A simple,low-cost bubble CPAP system for use in the delivery room and during transport to the NICU for infants with respiratory distress: A feasibility study

Abstract

Background

To assess the feasibility and efficacy of Vayu continuous positive airway pressure (vCPAP) for preterm and term infants with respiratory distress in the delivery room.

Methods

Feasibility study of infants of any gestational age presenting with respiratory distress defined as a Silverman–Anderson Score (SAS) ≥4 in the delivery room, who were started on vCPAP prior to transfer to the NICU and maintained during transport. Efficacy was assessed by comparing SAS, FiO₂, and SpO₂ before initiation of vCPAP, 1 min after initiation, and at the time of NICU admission. Secondary outcomes were feasibility accessed by a survey applied to all health care professionals (HCP), and safety (pneumothorax or clinical deterioration). Descriptive analysis and parametric and non-parametric tests were applied (alpha of 5%).

Results

10 preterm and 10 term infants were initially enrolled, but one term was excluded because of a protocol deviation. The median gestational age was 37.6 ± 1.1 weeks for preterm and 34.2 ± 1.6 weeks for term infants. A significant improvement in SAS from five prior to vCPAP initiation (IQR 4–6) to three 1 min after initiation (IQR 2–4, p < 0.01), to two on NICU admission (IQR 1–3, p < 0.001). No significant differences in FiO₂, SpO₂, or CPAP pressure over these time periods were identified. Among HCP, ease of use and satisfaction were highlighted. No complications were observed.

Conclusion

In neonates with respiratory distress after birth, a clinical improvement was noted after initiation of vCPAP in the DR and during transport to the NICU.

Keywords

respiratory distress prematurity delivery room care continuous positive airway pressure bubble CPAP neonatal transport

Introduction

Neonatal respiratory distress accounts for 30% to 40% of all admissions to the Neonatal Intensive Care Unit (NICU) globally.¹ In premature infants (<37 weeks of gestational age), several randomized clinical trials have demonstrated that initiation of nasal continuous positive airway pressure (CPAP) in the delivery room was associated with decreased duration of mechanical ventilation, mortality, and the combined outcome of death/bronchopulmonary dysplasia (BPD).² Initiation of CPAP in the delivery room and during transport to the NICU maintains functional residual capacity and pulmonary reserve resulting in less need for intubation and mechanical ventilation.³ However, the availability of CPAP systems that can be used in the DR and during transport in low- and middle-income countries (LMICs) is small.⁴ CPAP systems require electricity, compressed air, oxygen blenders, heaters, and humidifiers making them expensive to maintain and impractical for use in much of the world.

The Vayu bCPAP (Vayu Global Health Innovations, Boston, MA, USA) is a low-cost system that does not require electricity or compressed air.⁵ It does not have a heater, and humidification is provided by the use of an extra water chamber. The oxygen is mixed with room air by using a venturi, allowing provision of oxygen (O₂) concentrations between 30% and 100%. Therefore, vCPAP can be easily placed in the DR and used during transport to the NICU. The objective of this pilot study was to assess the feasibility of vCPAP in infants with respiratory distress immediately after birth and during transport to the NICU.

Methods

Study design

Site

This feasibility study was performed at the Santa Casa de São Paulo level III NICU, between November 2022 and March 2023. In the delivery room, as the standard of care, CPAP is provided with a T-piece device and face masks, which is also used for transportation to the NICU. During the study, the unit had 4 manual T-piece devices (Babypuff®) and one bubble CPAP (BabyPAP; FANEM, SP, Brazil). The institution follows a CPAP protocol without specifications on which type of CPAP to use. Therefore, there were no previous experience with the Vayu system. Patients were enrolled, and as soon as possible, the family was informed of the study and advised of the option to withdraw or consent for continued participation.⁶ The study, including the deferred consent process, was approved by the ethics board of the Institution. Written consent was obtained. No families later refused or withdrew from the study.

Inclusion and exclusion criteria

Preterm (<37 weeks) and/or term (≥37 weeks) infants presenting with respiratory distress immediately after birth, with Silverman–Anderson Score ≥4. Infants with major congenital malformations, or extremely low birth weight infants (<1000 g) were excluded of this study.

