Comparison of different definitions of bronchopulmonary dysplasia based on the prediction of adverse outcomes: Followed up to 18-24 months corrected age

Comparison of different definitions of bronchopulmonary dysplasia based on the prediction of adverse outcomes: Followed up to 18-24 months corrected age | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparison of different definitions of bronchopulmonary dysplasia based on the prediction of adverse outcomes: Followed up to 18-24 months corrected age Ruiwen Li, Li Wang, Jianhui Wang, Hui Liu, Yuan Shi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1935674/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background In clinical work, the BPD definition has not been clearly unified and standardized, which limits clinical progress. A BPD diagnostic screening standard that can effectively predict the prognosis, as well as standardize the clinical early diagnosis and treatment of BPD, is needed. Methods We conducted an ambispective cohort study to compare the effects of the three different definitions of BPD on clinical diagnosis and the predictive ability of prognosis (followed to 18–24 months corrected age). Findings: The diagnostic rate of BPD defined in 2001 was significantly higher than that created in 2018 or 2019 (P < 0.05), while the probability of adverse outcomes in infants with moderate and severe BPD diagnosed by the 2018 and 2019 definitions was significantly higher than those diagnosed by the 2001 definition (P < 0.05). Interpretation: The 2018 and 2019 diagnostic definitions are more accurate in predicting BPD-related adverse outcomes, especially respiratory outcomes. We suggest that for infants with BPD diagnosed via the 2001 definition, moderate and severe BPD should be screened again using the 2019 definition (which is easier to define than 2018), and early preventive intervention should be carried out. Bronchopulmonary Dysplasia Definition Adverse Outcomes 18-24 Months Corrected Age Figures Figure 1 1. Introduction Bronchopulmonary dysplasia (BPD), first reported and named by Northway and colleagues in 1967 [ 1 ] , is among the most common and severe sequelae of preterm birth. [ 2 , 3 ] BPD as a lung injury in preterm infants, resulting from oxygen and mechanical ventilation, results in a huge expense for public health care systems, which may increase in the coming years due to the rising incidence and survival of preterm babies. [ 4 ] The development of new therapies and preventative strategies to decrease the incidence of BPD and BPD-associated morbidities should be a priority. [ 5 – 6 ] However, in clinical work, the BPD definition has not been clearly unified and standardized, which limits clinical progress. [ 6 , 7 ] In 1979, the diagnostic standard of BPD was first published. [ 8 ] In the following decades, the diagnostic standard of BPD has undergone numerous improvements and updates, among which the representative diagnosis recognized by the industry was mainly in the 2001, 2018, and 2019 updates, [ 9 – 11 ] but which definition was the most valid is still not definitive. An appropriate definition of BPD would help predict adverse outcomes, reduce the incidence of late complications and serious complications through early intervention, and improve the quality of life of children. [ 12 ] Therefore, it is necessary to create a BPD screening diagnostic standard that can effectively predict a prognosis to standardize the early clinical diagnosis and treatment of BPD. This study was an ambispective cohort study that aimed to compare the effects of the 2001, 2018, and 2019 definitions on clinical diagnosis, along with the predictive ability of prognosis, to provide a reference for clinical treatment and prognosis evaluation. 2. Methods 2.1 Participants Source study data were from the Department of Neonatology, Children`s Hospital of Chongqing Medical University. The neonatal research retrospectively obtained clinical data from preterm infants with gestational age 14 days, from January 1, 2018, to May 30, 2019. Prior to June 1, 2021, postdischarge outcome data were collected at 18–24 months corrected age. Eligible infants survived 36 weeks PMA and either completed 18–24 months follow-up or died prior to anticipated follow-up. The exclusion criteria were severe congenital malformations, missing key study data, or loss to follow-up. 2.2 Definitions of Bronchopulmonary Dysplasia (Details in Table 1 ) In 2001, according to clinical variations in oxygen administration, a workshop convened by the National Institute of Child Health and Human Development proposed severity-based diagnostic criteria for BPD (hereafter referred to as the “2001 definition”): infants born < 32 weeks gestation treated with supplemental oxygen for at least 28 days and an assessment of respiratory support at 36 weeks postmenstrual age (PMA). BPD levels were regarded as none, mild, moderate, and serve, which was based on oxygen support. [ 9 ] Mild BPD means no use of oxygen after PMA36 weeks. Moderate BPD was defined as < 30% oxygen, and severe BPD was defined as any form of ventilatory support and/or ≥ 30% oxygen. Table 1 Bronchopulmonary dysplasia (BPD) definition NIH 2001 definition Grade Mild Moderate Serve Breathing in room air at 36 weeks PMA Need for < 30% oxygen at 36 weeks PMA Need for ≥ 30% oxygen with any form of ventilatory support at 36 weeks PMA NIH 2018 definition Grade Invasive IPPV NCPAP, NIPPV, or nasal cannula Nasal cannula flow of 1- <3 L/min Hood oxygen Nasal cannula flow of < 1 L/min I - 21 22–29 22–29 22–70 II 21 22–29 ≥ 30 ≥ 30 ＞70 III ＞21 ≥ 30 - - - III A Early death (between 14 days of postnatal age and 36 weeks) owing to persistent parenchymal lung disease and respiratory failure that cannot be attributable to other neonatal morbidities (e.g.. necrotizing enterocolitis, intraventricular haemorrhage, redirection of care, episodes of sepsis, etc.). 2019 Jesen definition Grade I Need for oxygen with nasal catheter ≤ 2 L/min II Need for oxygen with nasal catheter＞2 L/min, or NIV III Need for oxygen with invasive positive pressure *Definitions for bronchopulmonary dysplasia assessed at 36 weeks postmenstrual age. *Abbreviations: PMA: postmenstrual age; NIV, noninvasive ventilator; NIPPV: noninvasive positive pressure ventilation; NCPAP: nasal continuous positive airway pressure In 2018, another workshop sponsored by the National Institutes of Health revealed a new BPD definition to help identify varying severity (hereafter referred to as “2018 definition”): [ 10 ] Infants < 32 weeks gestation survived to 36 weeks PMA with radiographic evidence of lung disease who required supplemental oxygen/respiratory support. Infants with BPD were classified according to treatment with different respiratory support. They proposed using new terms, assessed at 36 weeks PMA, of grades I, II, and III instead of mild, moderate, and severe. In 2019, Jensen et al. found that the optimal definition categorized BPD severity only according to the mode of respiratory support administered at 36 weeks PMA (hereinafter referred to as the “2019 definition”), which better affects contemporary neonatal care and adequately predicts childhood morbidity. [ 11 , 13 ] 2.3 Outcome Variables 2.3.1 Adverse Outcomes We counted the adverse outcomes of the enrolled infants at 18–24 months corrected age and compared the probability differences of adverse outcomes under the three definitions of BPD to speculate the prediction accuracy of the 3 prespecified diagnostic criteria for adverse outcomes. An adverse outcome was defined as the occurrence of at least one of the following: (1) Respiratory adverse outcomes; [ 14 , 15 ] (2) severe neurological outcomes defined as brain retardation assessed by the Child Neurological Development Scale, developmental quotient (DQ) score < 85 assessed by the Gesell developmental schedules of infants, or brain damage requiring rehabilitation treatment assessed by a qualified physical therapist; [ 16 , 17 ] and (3) low development level (height, weight or head circumference < 3rd percentile for corrected gestational age and sex, growth percentiles defined using the World Health Organization Child Growth Standards) at 18–24 months corrected age; (4) retinopathy of prematurity (ROP) requiring laser therapy for treatment; [ 18 , 19 ] (5) haemodynamically significant patent ductus arteriosus (PDA) requiring surgical treatment; [ 20 , 21 ] and (6) death between 36 weeks PMA and 18–24 months follow-up for respiratory disease. 