants. If so, this should be added to the device attributes subsection.

RESPONSE: This is a very interesting question that we have also considered while reviewing the included studies and preparing this manuscript. However, the papers cited did not describe any concrete examples for why this association existed besides the stipulation that lower gestational age and lower birthweight patients had more fragile skin. Since there was not a specific finding or evidence-based conclusion to suggest the reason for this relationship, we have not been able to include this additional detail in our results.

26. The six main categories should be condensed as the first four discuss aspects of CPAP use with barriers and facilitators described. The final two sections on barriers and facilitators should be reworked into the first four categories. Currently, there is overlap and some repetition.

RESPONSE: We appreciate the reviewers approach to try and condense findings to make them more digestible. We agree that there is natural overlap as all of these topics have important intersections. We also considered this approach initially, but decided to keep them separate as each of these categories should be considered in implementation. The device attributes should be considered by device development groups and organizations selecting a device for implementation. The overall discussion of barriers and facilitators are important considerations for any group to consider and provide a broad overview. The specific sections on providers, parents, and patients provide a more detailed analysis when engaging with key stakeholders.

Discussion:

27. Table 2 should be reported as part of the results, not the discussion.

RESPONSE: We originally included Table 2 as an alternative way to visualize and organize the main findings on barriers and facilitators but upon reflection and addressing comments from the reviewers, we have decided to eliminate it.

28. Regarding "challenges and priorities" (line 284), it is unclear how challenges are different from barriers (see comment 14). Additionally, the results currently do not report priorities. More clarity overall and reporting in the results is required around priority setting.

RESPONSE: Our research question includes mention of “challenges and priorities” because we expected these to be areas that needed evidence to be synthesized in order to understand. We did not come across any previous studies that defined a list of known challenges and priorities for future direction of CPAP implementation. The priorities highlighted in this study come from the inductive content analysis and the discussion emphasizes three priority areas for consideration: user-friendly devices and human-centered design, sustainable supply chains, and training. While not all studies explicitly state or declare priorities, the synthesis of our findings pointed to these specific suggested priority areas.

29. Line 291-292 "lack of bioengineering for CPAP device maintenance and repair" - please rephrase as it is unclear what is meant by bioengineering. Do the authors mean a locally available bioengineering department or that devices need bioengineering development to reduce maintenance and repair needs. If the latter, please discuss some of the innovative systems like Pumani which have aimed to address these concerns.

RESPONSE: We have expanded this part of the discussion to elaborate on the meaning of bioengineering support (page 15, lines 362-365 & 369-372). The theme of bioengineering support refers to the difficulty of maintenance and repair for devices from high-resource settings, ultimately reducing the sustainability of these devices. Per the reviewer’s question, we do feel that it is important to develop devices with this need in mind, and thus we have included the example of the polite bCPAP which was developed alongside Nigerian HCPs.

30. Line 296 regarding devices are easy to assemble, use and maintain: please highlight here that there are different forms of CPAP devices covered in review. Only the Nigerian version was described but this is a form of bubble CPAP. What about different forms of CPAP overall?

RESPONSE: In this part of the discussion, we are highlighting the relevance of human-centered design and this was the best example of that point. This is something that could be appropriate and applied to other CPAPs but we did not see that in our included studies. This example describes how HCPs were surveyed and how this informed their “main conceptual constraint of politeCPAP was the requirement for high clinical efficiency, i.e. lightweight for easy transport, collapsible for ambulatory use, affordable in low-income settings and powered by mains and battery/solar power for ease of use in remote locations where grid electricity is unavailable.” We have incorporated additional detail in this paragraph to clarify that it isn’t necessarily just about CPAPs that are easy to use, but that they are designed with end users in mind, which therefore has implications for ease of use, sustainability, and overall implementation (pages 15-16, lines 377-404).

31. Are there any policy implications or recommendations?

RESPONSE: Thank you to the reviewer for highlighting this very pragmatic question. In the discussion, we focus on three of the main potential priorities for implementation of CPAP (page 14, line 350) – easy to assemble and use devices, sustainable supply chains, and quality training and mentorship. We summarize this again in the conclusion – highlighting the importance of considering sustainable implementation in future research as well, rather than just intermediate health outcomes.

