Home Oxygen Therapy for Thai Preterm Infants with Bronchopulmonary Dysplasia. What Are the Predictive Factors for Successful Weaning: A 20-year Review

Home Oxygen Therapy for Thai Preterm Infants with Bronchopulmonary Dysplasia. What Are the Predictive Factors for Successful Weaning: A 20-year Review | 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 Research Article Home Oxygen Therapy for Thai Preterm Infants with Bronchopulmonary Dysplasia. What Are the Predictive Factors for Successful Weaning: A 20-year Review Vipada Grajangdara, Anchalee Limrungsikul, Allan L. Coates, Harutai Kamalaporn This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4014163/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jan, 2025 Read the published version in BMC Pediatrics → Version 1 posted 6 You are reading this latest preprint version Abstract Background Consequences of lung injury and inflammation in preterm infants with bronchopulmonary dysplasia (BPD) contribute to prolonged oxygen requirements. Home oxygen therapy (HOT) is an alternative way of respiratory support in BPD infants. However, there is no consensus on weaning guidelines either under the supervision of physicians or unsupervised weaning by parents. Our objective is to identify the median age of home oxygen discontinuation and the factors that might predict the duration of HOT in a resource poor country. Methods All preterm (≤ 36 weeks' gestation) infants diagnosed BPD who required HOT after discharged from Ramathibodi Hospital during January 2000 – December 2019 comprised this retrospective study. Timing of HOT withdrawal was identified. Demographic data, severity of BPD, history of respiratory support, procedures, prenatal history, comorbidities, and complications were recorded and analyzed as factors associated of home oxygen withdrawal. Results Of 8581 preterm infants born during the 20-year period, 563 (6.6%) had BPD. Among 40 infants treated with HOT, 18 (45%) were successfully weaned oxygen within 12 months. The median corrected age (CA) of oxygen withdrawal was 13.8 months (8.5, 22.1). Longer duration of total respiratory support, longer length of hospital stay, and poor weight gain were associated with longer duration of HOT. Greater weight gain was associated with a shorter duration of HOT at 12 months CA (adjusted OR, 1.97; 95% CI, 1.13–3.23; p = 0.015). Conclusions The median corrected age of oxygen withdrawal in Thai BPD infants was 13.8 months. Severe BPD and poor weight gain were associated with prolonged home oxygen use. Despite not being able to follow all the guidelines due to economic constraints, the clinical outcomes were comparable to the resource rich countries. Bronchopulmonary dysplasia Home oxygen Preterm infants Oxygen withdrawal Resource poor country Figures Figure 1 Figure 2 Introduction Bronchopulmonary dysplasia (BPD) is a common complication in premature infants requiring mechanical ventilation. While advances in neonatal care increases survival at earlier gestational ages (GA), chronic neonatal respiratory disease remains a challenge. BPD is now characterized by impairment of alveolarization resulted from immaturity more than lung injury from mechanical ventilator. 1–4 The 2001 definition of BPD as more than 28 days of supplemental oxygen (O 2 ) and severity defined by need for O 2 or positive pressure support at 36 weeks GA if born at < 32 weeks GA, 56 days chronological age, or at the time of discharge if born at ≥ 32 weeks GA, is simple but may be outdated. 2, 5–9 The main endpoint of O 2 therapy in BPD patients is to maintain target O 2 saturation of 90–95% and to prevent pulmonary hypertension (PH). 10–14 If weaning to room air cannot happen, before discharge, an alternative is to give O 2 at home which improves the quality of life, prevents nosocomial infection and saves costs. 10, 14–15 Although home O 2 therapy (HOT) is worldwide, there is no consensus on weaning guidelines either under the supervision of physicians or unsupervised weaning by parents. 10, 14–17 European Respiratory Society (ERS) guidelines on management of children with BPD has suggested the “O 2 reduction test” assessing O 2 saturation during weaning to room air. The utility of home O 2 saturation monitoring is unclear. 14 In United States, weaning is recommended to be under the supervision of a pediatric pulmonologist using pulse- oximetry while awake with subsequent weaning during sleep assessed through overnight polysomnography or home pulse-oximetry. However, home O 2 withdrawal without physicians’ supervision were observed in 32% of BPD children in this study. 16 Studies have shown a median age, from 2 to 12.5 months, when HOT was discontinued. 17–21 Factors associated with earlier HOT discontinuation were shorter duration of NICU stay 21 and lower flow requirements. 16 There are various O 2 generator devices and different assessment modes of O 2 weaning 10 but no practical guidelines for HOT weaning in a resource- poor country. At Ramathibodi Hospital, a tertiary care center in Thailand, a HOT program for BPD children has been active for more than 20 years. Our multidisplinary very-low-birthweight (VLBW) clinic consists of neonatologists, pediatric pulmonologists, gastroenterologists, nutritionists and nurse coordinators. The pediatric pulmonologists consider O 2 weaning based on physical examination, O 2 saturation in room air, parental record of pulse oximetry monitoring at home > 92% with various activities in patients without PH, > 95% in patients with PH, and adequate weight gain. Some physicians may perform O 2 stress test or O 2 reduction test. Overnight pulse oximetry or polysomnography are reserved for the patients with complications such as PH, bronchomalacia, subglottic stenosis or patients with home ventilators. The O 2 delivery systems included O 2 tanks and O 2 concentrators, available since 2010. While the O 2 concentrator was convenient and less expensive, it was impossible to titrate O 2 flows accurately below 1 L/min. Thai system of national health coverage does not include HOT and has less resources for evaluating readiness for weaning. Low flow O 2 devices and polysomnography are not available in most of the hospitals. With the economic burden, the most frequently asked question from parents is when they could expect the HOT withdrawal. Thus, to provide prognostic information for parents, the aim of this 20-year retrospective study was to identify the median age of HOT discontinuation and the factors that might predict prolonged HOT. Comparisons of the outcomes such as mortality and readmission to the resource- rich countries were the secondary objectives. Materials and Methods Study population This retrospective study was performed in the division of pediatric pulmonology, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand during January 2000 - December 2019. Electronic medical records of infants with BPD who required HOT were reviewed. The 2001 definition of BPD 2 was used since it was the accepted definition at enrollment into the study. All preterm infants born before 36 GA, diagnosed with BPD based on National Institutes of Health (NIH) criteria 2001, and followed up in the VLBW and chest clinic were recruited. We excluded patients who required HOT due to other causes such as congenital cyanotic heart diseases, congenital airway anomalies, or congenital diaphragmatic hernia. This study was approved by Ramathibodi Human Research Ethics Committee (COA. MURA2020/901). The need for informed consent was waived by an IRB as it was unnecessary according to national regulations. Outcomes The primary outcome was the median corrected age (CA) when home O 2 use was discontinued. O 2 withdrawal was defined as either under the supervision of a physician or the unsupervised discontinuation by parents. Small for gestational age (SGA) was defined as birth weight < 10th percentile based on Fenton 2013 preterm growth chart. 22 Demographic and clinical data including GA, prenatal history, severity of BPD, history of surfactant administration, duration of mechanical ventilation and O 2 supplementation, procedures and medications, comorbidities, and complications were recorded. Weight gain at O 2 withdrawal was calculated from the subtraction of weight at the time of discharge and the time of O 2 withdrawal divided by the duration of HOT. The method of weaning and evaluation of O 2 cessation were included. Statistical analyses Baseline characteristics were tested for normality by Kolmogorov-Smirnov or Shapiro-Wilk test and presented as means with standard deviation or medians with interquartile range. Mann-Whitney U test and t -test were used to compare continuous variables with non-normally distributed and normally distributed, respectively, while chi-square was used to compare categorical variables. Adjusted odd ratios were assessed by logistic regression analysis to identify correlation between possible prognostic factors and the corrected age of O 2 withdrawal at 12 months. Statistical significance was considered when P-values < 0.05. The 20-year delivery period was divided into 2 periods (2000 to 2009, the pre-surfactant era and 2010 to 2019, the post-surfactant era) with regard to differences of home O 2 use. The associations were analyzed based on univariate and multivariate logistic regression analysis. Results During January 2000 – December 2019, 8581 preterm infants were born at Ramathibodi Hospital. The prevalence of BPD was 563 of 8581 (6.6%) of the preterm infants (Figure 1). Figure 1. The number of infants with BPD and those who were sent home with oxygen supplementation during the year 2000-2019 Fifty-three of 563 (9.4%) infants with BPD were discharged home on HOT. Thirteen patients were excluded; 2 patients died before the O 2 cessation (the first patient died at 4 months CA from severe pneumonia, another died from severe pulmonary hemorrhage and PH at 7 months CA), 2 patients had congenital diaphragmatic hernia, 1 had Pierre- Robin syndrome, and 8 patients were lost to follow- up. Therefore 40 BPD patients who received HOT were recruited. The baseline characteristics of infants with BPD and those who were sent home on HOT during the year 2000-2019 is shown in Table 1. Table 1. Baseline characteristics Variables Home oxygen (n = 40) Male sex (%) Gestational