2.3.2 Subgroup: Respiratory Outcomes According to studies on the late complications of BPD, respiratory diseases are the most common complication. [ 14 , 16 , 22 ] Therefore, we performed subgroup analysis of respiratory outcomes alone and described the respiratory outcomes further as follows: (1) ≥ 5 outpatient services for respiratory reasons during follow-up; (2) ≥ 2 rehospitalizations for respiratory reasons during follow-up; (3) hospitalization for respiratory infectious cases; (4) hospitalization for respiratory noninfectious cases; and (5) use of invasive ventilators. [ 23 , 24 ] The study protocol was approved by the Ethics Committees of Children’s Hospital, Chonqqing Medical University(2019 − 208). Informed consent was obtained from all subjects’ legal guardians. All methods were carried out in accordance with relevant guidelines and regulations. 2.4 Statistical Analysis All analyses were performed with SPSS version 24.0. Maternal and infant characteristics were summed up with descriptive statistics, including risk factors, labour and delivery outcomes, and infant characteristics at birth. Categorical variables were expressed as a percentage and processed with either χ2-test or Fisher's exact test, while normally distributed variables were expressed as the mean standard deviation. All statistical tests were two‐sided and at the 0.05 level of significance. 3. Results 3.1 Participant Characteristics During the study period, 322 infants were assessed. Seventeen infants with severe congenital malformations or missing key study data were excluded. Before 36 weeks, there were 9 deaths. Twenty-six infants were lost to follow-up. A total of 270 infants completed clinical and follow-up data. (Fig. 1) The characteristics of perinatal women and infants are shown in Table 2 . For perinatal women, the mean productive age was 30.0 ± 5.2 years old, with 20.0% over 35 years of age. The caesarean delivery rate was 51.1%, and 60.0% of perinatal women accepted antenatal corticosteroid therapy to promote foetal lung maturation. For infants, the mean gestational age (GA) was 29.7 ± 1.4 weeks; the mean birth weight (BW) was 1411.3 ± 285.3 g; 71.9% of preterm infants received surfactant replacement therapy after birth; respiratory support was used for 93.7% (n = 253) of the infants; 53.0% of them used noninvasive ventilators as the supplemental oxygen supplements; 38.9% of them used invasive ventilators; and the average length of hospital stay was 43.6 ± 19.5 days. Other detailed data are shown in Table 2 . Table 2 Characteristics and outcomes of the study infants. Characteristic Full study cohort N = 270 Hospital stays, days-mean(SD) 43.6(19.5) Gestational age, weeks<28, N(%) 21(7.8) Gestational age, weeks – mean (SD) 29.7(1.4) Twins or multiple pregnancy, n(%) 82(30.4) elderly primipara, years ≥ 35, n(%) 54(20.0) productive age, yeas-mean(SD) 30.0(5.2) Antenatal corticosteroid therapy, n(%) 162(60.0) normal delivery, n(%) 132(48.9) caesarean births, n(%) 138(51.1) Male sex, n (%) 156(57.8) Female sex, n (%) 114(42.2) Birth weight, g – mean (SD) 1411.3(285.3) Small for gestational age, n (%)* 12(4.4) pulmonary surfactant, n(%) 194(71.9) cardio-pulmonary resuscitation, n, % 56(20.7) RBC transfusion, n(%) 179(66.3) FFP or Cryo transfusion, n(%) 60(22.2) Antibiotic, course＞7 days, n(%) 172(63.7) Postpartum corticosteroid therapy, n(%) 18(6.7) Without oxygen therapy, n(%) 17(6.3) Oxygen therapy in Infant incubator**, n(%) 4(1.5) nasal catheter oxygen inhalation, n(%) 1(0.4) Non Invasive Ventilation, n(%) 143(53.0) invasive positive pressure, n(%) 105(38.9) Oxygen supplement, n(%) 253(93.7) ventilator supporting time, days - mean(SD) 17.1(18.6) Oxygen therapy time, days - mean(SD) 36.1(24.8) Calculated for the 270 infants who survived to follow-up testing. Abbreviations: RBC: red blood cell; FFP: fresh frozen plasma, Cryo: cryoprecipitate. * Defined as a birth weight < 10th percentile for gestational age and sex (25). **Defined as low flow rate oxygen inhalation to infant incubator. 3.2 Incidence and Grading of BPD According to Different Definitions Among the included subjects, the diagnostic rate of BPD defined by the 2001 criteria was 66.3%, which was significantly higher than that by the 2018 (48.1%) and 2019 (48.1%) ( P 0.05). For BPD grade II or moderate, the diagnostic rate of BPD defined by the 2001 criteria was significantly higher than that defined by the 2018 and 2019 ( P < 0.05) definitions. For BPD grade III or severe, the diagnosis rate of BPD defined by the 2001 definitions was also significantly higher than that defined by the 2019 ( P < 0.05) definition. Based on previous results, we tried to combine moderate and severe BPD under the three definitions, and similar results were obtained. Both the diagnostic rates of mild BPD and moderate/severe BPD by the 2001 definition was significantly higher than those of the other two definitions. Therefore, due to the small total sample size of this study, we combined moderate and severe BPD in subsequent statistics (Table 3 ). Table 3 BPD morbidity in the Prematurity Program cohort using the three definitions Total (n = 270) 2001 definition 2018 definition 2019 definition P 1 * Significant Group P 2 * No BPD, n (%) 91(33.7) 140(51.9) 140(51.9) 0.000 2001&2018 2001&2019 2018&2019 0.000 0.000 1.000 BPD, n (%) 179(66.3) 130(48.1) 130(48.1) 0.000 2001&2018 2001&2019 2018&2019 0.000 0.000 1.000 Grade Ⅰ or mild, n (%) 49(18.1) 61(22.6) 59(21.9) 0.396 / / Grade Ⅱ or moderate, n (%) 83(30.7) 39(14.4) 49(18.1) 0.000 2001&2018 2001&2019 2018&2019 0.000 0.000 0.244 Grade Ⅲ or severe, n (%) 47(17.4) 30(11.1) 22(8.5) 0.004 2001&2018 2001&2019 2018&2019 0.055 0.001 0.190 *P 1 : Comparison between the three definitions. *P 2 : Pairwise comparison between the Significant Group. 3.3 Adverse Outcomes of Premature Infants A total of 32.2% of the infants had adverse outcomes, and 5 died before 18–24 months. Among them, the proportion of respiratory adverse outcomes was the highest, reaching 29.6%. The morbidity of neural adverse outcomes, low development level, ROP surgery, and PDA surgery were 5.2%, 8.5%, 1.1%, and 0.7%, respectively (Table 4 and Table 5 ). Table 4 Adverse Outcomes 2001 s definition 2018 definition 2019 definition BPD = YES (N = 179) Mild (N = 49) Moderate &Serve N= (130) BPD = YES (N = 130) GradeⅠ (N = 61) GradeⅡ &GradeⅢ N= (69) BPD = YES (N = 130) GradeⅠ (N = 59) GradeⅡ &GradeⅢ N= (71) Respiratory adverse outcomes 70/179(39.1) 10/49(20.4) 60/130(46.2) 60/130(46.2) 15/61(24.6) 45/69 (65.2) a 60/130(46.2) 13/59(22.0) 47/71(66.2) a Neural adverse Outcomes 12/179(6.7) 1/49(2.0) 11/130(8.5) 11/130(8.5) 3/61(4.9) 8/69(11.6) 11/130(8.5) 3/59(5.1) 8/71(11.3) Low Development level 20/179(11.2) 2/49(4.1) 18/130(13.8) 18/130(13.8) 4/61(6.6) 14/69(20.3) 18/130(13.8) 3/59(5.1) 15/71(21.1) ROP surgery 3/179(1.7) 0/49(0) 3/130(2.3) 3/130(2.3) 1/61(1.6) 2/69(2.9) 3/130(2.3) 1/59(1.7) 2/71(2.9) PDA surgery 2/179(1.1) 0/49(0) 2/130(1.5) 2/130(1.5) 0/61(0) 2/69(2.9) 2/130(1.5) 0/59(0) 2/71(2.9) Late death 5/179(2.8) 1/49(2.0) 4/130(3.1) 4/130(3.1) 0/61(0) 4/69(5.8) 4/130(3.1) 0/59(0) 4/71(5.6) Total infants 74/179(41.3) 10/49(20.4) 64/130(49.2) 64/130(49.2) 17/61(27.9) 47/69(68.1) a 64/130(49.2) 15/25.4 49/71(69.0) a Abbreviations: BPD: bronchopulmonary dysplasia; ROP: retinopathy of prematurity; PDA: patent ductus arteriosus; Late Death: death after PMA 36 weeks for respiratory disease; Low Development level: length, weight or head circumference < 3rd percentile for corrected gestational age and sex. Growth percentiles defined using the World Health Organization Child Growth Standards. *Infants with multiple adverse outcomes were included in multiple subgroups. *Respiratory adverse outcomes, Neural adverse outcomes as shown in the Methods. a: Compared to the 2001 s definitions, p < 0.05. Table 5 Subgroup analysis: Respiratory Outcomes 2001 definition 2018 definition 2019 definition BPD = YES (N = 179) Mild (N = 49) Moderate &Serve N= (130) BPD = YES (N = 130) GradeⅠ (N = 61) GradeⅡ &GradeⅢ N= (69) BPD = YES (N = 130) GradeⅠ (N = 59) GradeⅡ &GradeⅢ N= (71) Outpatient Service ≥ 5 times 61/179(34.1) 8/49(16.3) 53/130(40.1) 53/130(40.8) 13/61(21.3) 40/69(58.0) a 53/130(40.8) 12/59(20.3) 41/71(57.7) a Readmission ≥ 2 times 63/179(35.2) 8/49(16.3) 55/130(42.3) 55/130(42.3) 15/61(24.6) 40/69(58.0) a 55/130(42.3) 13/59(22.0) 42/71(59.2) a hospitalized for infectious case 57/179(31.8) 8/49(16.3) 49/130(37.7) 49/130(37.7) 13/61(21.3) 36/69(52.2) a 49/130(37.7) 12/59(20.3) 37/71(52.1) a hospitalized for noninfectious case 6/179(3.4) 0/49(0) 6/130(4.6) 6/130(4.6) 2/61(3.3) 4/69(5.8) 6/130(4.6) 1/59(1.7) 5/71(7.0) Use of Invasive ventilator 7/179(3.9) 1/49(2.0) 3/130(2.3) 6/130(4.6) 0/61(0) 6/69(8.7) 6/130(4.6) 0/59(0) 6/71(8.4) Abbreviations: BPD: bronchopulmonary dysplasia; infectious case noninfectious case: lung diseases caused by pathogens; lung diseases other than infections: including but not limited to acute respiratory distress syndrome or asthma. *All incidents occurred as a result of respiratory disease. *Infants with multiple adverse outcomes were included in multiple subgroups. *Respiratory adverse outcomes, neural adverse outcomes as shown in the Methods. a: Compared to the 2001 definition, P < 0.05. 