Comparison of efficacy between beractant and poractant-alfa in respiratory distress syndrome among preterm infants (28-33+6 weeks gestational age) using the less invasive surfactant administration (LISA) technique: A randomized controlled trial

Comparison of efficacy between beractant and poractant-alfa in respiratory distress syndrome among preterm infants (28-33+6 weeks gestational age) using the less invasive surfactant administration (LISA) technique: A randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparison of efficacy between beractant and poractant-alfa in respiratory distress syndrome among preterm infants (28-33+6 weeks gestational age) using the less invasive surfactant administration (LISA) technique: A randomized controlled trial Bijan saha, Ashadur Zamal, Md Habibullah Sk, Avijit Hazra This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3882168/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Apr, 2024 Read the published version in Journal of Perinatology → Version 1 posted 9 You are reading this latest preprint version Abstract Objective: Exogenous surfactant therapy is vital in managing respiratory distress syndrome (RDS) in preterm infants, with less invasive surfactant administration (LISA) gaining popularity. This study aimed to assess the efficacy and short-term outcomes of LISA using beractant and poractant alfa. Study Design: In a randomized controlled trial , we enrolled preterm infants (28-33 +6 weeks) with RDS requiring surfactant. LISA was employed, with beractant at 100 mg/kg or poractant-alfa at 200 mg/kg. Primary outcome was the need for intubation within 72 hours. Results: Among 120 infants, 3.3% in both groups required intubation within 72 hours (p value 1.00, 95% CI 0.14 - 6.86). No significant differences in secondary outcomes were noted, except a trend towards increased necrotizing enterocolitis with beractant . Beractant was significantly more economical. Conclusion: Beractant and poractant-alfa exhibit similar efficacy in LISA for preterm infants with RDS. Economic considerations, especially in LMICs, favour beractant. The trial is registered in the clinical trial registry of India (CTRI/2023/03/050375). Health sciences/Diseases/Respiratory tract diseases Health sciences/Signs and symptoms/Respiratory signs and symptoms Less invasive surfactant administration Poractant-alfa Beractant Respiratory distress syndrome Preterm infants Figures Figure 1 Figure 2 Introduction Exogenous surfactant therapy has been a significant advance in the care of preterm infants with respiratory distress syndrome (RDS) and has now become an integral component of the standard approach in managing these infants( 1 ). The preferred method for administering surfactant is shifting towards less invasive surfactant administration (LISA), which avoids both endotracheal intubation and positive pressure ventilation( 1 , 2 ).LISA has been associated with a reduced need for mechanical ventilation in the initial 72 hours, lower rates of death or bronchopulmonary dysplasia (BPD), a decreased occurrence of major complications, and a decline in in-hospital mortality( 3 ).While LISA is increasingly becoming a standardized method for surfactant administration, there is considerable variability in the technique. This includes uncertainties regarding the impact of using different surfactants on outcomes in LISA. Two primary types of animal-derived surfactants are commonly used: porcine-derived poractant-alfa (Curosurf—Chiesi Pharmaceuticals, Parma, Italy) and beractant derived from minced bovine lung (Survanta—Abbott Laboratories Inc., Columbus, OH, USA)( 4 ). Animal derived surfactants exhibit substantial variations in their compositions, including levels of phospholipids, surfactant proteins B and C, as well as differences in viscosity and volume. These variances have the potential to impact clinical outcomes. Beractant has a phospholipid concentration of 25 mg/mL. It is modified with dipalmitoylphosphatidylcholine, palmitic acid, and tripalmitin, and includes an unspecified amount of SP-B. The recommended dosage is 4 mL/kg birth weight (100 mg/kg)( 5 ). Poractant alfa boasts the highest phospholipid concentration at 80 mg/mL, with an SP-B content of 0.45 mg/mL. The recommended initial dose is 2.5 mL/kg birth weight (200 mg/kg) ( 6 ). As per the American Academy of Pediatrics, it remains uncertain whether notable differences in clinical outcomes exist among the available animal-derived products( 7 ). Recent research indicates that porcine minced lung extract, particularly in higher doses(200mg/kg), may exhibit greater efficacy compared to bovine surfactant in enhancing acute respiratory status and reducing mortality or BPD in infants with RDS( 8 ).European guidelines on the management of respiratory distress syndrome (RDS) prescribe a minimum surfactant dose of 100 mg/kg. Nevertheless, the guidelines advocate a superior efficacy of a high dose, specifically 200 mg/kg of poractant alfa, compared to a lower dose (100 mg/kg) of either poractant-alfa or beractant( 1 ). The statistical difference between the two surfactant types remains uncertain, whether it is linked to the source of extraction (porcine vs. bovine) or the higher initial dose of porcine surfactant. Until now, most trials and meta-analyses have compared beractant versus poractant-alfa using the intubation surfactant administration extubation (INSURE) technique( 9 , 10 ). While Poractant-α is widely used in the LISA technique, there is currently limited research comparing Beractant versus Poractant-α using this approach. The OPTIMIST-A trial utilized a dose of 200 mg/kg, while the NINSAPP trial employed poractant alfa surfactant at a dosage of at least 1.25 mL/kg of body weight (100 mg/kg), up to the entire vial content (1.5 mL containing 120 mg of surfactant)( 11 , 12 ). The cost of poractant-alfa is higher in comparison to beractant. Implementing LISA in low- and middle-income countries (LMICs) with poractant-alfa may encounter challenges related to its affordability. Given the known significant differences in composition and biochemical properties between beractant and poractant-alfa, our objective is to evaluate the efficacy and short-term outcomes of surfactant administration through the LISA method between these two. Materials And Methods Study design, settings and participants This randomized controlled trial was conducted in a level III neonatal intensive care unit (NICU) in a tertiary care hospital in India. The study consecutively enrolled preterm infants with a gestational age ranging from 28 to 33 + 6 weeks, from April 15, 2023, to October 31, 2023, who had RDS and required surfactant administration without the need for tracheal intubation in the delivery room. Infants were excluded if they had perinatal asphyxia (cord blood pH < 7.20), severe congenital malformations, or known chromosomal anomalies. Intervention Infants meeting the eligibility criteria, RDS and requiring non-invasive positive pressure ventilation (NIPPV) with FiO 2 ≥ 30% to maintain SpO 2 between 90–95% within the first 6 hours of life, were randomly assigned to receive surfactant via the LISA technique using either poractant alfa or beractant. The dosing regimen included poractant at 200mg/kg (2.5ml/kg) and beractant at 100mg/kg (4ml/kg). Throughout the study, we adhered to the following LISA procedure: Firstly, written informed consent was obtained from the infant's parents for their participation. Before initiating the LISA technique, the nasal interface and nasal mask were changed with a RAM cannula to deliver NIPPV. Subsequently, a direct laryngoscopy was performed using an appropriately sized blade, and a 5Fr infant feeding tube was inserted through the vocal cords to the desired depth without the assistance of Magill forceps. The insertion depth was determined by the formula [weight (kg) + 7] cm( 13 ). The procedure was conducted by two trained doctors, while a nurse documented the entire process. After the placement of the feeding tube, the laryngoscope was removed, and the required amount of surfactant was instilled into the trachea in small 1 mL aliquots over 1–3 minutes. For infants desaturating to ≤ 85% during LISA, FiO 2 was increased in increments of 5% to maintain SpO 2 within the target range of 90–95%. If an infant experienced apnea lasting more than 20 seconds, positive pressure ventilation was initiated following the NICU protocol. Following the procedure, aspiration through the infant feeding tube was performed to detect and quantify the degree of surfactant reflux in the stomach. The infants were closely monitored for episodes of desaturation, bradycardia, cough, surfactant reflux from the trachea, and vomiting. If the infant continued to require FiO 2 ≥ 30% after 6 hours of surfactant administration, a second dose of surfactant was given using the same technique. Subsequent to the LISA