F1000Research F1000Research 2046-1402 F1000 Research Limited London, UK 10.12688/f1000research.149883.1 Study Protocol Articles Effect of physical rehabilitation using oromotor stimulation, manual airway clearance technique, positioning, tactile and kinaesthetic stimulation (PROMPT) protocol on respiratory and neuromuscular function in neonatal respiratory distress syndrome (NRDS)- a protocol for randomized controlled trial

[version 1; peer review: 1 approved with reservations]

 Hullumani Sharath Conceptualization Data Curation Formal Analysis Funding Acquisition Investigation Methodology Project Administration Resources Software Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0009-0000-2926-5609 a 1 Qureshi Moh’d Irshad Conceptualization Data Curation Funding Acquisition Investigation Software Supervision Validation 2 Raghuveer Raghumahanti Conceptualization Data Curation Methodology Project Administration Resources Software Supervision Validation Writing – Review & Editing https://orcid.org/0000-0001-7696-0786 2 Department of Paediatrics Physiotherapy, Ravi Nair Physiotherapy College, Datta Meghe Institute Higher Education and Research (DU), Sawangi Meghe, Wardha, MH, 442004, India Department of Neuro Physiotherapy, Ravi Nair Physiotherapy College, Datta Meghe Institute Higher Education and Research (DU), Sawangi Meghe, Wardha, MH, 442004, India sharathhullumani@gmail.com

No competing interests were disclosed.

 24 5 2024 2024 13 536 9 5 2024 Copyright: © 2024 Hullumani S et al. 2024 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background

Neonatal Respiratory Distress Syndrome (NRDS) remains a significant challenge in neonatal care, often leading to respiratory compromise and neuromuscular dysfunction. While advances in medical management have improved outcomes, adjunctive therapies such as physical rehabilitation offer potential benefits yet require further investigation. This protocol outlines a randomized controlled trial aiming to evaluate the effect of Physical Rehabilitation using Oro Motor Stimulation, Manual Airway Clearance Technique, Positioning, Tactile, and Kinesthetic Stimulation (PROMPT) protocol on respiratory and neuromuscular function in neonates with NRDS.

 Methods

The trial will include 38 neonates diagnosed with NRDS, randomly allocated into two groups: the intervention group receiving the PROMPT protocol alongside standard care, and the control group receiving standard care alone. The PROMPT protocol comprises a comprehensive approach targeting oromotor stimulation, manual airway clearance technique, optimal positioning, and tactile/kinesthetic stimulation.

 Outcome measures

Primary outcomes will focus on respiratory parameters such as oxygenation index, ventilatory support requirements, and neuromuscular function assessed through muscle tone and reflexes. Secondary outcomes will encompass length of hospital stay, incidence of complications, and neurodevelopmental outcomes at follow-up.

 Results

Data analysis will employ appropriate statistical methods to compare outcomes between the intervention and control groups, with adjustments for potential confounders. Ethical approval has been obtained, and informed consent will be obtained from parents or legal guardians before enrolment.

 Conclusion

This trial protocol aims to provide valuable insights into the efficacy and safety of the PROMPT protocol as a rehabilitative intervention for NRDS. The findings may inform future clinical practice and contribute to optimizing care strategies for neonates with NRDS, ultimately improving their short- and long-term outcomes.

 Registration

CTRI/2024/03/064911

 respiratory distress syndrome respiratory distress NRDS IRDS The author(s) declared that no grants were involved in supporting this work. Introduction

Hyaline membrane disease, also referred to as Neonatal Respiratory Distress Syndrome (NRDS), is a serious respiratory illness that primarily affects premature babies. The hallmark of this disease is decreased lung function based on by an absence of pulmonary surfactant, which is essential for preserving alveolar stability and averting collapse during expiration. Being the primary cause of respiratory distress in infants, non-respiratory distress syndrome (NRDS) presents a complicated range of difficulties for medical practitioners, demanding early diagnosis and treatment to maximize results. Premature babies, particularly those born before 28 weeks of gestation, have a higher prevalence of (NRDS), which has an inverse relationship with gestational age. The significance of surfactant, a lipid-protein complex generated by type II alveolar cells in the lungs, is shown by this association. Premature babies frequently don’t have enough surfactant, which causes surface tension to rise and alveolar collapse, which prevents enough oxygen exchange. RDS, also known as neonatal respiratory distress syndrome, is a common cause of respiratory distress in infants. It often manifests itself a few hours after birth, usually right after delivery. RDS mostly affects preterm newborns, with term infants affected sporadically as well. The incidence of RDS is negatively correlated with the infant’s gestational age, with smaller and more preterm neonates experiencing more severe illness. RDS remains the primary cause of morbidity and mortality in preterm infants, despite the fact that treatment techniques such as prenatal corticosteroids, surfactants, and sophisticated respiratory care of the newborn have improved the results for patients affected by the condition. 1

