The influence of chorioamnionitis on respiratory drive and spontaneous breathing of premature infants at birth: a narrative review.

Most very premature infants breathe at birth but require respiratory support in order to stimulate and support their breathing. A significant proportion of premature infants are affected by chorioamnionitis, defined as an umbrella term for antenatal inflammation of the foetal membranes and umbilical vessels. Chorioamnionitis produces inflammatory mediators that potentially depress the respiratory drive generated in the brainstem. Such respiratory depression could maintain itself by delaying lung aeration, hampering respiratory support at birth and putting infants at risk of hypoxic injury. This inflammatory-mediated respiratory depression may contribute to an association between chorioamnionitis and increased requirement of neonatal resuscitation in premature infants at birth. This narrative review summarises mechanisms on how respiratory drive and spontaneous breathing could be influenced by chorioamnionitis and provides possible interventions to stimulate spontaneous breathing.  Conclusion: Chorioamnionitis could possibly depress respiratory drive and spontaneous breathing in premature infants at birth. Interventions to stimulate spontaneous breathing could therefore be valuable. What is Known: • A large proportion of premature infants are affected by chorioamnionitis, antenatal inflammation of the foetal membranes and umbilical vessels. What is New: • Premature infants affected by chorioamnionitis might be exposed to higher concentrations of respiratory drive inhibitors which could depress breathing at birth. • Premature infants affected by chorioamnionitis seem to be associated with a higher and more extensive requirement of resuscitation at birth.

Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial.

BACKGROUND: Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy. OBJECTIVES: To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant. METHODS: We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27+0 and 34+6 weeks' gestation, presenting respiratory distress after birth. EXCLUSION CRITERIA: endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH2O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results. RESULTS: We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH2O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH2O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH2O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support. CONCLUSION: Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.

Ventilación en posición prona en el manejo de pacientes con síndrome de dificultad respiratoria aguda / Prone ventilation in the management of patients with acute respiratory distress syndrome

INTRODUCCIÓN. El posicionamiento prono es una de las estrategias ventilatorias más estudiadas y difundidas de la medicina intensiva, forma parte del manejo de ventilación protectiva con impacto en disminución de la mortalidad en pacientes con síndrome de dificultad respiratoria aguda. OBJETIVO. Revisar la evidencia disponible acerca de ventilación en posición prona en pacientes con síndrome de dificultad respiratoria aguda, enfocada en el análisis fisiopatológico y clínico. MATERIALES Y MÉTODOS. Se realizó una revisión bibliográfica en la base de datos de buscadores académicos como PubMed, Google Scholar y Elsevier, en los idiomas español e inglés, en el período comprendido entre los años 1970-2020; se seleccionaron 16 publicaciones en texto completo: 3 metaanálisis, 10 estudios randomizado, 3 revisiones sistemáticas. CONCLUSIÓN. En base a la evidencia y percepción recopilada de la experiencia de los autores, la ventilación en posición prona es una estrategia de manejo de primera línea, fiable, que no requiere para su empleo equipamiento costoso ni complejo y ha demostrado mejoría en desenlaces relevantes en el tratamiento del paciente crítico respiratorio como disminución en la mortalidad y optimización de los parámetros ventilatorios y de oxigenación.

INTRODUCTION. Prone positioning is one of the most studied and widespread ventilatory strategies in intensive medicine, it is part of protective ventilation management with an impact on mortality reduction in patients with acute respiratory distress syndrome. OBJECTIVE. To review the available evidence about ventilation in the prone position in patients with acute respiratory distress syndrome, focused on the pathophysiological and clinical analysis. MATERIALS AND METHODS. A bibliographic review was carried out in the databases of academic search engines such as PubMed, Google Scholar and Elsevier, in the Spanish and English languages, in the period between the years 1970-2020, 16 full text publications were selected: 3 meta-analyses, 10 randomized studies, 3 systematic reviews. CONCLUSION. Based on the evidence and perception gathered from the authors' experience, prone ventilation is a reliable first-line management strategy that does not require costly or complex equipment for its use and has demonstrated improvements in relevant outcomes in the treatment of the critically ill respiratory patient, such as decreased mortality and optimization of ventilatory and oxygenation parameters.

Models for IGHMBP2-associated diseases: an overview and a roadmap for the future.