age (weeks) a Birth weight (g) b Small for gestational age (%) Cesarean section (%) Maternal chorioamnionitis (%) Complete antenatal steroids (%) Premature rupture of membrane (%) Oxygen required at delivery (%) Surfactant (%) Invasive ventilation (days) b Noninvasive ventilation (days) a Total respiratory support (days) b High-frequency oscillatory ventilation (%) High-frequency oscillatory ventilation (days) b Severe BPD (%) Surgical PDA ligation Inhaled corticosteroids (%) Length of hospital stay (days) a CA at discharge (weeks) b CA at O 2 withdrawal (months) c Duration of home O 2 therapy (months) c 15 (60) 27.9 ± 2.5 845 (722.5, 1040) 13 (32.5) 28 (70) 4 (11) 26 (65) 10 (25) 36 (94.7) 28 (70) 29 (14, 38) 68 ± 39 146 (126, 178) 29 (72.5) 12 (6, 22) (n = 29) 35 (87.5) 6 (15) 26 (65) 159 ± 48 8.6 (5.3, 12.6) 13.8 (8.5, 22.1) 11.3 (5.6, 17.5) Abbreviations: CA, corrected age; O 2 , oxygen; PDA, patent ductus arteriosus; SGA, small for gestational age defines as birth weight < 10 th percentile based on Fenton 2013 preterm growth chart. a Continuous variables were expressed as mean ± standard deviation b Continuous variables were expressed as median (interquartile range) c Continuous variables were expressed as median (interquartile range) excluded infants who continued oxygen use (n = 37). The subjects had a mean GA of 27.9 ± 2.5 weeks and a median birth weight of 845 g (722.5, 1040). Thirty-five (87.5%) had severe BPD. The total length of hospital stay was 159 ± 48 days. Twelve subjects (30%) had echocardiogram confirmed PH. Of the 40 infants, 37 (92.5%) discontinued HOT during the study period and 18 of 40 infants (45%) successfully weaned off O 2 by 12 months (Table 2, Figure 2). Table 2. Comparisons of factors in BPD infants with oxygen withdrawal at 12 months CA cutoff Factors O 2 withdrawal ≤ CA 12 mo (n = 18) O 2 withdrawal > CA 12 mo (n = 22) P-value Gestational age (weeks) b Birth weight (g) b Invasive ventilation (days) a Noninvasive ventilation (days) a Total respiratory support in hospital (days) a HFOV (%) HFOV (days) b Maximum MAP of HFOV a Inhaled corticosteroids (%) Severe BPD (%) DOL at ICS started (day) b DOL at post-natal steroids started (day) b Length of hospital stay (days) b CA at discharge (weeks) b Weight at discharge (g) a Weight at O 2 withdrawal (g) a Weight gain at O 2 withdrawal (g/day) a 28.4 (26.7, 30.7) 965 (710, 1165) 26 ± 16 46 ± 27 136 ± 34 11 (61.1) 12 (4, 16) 14 ± 2.7 10 (55.6) 13 (72.2) 16 (13, 48) 25 (19, 37) 126 (111, 170) 5.9 (4, 11.4) 4291 ± 897 7083 ± 1818 17 ± 7.3 27.1 (25.9, 28.6) 825 (713, 945) 34 ± 25 85 ± 40 174 ± 49 18 (81.8) 13 (6, 23) 15.4 ± 3.1 16 (72.7) 22 (100) 41 (22, 66) 31 (24, 50) 161 (134, 211) 10.1 (7.6, 17) 5178 ± 960 10072 ± 1330 8.8 ± 2.6 0.138 0.192 0.242 0.001 0.010 0.173 0.589 0.226 0.257 0.013 0.073 0.341 0.008 0.019 0.005 <0.001 <0.001 Abbreviation: HFOV, High-frequency oscillatory ventilation; MAP, mean airway pressure; CA, corrected age; O 2 , oxygen; DOL, day of life; HHHFNC, Heated humidified high flow nasal cannula; ICS, inhaled corticosteroid a Continuous variables were expressed as mean ± standard deviation; b Continuous variables were expressed as median (interquartile range) Fig. 2 Kaplan-Meier Plot demonstrating the age of oxygen withdrawal in 40 BPD infants The median CA of O 2 withdrawal was 13.8 months (8.5, 22.1) and the median was 11.3 months (5.6, 17.5). There were six patients with prolonged HOT beyond the corrected age of 2 years. All of them had severe BPD and had been treated with high-frequency oscillatory ventilation (HFOV). The characteristics of these patients are shown in Table 3. Table 3. Characteristics of the BPD patients with prolonged home oxygen therapy beyond the corrected age of 24 month Subject No. Year of birth GA (wk) BW (g) PPHN LOS (d) Readmission (n) Age at O 2 withdrawal (mo) Remarks* 1 2009 34 720 No 232 0 24.3 bronchomalacia, atelectasis, GERD 2 a 2013 25 845 Yes 225 2 (PICU) 29.8 pulmonary hypertension, subglottic stenosis, GERD 3 a 2014 27 770 No 146 3 24.7 BBA 4 2017 26 800 No 184 1 31.2 Triplets, BHR 5 a 2018 25 675 Yes 135 6 (1 PICU) 37.2 GERD, aspiration pneumonia 6 2018 29 930 Yes 133 1 (PICU) 29.8 bronchomalacia, ARDS, subglottic stenosis, GERD Abbreviation: GA, gestational age; BW, birth weight; PPHN, persistent pulmonary hypertension of the newborn; LOS, length of hospital stay; O 2 , oxygen; CA, corrected age; ARDS, acute respiratory distress syndrome; GERD, gastroesophageal reflux disease; BHR, bronchial hyperresponsiveness; BBA, birth before arrival *All patients had severe BPD a Patients has never received antenatal steroids Table 2 lists the factors associated with O 2 withdrawal at 12 months CA which were shorter duration of respiratory support in hospital (136 vs. 174 days, p = 0.01), shorter length of hospital stay (126 vs. 161 days, p=0.008), higher weight gain at O 2 withdrawal (17 ± 7.3 vs. 8.8 ± 2.6 g/day, p <0.001) and less severe BPD (72.2% vs. 100%, p =0.013). Multivariate logistic regression analysis revealed that only the higher weight gain remained a significant factor for O 2 withdrawal at 12 months CA (adjusted OR, 1.91; 95% CI, 1.13-3.23; p = 0.015). The overall survival rate of those born weighing <2500 grams in the pre-surfactant era was 94.0% vs. 96.4% in the post-surfactant era (p<0.01) while the incidence of BPD in these group was 4.2 and 8.4% respectively (p<0.005). However, the pre surfactant babies were 2 weeks more mature than the post and weighed significantly more Table 4. The modality of respiratory support including the use of inhaled corticosteroids (ICS) differed due to changes in care over time. Table 4. Comparison of infants required home oxygen therapy who were born during 2000-2009 and 2010-2019 Variables Year 2000-2009 (n = 9) Year 2010-2019 (n = 31) P-value Gestational age (weeks) a Birth weight (g) b SGA (%) Maternal chorioamnionitis (%) Surfactant administration (%) Invasive ventilation (days) b Noninvasive ventilation (days) a Total respiratory support (days) b HHHFNC (%) HFOV (%) HFOV (days) a Maximum MAP of HFOV a Inhaled corticosteroids (%) Severe BPD (%) Length of hospital stay (days) b Weight at discharge (g) a CA at O 2 withdrawal (months) a Duration of home O 2 (months) a Weight at O 2 withdrawal (g) a Weight gain at O 2 withdrawal (g/day) b Overnight SpO 2 monitoring (%) Oxygen concentrator use (%) Readmission due to respiratory illnesses (%) 29.7 ± 2.8 1100 (825, 1355) 3 (33.3) 0 (0) 1 (11.1) 28 (7, 31) 37 ± 25 145 (119, 174) 0 (0) 3 (33.3) 5 ± 2 10.3 ± 3.5 3 (33.3) 8 (88.9) 150 (118, 180) 4756 ± 613 9.9 ± 7 7.3 ± 6 7123 ± 1739 14.7 (5.8, 21.4) 4 (57.1) 0 (0) 4 (44.4) 27.4 ± 2.3 820 (690, 990) 10 (32.3) 4 (13.3) 27 (87.1) 29 (16, 39) 77 ± 38 146 (127, 181) 29 (93.5) 26 (83.9) 14 ± 9 15.5 ± 2.5 23 (74.2) 27 (87.1) 145 (126, 179) 4786 ± 1123 16.8 ± 8.6 14.5 ± 8.2 9033 ± 2119 10.3 (7.9, 15.6) 15 (51.7) 30 (96.8) 20 (64.5) 0.016 0.041 1.000 0.560 <0.001 0.438 0.006 0.503 <0.001 0.007 <0.001 0.003 0.044 1.000 0.871 0.939 0.033 0.019 0.047 0.484 0.074 < 0.001 0.441 Abbreviation: HFOV, High-frequency oscillatory ventilation; MAP, mean airway pressure; CA, corrected age; O 2 , oxygen; DOL, day of life; HHHFNC, heated humidified high flow nasal cannula; ICS, inhaled corticosteroid; SpO 2 , oxygen saturation a Continuous variables were expressed as mean ± standard deviation b Continuous variables were expressed as median (interquartile range) Preterm infants delivered during 2010-2019 had longer duration of HOT compared with those born during 2000-2009 (14.5 vs. 7.3 months, p = 0.019 and almost all used an O 2 concentrator (97% vs. 0 (p<0.001)) (Table 4). These differences did not extend to the use of overnight oximetry monitoring (57.1% vs. 51.7%, p = 0.074). The hospital admission due to respiratory tract infection and BPD complication, such as PH leading to heart failure and fluid intolerance, were not significantly different. After discharge home, there were 51 respiratory readmissions including pneumonia, atelectasis, ARDS in 24 patients. PH was diagnosed in 3 patients. Discussion The median CA of children with BPD discharged from supplemental O 2 was 13.8 months, longer than previous studies where CA at O 2 discontinuation was 2 to 12.5 months due to different patient characteristics, mode of O 2 support and weaning protocols. 16-21 The most recent study in 2021 reported that the median CA at O 2 cessation of 149 babies was 6.8 months with 87.2% of infants weaned by 12 months CA 21 compared to 45% (18 of 40) in our study. In contrast with Wong et al’s study in 2021, we had a higher proportion of SGA (32.5% vs. 8.7%), need longer respiratory support (146 vs. 73 days) and higher proportion of using HFOV (72.5% vs. 53%). Our study and Wong et al used overnight pulse oximetry monitoring as the assessment method of weaning while Yeh and Saletti used polysomnography. 16,19,21 Only one study in 2004 reported the rapid weaning at of 2 months CA by abrupt cessation of oxygen at the out-patient department when the level of oxygen saturation was more than 95% for 15 minutes. 19 The duration of HOT more than 12 months CA was associated with more severe BPD, longer duration of respiratory support, longer hospital stay and infants with poor weight gain (Table 2) as has been seen previously. 21 Hypercarbia on capillary blood gas has been associated with prolonged O 2 need 23 but was not performed in our study. While higher O 2 flow at discharge was a predictor of later home O 2 weaning 16,21 , the O 2 flow in our study did not predict the age of weaning. The analysis was divided into 2 time periods because the surfactant and non-invasive ventilation, especially the nasal CPAP and the heated humidified high flow nasal cannula were widely used in NICU after 2009. Comparing time periods, (2000-2009 vs. 2010-2019) (Table 4), infants born during 2010-2019 required longer HOT (9.9 vs. 16.8 months). Despite the attempt to reduce barotrauma, use of surfactant and ICS, the proportion of severe BPD remained unchanged, presumably because infants born in the latter period had earlier GA and lower birth weight. There was a slight but significant increase in survival during the later period which may also have led to a higher incidence of BPD. From previous studies 16,18 , as many as 36.7 – 47% of preterm infants with BPD were treated with HOT whereas only 9.4% (53 of 563) in our center. (Fig.1) The expense of HOT is not included in the national health coverage, some parents whose children were eligible for HOT may not be able to afford it. Hence, only the more severe patients are in our study, in which case if the parent could not afford home O 2 the team made great efforts to find some alternative funding. The most common equipment of home O 2 used in Thailand was O 2 concentrator, available in the last half of the study period, which delivered O 2 range from 0.5 -10 L/min, typically 1-2 L/min. The British Thoracic Society guidelines propose O 2 concentrators for long term HOT and compressed O 2 with a low flow regulator at a rate of 0.1-1 L/min for the short anticipated duration of HOT. 10 The median discharge O 2 flow in Wong et al study was only 0.25 L/min. 21 Most of participants (89%) in Yeh et al study required less than 0.5 L/min of O 2 supplement at discharge. 