Respiratory Severity Score and Oxygen Saturation Index during the first two hours of life as predictors for non-invasive respiratory support failure in moderate preterm infants with respiratory distress syndrome

Respiratory Severity Score and Oxygen Saturation Index during the first two hours of life as predictors for non-invasive respiratory support failure in moderate preterm infants with respiratory distress syndrome | 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 Respiratory Severity Score and Oxygen Saturation Index during the first two hours of life as predictors for non-invasive respiratory support failure in moderate preterm infants with respiratory distress syndrome Dinushan Kaluarachchi, Henry Zapata, Jack Koueik, Heather Becker, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3898586/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Noninvasive respiratory support (NRS) failure is common in preterm infants with respiratory distress syndrome (RDS). We evaluated the utility of Respiratory Severity Score (RSS) and Oxygen Saturation Index (OSI) during the first two hours of life (HOL) as a predictor for NRS failure. Methods We conducted a retrospective cohort study of infants born between 28 0/7 to 33 6/7 weeks with RDS. Univariate and multivariable logistic regression analysis were used to assess whether the RSS and OSI summary measures were associated with NRS failure. Results Among 282 infants included in the study 58 (21%) developed NRS failure. RSS and OSI summary measures in the first 2 HOL were associated with NRS failure within 72 HOL. Conclusion RSS and OSI during the first two HOL can predict NRS failure. Optimal RSS and OSI cutoffs for prediction of NRS failure need to be determined in large cohort studies. Health sciences/Diseases/Respiratory tract diseases Biological sciences/Physiology/Respiration Respiratory Distress Syndrome Surfactant Non-invasive Respiratory Support Failure failure CPAP Failure Respiratory Severity Score Oxygen Saturation Index Figures Figure 1 INTRODUCTION Respiratory distress syndrome (RDS) is commonly seen in premature neonates and is associated with major morbidity and mortality. ( 1 ) Non-invasive respiratory support (NRS), such as Continuous Positive Airway Pressure (CPAP) and surfactant replacement therapy are considered the standard of care for RDS management. ( 2 – 6 ) Currently, administering NRS immediately after birth and subsequent selective surfactant replacement therapy (SRT) is considered the standard of care. ( 2 – 6 ) The overall aim is to avoid invasive mechanical ventilation and administer surfactant as early as possible to treat RDS once it is deemed necessary. Unfortunately, a significant proportion of infants develop NRS failure. ( 7 – 9 ) These infants are at risk of adverse outcomes such as pneumothorax, need for prolonged respiratory support, chronic lung disease, and longer duration of hospital stay. ( 7 – 9 ) Therefore, it is desirable to identify infants at risk of NRS failure. Early identification allows implementation of targeted interventions aimed at prevention of NRS failure. ( 10 ) Respiratory Severity Score (RSS) and Oxygen Saturation Index (OSI) are continuous non-invasive markers to assess pulmonary status ( 11 – 15 ). In this study, we evaluate the utility of RSS and OSI during the first 2 HOL as a predictor for NRS failure in preterm infants during the first 72 HOL. METHODS Study population This is a retrospective cohort study of preterm infants born from 1/1/2017 to 12/31/2020 at Unitypoint Health Meriter Hospital in Madison, WI. All preterm infants born at gestational ages of 28 0/7 to 33 6/7 weeks with a clinical diagnosis of RDS were included in the study. Exclusion criteria were death before 2 hours of life (HOL), intubation and/or surfactant administration before 2 HOL, major congenital anomalies, 5-minute Apgar score < 5, infants on room air during the first 2 HOL, transfer to a different hospital prior to 72 hours. Procedures The UnityPoint Health Meriter Institutional Review Board granted exemption status for this study. Demographic and clinical data were collected by a medical chart review. NRS failure was defined as administration of surfactant and/or need for mechanical ventilation during the first 72 hours of life. MAP calculated or estimated as described in previous studies.( 16 – 17 ). RSS was calculated as Fraction of oxygen (FiO2) × Mean airway pressure (MAP). OSI was calculated as RSS / Oxygen saturation (SpO2). Surfactant was administered when FiO2 reached 30–40% in infants who require non-invasive respiratory support. During the study period surfactant was administered only through an endotracheal tube. Decision to use Intubation-Surfactant-Extubation technique (INSURE) or continue mechanical ventilation following surfactant administration was decided by the treating physicians based on clinical circumstances. The goal SpO2 range for preterm infants < 37 weeks was 90–94%. Statistical analysis Data were summarized with frequencies and percentages for categorical factors or with the median and interquartile range (IQR) for continuous variables. The average of MAP, FiO2, RSS and OSI for each patient was calculated along with the difference of each measure over those same two HOL. These differences (computed as response at HOL 2 minus the response at HOL 1) also represent a slope since the simple change is measured over a 1-hour span of time. Time to NRS failure was analyzed using Kaplan-Meier plots, long-rank tests, and Cox proportional hazard models. Log-binomial regression was used to estimate relative risks for failure of non-invasive respiratory support (within 72 hours) as a function of gestational age, average RSS or average OSI. We used logistic regression to determine whether odds of NRS failure were associated with demographic or clinical factors and respiratory status (RSS and OSI) during the first two hours of life. Multivariable logistic models were used to estimate adjusted odds ratios involving early respiratory status while adjusting for key demographic/clinical features. Discriminative ability of each model, as measured by the C-index, was calculated and compared against other models using DeLong’s test.( 18 ) Statistical significance was defined as P < 0.05 with no adjustment for multiple testing. Analyses were performed using R (v.4.2.2). ( 19 ) RESULTS A total of 438 infants were born between gestational ages 28 0/7–33 6/7 weeks at the UnityPoint Health Meriter Hospital were eligible for inclusion. There were 156 infants who met exclusion criteria including 57 who required intubation prior to 2 HOL and 76 who were on room air during the first 2 HOL. The final study cohort included 282 infants delivered from 234 women. Median GA and birthweights were 32 weeks (IQR 30.6–33.1) and 1.7 Kg (IQR 1.4, 2.0), respectively. Over half the sample (55%) was male, 64% were singleton births, and 35% were born by vaginal delivery. Eighty-three percent of infants were exposed to antenatal steroids. Maternal and neonatal characteristics are presented in Table 1 . Table 1 Maternal and neonatal characteristics. Variable Median (IQR) or n (%) Maternal age [a] 30 (27,34) Race/Ethnicity [a] White 168 (71.8) Black 20 (8.5) Hispanic 15 (6.4) Other 31 (13.2) Mode of delivery C-section 183 (64.9) Vaginal 99 (35.1) Antenatal Steroids No 9 (3.2) Yes 233 (82.6) Unknown 40 (14.2) Gestational age (weeks) 32.0 (30.6, 33.1) Birthweight (Kg) 1.7 (1.4, 2.0) Birthweight percentile 50.5 (27.2, 73.8) Male Sex 155 (55.0) Singleton birth 180 (63.8) [a] Computed among 234 distinct women Fifty-six infants (19.9%) received SRT while 45 (16%) required mechanical ventilation. Forty three infants (15.2%) received both SRT and mechanical ventilation. Overall, 58 infants (20.6%) experienced failure of NRS. Median time to failure among these 58 infants was 10.5 (IQR: 4.8–22.0) hours. Fourteen cases of pneumothorax (14/281; 5%) were noted and occurred after a median time of 25 hours (IQR 20, 33). Time to NRS failure according to three gestational age subgroups (28–29, 39 − 31, 32–33 weeks) is shown in Fig. 1 . Across the three groups, risk of NRS failure decreased risk of NRS failure with increasing gestational age (HR = 0.70 per 2 weeks; 95% CI: 0.51–0.97, p = 0.03). A majority of infants were on continuous positive airway pressure at 1 HOL (80.1%) and 2 HOL (76.8%). Measurements of MAP, FiO2, RSS, and OSI during the first 2 HOL are described in Table 2 . The same MAP and FiO2 was recorded on 69% (MAP) and 57%(FiO2) of the infants at both time points. The average MAP and FiO2 was 6 (IQR 5.1,7) and 0.22 (IQR 0.21, 0.25) respectively. RSS and OSI averaged over the two HOL had median and IQR of 1.44 (1.16, 1.78) and 1.53 (1.22, 1.93) respectively. Table 2 Hourly measurements of mean airway pressure (MAP), fraction of oxygen (FiO2), respiratory severity score (RSS) and oxygen saturation index (OSI) Hour of life (HOL) Number Median (IQR) MAP HOL 1 282 6.0 (5.1, 7.0) HOL 2 268 6.0 (5.0, 7.0) Average 268 6.0 (5.1, 7.0) Difference (2 − 1) 268 0 (0–0) FiO2 HOL 1 279 21 (21, 28) HOL 2 275 21 (21, 25) Average 273 22.0 (21.0, 25.5) Difference (HOL 2- HOL1) 273 0 (-2, 0) RSS HOL 1 279 1.47 (1.25, 1.92) HOL 2 265 1.38 (1.05, 1.80) Average 264 1.44 (1.16, 1.78) Difference (HOL 2- HOL1) 264 0 (-0.2, 0) OSI HOL 1 278 1.52 (1.26, 2.03) HOL 2 264 1.43 (1.15, 1.93) Average 262 1.53 (1.22, 1.93) Difference (HOL 2- HOL1) 262 -0.03 (-0.2, 0.03) Crude odds ratios involving demographic and clinical characteristics associated with NRS failure are shown in Table 3 . Odds of NRS failure tended to decrease with increasing maternal age (OR = 0.76; 95% CI: 0.57–0.98, p = 0.03), and with increasing completed weeks of gestation (OR = 0.82; 95% CI: 0.67–0.99, p = 0.03). Receiving a course of antenatal steroids was also associated with an 80% reduction in odds of NRS failure relative to those who did not receive antenatal steroids (OR 0.2; 95% CI: 0.05–0.77, p = 0.02). RSS and OSI showed a strong association with odds of NRS failure, both for the average and slope over HOL 1 and 2, and with similar estimated odds ratios for RSS and OSI. Higher slopes (i.e., steeper rising linear trend) and greater average response for each measure were each associated with greater odds of NRS failure. Table 3. Odds ratios (OR) and 95% confidence intervals (CI) showing the association between demographic and clinical variables to non-invasive respiratory support failure during first 72 hours. Variable OR (95% CI) P Value Maternal age (per 5 years) 0.76 (0.57, 0.98) 0.03 Mode of delivery C section Vaginal ref 0.97 (0.52, 1.76) 0.91 Antenatal Steroids No Yes Unknown ref 0.20 (0.05, 0.77) 0.17 (0.03, 0.79) 0.02 0.02 Sex Female Male ref 1.01 (0.57, 1.82) 0.97 Multiple Gestation Singleton Multiple ref 0.83 (0.44, 1.51) 0.54 APGAR score at 5 min (per 1 point) 0.92 (0.68, 1.26) 0.61 Gestational age (per 1 week) 0.82 (0.67, 0.99) 0.03 Birth weight (per 100g) 1.00 (0.93, 1.06) 0.92 Birth weight percentile (per 10% points) 1.06 (0.95, 1.18) 0.32 RSS during HOL 1-2 (n=264) Average (per 0.5 point) Slope (per 0.5 point) 2.26 (1.69, 3.11) 1.75 (1.22, 2.63) <0.001 0.002 OSI during HOL 1-2 (n=262) Average (per 0.5 point) Slope (per 0.5 point) 2.27 (1.72, 3.08) 1.80 (1.28, 2.71) <0.001 <0.001 Separate multivariable logistic regressions (one for each of RSS and OSI) involving NRS failure were fit with explanatory variables of maternal age, completed gestational age, antenatal steroid exposure and the given measure of respiratory status. Sample size for both models was limited to n = 262 neonates with non-missing averages and slopes for both measures of respiratory status. Maternal age and completed gestational age were found not to be necessary in the models once ANS, and the average and slope were included. Table 4 shows adjusted odds ratio (aOR) for measure of the average and slope involving RSS and OSI. Again, adjusted odds ratios showed that higher averages and slopes of RSS and OSI were associated with greater odds of NRS failure. Table 4 Multivariable logistic regression for odds of non-invasive respiratory support failure during first 72 hours. Model 1 for RSS Variable aOR (95%CI) p-value Antenatal Steroids No Ref Yes 0.11 (0.02, 0.57) 0.009 Unknown 0.18 (0.03, 1.13) 0.07 RSS Average (per 0.5 units) 3.04 (2.07, 4.65) < 0.001 Slope (per 0.5 units) 2.07 (1.36, 3.37) < 0.001 Model 2 for OSI Variable aOR (95%CI) p-value Antenatal Steroids No Ref Yes 0.11 (0.02, 0.58) 0.01 Unknown 0.20 (0.03, 1.33) 0.09 OSI Average (per 0.5 units) 3.08 (2.13, 4.66) < 0.001 Slope (per 0.5 units) 2.19(1.44, 3.55) < 0.001 The multivariable models had strong ability to predict a neonate who developed NRS failure. C-indices for each model are at least 80% for each. Tests revealed that OSI has better discrimination ability compared to RSS (81.8% vs 80.3%; p = 0.006). Having statistical significance declared for two measures that differ by 1.5 percentage points is due to average RSS and average OSI being highly correlated with each other (Pearson’s correlation coefficient = 0.997, concordance correlation coefficient = 0.982). This positive correlation reduces variability for the difference to such a degree as to make 81.8% vs 80.3% appear strongly significant. DISCUSSION In this study, we demonstrated that summary measures of RSS and OSI during the first two hours of life are associated with NRS failure in moderate preterm infants. Statistical tests indicated that OSI has better predictive ability but in practical terms the predictive ability was similar, only separated by 1.5 percentage points between these two strongly correlated markers of respiratory disease severity. Gestational age, antenatal steroid status and maternal age were also associated with NRS failure. A substantial proportion of preterm infants who are managed on noninvasive respiratory support eventually develop NRS failure. Dargaville and colleagues reported that that 25% of infants born at 25 to 32 weeks developed NRS failure. ( 7 ) Grouping by gestational ages revealed that 43% of infants born at 25–28 weeks and 21% of infants born at 29–32 weeks developed NRS failure. Infants who developed NRS failure were at higher risks of death, BPD, pneumothorax, intraventricular hemorrhage, and prolonged hospitalization. ( 7 ) Despite efforts to optimize NRS, many preterm infants fail initial NRS strategy and necessitate exogenous surfactant administration and/or need for mechanical ventilation, therefore preventive actions against NRS failure are crucial. It is important to distinguish these at-risk infants soon after birth to provide targeted therapy and optimize the positive effects of NRS. In this study we focused on moderate preterm infants as these infants constitute a larger proportion of infants with RDS treated in neonatal intensive care units. ( 19 ) Time point of two hours was selected in order to identify infants at risk of NRS failure without much delay after allowing an initial period of stabilization. A number of risk factors for NRS failure have been identified in previous research which include lower antenatal steroid exposure, birth by cesarean section without labor, male sex, lower birthweight, lower GA, multiple gestation, need for positive pressure ventilation at delivery, lower 5- minute Apgar score, higher FiO2 in the first 1 to 2 hours (FiO2 > 0.25 or > 0.3), severe RDS on chest x ray, elevated alveolar– arterial oxygen tension gradient, and lower arterial/alveolar PO2 ratio.