procedure, the nasal interface was switched back to the standard nasal mask and nasal tubing for delivering NIPPV . Outcomes Primary Outcome The primary outcome measure was the need for intubation within the initial 72 hours of life. Secondary Outcomes Complications occurring during the procedure (Surfactant reflux during the procedure, SpO2 < 85%, hypotension with mean below GA, bradycardia < 80 bpm) Need for the second dose of Surfactant Pulmonary haemorrhage Pulmonary air leak syndromes Hemodynamically significant patent ductus arteriosus(hsPDA)( 14 ) Grade 3 and grade 4 Intraventricularhaemorrhage ( 15 ) Retinopathy of prematurity requiring treatment( 16 ) Necrotizing enterocolitis ≥ Stage 2( 17 ) Bronchopulmonary dysplasia(BPD)( 18 ) Duration of respiratory support (invasive and non-invasive) and hospital stay Death before hospital discharge Sample size Using a recent study with a similar gestational age, the anticipated failure rate for poractant alfa therapy was 58.8%( 19 ). Assuming beractant could reduce the failure rate by at least 25% in absolute terms, a sample size of 62 subjects per group was calculated to detect a statistical difference with 80% power and a 5% probability of type 1 error. No margin was allotted for dropouts. MedCalc version 19.6 (MedCalc Software Ltd, Ostend, Belgium, 2020) was used for sample size calculation. Randomisation We employed computer-generated random numbers with variable block sizes to assign infants to the two groups. Stratification based on gestational age (28–31 + 6 weeks and 32–33 + 6 weeks) was conducted, and the allocation ratio was maintained at 1:1. Concealment was ensured by utilizing sequentially numbered opaque sealed envelopes. The randomization sequence was prepared by an investigator not involved in collecting baseline data, applying the intervention, or measuring outcomes. Due to the nature of the study, blinding was not feasible. Nevertheless, both data collection staff and trial analysts remained blinded. Statistical analysis Numerical variables with a normal distribution were presented as the mean and standard deviation, while skewed numerical variables were represented by the median and interquartile range. Categorical variables were expressed as counts and percentages. Continuous variables with a normal distribution underwent two-sample unpaired t-tests (Student’s t), and for skewed distributions, the Wilcoxon rank-sum test was applied. Chi-square analysis was employed to assess differences in categorical variables. The significance level for all tests was set at p < 0.05. Data analysis was conducted on an intention-to-treat basis. Statistica version 8 (Tulsa, Oklahoma: StatSoft Inc., 2007) was utilized for data analysis. Ethics The study adhered to ethical principles based on the Declaration of Helsinki and aligned with Good Clinical Practice. Approval was granted by the institutional ethics committee at the Institute of Post Graduate Medical Education and Research, Kolkata, India (IPGME&R/IEC/2023/412). All legal guardians provided written informed consent before participating. The trial is registered in the clinical trial registry of India (CTRI/2023/03/050375). Results Over the study duration, 148 infants were admitted with RDS. After excluding 18 infants, a total of 120 were then randomized into the two surfactant groups. The participant flow in the study is depicted in Fig. 1 . There was no statistical difference observed between the groups regarding the administration of antenatal steroids. Other baseline demographic variables between the two groups were deemed comparable (Table 1 ). Table 1 Baseline characteristics of infants (n = 120) Beractant (n = 60) Poractant-alfa (n = 60) p value Maternal age, years a 27.6 ± 4.12 27.7 ± 4.11 0.825 Conception Spontaneous b IVF b 52 (86.67%) 8 (13.33%) 54 (90.00%) 6 (10.00%) 0.777 Antenatal steroid Received (Any) b 41 (68.33%) 48 (80.00%) 0.210 Caesarean section delivery b 35 (58.33%) 31 (51.67%) 0.582 Gestational age , weeks a 30.8 ± 1.93 30.9 ± 2.20 0.860 Birth weight, grams a 1414.3 ± 328.61 1335.6 ± 340.38 0.200 Male gender b 38(63.33%) 33(55%) 0.458 Small for gestational age b 5(8.33%) 11(18.33%) 0.178 Umbilical cord pH c 7.3 (7.2, 7.3) 7.3 (7.2, 7.3) 0.749 Apgar score at 1 min c 7(6, 7) 7(6, 7) 0.979 Apgar score at 5 min c 8(8, 9) 8(8, 9) 0.508 Silverman Anderson Score c 5.2(5,6) 5.0(4.5,6.0) 0.795 Age at LISA (minute) c 40 (35–60) 45 (40–60) 0.214 Data are presented as: a Mean (SD). b n (%). c Median (IQR). The outcomes for both primary and secondary measures are presented in Table 2 .The need for intubation within the first 72 hours of life showed no significant difference between the groups (3.3% for both). There were no significant differences observed in the number of doses surpassing one, surfactant reflux, and surfactant cost between the groups. Necrotizing enterocolitis (> stage 2) was observed in 10% of the beractant group and 1.67% in the poractant-α group (p-value 0.114, 95% CI 0.74–48.34).A significant difference in surfactant cost was observed, indicating that beractant is considerably more economical than poractant-alfa (14322.1 ± 4624.98 vs. 25208.9 ± 6822.64, p < 0.001). No variations were observed in FiO 2 requirement, SpO 2 , HR, or mean blood pressure between the two groups at four different time points (before LISA ,1 min, 5 min, and 60 min) (Table 3 ). Figure 2 illustrates the Kaplan-Meier analysis, revealing no significant differences in time to discharge and death between the two study groups. Table 2 Primary and secondary outcome measure Beractant (n = 60) Poractant-alfa (n = 60) p value Relative risk (95% confidence interval) Need for intubation in first 72 hr of life a 2 (3.3) 2(3.3) 1.00 1.00 (0.14–6.86) Air Leaks a 2(3.33%) 1(1.67%) 1.00 2.0 (0.18–21.47) Laryngoscopy attempt > 1 a 4 (6.6) 5 (8.3) 0.877 0.80 (0.22–2.83) Number of Surfactant Doses > 1 a 11 (18.3) 9 (15.0) 0.753 1.22 (0.54–2.73) Surfactant Reflux (ml) b 0.61 ± 0.22 0.30 ± 0.20 0.656 Surfactant Cost (Rupees) b 14322.1 ± 4624.98 25208.9 ± 6822.64 < 0.001 Hemodynamically significant patent ductus arteriosus required medical treatment b 18(30%) 18(30%) 1.00 1.00( 0.57–1.73) Culture positive sepsis a 7(11.67%) 6(10%) 1.00 1.17 (0.41–3.27) Intraventricular hemorrhage (> Grade 2) a 3(5%) 5(8.33) 0.752 0.60 (0.15–2.39) Necrotizing enterocolitis (> stage 2 ) a 6(10) 1(1.67) 0.114 6.0 (0.74–48.34) Retinopathy of prematurity required intervention a 6(10%) 5(8.33) 1.00 1.20 (0.38–3.72) Duration of invasive ventilation (day) b 0.6 (0.96) 0.4 (0.73) 0.635 Duration of respiratory support (day ) b 12.9 (11.9) 10.8 (8.54) 0.631 Bronchopulmonary dysplasia/mortality before discharge a 16 (26.67) 13 (21.67) 0.670 1.23 (0.65–2.33) BPD a 7(11.67%) 6(10%) 1.00 1.17 (0.41–3.27) Mortality a 9(15%) 7(11.67%) 0.789 1.28 (0.51–3.22) Data are presented as: a n (%) b Mean(SD) Table 3 Comparative Analysis of FiO 2 , SpO 2 , HR, and MAP Between Beractant and Poractant-alfa Groups during LISA Procedure Beractant(n = 60) Poractant-alfa(n = 60) p value FiO 2 Pre-LISA 34.8 ± 4.94 36.0 ± 5.28 0.253 After 1minute 31.9 ± 4.20 34.6 ± 5.06 0.005 After 5 minutes 27.6 ± 2.98 29.9 ± 3.39 < 0.001 After 60 minutes 25.3 ± 2.56 27.1 ± 3.47 < 0.001 SpO 2 Pre-LISA 92.2 ± 1.61 92.3 ± 0.95 0.232 After 1minute 92.8 ± 1.13 93.2 ± 1.08 0.023 After 5minutes 93.2 ± 1.16 93.3 ± 1.15 0.594 After 60minutes 92.3 ± 11.77 93.7 ± 1.07 0.669 HR Pre-LISA 132.2 ± 8.27 133.6 ± 8.8 0.389 After 1minute 133.4 ± 6.03 132.5 ± 6.51 0.434 After 5minutes 134.2 ± 6.11 133.2 ± 6.49 0.428 After 60 minutes 134.9 ± 7.04 133.8 ± 6.06 0.333 MAP Pre-LISA 7 ± 0.66 7.0 ± 0.65 0.890 After 1minute 6.6 ± 0.67 6.5 ± 0.68 0.343 After 5minutes 5.9 ± 0.63 6.0 ± 0.65 0.477 After 60minutes 5.5 ± 0.57 5.5 ± 0.57 0.872 Data are expressed as mean (SD). FiO2, fraction of inspired oxygen; SpO2, oxygen saturation; HR, heart rate; MAP, mean arterial pressure. Discussion In this randomized controlled trial, we noted comparable rates of intubation requirements within the initial 72 hours of life between the two surfactant groups. The beractant group exhibited a higher proportion of infants with surfactant reflux, a greater requirement for additional doses, and an extended duration of respiratory support. However, these differences were not statistically significant, and the study was not powered to detect variations in this outcome. No disparities in mortality, BPD or other outcomes were observed between the two groups. LISA has primarily involved natural modified surfactants derived from animals, with varying preparations and doses. In the AMV trial, a dose of 100 mg/kg led to instillation volumes of 1.25 mL/kg for poractant alfa, compared to beractant's 4 mL/kg. However, the sample size was insufficient for meaningful subgroup analyses ( 20 ). In the recently concluded OPTIMIST-A trial, a dose of 200 mg/kg of poractant-alfa was administered during LISA ( 11 ). However, there are no head-to-head randomized controlled trials comparing different surfactants and doses specifically within the LISA technique. No evidence currently supports the advantage of a more concentrated or dilute surfactant preparation for LISA. In our study, there was no observed difference in LISA failure, defined as the need for invasive ventilation within the initial 72 hours after the initial stabilization with NIPPV/CPAP support, when comparing the use of 100mg/kg beractant to 200 mg/kg poractant-alfa. Prior studies, primarily employing the INSURE technique with beractant and poractant-alfa at equivalent doses, have yielded varied results. Some indicate similar efficacy ( 21 , 22 ) or enhanced short-term advantages, such as reduced intubation duration, with poractant alfa, albeit without impacting mortality ( 23 ). Conversely, certain studies suggest fewer doses and improved mortality with poractant alfa compared to beractant ( 24 , 25 ). A recent Cochrane review suggests that higher doses (200mg/kg) of porcine minced lung extract may be more effective than bovine surfactant in improving acute respiratory status and reducing mortality or BPD in infants with RDS ( 8 ). However, uncertainties persist regarding whether the observed differences result from variations in dose or extraction source (porcine vs. bovine) due to the absence of dose-equivalent comparison groups with sufficient sample size.The extent of the alterations in outcomes appears to be influenced by factors beyond what would be anticipated solely from the type of surfactant used. These outcomes are probably affected by confounding variables, such as shifts in neonatal care practices over the year, notably the increased use of early continuous positive airway pressure and the adoption of NIPPV. Finally, in surfactant RCTs, full blinding is often unattainable due to variations in volumes and administration methods among products. This potential bias could impact study personnel. There is a prevailing belief that higher doses are challenging to administer with beractant due to their lower concentration and higher viscosity, necessitating larger volumes for administration ( 26 ). This concern is particularly relevant when applying less invasive methods like LISA. Akar S et al. demonstrated significantly higher rates of surfactant reflux with beractant compared to poractant-alfa, potentially attributed to the requirement for a greater administration volume of beractant ( 19 ). Our study observed a trend of increased reflux with beractant, although statistical significance was not reached. However, in theory, a larger volume may allow for a slower, more "drop-wise" approach during surfactant delivery, thereby facilitating better distribution to reach the distal airways ( 27 ). In our study, the beractant group exhibited a higher incidence of necrotizing enterocolitis (NEC) compared to the poractant alfa group. NEC is a multifaceted condition arising from intricate interactions of various factors, including hypoxic-ischemic insults. The primary instigating event appears to be an excessive and inappropriate inflammatory response within the intestinal tract. Terek D et al., reported an earlier normalization of inflammatory or oxidative stress with poractant alfa ( 28 ). Further research is needed to establish the reproducibility of this difference and to identify the underlying factors contributing to this observation. Our study found no difference in bronchopulmonary dysplasia/mortality before discharge between the two surfactant groups. A meta-analysis by Tridente et al. recently concluded that poractant-alfa is more effective than bovine-derived surfactants in preventing BPD in preterm infants with RDS ( 9 ). However, this finding may not be directly comparable to our study as it was based on combined data from beractant and two other bovine-derived surfactants (bovactant and bovine lipid extract surfactant suspension), which may have non-equivalent properties. In fact, BPD or in-hospital mortality is an extremely complex outcome and may be influenced by other additional factors. Finally, in the Indian market, the cost for the Beractant group was Rs-14322/- compared to Rs-25208/- for Poractant-alfa. This is a crucial consideration for low and middle-income countries like India, which experience a significant number of preterm births annually. In a study from a developed world, adjusted NICU length of stay and costs were comparable between beractant and poractant-alfa ( 29 ). The explanation provided is that beractant is linked to more additional doses of surfactant, while fewer infants in the poractant-alfa group required mechanical ventilation in the first 7 days. This suggests a balance in total costs due to reduced resources needed to support mechanically ventilated infants. In the current study, length of stay, mechanical ventilation days, and mortality were similar between the two surfactant groups. To the best of our knowledge, our study is the first from a Low- and Middle-Income Country (LMIC) comparing outcomes with two surfactants during the LISA technique. The study's strengths include a homogeneous population of inborn preterm infants from a single perinatal tertiary centre, all managed with nearly identical clinical protocols. The study has limitations, including an uncalculated sample size due to logistical constraints, impacting generalizability and statistical power. Its single-centre design at a tertiary care hospital may limit external validity. Exclusion of infants below 28 weeks' gestation restricts the findings' applicability. The study lacks long-term outcome assessment, crucial for understanding neurodevelopmental impacts. Additionally, the nature of the study did not allow for blinding, introducing the possibility of bias in outcome assessment. Conclusion The outcomes of surfactant administration in preterm infants with RDS are contingent on various factors, including the provision of optimal prenatal care, early selective surfactant administration, and the less invasive mode of surfactant delivery, rather than the surfactant preparations themselves. No differences were observed in LISA failure, short- and long-term respiratory morbidity, or mortality between the two types of surfactants at their licensed dose in our study. Using a larger volume of beractant did not result in complications. Given the similar efficacy, other factors, such as cost, become more important, especially with poractant alfa in low- to middle-income countries (LMICs). Further large, adequately powered randomized trials are required to determine outcomes related to long-term respiratory morbidity and neurodevelopmental effects. Declarations Funding None Authors' contributions Dr. Ashadur Zamal conceived and designed the study, formulated the protocol, managed patient care, and prepared the initial draft. Dr. Md Habibullah Sk contributed to protocol development, coordinated and supervised data collection, and reviewed and revised the manuscript at all stages. Dr. Bijan Saha assisted in protocol development, coordinated data collection, and provided oversight, while also contributing to the review and revision of the manuscript. Dr. Avijit Hazra played a key role in protocol development, critically reviewed the manuscript to enhance its content, and performed the statistical analysis of the data. All authors have given their approval for the final manuscript as submitted and have committed to being accountable for all aspects of the work. Consent to participate Informed consent was obtained from the legal guardian of all included participants. Conflicts of interest/Competing interests The authors declare no competing interests. Acknowledgements We would like to thank Dr. Rajib Losan Bora for generation of random sequence and assigning participants to intervention. 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Ophthalmology. 2021;128(10):e51-e68. doi: 10.1016/j.ophtha.2021.05.031 . Epub 2021 Jul 8. PMID: 34247850. Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr. 1987;17(4):213–88. doi: 10.1016/0045-9380(87)90031-4 . PMID: 3556038; PMCID: PMC7130819. Jobe A, Bancalari E. Bronchopulmonary dysplasia: NICHD/NHLBI/ORD workshop summary. Am J Respir Crit Care Med 2001;163:1723–9. Akar S, Topcuoglu S, Dincer E, Ozalkaya E, Karatekin G, Gokmen Yildirim T. Comparison of Efficacy of Beractant and Poractant Treatment Performed with Minimal Invasive Technique. Iranian Journal of Neonatology. 2021 Jan: 12(1). DOI: 10.22038/ijn.2020.48388.1838 . Göpel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, et al.; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet. 2011; 378(9803): 1627–34. Trembath A, Hornik CP, Clark R, et al. Comparative effectiveness of surfactant preparations in premature infants. J Pediatr. 