Outcomes

The primary outcome was feasibility of the vCPAP system use. Feasibility was determined by the ability to initiate vCPAP in the DR, the time between the decision to initiate CPAP and when the device was effectively applied and functioning, and responses to a specific survey developed for the study. Secondary outcomes were efficacy by comparing changes on the Silverman–Anderson Score (SAS), fraction of inspired oxygen (FiO₂), oxygen saturation (SpO₂), and CPAP pressures between three specific points: before vCPAP initiation, 1 min after starting vCPAP, and at the time of NICU admission and safety defined by the occurrence of pneumothorax diagnosed at admission by CXR or sudden clinical deterioration (SpO2 <80% and/or HR <100 bpm) occurring only while on the vCPAP.

Training on Vayu CPAP

Prior to study initiation, training on the system was provided in person, by the vCPAP professional team, to 10 neonatologists and nine respiratory therapists (RT). Each session lasted 3 h and covered several technical and practical aspects of the device and its components. It included training in system assembling and installation, use in the DR and during transport, monitoring, cleaning, and troubleshooting.

Procedures

Delivery room stabilization

The delivery room team consisted of two neonatologists, one RT, and one NICU nurse, all trained on neonatal resuscitation. After birth, all interventions followed the Neonatal Resuscitation Program Guidelines.^7,8 If needed, positive pressure ventilation was provided by using a T-piece device (BabyPuff®, FANEM, SP, Brazil) and FiO₂ adjusted to keep the SpO₂ within the NRP target range. After the decision to initiate an infant on vCPAP was taken by the resuscitation team in infants with SAS ≥4 were considered for CPAP initiation; once the decision was made the vCPAP was assembled by the RT and placed on the infant. The duration in minutes between the decision to initiate CPAP and the successful application of the vCPAP device was recorded.

Transport to the NICU

Transport was conducted by the same team attending the DR, and FiO₂ levels were adjusted to maintain the SpO₂ target. Upon admission to the NICU, patients still requiring vCPAP support were transitioned to the unit’s CPAP system.

Survey

To elicit feedback from health care providers (HCP), a 14-question survey was developed (see Appendix A). The survey consisted of 14 questions in a numerical 4-point Likert scale format. It included first and/or previous experiences with vCPAP, and general satisfaction when compared to other non-invasive respiratory devices. Regarding the DR context, there were questions about ease of use for assembling and placing the device on the newborn, verifying expiratory pressure and FiO₂, and dynamic adjustments according to patient needs. About transport, questions ranged from ease of use when moving from the DR resuscitation unit to the transport incubator, and from transport to the NICU bed. SpO₂ stability was also assessed in this step of the survey. The final question was about perceived clinical response and changes on SAS. The survey was administered to all HCP who participated in training and data collection. The full survey is provided as supplemental material in Appendix A.

Sample size and data analysis

This pilot study was not powered a priori, as its primary aim was feasibility. With a final sample of 19 infants and a large observed within-subject effect (median reduction in Silverman–Anderson Score from 5 to 2), post-hoc estimation suggests a high statistical power (>85%) for detecting the observed change. These findings support the presence of a strong physiological signal and provide effect size estimates to inform the design of adequately powered future trials. Descriptive analysis was performed for maternal and neonatal characteristics using frequency and normal distribution analyses.

The Student’s t-test was used to compare continuous data and the Wilcoxon rank sum test to determine differences in the medians using SAS. A significance level of p < 0.05 was used for all analyses. The Wilcoxon Rank Sum Test was used to determine differences in the medians [IQR] of SAS, FiO₂, SpO₂, and vCPAP pressures between baseline, 1 min after initiation, and at NICU admission. A p-value <0.05 was considered statistically different.

Results

A total of 10 preterm and 10 term infants were enrolled. However, due to a protocol deviation, one term participant was excluded from the analysis, resulting in a final cohort of 19 patients. Details about population demographics and clinical characteristics are provided (Table 1). The mean birth weight (±SD) was 2.542 ± 732 g. After birth, six (31%) patients required positive pressure ventilation using the T-piece device. Upon arrival at the NICU, 12 (63%) infants remained on conventional CPAP and 7 (36%) were transitioned to room air. All patients included in the study had a final diagnosis of transient tachypnea of the newborn (TTN). All patients were discharged home without any type of respiratory support. More information about all 19 patients included in the analysis is presented in Appendix B.

