Summary Background Neonatal mortality remains a major global public health challenge, with about 2.4 million newborn deaths occurring within the first month of life in 2020. Central and Southern Asia account for 36% of these deaths, with a neonatal mortality rate (NMR) of 23 per 1,000 live births. Birth asphyxia is a leading cause, responsible for nearly 900,000 deaths annually.

In Nepal, neonatal mortality has remained stagnant over the past decade, with an NMR of 21 per 1,000 live births in both 2016 and 2022. This is far above the national Sustainable Development Goal target of 12 per 1,000 by 2030. Despite initiatives such as the Every Newborn Action Plan, more than 80% of neonatal deaths are still due to preventable causes such as prematurity, birth asphyxia, and infections.

Although Nepal has expanded services through 61 Special Newborn Care Units (SNCUs), improvements in neonatal outcomes have been limited due to persistent gaps in quality of care and health worker skills. Studies highlight shortages of essential equipment, including neonatal resuscitation devices, and inadequate competency among providers, especially in managing non-breathing newborns. Provincial disparities further worsen outcomes and Lumbini provinces showing the highest NMRs. Poor facility readiness, lack of training, and limited availability of drugs and equipment contribute to suboptimal care. Hypothermia and inadequate Kangaroo Mother Care (KMC) practices also increase risks, particularly among low-birth-weight infants.

Simulation-based training has emerged as an effective strategy to strengthen healthcare providers' skills in neonatal resuscitation. Evidence from countries like Tanzania shows improved clinical performance and reduced neonatal complications. The NeoNatalie™ simulator, a low-cost and portable training tool, has been effective in enhancing providers' competence and confidence. In Nepal's context of limited resources and skill gaps, such training offers a practical and scalable solution to improve neonatal outcomes and accelerate progress toward SDG targets.

This study aims to evaluate the effectiveness of simulation-based training in improving the knowledge, skills, and performance of newborn care providers and reducing neonatal mortality in Nepal.

Methods The study is designed as a two-arm, parallel cluster randomized controlled trial conducted in SNCUs across Lumbini province of Nepal. Hospitals will serve as clusters, with equal allocation into intervention and control groups. Participants will include medical officers, nurses, and paramedics working in SNCUs for at least six months. A total of 240 providers (120 per arm) will be enrolled, accounting for clustering and potential attrition. Randomization will be conducted by an independent statistician, with allocation concealment ensured.

Intervention The intervention includes a three-day simulation-based training using the Helping Babies Breathe (HBB) program and NeoNatalie™ simulator. It covers essential newborn care, neonatal resuscitation within the "Golden Minute," breastfeeding, hypothermia prevention, KMC, and infection management. This will be followed by twelve months of mentoring and coaching by trained health workers. The control group will continue routine care.

Data collection and analysis Data will be collected using standardized tools and electronic systems, ensuring quality monitoring.

Data analysis will use appropriate statistical methods, including Analysis of Covariance (ANCOVA), to compare outcomes between groups. Ethical approval will be obtained from Nepal Health Research Council, and informed consent will be ensured. Data confidentiality and trial registration will also be maintained.

Study Management This study will be conducted in coordination with the Provincial Health Training Center, Provincial Health Directorate and provincial hospitals of Lumbini province and led by a team of experts in newborn health, research and epidemiology. Overall, this study addresses critical gaps in newborn care in Nepal by testing a context-specific, skill-based intervention. The study has the potential to improve provider performance, enhance quality of care, and significantly reduce preventable neonatal deaths in resource limited settings in Nepal and elsewhere globally.

Expected outcome and measures Key outcomes include provider knowledge, confidence, and clinical skills assessed through structured questionnaires and Objective Structured Clinical Examinations (OSCEs). These will measure both routine newborn care and management of non-breathing infants, along with KMC implementation.

1. Background 1.1 Introduction Globally, neonatal mortality remains one of the most pressing public health concerns. In 2020, an estimated 2.4 million children died within the first month of life. Central and Southern Asia alone accounted for 36% of these deaths, with a neonatal mortality rate (NMR) of 23 per 1,000 live births . Birth asphyxia, classified as an intrapartum-related complication. The condition continues to be a major cause of neonatal death worldwide, responsible for nearly 900,000 deaths each year.

   In Nepal, neonatal mortality has remained stagnant over the past decade. Findings from the Nepal Demographic and Health Survey (NDHS) revealed that the NMR stood at 21 per 1,000 live births in both 2016 and 2022. This level of mortality is considerably higher than Nepal's Sustainable Development Goal (SDG) target, which aims to reduce NMR to 12 per 1,000 live births by 2030. The slow progress reflects systemic gaps in both service coverage and quality of care for mothers and newborns.