Surfactant deficit is the cause of neonatal respiratory distress syndrome, particularly when the lungs are still developing. A lack of surfactant causes the surface tension in the alveoli and tiny airways to rise, which lowers the juvenile lung’s compliance. To stop the alveolus from collapsing or from filling with fluid, the pressures at the air-fluid interface must be carefully balanced. 2

The clinical course of neonatal respiratory distress syndrome (RDS) and the long-term outcomes of the neonates are the primary factors associated with complications of RDS. Even though the morbidity linked to RDS has decreased with surfactant therapy, many individuals still experience problems both during and after the acute phase of the disease. Acute side effects from invasive mechanical ventilation or positive pressure ventilation include pneumothorax, pneumomediastinum, and pulmonary interstitial emphysema, which are air-leak syndromes. In very low birth weight newborns with RDS, there is also an increased risk of cerebral bleeding and patent ductus arteriosus, however these conditions are not directly related to preterm. 3

One long-term RDS consequence is BPD. The etiology of BPD includes inflammation and lung damage in addition to stunted lung growth. In addition to lacking surfactant, the premature infant’s immature lung also has reduced compliance, impaired fluid clearance, and immature vascular development, all of which put the lung at risk for damage and inflammation and further interfered with the alveolar and pulmonary vasculature’s normal development. 4 – 6 Additionally, reduced antioxidant capacities of the premature lung and oxidative stress from hyperoxia brought on by mechanical breathing both cause the lung to deteriorate further by increasing the production of pro-inflammatory cytokines such TGF-β1.

Another complication of RDS is neurodevelopmental delay, which is more common in infants who have had prolonged mechanical breathing. In addition, newborns with RDS had a higher incidence of cerebral palsy, which decreased with increasing gestational age. 7 There is a correlation between the duration of artificial ventilation and higher incidence of cerebral palsy and neurodevelopmental delay. 8

Oro motor stimulation, positioning, tactile, and kinesthetic stimulation (PROMPT) is one physical rehabilitation strategy that has shown promise in treating preterm newborns’ respiratory, pulmonary, and neuromuscular problems. But there is still a dearth of empirical data demonstrating the effectiveness of these kinds of therapies, especially when used in randomized controlled trials (RCTs). 9

By examining the complete effects of PROMPT on respiratory, pulmonary, and neuromuscular outcomes in preterm newborns with NRDS, this study aims to close this information gap. The application of a randomized controlled trial design facilitates a thorough analysis of the intervention’s effects, offering important new information to the developing field of newborn care.

By carefully examining these aspects, this research hopes to improve neonatal care practices and lay the groundwork for future developments aimed at enhancing the well-being and results of this susceptible group.

 Objective of the study

To determine the effectiveness of PROMPT protocol in adjunct to medical treatment on respiratory outcomes (ABG, SPO2, APGAR, The Silverman Andersen Respiratory Severity Score RSS Questionnaire) in Neonatal Respiratory Distress Syndrome.

To determine the effectiveness of PROMPT protocol in adjunct to medical treatment on Neuromuscular Function (Ballard Score, Oral motor assessment scale, General Movement Assessment) in Neonatal Respiratory Distress Syndrome.

To determine the effective rehabilitation treatment between PROMPT protocol and conventional physiotherapy in adjunct to medical treatment in improving pulmonary and neuromuscular function in Neonatal Respiratory Distress Syndrome.

To study the length of Neonatal Intensive Care Unit (NICU) stay and length of hospital stay of neonates with Respiratory Distress Syndrome who are treated with PROMPT protocol and conventional physiotherapy in adjunct to medical treatment.