( 7 , 8 , 20 – 24 ) Lung ultrasound is another valuable tool that has shown great promise for early identification of high-risk infants. Studies have shown that lung ultrasound score at 2 hours of age can be used to identify infants at risk of NRS failure. ( 25 , 26 ) Limited data exists on the utility of RSS and OSI, two important clinical indicators of that are readily available at bedside. RSS and OSI provides a quick, objective, noninvasive way to assess respiratory status. Our group evaluated the utility of RSS during the first 3 hours using data from a clinical trial which revealed that the average RSS and the RSS trend is associated with NRS failure. ( 13 ) Given the limitations of using subjects from a clinical trial such as selection bias and small sample size we decided to replicate our findings using a birth cohort of moderately preterm infants. We propose evaluating the utility of RSS and OSI on predicting NRS failure using large, multi-center prospective studies to define optimal thresholds for patient identification. Such models should include other important variables such a gestational age, antenatal steroid use and lung ultrasound scores. These variables could potentially be incorporated into a calculator that can be easily used at bedside for clinical decision making. There have been several therapeutic strategies that have emerged for potential prevention of NRS failure. Less invasive surfactant administration techniques such as INSURE technique, ( 27 ) thin catheter surfactant administration,( 28 , 29 ) surfactant administration through laryngeal or supraglottic airways (SALSA) ( 30 – 32 ) and aerosolization ( 33 – 37 ) has shown favorable safety and efficacy profiles. In particular, aerosolized surfactant when widely available will be an attractive therapeutic option given its true noninvasive nature. SALSA is also attractive given it doesn’t involve laryngoscopy. Some therapeutic strategies such as the use of high levels of CPAP and early initiation of noninvasive ventilation should be explored in well-designed clinical trials given their promising results in preventing extubation failure. ( 38 – 40 ) This study provides important data on the use of RSS and OSI for early identification of moderate preterm infants at risk of NRS failure. However, there are several notable limitations. Single center study design, small sample size and retrospective nature of the data collection are major limitations. Also, decision to provide surfactant and/or mechanical ventilation was not protocolized. Goal time to remove the endotracheal tube was not protocolized as well. For the purpose of the study, INSURE was defined as removal of endotracheal within 1 hour of SRT. CONCLUSION We demonstrated that RSS and OSI during the first two hours could be used as a predictor for NRS failure in moderately preterm infants. Early identification of infants at risk of NRS failure are important to provide potential target therapies. Optimal RSS and OSI thresholds for prediction of NRS failure need to be evaluated in large, multi-center prospective cohort studies. Declarations Funding source: none Conflicts of Interest statement: DK and SG serve as consultants for ONY Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The data that support the findings of this study are available from the corresponding author, [DK], upon request. Contributors Statement: Henry A. Zapata: Dr. Zapata involved in designing of the study, drafted the project proposal, reviewed and approved final manuscript as submitted. Jack Koueik: Dr. Koueik involved in designing of the study, reviewed and approved final manuscript as submitted. Michael R. Lasarev: Mr. Lasarev involved in designing of the study, did the data analysis, reviewed and approved final manuscript as submitted. Heather Becker: Ms. Becker involved in designing of the study, reviewed and approved final manuscript as submitted. Scott O. Guthrie: Dr. Guthrie involved in designing of the study, reviewed and approved final manuscript as submitted. 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Minocchieri S, Berry CA, Pillow JJ, CureNeb Study Team. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomized controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019;104:F313–9. Gaertner VD, Thomann J, Bassler D, Ruegger CM. Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis. Pediatrics. 2021;148(5). Kidman AM, Manley BJ, Boland RA, Malhotra A, Donath SM, et al. Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (ÉCLAT): a multicentre, randomised, superiority trial. https://doi.org/10.1016/S2352-4642(23)00235-3. Buzzella B, Claure N, D’Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr 2014; 164: 46–51. Lemyre B, Deguise MO, Benson P, Kirpalani H, De Paoli AG, Davis PG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2023 J;7(7):CD003212. Additional Declarations Yes there is potential conflict of interest. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-3898586","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":269780906,"identity":"59cca056-38b5-4e5c-b83a-24f45ee57d63","order_by":0,"name":"Dinushan Kaluarachchi","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0001-8334-6282","institution":"University of Wisconsin - Madison","correspondingAuthor":true,"prefix":"","firstName":"Dinushan","middleName":"","lastName":"Kaluarachchi","suffix":""},{"id":269780907,"identity":"e2add671-fb8e-419e-94ee-67f44e8e7af6","order_by":1,"name":"Henry Zapata","email":"","orcid":"","institution":"University of Florida School of Medicine -Jacksonville","correspondingAuthor":false,"prefix":"","firstName":"Henry","middleName":"","lastName":"Zapata","suffix":""},{"id":269780908,"identity":"d91d6c78-2290-488e-b5a7-45fcfb3164a4","order_by":2,"name":"Jack Koueik","email":"","orcid":"","institution":"University of Wisconsin-Madison","correspondingAuthor":false,"prefix":"","firstName":"Jack","middleName":"","lastName":"Koueik","suffix":""},{"id":269780909,"identity":"d1c8d061-5180-454f-8a81-024d7950f114","order_by":3,"name":"Heather Becker","email":"","orcid":"","institution":"University of Wisconsin-Madison","correspondingAuthor":false,"prefix":"","firstName":"Heather","middleName":"","lastName":"Becker","suffix":""},{"id":269780910,"identity":"1fcc5f78-fa51-49d7-8ab1-23496f3aa0ac","order_by":4,"name":"Michael Lasarev","email":"","orcid":"https://orcid.org/0000-0002-1896-2705","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Lasarev","suffix":""},{"id":269780911,"identity":"edb14f3e-78fa-4eb4-8fd7-5fdc3b813c5a","order_by":5,"name":"Scott Guthrie","email":"","orcid":"https://orcid.org/0000-0001-9703-5266","institution":"Vanderbilt University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Scott","middleName":"","lastName":"Guthrie","suffix":""}],"badges":[],"createdAt":"2024-01-25 23:50:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3898586/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3898586/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50458295,"identity":"596ac8ca-44eb-49c6-8581-83ece1c3ca00","added_by":"auto","created_at":"2024-01-31 20:10:30","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":113544,"visible":true,"origin":"","legend":"\u003cp\u003eTime to noninvasive respiratory support failure during the first 72 hours of life by gestational age subgroups.