Comparison of Unplanned Extubations Associated with Orotracheal versus Nasotracheal Intubation in Neonates

Comparison of Unplanned Extubations Associated with Orotracheal versus Nasotracheal Intubation in Neonates | 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 Unplanned Extubations Associated with Orotracheal versus Nasotracheal Intubation in Neonates Pavani Chitamanni, Thomas Hays, Diana Vargas, Takeya Patterson, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7285543/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Apr, 2026 Read the published version in Journal of Perinatology → Version 1 posted 8 You are reading this latest preprint version Abstract Objective To evaluate the association between orotracheal versus nasotracheal intubation route and unplanned extubation (UE) risk among neonates. Study Design: This retrospective cohort study included all tracheal intubation (TI) events among neonates admitted to a level IV NICU from 2022 to 2024. Kaplan-Meier survival analysis was used to assess UE risk by TI route. Result There were 1,160 TI events and 23 UEs during the study period. The UE rate was three times lower in nasotracheal intubation group compared to orotracheal (0.01 vs 0.03 per 100 ventilator days). UE risk was significantly higher in orotracheally intubated infants (p = 0.03) with no differences when stratified by sex, gestational age, or birth weight. Conclusion Nasotracheal intubation was associated with lower UE risk in neonates in a unit that predominantly performs nasotracheal intubation. Prospective randomized studies are needed to further investigate if TI route may contribute to fewer UEs in this population. Health sciences/Health care/Paediatrics Health sciences/Risk factors Figures Figure 1 Figure 2 Introduction Tracheal intubation (TI) is a standard procedure commonly performed in infants who are critically ill or require perioperative anesthesia. A multicenter observational study done across Neonatal Intensive Care Units (NICUs) in United States, Canada and Poland from May 2015 to July 2016 reports that about 74% of neonates born at 26–28 weeks require TI, while 33% of those born at 29–32 weeks and 16% of those born at 33–34 weeks require TI ( 1 ). About 2% of term neonates also need alternate airway placement in the delivery room ( 2 ). TI can be performed via the nasal or oral route. Nasotracheal intubation (NTI) involves inserting the tube through the naris, nasal cavity, pharynx, then through the larynx into the trachea. Orotracheal intubation (OTI) involves inserting the tube through the mouth and pharynx, and then through the larynx into the trachea. While the oral axis is nearly perpendicular to the laryngeal axis, the nasopharyngeal axis is more parallel with the laryngeal axis thereby following a more anatomic course ( 3 – 5 ). The first documented NTI was published in the 19th century by a surgeon, Franz Kuhn, who noted that the nasotracheal tube “lies better” and keeps the mouth unobstructed for surgical procedures. ( 6 ) Studies have attempted to compare complications related to NTI versus OTI in neonates and infants, but are limited due to small sample sizes and heterogeneous patient populations with inconclusive findings ( 5 , 7 – 16 ). But despite lack of evidence demonstrating a clear benefit, OTI is more commonly performed in NICUs. Based on retrospective analysis of data on TI from the National Emergency Airway Registry for Neonates (NEAR4NEOS), more than 93% of the TIs in the NICUs were performed orotracheally ( 17 ). TIs carry the risk of complications, i.e., adverse TI associated events, including esophageal intubation, hypotension, laryngospasm, pneumothorax, pneumomediastinum, direct airway injury, mainstem bronchial intubation, and dysrhythmias ( 18 ). Unplanned extubations (UEs) occur when an endotracheal tube (ETT) is accidentally dislodged from the trachea, and can potentially result in rapid cardiorespiratory deterioration ( 19 , 20 ). Neonates are more susceptible to UEs compared to children due to factors such as prolonged intubation, shorter tracheas, use of uncuffed ETTs, and potentially lighter or lack of sedation ( 21 ). The incidence of UEs in NICUs varies, ranging from 0.56 to 5.3 per 100 ventilator days with differences attributed to multiple factors such as NICU size, level of care, nursing staff experience and workload, ETT securement methods and sedation practices ( 22 ). Thus, reducing UEs has become a prioritized quality improvement (QI) initiative across NICUs ( 23 – 27 ). However, scarce data exists describing the rate of UEs in OTI versus NTI in neonates. In our NICU, TI via the nasal route has been preferentially performed for over five decades. However, neonates and infants often undergo OTI for multiple reasons including provider preference and TI at referring institutions prior to transfer to our NICU. Therefore, we aimed to determine the association between TI route and risk of UEs in our population. We hypothesized that NTI is associated with a lower risk of UE compared to OTI. Methods This was a retrospective observational cohort study using data previously gathered in a QI project in infants admitted to a level IV NICU at Columbia University Irving Medical Center ( 26 ). Our hospital has a 17-bed infant cardiac NICU and a 58-bed general NICU. Inclusion criteria included all intubated infants admitted to either the general or the infant cardiac NICU from January 2022 to December 2024 regardless of location of TI (e.g., NICU, delivery room, operating room, referring institution). Of note, beginning in December 2022, our institution expanded resuscitation to include infants born at or after 22 weeks’ gestation, whereas previously it was limited to those born at or after 23 weeks’ gestation. Starting in October 2017, a multidisciplinary team composed of neonatal clinicians, nurses, educators and respiratory therapists spearheaded a QI initiative to reduce UEs in the NICU. Through this initiative, standardization of data collection included automatically generated reports to track ventilator days through the electronic medical record, which transitioned to Epic in 2020, a process to report UEs through the hospital’s portal for adverse events known as “Keepsafe,” and creation of a REDCap database to collect information regarding each UE. Data included demographic and clinical characteristics, and clinical complications related to UEs. Through that QI initiative, we demonstrated a reduction in our UE rate, typically reported as the number of UEs per 100 ventilator days, from 0.45 to 0.02 followed by a span of 480 consecutive days without a UE in the infant cardiac NICU ( 26 ). Following that QI initiative, we sought to determine if the route of TI affected the UE rate. We were uniquely poised to study this given our NICU’s population of predominantly infants with NTI, as well as infants with OTI. Routinely in the NICU, the bedside nurse and/or respiratory therapist records the route of TI (NTI versus OTI) in the Lines, Drains, Airways (LDA) Flowsheet and Avatar in Epic. Thus, reports were generated from January 2022 to December 2024 to determine ventilator days broken down by route for each TI episode for any infant admitted to the NICU. The number of ventilator days were calculated by determining the difference between the start date and time of ETT placement and end date and time of ETT removal. The ventilator days were then categorized by TI site as OTI versus NTI. If the TI site data was omitted from the LDA Avatar, then manual chart review was done to extract this data, commonly found in the TI procedure notes. Additionally, data were collected for each infant who experienced an UE via chart review including gestational age, birth weight, route of TI, and any complication from an UE. The hospital portal was also queried over the study period to determine if any medical device-related pressure injuries (MDRPIs) were reported for either OTI or NTI for any infant in the NICU. The MDRPIs were staged 1 through 4 according to the 2019 Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline ( 28 , 29 ). Statistical analysis We compared characteristics of infants who underwent NTI versus OTI by chi-square for categorical data and by two-tailed T-test for continuous data. We also compared characteristics of infants who experienced UE versus those who did not. In this analysis, Mann-Whitney U-test was performed, given the smaller sample size. Next, we conducted Kaplan-Meier univariate survival analyses to determine the risk of the endpoint of UE. Data were censored for planned extubation, death while intubated, or transfer out of the NICU while intubated. In the first survival analysis, we stratified infants by route of intubation. Next, we stratified