Protocol

This protocol has been registered with CTRI registration number CTRI/2024/03/064911.

 Ethics and consent

This study will be conducted with written informed consent & assent from all the parents Ethical approval was received from Datta Meghe Institute of Higher Education and research (DU), Sawangi (Meghe), Wardha, on 30th January 2024 with Ref No. DMIHER/IEC/2024/65.

 Trial design

The neonates will be subjected to evaluation using defined inclusion and exclusion criteria and will be enrolled from the Neonatal Intensive Care Unit (NICU) located at Acharya Vinoba Bhave Rural Hospital in Sawangi. Subsequently, written informed consent will be obtained, and if the neonate’s caregiver agrees, selection will occur through simple random sampling using computer-generated random numbers aligned with eligibility criteria. The study procedures will be explained to parents, and written consent will be obtained from them. Neonates medically diagnosed with neonatal distress syndrome will be assigned to the study.

Following treatment, the same outcome measures will be applied.

 Inclusion criteria

Age: Participation is open to individuals within the age range of birth to 28 days, specifically focusing on preterm neonates born before completing 36 weeks of gestation.

Vital signs: Inclusion criteria involve neonates with a pulse rate (PR) surpassing 160 beats per minute, a respiratory rate (RR) exceeding 60 breaths per minute or exhibiting apnea, and a diastolic blood pressure (DBP) below 60 mmHg.

Chest examination: Eligibility encompasses neonates displaying reduced bilateral or unilateral airway entry, abnormal sounds such as grunting, indications of intercostal retractions, substernal retractions, suprasternal retractions, and nasal flaring. Additionally, X-ray findings indicating white lungs, fine reticular granularity of the parenchyma, and airway bronchograms are considered.

Skin examination: Neonates with pale or bluish-colored skin are candidates for inclusion.

ABG analysis: Inclusion criteria cover neonates with arterial blood pH below 7.20, arterial blood PCO2 of 60 mm Hg or higher, arterial blood PO2 of 50 mm Hg or less, and an oxygen saturation ranging from 70% to 100% and diagnosed as NRDS.

Mechanical ventilation: Eligibility standards include neonates undergoing mechanical ventilation in incubators and being monitored with oxygen support.

Primitive reflexes: Inclusion involves neonates demonstrating the absence or poor presence of survival reflexes such as the rooting reflex, sucking reflex, palmar reflex, and plantar reflex.

Exclusion criteria

Significant Congenital Abnormalities.

Profound Hemodynamic Instability.

Life-Threatening Situations: Neonates with urgent and critical medical conditions other than NRDS, necessitating immediate interventions, may be ineligible.

Serious Neurological Complications: Neonates with severe neurological issues that could independently affect neuromuscular function, apart from NRDS, may be excluded.

Parental Denial or Incapacity to Participate: Parents or guardians who decline to provide consent for their neonate to participate in the study or are unable to adhere to study requirements may be excluded.

Unstable Respiratory Condition: Neonates with an unstable respiratory status hindering the initiation or continuation of the rehabilitation intervention may be excluded.

Severe Coagulation Disorders: Neonates with significant coagulation disorders that may pose risks to the safety of rehabilitation interventions may be excluded.

Group A will receive the PROMPT protocol as an adjunct to medical treatment by paediatric physiotherapist. for 6 weeks daily, for 30 minutes, or until the neonate/infant is successfully weaned off the mechanical ventilator, based on their medical condition, or until the intervention concludes on the last day of the neonate’s transfer from the NICU to the ward.

Group B will receive standardized medical treatment protocols + Conventional Physiotherapy (Chest percussion, vibration and suctioning) administered by neonatal specialists and paediatric physiotherapist. Both groups will continue treatment until the neonate/infant is successfully weaned off the mechanical ventilator, based on their medical condition, or until the intervention concludes on the last day of the neonate’s transfer from the NICU to the ward. Assessments will be conducted at baseline, 2nd week, 4th week, 6th week, and after a 3-month follow-up, infant will be evaluated in high-risk clinic, where both primary and secondary variables will be evaluated ( Figure 1).

CONSORT flow chart.