32. Line 337-339 regarding the current COVID- 19 pandemic reads disjointed from the rest of the manuscript and requires further elaboration on what is meant by a it and a "holistic lens".

RESPONSE: We agree with the reviewer that this is a bit disjointed from the rest of the manuscript and have taken out this reference to the current pandemic and have restructured the conclusion (pages 16-17, lines 423-443).

33. Line 339-340 is a really important point that needs to be made more explicit. Current impact on neonatal survival is still not adequately determined. What do the authors mean by "true impact"?

RESPONSE: This line has been reworked in the process of adding a more distinct and impactful conclusion (pages 16-17, lines 423-443).

Conclusion:

34. The manuscript would benefit from a conclusion section as it appears missing right now. What is the take home messages and linkages to the bigger picture of neonatal health that the authors would like to conclude after doing their review? Note that this is item 21 in the PRISMA checklist, which is currently inadequately completed

RESPONSE: Thank you to the reviewer for this comment. We have incorporated a more explicit Conclusion section with a heading (pages 16, line 423).

Reviewer #2

This is a nice scoping review, the primary aim of which is to provide an overview of the available research evidence without producing a summary answer to a “discrete research question”, and instead, focuses on a broad research question (well-defined here). In that regard, the manuscript fits all the requirements necessary for a successful scoping review. In that regard, there is not much statistical analysis to conduct, other than efficient data summarization. I do have some minor comments:

1. Page 8, line 150: I do not understand how one can have “n = 10” RCTs, when the total number of studies is 54. Is it 40 (unless, the total can’t be 54), or am I mistaken?

RESPONSE: In this section we reported the three most common study designs across the 54 studies – 10 were RCTs, 8 were described as observational, and 6 were prospective cohort studies. The other 30 studies used a variety of other methodologies or study designs such as case studies, cost-effective analyses, qualitative interviews. All of the studies and their designs are listed in Table 1 (pages 19-23).

2. Page 8, lines 151-153: Same here; the study populations mentioned do not add to 54

RESPONSE: This is similar to the study designs described below. In this part of the text we are reporting the three most common study populations – 18 focused on term and preterm neonates, 11 only on preterm neonates, and 15 targeted healthcare providers. The remaining 10 studies targeted “infants” (which could range in exact definition/age range) or other specific populations such as very low birthweight infants or specific gestational ages. All of the studies and their participant categories are listed in Table 1 (pages 19-23).

Reviewer #3

1. The authors state that they used a scoping review framework referring to the PRISMA checklist. The PRISMA checklist, however, is a framework for reporting the results of a scoping review. It remains unclear which framework the authors used for conducting the scoping review and which considerations determined their decisions. How did the authors deal with critique and recommendations by other scholars, such as Levac and colleagues? This is also not described in the research protocol referred to in the methods section.

RESPONSE: We have clarified in the methodology that we used Chapter 11 of the Joanna Briggs Reviewer’s manual to inform the methodology of this scoping review (page 5, line 111). We believe the response to the below comment #2 also addresses the reviewer’s concerns here.

2. The authors state that they conducted a systematic search. It remains unclear which quality standards/recommendations were applied for conducting the search. A reference to/description of the used framework is missing.

RESPONSE: We have previously described in the methodology that we carried out this review and reported it in compliance with PRISMA-ScR (http://www.prisma-statement.org/Extensions/ScopingReviews). However, to address the reviewer’s comments we have further clarified the methodology and framework used from the Joanna Briggs Reviewer’s manual Chapter 11 which is based on the Arksey and O’Malley framework (page 5, lines 109-113).

3. The authors did not search Pubmed. Why? Pubmed has a broader scope compared to Medline, for example including ahead of print citations.

RESPONSE: Thank you to the reviewer for bringing this up. We have consulted with the librarian that assisted us with the search query and database search and he has provided the following additional explanation: The data that is covered in MEDLINE in the sets we searched: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) 1946 to March 06, 2020 (https://www.ovid.com/product-details.901.html) is almost to the day exactly the same as the material in PubMed. While we understand that PubMed is typically broader than the MEDLINE subset, the “MEDLINE” data we searched includes that additional material.