infants by sex, gestational age, constitutional age, and birth weight. Results A total of 1,160 TI events were included, of which 602 (51.9%) were NTI and 558 (48.1%) were OTI. The baseline characteristics comparing the two groups are presented in Table 1 . Infants who underwent a NTI were born at a lower gestational age with a smaller birth weight and were intubated earlier in their NICU stay compared to those who underwent an OTI. There were no significant differences in birth weight Z-score (normalized by sex and gestational age) ( 30 ) and sex distribution. Among 602 NTIs, 6 cases of MDRPI of the naris were identified. Of these, 2 were unstageable, 2 were classified as stage I, and 2 as stage II. No MDRPIs were reported in the OTI group. Table 1 Baseline Characteristics of Infants with Nasotracheal (NTI) and Orotracheal Intubations (OTI) Characteristic 1 NTI (N = 602) OTI (N = 558) p-value 2 Gestational Age (weeks) 33.8 (5.45) 34.6 (5.33) 0.009 Range 22–41 22–41 Birth Weight (Z-score) 3 -0.390 (1.12) -0.373 (1.33) 0.823 Range -4.572–9.215 -3.241–12.274 Birth Weight (g) 2220 (1080) 2410 (1090) 0.003 Range 336–4500 336–4430 Female Sex 284 (47.2%) 267 (47.8%) 0.865 Age at Intubation (weeks) 3.14 (6.08) 6.68 (9.80) < 0.001 Range 0–56.9 0–90.0 1 Data are shown as mean (SD), or n (%) 2 chi square or T-test as indicated 3 Z-score normalized by sex and gestational age by Fenton curve ( 30 ) A total of 23 UEs occurred during the study period—9/23 (39.1%) were in the NTI group, and 14/23 (60.9%) were in the OTI group. The characteristics of the infants who had UEs in both the groups are presented in Table 2 . There were no significant differences in gestational age, birth weight, age at TI, or duration of TI prior to UE among infants with UEs between the two groups (Table 2 ). NTIs accounted for a total of 67,757 patient ventilator-days, while OTIs accounted for 45,080 patient ventilator-days. The UE rate was lower in the NTI group compared to the OTI group (0.01 versus 0.03 per 100 patient ventilator-days). Table 2 Characteristics of Infants with UEs in Nasotracheal (NTI) and Orotracheal Intubation (OTI) Groups Characteristic 1 NTI Group (N = 9) OTI Group (N = 14) p-value 2 Gestational Age (weeks) 29.44 (5.66) 29.86 (6.69) 0.79 Range 23–39 23–39 Birth Weight (Z-score) 3 -0.40 (0.96) -0.46 (1.19) 0.91 Range -2.07–1.51 -2.15–1.98 Birth Weight (g) 1500.89 (1262.02) 1512.50 (928.19) 0.97 Range 543–3970 460–3115 Female Sex 2 (22.2%) 5 (35.7%) 0.50 Age at ETT Placement (weeks) 38.44 (8.13) 31.93 (7.07) 0.07 Range 28–50 23–40 Duration of Intubation (hours) 213.52 (192.58) 154.46 (351.61) 0.95 Range 106–597 7–1366 1 Data are shown as mean (SD), or n (%) 2 Chi squared, t-test or Mann-Whitney U test as indicated 3 Z-score normalized by sex and gestational age by Fenton curve ( 30 ) Survival analysis demonstrated that infants with an OTI were less likely to remain intubated versus infants with an NTI (Fig. 1 , p value = 0.03). Our survival analysis did not demonstrate differences in UE risk when stratifying infants by sex, gestational age, constitutional age, or birth weight (Fig. 2 A-D). Discussion In this retrospective review of 1,160 TI events amongst neonates and infants in the NICU, we found that the risk of UE was significantly higher in infants with OTI compared to infants with NTI. During the study period, the average overall UE rate in our NICU was 0.02 per 100 patient ventilator days while the UE rate in the NTI group was three times lower than the rate in the OTI group. In addition, infants with NTI had a low rate of MDRPIs. UEs are one of the adverse events associated with TI that can result in possible significant cardiorespiratory compromise and complications including intraventricular hemorrhage, tracheal injury, and pulmonary injury, particularly when emergent reintubation is needed ( 20 ). Multiple studies, including systematic reviews and previous QI efforts, have evaluated various risk factors for UEs in neonates. These include lower gestational age, especially < 29 weeks, due to shorter tracheal length and difficulty securing the ETT, infrequent sedation use, prolonged TI, low nurse-to-patient ratios, patient movement, bedside procedures, and excessive secretions ( 31 ). Carvalho et al. found that each additional day on mechanical ventilation increased UE risk by 3% ( 32 ). Despite the extensive literature available on risk factors for UE, there are limited descriptions of the association between the route of TI and the risk of UE in the NICU population. Anecdotal reports note that UEs more common following OTI compared to NTI ( 5 , 7 , 10 , 13 – 15 ). The Cochrane systematic review published in 2000, comparing OTI and NTI included only two studies, each with a sample size of less than 100 neonates and with inconclusive results ( 7 ). Of note, the analysis in these studies did not account for planned extubations. In our study, we addressed this limitation by using Kaplan-Meier survival analysis, which allowed us to account for planned extubations. Furthermore, our institution’s practice of predominantly performing NTIs in neonates since 1970s provided a robust cohort of neonates intubated by both routes, with a total of 1,160 TI events available for review during our study period. The literature on contraindications to and complications of NTI in neonates is limited. Basilar skull fracture and coagulopathy have been reported as contraindications to NTI in children ( 33 ). Though there is no published literature regarding specific contraindications in neonates, potential limitations may include anatomical conditions that obstruct passage of the ETT through the nasal cavity, such as choanal atresia, choanal stenosis, or midfacial anomalies like congenital pyriform aperture stenosis. In our NICU, there is no minimum gestational age or weight threshold below which NTI is considered contraindicated. Potential complications of NTI, such as nasal trauma, epistaxis, sinusitis, nasal ala necrosis, and retropharyngeal perforation, have been reported primarily in the pediatric population ( 33 ). To date, five cases of traumatic perforation of lamina cribrosa during NTI in neonates have been reported in the literature ( 34 ). To reduce the risk of trauma, the use of a soft guide, such as a suction catheter inserted into the ETT has been recommended ( 35 ). An adult study done in 1993 on complications and late sequalae of NTI in adults reported bleeding from nasal cavity in 19% of patients ( 36 ). In contrast, a more recent study by Abdelbaser et al. involving 220 infants undergoing cardiac surgery found that only 3 out of 98 infants who underwent NTI experienced transient, self-limited nasal bleeding, likely due to the use of uncuffed, well-lubricated ETTs ( 5 ). Another complication associated with NTIs is nasal pressure injury, which has been reported in about 40–70% in older children ( 37 ). However, there is limited data in neonates. A recent study by Vogt et al comparing NTI and OTI in neonates who underwent cardiac surgery, reported skin breakdown in 8.9% of those with NTI versus 1.1% of those with OTI ( 16 ). In our unit, six MDRPIs of the naris were reported in the NTI group during the study period, which is an incidence of only 1%, while none were reported in the OTI group. Lastly, although some reports suggest that OTI is easier and faster to perform under direct laryngoscopy ( 12 ), data from NICUs where NTI is a standard practice challenge this assumption. A study done in a European NICU where NTIs were performed in 98% of cases reported a first-attempt TI success rate of 42% compared to 49% reported by the NEARS4NEO registry, where 93% of TIs were in infants with an OTI ( 18 , 38 ). TI associated events were also similar in frequency amongst both studies (57.4% versus 66%, respectively). These findings suggest that with appropriate provider training, NTI can achieve success rates comparable to OTI. Some recent studies also reported potential benefits of NTI beyond UE prevention including reduced postoperative sedation use and faster progression to full oral feeds with less oral aversion, but were limited by small sample size and focus on term infants who required cardiac surgery ( 5 , 10 ). Data comparing these outcomes in preterm neonates remains limited. Given the scarcity of data surrounding NTI in neonates, further studies comparing both TI routes, along with consistent provider training in both NTI and OTI techniques, would enable a more individualized approach to neonatal airway management. This would allow healthcare providers to assess risks and benefits, selecting the most appropriate TI route for each patient rather than defaulting to the oral route for all neonates. Limitations : While our findings offer valuable insights, our