3.3.1 Incidence of Adverse Outcomes Using Different Definitions Comparing the incidence of various adverse outcomes in infants with different degrees of BPD under the three definitions showed that the probability of total adverse outcomes in infants with moderate and severe BPD under the 2018 and 2019 definitions was significantly higher than that under the 2001 definition (P < 0.05). Among them, the probability of respiratory adverse outcomes in infants with moderate and severe BPD defined by the 2018 and 2019 criteria was significantly higher than that defined by the 2001 criteria ( P 0.05). Other detailed data are shown in Table 4 . 3.3.2 Subgroup Analysis We further analysed respiratory outcomes under different definitions during follow-up. Our analysis showed that due to respiratory diseases, the probability of “Outpatient service ≥ 5 times”, “Readmission ≥ 2 times”, and “Hospitalized for respiratory infectious case” in moderate and severe BPD defined by the 2018 and 2019 criteria were significantly higher than that defined by the 2001 criteria ( P <0.05), while there was no significant difference between the definitions of 2018 and 2019 ( P ＞0.05). No significant difference was found in the probability of “hospitalized for respiratory noninfectious cases” and “use of invasive ventilators” in infants with BPD among the three definitions ( P > 0.05). Other detailed data are shown in Table 5 . 3.3.3 Performance Evaluation Through the sensitivity and specificity calculation formula, we calculated the diagnostic efficacy of the three definitions by taking the occurrence of adverse respiratory outcomes as a positive indicator. The susceptibility and specificity of the 2001 definition in the whole cohort were 0.85 and 0.43, respectively, and the negative predictive value and positive predictive value were 0.41 and 0.86, respectively. Compared to the 2019 and 2018 definitions, the 2001 definition had a high susceptibility but a low specificity for the prediction of severe respiratory outcomes, especially in the moderate and severe grades of BPD (Table 6 ). Table 6 Performance Evaluation sensitivity Specificity Positive predictive value Negative predictive value Total cohort 2001 definition 0.85 0.43 0.41 0.86 2018 definition 0.74 0.64 0.41 0.84 2019 definition 0.74 0.64 0.41 0.84 Moderate and serve 2001 definition 0.66 0.58 0.34 0.84 2018 definition 0.54 0.88 0.68 0.80 2019 definition 0.55 0.87 0.66 0.81 *Regarded the occurrence of adverse respiratory outcomes as a positive indicator. *Compared the efficiency of predicting the occurrence of this outcome. 4. Discussion With the improvement of treatment technology for premature infants, an increasing number of critical premature infants have successfully survived. However, the incidence of BPD has not decreased, and the progress of relevant research is slow. [ 15 ] One of the primary reasons is that the definition of BPD is still not uniform, and its diagnosis and grading standards lack objectivity. [ 25 ] It is well known that BPD is a chronic lung disease that may have a serious impact on the later quality of life of surviving preterm infants. [ 26 ] However, the diagnostic criteria of BPD in various medical units have not been unified, so it is difficult to formulate a clinical application guide for early intervention of different degrees of BPD. As Faith Kim et al. reported, [ 27 ] even within a single institution, the discordance between BPD incidence based on different definitions was significant, highlighting the difficulty in comparing BPD among centres without consistent diagnostic criteria. Therefore, it is necessary to evaluate the existing diagnostic criteria of BPD and standardize the clinical diagnosis. Among the definitions of BPD, the accurate prediction of adverse outcomes is an important standard to measure the feasibility of the definition. An important avenue for exploration will be the relationship between different grades of BPD under different definitions and their long-term adverse outcomes. In this study, we compared the morbidity and grading of BPD and the occurrence of adverse outcomes under three different definitions. The results found that the incidence of adverse outcomes was low in infants with mild BPD and increased with the severity of BPD in all three definitions. As mentioned previously, BPD is a common chronic lung disease of preterm infants that is critically affected from prenatal to early childhood and that increases the burden of social medical care and expenditure of households. [ 28 ] Therefore, we are more focused on the long-term prognosis. Our results show that both the 2018 and 2019 definitions systematically classified respiratory support patterns in a way that was more cautious and rigorous in diagnosis, and they had better predictive value of long-term prognosis. They could be used to guide the focus of early intervention and rehabilitation treatment and improve the early treatment effect and long-term quality of life of critically ill infants. On the other hand, more infants were considered to have no BPD or mild BPD according to the 2018 and 2019 definitions, which can reduce unnecessary excessive intervention in mildly affected infants, such as shorter hospital stays and lower costs of treatment, due to the low incidence of adverse outcomes in infants with mild BPD. Comparison of the 2018 and 2019 definitions showed that both were good predictors of long-term adverse outcomes. The primary difference between these two definitions were the classification of respiratory support patterns and whether radiographic evidence of lung disease was required. The 2018 definition required radiographic evidence of lung disease and used oxygen concentration combined with a respiratory support model and was classified in more detail. The 2019 definition shows the optimal definition of BPD severity using only the mode of respiratory support, which is more convenient for clinical implementation. There are several limitations to this study. First, this study was a single-centre retrospective study with a small sample size, which could have affected the accuracy of the analysis. Second, in our study, few infants used the HFNC support mode alone, which limits our discussion of HFNC patterns. Third, all three definitions did not fully separate HFNC from NIV, but there was still controversy between the two in the effectiveness difference of early treatment of dyspnoea and reduction of extubation failure in premature infants, suggesting that different noninvasive respiratory support methods may play a certain role in differentiating the severity of BPD. [ 29 ] Further classification may be needed in the future. 