Table 1.

Population demographics and clinical characteristics.

	All (n = 19)	Term (n = 9)	Preterm (n = 10)
Antenatal steroids	5 (26.3)	—	5 (50)
Magnesium sulfate	2 (10.5)	—	2 (20)
Vaginal delivery	5 (26.3)	2 (22.3)	3 (30)
Neonatal resuscitation	7 (36.8)	5 (55.5)	2 (20)
Gestational age, weeks	36.5 ± 2.5	37.6 ± 1.1	34.2 ± 1.6*
Birth weight, grams	2.700 ± 732	2975 ± 349	2.177 ± 779*
APGAR at 1 min	8 [7–8]	7 [6–8]	8 [7.25–8]
APGAR at 5 min	8 [8–9]	8 [7–9]	9 [8–9]*
CPAP indicated (min of life)	10 [6.5–30]	30 [9–36]	10 [6.2–13.7]
CPAP initiated (min of life)	30 [25–47]	40 [22–50]	28.5 [25.2–32.5]

Legend: Results are presented as n (%), median [IQR] or median ± standard deviation.

CPAP: continuous positive airway pressure.

*p < 0.05 for term versus preterm.

Efficacy

As shown in Figure 1, the SAS had a significant decrease from five (IQR 4–6) prior to vCPAP initiation to three (IQR 2–4) 1 min after initiation (p = 0.002). There was a further decrease to a SAS of two (IQR 1–3) at the time of NICU admission (p < 0.001). No differences were observed for FiO₂, SpO₂, or vCPAP pressure (Table 2).

Figure 1.

Efficacy—the Silverman–Anderson score trajectory from the DR to the NICU. Legend: CPAP: continuous positive airway pressure; NICU: neonatal intensive care unit. Each filled circle is a patient score. Results are presented as median and IQR; *p = 0.002; **p < 0.001; ***p = 0.006.

Table 2.

Efficacy - other respiratory outcomes.

		Before CPAP initiation	1 min after CPAP initiation^a	NICU admission
All (n = 19)	CPAP (cmH₂O)	5 [5–5]	5 [5–5]	5 [5–5]
	FiO₂ (%)	21 [21–30]	30 [30–30]	30 [30–30]
	SpO₂ (%)	96 [93.5–96]	97 [95.5–100]	98 [95.5–100]
Term (n = 9)	CPAP (cmH₂O)	5 [5–5]	5 [5–5]	5 [5–5]
	FiO₂ (%)	21 [21–23.2]	30 [30–30]	30 [0–30]
	SpO₂ (%)	96 [95–96]	97 [96–99]	96 [95–100]
Preterm (n = 10)	CPAP (cmH₂O)	5 [5–5]	5 [5–5]	5 [5–5]
	FiO₂ (%)	23 [21–30]	30 [30–30]	30 [30–30]
	SpO₂ (%)	95 [91–96]	98 [95–100]	98 [97–99]

Legend: Results are presented as median [IQR]. CPAP: continuous positive airway pressure; NICU: neonatal intensive care unit. FiO₂: fraction of inspired oxygen. SpO₂: oxygen saturation.

^aThe lowest FiO₂ provided by Vayu system is 30%.

Feasibility and safety

The decision to start the vCPAP system was taken at a median age of 10 min (IQR = 6.5–30) and initiated at a median of 30 min (IQR 25–47). A total of 17 HCPs participated in the care of the 19 patients enrolled in the study. Survey evaluations were performed with these professionals, nine (53%) by physicians and eight (47%) by RTs. Assembly of the system was described as “easy” and “regular” by 12 (70.5%) and 5 (29.5%) professionals, respectively. Ninety-four percent of HCP reported an improvement in the infan’s respiratory symptoms after initiation of vCPAP.

During transport 88% of HCP described use of vCPAP as “easy” and 12% described it as “reasonable.” An improvement in SpO₂ was perceived by 10 (59%) professionals, and no changes by 6 (35%). In comparison with other positive pressure devices used in DR and transport, the Vayu system was described as “better” than the other CPAP devices by 14 (82%) or indifferent by 3 (18%) professionals. Figure 2 outlines these feasibility outcomes as perceived by HCP who completed the survey.