study does have limitations. First, as a retrospective study, we could only demonstrate an association but not a cause-effect relationship and the retrospective study design is inherently subject to selection and ascertainment biases. Second, we did not control for potential confounding variables, such as sedation use, suctioning frequency, or nurse-to-patient ratios. Additionally, there were differences between the baseline characteristics of infants who underwent a NTI versus an OTI. Infants who underwent OTI were born at a higher gestational age, with greater birth weight, and had older constitutional age at TI. While our survival analysis did not detect differences in UE risk when accounting for these factors, we cannot exclude the possibility that these underlying differences confounded our findings. Third, our reliance on hospital safety-portal reports may have led to underreporting of TI-related complications other than UEs. Fourth, we did not assess long-term outcomes such as nasal or palatal deformities (e.g. palatal grooves after an OTI) that may require intervention, particularly since palatal grooves have been reported in up to 35% of preterm neonates with OTI in the literature ( 40 ). Finally, the study was conducted at a single level IV NICU with extensive experience in performing NTIs in addition to maintenance and securement of nasotracheal tubes at the bedside. Our overall UE rate was substantially lower than the average rate of 0.61 per 100 patient ventilator days reported by the Solutions for Patient Safety Network, which included data from about 120 NICUs during this study period ( 19 ). This difference is likely due to a multitude of reasons including use of an airway safety bundle and potentially the route of TI ( 26 ). These aspects limit the generalizability of our findings. Thus, more prospective randomized controlled trials are needed to investigate the association of UE with route of TI. Conclusion and future directions To date, no definitive evidence exists to recommend one TI route over the other in the neonatal population; however, OTI continues to be the standard approach adopted in many NICUs across the United States ( 17 ). Our study demonstrated that NTI is associated with a significantly lower rate of UEs compared to OTI in our population. Given the substantial impact of UEs and the limited data surrounding NTI, there is a need for prospective randomized controlled trials to further support our findings. Declarations Competing interests: The authors declare no competing interests. Ethics approval: This project was determined to be exempt from ethics approval and consent by the Columbia University Institutional Review Board, given this is a study of de-identified data generated in a prior QI project. The study was performed in accordance with the Declaration of Helsinki. References Moya FR, Mazela J, Shore PM, Simonson SG, Segal R, Simmons PD, et al. Prospective observational study of early respiratory management in preterm neonates less than 35 weeks of gestation. BMC Pediatr. 2019 May 11;19(1):147. Wyllie J, Perlman JM, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, et al. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2015 Oct;95:e169-201. Bannister F. DIRECT LARYNGOSCOPY AND TRACHEAL INTUBATION. The Lancet. 1944 Nov;244(6325):651–4. Greenland KB. Two curves and three columns–A reappraisal of direct laryngoscopy. Oper Tech Otolaryngol-Head Neck Surg. 2020 Jun;31(2):83–8. Abdelbaser I, Abourezk AR, Magdy M, Elnegerey N, Sabry R, Tharwat M, et al. Comparison of the Outcomes of Oral Versus Nasal Endotracheal Intubation in Neonates and Infants Undergoing Cardiac Surgery: A Randomized Controlled Study. J Cardiothorac Vasc Anesth. 2023 Oct;37(10):2012–9. Gillespie NA. The evolution of endotracheal anaesthesia. J Hist Med Allied Sci. 1946 Oct;1(4):583–94. Spence K, Barr P. Nasal versus oral intubation for mechanical ventilation of newborn infants. Cochrane Database Syst Rev. 2000;1999(2):CD000948. Schou J. Nasotracheal versus orotracheal intubation--a balanced conclusion? Acta Anaesthesiol Scand. 1994 Feb;38(2):192–3. Spitzer AR, Fox WW. Postextubation atelectasis-the role of oral versus nasal endotracheal tubes. J Pediatr. 1982 May;100(5):806–10. Yildirim MI, Spaeder MC, Castro BA, Chamberlain R, Fuzy L, Howard S, et al. The Impact of Nasal Intubation on Feeding Outcomes in Neonates Requiring Cardiac Surgery: A Randomized Control Trial. Pediatr Cardiol. 2024 Feb;45(2):426–32. Alves PVM, Luiz RR. The influence of orotracheal intubation on the oral tissue development in preterm infants. Oral Health Prev Dent. 2012;10(2):141–7. Holzapfel L. Nasal vs oral intubation. Minerva Anestesiol. 2003 May;69(5):348–52. Stewart AR, Finer NN, Moriartey RR, Ulan OA. Neonatal nasotracheal intubation: an evaluation. The Laryngoscope. 1980 May;90(5 Pt 1):826–31. McMillan DD, Rademaker AW, Buchan KA, Reid A, Machin G, Sauve RS. Benefits of orotracheal and nasotracheal intubation in neonates requiring ventilatory assistance. Pediatrics. 1986 Jan;77(1):39–44. Angelos GM, Smith DR, Jorgenson R, Sweeney EA. Oral complications associated with neonatal oral tracheal intubation: a critical review. Pediatr Dent. 1989 Jun;11(2):133–40. Vogt P, Downey L, Gleason ME, Dresner LD, Clark S, Shashidharan S, et al. Outcomes of Nasotracheal Versus Orotracheal Intubation in Neonates After Cardiopulmonary Bypass Surgery: A Retrospective Cross-Sectional Analysis. Paediatr Anaesth. 2025 Jul 9; Brei BK, Sawyer T, Umoren R, Gray MM, Krick J, Foglia EE, et al. Associations between family presence and neonatal intubation outcomes: a report from the National Emergency Airway Registry for Neonates: NEAR4NEOS. Arch Dis Child Fetal Neonatal Ed. 2021 Jul;106(4):392–7. Foglia EE, Ades A, Napolitano N, Leffelman J, Nadkarni V, Nishisaki A. Factors Associated with Adverse Events during Tracheal Intubation in the NICU. Neonatology. 2015;108(1):23–9. Solutions for Patient Safety [Internet]. [cited 2025 Feb 20]. Unplanned Extubations. Available from: https://www.solutionsforpatientsafety.org/unplannedextubations Silva PSL da, Reis ME, Aguiar VE, Fonseca MCM. Unplanned extubation in the neonatal ICU: a systematic review, critical appraisal, and evidence-based recommendations. Respir Care. 2013 Jul;58(7):1237–45. Merkel L, Beers K, Lewis MM, Stauffer J, Mujsce DJ, Kresch MJ. Reducing unplanned extubations in the NICU. Pediatrics. 2014 May;133(5):e1367-1372. Lamy Filho F, Silva AAM da, Lopes JMA, Lamy ZC, Simões VMF, Dos Santos AM. Staff workload and adverse events during mechanical ventilation in neonatal intensive care units. J Pediatr (Rio J). 2011;87(6):487–92. Crezeé KL, DiGeronimo RJ, Rigby MJ, Carter RC, Patel S. Reducing Unplanned Extubations in the NICU Following Implementation of a Standardized Approach. Respir Care. 2017 Aug;62(8):1030–5. Ahn E, Cullen SM, Osorio SN, Ehret C, Jonas K, Blake CE, et al. Reducing NICU Unplanned Extubations From Tube Dislodgement. Pediatrics. 2024 Jun 1;153(6):e2022061170. Galiote JP, Ridoré M, Carman J, Zell L, Brant K, Gayle C, et al. Reduction in Unintended Extubations in a Level IV Neonatal Intensive Care Unit. Pediatrics. 2019 May;143(5):e20180897. Kim F, Eckels VB, Brachio SS, Brooks C, Ehret C, Gomez G, et al. Use of an airway bundle to reduce unplanned extubations in a neonatal intensive care unit. J Perinatol Off J Calif Perinat Assoc. 2024 Feb;44(2):314–20. Nair V, Smith H. Phased Quality Improvement Interventions in Reducing Unplanned Extubation in the Neonatal ICU. Respir Care. 2020 Oct;65(10):1511–8. International Guideline [Internet]. [cited 2025 Apr 12]. 2019 Guideline. Available from: https://internationalguideline.com/2019 Kottner J, Cuddigan J, Carville K, Balzer K, Berlowitz D, Law S, et al. Prevention and treatment of pressure ulcers/injuries: The protocol for the second update of the international Clinical Practice Guideline 2019. J Tissue Viability. 2019 May;28(2):51–8. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013 Apr 20;13:59. Fontánez-Nieves TD, Frost M, Anday E, Davis D, Cooperberg D, Carey AJ. Prevention of unplanned extubations in neonates through process standardization. J Perinatol Off J Calif Perinat Assoc. 2016 Jun;36(6):469–73. Carvalho FL, Mezzacappa MA, Calil R, Machado H da C. Incidence and risk factors of accidental extubation in a neonatal intensive care unit. J Pediatr (Rio J). 2010;86(3):189–95. Kim J, Jeon S. Nasotracheal intubation in pediatrics: a narrative review. J Dent Anesth Pain Med. 2024 Apr;24(2):81–90. Lupi F, Staffler A, Parmeggiani L, Klemme M, Dalla Pozza R, Stuefer J, et al. Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature. Clin Case Rep. 2021 Sep;9(9):e04650. Cameron D, Lupton BA. Inadvertent brain penetration during neonatal nasotracheal intubation. Arch Dis Child. 