5. Conclusion Compared to the 2001 definition, the 2018 and 2019 definitions are more accurate in predicting BPD-related adverse outcomes, especially respiratory outcomes, in critical infants. Early prediction of chronic lung disease through BPD diagnosis can help early preventive intervention accurately, which can improve prognosis and reduce medical burden. Therefore, we suggest that clinical treatment and research for BPD choose an appropriate definition based on the actual situation. For example, for infants with BPD diagnosed by the 2001 definition, we suggest screening for moderate and severe BPD again using the 2019 definition (which is easier to define than 2018) and carrying out early preventive intervention. Declarations Competing interests: None declared. Ethical approval: This study was approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University. Patient consent: Obtained. Data sharing: No additional data are available. Author Contributions: Yuan Shi: Prof. Shi conceptualized and designed the study, drafted the manuscript, and approved the final manuscript as submitted. Li Wang and Ruiwen Li: Drs. Wang, et al designed the data collection instruments, coordinated and supervised the data collection, carried out the initial analyses, drafted the manuscript, and approved the final manuscript as submitted. Jianhui Wang and Hui Liu: Dr Wang,et al coordinated and supervised the data collection, and approved the final manuscript as submitted. Funding Source: Funding was from Key R & D projects in the field of health in the special project for technological innovation and application development of Chongqing Bureau of science and technology, China. [(2021)168]. Conflicts of Interest: None of the authors have conflicts of interest to disclose. Financial Disclosure: None of the authors have financial relationships relevant to this article to disclose. Clinical Trial Registration: Number: NCT04184648；Date of first registration：29/11/2019. Availability of Data and Materials: All data generated or analyzed during this study are included in this published article and its supplementary information files. References Northway WH, Jr., Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967;276(7):357–68. Piersigilli F, Bhandari V. Metabolomics of bronchopulmonary dysplasia. Clin Chim Acta. 2020;500:109–14. Bancalari E, Jain D. Bronchopulmonary Dysplasia: 50 Years after the Original Description. Neonatology. 2019;115(4):384–91. Underwood MA, Wedgwood S, Lakshminrusimha S, Steinhorn RH. Somatic growth and the risks of bronchopulmonary dysplasia and pulmonary hypertension: connecting epidemiology and physiology (1). Can J Physiol Pharmacol. 2019;97(3):197–205. Alvarez-Fuente M, Arruza L, Muro M, Zozaya C, Avila A, Lopez-Ortego P, et al. 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Tracy MK, Berkelhamer SK. Bronchopulmonary Dysplasia and Pulmonary Outcomes of Prematurity. Pediatr Ann. 2019;48(4):e148-e53. Davidson LM, Berkelhamer SK. Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long-Term Pulmonary Outcomes. J Clin Med. 2017;6(1). Poindexter BB, Feng R, Schmidt B, Aschner JL, Ballard RA, Hamvas A, et al. Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program. Ann Am Thorac Soc. 2015;12(12):1822–30. Sahni M, Bhandari V. Recent advances in understanding and management of bronchopulmonary dysplasia. F1000Res. 2020;9. Faith Kim, David A, Bateman, Nimrod Goldshtrom, Rakesh Sahni, Jen Tien Wung, Aaron Wallman-Stokes. Revisiting the definition of bronchopulmonary dysplasia in premature infants at a single center quaternary neonatal intensive care unit. Journal of Perinatology. 2021; 41: 756–763. Kurihara C, Zhang L, Mikhael M. Newer bronchopulmonary dysplasia definitions and prediction of health economics impacts in very preterm infants. Pediatr Pulmonol. 2021;56(2):409–17. Shi Y, Muniraman H, Biniwale M, Ramanathan R. A Review on Non-invasive Respiratory Support for Management of Respiratory Distress in Extremely Preterm Infants. Front Pediatr. 2020;8:270. Additional Declarations No competing interests reported. Supplementary Files rawdata.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1935674","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":131288895,"identity":"66c337ba-7475-49ba-9a0a-5c6b1eb838f5","order_by":0,"name":"Ruiwen Li","email":"","orcid":"","institution":"National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ruiwen","middleName":"","lastName":"Li","suffix":""},{"id":131288900,"identity":"97ceee6d-b280-47c8-ad47-e7048e6b7b58","order_by":1,"name":"Li Wang","email":"","orcid":"","institution":"Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Wang","suffix":""},{"id":131288902,"identity":"f56616a4-5152-437e-88df-a935e0617d4d","order_by":2,"name":"Jianhui Wang","email":"","orcid":"","institution":"National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianhui","middleName":"","lastName":"Wang","suffix":""},{"id":131288903,"identity":"e94f92db-d1ba-4d96-b951-120cee863b4a","order_by":3,"name":"Hui Liu","email":"","orcid":"","institution":"Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Liu","suffix":""},{"id":131288907,"identity":"93e5eae5-3cb2-433e-a86b-98a185ce06d3","order_by":4,"name":"Yuan Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABIElEQVRIie3PMUsDMRQH8CcnueWJa0DbfoXIwRWh9LPkKNwtdhVBQeGgXaSzon6HgKi4nQS8pR8gYofekqmDk3RScx4RhFQdHfInJJCXH3kPwMfnP4aundRHm9U7B9i2heb+BxI1hAP+gTRHIqD55nfSuchHW3g0y+7CsZ5Xyz5CKG+uEXotUQR67iBs9mDIox7en067jPMBAqb7zwhpJArSZS5CE0OIHAq1RyjnAQLF2BCZiAIJdTV2VpM3mTGVaUOOLXlfSUAZsjGSnCkeGyItKVYSppJ892oid8S0niUtkZhZni7ZIDqXJHY3llVq8So7rBzratk7bG+G8lYtDvqtSZlrZ2MA6/ae2J19Lgjc7+vKyzcCzXsfHx8fn698APsNYklvmV10AAAAAElFTkSuQmCC","orcid":"","institution":"National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children’s Hospital of Chongqing Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2022-08-06 11:14:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1935674/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1935674/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":25793067,"identity":"f0c394f9-9278-4ce3-8529-a641eb9a61ac","added_by":"auto","created_at":"2022-08-29 13:53:52","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39883,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1935674/v1/e505c33307ba349a679c131b.jpg"},{"id":26952402,"identity":"958c53fd-0a5c-4342-a1bd-f8d4329e762d","added_by":"auto","created_at":"2022-09-26 06:44:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":462327,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1935674/v1/4299150b-3544-43a6-a096-bfac5cfed9ec.pdf"},{"id":25793068,"identity":"f2e9d074-538c-4ec3-af3e-6af6d4b9d345","added_by":"auto","created_at":"2022-08-29 13:53:52","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":118052,"visible":true,"origin":"","legend":"","description":"","filename":"rawdata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-1935674/v1/3c80d1b6721dff8f8904547b.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of different definitions of bronchopulmonary dysplasia based on the prediction of adverse outcomes: Followed up to 18-24 months corrected age","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBronchopulmonary dysplasia (BPD), first reported and named by Northway and colleagues in 1967\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, is among the most common and severe sequelae of preterm birth.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e BPD as a lung injury in preterm infants, resulting from oxygen and mechanical ventilation, results in a huge expense for public health care systems, which may increase in the coming years due to the rising incidence and survival of preterm babies.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e The development of new therapies and preventative strategies to decrease the incidence of BPD and BPD-associated morbidities should be a priority.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e However, in clinical work, the BPD definition has not been clearly unified and standardized, which limits clinical progress.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn 1979, the diagnostic standard of BPD was first published.\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e In the following decades, the diagnostic standard of BPD has undergone numerous improvements and updates, among which the representative diagnosis recognized by the industry was mainly in the 2001, 2018, and 2019 updates,\u003csup\u003e[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e but which definition was the most valid is still not definitive. An appropriate definition of BPD would help predict adverse outcomes, reduce the incidence of late complications and serious complications through early intervention, and improve the quality of life of children.