Figure 2.

Feasibility—professional perspectives with Vayu CPAP use in the DR and during transport to the NICU. Legend: DR: delivery room, NICU: neonatal intensive care unit, SpO₂: oxygen saturation. Results are presented as absolute values on the X axis for a total of 17 answers.

There were no cases of pneumothorax or clinical deterioration.

Discussion

This study is the first to evaluate the feasibility and efficacy of vCPAP for infants 31–40 weeks’ gestation presenting with respiratory distress in the delivery room defined as an SAS ≥4. We found the system to be feasible with 82% of HCP reporting a better experience with vCPAP over current standard of care using a t-piece or bubble CPAP device. Use of vCPAP resulted in a significant improvement in SAS both 1 min after initiation and at the time of NICU admission. No infants in the cohort were diagnosed with pneumothorax or required escalation of respiratory support during their birth hospitalization.

The use of CPAP for infants presenting with respiratory distress at the DR is a well-established clinical practice and a formal recommendation for neonatal global care.⁹ There is strong evidence indicating a reduction in intubation rates, shorter length of hospitalization, decreased surfactant use, and a reduction in death and severe BPD, especially among preterm and extremely preterm infants.^10–12 vCPAP does not require compressed medical air or electricity thus is an excellent option for LMICs.^13–15 The compact and portable design of vCPAP allows it to be easily used during transport from the DR to the NICU.

The SAS provides a quick assessment of respiratory distress based on non-invasive clinical evaluation done at the bedside.^16,17 Our findings that vCPAP initiation resulted in a significant decrease in SAS are consistent with prior literature.^13,18 SAS ≥5 in the first hour of life are associated with increased need for respiratory support during the first 24 h of life.¹⁷ A reduction in SAS, heart and respiratory rates, and FiO₂ at one and 24 h after vCPAP initiation, has been demonstrated on a single center study.¹⁸ While vCPAP has previously been shown to reduce heart rate, respiratory rate, and Fi0₂ requirement, we did not find a significant difference in similar physiologic parameters (Sp0₂ and Fi0₂). This may be explained by the overall normal ranges of Fi0₂ and Sp0₂ in our cohort prior to vCPAP initiation and the mild degree of respiratory distress with seven infants in the cohort not requiring CPAP at the time of NICU admission and all infants receiving a diagnosis of TTN.^12,19,20

We found a median interval of 19 min between the decision to start vCPAP and its initiation. This is likely due to the study design, including not opening and setting up the vCPAP device prior to delivery, and would not be desirable in more urgent scenarios. . Therefore, assembly of the system prior to birth, in selected patients, could reduce this delay.²¹ In addition, continuous training and development of standardized operating procedures may improve these results.²²

Most HCP in our cohort described the experience with Vayu as easy and overall better when compared to other CPAP devices used in DR and transport. Structured survey results from HCP participating in the study found vCPAP feasible to use in the DR and during transport. The clinical acceptance of a new device is a critical point for successful integration.^14,21,22 Factors, such as ease of assembly and use, adequate application and monitoring, and affordability, are key points for positive outcomes.

The use of vCPAP was also safe, with no adverse events such as pneumothorax or clinical deterioration as reported before.²¹ Safety is especially relevant for a low-cost and potentially widely applicable device. Our lack of safety events may both reflect the effective training session with proper use of the device and the overall health of the infants included in this study.¹⁸

The study has several limitations. First, this was a small prospective study, and respiratory distress was assessed using SAS, which is prone to individual subjectivity. vCPAP can only deliver ≥30% oxygen. Since baseline FiO₂ values were already close to this lower limit, FiO₂ was a relatively insensitive outcome measure in this study. Additionally, there are several limitations of the vCPAP devices including lack of heat and humidification that may make its use challenging for smaller and sicker infants thus limiting the generalizability of our results to these populations. However, given the demographics of the population studied and the short period of exposure, both issues are likely to be not clinically relevant. At last, all final diagnoses of TTN might limit the generalizability to other causes of respiratory distress and since TTN is a self-limiting condition and the study does not include a control group, the observed clinical improvement cannot be solely attributed to vCPAP treatment. The effect of no heating in more immature infants prone to hypothermia, or unknown humidification for longer periods, needs to be evaluated in future studies. Further investigation is needed including larger sample size, multiple institutions, and higher-risk populations with other respiratory conditions, to confirm efficacy and safety, and enhance generalizability. Randomized controlled trials aiming for head-to-head comparisons with other established CPAP devices would also provide stronger evidence.