Models are practical tools with which to establish the basic aspects of a diseases. They allow systematic research into the significance of mutations, of cellular and molecular pathomechanisms, of therapeutic options and of functions of diseases associated proteins. Thus, disease models are an integral part of the study of enigmatic proteins such as immunoglobulin mu-binding protein 2 (IGHMBP2). IGHMBP2 has been well defined as a helicase, however there is little known about its role in cellular processes. Notably, it is unclear why changes in such an abundant protein lead to specific neuronal disorders including spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth type 2S (CMT2S). SMARD1 is caused by a loss of motor neurons in the spinal cord that results in muscle atrophy and is accompanied by rapid respiratory failure. In contrast, CMT2S manifests as a severe neuropathy, but typically without critical breathing problems. Here, we present the clinical manifestation of IGHMBP2 mutations, function of protein and models that may be used for the study of IGHMBP2-associated disorders. We highlight the strengths and weaknesses of specific models and discuss the orthologs of IGHMBP2 that are found in different systems with regard to their similarity to human IGHMBP2.

Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks.

OBJECTIVE: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. MATERIALS AND METHODS: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. RESULTS: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. CONCLUSION: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age.

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.

OBJECTIVE: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. STUDY DESIGN: EPT infants (240/7-276/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. RESULTS: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score <85 at 18-22 months corrected age (P = .002). CONCLUSIONS: EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation.

Hemodynamic effects of high frequency oscillatory ventilation with volume guarantee in a piglet model of respiratory distress syndrome.

Respiratory failure is a common condition faced by critically ill neonates with respiratory distress syndrome (RDS). High frequency oscillatory ventilation (HFOV) is often used for neonates with refractory respiratory failure related to RDS. Volume guarantee (VG) mode has been added to some HFOV ventilators for providing consistent tidal volume. We sought to examine the impact of adding the VG mode during HFOV on systemic and cerebral hemodynamics, which has not been studied to date. A neonatal piglet model of moderate to severe RDS was induced by saline lavage. Piglets (full term, age 1-3 days, weight 1.5-2.4 kg) were randomized to have RDS induced and receive either HFOV or HFOV+VG (n = 8/group) or sham-operation (n = 6) without RDS. Cardiac function measured by a Millar® catheter placed in the left ventricle as well as systemic and carotid hemodynamic and oxygen tissue saturation parameters were collected over 240 min of ventilation. Mean airway pressure, alveolar-arterial oxygen difference and left ventricular cardiac index of piglets on HFOV vs. HFOV+VG were not significantly different during the experimental period. Right common carotid artery flow index by in-situ ultrasonic flow measurement and cerebral tissue oxygen saturation (near-infrared spectroscopy) significantly decreased in HFOV+VG at 240 min compared to HFOV (14 vs. 31 ml/kg/min, and 30% vs. 43%, respectively; p<0.05). There were no significant differences in lung, brain and heart tissue markers of oxidative stress, ischemia and inflammation. HFOV+VG compared to HFOV was associated with similar left ventricular function, however HFOV+VG had a negative effect on cerebral blood flow and oxygenation.

Glucocorticoids, sodium transport mediators, and respiratory distress syndrome in preterm infants.

BACKGROUND: Antenatal glucocorticoids (GCs) reduce respiratory distress syndrome (RDS) in preterm infants and are associated with reduced lung liquid content. Our aim was to assess whether airway gene expression of mediators of pulmonary epithelial sodium and liquid absorption, and further, respiratory morbidity, associate with cord blood GC concentrations. METHODS: The study included 64 infants delivered <32 weeks gestation. Cortisol and betamethasone in umbilical cord blood were quantified with liquid chromatography-tandem mass spectrometry. The total GC concentration was calculated. Gene expression of the epithelial sodium channel (ENaC), Na,K-ATPase, and serum- and GC-inducible kinase 1 at <2 h and at 1 day postnatally in nasal epithelial cell samples was quantified with reverse transcription-polymerase chain reaction. The mean oxygen supplementation during the first 72 h was calculated. RESULTS: Concentrations of cord blood betamethasone and total GC were significantly lower in infants with RDS and correlated with mean oxygen supplementation. Expression of αENaC and α1- and ß1Na,K-ATPase at <2 h correlated with betamethasone and total GC concentrations. Expression of Na,K-ATPase was lower in infants with RDS. CONCLUSION: Enhancement of lung liquid absorption via increased expression of sodium transporters may contribute to the beneficial pulmonary effects of antenatal GCs. IMPACT: RDS is related to lower umbilical cord blood GC concentrations and lower airway expression of sodium transporters. In addition to the timing of antenatal GC treatment, resulting concentrations may be of importance in preventing RDS. Induction of sodium transport may be a factor contributing to the pulmonary response to antenatal GCs.