\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e Therefore, it is necessary to create a BPD screening diagnostic standard that can effectively predict a prognosis to standardize the early clinical diagnosis and treatment of BPD.\u003c/p\u003e \u003cp\u003eThis study was an ambispective cohort study that aimed to compare the effects of the 2001, 2018, and 2019 definitions on clinical diagnosis, along with the predictive ability of prognosis, to provide a reference for clinical treatment and prognosis evaluation.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv class=\"Section2\" id=\"Sec3\"\u003e\n \u003ch2\u003e2.1 Participants\u003c/h2\u003e\n \u003cp\u003eSource study data were from the Department of Neonatology, Children`s Hospital of Chongqing Medical University. The neonatal research retrospectively obtained clinical data from preterm infants with gestational age\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks, and length of hospital stay\u0026thinsp;\u0026gt;\u0026thinsp;14 days, from January 1, 2018, to May 30, 2019. Prior to June 1, 2021, postdischarge outcome data were collected at 18\u0026ndash;24 months corrected age. Eligible infants survived 36 weeks PMA and either completed 18\u0026ndash;24 months follow-up or died prior to anticipated follow-up. The exclusion criteria were severe congenital malformations, missing key study data, or loss to follow-up.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec4\"\u003e\n \u003ch2\u003e2.2 Definitions of Bronchopulmonary Dysplasia (Details in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/h2\u003e\n \u003cp\u003eIn 2001, according to clinical variations in oxygen administration, a workshop convened by the National Institute of Child Health and Human Development proposed severity-based diagnostic criteria for BPD (hereafter referred to as the \u0026ldquo;2001 definition\u0026rdquo;): infants born\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks gestation treated with supplemental oxygen for at least 28 days and an assessment of respiratory support at 36 weeks postmenstrual age (PMA). BPD levels were regarded as none, mild, moderate, and serve, which was based on oxygen support.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e Mild BPD means no use of oxygen after PMA36 weeks. Moderate BPD was defined as \u0026lt;\u0026thinsp;30% oxygen, and severe BPD was defined as any form of ventilatory support and/or \u0026ge;\u0026thinsp;30% oxygen.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBronchopulmonary dysplasia (BPD) definition\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eNIH 2001 definition\u003c/p\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eServe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eBreathing in room air at 36 weeks PMA\u003c/p\u003e\n \u003cp\u003eNeed for \u0026lt;\u0026thinsp;30% oxygen at 36 weeks PMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eNeed for \u0026ge;\u0026thinsp;30% oxygen with any form of ventilatory support at 36 weeks PMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eNIH 2018 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInvasive IPPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNCPAP, NIPPV, or nasal cannula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNasal cannula flow of 1- \u0026lt;3 L/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHood oxygen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNasal cannula flow of \u0026lt;\u0026thinsp;1 L/min\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u0026ndash;29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u0026ndash;29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u0026ndash;70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u0026ndash;29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003csub\u003eA\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eEarly death (between 14 days of postnatal age and 36 weeks) owing to persistent parenchymal lung disease and respiratory failure that cannot be attributable to other neonatal morbidities (e.g.. necrotizing enterocolitis, intraventricular haemorrhage, redirection of care, episodes of sepsis, etc.).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e2019 Jesen definition\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eNeed for oxygen with nasal catheter\u0026thinsp;\u0026le;\u0026thinsp;2 L/min\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eNeed for oxygen with nasal catheter＞2 L/min, or NIV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eNeed for oxygen with invasive positive pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e*Definitions for bronchopulmonary dysplasia assessed at 36 weeks postmenstrual age.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e*Abbreviations: PMA: postmenstrual age; NIV, noninvasive ventilator; NIPPV: noninvasive positive pressure ventilation; NCPAP: nasal continuous positive airway pressure\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eIn 2018, another workshop sponsored by the National Institutes of Health revealed a new BPD definition to help identify varying severity (hereafter referred to as \u0026ldquo;2018 definition\u0026rdquo;):\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e Infants\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks gestation survived to 36 weeks PMA with radiographic evidence of lung disease who required supplemental oxygen/respiratory support. Infants with BPD were classified according to treatment with different respiratory support. They proposed using new terms, assessed at 36 weeks PMA, of grades I, II, and III instead of mild, moderate, and severe.\u003c/p\u003e\n \u003cp\u003eIn 2019, Jensen et al. found that the optimal definition categorized BPD severity only according to the mode of respiratory support administered at 36 weeks PMA (hereinafter referred to as the \u0026ldquo;2019 definition\u0026rdquo;), which better affects contemporary neonatal care and adequately predicts childhood morbidity.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec5\"\u003e\n \u003ch2\u003e2.3 Outcome Variables\u003c/h2\u003e\n \u003cdiv class=\"Section3\" id=\"Sec6\"\u003e\n \u003ch2\u003e2.3.1 Adverse Outcomes\u003c/h2\u003e\n \u003cp\u003eWe counted the adverse outcomes of the enrolled infants at 18\u0026ndash;24 months corrected age and compared the probability differences of adverse outcomes under the three definitions of BPD to speculate the prediction accuracy of the 3 prespecified diagnostic criteria for adverse outcomes.\u003c/p\u003e\n \u003cp\u003eAn adverse outcome was defined as the occurrence of at least one of the following:\u003c/p\u003e\n \u003cp\u003e(1) Respiratory adverse outcomes;\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e (2) severe neurological outcomes defined as brain retardation assessed by the Child Neurological Development Scale, developmental quotient (DQ) score\u0026thinsp;\u0026lt;\u0026thinsp;85 assessed by the Gesell developmental schedules of infants, or brain damage requiring rehabilitation treatment assessed by a qualified physical therapist;\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e and (3) low development level (height, weight or head circumference\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile for corrected gestational age and sex, growth percentiles defined using the World Health Organization Child Growth Standards) at 18\u0026ndash;24 months corrected age; (4) retinopathy of prematurity (ROP) requiring laser therapy for treatment;\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e (5) haemodynamically significant patent ductus arteriosus (PDA) requiring surgical treatment;\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e and (6) death between 36 weeks PMA and 18\u0026ndash;24 months follow-up for respiratory disease.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec7\"\u003e\n \u003ch2\u003e2.3.2 Subgroup: Respiratory Outcomes\u003c/h2\u003e\n \u003cp\u003eAccording to studies on the late complications of BPD, respiratory diseases are the most common complication.