PROMPT Treatment Protocol:

Physical

Rehabilitation

Oro motor stimulation ( Table 1)

ORO motor stimulation (O).
Treatment Descriprtion Intensity
Cheek stretch Apply light pressure to compress the tissue by placing the index finger at the base of the nose. Forming a C shape, move the finger first toward the ear and then downhill to the lip corner. On the other side, repeat the identical process. 2 minutes
Upper lip stimulation Press the index finger gently against the top lip's corner to compress the tissue. Take a circular motion with the finger, moving it from one corner to the center and back again to the other corner. Proceed in reverse to change the direction. 2 minutes
Lower lip stimulation Press down on the lower lip's corner with your index finger to compress the skin. Move the finger in a circular manner, starting from the corner and going all the way to the centre and back again to the other corner. 2 minutes
Upper gum stimulation Applying firm pressure gradually, place the finger in the middle of the gum and slide it toward the rear of the mouth, then back towards the center. 2 minutes
Lower gum stimulation Place the finger in the middle of the gum, press firmly and consistently, and then work your way slowly towards the back of the mouth. 2 minutes
Tongue stimulation Position the finger between the lower gum and the lateral aspect of the tongue at the level of the molars. Press down to move the tongue in the other direction as you move the finger in the direction of the midline. Quickly press the finger into the cheek to produce a squeezing feeling, and then press firmly on the hard palate for three seconds. After that, press the finger down until it touches the middle of the tongue. 2 minutes
TMJ stroke To incorporate Temporomandibular Joint (TMJ) strokes into oro motor stimulation, methods that target the muscles surrounding the jaw joint must be used. These techniques include kneading the jaw joint gently, moving in circles, and applying pressure with concentration to the surrounding muscles. Improving blood flow, relieving tense muscles, and enhancing orofacial muscular coordination are the goals. 2 minutes

Manual airway clearance technique ( Table 2)

Manual airway clearance technique (M). <sup> <xref ref-type="bibr" rid="ref10">10</xref> </sup>
Treatment Descriprtion Intensity
Percussion Chest percussion involves tapping the chest using percussor cups, resembling suction cups, to create vibrations in the airways of the lungs. These vibrations aid in loosening mucus, facilitating its removal through coughing. 30 percussion for 5 sets
Active gentle vibration A rapid, sensitive trill-type movement was used to actively deliver gentle vibrations while exhaling. Mild vibrations were applied after percussion to help shift secretions in the direction of the bigger airways. Each newborn's chest vibrations were manually applied by covering the targeted region with one hand's fingers on the chest wall. A faint vibrating motion was produced by the isometric contraction of the hand and forearm muscles. Concurrently, the other hand supported the head of the infant, keeping the palm cupped to cradle the head for the length of the treatment. 30 vibration for 5 sets
Postural drainage The newborn was kept in a flat supine position during the anterior segment drainage of the left and right upper lobes. To address the right and left lateral basal segments of the lower lobes, drainage was performed as the neonate leaned forward at a 90-degree angle, followed by percussion over the uppermost sections of the lower ribs. Percussion was applied over the side of the chest beneath the clavicles, extending towards the nipple area, with caution to avoid direct pressure on the sternum. Each drainage position was applied for a duration of 5 minutes per position.
Reflex stimulation for respiratory facilitation The neonate is positioned in the supine decubitus, and gentle digital pressure is applied to a specific point on the hemithorax, precisely between the 7th and 8th ribs (corresponding to the diaphragm muscle insertion) along the mammillary line. This designated area is referred to as a “trigger point.” Activation of the trigger point induces respiratory activity by causing compression on the stimulated side, leading to an increase in ipsilateral pulmonary ventilation per minute and facilitating contralateral pulmonary expansion (3 minutes and repeated 4 to 6 times consecutively, involving the 7th right hemitoracic space for 3 minutes, followed by the 7th left hemithorax space for 3 minutes, and repeating this sequence for both the 7th right and left spaces. If secretions are present, the respiratory facilitation technique is combined with a prolonged slow expired technique tailored for preterm infants.) This program is implemented three times a day until the neonate achieves complete respiratory autonomy.
Suctioning The goal of nasotracheal suctioning (NTS) for tracheal aspiration was to remove accumulated sputum, blood, pulmonary secretions, saliva, and other foreign materials from the nasopharyngeal and trachea. The process was carried out by the nurse, who used sub-atmospheric pressure to extract a sterile, flexible, multi-eyed catheter. The neonate's sub-atmospheric pressure to between 80 and 100 mm Hg in order to remove secretions. Active mild vibrations were applied first, and then suctioning was done. Suctioning was performed after the use of active gentle vibrations.