   Nepal's Every Newborn Action Plan outlines strategic interventions such as promotion of birth preparedness, essential newborn care, timely postnatal visits, effective management of non-breathing babies at birth, and care for preterm, low birth weight, and septic newborn. Despite these commitments, neonatal deaths in Nepal remain largely attributable to preventable and treatable conditions. More than 80% of newborn deaths result from three major causes: complications of prematurity, intrapartum-related causes (including birth asphyxia), and neonatal infections.

   1.2 Problem Statement Although Nepal has made progress in expanding newborn care services and establishing Special Newborn Care Units (SNCUs), the neonatal mortality rate has not declined in recent years. Currently, 61 SNCUs are functional across the country, but gaps remain in service quality and health worker competencies. Multiple assessments have identified shortages of essential equipment, such as bag and mask devices for neonatal resuscitation, in delivery rooms. Furthermore, studies show that many health workers lack adequate knowledge and practical skills in neonatal resuscitation, resulting in poor outcomes even in facility-based deliverie Geographic and provincial disparities exacerbate the problem. Lumbini provinces record the highest NMRs, at 24 per 1,000 live births. Analysis of the 2021 Nepal Health Facility Survey highlighted that Lumbini Province, in particular, performed poorly in facility readiness, staff training, and availability of essential drugs and equipment for neonatal care. This evidence indicates that existing maternal and child health interventions, while necessary, are insufficient to drive significant reductions in neonatal deaths, particularly from birth asphyxia, the second leading cause of neonatal mortality after sepsis. Further, hypothermia remains the problem of neonatal deaths in low-birth-weight babies and need health workers' expertise in Kangaroo Mother Care practices.

   1.3 Rationale Simulation-based training has emerged as an effective strategy to strengthen health workers' skills in neonatal resuscitation. Evidence from Tanzania demonstrated that such training significantly improved providers' clinical performance and reduced adverse perinatal outcomes Similarly, use of the NeoNatalie™ simulator, a low-cost, portable, and realistic manikin, which has been shown to enhance midwives' competence and motivation in neonatal resuscitation. In the Nepalese context, where neonatal mortality remains high, health facilities often lack adequate equipment, and providers demonstrate limited resuscitation skills, the integration of simulation-based training represents a timely and contextually relevant intervention. By building provider competence and confidence in managing birth asphyxia, simulation training has the potential to improve neonatal survival and accelerate progress toward Nepal's SDG target of reducing NMR to 12 per 1,000 live births by 2030. The low-birth-weight prevalence is around 12% in the country and they need to provide Kangaroo Mother Care (KMC) as well. However, the skill of health workers needs to be enhanced through simulator-based training and required indication of KMC. Therefore, this study aims to evaluate the effectiveness of simulation-based training to improve skills and performance of neonatal care service providers and reduce newborn mortality in Nepal.

2. Methods 2.1 Study Design and Settings This study is designed as a two-arm, parallel cluster randomized controlled trial (RCT) with an allocation ratio of 1:1. The trial will be conducted in Special Newborn Care Units (SNCUs) (including KMC units) located in Lumbini and Madhesh Provinces, Nepal. Clusters will be defined at the hospital level to minimize contamination across providers. 2.2 Inclusion and exclusion criteria All newborn care providers (medical officers, nurses, and paramedics) working in the selected SNCUs for at least six months prior to baseline assessment. Providers who are on long-term leave or those not directly engaged in newborn care at the SNCU. 2.3 Sample Size Using a two-sample comparison of means (two-sided α=0.05, 90% power), with σ=1.6 (KC A. et al. 2017) and Δ=1.0, the individually randomized per-arm sample size is 54. Applying a design effect DEFF=2.0 to account for clustering at the hospital/SNCU level and inflating by 10% for attrition yields 120 providers per arm (total N=240). With 12 hospitals (6 per arm), the average cluster size is m=20 providers/SNCU, which implies an ICC of approximately 0.053. Recruitment targets are therefore 20 eligible providers per SNCU (six SNCU each in each arm) to achieve the required power.

2.4 Randomization and allocation concealment Random allocation of the 12 SNCUs into intervention and control arms will be performed by an independent statistician using a computer-generated random sequence. Allocation results will be concealed in sealed opaque envelopes. At a study design workshop with the Ministry of Health and Population (MoHP) and the national maternal and neonatal technical working group, the envelopes will be opened by the group chair to assign hospitals to trial arms.