Blood urea in preterm infants on routine parenteral nutrition: A multiple linear regression analysis.

BACKGROUND: Blood urea is considered a marker of amino acid utilization in preterm infants on routine parenteral nutrition. However, the association between blood urea and intravenous amino acid intake remains debated. AIMS: To evaluate the association between blood urea and both nutrition and clinical data, in a large cohort of preterm infants. METHODS: Consecutively admitted preterm infants with a gestational age of less than 32 weeks and a birth weight lower than 1250 g on routine parenteral nutrition from the first hour of life were studied. Clinical and nutrition data collected hourly during the hospitalization were used in multiple linear regression analysis. RESULTS: We studied 674 patients and 1863 blood urea determinations. Blood urea concentration was positively associated with blood creatinine concentration, intravenous amino acid intake, patent ductus arteriosus and respiratory distress syndrome, and negatively associated with intravenous non-protein energy intakes, daily weight change, gestational age, being small for gestational age, antenatal steroids therapy and reverse flow in the umbilical artery (p < 0.001; R = 0.7). CONCLUSIONS: From a nutrition perspective, in our large cohort of small preterm infants blood urea was positively correlated with intravenous amino acid intake and negatively correlated with intravenous non-protein energy intake. This is in line with current knowledge in human physiology and suggest that a reduction of intravenous amino acid intake based on blood urea concentrations was justified.

Prone versus Supine Position for Lung Ultrasound in Neonates with Respiratory Distress.

OBJECTIVE: To study the feasibility of lung ultrasound (LUS) in prone position and to compare it with supine position in neonates with respiratory distress. STUDY DESIGN: Neonates ≥ 29 weeks of gestational age with respiratory distress requiring respiratory support within first 12 hours of life were enrolled prospectively. First LUS (fLUS) was done in the position infant was nursed (supine or prone), infant's position changed, a second LUS (sLUS) was performed immediately and a third LUS (tLUS) was done 1 to 2 hours later. Primary outcome was the comparison of LUS scores (LUSsc) between fLUS and sLUS. RESULTS: Sixty-four neonates were enrolled. Common respiratory diagnoses were transient tachypnea of newborn (TTN; 53%) and respiratory distress syndrome (RDS; 41%). LUSsc was different between fLUS and sLUS (fLUSsc 6 [interquatile range: 4, 7] vs. sLUSsc 7 [4, 10], p < 0.001), while there was no difference between the fLUS and tLUS (fLUSsc 6 [4, 7] vs. tLUSsc 5 [3, 7], p = 0.43). Subgroup analysis confirmed similar findings in neonates with TTN, while in babies with RDS, all the three LUSsc were similar. CONCLUSION: LUS is feasible in prone position in neonates. LUS scores were higher immediately after a change in position but were similar to baseline 1 hour after the change in position.

Combined Genome Sequencing and RNA Analysis Reveals and Characterizes a Deep Intronic Variant in IGHMBP2 in a Patient With Spinal Muscular Atrophy With Respiratory Distress Type 1.

BACKGROUND: Pathogenic variants in the IGHMBP2 gene cause recessive spinal motor neuropathies of variable phenotype, including a predominantly distal motor impairment of Charcot-Marie-Tooth type 2S and the more severe condition of spinal muscular atrophy with respiratory distress type 1 in which infantile respiratory failure predominates. METHODS: We describe the first reported case of spinal muscular atrophy with respiratory distress type 1 caused by a novel deep intronic variant in IGHMBP2 (NM_002180c.712-610A>G). RESULTS: The variant was detected by whole genome sequencing. Reverse transcription-polymerase chain reaction and complimentary DNA sequencing were used to characterize the impact of the novel variant. CONCLUSIONS: This report illustrates the utility in clinical practice of genome sequencing and RNA analysis, compared with exome sequencing alone.

Respuesta inmune disfuncional en pacientes con COVID-19. ¿Qué nos dice la evidencia? / Dysfunctional immune response in COVID-19 patients. What does the evidence tell us?