Positioning ( Table 3)

Positioning. <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup> <sup>,</sup> <sup> <xref ref-type="bibr" rid="ref12">12</xref> </sup>
Treatment Descriprtion Intensity
Swaddling Positing Swaddling is a traditional practice of wrapping infants snugly in a blanket or cloth to restrict their movement. It is often done to help babies sleep better and feel more secure. However, it's important to note that swaddling should be done safely to avoid potential risks. Here are some general guidelines on the swaddling position: Back Position Loose at the Hips: Hands Up or Hands-to-Face Flexed Legs. 3 hours per day
Hammock handling The approach known as "hammock positioning," which is thought to be easy and inexpensive, entails placing the PTNB (Premature new born) in a rectangular-shaped hammock that is secured at the ends of the incubators and is usually made of fabric. This approach's therapeutic position minimizes postural irregularities and asymmetries linked to preterm and NICU stay while theoretically simulating the intrauterine environment. It also promotes relaxation and the development of spontaneous and functional motor abilities. 3 hours per day

Tactile and Kinesthetic stimulation ( Table 4)

APGAR: The APGAR score was created in 1952 by Columbia University anaesthesiologist Dr. Virginia Apgar. Coincidentally, APGAR serves as a helpful acronym to represent the elements of the score: appearance, respiration, activity, pulse, and grimace. Neonatal can be quickly assessed using the score both at the time of delivery and during resuscitation. The Apgar score is based on several factors, such as colour, breathing, muscular tone, heart rate, and reflexes. In order to detect hemodynamic compromise symptoms such cyanosis, hypoperfusion, bradycardia, hypotonia, respiratory depression, or apnoea, Apgar score is used. Each component receives a score of either 1 or 2. All new-borns have their scores recorded at one minute and five minutes, with extended recordings made at five-minute intervals for those who score seven or lower at that point. In people who need resuscitation as a way to track their reaction. 7 to 10 is considered a reassuring score. 13

ABG Analysis: Arterial blood gas (ABG) analysis is a crucial tool for assessing a newborn’s respiratory and metabolic status, especially if they are in the NICU. An ABG assay provides information on acid-base balance, ventilation, oxygenation, and electrolyte status. The specific physiology and normal values for this particular group must be taken into consideration when interpreting the results of the newborn ABG.

Tactile and kinesthetic stimulation [T].
Treatment Descriprtion Intensity
Tactile stimulation For tactile stimulation, the neonate was stroked with moderate pressure, a procedure that required the use of both hands. While getting tactile stimulation, the newborn was placed in the prone (face-down) position. Each stimulation session involved a 10-minute duration of gentle Stimulation sessions were conducted twice daily, with a minimum interval of 30 minutes after feeding and at least 2 hours after the preceding session.
Kinaesthetic stimulation Kinesthetic stimulation was applied to the infant's hip, knee, ankle, shoulder, elbow, and wrist through passive movements. During this phase, the infant was placed face-up in a crib or on the parent's lap. Each stimulation session involved a 10-minute duration of gentle Stimulation sessions were conducted twice daily, with a minimum interval of 30 minutes after feeding and at least 2 hours after the preceding session.

Secondary outcome measure:

Silverman-Anderson Respiratory Severity Score (RSS): Silverman-Anderson Respiratory Severity Score (RSS): The Silverman-Anderson Respiratory Severity Score (RSS), created by doctors Sidney Silverman and Stuart L. Anderson, is a clinical instrument used to evaluate the level of respiratory distress in neonates, especially those with respiratory distress syndrome (RDS). This tool, which is frequently used in neonatal intensive care units (NICUs), helps medical personnel determine whether a patient needs breathing support or interventions by helping them measure the patient’s level of respiratory distress 14 , 15

IICC: 62.5% sensitivity, 61.9% specificity, 24.7% PPV, 89.2% NPV, and an overall diagnostic accuracy of 61.9%.