16 In US, the recommended home O 2 flow rate starts from 1/8 L/min or 0.1 L/min depends on the available devices. 17 In Thailand, we sent most of the babies home with at least 1 L/min of home O 2 because the low flow O 2 was not widely available. The supplemental O 2 improves growth in infants with BPD. 6,13,24 Intermittent hypoxemia has been shown to be associated with poor growth. 15 The proposed home O 2 weaning protocol in US suggests a slower wean for if growth is stagnant. 17 Our study would support these finding with the association between early O 2 withdrawal and higher weight gain. Most of BPD children should outgrow the need for supplemental O 2 by 2 years of life. 15, 24 We demonstrated six patients who required prolonged HOT in Table 3. All of them presented with severe BPD. Five patients were born during 2013-2018 and had many complications such as bronchomalacia, gastroesophageal reflux disease, PH and some had subglottic stenosis. The repeated infections and inflammations led to frequent readmission and subsequent weaning difficulty. Previous studies have shown that BPD infants who required HOT were more likely to be re-hospitalized for respiratory illness (38% vs. 28%; adjusted relative risk 1.33; 95% CI 1.16 to 1.53). 24 Sun L et al reported 48 of 62 (77%) BPD children had > 2 readmissions within 18-24 months 9 which is comparable to our study which revealed 24 of 40 (60%) BPD patients with HOT resulted in respiratory re-hospitalization. Interestingly, the prevalence of PH in our population was lower than previous studies. This may be derived from the higher flow of O 2 provided and/or the sick infants with PH in our setting could not be discharged. This study’s strength was a long duration of study period and comparisons between the pre-surfactant and aggressive ventilation era vs. the post-surfactant and non-invasive ventilation era. Limitations were due to the retrospective study design, there were missing data on radiography, environmental and socioeconomic factors. Using the NIH 2001 definition, the prevalence of BPD is higher than NICHD 2018. Mild BPD using 2001 criteria may not be diagnosed compared to 2018 criteria. 8-9 However the majority (87.5%) of our subjects had severe BPD which is not significantly different between the 2 definitions. In terms of the predictive ability on HOT and death from respiratory illnesses, the NICHD 2018 definition is superior to the NIH 2001 definition. 5, 7-9 Conclusion This 20-year review discovered that the median corrected age of HOT withdrawal in Thai infants with BPD was 13.8 months. Prolonged O 2 requirement was associated with longer duration of respiratory support in hospital, longer length of hospitalization and poor weight gain. Despite not being able to follow all the guidelines due to economic constraints, the outcomes were comparable to the resource-rich countries. Declarations AUTHOR CONTRIBUTIONS Vipada Grajangdara: conceptualization (equal); data curation (lead); formal analysis (lead); methodology (equal); project administration (lead); writing original draft (equal). Anchalee Limrungsikul: conceptualization (equal), resources (lead), data curation (equal); writing review & editing (supporting). Allan L. Coates: conceptualization (equal), data curation (equal), supervision (equal), writing review & editing (equal). Harutai Kamalaporn: conceptualization (lead); data curation (equal); formal analysis (supporting); methodology (equal); supervision (lead); writing original draft (equal); writing review & editing (equal). DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions. CONFLICT OF INTERESTS Harutai Kamalaporn received lecture fees from AstraZeneca, GlaxoSmithKline, and Organon. The remaining authors have nothing to disclose. The authors did not receive payment for development of this manuscript. HUMAN ETHICS APPROVAL DECLARATION This study was performed in accordance with the Declaration of Helsinki and approved by Ramathibodi Human Research Ethics Committee, Mahidol University (COA. MURA2020/901). References Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357:1946–55. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9. Thekkeveedu RK, Guaman MC, Shivanna B. Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology. Respir Med. 2017;132:170–7. Higgins RD, Jobe AH, Koso-Thomas M, Bancalari E, Viscardi RM, Hartert TV, Ryan RM, Kallapur SG, Steinhorn RH, Konduri GG, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr. 2018;197:300–8. Bancalari E, Jain D. Bronchopulmonary dysplasia: 50 years after the original description. Neonatology. 2019;115:384–91. Allen J, Panitch H. Bronchopulmonary dysplasia-a historical perspective. Pediatr Pulmonol. 2021;56:3478–89. Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach. Am J Respir Crit Care Med. 2019;200:751–9. Saengrat P, Limrungsikul A. Predictive Ability of the New Bronchopulmonary Dysplasia Definition on Pulmonary Outcomes at 20 to 24 months' Corrected Age of Preterm Infants. Am J Perinatol. 2021. 10.1055/s-0041-1735219 . Online ahead of print. Sun L, Zhang H, Bao Y, Li W, Wu J, He Y, Zhu J. Long-term outcomes of bronchopulmonary dysplasia under two different diagnostic criteria: a retrospective cohort study at a Chinese tertiary center. Front Pediatr. 2021;9:648972. Balfour-Lynn IM, Field DJ, Gringras P, Hicks B, Jardine E, Jones RC, Magee AG, Primhak RA, Samuels MP, Shaw NJ, et al. BTS guidelines for home oxygen in children. Thorax. 2009;64(Suppl II):ii1–26. Cherian S, Morris I, Evans J, Kotecha S. Oxygen therapy in preterm infants. Paediatr Respir Rev. 2014;15(2):135–41. Cummings JJ, Polin RA. Committee on fetus and newborn. Oxygen targeting in extremely low birth weight infants. Pediatrics. 2016;138(2):e20161576. Allen J, Zwerdling R, Ehrenkranz R, Gaultier C, Geggel R, Greenough A, Kleinman R, Klijanowicz A, Martinez F, Ozdemir A, et al. Statement on the care of the child with chronic lung disease of infancy and childhood. Am J Respir Crit Care Med. 2003;168(3):356–96. Duijts L, van Meel ER, Moschino L, Baraldi E, Barnhoorn M, Bramer WM, Bolton CE, Boyd J, Buchvald F, del Cerro MJ, et al. European Respiratory Society guideline on long-term management of children with bronchopulmonary dysplasia. Eur Respir J. 2020;55:1900788. Bhandari A, Panitch H. An update on the post-NICU discharge management of bronchopulmonary dysplasia. Semin Perinatol. 2018;42:471–7. Yeh J, McGrath-Morrow SA, Collaco JM. Oxygen weaning after hospital discharge in children with bronchopulmonary dysplasia. Pediatr Pulmonol. 2016;51(11):1206–11. Anderson C, Hillman NH. Bronchopulmonary dysplasia: When the very preterm baby comes home. Mo Med. 2019;116(2):117–22. Ejiawoko A, Lee HC, Lu T, Lagatta J. Home oxygen use for preterm infants with bronchopulmonary dysplasia in California. J Pediatr. 2019;210:55–62. e51. Saletti A, Stick S, Doherty D, Simmer K. Home oxygen therapy after preterm birth in Western Australia. J Paediatr Child Health. 2004;40(9–10):519–23. Norzila MZ, Azizi BH, Norrashidah AW, Yeoh NM, Deng CT. Home oxygen therapy for children with chronic lung diseases. Med J Malaysia. 2001;56(2):151–7. Wong MD, Neylan M, Williams G, Zahir SF, Chawla J. Predictors of home oxygen duration in chronic neonatal lung disease. Pediatr Pulmonol. 2021;56(5):992–9. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59. Dawson SK, D'Andrea LA, Lau R, Lagatta JM. Using a home oxygen weaning protocol and pCO 2 to evaluate outcomes for infants with bronchopulmonary dysplasia discharged on home oxygen. Pediatr Pulmonol. 2020;55(12):3293–303. DeMauro SB, Jensen EA, Bann CM, Bell EF, Hibbs AM, Hintz SR, Lorch SA. Home oxygen and 2-year outcomes of preterm infants with bronchopulmonary dysplasia. Pediatrics. 2019;143(5):e20182956. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 11 Jan, 2025 Read the published version in BMC Pediatrics → Version 1 posted Reviewers agreed at journal 09 Mar, 2024 Reviewers invited by journal 08 Mar, 2024 Editor assigned by journal 08 Mar, 2024 Editor invited by journal 05 Mar, 2024 Submission checks completed at journal 05 Mar, 2024 First submitted to journal 04 Mar, 2024 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-4014163","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":277030054,"identity":"f2fe19ed-3ecc-4dd1-bce5-88bceb8d1dc2","order_by":0,"name":"Vipada Grajangdara","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Vipada","middleName":"","lastName":"Grajangdara","suffix":""},{"id":277030055,"identity":"316cc382-d2d2-4cf7-a6eb-43dc6f3b82f1","order_by":1,"name":"Anchalee Limrungsikul","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Anchalee","middleName":"","lastName":"Limrungsikul","suffix":""},{"id":277030056,"identity":"00d9a58e-1252-447c-afa0-5441e4405123","order_by":2,"name":"Allan L. Coates","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"Allan","middleName":"L.","lastName":"Coates","suffix":""},{"id":277030057,"identity":"3bcb0247-bb61-4e1f-a19d-b0e4ee5dbc86","order_by":3,"name":"Harutai Kamalaporn","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYBACAwglAYQMjA8YGA7wMBxgbkCWwq7lAEQLswFECyNYiwQBLSB7GNgkwExCWszZzz6T/lBjwSDZfjqt6kbNHRm+440NDD9qGOrMcWix7Ek3kzhwTIJBmid32+2cY894JM8cbGDsOcYgYdmAw2EH0tgkDgCdJMcA0sJ2mMfgRmIDA28D0GEHcGg5/wyo5R9QC//bbcU5/yBaGP/i03IDaMvBNqDDJHK3Mee2QbQw47XlxjNmi7N9EjySM95uls7tOwz2y2GZYxKSG3A6LI3xRsW3OjmJ87kbP+d8O2zPd7z54MM3NTb8uGyBAR4U3gFwPI2CUTAKRsEoIBsAAOM5X3CravKYAAAAAElFTkSuQmCC","orcid":"","institution":"Mahidol