2013;163(4):955–960. Paul S, Rao S, Kohan R, et al. Poractant alfa versus beractant for respiratory distress syndrome in preterm infants: a retrospective cohort study. J Paediatr Child Health. 2013;49(10):839–844. Fujii AM, Patel SM, Allen R, et al. Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome. J Perinatol. 2010;30(10):665–670. Dizdar E, Sari F, Aydemir C, et al. A randomized, controlled trial of poractant alfa versus beractant in the treatment of preterm infants with respiratory distress syndrome. Am J Perinatol. 2012;29(2):95–100. Ramanathan R, Rasmussen MR, Gerstmann DR, et al. A randomized, multicenter masked comparison trial of poractant alfa (curosurf) versus beractant (survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol. 2004;21(3):109–119. Lu KW, Pérez-Gil J, Taeusch H. Kinematic viscosity of therapeutic pulmonary surfactants with added polymers. Biochim Biophys Acta. 2009;1788(3):632–7. doi: 10.1016/j.bbamem.2009.01.005 . PMID: 19366601; PMCID: PMC2671574. Vento M, Bohlin K, Herting E, Roehr CC, Dargaville PA. Surfactant Administration via Thin Catheter: A Practical Guide. Neonatology. 2019;116(3):211–226. doi: 10.1159/000502610 . Epub 2019 Aug 28. PMID: 31461712. Terek D, Gonulal D, Koroglu OA, Yalaz M, Akisu M, Kultursay N. Effects of Two Different Exogenous Surfactant Preparations on Serial Peripheral Perfusion Index and Tissue Carbon Monoxide Measurements in Preterm Infants with Severe Respiratory Distress Syndrome. Pediatr Neonatol. 2015;56(4):248–55. doi: 10.1016/j.pedneo.2014.11.004. Epub 2014 Dec 19. PMID: 25603725. Sekar K, Fuentes D, Krukas-Hampel MR, Ernst FR. Health Economics and Outcomes of Surfactant Treatments for Respiratory Distress Syndrome Among Preterm Infants in US Level III/IV Neonatal Intensive Care Units. J Pediatr Pharmacol Ther. 2019 Mar-Apr;24(2):117–127. doi: 10.5863/1551-6776-24.2.117 . PMID: 31019404; PMCID: PMC6478364. Additional Declarations There is NO conflict of interest to disclose. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3882168","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":268771503,"identity":"89f7f491-b4db-49e4-9ee0-451f1d25ba4e","order_by":0,"name":"Bijan saha","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBACA2aGBBCdwMDMfPABkMHDR7wWdrZkA5AWNoJaoHQCAz+PmQSIRVCLOTvDw88Ff+zy+JvZ0iq/5tjJsDEwP3x0A48Wy2aGZOmZbcnFEoeZj92W3ZYMdBibsXEOPocdZkiQ5m1gTmw4zJZ2W3IbM1ALD5s0AS3Jv3n+1CfOP8xjViy5rZ4oLWnSPGyHEzcAtTB+3HaYsBagX9KseduOJ248zJYszbjtOA8bMwG/mPOfSb7N86c6cd75wwc//txWbc/P3vzwMT4twLhLgDOZecAkXuUgwH4AzmT8QVD1KBgFo2AUjEQAAAgGREwQxEPMAAAAAElFTkSuQmCC","orcid":"","institution":"IPGME\u0026R, SSKM Hospital","correspondingAuthor":true,"prefix":"","firstName":"Bijan","middleName":"","lastName":"saha","suffix":""},{"id":268771504,"identity":"7c796b9a-e276-4e08-9270-3da14bdd01ad","order_by":1,"name":"Ashadur Zamal","email":"","orcid":"https://orcid.org/0000-0003-0990-392X","institution":"IPGMER \u0026 SSKM Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ashadur","middleName":"","lastName":"Zamal","suffix":""},{"id":268771505,"identity":"3effbeb8-6863-4673-a0f9-76a12d36c645","order_by":2,"name":"Md Habibullah Sk","email":"","orcid":"","institution":"IPGMER \u0026 SSKM Hospital","correspondingAuthor":false,"prefix":"","firstName":"Md","middleName":"Habibullah","lastName":"Sk","suffix":""},{"id":268771506,"identity":"d3abae49-f19d-4ded-b288-5aa0764599b7","order_by":3,"name":"Avijit Hazra","email":"","orcid":"","institution":"IPGMER \u0026 SSKM HOPSITAL","correspondingAuthor":false,"prefix":"","firstName":"Avijit","middleName":"","lastName":"Hazra","suffix":""}],"badges":[],"createdAt":"2024-01-20 17:35:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3882168/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3882168/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41372-024-01962-y","type":"published","date":"2024-04-12T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50188651,"identity":"553b60b3-ef69-4f4b-b4da-562a0e5c2b97","added_by":"auto","created_at":"2024-01-25 21:37:45","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":832796,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT Flow chart of the study patients\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3882168/v1/d04c26f665cea93249d654ce.jpeg"},{"id":50188408,"identity":"3eee0cba-695e-485b-b56d-7393a262a1db","added_by":"auto","created_at":"2024-01-25 21:29:45","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":237137,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier analysis compared between the two groups (Group A-Beractant Group B -Poractant alfa) . (a) Discharge (b) Death\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage219.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3882168/v1/c35dccd51e1f78eac8264ccc.jpeg"},{"id":54613713,"identity":"2abbf0a3-5fa3-4199-8b5b-f8c30f98de65","added_by":"auto","created_at":"2024-04-13 07:07:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":635058,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3882168/v1/7ff9cd9f-5244-416b-aa98-e32fc44674b9.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Comparison of efficacy between beractant and poractant-alfa in respiratory distress syndrome among preterm infants (28-33+6 weeks gestational age) using the less invasive surfactant administration (LISA) technique: A randomized controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eExogenous surfactant therapy has been a significant advance in the care of preterm infants with respiratory distress syndrome (RDS) and has now become an integral component of the standard approach in managing these infants(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The preferred method for administering surfactant is shifting towards less invasive surfactant administration (LISA), which avoids both endotracheal intubation and positive pressure ventilation(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).LISA has been associated with a reduced need for mechanical ventilation in the initial 72 hours, lower rates of death or bronchopulmonary dysplasia (BPD), a decreased occurrence of major complications, and a decline in in-hospital mortality(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).While LISA is increasingly becoming a standardized method for surfactant administration, there is considerable variability in the technique. This includes uncertainties regarding the impact of using different surfactants on outcomes in LISA.\u003c/p\u003e \u003cp\u003eTwo primary types of animal-derived surfactants are commonly used: porcine-derived poractant-alfa (Curosurf\u0026mdash;Chiesi Pharmaceuticals, Parma, Italy) and beractant derived from minced bovine lung (Survanta\u0026mdash;Abbott Laboratories Inc., Columbus, OH, USA)(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Animal derived surfactants exhibit substantial variations in their compositions, including levels of phospholipids, surfactant proteins B and C, as well as differences in viscosity and volume. These variances have the potential to impact clinical outcomes. Beractant has a phospholipid concentration of 25 mg/mL. It is modified with dipalmitoylphosphatidylcholine, palmitic acid, and tripalmitin, and includes an unspecified amount of SP-B. The recommended dosage is 4 mL/kg birth weight (100 mg/kg)(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Poractant alfa boasts the highest phospholipid concentration at 80 mg/mL, with an SP-B content of 0.45 mg/mL. The recommended initial dose is 2.5 mL/kg birth weight (200 mg/kg) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs per the American Academy of Pediatrics, it remains uncertain whether notable differences in clinical outcomes exist among the available animal-derived products(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Recent research indicates that porcine minced lung extract, particularly in higher doses(200mg/kg), may exhibit greater efficacy compared to bovine surfactant in enhancing acute respiratory status and reducing mortality or BPD in infants with RDS(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).European guidelines on the management of respiratory distress syndrome (RDS) prescribe a minimum surfactant dose of 100 mg/kg. Nevertheless, the guidelines advocate a superior efficacy of a high dose, specifically 200 mg/kg of poractant alfa, compared to a lower dose (100 mg/kg) of either poractant-alfa or beractant(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe statistical difference between the two surfactant types remains uncertain, whether it is linked to the source of extraction (porcine vs. bovine) or the higher initial dose of porcine surfactant.