Ballard Score: A clinical method for estimating a new-born’s gestational age, the Ballard Score is also referred to as the Ballard Maturational Assessment. This scoring system was created in 1979 by Dr. Jeanne L. Ballard to assist medical professionals in assessing a variety of physical and developmental features in order to determine the level of physical and neuromuscular maturation. 16

Sample size

Formula using mean difference n 1 = n 2 = 2 ( Z α + Z β ) 2 σ 2 ( δ ) 2 Z α = 1.96 α = Type I error at 5% at both sides two tailed Z β = 0.84 = Power at 80%

Primary variable:- Arterial Blood gas (ABG) PCO 2 (The partial pressure of carbon dioxide) Where,

Mean ± Sd value of Arterial PCO 2 in neonates for intubated groups (Experimental) = 61.9 ± 17.7.

Mean ± Sd value of Arterial PCO 2 in neonates for non-intubated groups (Control) = 52.3 ± 11.5.

Mean difference = 61.9-52.3 = 9.6. (As per ref. article)

Pooled Standard deviation σ = (17.7+11.5)/2 =14.6

Minimum sample size required; Sample size N = n 1 = n 2 = 2 ( 1.96 + 0.84 ) 2 ( 14.6 ) 2 ( 9.6 ) 2 = 36 per group

Considering 10% drop out = 4

Thus Total sample size required = 36 + 4 = 40 per group.

Ref art. Hedstrom AB, Gove NE, Mayock DE, Batra M. Performance of the Silverman Andersen Respiratory Severity Score in predicting PCO 2 and respiratory support in newborns: a prospective cohort study. J Perinatol. 2018 May;38(5):505-511. doi: 10.1038/s41372-018-0049-3. Epub 2018 Feb 9. PMID: 29426853; PMCID: PMC5998375 11

METHODS: DATA COLLECTION, MANAGEMENT, AND ANALYSIS

ALLOCATION

SEQUENCE GENERATION: Computer-generated random numbers will be used for the study.

ALLOCATION CONCEALMENT MECHANISM: Simple random Sampling-Computer generated random numbers will be used for the randomization of the study subjects.

IMPLEMENTATION: The random number sequence will be generated by a blinded person from a non-healthcare background. Enrolment and assignment of participants to the interventions will be done by the Principal Investigator of the study.

BLINDING: The trial participants will be blinded to the intervention.

METHODS: DATA COLLECTION, MANAGEMENT, AND ANALYSIS

DATA COLLECTION METHODS: The assessment and collection of outcomes will be done in the preintervention stage after assigning them to the intervention groups. Post-intervention data will be collected on the same day. This will be followed by the collection of post-intervention data after the completion of 4 weeks of intervention.

DATA MANAGEMENT: The collected information will be summarized by using frequency percentage for qualitative data and mean and standard deviation for quantitative data.

STATISTICAL METHODS: The demographic data (Gender) will be analysed using descriptive statistics. Descriptive statistics including mean, standard deviation, n (%), chi square test and independent t-test were used to check the homogeneity of the descriptive statistics. Inferential statistics between two groups comparison will be analysed by using unpaired t-test then with group comparison were analysed by using t-test and by software SPSS version 21.0. The p-value less than 0.05 considered significant for the study.

METHODS: MONITORING

DATA MONITORING : The data will be monitored by the Data Monitoring Committee of Ravi Nair Physiotherapy College.

HARMS:

Any episode of the adverse events shall be reported to the Ethical Committee and the clinician in charge for assessing and managing the solicited and spontaneous adverse events and other unintended effects of trial interventions or trial conduct.

 Ethics and dissemination

RESEARCH ETHICS APPROVAL:

The study has been presented in the IEC and got approval from Datta Meghe Institute of Higher Education and research (DU), Sawangi (Meghe), Wardha, on 30th January 2024 with Ref No. DMIHER/IEC/2024/65.

CONSENT AND ASSENT: All neonates before giving the intervention, the informed assent and consent will be taken from the parents.

CONFIDENTIALITY: Any information pertaining to the subjects participating in the study shall be maintained confidential. Any patient-related information will only be used with due permission from the subjects.

DECLARATION OF INTERESTS: There are no financial or competing interests to mention.