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3898586/v1/942e9f514c391cfbe913c84a.jpeg"},{"id":51763075,"identity":"19eb9e5e-efa8-4dad-81d4-094dccac3d2f","added_by":"auto","created_at":"2024-02-28 17:06:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":293583,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3898586/v1/0ab995c5-8fac-4f43-b93c-5ba007be4a81.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential conflict of interest.","formattedTitle":"Respiratory Severity Score and Oxygen Saturation Index during the first two hours of life as predictors for non-invasive respiratory support failure in moderate preterm infants with respiratory distress syndrome","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eRespiratory distress syndrome (RDS) is commonly seen in premature neonates and is associated with major morbidity and mortality. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Non-invasive respiratory support (NRS), such as Continuous Positive Airway Pressure (CPAP) and surfactant replacement therapy are considered the standard of care for RDS management. (\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCurrently, administering NRS immediately after birth and subsequent selective surfactant replacement therapy (SRT) is considered the standard of care. (\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) The overall aim is to avoid invasive mechanical ventilation and administer surfactant as early as possible to treat RDS once it is deemed necessary. Unfortunately, a significant proportion of infants develop NRS failure. (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) These infants are at risk of adverse outcomes such as pneumothorax, need for prolonged respiratory support, chronic lung disease, and longer duration of hospital stay. (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Therefore, it is desirable to identify infants at risk of NRS failure. Early identification allows implementation of targeted interventions aimed at prevention of NRS failure. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eRespiratory Severity Score (RSS) and Oxygen Saturation Index (OSI) are continuous non-invasive markers to assess pulmonary status (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In this study, we evaluate the utility of RSS and OSI during the first 2 HOL as a predictor for NRS failure in preterm infants during the first 72 HOL.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThis is a retrospective cohort study of preterm infants born from 1/1/2017 to 12/31/2020 at Unitypoint Health Meriter Hospital in Madison, WI. All preterm infants born at gestational ages of 28 0/7 to 33 6/7 weeks with a clinical diagnosis of RDS were included in the study. Exclusion criteria were death before 2 hours of life (HOL), intubation and/or surfactant administration before 2 HOL, major congenital anomalies, 5-minute Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;5, infants on room air during the first 2 HOL, transfer to a different hospital prior to 72 hours.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eProcedures\u003c/h2\u003e \u003cp\u003eThe UnityPoint Health Meriter Institutional Review Board granted exemption status for this study. Demographic and clinical data were collected by a medical chart review. NRS failure was defined as administration of surfactant and/or need for mechanical ventilation during the first 72 hours of life. MAP calculated or estimated as described in previous studies.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). RSS was calculated as Fraction of oxygen (FiO2) \u0026times; Mean airway pressure (MAP). OSI was calculated as RSS / Oxygen saturation (SpO2).\u003c/p\u003e \u003cp\u003eSurfactant was administered when FiO2 reached 30\u0026ndash;40% in infants who require non-invasive respiratory support. During the study period surfactant was administered only through an endotracheal tube. Decision to use Intubation-Surfactant-Extubation technique (INSURE) or continue mechanical ventilation following surfactant administration was decided by the treating physicians based on clinical circumstances. The goal SpO2 range for preterm infants\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks was 90\u0026ndash;94%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were summarized with frequencies and percentages for categorical factors or with the median and interquartile range (IQR) for continuous variables. The average of MAP, FiO2, RSS and OSI for each patient was calculated along with the difference of each measure over those same two HOL. These differences (computed as response at HOL 2 minus the response at HOL 1) also represent a slope since the simple change is measured over a 1-hour span of time.\u003c/p\u003e \u003cp\u003eTime to NRS failure was analyzed using Kaplan-Meier plots, long-rank tests, and Cox proportional hazard models. Log-binomial regression was used to estimate relative risks for failure of non-invasive respiratory support (within 72 hours) as a function of gestational age, average RSS or average OSI.\u003c/p\u003e \u003cp\u003eWe used logistic regression to determine whether odds of NRS failure were associated with demographic or clinical factors and respiratory status (RSS and OSI) during the first two hours of life. Multivariable logistic models were used to estimate adjusted odds ratios involving early respiratory status while adjusting for key demographic/clinical features. Discriminative ability of each model, as measured by the C-index, was calculated and compared against other models using DeLong\u0026rsquo;s test.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) Statistical significance was defined as P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 with no adjustment for multiple testing. Analyses were performed using R (v.4.2.2). (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 438 infants were born between gestational ages 28 0/7\u0026ndash;33 6/7 weeks at the UnityPoint Health Meriter Hospital were eligible for inclusion. There were 156 infants who met exclusion criteria including 57 who required intubation prior to 2 HOL and 76 who were on room air during the first 2 HOL. The final study cohort included 282 infants delivered from 234 women. Median GA and birthweights were 32 weeks (IQR 30.6\u0026ndash;33.1) and 1.7 Kg (IQR 1.4, 2.0), respectively. Over half the sample (55%) was male, 64% were singleton births, and 35% were born by vaginal delivery. Eighty-three percent of infants were exposed to antenatal steroids. Maternal and neonatal characteristics are presented in 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\u003eMaternal and neonatal characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian (IQR) or n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age [a]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (27,34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace/Ethnicity [a]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168 (71.