Conclusion

In conclusion, we found vCPAP to be feasible and efficacious in reducing SAS score from the DR to NICU admission in a small cohort of infants born at 31–40 weeks’ gestation with a final diagnosis of TTN. This simple, low-cost system is likely of high value for use in infants with respiratory distress when other forms of CPAP are not available.²³

Supplemental material

Supplemental Material - A simple, low-cost bubble CPAP system for use in the delivery room and during transport to the NICU for infants with respiratory distress: A feasibility study

Supplemental Material for A simple, low-cost bubble CPAP system for use in the delivery room and during transport to the NICU for infants with respiratory distress: A feasibility study by Danieli M. K. Leandro, Elisa S. B. Medeiros, Lidiaine N. Oliveira, Gabriel F. T. Variane, Mariana Werneck, Tayane do Vale Bertanha, Rafaela F. R. Pietrobom, Juliana Q. Teixeira, Anna K. S. Nazareth, Daniela P. Rodrigues, Maurício Magalhaes, and Guilherme Sant’Anna in Journal of Neonatal-Perinatal Medicine.

Footnotes

Acknowledgments

The authors would like to express gratitude to the clinical and nursing staff at Hospital da Santa Casa de Misericórdia de São Paulo for their invaluable cooperation and technical support during the data collection phase. We are also profoundly grateful to the families of the neonates included in this study for their participation.

ORCID iDs

Elisa S. B. Medeiros

Gabriel F. T. Variane

Tayane do Vale Bertanha

Rafaela F. R. Pietrobom

Daniela P. Rodrigues

Maurício Magalhaes

Guilherme Sant’Anna

Author contributions

The authors disclose that the Vayu Bubble CPAP equipment was kindly donated by Vayu Global Health Innovations. The manufacturer had no role in study design, data collection, statistical analysis, or the developing and submitting processes of this manuscript. The authors have no financial affiliation with Vayu Global Health Innovations.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental material

Supplemental material for this article is available online.

References

Lawn

Bhutta

Ezeaka

, et al. Ending preventable neonatal deaths: multicountry evidence to inform accelerated progress to the sustainable development goal by 2030. Neonatology 2023; 120(4): 491–499. https://doi.org/10.1159/000530496

Carlo

. Gentle ventilation: the new evidence from the SUPPORT, COIN, VON, CURPAP, Colombian network, and neocosur network trials. Early Hum Dev 2012; 88(Suppl 2): S81–S83. https://doi.org/10.1016/S0378-3782(12)70022-1

Lee

Strand

Finan

, et al. Edgardo szyld; part 5: neonatal resuscitation: 2025 American heart association and American academy of pediatrics guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics 2025; 157: e2025074352. https://doi.org/10.1542/peds.2025-074352

Saugstad

Kapadia

Vento

. Delivery room handling of the newborn: filling the gaps. Neonatology 2024; 121(5): 553–561. https://doi.org/10.1159/000540079

Vayu Global Health Innovations . Breathing for babies: vayu global health innovations. Vayu Global Health Innovations, 2023. Available from: https://vayuinnovations.org/vayu-bcpap-system/

Katheria

Reister

Essers

, et al. Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 2019; 322: 1877–1886. https://doi.org/10.1001/jama.2019.16004

Guinsburg

Almeida

MFB

State Coordinators and Executive Group of the PRN-SBP; Scientific Council of the SBP Neonatology Department . Neonatal resuscitation of newborns <34 weeks’ gestation in the delivery room: 2022 guidelines of the Brazilian Society of sediatrics. Brazilian Society of Pediatrics, 2022. Available from: https://www.sbp.com.br/fileadmin/user_upload/sbp/2022/maio/20/DiretrizesSBP-Reanimacao-RNmenor34semanas-MAIO2022.pdf