4. The authors state in the review protocol that included studies were supposed to be assessed for risk of bias/quality assessment. However, they decided not to exclude studies based on quality assessment. On page 7 of the manuscript, the authors state that “due to standard scoping review guidelines and variations in study designs, critical appraisals were not conducted” (here, again, it remains unclear which framework the authors used for conducting the scoping review). However, I don‘t believe this is a valid reason to not conduct critical appraisal — just because it does not conventional for scoping reviews. The authors could have decided to use a different method. The question is whether they believe critical appraisal is necessary, and if not, why.

RESPONSE: Thank you to the reviewer for raising this point. We did not believe it was necessary to conduct critical appraisals largely due to the fact that we would not be excluding any studies based on quality. In order to remain broad and encompassing as a scoping review, we wanted to be able to capture and present all the relevant, existing data in the literature. We have specified this in the manuscript methodology as well (page 7, lines 166-168).

5. The authors state that they used a grounded theory approach for the data extraction. It remains unclear which framework the authors used. Grounded theory approach is used to develop new theory from data. However, this is not what the authors have done. They merely conducted a descriptive analysis.

RESPONSE: We originally set out to present these six themes as a set of indicators/categories relevant to consider in CPAP implementation – hence the grounded theory approach. However, upon further reflection and because some interpretations of grounded theory call for a proposed framework or theory to be presented at the end of the analysis, we agree with the reviewer that this was not clear. We have edited the manuscript to explain that we used an inductive content/descriptive analysis and describe the process (pages 6-7, lines 152-161). It is an inductive approach because we did not develop these categories a priori but were developed as we began coding.

6. They research question is limited to the use of CPAP in resource poor setting. What did the authors do with studies in the search result concerning high-resource countries, and why?

RESPONSE: Our search strategy was developed with the guidance of a senior librarian at Harvard and actually included terms for low/poor-resource settings. As a result of this more specified search strategy, we had very few if any studies in high-resource settings in our original list of records. One study was excluded at full text review because of “wrong setting” (figure 1, PRISMA). We decided to focus on low-resource settings from the start because the experiences with CPAP implementation in high versus low-resource settings are very different and likely not comparable. While CPAP is the assumed standard of care in high-resource settings, low-resource settings may not even have CPAP treatments that are accessible or available. The literature on (and experiences with implementation of) CPAP in low-resource settings is growing and the purpose of this review was to synthesize and understand the varying factors that influence that implementation. The reasoning for focusing on low-resource settings has also been further clarified in the abstract (page 2, lines 26-29) and introduction (pages 4-5, lines 81-101).

7. The use/experiences/implementation of CPAP directly after birth is very different from for example 8 months postpartum. This difference is not addressed in the result section. I wonder whether the authors paid attention to the relation between age and the use/experiences/implementation.

RESPONSE: We thank the review for the comment as we have tried to clarify this terminology. Only four studies looked at infants compared to the vast number of other studies that looked at term and preterm neonates. We have added language explaining how the results focused on this population (page 8, line 193-197). We have gone through and updated the results section when a paper specifically looked and infants and the findings were pertinent to differences in age (page 11, line 286; page 14 lines 338-339).

8. In the discussion section, the authors make a few recommendations, for example regarding the availability of consumables. However, they do not address why consumables are not available and what the steps are to making consumable available in in low-resource setting. How is this discussed amongst scholars and in public debate? The analysis remains rather superficial and misses depth in terms of, for example, critically discussing the results in relation to the contemporary body of knowledge, ethics and equity.

RESPONSE: We deeply appreciate this comment as it is a crucial finding of this paper that we would like to provide a deep and enriching discussion on. We have revised all three subsections of the discussion to include additional references to previous literature on design, consumables & medical waste, and contextual and engaging education (pages 14-15, lines 362-414). We have also revised the conclusion to focus on these three elements, specifically on how they are related and should be a focus of future work (page 17, lines 436-443).

Decision Letter 1

Jacqueline J Ho

21 May 2021

Experiences with implementation of continuous positive airway pressure for neonates and infants in resource-poor settings: a scoping review

PONE-D-20-36892R1

Dear Dr. Dada,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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PLOS ONE

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Acceptance letter

Jacqueline J Ho

3 Jun 2021

PONE-D-20-36892R1

Experiences with implementation of continuous positive airway pressure for neonates and infants in low-resource settings: a scoping review

Dear Dr. Dada:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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