ACCESS TO DATA : All the data collected during or after the study shall be stored and maintained by the study’s Principal Investigator. The PI will have access to the final trial dataset, and it will be shared with de-identification after receiving a formal request for research and publication purposes only.

ANCILLARY AND POST-TRIAL CARE: Care shall be provided to the study subjects in case of events leading to harm from trial participation by the PI in accordance with the policy of Ravi Nair Physiotherapy College and DMIHER.

DISSEMINATION POLICY: Any data collected during or after the study will only be used for academic and research-related purposes culminating in a publication in a reputed journal.

Participant timeline

Data will be collected on the baseline as pre and post-data, followed by intervention for 4 weeks and post-intervention data on the last day of the 4 th week is again recorded.

 Discussion

The proposed study has significant implications for neonatal care by exploring the potential benefits of physical rehabilitation, specifically the PROMPT protocol, in managing neonatal respiratory distress syndrome (NRDS). If the results demonstrate positive effects on respiratory and neuromuscular function, it could lead to the development of new therapeutic interventions to improve outcomes for neonates with NRDS. Additionally, the study may contribute to the growing body of evidence supporting the role of physical rehabilitation in neonatal care, potentially influencing clinical practice guidelines and standards of care. NRDS is a common and life-threatening condition in neonates, often requiring intensive medical management. Investigating non-pharmacological interventions like physical rehabilitation is clinically relevant, especially considering the potential long-term respiratory and neurodevelopmental consequences of NRDS. Addressing respiratory and neuromuscular function early in neonates with NRDS may lead to improved short- and long-term outcomes, including reduced respiratory complications, shorter hospital stays, and improved neurodevelopmental outcomes.

The PROMPT protocol focuses on enhancing motor function and coordination through tactile-kinesthetic stimulation, potentially promoting the development of respiratory and neuromuscular control in neonates with NRDS. By incorporating gentle, hands-on techniques, the PROMPT protocol may facilitate respiratory muscle activation, improve chest wall compliance, and enhance overall respiratory mechanics in neonates with NRDS. Successful completion of this trial may warrant further research to optimize the implementation of physical rehabilitation interventions in neonatal care settings. Future studies could explore the feasibility and efficacy of integrating the PROMPT protocol into multidisciplinary neonatal care protocols or early intervention programs for infants at risk of respiratory and neuromuscular dysfunction. In conclusion, the proposed randomized controlled trial investigating the effect of physical rehabilitation with the PROMPT protocol on respiratory and neuromuscular function in neonates with NRDS holds promise for improving clinical outcomes and advancing our understanding of non-pharmacological interventions in neonatal care. Addressing the study’s implications, clinical relevance, potential mechanisms of action, limitations, and future directions is essential for informing researchers, clinicians, and policymakers about the potential benefits and challenges associated with this innovative approach.

Ethical approval and consent

The study has been presented in the IEC and got approval from Datta Meghe Institute of Higher Education and research (DU), Sawangi (Meghe), Wardha, on 30th January 2024 with Ref No. DMIHER/IEC/2024/65.

CONSENT AND ASSENT: All neonates before giving the intervention, the informed assent and consent will be taken from the parents

 Data availability Underlying data

No data are associated with this article.

 Extended data

Figshare: Completed_SPIRIT_checklist for Effect of Physical Rehabilitation using Oro Motor Stimulation, Manual Airway Clearance Technique, Positioning, Tactile and Kinesthetic Stimulation (PROMPT) protocol on Respiratory and Neuromuscular Function in Neonatal Respiratory Distress Syndrome (NRDS) - A Protocol for Randomized Controlled.pdf, https://doi.org/10.6084/m9.figshare.25744512.v1. 17

Data are available under the terms of the Creative Commons Attribution license (CC BY 4.0).

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Competing interests: No competing interests were disclosed.

 23 9 2024 Copyright: © 2024 Cornejo R 2024 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve-with-reservations

Thank you for the opportunity to review the manuscript by Hullumani and coworkers "Effect of physical rehabilitation using oromotor stimulation, manual airway clearance technique, positioning, tactile and kinaesthetic stimulation (PROMPT) protocol on respiratory and neuromuscular function in neonatal respiratory distress syndrome (NRDS)- a protocol for randomized controlled trial.