1993 Jul;69(1 Spec No):79–80. Holdgaard HO, Pedersen J, Schurizek BA, Melsen NC, Juhl B. Complications and late sequelae following nasotracheal intubation. Acta Anaesthesiol Scand. 1993 Jul;37(5):475–80. Chen J, Chen J, Yang J, Chen Y, Liang Y, Lin Y. Investigating the Efficacy of Hydrocolloid Dressing for Preventing Nasotracheal Tube-Related Pressure Injury in the PICU. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2020 Sep;21(9):e752–8. Tippmann S, Haan M, Winter J, Mühler AK, Schmitz K, Schönfeld M, et al. Adverse Events and Unsuccessful Intubation Attempts Are Frequent During Neonatal Nasotracheal Intubations. Front Pediatr. 2021;9:675238. Foglia EE, Ades A, Sawyer T, Glass KM, Singh N, Jung P, et al. Neonatal Intubation Practice and Outcomes: An International Registry Study. Pediatrics. 2019 Jan;143(1):e20180902. Cortines AAO, Costa LR. Associated factors and persistence of palatal groove in preterm infants: a cohort study. BMC Pediatr. 2016 Aug 24;16(1):143. Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Published Journal Publication published 13 Apr, 2026 Read the published version in Journal of Perinatology → Version 1 posted Editorial decision: revise 28 Aug, 2025 Review # 1 received at journal 16 Aug, 2025 Reviewer # 1 agreed at journal 15 Aug, 2025 Reviewers invited by journal 12 Aug, 2025 Submission checks completed at journal 11 Aug, 2025 First submitted to journal 10 Aug, 2025 Unknown event 04 Aug, 2025 Editor assigned by journal 03 Aug, 2025 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. 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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-7285543","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":499483236,"identity":"aa71c61a-6727-4671-9da2-a7ed921e6054","order_by":0,"name":"Pavani Chitamanni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYFACxgYgYSPHD2InFBCvJc1YEkQlGBBv1eHEDQdANDFa+Gc3tz342ZaWuPn86sQPDwwY5PnFDuDXInHnYLthb5uN8bYbbzdLAB1mOHN2AgFrbiS2SfCcSZPdduPsBpCWBIPbBLTIA7VI/jlzmHHzjLObfxClxQCoRZqn4rDiBv7ebcTZYngjsd1YpiLNWOIG7zaLBAMJwn6Ru5H+7OEbA2BU9p/dfPNHhY08vzQBLUDABqEkwColCCpH0sJ/gCjVo2AUjIJRMAIBAJLqSOn3RdPvAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-8465-0358","institution":"Columbia University Irving Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Pavani","middleName":"","lastName":"Chitamanni","suffix":""},{"id":499483237,"identity":"ccf2d6fb-2fbc-4748-85f2-aa68540295cc","order_by":1,"name":"Thomas Hays","email":"","orcid":"https://orcid.org/0000-0002-3705-8973","institution":"Columbia University","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Hays","suffix":""},{"id":499483238,"identity":"9f463191-ff63-4b40-9c27-922ff10fbe96","order_by":2,"name":"Diana Vargas","email":"","orcid":"https://orcid.org/0000-0002-2845-2696","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Diana","middleName":"","lastName":"Vargas","suffix":""},{"id":499483239,"identity":"ca97ed7b-9896-4850-b306-a30f3cc65d97","order_by":3,"name":"Takeya Patterson","email":"","orcid":"","institution":"New York Presbyterian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takeya","middleName":"","lastName":"Patterson","suffix":""},{"id":499483240,"identity":"93e05dd1-da2e-4ecb-9a43-fc60e656be6c","order_by":4,"name":"Gloria Lush","email":"","orcid":"","institution":"New York Presbyterian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gloria","middleName":"","lastName":"Lush","suffix":""},{"id":499483241,"identity":"d5906369-9632-4467-a1d4-c9e9b6da0cb6","order_by":5,"name":"Alex Lyford","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"","lastName":"Lyford","suffix":""},{"id":499483242,"identity":"dcc90ef1-9b63-42b7-843b-322241d8758c","order_by":6,"name":"Rakesh Sahni","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Rakesh","middleName":"","lastName":"Sahni","suffix":""},{"id":499483243,"identity":"82ed5a2c-f7ce-4280-a180-a4acdb079825","order_by":7,"name":"Faith Kim","email":"","orcid":"https://orcid.org/0000-0002-0344-0613","institution":"Columbia University Irving Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Faith","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2025-08-03 22:10:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7285543/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7285543/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41372-026-02615-y","type":"published","date":"2026-04-13T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89467867,"identity":"bab3f7b4-7bbc-4c4c-aca3-362d1d3c1b03","added_by":"auto","created_at":"2025-08-20 08:54:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":241391,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier analysis of remaining intubated stratified by route of intubation.\u003c/strong\u003e Kaplan-Meier analysis was performed to determine the probability of remaining intubated in infants, with the endpoint consisting of unplanned extubations, and censoring events of planned extubations, death while intubated, or transfer out of NICU while intubated. Infants were stratified by route of intubation, with the solid line representing NTI and the dashed line representing OTI. Infants with NTI were more likely to remain intubated (p = 0.03).\u003c/p\u003e","description":"","filename":"Figure1PChitamanniNTIvsOTI.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7285543/v1/01cfbc850aad92c312336f9e.jpg"},{"id":89467879,"identity":"fcd82c3c-9c9a-4a71-9c1a-b8bb86e4d9f4","added_by":"auto","created_at":"2025-08-20 08:55:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":640813,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier analysis of remaining intubated stratified by infant characteristics.\u003c/strong\u003e Kaplan-Meier analysis was performed to determine the probability of remaining intubated in infants, with the endpoint consisting of unplanned extubations, and censoring events of planned extubations, death while intubated, or transfer out of NICU while intubated. Infants were stratified by sex (A), gestational age (B), constitutional age at intubation (C), and birth weight as a Z-score normalized to sex and gestational age by Fenton curve (D).\u003c/p\u003e\n\u003cp\u003eAbbreviations: BW (birth weight)\u003c/p\u003e","description":"","filename":"Figure2PChitamanniNTIvsOTI.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7285543/v1/a598dab945bd1ee41f8aab21.jpg"},{"id":106853947,"identity":"9487ab36-f8fe-4b81-abc7-1bca4aa30b9d","added_by":"auto","created_at":"2026-04-14 07:06:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1571776,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7285543/v1/1f5d88f1-3913-465f-bcf0-b80ff633a1b4.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Comparison of Unplanned Extubations Associated with Orotracheal versus Nasotracheal Intubation in Neonates","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTracheal intubation (TI) is a standard procedure commonly performed in infants who are critically ill or require perioperative anesthesia. A multicenter observational study done across Neonatal Intensive Care Units (NICUs) in United States, Canada and Poland from May 2015 to July 2016 reports that about 74% of neonates born at 26–28 weeks require TI, while 33% of those born at 29–32 weeks and 16% of those born at 33–34 weeks require TI (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). About 2% of term neonates also need alternate airway placement in the delivery room (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). TI can be performed via the nasal or oral route. Nasotracheal intubation (NTI) involves inserting the tube through the naris, nasal cavity, pharynx, then through the larynx into the trachea. Orotracheal intubation (OTI) involves inserting the tube through the mouth and pharynx, and then through the larynx into the trachea. While the oral axis is nearly perpendicular to the laryngeal axis, the nasopharyngeal axis is more parallel with the laryngeal axis thereby following a more anatomic course (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e–\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The first documented NTI was published in the 19th century by a surgeon, Franz Kuhn, who noted that the nasotracheal tube “lies better” and keeps the mouth unobstructed for surgical procedures. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Studies have attempted to compare complications related to NTI versus OTI in neonates and infants, but are limited due to small sample sizes and heterogeneous patient populations with inconclusive findings (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e–\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). But despite lack of evidence demonstrating a clear benefit, OTI is more commonly performed in NICUs. Based on retrospective analysis of data on TI from the National Emergency Airway Registry for Neonates (NEAR4NEOS), more than 93% of the TIs in the NICUs were performed orotracheally (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTIs carry the risk of complications, i.e., adverse TI associated events, including esophageal intubation, hypotension, laryngospasm, pneumothorax, pneumomediastinum, direct airway injury, mainstem bronchial intubation, and dysrhythmias (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Unplanned extubations (UEs) occur when an endotracheal tube (ETT) is accidentally dislodged from the trachea, and can potentially result in rapid cardiorespiratory deterioration (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Neonates are more susceptible to UEs compared to children due to factors such as prolonged intubation, shorter tracheas, use of uncuffed ETTs, and potentially lighter or lack of sedation (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The incidence of UEs in NICUs varies, ranging from 0.56 to 5.3 per 100 ventilator days with differences attributed to multiple factors such as NICU size, level of care, nursing staff experience and workload, ETT securement methods and sedation practices (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Thus, reducing UEs has become a prioritized quality improvement (QI) initiative across NICUs (\u003cspan additionalcitationids=\"CR24 CR25 CR26\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e–\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). However, scarce data exists describing the rate of UEs in OTI versus NTI in neonates. In our NICU, TI via the nasal route has been preferentially performed for over five decades. However, neonates and infants often undergo OTI for multiple reasons including provider preference and TI at referring institutions prior to transfer to our NICU. Therefore, we aimed to determine the association between TI route and risk of UEs in our population. We hypothesized that NTI is associated with a lower risk of UE compared to OTI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a retrospective observational cohort study using data previously gathered in a QI project in infants admitted to a level IV NICU at Columbia University Irving Medical Center (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Our hospital has a 17-bed infant cardiac NICU and a 58-bed general NICU. Inclusion criteria included all intubated infants admitted to either the general or the infant cardiac NICU from January 2022 to December 2024 regardless of location of TI (e.g., NICU, delivery room, operating room, referring institution). Of note, beginning in December 2022, our institution expanded resuscitation to include infants born at or after 22 weeks’ gestation, whereas previously it was limited to those born at or after 23 weeks’ gestation.\u003c/p\u003e\u003cp\u003eStarting in October 2017, a multidisciplinary team composed of neonatal clinicians, nurses, educators and respiratory therapists spearheaded a QI initiative to reduce UEs in the NICU. Through this initiative, standardization of data collection included automatically generated reports to track ventilator days through the electronic medical record, which transitioned to Epic in 2020, a process to report UEs through the hospital’s portal for adverse events known as “Keepsafe,” and creation of a REDCap database to collect information regarding each UE. Data included demographic and clinical characteristics, and clinical complications related to UEs. Through that QI initiative, we demonstrated a reduction in our UE rate, typically reported as the number of UEs per 100 ventilator days, from 0.45 to 0.02 followed by a span of 480 consecutive days without a UE in the infant cardiac NICU (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Following that QI initiative, we sought to determine if the route of TI affected the UE rate. We were uniquely poised to study this given our NICU’s population of predominantly infants with NTI, as well as infants with OTI.\u003c/p\u003e\u003cp\u003eRoutinely in the NICU, the bedside nurse and/or respiratory therapist records the route of TI (NTI versus OTI) in the Lines, Drains, Airways (LDA) Flowsheet and Avatar in Epic. Thus, reports were generated from January 2022 to December 2024 to determine ventilator days broken down by route for each TI episode for any infant admitted to the NICU. The number of ventilator days were calculated by determining the difference between the start date and time of ETT placement and end date and time of ETT removal. The ventilator days were then categorized by TI site as OTI versus NTI. If the TI site data was omitted from the LDA Avatar, then manual chart review was done to extract this data, commonly found in the TI procedure notes.\u003c/p\u003e\u003cp\u003eAdditionally, data were collected for each infant who experienced an UE via chart review including gestational age, birth weight, route of TI, and any complication from an UE. The hospital portal was also queried over the study period to determine if any medical device-related pressure injuries (MDRPIs) were reported for either OTI or NTI for any infant in the NICU. The MDRPIs were staged 1 through 4 according to the 2019 Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eWe compared characteristics of infants who underwent NTI versus OTI by chi-square for categorical data and by two-tailed T-test for continuous data. We also compared characteristics of infants who experienced UE versus those who did not. In this analysis, Mann-Whitney U-test was performed, given the smaller sample size. Next, we conducted Kaplan-Meier univariate survival analyses to determine the risk of the endpoint of UE. Data were censored for planned extubation, death while intubated, or transfer out of the NICU while intubated. In the first survival analysis, we stratified infants by route of intubation. Next, we stratified infants by sex, gestational age, constitutional age, and birth weight.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 1,160 TI events were included, of which 602 (51.9%) were NTI and 558 (48.1%) were OTI. The baseline characteristics comparing the two groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Infants who underwent a NTI were born at a lower gestational age with a smaller birth weight and were intubated earlier in their NICU stay compared to those who underwent an OTI. There were no significant differences in birth weight Z-score (normalized by sex and gestational age) (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) and sex distribution. Among 602 NTIs, 6 cases of MDRPI of the naris were identified. Of these, 2 were unstageable, 2 were classified as stage I, and 2 as stage II. No MDRPIs were reported in the OTI group.\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 with Nasotracheal (NTI) and Orotracheal Intubations (OTI)\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\u003cp\u003eCharacteristic\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNTI\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;602)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOTI\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;558)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003csup\u003e2\u003c/sup\u003e\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\u003eGestational Age (weeks)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.8 (5.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.6 (5.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u0026ndash;41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u0026ndash;41\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\u003e\u003cb\u003eBirth Weight (Z-score)\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.390 (1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.373 (1.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.823\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-4.572\u0026ndash;9.215\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-3.241\u0026ndash;12.274\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\u003e\u003cb\u003eBirth Weight (g)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2220 (1080)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2410 (1090)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e336\u0026ndash;4500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e336\u0026ndash;4430\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\u003e\u003cb\u003eFemale Sex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e284 (47.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e267 (47.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.865\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge at Intubation (weeks)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.14 (6.