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (6.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (13.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e183 (64.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (35.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal Steroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233 (82.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (14.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.0 (30.6, 33.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight (Kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7 (1.4, 2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.5 (27.2, 73.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale Sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155 (55.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingleton birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e180 (63.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e[a] Computed among 234 distinct women\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFifty-six infants (19.9%) received SRT while 45 (16%) required mechanical ventilation. Forty three infants (15.2%) received both SRT and mechanical ventilation. Overall, 58 infants (20.6%) experienced failure of NRS. Median time to failure among these 58 infants was 10.5 (IQR: 4.8\u0026ndash;22.0) hours. Fourteen cases of pneumothorax (14/281; 5%) were noted and occurred after a median time of 25 hours (IQR 20, 33). Time to NRS failure according to three gestational age subgroups (28\u0026ndash;29, 39\u0026thinsp;\u0026minus;\u0026thinsp;31, 32\u0026ndash;33 weeks) is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Across the three groups, risk of NRS failure decreased risk of NRS failure with increasing gestational age (HR\u0026thinsp;=\u0026thinsp;0.70 per 2 weeks; 95% CI: 0.51\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.03).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA majority of infants were on continuous positive airway pressure at 1 HOL (80.1%) and 2 HOL (76.8%). Measurements of MAP, FiO2, RSS, and OSI during the first 2 HOL are described in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The same MAP and FiO2 was recorded on 69% (MAP) and 57%(FiO2) of the infants at both time points. The average MAP and FiO2 was 6 (IQR 5.1,7) and 0.22 (IQR 0.21, 0.25) respectively. RSS and OSI averaged over the two HOL had median and IQR of 1.44 (1.16, 1.78) and 1.53 (1.22, 1.93) respectively.\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\u003eHourly measurements of mean airway pressure (MAP), fraction of oxygen (FiO2), respiratory severity score (RSS) and oxygen saturation index (OSI)\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=\"char\" char=\".\" 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\u003eHour of life (HOL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eMAP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.0 (5.1, 7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.0 (5.0, 7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.0 (5.1, 7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDifference (2\u0026thinsp;\u0026minus;\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026ndash;0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eFiO2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (21, 28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e275\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (21, 25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.0 (21.0, 25.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDifference (HOL 2- HOL1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (-2, 0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eRSS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.47 (1.25, 1.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.38 (1.05, 1.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.44 (1.16, 1.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDifference (HOL 2- HOL1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (-0.2, 0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eOSI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e278\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.52 (1.26, 2.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHOL 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.43 (1.15, 1.93)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.53 (1.22, 1.93)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDifference (HOL 2- HOL1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.03 (-0.2, 0.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCrude odds ratios involving demographic and clinical characteristics associated with NRS failure are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Odds of NRS failure tended to decrease with increasing maternal age (OR\u0026thinsp;=\u0026thinsp;0.76; 95% CI: 0.57\u0026ndash;0.98, p\u0026thinsp;=\u0026thinsp;0.03), and with increasing completed weeks of gestation (OR\u0026thinsp;=\u0026thinsp;0.82; 95% CI: 0.67\u0026ndash;0.99, p\u0026thinsp;=\u0026thinsp;0.03). Receiving a course of antenatal steroids was also associated with an 80% reduction in odds of NRS failure relative to those who did not receive antenatal steroids (OR 0.2; 95% CI: 0.05\u0026ndash;0.77, p\u0026thinsp;=\u0026thinsp;0.02). RSS and OSI showed a strong association with odds of NRS failure, both for the average and slope over HOL 1 and 2, and with similar estimated odds ratios for RSS and OSI. Higher slopes (i.e., steeper rising linear trend) and greater average response for each measure were each associated with greater odds of NRS failure.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eOdds ratios (OR) and 95% confidence intervals (CI) showing the association between demographic and clinical variables to non-invasive respiratory support failure during first 72 hours. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eMaternal age (per 5 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e0.76 (0.57, 0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eMode of delivery\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; C section\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Vaginal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;ref\u003cbr\u003e\u0026nbsp;0.97 (0.52, 1.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eAntenatal Steroids\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;ref\u003cbr\u003e\u0026nbsp;0.20 (0.05, 0.77)\u003cbr\u003e\u0026nbsp;0.17 (0.03, 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;0.02\u003cbr\u003e\u0026nbsp;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eSex\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Female\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;ref\u003cbr\u003e\u0026nbsp;1.01 (0.57, 1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eMultiple Gestation\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Singleton\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Multiple\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;ref\u003cbr\u003e\u0026nbsp;0.83 (0.44, 1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eAPGAR score at 5 min (per 1 point)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e0.92 (0.68, 1.