University","correspondingAuthor":true,"prefix":"","firstName":"Harutai","middleName":"","lastName":"Kamalaporn","suffix":""}],"badges":[],"createdAt":"2024-03-04 19:15:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4014163/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4014163/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-024-05354-1","type":"published","date":"2025-01-11T15:57:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52454155,"identity":"ffe460a1-cadc-4388-9995-6b6b9ec64ae0","added_by":"auto","created_at":"2024-03-11 19:36:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":182355,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe number of infants with BPD and those who were sent home with oxygen supplementation during the year 2000-2019\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4014163/v1/295eb118092e193ce71bd34c.png"},{"id":52454156,"identity":"9ea8d3fb-4da2-41ca-8c62-22bbf12257a8","added_by":"auto","created_at":"2024-03-11 19:36:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":267363,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier Plot demonstrating the age of oxygen withdrawal in 40 BPD infants\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4014163/v1/d423849e956d227dc510367b.png"},{"id":73693903,"identity":"53c4f46d-c525-4d6d-8337-ba348e9e7638","added_by":"auto","created_at":"2025-01-13 16:09:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1854075,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4014163/v1/5ad8c809-90f0-4ba0-8823-92e8a272dcee.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Home Oxygen Therapy for Thai Preterm Infants with Bronchopulmonary Dysplasia. What Are the Predictive Factors for Successful Weaning: A 20-year Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBronchopulmonary dysplasia (BPD) is a common complication in premature infants requiring mechanical ventilation. While advances in neonatal care increases survival at earlier gestational ages (GA), chronic neonatal respiratory disease remains a challenge. BPD is now characterized by impairment of alveolarization resulted from immaturity more than lung injury from mechanical ventilator.\u003csup\u003e1\u0026ndash;4\u003c/sup\u003e The 2001 definition of BPD as more than 28 days of supplemental oxygen (O\u003csub\u003e2\u003c/sub\u003e) and severity defined by need for O\u003csub\u003e2\u003c/sub\u003e or positive pressure support at 36 weeks GA if born at \u0026lt;\u0026thinsp;32 weeks GA, 56 days chronological age, or at the time of discharge if born at \u0026ge;\u0026thinsp;32 weeks GA, is simple but may be outdated.\u003csup\u003e2, 5\u0026ndash;9\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe main endpoint of O\u003csub\u003e2\u003c/sub\u003e therapy in BPD patients is to maintain target O\u003csub\u003e2\u003c/sub\u003e saturation of 90\u0026ndash;95% and to prevent pulmonary hypertension (PH).\u003csup\u003e10\u0026ndash;14\u003c/sup\u003e If weaning to room air cannot happen, before discharge, an alternative is to give O\u003csub\u003e2\u003c/sub\u003e at home which improves the quality of life, prevents nosocomial infection and saves costs.\u003csup\u003e10, 14\u0026ndash;15\u003c/sup\u003e Although home O\u003csub\u003e2\u003c/sub\u003e therapy (HOT) is worldwide, there is no consensus on weaning guidelines either under the supervision of physicians or unsupervised weaning by parents.\u003csup\u003e10, 14\u0026ndash;17\u003c/sup\u003e European Respiratory Society (ERS) guidelines on management of children with BPD has suggested the \u0026ldquo;O\u003csub\u003e2\u003c/sub\u003e reduction test\u0026rdquo; assessing O\u003csub\u003e2\u003c/sub\u003e saturation during weaning to room air. The utility of home O\u003csub\u003e2\u003c/sub\u003e saturation monitoring is unclear.\u003csup\u003e14\u003c/sup\u003e In United States, weaning is recommended to be under the supervision of a pediatric pulmonologist using pulse- oximetry while awake with subsequent weaning during sleep assessed through overnight polysomnography or home pulse-oximetry. However, home O\u003csub\u003e2\u003c/sub\u003e withdrawal without physicians\u0026rsquo; supervision were observed in 32% of BPD children in this study.\u003csup\u003e16\u003c/sup\u003e Studies have shown a median age, from 2 to 12.5 months, when HOT was discontinued.\u003csup\u003e17\u0026ndash;21\u003c/sup\u003e Factors associated with earlier HOT discontinuation were shorter duration of NICU stay\u003csup\u003e21\u003c/sup\u003e and lower flow requirements.\u003csup\u003e16\u003c/sup\u003e There are various O\u003csub\u003e2\u003c/sub\u003e generator devices and different assessment modes of O\u003csub\u003e2\u003c/sub\u003e weaning\u003csup\u003e10\u003c/sup\u003e but no practical guidelines for HOT weaning in a resource- poor country.\u003c/p\u003e \u003cp\u003eAt Ramathibodi Hospital, a tertiary care center in Thailand, a HOT program for BPD children has been active for more than 20 years. Our multidisplinary very-low-birthweight (VLBW) clinic consists of neonatologists, pediatric pulmonologists, gastroenterologists, nutritionists and nurse coordinators. The pediatric pulmonologists consider O\u003csub\u003e2\u003c/sub\u003e weaning based on physical examination, O\u003csub\u003e2\u003c/sub\u003e saturation in room air, parental record of pulse oximetry monitoring at home\u0026thinsp;\u0026gt;\u0026thinsp;92% with various activities in patients without PH, \u0026gt; 95% in patients with PH, and adequate weight gain. Some physicians may perform O\u003csub\u003e2\u003c/sub\u003e stress test or O\u003csub\u003e2\u003c/sub\u003e reduction test. Overnight pulse oximetry or polysomnography are reserved for the patients with complications such as PH, bronchomalacia, subglottic stenosis or patients with home ventilators. The O\u003csub\u003e2\u003c/sub\u003e delivery systems included O\u003csub\u003e2\u003c/sub\u003e tanks and O\u003csub\u003e2\u003c/sub\u003e concentrators, available since 2010. While the O\u003csub\u003e2\u003c/sub\u003e concentrator was convenient and less expensive, it was impossible to titrate O\u003csub\u003e2\u003c/sub\u003e flows accurately below 1 L/min. Thai system of national health coverage does not include HOT and has less resources for evaluating readiness for weaning. Low flow O\u003csub\u003e2\u003c/sub\u003e devices and polysomnography are not available in most of the hospitals.\u003c/p\u003e \u003cp\u003eWith the economic burden, the most frequently asked question from parents is when they could expect the HOT withdrawal. Thus, to provide prognostic information for parents, the aim of this 20-year retrospective study was to identify the median age of HOT discontinuation and the factors that might predict prolonged HOT. Comparisons of the outcomes such as mortality and readmission to the resource- rich countries were the secondary objectives.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e \u003cb\u003eStudy population\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eThis retrospective study was performed in the division of pediatric pulmonology, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand during January 2000 - December 2019. Electronic medical records of infants with BPD who required HOT were reviewed. The 2001 definition of BPD\u003csup\u003e2\u003c/sup\u003e was used since it was the accepted definition at enrollment into the study. All preterm infants born before 36 GA, diagnosed with BPD based on National Institutes of Health (NIH) criteria 2001, and followed up in the VLBW and chest clinic were recruited. We excluded patients who required HOT due to other causes such as congenital cyanotic heart diseases, congenital airway anomalies, or congenital diaphragmatic hernia. This study was approved by Ramathibodi Human Research Ethics Committee (COA. MURA2020/901). The need for informed consent was waived by an IRB as it was unnecessary according to national regulations.\u003c/p\u003e \u003cp\u003e \u003cb\u003eOutcomes\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe primary outcome was the median corrected age (CA) when home O\u003csub\u003e2\u003c/sub\u003e use was discontinued. O\u003csub\u003e2\u003c/sub\u003e withdrawal was defined as either under the supervision of a physician or the unsupervised discontinuation by parents. Small for gestational age (SGA) was defined as birth weight\u0026thinsp;\u0026lt;\u0026thinsp;10th percentile based on Fenton 2013 preterm growth chart.\u003csup\u003e22\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDemographic and clinical data including GA, prenatal history, severity of BPD, history of surfactant administration, duration of mechanical ventilation and O\u003csub\u003e2\u003c/sub\u003e supplementation, procedures and medications, comorbidities, and complications were recorded. Weight gain at O\u003csub\u003e2\u003c/sub\u003e withdrawal was calculated from the subtraction of weight at the time of discharge and the time of O\u003csub\u003e2\u003c/sub\u003e withdrawal divided by the duration of HOT. The method of weaning and evaluation of O\u003csub\u003e2\u003c/sub\u003e cessation were included.