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e Therefore, we performed subgroup analysis of respiratory outcomes alone and described the respiratory outcomes further as follows:\u003c/p\u003e\n \u003cp\u003e(1)\u0026thinsp;\u0026ge;\u0026thinsp;5 outpatient services for respiratory reasons during follow-up; (2)\u0026thinsp;\u0026ge;\u0026thinsp;2 rehospitalizations for respiratory reasons during follow-up; (3) hospitalization for respiratory infectious cases; (4) hospitalization for respiratory noninfectious cases; and (5) use of invasive ventilators.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eThe study protocol was approved by the Ethics Committees of Children\u0026rsquo;s Hospital, Chonqqing Medical University(2019\u0026thinsp;\u0026minus;\u0026thinsp;208). Informed consent was obtained from all subjects\u0026rsquo; legal guardians. All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec8\"\u003e\n \u003ch2\u003e2.4 Statistical Analysis\u003c/h2\u003e\n \u003cp\u003eAll analyses were performed with SPSS version 24.0. Maternal and infant characteristics were summed up with descriptive statistics, including risk factors, labour and delivery outcomes, and infant characteristics at birth. Categorical variables were expressed as a percentage and processed with either \u0026chi;2-test or Fisher\u0026apos;s exact test, while normally distributed variables were expressed as the mean standard deviation. All statistical tests were two‐sided and at the 0.05 level of significance.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv class=\"Section2\" id=\"Sec10\"\u003e\n \u003ch2\u003e3.1 Participant Characteristics\u003c/h2\u003e\n \u003cp\u003eDuring the study period, 322 infants were assessed. Seventeen infants with severe congenital malformations or missing key study data were excluded. Before 36 weeks, there were 9 deaths. Twenty-six infants were lost to follow-up. A total of 270 infants completed clinical and follow-up data. (Fig.\u0026nbsp;1)\u003c/p\u003e\n \u003cp\u003eThe characteristics of perinatal women and infants are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. For perinatal women, the mean productive age was 30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 years old, with 20.0% over 35 years of age. The caesarean delivery rate was 51.1%, and 60.0% of perinatal women accepted antenatal corticosteroid therapy to promote foetal lung maturation. For infants, the mean gestational age (GA) was 29.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 weeks; the mean birth weight (BW) was 1411.3\u0026thinsp;\u0026plusmn;\u0026thinsp;285.3 g; 71.9% of preterm infants received surfactant replacement therapy after birth; respiratory support was used for 93.7% (n\u0026thinsp;=\u0026thinsp;253) of the infants; 53.0% of them used noninvasive ventilators as the supplemental oxygen supplements; 38.9% of them used invasive ventilators; and the average length of hospital stay was 43.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.5 days. Other detailed data are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCharacteristics and outcomes of the study infants.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFull study cohort\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;270\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital stays, days-mean(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.6(19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational age, weeks\u0026lt;28, N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational age, weeks \u0026ndash; mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.7(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTwins or multiple pregnancy, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eelderly primipara, years\u0026thinsp;\u0026ge;\u0026thinsp;35, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eproductive age, yeas-mean(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.0(5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntenatal corticosteroid therapy, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e162(60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enormal delivery, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132(48.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecaesarean births, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138(51.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e156(57.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e114(42.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBirth weight, g \u0026ndash; mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1411.3(285.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall for gestational age, n (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epulmonary surfactant, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e194(71.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecardio-pulmonary resuscitation, n, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRBC transfusion, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e179(66.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFFP or Cryo transfusion, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60(22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntibiotic, course＞7 days, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e172(63.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePostpartum corticosteroid therapy, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout oxygen therapy, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOxygen therapy in Infant incubator**, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enasal catheter oxygen inhalation, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon Invasive Ventilation, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e143(53.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einvasive positive pressure, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e105(38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOxygen supplement, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e253(93.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eventilator supporting time, days - mean(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.1(18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOxygen therapy time, days - mean(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.1(24.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eCalculated for the 270 infants who survived to follow-up testing.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eAbbreviations: RBC: red blood cell; FFP: fresh frozen plasma, Cryo: cryoprecipitate.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e* Defined as a birth weight\u0026thinsp;\u0026lt;\u0026thinsp;10th percentile for gestational age and sex (25).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e**Defined as low flow rate oxygen inhalation to infant incubator.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec11\"\u003e\n \u003ch2\u003e3.2 Incidence and Grading of BPD According to Different Definitions\u003c/h2\u003e\n \u003cp\u003eAmong the included subjects, the diagnostic rate of BPD defined by the 2001 criteria was 66.3%, which was significantly higher than that by the 2018 (48.1%) and 2019 (48.1%) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) criteria. Among infants with BPD, there was no significant difference in the diagnostic rate of BPD grade I or mild among the three definitions (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). For BPD grade II or moderate, the diagnostic rate of BPD defined by the 2001 criteria was significantly higher than that defined by the 2018 and 2019 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) definitions. For BPD grade III or severe, the diagnosis rate of BPD defined by the 2001 definitions was also significantly higher than that defined by the 2019 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) definition. Based on previous results, we tried to combine moderate and severe BPD under the three definitions, and similar results were obtained. Both the diagnostic rates of mild BPD and moderate/severe BPD by the 2001 definition was significantly higher than those of the other two definitions. Therefore, due to the small total sample size of this study, we combined moderate and severe BPD in subsequent statistics (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBPD morbidity in the Prematurity Program cohort using the three definitions\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;270)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2001\u003c/p\u003e\n \u003cp\u003edefinition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003cp\u003edefinition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003cp\u003edefinition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003csub\u003e1\u003c/sub\u003e*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSignificant\u003c/p\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003csub\u003e2\u003c/sub\u003e*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo BPD,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91(33.