Almeida

MFB

Guinsburg

State Coordinators and Executive Group of the PRN-SBP and Scientific Council of the SBP Neonatology Department . Neonatal resuscitation of newborns ≥34 weeks’ gestation in the delivery room: 2022 guidelines of the Brazilian Society of Pediatrics. Brazilian Society of Pediatrics, 2022. Available from: https://www.sbp.com.br/fileadmin/user_upload/sbp/2022/maio/20/DiretrizesSBP-Reanimacao-RNigualMaior34semanas-MAIO2022.pdf

World Health Organization . WHO recommendations on newborn health: guidelines approved by the WHO Guidelines Review Committee. World Health Organization, 2017. https://iris.who.int/handle/10665/259269

10.

de Carvalho Nunes

Barbosa de Oliveira

Zeid

, et al. Early bubble CPAP protocol implementation and rates of death or severe BPD. Pediatrics 2024; 154(1): e2023065373. https://doi.org/10.1542/peds.2023-065373

11.

Subramaniam

Davis

. Prophylactic or very early initiation of continuous positive airway pressure (CPAP) for preterm infants. Cochrane Database Syst Rev 2021; 10(10): CD001243. https://doi.org/10.1002/14651858.CD001243.pub4

12.

Andersen

Eriksen

Viuff

A-CF

, et al. Portable bedside nasal continuous positive airway pressure in the delivery room reduces length of stay. Acta Paediatr 2025; 114: 1945–1952. https://doi.org/10.1111/apa.70062

13.

Rauschendorf

Bou

Meara

, et al. Effectiveness of a novel bubble CPAP system for neonatal respiratory support at a referral hospital in the Philippines. Front Pediatr 2023; 11: 1323178. https://doi.org/10.3389/fped.2023.1323178

14.

Dada

Ashworth

Sobitschka

, et al. Experiences with implementation of continuous positive airway pressure for neonates and infants in low-resource settings: a scoping review. PLoS One 2021; 16(6): e0252718. https://doi.org/10.1371/journal.pone.0252718

15.

Dundek

Brazil

, et al. Evaluation of a bubble CPAP system for low resource settings. Respir Care 2021; 66(10): 1572–1581. https://doi.org/10.4187/respcare.08948

16.

Silverman

Anderson

. Controlled clinical trial of effects of water mist on obstructive respiratory signs, death rate and necropsy findings among premature infants. Pediatrics 1956; 171: 1.

17.

Hedstrom

Gove

Mayock

, et al. Performance of the Silverman Andersen respiratory severity score in predicting PCO₂ and respiratory support in newborns: a prospective cohort study. J Perinatol 2018; 38(5): 505–511. https://doi.org/10.1038/s41372-018-0049-3

18.

Ahn

Shayo

Mselle

, et al. Implementation of a novel bubble continuous positive airway pressure system with a blender in preterm infants in a low resource setting. J Perinatol 2025; 45: 63–67. https://doi.org/10.1038/s41372-024-02153-5

19.

Guay

Carvi

Raines

, et al. Care of the neonate on nasal continuous positive airway pressure: a bedside guide. Neonatal Network 2018; 37: 24–32. https://doi.org/10.1891/0730-0832.37.1.24

20.

Bruschettini

Hassan

Romantsik

, et al. Interventions for the management of transient tachypnoea of the newborn - an overview of systematic reviews. Cochrane Database Syst Rev 2022; 2(2): CD013563. https://doi.org/10.1002/14651858.CD013563.pub2

21.

Meara

Saba

Roodaki

, et al. Evaluating the feasibility of a nonelectric bubble CPAP system in the NICU of a Philippine regional referral hospital: a qualitative study. Int J Pediatr 2025; 2025: 5529978. https://doi.org/10.1155/ijpe/5529978

22.

Banik

Halim

Md Abdullah

, et al. Vayu bubble continuous positive airway pressure is a promising solution with favorable treatment outcomes for respiratory distress syndrome in newborns: a qualitative study in Bangladesh. Front Pediatr 2024; 12: 1359406. https://doi.org/10.3389/fped.2024.1359406

23.

Rosner

Glynn

. Power and sample size estimation for the clustered wilcoxon test. Biometrics 2011; 67(2): 646–653. https://doi.org/10.1111/j.1541-0420.2010.01488.x

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