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analyses\u003c/b\u003e \u003c/p\u003e \u003cp\u003eBaseline characteristics were tested for normality by Kolmogorov-Smirnov or Shapiro-Wilk test and presented as means with standard deviation or medians with interquartile range. Mann-Whitney \u003cem\u003eU\u003c/em\u003e test and \u003cem\u003et\u003c/em\u003e-test were used to compare continuous variables with non-normally distributed and normally distributed, respectively, while chi-square was used to compare categorical variables. Adjusted odd ratios were assessed by logistic regression analysis to identify correlation between possible prognostic factors and the corrected age of O\u003csub\u003e2\u003c/sub\u003e withdrawal at 12 months. Statistical significance was considered when P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eThe 20-year delivery period was divided into 2 periods (2000 to 2009, the pre-surfactant era and 2010 to 2019, the post-surfactant era) with regard to differences of home O\u003csub\u003e2\u003c/sub\u003e use. The associations were analyzed based on univariate and multivariate logistic regression analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring January 2000 \u0026ndash; December 2019, 8581 preterm infants were born at Ramathibodi Hospital. The prevalence of BPD was 563 of 8581 (6.6%) of the preterm infants (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1. The number of infants with BPD and those who were sent home with oxygen supplementation during the year 2000-2019\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFifty-three of 563 (9.4%) infants with BPD were discharged home on HOT. Thirteen patients were excluded; 2 patients died before the O\u003csub\u003e2\u003c/sub\u003e cessation (the first patient died at 4 months CA from severe pneumonia, another died from severe pulmonary hemorrhage and PH at 7 months CA), 2 patients had congenital diaphragmatic hernia, 1 had Pierre- Robin syndrome, and 8 patients were lost to follow- up. Therefore 40 BPD patients who received HOT were recruited. The baseline characteristics of infants with BPD and those who were sent home on HOT during the year 2000-2019 is shown in Table 1. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Baseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.04225352112676%\" valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.95774647887324%\" valign=\"top\"\u003e\n \u003cp\u003eHome oxygen (n = 40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.04225352112676%\" valign=\"top\"\u003e\n \u003cp\u003eMale sex (%)\u003c/p\u003e\n \u003cp\u003eGestational age (weeks)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eBirth weight (g)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eSmall for gestational age (%)\u003c/p\u003e\n \u003cp\u003eCesarean section (%)\u003c/p\u003e\n \u003cp\u003eMaternal chorioamnionitis (%)\u003c/p\u003e\n \u003cp\u003eComplete antenatal steroids (%)\u003c/p\u003e\n \u003cp\u003ePremature rupture of membrane (%)\u003c/p\u003e\n \u003cp\u003eOxygen required at delivery (%)\u003c/p\u003e\n \u003cp\u003eSurfactant (%)\u003c/p\u003e\n \u003cp\u003eInvasive ventilation (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eNoninvasive ventilation (days)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eTotal respiratory support (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eHigh-frequency oscillatory ventilation (%)\u003c/p\u003e\n \u003cp\u003eHigh-frequency oscillatory ventilation (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eSevere BPD (%)\u003c/p\u003e\n \u003cp\u003eSurgical PDA ligation\u003c/p\u003e\n \u003cp\u003eInhaled corticosteroids (%)\u003c/p\u003e\n \u003cp\u003eLength of hospital stay (days)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eCA at discharge (weeks)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eCA at O\u003csub\u003e2\u003c/sub\u003e withdrawal (months)\u003csup\u003e\u0026nbsp;c\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eDuration of home O\u003csub\u003e2\u003c/sub\u003e therapy (months)\u003csup\u003e\u0026nbsp;c\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.95774647887324%\" valign=\"top\"\u003e\n \u003cp\u003e15 (60)\u003c/p\u003e\n \u003cp\u003e27.9 \u0026plusmn; 2.5\u003c/p\u003e\n \u003cp\u003e845 (722.5, 1040)\u003c/p\u003e\n \u003cp\u003e13 (32.5)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (70)\u003c/p\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003cp\u003e26 (65)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (25)\u003c/p\u003e\n \u003cp\u003e36 (94.7)\u003c/p\u003e\n \u003cp\u003e28 (70)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (14, 38)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68 \u0026plusmn; 39\u003c/p\u003e\n \u003cp\u003e146 (126, 178)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (72.5)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (6, 22) (n = 29)\u003c/p\u003e\n \u003cp\u003e35 (87.5)\u003c/p\u003e\n \u003cp\u003e6 (15)\u003c/p\u003e\n \u003cp\u003e26 (65)\u003c/p\u003e\n \u003cp\u003e159 \u0026plusmn; 48\u003c/p\u003e\n \u003cp\u003e8.6 (5.3, 12.6)\u003c/p\u003e\n \u003cp\u003e13.8 (8.5, 22.1)\u003c/p\u003e\n \u003cp\u003e11.3 (5.6, 17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e CA, corrected age; O\u003csub\u003e2\u003c/sub\u003e, oxygen; PDA, patent ductus arteriosus; SGA, small for gestational age defines as birth weight \u0026lt; 10\u003csup\u003eth\u003c/sup\u003e percentile based on Fenton 2013 preterm growth chart.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eContinuous variables were expressed as mean \u0026plusmn; standard deviation\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Continuous variables were expressed as median (interquartile range)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ec\u0026nbsp;\u003c/sup\u003eContinuous variables were expressed as median (interquartile range) excluded infants who continued oxygen use (n = 37).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe subjects had a mean GA of 27.9 \u0026plusmn; 2.5 weeks and a median birth weight of 845 g (722.5, 1040). Thirty-five (87.5%) had severe BPD. The total length of hospital stay was 159 \u0026plusmn; 48 days. Twelve subjects (30%) had echocardiogram confirmed PH.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf the 40 infants, 37 (92.5%) discontinued HOT during the study period and 18 of 40 infants (45%) successfully weaned off O\u003csub\u003e2\u003c/sub\u003e by 12 months (Table 2, Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Comparisons of factors in BPD infants with oxygen withdrawal at 12 months CA\u003c/strong\u003e \u003cstrong\u003ecutoff\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.70932069510268%\" valign=\"top\"\u003e\n \u003cp\u003eFactors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.43127962085308%\" valign=\"top\"\u003e\n \u003cp\u003eO\u003csub\u003e2\u003c/sub\u003e withdrawal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026le; CA 12 mo\u003c/p\u003e\n \u003cp\u003e(n = 18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.85308056872038%\" valign=\"top\"\u003e\n \u003cp\u003eO\u003csub\u003e2\u003c/sub\u003e withdrawal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026gt; CA 12 mo\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(n = 22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.006319115323855%\" valign=\"top\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.70932069510268%\" valign=\"top\"\u003e\n \u003cp\u003eGestational age (weeks)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eBirth weight (g)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eInvasive ventilation (days)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eNoninvasive ventilation (days)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eTotal respiratory support in hospital (days)\u003csup\u003e\u0026nbsp;a\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eHFOV (%)\u003c/p\u003e\n \u003cp\u003eHFOV (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eMaximum MAP of HFOV\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eInhaled corticosteroids (%)\u003c/p\u003e\n \u003cp\u003eSevere BPD (%)\u003c/p\u003e\n \u003cp\u003eDOL at ICS started (day)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eDOL at post-natal steroids started (day)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e Length of hospital stay (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eCA at discharge (weeks)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eWeight at discharge (g)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eWeight at O\u003csub\u003e2\u003c/sub\u003e withdrawal (g)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eWeight gain at O\u003csub\u003e2\u003c/sub\u003e withdrawal (g/day)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.43127962085308%\" valign=\"top\"\u003e\n \u003cp\u003e28.4 (26.7, 30.7)\u003c/p\u003e\n \u003cp\u003e965 (710, 1165)\u003c/p\u003e\n \u003cp\u003e26 \u0026plusmn; 16\u003c/p\u003e\n \u003cp\u003e46 \u0026plusmn; 27\u003c/p\u003e\n \u003cp\u003e136 \u0026plusmn; 34\u003c/p\u003e\n \u003cp\u003e11 (61.1)\u003c/p\u003e\n \u003cp\u003e12 (4, 16)\u003c/p\u003e\n \u003cp\u003e14 \u0026plusmn; 2.7\u003c/p\u003e\n \u003cp\u003e10 (55.6)\u003c/p\u003e\n \u003cp\u003e13 (72.2)\u003c/p\u003e\n \u003cp\u003e16 (13, 48)\u003c/p\u003e\n \u003cp\u003e25 (19, 37)\u003c/p\u003e\n \u003cp\u003e126 (111, 170)\u003c/p\u003e\n \u003cp\u003e5.9 (4, 11.4)\u003c/p\u003e\n \u003cp\u003e4291 \u0026plusmn; 897\u003c/p\u003e\n \u003cp\u003e7083 \u0026plusmn; 1818\u003c/p\u003e\n \u003cp\u003e17 \u0026plusmn; 7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.85308056872038%\" valign=\"top\"\u003e\n \u003cp\u003e27.1 (25.9, 28.6)\u003c/p\u003e\n \u003cp\u003e825 (713, 945)\u003c/p\u003e\n \u003cp\u003e34\u0026nbsp;\u0026plusmn; 25\u003c/p\u003e\n \u003cp\u003e85\u0026nbsp;\u0026plusmn; 40\u003c/p\u003e\n \u003cp\u003e174\u0026nbsp;\u0026plusmn; 49\u003c/p\u003e\n \u003cp\u003e18 (81.8)\u003c/p\u003e\n \u003cp\u003e13 (6, 23)\u003c/p\u003e\n \u003cp\u003e15.4 \u0026plusmn; 3.1\u003c/p\u003e\n \u003cp\u003e16 (72.7)\u003c/p\u003e\n \u003cp\u003e22 (100)\u003c/p\u003e\n \u003cp\u003e41 (22, 66)\u003c/p\u003e\n \u003cp\u003e31 (24, 50)\u003c/p\u003e\n \u003cp\u003e161 (134, 211)\u003c/p\u003e\n \u003cp\u003e10.1 (7.6, 17)\u003c/p\u003e\n \u003cp\u003e5178 \u0026plusmn; 960\u003c/p\u003e\n \u003cp\u003e10072\u0026nbsp;\u0026plusmn; 1330\u003c/p\u003e\n \u003cp\u003e8.8\u0026nbsp;\u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.006319115323855%\" valign=\"top\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003cp\u003e0.173\u003c/p\u003e\n \u003cp\u003e0.589\u003c/p\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003cp\u003e0.257\u003c/p\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: HFOV, High-frequency oscillatory ventilation; MAP, mean airway pressure; CA, corrected age; O\u003csub\u003e2\u003c/sub\u003e, oxygen; DOL, day of life; HHHFNC, Heated humidified high flow nasal cannula; ICS, inhaled corticosteroid \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eContinuous variables were expressed as mean \u0026plusmn; standard deviation; \u003csup\u003eb\u003c/sup\u003e Continuous variables were expressed as median (interquartile range)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig. 2 Kaplan-Meier Plot demonstrating the age of oxygen withdrawal in 40 BPD infants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median CA of O\u003csub\u003e2\u003c/sub\u003e withdrawal was 13.8 months (8.5, 22.1) and the median was 11.3 months (5.6, 17.5). There were six patients with prolonged HOT beyond the corrected age of 2 years. All of them had severe BPD and had been treated with high-frequency oscillatory ventilation (HFOV). The characteristics of these patients are shown in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Characteristics of the BPD patients with prolonged home oxygen therapy beyond the corrected age of 24 month\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"636\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubject No.