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.68 (9.80)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u0026ndash;56.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u0026ndash;90.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e1\u003c/sup\u003e Data are shown as mean (SD), or n (%)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e2\u003c/sup\u003e chi square or T-test as indicated\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e3\u003c/sup\u003e Z-score normalized by sex and gestational age by Fenton curve (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA total of 23 UEs occurred during the study period\u0026mdash;9/23 (39.1%) were in the NTI group, and 14/23 (60.9%) were in the OTI group. The characteristics of the infants who had UEs in both the groups are presented in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. There were no significant differences in gestational age, birth weight, age at TI, or duration of TI prior to UE among infants with UEs between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). NTIs accounted for a total of 67,757 patient ventilator-days, while OTIs accounted for 45,080 patient ventilator-days. The UE rate was lower in the NTI group compared to the OTI group (0.01 versus 0.03 per 100 patient ventilator-days).\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\u003eCharacteristics of Infants with UEs in Nasotracheal (NTI) and Orotracheal Intubation (OTI) Groups\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\u003cp\u003eCharacteristic\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNTI Group\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOTI Group\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003csup\u003e2\u003c/sup\u003e\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\u003eGestational Age (weeks)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.44 (5.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.86 (6.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23\u0026ndash;39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u0026ndash;39\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\u003e\u003cb\u003eBirth Weight (Z-score)\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.40 (0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.46 (1.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.07\u0026ndash;1.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.15\u0026ndash;1.98\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\u003e\u003cb\u003eBirth Weight (g)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1500.89 (1262.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1512.50 (928.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e543\u0026ndash;3970\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e460\u0026ndash;3115\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\u003e\u003cb\u003eFemale Sex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (35.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge at ETT Placement (weeks)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.44 (8.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.93 (7.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u0026ndash;50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u0026ndash;40\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\u003e\u003cb\u003eDuration of Intubation (hours)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e213.52 (192.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e154.46 (351.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRange\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e106\u0026ndash;597\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u0026ndash;1366\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e1\u003c/sup\u003e Data are shown as mean (SD), or n (%)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e2\u003c/sup\u003e Chi squared, t-test or Mann-Whitney U test as indicated\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e3\u003c/sup\u003e Z-score normalized by sex and gestational age by Fenton curve (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSurvival analysis demonstrated that infants with an OTI were less likely to remain intubated versus infants with an NTI (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, p value\u0026thinsp;=\u0026thinsp;0.03). Our survival analysis did not demonstrate differences in UE risk when stratifying infants by sex, gestational age, constitutional age, or birth weight (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-D).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective review of 1,160 TI events amongst neonates and infants in the NICU, we found that the risk of UE was significantly higher in infants with OTI compared to infants with NTI. During the study period, the average overall UE rate in our NICU was 0.02 per 100 patient ventilator days while the UE rate in the NTI group was three times lower than the rate in the OTI group. In addition, infants with NTI had a low rate of MDRPIs.\u003c/p\u003e\u003cp\u003eUEs are one of the adverse events associated with TI that can result in possible significant cardiorespiratory compromise and complications including intraventricular hemorrhage, tracheal injury, and pulmonary injury, particularly when emergent reintubation is needed (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Multiple studies, including systematic reviews and previous QI efforts, have evaluated various risk factors for UEs in neonates. These include lower gestational age, especially \u0026lt; 29 weeks, due to shorter tracheal length and difficulty securing the ETT, infrequent sedation use, prolonged TI, low nurse-to-patient ratios, patient movement, bedside procedures, and excessive secretions (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Carvalho et al. found that each additional day on mechanical ventilation increased UE risk by 3% (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDespite the extensive literature available on risk factors for UE, there are limited descriptions of the association between the route of TI and the risk of UE in the NICU population. Anecdotal reports note that UEs more common following OTI compared to NTI (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e–\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The Cochrane systematic review published in 2000, comparing OTI and NTI included only two studies, each with a sample size of less than 100 neonates and with inconclusive results (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Of note, the analysis in these studies did not account for planned extubations. In our study, we addressed this limitation by using Kaplan-Meier survival analysis, which allowed us to account for planned extubations. Furthermore, our institution’s practice of predominantly performing NTIs in neonates since 1970s provided a robust cohort of neonates intubated by both routes, with a total of 1,160 TI events available for review during our study period.\u003c/p\u003e\u003cp\u003eThe literature on contraindications to and complications of NTI in neonates is limited. Basilar skull fracture and coagulopathy have been reported as contraindications to NTI in children (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Though there is no published literature regarding specific contraindications in neonates, potential limitations may include anatomical conditions that obstruct passage of the ETT through the nasal cavity, such as choanal atresia, choanal stenosis, or midfacial anomalies like congenital pyriform aperture stenosis. In our NICU, there is no minimum gestational age or weight threshold below which NTI is considered contraindicated.\u003c/p\u003e\u003cp\u003ePotential complications of NTI, such as nasal trauma, epistaxis, sinusitis, nasal ala necrosis, and retropharyngeal perforation, have been reported primarily in the pediatric population (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). To date, five cases of traumatic perforation of lamina cribrosa during NTI in neonates have been reported in the literature (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). To reduce the risk of trauma, the use of a soft guide, such as a suction catheter inserted into the ETT has been recommended (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). An adult study done in 1993 on complications and late sequalae of NTI in adults reported bleeding from nasal cavity in 19% of patients (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). In contrast, a more recent study by Abdelbaser et al. involving 220 infants undergoing cardiac surgery found that only 3 out of 98 infants who underwent NTI experienced transient, self-limited nasal bleeding, likely due to the use of uncuffed, well-lubricated ETTs (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAnother complication associated with NTIs is nasal pressure injury, which has been reported in about 40–70% in older children (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). However, there is limited data in neonates. A recent study by Vogt et al comparing NTI and OTI in neonates who underwent cardiac surgery, reported skin breakdown in 8.9% of those with NTI versus 1.1% of those with OTI (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In our unit, six MDRPIs of the naris were reported in the NTI group during the study period, which is an incidence of only 1%, while none were reported in the OTI group.