\u003c/p\u003e \u003cp\u003eUntil now, most trials and meta-analyses have compared beractant versus poractant-alfa using the intubation surfactant administration extubation (INSURE) technique(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). While Poractant-α is widely used in the LISA technique, there is currently limited research comparing Beractant versus Poractant-α using this approach. The OPTIMIST-A trial utilized a dose of 200 mg/kg, while the NINSAPP trial employed poractant alfa surfactant at a dosage of at least 1.25 mL/kg of body weight (100 mg/kg), up to the entire vial content (1.5 mL containing 120 mg of surfactant)(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe cost of poractant-alfa is higher in comparison to beractant. Implementing LISA in low- and middle-income countries (LMICs) with poractant-alfa may encounter challenges related to its affordability.\u003c/p\u003e \u003cp\u003eGiven the known significant differences in composition and biochemical properties between beractant and poractant-alfa, our objective is to evaluate the efficacy and short-term outcomes of surfactant administration through the LISA method between these two.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design, settings and participants\u003c/h2\u003e \u003cp\u003eThis randomized controlled trial was conducted in a level III neonatal intensive care unit (NICU) in a tertiary care hospital in India. The study consecutively enrolled preterm infants with a gestational age ranging from 28 to 33\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks, from April 15, 2023, to October 31, 2023, who had RDS and required surfactant administration without the need for tracheal intubation in the delivery room. Infants were excluded if they had perinatal asphyxia (cord blood pH\u0026thinsp;\u0026lt;\u0026thinsp;7.20), severe congenital malformations, or known chromosomal anomalies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eIntervention\u003c/h2\u003e \u003cp\u003eInfants meeting the eligibility criteria, RDS and requiring non-invasive positive pressure ventilation (NIPPV) with FiO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026ge;\u0026thinsp;30% to maintain SpO\u003csub\u003e2\u003c/sub\u003e between 90\u0026ndash;95% within the first 6 hours of life, were randomly assigned to receive surfactant via the LISA technique using either poractant alfa or beractant. The dosing regimen included poractant at 200mg/kg (2.5ml/kg) and beractant at 100mg/kg (4ml/kg).\u003c/p\u003e \u003cp\u003e Throughout the study, we adhered to the following LISA procedure: Firstly, written informed consent was obtained from the infant's parents for their participation. Before initiating the LISA technique, the nasal interface and nasal mask were changed with a RAM cannula to deliver NIPPV. Subsequently, a direct laryngoscopy was performed using an appropriately sized blade, and a 5Fr infant feeding tube was inserted through the vocal cords to the desired depth without the assistance of Magill forceps. The insertion depth was determined by the formula [weight (kg)\u0026thinsp;+\u0026thinsp;7] cm(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The procedure was conducted by two trained doctors, while a nurse documented the entire process. After the placement of the feeding tube, the laryngoscope was removed, and the required amount of surfactant was instilled into the trachea in small 1 mL aliquots over 1\u0026ndash;3 minutes. For infants desaturating to \u0026le;\u0026thinsp;85% during LISA, FiO\u003csub\u003e2\u003c/sub\u003e was increased in increments of 5% to maintain SpO\u003csub\u003e2\u003c/sub\u003e within the target range of 90\u0026ndash;95%. If an infant experienced apnea lasting more than 20 seconds, positive pressure ventilation was initiated following the NICU protocol. Following the procedure, aspiration through the infant feeding tube was performed to detect and quantify the degree of surfactant reflux in the stomach. The infants were closely monitored for episodes of desaturation, bradycardia, cough, surfactant reflux from the trachea, and vomiting. If the infant continued to require FiO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026ge;\u0026thinsp;30% after 6 hours of surfactant administration, a second dose of surfactant was given using the same technique. Subsequent to the LISA procedure, the nasal interface was switched back to the standard nasal mask and nasal tubing for delivering NIPPV .\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003ePrimary Outcome\u003c/h2\u003e \u003cp\u003eThe primary outcome measure was the need for intubation within the initial 72 hours of life.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Outcomes\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eComplications occurring during the procedure (Surfactant reflux during the procedure, SpO2\u0026thinsp;\u0026lt;\u0026thinsp;85%, hypotension with mean below GA, bradycardia\u0026thinsp;\u0026lt;\u0026thinsp;80 bpm)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNeed for the second dose of Surfactant\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePulmonary haemorrhage\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePulmonary air leak syndromes\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHemodynamically significant patent ductus arteriosus(hsPDA)(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eGrade 3 and grade 4 Intraventricularhaemorrhage (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRetinopathy of prematurity requiring treatment(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNecrotizing enterocolitis\u0026thinsp;\u0026ge;\u0026thinsp;Stage 2(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eBronchopulmonary dysplasia(BPD)(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDuration of respiratory support (invasive and non-invasive) and hospital stay\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDeath before hospital discharge\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSample size\u003c/h2\u003e \u003cp\u003eUsing a recent study with a similar gestational age, the anticipated failure rate for poractant alfa therapy was 58.8%(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Assuming beractant could reduce the failure rate by at least 25% in absolute terms, a sample size of 62 subjects per group was calculated to detect a statistical difference with 80% power and a 5% probability of type 1 error. No margin was allotted for dropouts. MedCalc version 19.6 (MedCalc Software Ltd, Ostend, Belgium, 2020) was used for sample size calculation.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eRandomisation\u003c/h2\u003e \u003cp\u003eWe employed computer-generated random numbers with variable block sizes to assign infants to the two groups. Stratification based on gestational age (28\u0026ndash;31\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks and 32\u0026ndash;33\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks) was conducted, and the allocation ratio was maintained at 1:1. Concealment was ensured by utilizing sequentially numbered opaque sealed envelopes. The randomization sequence was prepared by an investigator not involved in collecting baseline data, applying the intervention, or measuring outcomes. Due to the nature of the study, blinding was not feasible. Nevertheless, both data collection staff and trial analysts remained blinded.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eNumerical variables with a normal distribution were presented as the mean and standard deviation, while skewed numerical variables were represented by the median and interquartile range. Categorical variables were expressed as counts and percentages. Continuous variables with a normal distribution underwent two-sample unpaired t-tests (Student\u0026rsquo;s t), and for skewed distributions, the Wilcoxon rank-sum test was applied. Chi-square analysis was employed to assess differences in categorical variables. The significance level for all tests was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Data analysis was conducted on an intention-to-treat basis. Statistica version 8 (Tulsa, Oklahoma: StatSoft Inc., 2007) was utilized for data analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003e The study adhered to ethical principles based on the Declaration of Helsinki and aligned with Good Clinical Practice. Approval was granted by the institutional ethics committee at the Institute of Post Graduate Medical Education and Research, Kolkata, India (IPGME\u0026amp;R/IEC/2023/412). All legal guardians provided written informed consent before participating. The trial is registered in the clinical trial registry of India (CTRI/2023/03/050375).