This is an interesting topic, with empirical evidence of potential clinical impact and scientific productivity, supporting the development of clinical studies such as the one proposed. Unfortunately, The manuscript has several important areas that could benefit from further attention and improvement.

The introduction is unfocused on the core elements of the study. There is little discussion of the concepts, evidence, and background supporting the underlying hypothesis (the connection between the intervention and the expected outcomes is lacking). Instead, it addresses pathophysiological concepts or mechanisms of NRDS that will not be explored in the study.

Additionally, there are several Styling issues, including the repetition of ideas and even acronyms representing different entities (such as NRDS, which is presented as both Non-Respiratory Distress Syndrome and Neonatal Respiratory Distress Syndrome).

The discussion of the PROMPT strategy's utility and safety could be enhanced, as this information is crucial given the population involved in the intervention.

The structure of the methods section follows more of a thesis format than that of a manuscript, including explanations and details (for example, regarding the evaluations) that any reader within the disciplinary area would already be familiar with.

Numerous outcomes are introduced without specifying their relevance or which are primary and which are secondary.

The third objective is redundant.

The inclusion criteria should be more precise and straightforward (for example, requiring a diagnosis of NRDS and a specific level of the Silverman-Anderson Respiratory Severity Score (RSS) or another criterion that is precise and easy to reproduce) to enhance the external validity of the study.

Is there a validated weaning protocol available? Considering this is a relevant outcome, it is problematic that it relies solely on the subjective evaluation of the attending physician.

Are the evaluators of the various dimensions/outcomes blinded to the interventions?

It appears that some references have been inadvertently included in the main text.

The sample size estimation should be reevaluated. It is not clear whether a change in PaCO2 will help answer the hypothesis.

Is the study design appropriate for the research question?

Partly

Is the rationale for, and objectives of, the study clearly described?

Partly

Are sufficient details of the methods provided to allow replication by others?

Partly

Are the datasets clearly presented in a useable and accessible format?

Partly

Reviewer Expertise:

Intensive Care Medicine

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Hullumani V Dr. Sharath

Competing interests: None

 12 1 2025

Thank you for your detailed feedback. Below is our response to each point raised:

Introduction's focus:

We acknowledge that the introduction may have diverged from the core elements of the study. We will revise it to emphasize the concepts, evidence, and background directly supporting the hypothesis, focusing on the connection between the intervention and the expected outcomes. Pathophysiological concepts or mechanisms not directly explored in the study will be minimized or removed to streamline the narrative.

Styling issues:

The repetition of ideas and inconsistent use of acronyms has been noted. We will ensure that each acronym, such as NRDS, is consistently defined (Neonatal Respiratory Distress Syndrome) and used throughout the text. Repetitive sections will be edited to improve readability and coherence.

Discussion of the PROMPT strategy:

We agree that the discussion of the PROMPT strategy's utility and safety should be expanded, given the vulnerable population involved. Additional evidence and context will be incorporated to provide a more comprehensive evaluation of these aspects.

Methods section structure:

We will revise the methods section to align with a standard manuscript format, removing details that are overly explanatory for the target audience. Key information will remain to ensure clarity, but redundant or assumed knowledge will be condensed.

Outcomes relevance and prioritization:

We will clearly identify the primary and secondary outcomes and elaborate on their relevance to the study objectives. This will ensure a focused and structured presentation of the study's goals and findings.

Third objective redundancy:

The third objective will be reviewed and potentially revised or removed if deemed redundant. We will consolidate it with other objectives where appropriate to avoid repetition.

Inclusion criteria precision:

The inclusion criteria will be revised to enhance specificity and reproducibility. For example, we will incorporate a precise diagnosis of NRDS and include a quantifiable criterion like the Silverman-Anderson Respiratory Severity Score or a similar validated measure.

Validated weaning protocol:

We recognize the need for a validated weaning protocol, especially given its relevance as an outcome. If an existing protocol is available, it will be incorporated. If not, we will outline plans to address this gap while acknowledging its limitations in the study.

Blinding of evaluators:

Blinding of evaluators is critical to ensure unbiased outcome assessments. We will clarify in the manuscript whether the evaluators are blinded to the interventions. If blinding was not implemented, we will discuss its implications as a limitation and provide a rationale