2.5 Experimental Design

The intervention consists of a structured simulation-based training program using the Helping Babies Breathe (HBB) package and the NeoNatalie™ simulator:

• Training: Three-day simulation-based training delivered by certified neonatologists/pediatricians with SNCU/NICU experience. Training covers preparation of the birthing unit, routine newborn care, neonatal resuscitation (within the "Golden Minute"), breastfeeding initiation, Kangaroo Mother Care (KMC), hypothermia prevention, feeding of low-birth-weight infants, and sepsis recognition and management.
• Follow-up support: Monthly mentoring and coaching sessions for six months post-training, led by neonatologists/pediatricians and nurses trained in simulation-based care.
• Control arm: Facilities continue providing routine newborn care services without additional intervention.

2.6 Study variables

Independent variables:

• Sociodemographic characteristics of providers (age, sex, academic qualifications).
• Work-related characteristics (number of deliveries conducted, previous training, duration of SNCU experience).
• Facility readiness (availability of drugs, equipment, and guidelines).

Outcome variables:

1. Knowledge and confidence in essential delivery and newborn care, measured through structured questionnaires.
2. Skills in neonatal resuscitation assessed using Objective Structured Clinical Examinations (OSCEs) aligned with HBB protocols:
3. OSCE A: Routine care of a healthy newborn (drying, warming, airway clearance, delayed cord clamping, breastfeeding initiation).
4. OSCE B: Management of a non-breathing newborn (airway positioning, bag-mask ventilation, chest rise recognition, heart rate assessment, communication with mother).
5. Implementation of Kangaroo Mother Care (KMC) for low-birth-weight infants. 2.7 Data Collection

Data collectors (a medical officer and a nurse/paramedic trained in SNCU practices) will be trained in data quality assurance and ethical procedures by the principal investigator (PI) and neonatologist co- investigator. Data collection tools include:

• Facility assessment checklists,
• Structured provider questionnaires, and
• OSCE performance checklists using the NeoNatalie™ simulator. Data will be captured electronically using KoBo Toolbox. Monitoring and supervision will be conducted by the PI, co-investigators, and a field manager, with real-time feedback provided to the field teams.

2.8 Data Analysis Comparisons between trial arms will be conducted using appropriate statistical tests based on type of variables. Knowledge and confidence scores will be analyzed as continuous outcomes, while OSCE results will be summarized both by item and as composite scores. Facility readiness will be assessed across domains (guidelines and training, equipment, essential medicines) and reported as summary readiness indices. Anvalysis of Covariance (ANCOVA) will be done for the continuous outcome with prespecified covariates. All analyses will be performed in R software (version 4.4, R Foundation for Statistical Computing, Vienna, Austria). Statistical significance will be defined as p < 0.05.

2.9 Ethical consideration Ethical approval will be obtained from the Nepal Health Research Council (NHRC). Informed consent will be secured from all participating health workers. Data confidentiality will be ensured through use of coded identifiers and secure storage. The trial will be preregistered in National Library of Medcinie's clinical trial registry (https://clinicaltrials.gov/).

3. Study Management This study will be conducted in coordination with the Provincial Health Training Center, Provincial Health Directorate and provincial hospitals of Lumbini province. Dr. Khem Pokhrel, an experienced neonatal health researcher in Nepal, will lead the overall process as the Principal Investigator. The training and intervention components will be led by Dr. Santhosh, a specialist neonatologist and master trainer for newborn care, while Ms. Apsara Pandey, Associate Professor of Neonatology at the Institute of Medicine, will oversee nursing procedures. Mr. Suman Sapkota, an epidemiologist, will be responsible for study design and data analysis. Ministry of Health and Population will ensure the quality assurance of the study.

Inclusion Criteria:

• Newborn care providers who have received Skilled Birth Attendant Training
• Newborn care providers who have worked in Special Newborn Care Unit at least six months of period

Exclusion Criteria:

• Newborn care providers who have not provided newborn care at special newborn care
• Not willing to participate
• Short tem contract (less than six months of working period)

The protocol will be shared with the formal request to the principal investigator.

May 2028-July 2028

The request should come from formal email.

Principle investigator along with other investigators will not be participating in radomiziation and allocation. Independent statistician will randomize the clusters and allocate the intervention and control. Allocation will be placed in the concealed invelope to have the name of the cluster for intervention and control arm.