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eGestational age (per 1 week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e0.82 (0.67, 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eBirth weight (per 100g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e1.00 (0.93, 1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eBirth weight percentile (per 10% points)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e1.06 (0.95, 1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eRSS during HOL 1-2 (n=264)\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Average (per 0.5 point)\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Slope (per 0.5 point)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;2.26 (1.69, 3.11)\u003cbr\u003e\u0026nbsp;1.75 (1.22, 2.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003cbr\u003e\u0026nbsp;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 55.0531%;\"\u003e\n \u003cp\u003eOSI during HOL 1-2 (n=262)\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Average (per 0.5 point)\u003cbr\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Slope (per 0.5 point)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 29.3463%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;2.27 (1.72, 3.08)\u003cbr\u003e\u0026nbsp;1.80 (1.28, 2.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\" style=\"width: 15.4081%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp\u003eSeparate multivariable logistic regressions (one for each of RSS and OSI) involving NRS failure were fit with explanatory variables of maternal age, completed gestational age, antenatal steroid exposure and the given measure of respiratory status. Sample size for both models was limited to n\u0026thinsp;=\u0026thinsp;262 neonates with non-missing averages and slopes for both measures of respiratory status. Maternal age and completed gestational age were found not to be necessary in the models once ANS, and the average and slope were included. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows adjusted odds ratio (aOR) for measure of the average and slope involving RSS and OSI. Again, adjusted odds ratios showed that higher averages and slopes of RSS and OSI were associated with greater odds of NRS failure.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable logistic regression for odds of non-invasive respiratory support failure during first 72 hours.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eModel 1 for RSS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eaOR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAntenatal Steroids\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.02, 0.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.18 (0.03, 1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eRSS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage (per 0.5 units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.04 (2.07, 4.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\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\u003eSlope (per 0.5 units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.07 (1.36, 3.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\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\u003eModel 2 for OSI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eaOR (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAntenatal Steroids\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.02, 0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.20 (0.03, 1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eOSI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage (per 0.5 units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.08 (2.13, 4.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\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\u003eSlope (per 0.5 units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.19(1.44, 3.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe multivariable models had strong ability to predict a neonate who developed NRS failure. C-indices for each model are at least 80% for each. Tests revealed that OSI has better discrimination ability compared to RSS (81.8% vs 80.3%; p\u0026thinsp;=\u0026thinsp;0.006). Having statistical significance declared for two measures that differ by 1.5 percentage points is due to average RSS and average OSI being highly correlated with each other (Pearson\u0026rsquo;s correlation coefficient\u0026thinsp;=\u0026thinsp;0.997, concordance correlation coefficient\u0026thinsp;=\u0026thinsp;0.982). This positive correlation reduces variability for the difference to such a degree as to make 81.8% vs 80.3% appear strongly significant.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we demonstrated that summary measures of RSS and OSI during the first two hours of life are associated with NRS failure in moderate preterm infants. Statistical tests indicated that OSI has better predictive ability but in practical terms the predictive ability was similar, only separated by 1.5 percentage points between these two strongly correlated markers of respiratory disease severity. Gestational age, antenatal steroid status and maternal age were also associated with NRS failure.\u003c/p\u003e \u003cp\u003eA substantial proportion of preterm infants who are managed on noninvasive respiratory support eventually develop NRS failure. Dargaville and colleagues reported that that 25% of infants born at 25 to 32 weeks developed NRS failure. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Grouping by gestational ages revealed that 43% of infants born at 25\u0026ndash;28 weeks and 21% of infants born at 29\u0026ndash;32 weeks developed NRS failure. Infants who developed NRS failure were at higher risks of death, BPD, pneumothorax, intraventricular hemorrhage, and prolonged hospitalization. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDespite efforts to optimize NRS, many preterm infants fail initial NRS strategy and necessitate exogenous surfactant administration and/or need for mechanical ventilation, therefore preventive actions against NRS failure are crucial. It is important to distinguish these at-risk infants soon after birth to provide targeted therapy and optimize the positive effects of NRS. In this study we focused on moderate preterm infants as these infants constitute a larger proportion of infants with RDS treated in neonatal intensive care units. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Time point of two hours was selected in order to identify infants at risk of NRS failure without much delay after allowing an initial period of stabilization.\u003c/p\u003e \u003cp\u003eA number of risk factors for NRS failure have been identified in previous research which include lower antenatal steroid exposure, birth by cesarean section without labor, male sex, lower birthweight, lower GA, multiple gestation, need for positive pressure ventilation at delivery, lower 5- minute Apgar score, higher FiO2 in the first 1 to 2 hours (FiO2\u0026thinsp;\u0026gt;\u0026thinsp;0.25 or \u0026gt;\u0026thinsp;0.3), severe RDS on chest x ray, elevated alveolar\u0026ndash; arterial oxygen tension gradient, and lower arterial/alveolar PO2 ratio.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) Lung ultrasound is another valuable tool that has shown great promise for early identification of high-risk infants. Studies have shown that lung ultrasound score at 2 hours of age can be used to identify infants at risk of NRS failure. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eLimited data exists on the utility of RSS and OSI, two important clinical indicators of that are readily available at bedside. RSS and OSI provides a quick, objective, noninvasive way to assess respiratory status. Our group evaluated the utility of RSS during the first 3 hours using data from a clinical trial which revealed that the average RSS and the RSS trend is associated with NRS failure. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Given the limitations of using subjects from a clinical trial such as selection bias and small sample size we decided to replicate our findings using a birth cohort of moderately preterm infants.\u003c/p\u003e \u003cp\u003eWe propose evaluating the utility of RSS and OSI on predicting NRS failure using large, multi-center prospective studies to define optimal thresholds for patient identification. Such models should include other important variables such a gestational age, antenatal steroid use and lung ultrasound scores. These variables could potentially be incorporated into a calculator that can be easily used at bedside for clinical decision making.\u003c/p\u003e \u003cp\u003eThere have been several therapeutic strategies that have emerged for potential prevention of NRS failure. Less invasive surfactant administration techniques such as INSURE technique, (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) thin catheter surfactant administration,(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) surfactant administration through laryngeal or supraglottic airways (SALSA) (\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) and aerosolization (\u003cspan additionalcitationids=\"CR34 CR35 CR36\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) has shown favorable safety and efficacy profiles. In particular, aerosolized surfactant when widely available will be an attractive therapeutic option given its true noninvasive nature. SALSA is also attractive given it doesn\u0026rsquo;t involve laryngoscopy. Some therapeutic strategies such as the use of high levels of CPAP and early initiation of noninvasive ventilation should be explored in well-designed clinical trials given their promising results in preventing extubation failure. (\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThis study provides important data on the use of RSS and OSI for early identification of moderate preterm infants at risk of NRS failure. However, there are several notable limitations. Single center study design, small sample size and retrospective nature of the data collection are major limitations. Also, decision to provide surfactant and/or mechanical ventilation was not protocolized. Goal time to remove the endotracheal tube was not protocolized as well. For the purpose of the study, INSURE was defined as removal of endotracheal within 1 hour of SRT.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eWe demonstrated that RSS and OSI during the first two hours could be used as a predictor for NRS failure in moderately preterm infants. Early identification of infants at risk of NRS failure are important to provide potential target therapies. Optimal RSS and OSI thresholds for prediction of NRS failure need to be evaluated in large, multi-center prospective cohort studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding source: none\u003c/p\u003e\n\u003cp\u003eConflicts of Interest statement: DK and SG serve as consultants for ONY Biotech. \u0026nbsp; The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, [DK], upon request.\u003c/p\u003e\n\u003cp\u003eContributors Statement:\u003c/p\u003e\n\u003cp\u003eHenry A. Zapata: Dr. Zapata involved in designing of the study, drafted the project proposal, reviewed and approved final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eJack Koueik: Dr. Koueik involved in designing of the study, reviewed and approved final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eMichael R. Lasarev: Mr. Lasarev \u0026nbsp;involved in designing of the study, did the data analysis, reviewed and approved final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eHeather Becker: Ms. Becker involved in designing of the study, reviewed and approved final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eScott O. Guthrie: Dr. Guthrie involved in designing of the study, reviewed and approved final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eDinushan Kaluarachchi: Dr. Kaluarachchi designed the study, drafted the project proposal, obtained data, drafted and approved final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWarren JB, Anderson JM. Core concepts: respiratory distress syndrome. NeoReviews 2009; 10:351\u0026ndash;361.\u003c/li\u003e\n\u003cli\u003ePolin RA, Carlo WA. Committee on Fetus and Newborn; American Academy of Pediatrics. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics. 2014;133:156-63.\u003c/li\u003e\n\u003cli\u003eSweet DG, Carnielli V, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, et al. European Consensus guidelines on the management of respiratory distress syndrome - 2022 update. Neonatology. 2023;120:3-23.\u003c/li\u003e\n\u003cli\u003eNg EH, Shah V, Fetus and Newborn Committee. Canadian Paediatric Society. Guidelines for surfactant replacement therapy in neonates. Paediatr Child Health. 2021;26:35-49.\u003c/li\u003e\n\u003cli\u003eBhandari V, Black R, Gandhi B, Hogue S, Kakkilaya V, Mikhael M, et al. RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS. J Perinatol. 2023;43:982-990.\u003c/li\u003e\n\u003cli\u003eBanerjee S, Fernandez R, Fox GF, Goss KCW, Mactier H, Reynolds P, et al. Surfactant replacement therapy for respiratory distress syndrome in preterm infants: United Kingdom national consensus. Pediatr Res. 2019;86:12-14.\u003c/li\u003e\n\u003cli\u003eDargaville PA, Gerber A, Johansson S, De Paoli AG, Kamlin CO, Orsini F, Davis PG; Australian, New Zealand Neonatal Network: Incidence and outcome of CPAP failure in preterm infants. Pediatrics 2016;138: e20153985.\u003c/li\u003e\n\u003cli\u003eDargaville PA, Aiyappan A, De Paoli AG, Dalton RGB, Kuschel CA, Orsini F, et al. Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences. Neonatology. 2013;104(1):8\u0026ndash;14.\u003c/li\u003e\n\u003cli\u003eChallis P, Nydert P, H\u0026aring;kansson S, Norman M. Association of Adherence to Surfactant Best Practice Uses With Clinical Outcomes Among Neonates in Sweden. JAMA Netw Open. 2021;4 :e217269.\u003c/li\u003e\n\u003cli\u003eGlaser K, Bamat NA, Wright CJ. Can we balance early exogenous surfactant therapy and non-invasive respiratory support to optimize outcomes in extremely preterm infants? A nuanced review of the current literature. Arch Dis Child Fetal Neonatal Ed 2023;108:554-560. \u003c/li\u003e\n\u003cli\u003eJung YH, Jang J, Kim HS, et al. Respiratory severity score as a predictive factor for severe bronchopulmonary dysplasia or death in extremely preterm infants. BMC Pediatr 2019;19:121.\u003c/li\u003e\n\u003cli\u003eMalkar MB, Gardner WP, Mandy GT, et al. Respiratory severity score on day of life 30 is predictive of mortality and the length of mechanical ventilation in premature infants with protracted ventilation. Pediatr Pulmonol 2015;50:363-369\u003c/li\u003e\n\u003cli\u003eZapata HA, Becker HL, Lasarev MR, Fort P, Guthrie SO, Kaluarachchi DC. Respiratory Severity Score during the First 3 Hours of Life as a Predictor for Failure of Noninvasive Respiratory Support and Need for Late Rescue Surfactant Administration. Am J Perinatol. 