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear of birth\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eGA (wk)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eBW (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPHN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eLOS (d)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eReadmission (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at O\u003csub\u003e2\u003c/sub\u003e withdrawal (mo)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eRemarks*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"30\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"NaN%\" height=\"86\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\"\u003e\n \u003cp\u003e2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\"\u003e\n \u003cp\u003e720\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\"\u003e\n \u003cp\u003e24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\"\u003e\n \u003cp\u003ebronchomalacia, atelectasis, GERD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"70\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\"\u003e\n \u003cp\u003e845\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\"\u003e\n \u003cp\u003e2 (PICU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\"\u003e\n \u003cp\u003e29.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\"\u003e\n \u003cp\u003epulmonary hypertension, subglottic stenosis, GERD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"88\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\"\u003e\n \u003cp\u003e770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\"\u003e\n \u003cp\u003e24.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\"\u003e\n \u003cp\u003eBBA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"21\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\"\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\"\u003e\n \u003cp\u003e800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e184\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\"\u003e\n \u003cp\u003e31.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\"\u003e\n \u003cp\u003eTriplets, BHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"35\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\"\u003e\n \u003cp\u003e675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\"\u003e\n \u003cp\u003e6 (1 PICU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\"\u003e\n \u003cp\u003e37.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\"\u003e\n \u003cp\u003eGERD, aspiration pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"53\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.534591194968554%\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.647798742138365%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.176100628930818%\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.70440251572327%\"\u003e\n \u003cp\u003e930\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.037735849056602%\"\u003e\n \u003cp\u003e1 (PICU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.622641509433961%\"\u003e\n \u003cp\u003e29.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19496855345912%\"\u003e\n \u003cp\u003ebronchomalacia, ARDS, subglottic stenosis, GERD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" height=\"106\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviation:\u0026nbsp;\u003c/strong\u003eGA, gestational age; BW, birth weight; PPHN, persistent pulmonary hypertension of the newborn; LOS, length of hospital stay; O\u003csub\u003e2\u003c/sub\u003e, oxygen; CA, corrected age; ARDS, acute respiratory distress syndrome; GERD, gastroesophageal reflux disease; BHR, bronchial hyperresponsiveness; BBA, birth before arrival\u003c/p\u003e\n\u003cp\u003e*All patients had severe BPD\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003ePatients has never received antenatal steroids\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 2 lists the factors associated with O\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewithdrawal at 12 months CA which were shorter duration of respiratory support in hospital (136 vs. 174 days, p = 0.01), shorter length of hospital stay (126 vs. 161 days, p=0.008), higher weight gain at O\u003csub\u003e2\u003c/sub\u003e withdrawal (17 \u0026plusmn; 7.3 vs. \u0026nbsp; 8.8 \u0026plusmn; 2.6 g/day, p \u0026lt;0.001) and less severe BPD (72.2% vs. 100%, p =0.013). Multivariate logistic regression analysis revealed that only the higher weight gain remained a significant factor for O\u003csub\u003e2\u003c/sub\u003e withdrawal at 12 months CA (adjusted OR, 1.91; 95% CI, 1.13-3.23; p = 0.015).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe overall survival rate of those born weighing \u0026lt;2500 grams in the pre-surfactant era was 94.0% vs. 96.4% in the post-surfactant era (p\u0026lt;0.01) while the incidence of BPD in these group was 4.2 and 8.4% respectively (p\u0026lt;0.005). However, the pre surfactant babies were 2 weeks more mature than the post and weighed significantly more Table 4. The modality of respiratory support including the use of inhaled corticosteroids (ICS) differed due to changes in care over time. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Comparison of infants required home oxygen therapy who were born during 2000-2009 and 2010-2019\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.552845528455286%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.601626016260163%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear 2000-2009\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.48780487804878%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear 2010-2019\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.357723577235772%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.552845528455286%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational age (weeks)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight (g)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSGA (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMaternal chorioamnionitis (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSurfactant administration (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eInvasive ventilation (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNoninvasive ventilation (days)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTotal respiratory support (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHHHFNC (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHFOV (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHFOV (days)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMaximum MAP of HFOV\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eInhaled corticosteroids (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSevere BPD (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLength of hospital stay (days)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eWeight at discharge (g)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCA at O\u003csub\u003e2\u003c/sub\u003e withdrawal (months)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of home O\u003csub\u003e2\u003c/sub\u003e (months)\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eWeight at O\u003csub\u003e2\u003c/sub\u003e withdrawal (g)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eWeight gain at O\u003csub\u003e2\u003c/sub\u003e withdrawal (g/day)\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOvernight SpO\u003csub\u003e2\u003c/sub\u003e monitoring (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOxygen concentrator use (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eReadmission due to respiratory illnesses\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.601626016260163%\" valign=\"top\"\u003e\n \u003cp\u003e29.7 \u0026plusmn; 2.8\u003c/p\u003e\n \u003cp\u003e1100 (825, 1355)\u003c/p\u003e\n \u003cp\u003e3 (33.3)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e1 (11.1)\u003c/p\u003e\n \u003cp\u003e28 (7, 31)\u003c/p\u003e\n \u003cp\u003e37 \u0026plusmn; 25\u003c/p\u003e\n \u003cp\u003e145 (119, 174)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e3 (33.3)\u003c/p\u003e\n \u003cp\u003e5 \u0026plusmn; 2\u003c/p\u003e\n \u003cp\u003e10.3 \u0026plusmn; 3.5\u003c/p\u003e\n \u003cp\u003e3 (33.3)\u003c/p\u003e\n \u003cp\u003e8 (88.9)\u003c/p\u003e\n \u003cp\u003e150 (118, 180)\u003c/p\u003e\n \u003cp\u003e4756\u0026nbsp;\u0026plusmn; 613\u003c/p\u003e\n \u003cp\u003e9.9 \u0026plusmn; 7\u003c/p\u003e\n \u003cp\u003e7.3 \u0026plusmn; 6\u003c/p\u003e\n \u003cp\u003e7123 \u0026plusmn; 1739\u003c/p\u003e\n \u003cp\u003e14.7 (5.8, 21.4)\u003c/p\u003e\n \u003cp\u003e4 (57.1)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e4 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.48780487804878%\" valign=\"top\"\u003e\n \u003cp\u003e27.4\u0026nbsp;\u0026plusmn; 2.3\u003c/p\u003e\n \u003cp\u003e820 (690, 990)\u003c/p\u003e\n \u003cp\u003e10 (32.3)\u003c/p\u003e\n \u003cp\u003e4 (13.3)\u003c/p\u003e\n \u003cp\u003e27 (87.1)\u003c/p\u003e\n \u003cp\u003e29 (16, 39)\u003c/p\u003e\n \u003cp\u003e77\u0026nbsp;\u0026plusmn; 38\u003c/p\u003e\n \u003cp\u003e146 (127, 181)\u003c/p\u003e\n \u003cp\u003e29 (93.5)\u003c/p\u003e\n \u003cp\u003e26 (83.9)\u003c/p\u003e\n \u003cp\u003e14\u0026nbsp;\u0026plusmn; 9\u003c/p\u003e\n \u003cp\u003e15.5\u0026nbsp;\u0026plusmn; 2.5\u003c/p\u003e\n \u003cp\u003e23 (74.2)\u003c/p\u003e\n \u003cp\u003e27 (87.1)\u003c/p\u003e\n \u003cp\u003e145 (126, 179)\u003c/p\u003e\n \u003cp\u003e4786 \u0026plusmn; 1123\u003c/p\u003e\n \u003cp\u003e16.8 \u0026plusmn; 8.6\u003c/p\u003e\n \u003cp\u003e14.5 \u0026plusmn; 8.2\u003c/p\u003e\n \u003cp\u003e9033 \u0026plusmn; 2119\u003c/p\u003e\n \u003cp\u003e10.3 (7.9, 15.6)\u003c/p\u003e\n \u003cp\u003e15 (51.7)\u003c/p\u003e\n \u003cp\u003e30 (96.8)\u003c/p\u003e\n \u003cp\u003e20 (64.