In December 2019 a novel coronavirus (SARS-CoV-2) was identified in Wuhan, China, and became rapidly the worst pandemic in 100 years. Coronaviruses are respiratory viruses that can cause diseases ranging from mild to fatal lower respiratory tract infections. In a fraction of the affected patients, coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, can lead to acute respiratory distress syndrome (ARDS) and intensive care unit (ICU) admission, both associated with high mortality. To date, the existing evidence suggests a leading role of the immune system in the pathogenesis of severe COVID-19, including mechanisms associated with hyperinflammation, immune evasion, cytokine release syndrome, depletion of functional T cells, and ineffective humoral immunity. Here we discuss the current evidence regarding these findings.

Implementing bubble continuous positive airway pressure in a lower middle-income country: a Nigerian experience.

Bubble CPAP (bCPAP) is used for respiratory distress (RD) in neonates. The leading causes of neonatal mortality can lead to severe RD. Many neonatal deaths are preventable using evidence-based interventions like bCPAP as part of a comprehensive approach. The study aimed to assess the implementation of a multi-center, comprehensive hospital-based bCPAP program in a low-middle-income country using a low-cost bCPAP device. Seven established hospitals in three Nigerian States were selected using purposive sampling. A respiratory support program was developed and implemented using the Pumani® bCPAP. Neonates <28 days old with severe RD, birth weight >1000g and breathing spontaneously, were eligible. The program lasted 22 months. Focus group discussions and in-depth interviews of healthcare workers and hospital administrators were used in program assessment. Content analysis of qualitative data completed. The staff reported that the bCPAP device was easy to use and effective. All staff reported comfort in eligible patient identification, effective set up and bCPAP administration. All study sites experienced varying degrees of electric power interruption and oxygen availability and affordability. Staff training, staffing disruptions, data collection challenges and use of improvised bCPAP contributed to low enrollment. Advocacy, direct program support, and innovation using locally available resources improved enrollment. Professional organization collaboration, competency-based training and peer mentoring contributed to program success. Thorough pre-program assessment, with comprehensive understanding of all aspects of the existing system within the local context which are likely to impact the introduction of a new program is important to implementation success.

The effectiveness of the neonatal diagnosis-related group scheme.

The goal of this study is to investigate the effectiveness of the neonatal diagnosis-related group scheme in patients affected by respiratory distress syndrome. The variable costs of individual patients in the same group are examined. This study uses the data of infants (N = 243) hospitalized in the Neonatal Intensive Care Unit of the Gaslini Children's Hospital in Italy in 2016. The care unit's operating and management costs are employed to estimate the average cost per patient. Operating costs include those related to personnel, drugs, medical supplies, treatment tools, examinations, radiology, and laboratory services. Management costs relate to administration, maintenance, and depreciation cost of medical equipment. Cluster analysis and Tobit regression are employed, allowing for the assessment of the total cost per patient per day taking into account the main cost determinants: birth weight, gestational age, and discharge status. The findings highlight great variability in the costs for patients in the same diagnosis-related group, ranging from a minimum of €267 to a maximum of €265,669. This suggests the inefficiency of the diagnosis-related group system. Patients with very low birth weight incurred costs approximately twice the reimbursement set by the policy; a loss of €36,420 is estimated for every surviving baby with a birth weight lower than 1,170 grams. On the contrary, at term, newborns cost about €20,000 less than the diagnosis-related group reimbursement. The actual system benefits hospitals that mainly treat term infants with respiratory distress syndrome and penalizes hospitals taking care of very low birth weight patients. As a result, strategic behavior and "up-coding" might occur. We conduct a cluster analysis that suggests a birth weight adjustment to determine new fees that would be fairer than the current costs.

Antenatal corticosteriods decrease forced vital capacity in infants born fullterm.

Antenatal corticosteroids (ACS) administration to pregnant women for threatened preterm labor is standard obstetric care to reduce neonatal respiratory distress syndrome and the associated respiratory morbidity. While ACS stimulates surfactant production in the fetal lung, the effects of ACS upon the subsequent growth and development of the lung are unclear. Follow-up studies outside of the neonatal period have been primarily limited to spirometry, and most subjects evaluated were born prematurely. To our knowledge, no study has assessed both airway and parenchymal function in infants or adults following ACS exposure. We hypothesized that ACS impairs lung growth and performed infant pulmonary function testing, which included spirometry, alveolar volume (VA ) and lung diffusion (DL ). As a pilot study, we limited our assessment to infants whose mothers received ACS for threatened preterm labor, but then proceeded to full term delivery. This approach evaluated a more homogenous population and eliminated the confounding effects of preterm birth. We evaluated 36 full-term infants between 4 to 12 months of age; 17 infants had ACS exposure and 19 infants had no ACS exposure. Infants exposed to ACS had a significantly lower forced vital capacity compared with non-ACS exposed infants (250 vs 313 mL; P = .0075). FEV0.5 tended to be lower for the ACS exposed group (205 vs 237 mL; P = .075). VA and DL did not differ between the two groups. These findings suggest that ACS may impair subsequent growth of the lung parenchyma.