2023 Aug 24. doi: 10.1055/s-0043-1772747. \u003c/li\u003e\n\u003cli\u003eVadi S. 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(Comparing the areas under two or more correlated receiver operating characteristic curves: a non-parametric approach. Biometrika. 1988; 44:837- 845.\u003c/li\u003e\n\u003cli\u003eTrembath AN, Payne AH, Colaizy TT, Bell EF, Walsh MC. The problems of moderate preterm infants. Semin Perinatol. 2016;40:370-373.\u003c/li\u003e\n\u003cli\u003eAmmari A, Suri M, Milisavljevic V, Sahni R, Bateman D, Sanocka U, et al. Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Pediatr 2005;147:341\u0026ndash; 347.\u003c/li\u003e\n\u003cli\u003eDe Jaegere AP, van der Lee JH, Cante C, van Kaam AH: Early prediction of nasal continu- ous positive airway pressure failure in pre- term infants less than 30 weeks gestation. Acta Paediatr 2012;101:374-379.\u003c/li\u003e\n\u003cli\u003eFuchs H, Lindner W, Leiprecht A, Mendler MR, Hummler HD: Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of \u0026lt;29 weeks gestational age. Arch Dis Child Fetal Neonatal Ed 2011; 96:F343-F347.\u003c/li\u003e\n\u003cli\u003eTagliaferro T, Bateman D, Ruzal- Shapiro C, Polin RA. Early radiologic evidence of severe respiratory distress syndrome as a predictor of nasal continuous positive airway pressure failure in extremely low birth weight newborns. J Perinatol. 2015;35:99\u0026ndash;103.\u003c/li\u003e\n\u003cli\u003eKakkilaya V, Wagner S, Mangona KLM, Brown LS, Jubran I, He H, et al. Early predictors of continuous positive airway pressure failure in preterm neonates. J Perinatol. 2019;39:1081-1088.\u003c/li\u003e\n\u003cli\u003eBrat R, Yousef N, Klifa R, Reynaud S, Shankar Aguilera S, De Luca D. Lung ultrasonography score to evaluate oxygenation and surfactant need in neonates treated with continuous positive airway pressure. JAMA Pediatr 2015;169:e151797.\u003c/li\u003e\n\u003cli\u003eDe Martino L, Yousef N, Ben-Ammar R, Raimondi F, Shankar- Aguilera S, De Luca D. Lung ultrasound score predicts surfac- tant need in extremely preterm neonates. Pediatrics 2018: e20180463.\u003c/li\u003e\n\u003cli\u003eIsayama T, Chatree C, McDonald SD. Noninvasive ventilation with vs without early surfactant to prevent chronic lung disease in preterm infants: a systematic review and meta-analysis. JAMA Pediatr. 2015;169:731-9.\u003c/li\u003e\n\u003cli\u003eHerting E, H\u0026auml;rtel C, G\u0026ouml;pel W.Less invasive surfactant administration: best practices and unanswered questions. Curr Opin Pediatr2020;32:228-234.\u003c/li\u003e\n\u003cli\u003eDargaville PA, Kamlin COF, Orsini F, Wang X, De Paoli AG, Kanmaz Kutman HG et al. Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants with Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial. JAMA. 2021;326:2478-87\u003c/li\u003e\n\u003cli\u003eZapata HA, Fort P, Roberts KD, Kaluarachchi DC, Guthrie SO. Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries. Front Pediatr. 2022;10:853831.\u003c/li\u003e\n\u003cli\u003eRoberts KD, Brown R, Lampland AL, Leone TA, Rudser KD, Finer NN, et al. Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial. J Pediatr. 2018;193:40-6.e1.\u003c/li\u003e\n\u003cli\u003eGallup JA, Ndakor SM, Pezzano C, Pinheiro JMB. Randomized Trial of Surfactant Therapy via Laryngeal Mask Airway Versus Brief Tracheal Intubation in Neonates Born Preterm. J Pediatr. 2023:254:17-24.e2.\u003c/li\u003e\n\u003cli\u003eCummings JJ, Gerday E, Minton S, Katheria A, Albert G, Flores-Torres J, et al. Aerosolized Calfactant for Newborns with Respiratory Distress: A Randomized Trial. Pediatrics. 2020;146(5).\u003c/li\u003e\n\u003cli\u003eKaluarachchi DC, Zapata HA, Becker HL, Lasarev MR, Fort P, Guthrie SO. Response to aerosolized calfactant in infants with respiratory distress syndrome; a post-hoc analysis of AERO-02 trial. Perinatol. 2023 ;43:998-1003.\u003c/li\u003e\n\u003cli\u003eSood B, Thomas R, Delaney-Black V, Xin Y, Sharma A, Chen X. Aerosolized beractant in neonatal respiratory distress syndrome: a randomized fixed-dose parallel-arm phase II trial. Pulm Pharm Ther. 2021;66:101986.\u003c/li\u003e\n\u003cli\u003eMinocchieri S, Berry CA, Pillow JJ, CureNeb Study Team. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomized controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019;104:F313\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eGaertner VD, Thomann J, Bassler D, Ruegger CM. Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis. Pediatrics. 2021;148(5).\u003c/li\u003e\n\u003cli\u003eKidman AM, Manley BJ, Boland RA, Malhotra A, Donath SM, et al. Higher versus lower nasal continuous positive airway pressure for extubation of extremely preterm infants in Australia (\u0026Eacute;CLAT): a multicentre, randomised, superiority trial. https://doi.org/10.1016/S2352-4642(23)00235-3.\u003c/li\u003e\n\u003cli\u003eBuzzella B, Claure N, D\u0026rsquo;Ugard C, Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J Pediatr 2014; 164: 46\u0026ndash;51.\u003c/li\u003e\n\u003cli\u003eLemyre B, Deguise MO, Benson P, Kirpalani H, De Paoli AG, Davis PG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2023 J;7(7):CD003212.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Respiratory Distress Syndrome, Surfactant, Non-invasive Respiratory Support Failure failure, CPAP Failure, Respiratory Severity Score, Oxygen Saturation Index","lastPublishedDoi":"10.21203/rs.3.rs-3898586/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3898586/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNoninvasive respiratory support (NRS) failure is common in preterm infants with respiratory distress syndrome (RDS). We evaluated the utility of Respiratory Severity Score (RSS) and Oxygen Saturation Index (OSI) during the first two hours of life (HOL) as a predictor for NRS failure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe conducted a retrospective cohort study of infants born between 28 0/7 to 33 6/7 weeks with RDS. Univariate and multivariable logistic regression analysis were used to assess whether the RSS and OSI summary measures were associated with NRS failure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong 282 infants included in the study 58 (21%) developed NRS failure. RSS and OSI summary measures in the first 2 HOL were associated with NRS failure within 72 HOL.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eRSS and OSI during the first two HOL can predict NRS failure. Optimal RSS and OSI cutoffs for prediction of NRS failure need to be determined in large cohort studies.\u003c/p\u003e","manuscriptTitle":"Respiratory Severity Score and Oxygen Saturation Index during the first two hours of life as predictors for non-invasive respiratory support failure in moderate preterm infants with respiratory distress syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-31 20:10:25","doi":"10.21203/rs.3.rs-3898586/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"66e34a1a-4104-496c-b66f-1b0a2844d07f","owner":[],"postedDate":"January 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28415353,"name":"Health sciences/Diseases/Respiratory tract diseases"},{"id":28415354,"name":"Biological sciences/Physiology/Respiration"}],"tags":[],"updatedAt":"2024-02-28T17:06:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-31 20:10:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3898586","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3898586","identity":"rs-3898586","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}