\u003c/p\u003e\u003cp\u003eLastly, although some reports suggest that OTI is easier and faster to perform under direct laryngoscopy (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), data from NICUs where NTI is a standard practice challenge this assumption. A study done in a European NICU where NTIs were performed in 98% of cases reported a first-attempt TI success rate of 42% compared to 49% reported by the NEARS4NEO registry, where 93% of TIs were in infants with an OTI (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). TI associated events were also similar in frequency amongst both studies (57.4% versus 66%, respectively). These findings suggest that with appropriate provider training, NTI can achieve success rates comparable to OTI.\u003c/p\u003e\u003cp\u003eSome recent studies also reported potential benefits of NTI beyond UE prevention including reduced postoperative sedation use and faster progression to full oral feeds with less oral aversion, but were limited by small sample size and focus on term infants who required cardiac surgery (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Data comparing these outcomes in preterm neonates remains limited.\u003c/p\u003e\u003cp\u003eGiven the scarcity of data surrounding NTI in neonates, further studies comparing both TI routes, along with consistent provider training in both NTI and OTI techniques, would enable a more individualized approach to neonatal airway management. This would allow healthcare providers to assess risks and benefits, selecting the most appropriate TI route for each patient rather than defaulting to the oral route for all neonates.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLimitations\u003c/span\u003e:\u003c/p\u003e\u003cp\u003eWhile our findings offer valuable insights, our study does have limitations. First, as a retrospective study, we could only demonstrate an association but not a cause-effect relationship and the retrospective study design is inherently subject to selection and ascertainment biases. Second, we did not control for potential confounding variables, such as sedation use, suctioning frequency, or nurse-to-patient ratios. Additionally, there were differences between the baseline characteristics of infants who underwent a NTI versus an OTI. Infants who underwent OTI were born at a higher gestational age, with greater birth weight, and had older constitutional age at TI. While our survival analysis did not detect differences in UE risk when accounting for these factors, we cannot exclude the possibility that these underlying differences confounded our findings. Third, our reliance on hospital safety-portal reports may have led to underreporting of TI-related complications other than UEs. Fourth, we did not assess long-term outcomes such as nasal or palatal deformities (e.g. palatal grooves after an OTI) that may require intervention, particularly since palatal grooves have been reported in up to 35% of preterm neonates with OTI in the literature (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFinally, the study was conducted at a single level IV NICU with extensive experience in performing NTIs in addition to maintenance and securement of nasotracheal tubes at the bedside. Our overall UE rate was substantially lower than the average rate of 0.61 per 100 patient ventilator days reported by the Solutions for Patient Safety Network, which included data from about 120 NICUs during this study period (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This difference is likely due to a multitude of reasons including use of an airway safety bundle and potentially the route of TI (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). These aspects limit the generalizability of our findings. Thus, more prospective randomized controlled trials are needed to investigate the association of UE with route of TI.\u003c/p\u003e"},{"header":"Conclusion and future directions","content":"\u003cp\u003eTo date, no definitive evidence exists to recommend one TI route over the other in the neonatal population; however, OTI continues to be the standard approach adopted in many NICUs across the United States (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Our study demonstrated that NTI is associated with a significantly lower rate of UEs compared to OTI in our population. Given the substantial impact of UEs and the limited data surrounding NTI, there is a need for prospective randomized controlled trials to further support our findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests:\u003c/h2\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u003cp\u003eThis project was determined to be exempt from ethics approval and consent by the Columbia University Institutional Review Board, given this is a study of de-identified data generated in a prior QI project. The study was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMoya FR, Mazela J, Shore PM, Simonson SG, Segal R, Simmons PD, et al. Prospective observational study of early respiratory management in preterm neonates less than 35\u0026thinsp;weeks of gestation. BMC Pediatr. 2019 May 11;19(1):147. \u003c/li\u003e\n\u003cli\u003eWyllie J, Perlman JM, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, et al. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2015 Oct;95:e169-201. \u003c/li\u003e\n\u003cli\u003eBannister F. DIRECT LARYNGOSCOPY AND TRACHEAL INTUBATION. The Lancet. 1944 Nov;244(6325):651\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eGreenland KB. Two curves and three columns\u0026ndash;A reappraisal of direct laryngoscopy. Oper Tech Otolaryngol-Head Neck Surg. 2020 Jun;31(2):83\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eAbdelbaser I, Abourezk AR, Magdy M, Elnegerey N, Sabry R, Tharwat M, et al. Comparison of the Outcomes of Oral Versus Nasal Endotracheal Intubation in Neonates and Infants Undergoing Cardiac Surgery: A Randomized Controlled Study. J Cardiothorac Vasc Anesth. 2023 Oct;37(10):2012\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eGillespie NA. The evolution of endotracheal anaesthesia. J Hist Med Allied Sci. 1946 Oct;1(4):583\u0026ndash;94. \u003c/li\u003e\n\u003cli\u003eSpence K, Barr P. Nasal versus oral intubation for mechanical ventilation of newborn infants. Cochrane Database Syst Rev. 2000;1999(2):CD000948. \u003c/li\u003e\n\u003cli\u003eSchou J. Nasotracheal versus orotracheal intubation--a balanced conclusion? Acta Anaesthesiol Scand. 1994 Feb;38(2):192\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003eSpitzer AR, Fox WW. Postextubation atelectasis-the role of oral versus nasal endotracheal tubes. J Pediatr. 1982 May;100(5):806\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eYildirim MI, Spaeder MC, Castro BA, Chamberlain R, Fuzy L, Howard S, et al. The Impact of Nasal Intubation on Feeding Outcomes in Neonates Requiring Cardiac Surgery: A Randomized Control Trial. Pediatr Cardiol. 2024 Feb;45(2):426\u0026ndash;32. \u003c/li\u003e\n\u003cli\u003eAlves PVM, Luiz RR. The influence of orotracheal intubation on the oral tissue development in preterm infants. Oral Health Prev Dent. 2012;10(2):141\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eHolzapfel L. Nasal vs oral intubation. Minerva Anestesiol. 2003 May;69(5):348\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eStewart AR, Finer NN, Moriartey RR, Ulan OA. Neonatal nasotracheal intubation: an evaluation. The Laryngoscope. 1980 May;90(5 Pt 1):826\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eMcMillan DD, Rademaker AW, Buchan KA, Reid A, Machin G, Sauve RS. Benefits of orotracheal and nasotracheal intubation in neonates requiring ventilatory assistance. Pediatrics. 1986 Jan;77(1):39\u0026ndash;44. \u003c/li\u003e\n\u003cli\u003eAngelos GM, Smith DR, Jorgenson R, Sweeney EA. Oral complications associated with neonatal oral tracheal intubation: a critical review. Pediatr Dent. 1989 Jun;11(2):133\u0026ndash;40. \u003c/li\u003e\n\u003cli\u003eVogt P, Downey L, Gleason ME, Dresner LD, Clark S, Shashidharan S, et al. Outcomes of Nasotracheal Versus Orotracheal Intubation in Neonates After Cardiopulmonary Bypass Surgery: A Retrospective Cross-Sectional Analysis. Paediatr Anaesth. 