Cerebral Autoregulation in Sick Infants: Current Insights.

Cerebrovascular autoregulation is the ability to maintain stable cerebral blood flow within a range of cerebral perfusion pressures. When cerebral perfusion pressure is outside the limits of effective autoregulation, the brain is subjected to hypoperfusion or hyperperfusion, which may cause vascular injury, hemorrhage, and/or hypoxic white matter injury. Infants born preterm, after fetal growth restriction, with congenital heart disease, or with hypoxic-ischemic encephalopathy are susceptible to a failure of cerebral autoregulation. Bedside assessment of cerebrovascular autoregulation would offer the opportunity to prevent brain injury. Clinicians need to know which patient populations and circumstances are associated with impaired/absent cerebral autoregulation.

Updates on Management for Acute and Chronic Phenotypes of Neonatal Pulmonary Hypertension.

Neonatal pulmonary hypertension is a heterogeneous disease in term and preterm neonates. It is characterized by persistent increase of pulmonary artery pressures after birth (acute) or an increase in pulmonary artery pressures after approximately 4 weeks of age (chronic); both phenotypes result in exposure of the right ventricle to sustained high afterload. In-depth clinical assessment plus echocardiographic measures evaluating pulmonary blood flow, pulmonary vascular resistance, pulmonary capillary wedge pressure, and myocardial contractility are needed to determine the cause and provide individualized targeted therapies. This article summarizes the causes, risk factors, hemodynamic assessment, and management of neonatal pulmonary hypertension.

Less invasive surfactant administration versus endotracheal surfactant instillation followed by limited peak pressure ventilation in preterm infants with respiratory distress syndrome in China: study protocol for a randomized controlled trial.

BACKGROUND: Less invasive surfactant administration (LISA) is a way of giving surfactant without endotracheal intubation and has shown to be promising in reducing the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, the mechanism underlying its beneficial effect and variations in the technique of administration may prevent its widespread use. This trial aims to evaluate the effects of two methods of surfactant administration, LISA or endotracheal surfactant administration followed by low peak pressure (LPPSA) ventilation, in preterm infants with respiratory distress syndrome (RDS). METHODS: The LISA Or Low Peak Pressure trial is to be conducted in 14 tertiary neonatal intensive care units in China. A total of 600 preterm infants born with gestational age between 250/7 and 316/7 weeks and with a primary diagnosis of RDS will be involved in the study. Infants will be randomized to the LISA or LPPSA group when surfactant therapy is indicated. Primary outcomes include mortality, severity of bronchopulmonary dysplasia at 36 weeks of postmenstrual age (PMA), and mechanical ventilation (MV) in the first 72 h of life. Secondary outcomes include the days of MV, duration of all sorts of non-invasive respiratory support, fraction of inspired oxygen, oxygen saturation before and after surfactant administration, and time required to perform the procedure for surfactant administration. The incidence of comorbidities, including retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), hemodynamically significant patent ductus arteriosus (hsPDA), pneumothorax, and massive pulmonary hemorrhage within 48 h of surfactant administration, and the failure rates of each technique will be determined. DISCUSSION: Data from recent systematic review and meta-analysis have suggested a possible improvement in outcomes of preterm infants with RDS by the LISA technique. However, robust evidence is lacking. Why LISA plays a potential role in reducing respiratory morbidity, mainly BPD in preterm infants, remains unclear. The possible explanations are the active and uninterrupted delivery of continuous positive airway pressure during the LISA procedure and the avoidance of complications caused by intubation and relatively high pressure/volume ventilation following surfactant administration. We hypothesized that LISA's effectiveness lies mainly in avoiding relatively high-pressure positive ventilation immediately following surfactant administration. Thus, this multicenter randomized controlled trial will focus on issues of endotracheal intubation and the pressure/volume used during conventional surfactant administration. The effectiveness, safety and comorbidities of preterm infants following LISA or LPPSA will be evaluated. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900020970. Registered on 23 January 2019.