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.357723577235772%\" valign=\"top\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.560\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e0.503\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.871\u003c/p\u003e\n \u003cp\u003e0.939\u003c/p\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003cp\u003e0.484\u003c/p\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003cp\u003e0.441\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviation:\u0026nbsp;\u003c/strong\u003eHFOV, High-frequency oscillatory ventilation; MAP, mean airway pressure; CA, corrected age; O\u003csub\u003e2\u003c/sub\u003e, oxygen; DOL, day of life; HHHFNC, heated humidified high flow nasal cannula; ICS, inhaled corticosteroid; SpO\u003csub\u003e2\u003c/sub\u003e, oxygen saturation \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eContinuous variables were expressed as mean \u0026plusmn; standard deviation\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Continuous variables were expressed as median (interquartile range)\u003c/p\u003e\n\u003cp\u003ePreterm infants delivered during 2010-2019 had longer duration of HOT compared with those born during 2000-2009 (14.5 vs. 7.3 months, p = 0.019 and almost all used an O\u003csub\u003e2\u003c/sub\u003e concentrator (97% vs. 0 (p\u0026lt;0.001)) (Table 4). These differences did not extend to the use of overnight oximetry monitoring (57.1% vs. 51.7%, p = 0.074). The hospital admission due to respiratory tract infection and BPD complication, such as PH leading to heart failure and fluid intolerance, were not significantly different. \u0026nbsp;\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter discharge home, there were 51 respiratory readmissions including pneumonia, atelectasis, ARDS in 24 patients. PH was diagnosed in 3 patients.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe median CA of children with BPD discharged from supplemental O\u003csub\u003e2\u003c/sub\u003e was 13.8 months, longer than previous studies where CA at O\u003csub\u003e2\u003c/sub\u003e discontinuation was 2 to 12.5 months due to different patient characteristics, mode of O\u003csub\u003e2\u003c/sub\u003e support and weaning protocols.\u003csup\u003e16-21\u003c/sup\u003e The most recent study in 2021 reported that the median CA at O\u003csub\u003e2\u003c/sub\u003e cessation of 149 babies was 6.8 months with 87.2% of infants weaned by 12 months CA\u003csup\u003e21\u0026nbsp;\u003c/sup\u003ecompared to 45% (18 of 40) in our study. In contrast with Wong et al\u0026rsquo;s study in 2021, we had a higher proportion of SGA (32.5% vs. 8.7%), need longer respiratory support (146 vs. 73 days) and higher proportion of using HFOV (72.5% vs. 53%). Our study and Wong et al used overnight pulse oximetry monitoring as the assessment method of weaning while Yeh and Saletti used polysomnography.\u003csup\u003e16,19,21\u003c/sup\u003e Only one study in 2004 reported the rapid weaning at of 2 months CA by abrupt cessation of oxygen at the out-patient department when the level of oxygen saturation was more than 95% for 15 minutes.\u003csup\u003e19\u003c/sup\u003e The duration of HOT more than 12 months CA was associated with more severe BPD, longer duration of respiratory support, longer hospital stay and infants with poor weight gain (Table 2) as has been seen previously.\u003csup\u003e21\u003c/sup\u003e Hypercarbia on capillary blood gas has been associated with prolonged O\u003csub\u003e2\u003c/sub\u003e need\u003csup\u003e23\u003c/sup\u003e but was not performed in our study. While higher O\u003csub\u003e2\u003c/sub\u003e flow at discharge was a predictor of later home O\u003csub\u003e2\u003c/sub\u003e weaning\u003csup\u003e16,21\u003c/sup\u003e, the O\u003csub\u003e2\u003c/sub\u003e flow in our study did not predict the age of weaning.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;The analysis was divided into 2 time periods because the surfactant and non-invasive ventilation, especially the nasal CPAP and the heated humidified high flow nasal cannula were widely used in NICU after 2009.\u0026nbsp;Comparing time periods, (2000-2009 vs. 2010-2019) (Table 4), infants born during 2010-2019 required longer HOT (9.9 vs. 16.8 months). Despite the attempt to reduce barotrauma, use of surfactant and ICS, the proportion of severe BPD remained unchanged, presumably because infants born in the latter period had earlier GA and lower birth weight. There was a slight but significant increase in survival during the later period which may also have led to a higher incidence of BPD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;From previous studies\u003csup\u003e16,18\u003c/sup\u003e, as many as 36.7 \u0026ndash; 47% of preterm infants with BPD were treated with HOT whereas only 9.4% (53 of 563) in our center. \u0026nbsp; (Fig.1) The expense of HOT is not included in the national health coverage, some parents whose children were eligible for HOT may not be able to afford it. Hence, only the more severe patients are in our study, in which case if the parent could not afford home O\u003csub\u003e2\u003c/sub\u003e the team made great efforts to find some alternative funding. The most common equipment of home O\u003csub\u003e2\u003c/sub\u003e used in Thailand was O\u003csub\u003e2\u003c/sub\u003e concentrator, available in the last half of the study period, which delivered O\u003csub\u003e2\u003c/sub\u003e range from 0.5 -10 L/min, typically 1-2 L/min. The British Thoracic Society guidelines propose O\u003csub\u003e2\u003c/sub\u003e concentrators for long term HOT and compressed O\u003csub\u003e2\u003c/sub\u003e with a low flow regulator at a rate of 0.1-1 L/min for the short anticipated duration of HOT.\u003csup\u003e10\u003c/sup\u003e The median discharge O\u003csub\u003e2\u003c/sub\u003e flow in Wong et al study was only 0.25 L/min.\u003csup\u003e21\u003c/sup\u003e Most of participants (89%) in Yeh et al study required less than 0.5 L/min of O\u003csub\u003e2\u003c/sub\u003e supplement at discharge.\u003csup\u003e16\u003c/sup\u003e In US, the recommended home O\u003csub\u003e2\u003c/sub\u003e flow rate starts from 1/8 L/min or 0.1 L/min depends on the available devices.\u003csup\u003e17\u003c/sup\u003e\u0026nbsp; In Thailand, we sent most of the babies home with at least 1 L/min of home O\u003csub\u003e2\u003c/sub\u003e because the low flow O\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas not widely available.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe supplemental O\u003csub\u003e2\u003c/sub\u003e improves growth in infants with BPD.\u003csup\u003e6,13,24\u003c/sup\u003e Intermittent hypoxemia has been shown to be associated with poor growth.\u003csup\u003e15\u003c/sup\u003e The proposed home O\u003csub\u003e2\u003c/sub\u003e weaning protocol in US suggests a slower wean for if growth is stagnant.\u003csup\u003e17\u003c/sup\u003e Our study would support these finding with the association between early O\u003csub\u003e2\u003c/sub\u003e withdrawal and higher weight gain.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Most of BPD children should outgrow the need for supplemental O\u003csub\u003e2\u003c/sub\u003e by 2 years of life.\u003csup\u003e15, 24\u003c/sup\u003e We demonstrated six patients who required prolonged HOT in Table 3. All of them presented with severe BPD. Five patients were born during 2013-2018 and had many complications such as bronchomalacia, gastroesophageal reflux disease, PH and some had subglottic stenosis. The repeated infections and inflammations led to frequent readmission and subsequent weaning difficulty.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies have shown that BPD infants who required HOT were more likely to be re-hospitalized for respiratory illness (38% vs. 28%; adjusted relative risk 1.33; 95% CI 1.16 to 1.53).\u003csup\u003e24\u003c/sup\u003e Sun L et al reported 48 of 62 (77%) BPD children had \u003cu\u003e\u0026gt;\u003c/u\u003e 2 readmissions within 18-24 months\u003csup\u003e9\u003c/sup\u003e which is comparable to our study which revealed 24 of 40 (60%) BPD patients with HOT resulted in respiratory re-hospitalization.\u003c/p\u003e\n\u003cp\u003eInterestingly, the prevalence of PH in our population was lower than previous studies. This may be derived from the higher flow of O\u003csub\u003e2\u003c/sub\u003e provided and/or the sick infants with PH in our setting could not be discharged.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;This study\u0026rsquo;s strength was a long duration of study period and comparisons between the pre-surfactant and aggressive ventilation era vs. the post-surfactant and non-invasive ventilation era. Limitations were due to the retrospective study design, there were missing data on radiography, environmental and socioeconomic factors.\u0026nbsp;Using the NIH 2001 definition, the prevalence of BPD is higher than NICHD 2018. Mild BPD using 2001 criteria may not be diagnosed compared to 2018 criteria.\u003csup\u003e8-9\u003c/sup\u003e However the majority (87.5%) of our subjects had severe BPD which is not significantly different between the 2 definitions. \u0026nbsp;In terms of the predictive ability on HOT and death from respiratory illnesses, the NICHD 2018 definition is superior to the NIH 2001 definition.