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOver the study duration, 148 infants were admitted with RDS. After excluding 18 infants, a total of 120 were then randomized into the two surfactant groups. The participant flow in the study is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was no statistical difference observed between the groups regarding the administration of antenatal steroids. Other baseline demographic variables between the two groups were deemed comparable (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of infants (n\u0026thinsp;=\u0026thinsp;120)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBeractant (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePoractant-alfa (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal age, years\u003c/b\u003e \u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eConception\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSpontaneous\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIVF \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (86.67%)\u003c/p\u003e \u003cp\u003e8 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (90.00%)\u003c/p\u003e \u003cp\u003e6 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntenatal steroid\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eReceived (Any)\u003c/b\u003e \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (68.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (80.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.210\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCaesarean section delivery\u003c/b\u003e \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (58.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (51.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGestational age\u003c/b\u003e, \u003cb\u003eweeks\u003c/b\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth weight, grams\u003c/b\u003e \u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1414.3\u0026thinsp;\u0026plusmn;\u0026thinsp;328.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1335.6\u0026thinsp;\u0026plusmn;\u0026thinsp;340.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale gender\u003c/b\u003e \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(63.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.458\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmall for gestational age\u003c/b\u003e \u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(8.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(18.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUmbilical cord pH\u003c/b\u003e \u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.3 (7.2, 7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3 (7.2, 7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eApgar score at 1 min\u003c/b\u003e \u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(6, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(6, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eApgar score at 5 min\u003c/b\u003e \u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(8, 9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(8, 9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSilverman Anderson Score\u003c/b\u003e \u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.2(5,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0(4.5,6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.795\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at LISA (minute)\u003c/b\u003e \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (35\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (40\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.214\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e Mean (SD).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003eb\u003c/sup\u003e n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ec\u003c/sup\u003e Median (IQR).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe outcomes for both primary and secondary measures are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.The need for intubation within the first 72 hours of life showed no significant difference between the groups (3.3% for both). There were no significant differences observed in the number of doses surpassing one, surfactant reflux, and surfactant cost between the groups. Necrotizing enterocolitis (\u0026gt;\u0026thinsp;stage 2) was observed in 10% of the beractant group and 1.67% in the poractant-α group (p-value 0.114, 95% CI 0.74\u0026ndash;48.34).A significant difference in surfactant cost was observed, indicating that beractant is considerably more economical than poractant-alfa (14322.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4624.98 vs. 25208.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6822.64, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No variations were observed in FiO\u003csub\u003e2\u003c/sub\u003e requirement, SpO\u003csub\u003e2\u003c/sub\u003e, HR, or mean blood pressure between the two groups at four different time points (before LISA ,1 min, 5 min, and 60 min) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e illustrates the Kaplan-Meier analysis, revealing no significant differences in time to discharge and death between the two study groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary and secondary outcome measure\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBeractant (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePoractant-alfa (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRelative risk\u003c/p\u003e \u003cp\u003e(95% confidence\u003c/p\u003e \u003cp\u003einterval)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeed for intubation in first 72 hr of life \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00 (0.14\u0026ndash;6.86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAir Leaks \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.0 (0.18\u0026ndash;21.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaryngoscopy attempt\u0026thinsp;\u0026gt;\u0026thinsp;1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.877\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.80 (0.22\u0026ndash;2.83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of Surfactant Doses\u0026thinsp;\u0026gt;\u0026thinsp;1 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.22 (0.54\u0026ndash;2.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurfactant Reflux (ml) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.656\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurfactant Cost (Rupees) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14322.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4624.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25208.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6822.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemodynamically significant patent ductus arteriosus required medical treatment \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00( 0.57\u0026ndash;1.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCulture positive sepsis \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(11.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.17 (0.41\u0026ndash;3.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraventricular hemorrhage (\u0026gt;\u0026thinsp;Grade 2) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.60 (0.15\u0026ndash;2.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNecrotizing enterocolitis (\u0026gt;\u0026thinsp;stage 2\u003csup\u003e) a\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.0 (0.74\u0026ndash;48.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetinopathy of prematurity required intervention \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.20 (0.38\u0026ndash;3.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of invasive ventilation (day) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6 (0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4 (0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.635\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of respiratory support (day ) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.9 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.8 (8.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.631\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchopulmonary dysplasia/mortality before discharge \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (26.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (21.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.23 (0.65\u0026ndash;2.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBPD\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(11.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.17 (0.41\u0026ndash;3.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(11.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.28 (0.51\u0026ndash;3.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e n (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e Mean(SD)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparative Analysis of FiO\u003csub\u003e2\u003c/sub\u003e, SpO\u003csub\u003e2\u003c/sub\u003e, HR, and MAP Between Beractant and Poractant-alfa Groups during LISA Procedure\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBeractant(n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePoractant-alfa(n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFiO\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-LISA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 1minute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 5 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e27.