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e140(51.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e140(51.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2001\u0026amp;2018\u003c/p\u003e\n \u003cp\u003e2001\u0026amp;2019\u003c/p\u003e\n \u003cp\u003e2018\u0026amp;2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e179(66.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130(48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130(48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2001\u0026amp;2018\u003c/p\u003e\n \u003cp\u003e2001\u0026amp;2019\u003c/p\u003e\n \u003cp\u003e2018\u0026amp;2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅰ\u003c/p\u003e\n \u003cp\u003eor mild,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61(22.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59(21.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅱ\u003c/p\u003e\n \u003cp\u003eor moderate,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83(30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2001\u0026amp;2018\u003c/p\u003e\n \u003cp\u003e2001\u0026amp;2019\u003c/p\u003e\n \u003cp\u003e2018\u0026amp;2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003cp\u003e0.244\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅲ\u003c/p\u003e\n \u003cp\u003eor severe,\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2001\u0026amp;2018\u003c/p\u003e\n \u003cp\u003e2001\u0026amp;2019\u003c/p\u003e\n \u003cp\u003e2018\u0026amp;2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.190\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e*P\u003csub\u003e1\u003c/sub\u003e: Comparison between the three definitions.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e*P\u003csub\u003e2\u003c/sub\u003e: Pairwise comparison between the Significant Group.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec12\"\u003e\n \u003ch2\u003e3.3 Adverse Outcomes of Premature Infants\u003c/h2\u003e\n \u003cp\u003eA total of 32.2% of the infants had adverse outcomes, and 5 died before 18\u0026ndash;24 months. Among them, the proportion of respiratory adverse outcomes was the highest, reaching 29.6%. The morbidity of neural adverse outcomes, low development level, ROP surgery, and PDA surgery were 5.2%, 8.5%, 1.1%, and 0.7%, respectively (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAdverse Outcomes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2001 s definition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2018 definition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2019 definition\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;179)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003e\u0026amp;Serve\u003c/p\u003e\n \u003cp\u003eN= (130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅠ\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅡ\u003c/p\u003e\n \u003cp\u003e\u0026amp;GradeⅢ\u003c/p\u003e\n \u003cp\u003eN= (69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅠ\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅡ\u003c/p\u003e\n \u003cp\u003e\u0026amp;GradeⅢ\u003c/p\u003e\n \u003cp\u003eN= (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespiratory\u003c/p\u003e\n \u003cp\u003eadverse\u003c/p\u003e\n \u003cp\u003eoutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70/179(39.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10/49(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60/130(46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60/130(46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15/61(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45/69 (65.2)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60/130(46.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13/59(22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47/71(66.2)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeural\u003c/p\u003e\n \u003cp\u003eadverse\u003c/p\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12/179(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/49(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11/130(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11/130(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/61(4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/69(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11/130(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/59(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/71(11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eDevelopment level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20/179(11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/49(4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18/130(13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18/130(13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/61(6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14/69(20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18/130(13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/59(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15/71(21.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROP\u003c/p\u003e\n \u003cp\u003esurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/179(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/49(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/130(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/130(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/61(1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/69(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/130(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/59(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/71(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePDA\u003c/p\u003e\n \u003cp\u003esurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/179(1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/49(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/130(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/130(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/61(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/69(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/130(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/59(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/71(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLate\u003c/p\u003e\n \u003cp\u003edeath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5/179(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/49(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/130(3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/130(3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/61(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/69(5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/130(3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/59(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/71(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003einfants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74/179(41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10/49(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64/130(49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64/130(49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17/61(27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47/69(68.1)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64/130(49.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15/25.