2025 Jul 9; \u003c/li\u003e\n\u003cli\u003eBrei BK, Sawyer T, Umoren R, Gray MM, Krick J, Foglia EE, et al. Associations between family presence and neonatal intubation outcomes: a report from the National Emergency Airway Registry for Neonates: NEAR4NEOS. Arch Dis Child Fetal Neonatal Ed. 2021 Jul;106(4):392\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eFoglia EE, Ades A, Napolitano N, Leffelman J, Nadkarni V, Nishisaki A. Factors Associated with Adverse Events during Tracheal Intubation in the NICU. Neonatology. 2015;108(1):23\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eSolutions for Patient Safety [Internet]. [cited 2025 Feb 20]. Unplanned Extubations. Available from: https://www.solutionsforpatientsafety.org/unplannedextubations\u003c/li\u003e\n\u003cli\u003eSilva PSL da, Reis ME, Aguiar VE, Fonseca MCM. Unplanned extubation in the neonatal ICU: a systematic review, critical appraisal, and evidence-based recommendations. Respir Care. 2013 Jul;58(7):1237\u0026ndash;45. \u003c/li\u003e\n\u003cli\u003eMerkel L, Beers K, Lewis MM, Stauffer J, Mujsce DJ, Kresch MJ. Reducing unplanned extubations in the NICU. Pediatrics. 2014 May;133(5):e1367-1372. \u003c/li\u003e\n\u003cli\u003eLamy Filho F, Silva AAM da, Lopes JMA, Lamy ZC, Sim\u0026otilde;es VMF, Dos Santos AM. Staff workload and adverse events during mechanical ventilation in neonatal intensive care units. J Pediatr (Rio J). 2011;87(6):487\u0026ndash;92. \u003c/li\u003e\n\u003cli\u003eCreze\u0026eacute; KL, DiGeronimo RJ, Rigby MJ, Carter RC, Patel S. Reducing Unplanned Extubations in the NICU Following Implementation of a Standardized Approach. Respir Care. 2017 Aug;62(8):1030\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eAhn E, Cullen SM, Osorio SN, Ehret C, Jonas K, Blake CE, et al. Reducing NICU Unplanned Extubations From Tube Dislodgement. Pediatrics. 2024 Jun 1;153(6):e2022061170. \u003c/li\u003e\n\u003cli\u003eGaliote JP, Ridor\u0026eacute; M, Carman J, Zell L, Brant K, Gayle C, et al. Reduction in Unintended Extubations in a Level IV Neonatal Intensive Care Unit. Pediatrics. 2019 May;143(5):e20180897. \u003c/li\u003e\n\u003cli\u003eKim F, Eckels VB, Brachio SS, Brooks C, Ehret C, Gomez G, et al. Use of an airway bundle to reduce unplanned extubations in a neonatal intensive care unit. J Perinatol Off J Calif Perinat Assoc. 2024 Feb;44(2):314\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eNair V, Smith H. Phased Quality Improvement Interventions in Reducing Unplanned Extubation in the Neonatal ICU. Respir Care. 2020 Oct;65(10):1511\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eInternational Guideline [Internet]. [cited 2025 Apr 12]. 2019 Guideline. Available from: https://internationalguideline.com/2019\u003c/li\u003e\n\u003cli\u003eKottner J, Cuddigan J, Carville K, Balzer K, Berlowitz D, Law S, et al. Prevention and treatment of pressure ulcers/injuries: The protocol for the second update of the international Clinical Practice Guideline 2019. J Tissue Viability. 2019 May;28(2):51\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eFenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013 Apr 20;13:59. \u003c/li\u003e\n\u003cli\u003eFont\u0026aacute;nez-Nieves TD, Frost M, Anday E, Davis D, Cooperberg D, Carey AJ. Prevention of unplanned extubations in neonates through process standardization. J Perinatol Off J Calif Perinat Assoc. 2016 Jun;36(6):469\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eCarvalho FL, Mezzacappa MA, Calil R, Machado H da C. Incidence and risk factors of accidental extubation in a neonatal intensive care unit. J Pediatr (Rio J). 2010;86(3):189\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eKim J, Jeon S. Nasotracheal intubation in pediatrics: a narrative review. J Dent Anesth Pain Med. 2024 Apr;24(2):81\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eLupi F, Staffler A, Parmeggiani L, Klemme M, Dalla Pozza R, Stuefer J, et al. Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature. Clin Case Rep. 2021 Sep;9(9):e04650. \u003c/li\u003e\n\u003cli\u003eCameron D, Lupton BA. Inadvertent brain penetration during neonatal nasotracheal intubation. Arch Dis Child. 1993 Jul;69(1 Spec No):79\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eHoldgaard HO, Pedersen J, Schurizek BA, Melsen NC, Juhl B. Complications and late sequelae following nasotracheal intubation. Acta Anaesthesiol Scand. 1993 Jul;37(5):475\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eChen J, Chen J, Yang J, Chen Y, Liang Y, Lin Y. Investigating the Efficacy of Hydrocolloid Dressing for Preventing Nasotracheal Tube-Related Pressure Injury in the PICU. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2020 Sep;21(9):e752\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eTippmann S, Haan M, Winter J, M\u0026uuml;hler AK, Schmitz K, Sch\u0026ouml;nfeld M, et al. Adverse Events and Unsuccessful Intubation Attempts Are Frequent During Neonatal Nasotracheal Intubations. Front Pediatr. 2021;9:675238. \u003c/li\u003e\n\u003cli\u003eFoglia EE, Ades A, Sawyer T, Glass KM, Singh N, Jung P, et al. Neonatal Intubation Practice and Outcomes: An International Registry Study. Pediatrics. 2019 Jan;143(1):e20180902. \u003c/li\u003e\n\u003cli\u003eCortines AAO, Costa LR. Associated factors and persistence of palatal groove in preterm infants: a cohort study. BMC Pediatr. 2016 Aug 24;16(1):143. \u003c/li\u003e\n\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":"","lastPublishedDoi":"10.21203/rs.3.rs-7285543/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7285543/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo evaluate the association between orotracheal versus nasotracheal intubation route and unplanned extubation (UE) risk among neonates.\u003c/p\u003e\u003ch2\u003eStudy Design:\u003c/h2\u003e\u003cp\u003eThis retrospective cohort study included all tracheal intubation (TI) events among neonates admitted to a level IV NICU from 2022 to 2024. Kaplan-Meier survival analysis was used to assess UE risk by TI route.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e\u003cp\u003eThere were 1,160 TI events and 23 UEs during the study period. The UE rate was three times lower in nasotracheal intubation group compared to orotracheal (0.01 vs 0.03 per 100 ventilator days). UE risk was significantly higher in orotracheally intubated infants (p\u0026thinsp;=\u0026thinsp;0.03) with no differences when stratified by sex, gestational age, or birth weight.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eNasotracheal intubation was associated with lower UE risk in neonates in a unit that predominantly performs nasotracheal intubation. Prospective randomized studies are needed to further investigate if TI route may contribute to fewer UEs in this population.\u003c/p\u003e","manuscriptTitle":"Comparison of Unplanned Extubations Associated with Orotracheal versus Nasotracheal Intubation in Neonates","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-20 08:54:55","doi":"10.21203/rs.3.rs-7285543/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-08-28T14:05:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-08-16T15:15:29+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-08-15T17:15:42+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-08-12T15:08:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-11T14:50:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Perinatology","date":"2025-08-10T18:02:56+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2025-08-04T09:23:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-03T22:09:32+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":"b38fb05a-f921-4b97-9297-74d2c5d7f23b","owner":[],"postedDate":"August 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":53056930,"name":"Health sciences/Health care/Paediatrics"},{"id":53056931,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-04-14T07:06:40+00:00","versionOfRecord":{"articleIdentity":"rs-7285543","link":"https://doi.org/10.1038/s41372-026-02615-y","journal":{"identity":"journal-of-perinatology","isVorOnly":false,"title":"Journal of Perinatology"},"publishedOn":"2026-04-13 04:00:00","publishedOnDateReadable":"April 13th, 2026"},"versionCreatedAt":"2025-08-20 08:54:55","video":"","vorDoi":"10.1038/s41372-026-02615-y","vorDoiUrl":"https://doi.org/10.1038/s41372-026-02615-y","workflowStages":[]},"version":"v1","identity":"rs-7285543","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7285543","identity":"rs-7285543","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}