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 60 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSpO\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-LISA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e92.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 1minute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e92.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 5minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e93.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.594\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 60minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e92.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-LISA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e132.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.389\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 1minute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e133.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 5minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e134.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 60 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e134.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMAP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-LISA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 1minute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 5minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter 60minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.872\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as mean (SD).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eFiO2, fraction of inspired oxygen; SpO2, oxygen saturation; HR, heart rate; MAP, mean arterial pressure.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this randomized controlled trial, we noted comparable rates of intubation requirements within the initial 72 hours of life between the two surfactant groups. The beractant group exhibited a higher proportion of infants with surfactant reflux, a greater requirement for additional doses, and an extended duration of respiratory support. However, these differences were not statistically significant, and the study was not powered to detect variations in this outcome. No disparities in mortality, BPD or other outcomes were observed between the two groups.\u003c/p\u003e \u003cp\u003eLISA has primarily involved natural modified surfactants derived from animals, with varying preparations and doses. In the AMV trial, a dose of 100 mg/kg led to instillation volumes of 1.25 mL/kg for poractant alfa, compared to beractant's 4 mL/kg. However, the sample size was insufficient for meaningful subgroup analyses (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In the recently concluded OPTIMIST-A trial, a dose of 200 mg/kg of poractant-alfa was administered during LISA (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, there are no head-to-head randomized controlled trials comparing different surfactants and doses specifically within the LISA technique. No evidence currently supports the advantage of a more concentrated or dilute surfactant preparation for LISA. In our study, there was no observed difference in LISA failure, defined as the need for invasive ventilation within the initial 72 hours after the initial stabilization with NIPPV/CPAP support, when comparing the use of 100mg/kg beractant to 200 mg/kg poractant-alfa.\u003c/p\u003e \u003cp\u003ePrior studies, primarily employing the INSURE technique with beractant and poractant-alfa at equivalent doses, have yielded varied results. Some indicate similar efficacy (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) or enhanced short-term advantages, such as reduced intubation duration, with poractant alfa, albeit without impacting mortality (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Conversely, certain studies suggest fewer doses and improved mortality with poractant alfa compared to beractant (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). A recent Cochrane review suggests that higher doses (200mg/kg) of porcine minced lung extract may be more effective than bovine surfactant in improving acute respiratory status and reducing mortality or BPD in infants with RDS (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, uncertainties persist regarding whether the observed differences result from variations in dose or extraction source (porcine vs. bovine) due to the absence of dose-equivalent comparison groups with sufficient sample size.The extent of the alterations in outcomes appears to be influenced by factors beyond what would be anticipated solely from the type of surfactant used. These outcomes are probably affected by confounding variables, such as shifts in neonatal care practices over the year, notably the increased use of early continuous positive airway pressure and the adoption of NIPPV. Finally, in surfactant RCTs, full blinding is often unattainable due to variations in volumes and administration methods among products. This potential bias could impact study personnel.\u003c/p\u003e \u003cp\u003eThere is a prevailing belief that higher doses are challenging to administer with beractant due to their lower concentration and higher viscosity, necessitating larger volumes for administration (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). This concern is particularly relevant when applying less invasive methods like LISA. Akar S et al. demonstrated significantly higher rates of surfactant reflux with beractant compared to poractant-alfa, potentially attributed to the requirement for a greater administration volume of beractant (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Our study observed a trend of increased reflux with beractant, although statistical significance was not reached. However, in theory, a larger volume may allow for a slower, more \"drop-wise\" approach during surfactant delivery, thereby facilitating better distribution to reach the distal airways (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, the beractant group exhibited a higher incidence of necrotizing enterocolitis (NEC) compared to the poractant alfa group. NEC is a multifaceted condition arising from intricate interactions of various factors, including hypoxic-ischemic insults. The primary instigating event appears to be an excessive and inappropriate inflammatory response within the intestinal tract. Terek D et al., reported an earlier normalization of inflammatory or oxidative stress with poractant alfa (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Further research is needed to establish the reproducibility of this difference and to identify the underlying factors contributing to this observation.\u003c/p\u003e \u003cp\u003eOur study found no difference in bronchopulmonary dysplasia/mortality before discharge between the two surfactant groups. A meta-analysis by Tridente et al. recently concluded that poractant-alfa is more effective than bovine-derived surfactants in preventing BPD in preterm infants with RDS (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). However, this finding may not be directly comparable to our study as it was based on combined data from beractant and two other bovine-derived surfactants (bovactant and bovine lipid extract surfactant suspension), which may have non-equivalent properties. In fact, BPD or in-hospital mortality is an extremely complex outcome and may be influenced by other additional factors.\u003c/p\u003e \u003cp\u003eFinally, in the Indian market, the cost for the Beractant group was Rs-14322/- compared to Rs-25208/- for Poractant-alfa. This is a crucial consideration for low and middle-income countries like India, which experience a significant number of preterm births annually. In a study from a developed world, adjusted NICU length of stay and costs were comparable between beractant and poractant-alfa (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). The explanation provided is that beractant is linked to more additional doses of surfactant, while fewer infants in the poractant-alfa group required mechanical ventilation in the first 7 days. This suggests a balance in total costs due to reduced resources needed to support mechanically ventilated infants. In the current study, length of stay, mechanical ventilation days, and mortality were similar between the two surfactant groups.