\u003csup\u003e5, 7-9\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis 20-year review discovered that the median corrected age of HOT withdrawal in Thai infants with BPD was 13.8 months. Prolonged O\u003csub\u003e2\u0026nbsp;\u003c/sub\u003erequirement was associated with longer duration of respiratory support in hospital, longer length of hospitalization and poor weight gain. Despite not being able to follow all the guidelines due to economic constraints, the outcomes were comparable to the resource-rich countries. \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAUTHOR CONTRIBUTIONS\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVipada Grajangdara:\u003c/strong\u003e conceptualization (equal); data curation (lead); formal\u003c/p\u003e\n\u003cp\u003eanalysis (lead); methodology (equal); project administration (lead); writing original draft (equal). \u003cstrong\u003eAnchalee Limrungsikul:\u003c/strong\u003e conceptualization (equal), resources (lead), data curation (equal); writing review \u0026amp; editing (supporting). \u003cstrong\u003eAllan L. Coates:\u003c/strong\u003e conceptualization (equal), data curation (equal), supervision (equal), writing review \u0026amp; editing (equal).\u003cstrong\u003e\u0026nbsp;Harutai Kamalaporn:\u003c/strong\u003e conceptualization (lead); data curation (equal); formal analysis (supporting); methodology (equal); supervision (lead); writing original draft (equal); writing review \u0026amp; editing (equal).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDATA AVAILABILITY STATEMENT\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e\n\u003cp\u003eCONFLICT OF INTERESTS\u003c/p\u003e\n\u003cp\u003eHarutai Kamalaporn received lecture fees from AstraZeneca, GlaxoSmithKline, and\u003c/p\u003e\n\u003cp\u003eOrganon. The remaining authors have nothing to disclose. The authors did not receive\u0026nbsp;\u003c/p\u003e\n\u003cp\u003epayment for development of this manuscript.\u003c/p\u003e\n\u003cp\u003eHUMAN ETHICS APPROVAL DECLARATION\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the Declaration of Helsinki and approved by\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRamathibodi Human Research Ethics Committee, Mahidol University (COA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMURA2020/901).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBaraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357:1946\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThekkeveedu RK, Guaman MC, Shivanna B. Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology. Respir Med. 2017;132:170\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiggins RD, Jobe AH, Koso-Thomas M, Bancalari E, Viscardi RM, Hartert TV, Ryan RM, Kallapur SG, Steinhorn RH, Konduri GG, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr. 2018;197:300\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBancalari E, Jain D. Bronchopulmonary dysplasia: 50 years after the original description. Neonatology. 2019;115:384\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllen J, Panitch H. Bronchopulmonary dysplasia-a historical perspective. Pediatr Pulmonol. 2021;56:3478\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach. Am J Respir Crit Care Med. 2019;200:751\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaengrat P, Limrungsikul A. Predictive Ability of the New Bronchopulmonary Dysplasia Definition on Pulmonary Outcomes at 20 to 24 months' Corrected Age of Preterm Infants. Am J Perinatol. 2021. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1055/s-0041-1735219\u003c/span\u003e\u003cspan address=\"10.1055/s-0041-1735219\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Online ahead of print.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun L, Zhang H, Bao Y, Li W, Wu J, He Y, Zhu J. Long-term outcomes of bronchopulmonary dysplasia under two different diagnostic criteria: a retrospective cohort study at a Chinese tertiary center. Front Pediatr. 2021;9:648972.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalfour-Lynn IM, Field DJ, Gringras P, Hicks B, Jardine E, Jones RC, Magee AG, Primhak RA, Samuels MP, Shaw NJ, et al. BTS guidelines for home oxygen in children. Thorax. 2009;64(Suppl II):ii1\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCherian S, Morris I, Evans J, Kotecha S. Oxygen therapy in preterm infants. Paediatr Respir Rev. 2014;15(2):135\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCummings JJ, Polin RA. Committee on fetus and newborn. Oxygen targeting in extremely low birth weight infants. Pediatrics. 2016;138(2):e20161576.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllen J, Zwerdling R, Ehrenkranz R, Gaultier C, Geggel R, Greenough A, Kleinman R, Klijanowicz A, Martinez F, Ozdemir A, et al. Statement on the care of the child with chronic lung disease of infancy and childhood. Am J Respir Crit Care Med. 2003;168(3):356\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuijts L, van Meel ER, Moschino L, Baraldi E, Barnhoorn M, Bramer WM, Bolton CE, Boyd J, Buchvald F, del Cerro MJ, et al. European Respiratory Society guideline on long-term management of children with bronchopulmonary dysplasia. Eur Respir J. 2020;55:1900788.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhandari A, Panitch H. An update on the post-NICU discharge management of bronchopulmonary dysplasia. Semin Perinatol. 2018;42:471\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeh J, McGrath-Morrow SA, Collaco JM. Oxygen weaning after hospital discharge in children with bronchopulmonary dysplasia. Pediatr Pulmonol. 2016;51(11):1206\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnderson C, Hillman NH. Bronchopulmonary dysplasia: When the very preterm baby comes home. Mo Med. 2019;116(2):117\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEjiawoko A, Lee HC, Lu T, Lagatta J. Home oxygen use for preterm infants with bronchopulmonary dysplasia in California. J Pediatr. 2019;210:55\u0026ndash;62. e51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaletti A, Stick S, Doherty D, Simmer K. Home oxygen therapy after preterm birth in Western Australia. J Paediatr Child Health. 2004;40(9\u0026ndash;10):519\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNorzila MZ, Azizi BH, Norrashidah AW, Yeoh NM, Deng CT. Home oxygen therapy for children with chronic lung diseases. Med J Malaysia. 2001;56(2):151\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong MD, Neylan M, Williams G, Zahir SF, Chawla J. Predictors of home oxygen duration in chronic neonatal lung disease. Pediatr Pulmonol. 2021;56(5):992\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDawson SK, D'Andrea LA, Lau R, Lagatta JM. Using a home oxygen weaning protocol and pCO\u003csub\u003e2\u003c/sub\u003e to evaluate outcomes for infants with bronchopulmonary dysplasia discharged on home oxygen. Pediatr Pulmonol. 2020;55(12):3293\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeMauro SB, Jensen EA, Bann CM, Bell EF, Hibbs AM, Hintz SR, Lorch SA. Home oxygen and 2-year outcomes of preterm infants with bronchopulmonary dysplasia. Pediatrics. 2019;143(5):e20182956.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bronchopulmonary dysplasia, Home oxygen, Preterm infants, Oxygen withdrawal, Resource poor country","lastPublishedDoi":"10.21203/rs.3.rs-4014163/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4014163/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eConsequences of lung injury and inflammation in preterm infants with bronchopulmonary dysplasia (BPD) contribute to prolonged oxygen requirements. Home oxygen therapy (HOT) is an alternative way of respiratory support in BPD infants. However, there is no consensus on weaning guidelines either under the supervision of physicians or unsupervised weaning by parents. Our objective is to identify the median age of home oxygen discontinuation and the factors that might predict the duration of HOT in a resource poor country.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAll preterm (\u0026le;\u0026thinsp;36 weeks' gestation) infants diagnosed BPD who required HOT after discharged from Ramathibodi Hospital during January 2000 \u0026ndash; December 2019 comprised this retrospective study. Timing of HOT withdrawal was identified. Demographic data, severity of BPD, history of respiratory support, procedures, prenatal history, comorbidities, and complications were recorded and analyzed as factors associated of home oxygen withdrawal.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf 8581 preterm infants born during the 20-year period, 563 (6.6%) had BPD. Among 40 infants treated with HOT, 18 (45%) were successfully weaned oxygen within 12 months. The median corrected age (CA) of oxygen withdrawal was 13.8 months (8.5, 22.1). Longer duration of total respiratory support, longer length of hospital stay, and poor weight gain were associated with longer duration of HOT. Greater weight gain was associated with a shorter duration of HOT at 12 months CA (adjusted OR, 1.97; 95% CI, 1.13\u0026ndash;3.23; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe median corrected age of oxygen withdrawal in Thai BPD infants was 13.8 months. Severe BPD and poor weight gain were associated with prolonged home oxygen use. Despite not being able to follow all the guidelines due to economic constraints, the clinical outcomes were comparable to the resource rich countries.\u003c/p\u003e","manuscriptTitle":"Home Oxygen Therapy for Thai Preterm Infants with Bronchopulmonary Dysplasia. What Are the Predictive Factors for Successful Weaning: A 20-year Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-11 19:36:15","doi":"10.21203/rs.3.rs-4014163/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"b1aabee8-9feb-477a-b3b4-549c96cd45da","date":"2024-03-09T06:38:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-08T22:47:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-08T22:39:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-05T18:08:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-05T17:58:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-03-04T18:56:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8f6e77f2-e93d-4b45-b95d-088d28b3e5df","owner":[],"postedDate":"March 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-13T16:02:20+00:00","versionOfRecord":{"articleIdentity":"rs-4014163","link":"https://doi.org/10.1186/s12887-024-05354-1","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-01-11 15:57:33","publishedOnDateReadable":"January 11th, 2025"},"versionCreatedAt":"2024-03-11 19:36:15","video":"","vorDoi":"10.1186/s12887-024-05354-1","vorDoiUrl":"https://doi.org/10.1186/s12887-024-05354-1","workflowStages":[]},"version":"v1","identity":"rs-4014163","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4014163","identity":"rs-4014163","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}