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, our study is the first from a Low- and Middle-Income Country (LMIC) comparing outcomes with two surfactants during the LISA technique. The study's strengths include a homogeneous population of inborn preterm infants from a single perinatal tertiary centre, all managed with nearly identical clinical protocols.\u003c/p\u003e \u003cp\u003eThe study has limitations, including an uncalculated sample size due to logistical constraints, impacting generalizability and statistical power. Its single-centre design at a tertiary care hospital may limit external validity. Exclusion of infants below 28 weeks' gestation restricts the findings' applicability. The study lacks long-term outcome assessment, crucial for understanding neurodevelopmental impacts. Additionally, the nature of the study did not allow for blinding, introducing the possibility of bias in outcome assessment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe outcomes of surfactant administration in preterm infants with RDS are contingent on various factors, including the provision of optimal prenatal care, early selective surfactant administration, and the less invasive mode of surfactant delivery, rather than the surfactant preparations themselves. No differences were observed in LISA failure, short- and long-term respiratory morbidity, or mortality between the two types of surfactants at their licensed dose in our study. Using a larger volume of beractant did not result in complications. Given the similar efficacy, other factors, such as cost, become more important, especially with poractant alfa in low- to middle-income countries (LMICs). Further large, adequately powered randomized trials are required to determine outcomes related to long-term respiratory morbidity and neurodevelopmental effects.\u003c/p\u003e"},{"header":"Declarations","content":" \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eAuthors' contributions\u003c/h2\u003e \u003cp\u003eDr. Ashadur Zamal conceived and designed the study, formulated the protocol, managed patient care, and prepared the initial draft. Dr. Md Habibullah Sk contributed to protocol development, coordinated and supervised data collection, and reviewed and revised the manuscript at all stages. Dr. Bijan Saha assisted in protocol development, coordinated data collection, and provided oversight, while also contributing to the review and revision of the manuscript. Dr. Avijit Hazra played a key role in protocol development, critically reviewed the manuscript to enhance its content, and performed the statistical analysis of the data. All authors have given their approval for the final manuscript as submitted and have committed to being accountable for all aspects of the work.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to participate\u003c/strong\u003e \u003cp\u003eInformed consent was obtained from the legal guardian of all included participants.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflicts of interest/Competing interests\u003c/strong\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe would like to thank Dr. Rajib Losan Bora for generation of random sequence and assigning participants to intervention.\u003c/p\u003e\u003ch2\u003eAvailability of Data and Materials:\u003c/h2\u003e \u003cp\u003eAvailable for viewing at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://drive.google.com/file/d/1MLvBi_uUrPB0iJhz_wNn2IRUvMAX01Bb/view\u003c/span\u003e\u003cspan address=\"https://drive.google.com/file/d/1MLvBi_uUrPB0iJhz_wNn2IRUvMAX01Bb/view\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3\u0026ndash;23. doi: 10.1159/000528914. Epub 2023 Feb 15. PMID: 36863329; PMCID: PMC10064400.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2017;102(1):F17-F23. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/archdischild-2015-310299\u003c/span\u003e\u003cspan address=\"10.1136/archdischild-2015-310299\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2016 Nov 15. PMID: 27852668.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKakkilaya V, Gautham KS. Should less invasive surfactant administration (LISA) become routine practice in US neonatal units? Pediatr Res. 2023;93(5):1188\u0026ndash;1198. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41390-022-02265-8\u003c/span\u003e\u003cspan address=\"10.1038/s41390-022-02265-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2022 Aug 19. PMID: 35986148; PMCID: PMC9389478.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor G, Jackson W, Hornik CP, Koss A, Mantena S, Homsley K, et al. Surfactant administration in preterm infants: drug development opportunities. J Pediatr. 2019;208:163\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSurvanta [package insert] North Chicago, IL: AbbVie, Inc; 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.rxabbvie.com/pdf/survanta_pi.pdf\u003c/span\u003e\u003cspan address=\"https://www.rxabbvie.com/pdf/survanta_pi.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e Accessed December 17, 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCurosurf [package insert] Parma, Italy: Chiesi Farmaceutici SpA; 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://resources.chiesiusa.com/Curosurf/CUROSURF_PI.pdf\u003c/span\u003e\u003cspan address=\"https://resources.chiesiusa.com/Curosurf/CUROSURF_PI.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). 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PMID: 31019404; PMCID: PMC6478364.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Less invasive surfactant administration, Poractant-alfa, Beractant, Respiratory distress syndrome, Preterm infants","lastPublishedDoi":"10.21203/rs.3.rs-3882168/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3882168/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective: Exogenous surfactant therapy is vital in managing respiratory distress syndrome (RDS) in preterm infants, with less invasive surfactant administration (LISA) gaining popularity. This study aimed to assess the efficacy and short-term outcomes of LISA using beractant and poractant alfa.\u003c/p\u003e\n\u003cp\u003eStudy Design: In a randomized controlled trial , we enrolled preterm infants (28-33\u003csup\u003e+6\u003c/sup\u003e weeks) with RDS requiring surfactant. LISA was employed, with beractant at 100 mg/kg or poractant-alfa at 200 mg/kg. Primary outcome was the need for intubation within 72 hours.\u003c/p\u003e\n\u003cp\u003eResults: Among 120 infants, 3.3% in both groups required intubation within 72 hours (p value 1.00, 95% CI 0.14 - 6.86). No significant differences in secondary outcomes were noted, except a trend towards increased necrotizing enterocolitis with beractant . Beractant was significantly more economical.\u003c/p\u003e\n\u003cp\u003eConclusion: Beractant and poractant-alfa exhibit similar efficacy in LISA for preterm infants with RDS. Economic considerations, especially in LMICs, favour beractant.\u003c/p\u003e\n\u003cp\u003eThe trial is registered in the clinical trial registry of India (CTRI/2023/03/050375).\u003c/p\u003e","manuscriptTitle":"Comparison of efficacy between beractant and poractant-alfa in respiratory distress syndrome among preterm infants (28-33+6 weeks gestational age) using the less invasive surfactant administration (LISA) technique: A randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-25 21:29:40","doi":"10.21203/rs.3.rs-3882168/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-02-12T14:22:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-11T02:55:50+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-05T03:58:29+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-01-24T21:34:09+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-01-23T12:03:36+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-01-23T11:56:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-22T17:28:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-20T17:34:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Perinatology","date":"2024-01-20T17:34:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0e012752-f401-4841-9807-97e9ab4c535c","owner":[],"postedDate":"January 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":28313846,"name":"Health sciences/Diseases/Respiratory tract diseases"},{"id":28313847,"name":"Health sciences/Signs and symptoms/Respiratory signs and symptoms"}],"tags":[],"updatedAt":"2024-04-13T07:07:37+00:00","versionOfRecord":{"articleIdentity":"rs-3882168","link":"https://doi.org/10.1038/s41372-024-01962-y","journal":{"identity":"journal-of-perinatology","isVorOnly":false,"title":"Journal of Perinatology"},"publishedOn":"2024-04-12 04:00:00","publishedOnDateReadable":"April 12th, 2024"},"versionCreatedAt":"2024-01-25 21:29:40","video":"","vorDoi":"10.1038/s41372-024-01962-y","vorDoiUrl":"https://doi.org/10.1038/s41372-024-01962-y","workflowStages":[]},"version":"v1","identity":"rs-3882168","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3882168","identity":"rs-3882168","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}