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49/71(69.0)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eAbbreviations: BPD: bronchopulmonary dysplasia; ROP: retinopathy of prematurity; PDA: patent ductus arteriosus; Late Death: death after PMA 36 weeks for respiratory disease; Low Development level: length, weight or head circumference\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile for corrected gestational age and sex. Growth percentiles defined using the World Health Organization Child Growth Standards.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*Infants with multiple adverse outcomes were included in multiple subgroups.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*Respiratory adverse outcomes, Neural adverse outcomes as shown in the Methods.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003ea: Compared to the 2001 s definitions, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab5\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSubgroup analysis: Respiratory Outcomes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2001 definition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2018 definition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2019 definition\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;179)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003e\u0026amp;Serve\u003c/p\u003e\n \u003cp\u003eN= (130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅠ\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅡ\u003c/p\u003e\n \u003cp\u003e\u0026amp;GradeⅢ\u003c/p\u003e\n \u003cp\u003eN= (69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBPD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅠ\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGradeⅡ\u003c/p\u003e\n \u003cp\u003e\u0026amp;GradeⅢ\u003c/p\u003e\n \u003cp\u003eN= (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOutpatient\u003c/p\u003e\n \u003cp\u003eService\u003c/p\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;5 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61/179(34.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/49(16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53/130(40.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53/130(40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13/61(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40/69(58.0)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53/130(40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12/59(20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41/71(57.7)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReadmission\u003c/p\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;2 times\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63/179(35.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/49(16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55/130(42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55/130(42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15/61(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40/69(58.0)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55/130(42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13/59(22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42/71(59.2)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehospitalized\u003c/p\u003e\n \u003cp\u003efor\u003c/p\u003e\n \u003cp\u003einfectious case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57/179(31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/49(16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49/130(37.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49/130(37.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13/61(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36/69(52.2)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49/130(37.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12/59(20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37/71(52.1)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehospitalized\u003c/p\u003e\n \u003cp\u003efor noninfectious case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/179(3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/49(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/130(4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/130(4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/61(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/69(5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/130(4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/59(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5/71(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUse of\u003c/p\u003e\n \u003cp\u003eInvasive\u003c/p\u003e\n \u003cp\u003eventilator\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/179(3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/49(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/130(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/130(4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/61(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/69(8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/130(4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/59(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/71(8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eAbbreviations: BPD: bronchopulmonary dysplasia; infectious case noninfectious case: lung diseases caused by pathogens; lung diseases other than infections: including but not limited to acute respiratory distress syndrome or asthma.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*All incidents occurred as a result of respiratory disease.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*Infants with multiple adverse outcomes were included in multiple subgroups.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e*Respiratory adverse outcomes, neural adverse outcomes as shown in the Methods.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003ea: Compared to the 2001 definition, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec13\"\u003e\n \u003ch2\u003e3.3.1 Incidence of Adverse Outcomes Using Different Definitions\u003c/h2\u003e\n \u003cp\u003eComparing the incidence of various adverse outcomes in infants with different degrees of BPD under the three definitions showed that the probability of total adverse outcomes in infants with moderate and severe BPD under the 2018 and 2019 definitions was significantly higher than that under the 2001 definition (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Among them, the probability of respiratory adverse outcomes in infants with moderate and severe BPD defined by the 2018 and 2019 criteria was significantly higher than that defined by the 2001 criteria (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Moreover, the incidence of other adverse outcomes was low overall, mainly in infants with moderate or severe BPD, and there was no significant difference among the three definitions (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Other detailed data are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec14\"\u003e\n \u003ch2\u003e3.3.2 Subgroup Analysis\u003c/h2\u003e\n \u003cp\u003eWe further analysed respiratory outcomes under different definitions during follow-up. Our analysis showed that due to respiratory diseases, the probability of \u0026ldquo;Outpatient service\u0026thinsp;\u0026ge;\u0026thinsp;5 times\u0026rdquo;, \u0026ldquo;Readmission\u0026thinsp;\u0026ge;\u0026thinsp;2 times\u0026rdquo;, and \u0026ldquo;Hospitalized for respiratory infectious case\u0026rdquo; in moderate and severe BPD defined by the 2018 and 2019 criteria were significantly higher than that defined by the 2001 criteria (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), while there was no significant difference between the definitions of 2018 and 2019 (\u003cem\u003eP\u003c/em\u003e＞0.05). No significant difference was found in the probability of \u0026ldquo;hospitalized for respiratory noninfectious cases\u0026rdquo; and \u0026ldquo;use of invasive ventilators\u0026rdquo; in infants with BPD among the three definitions (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Other detailed data are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec15\"\u003e\n \u003ch2\u003e3.3.3 Performance Evaluation\u003c/h2\u003e\n \u003cp\u003eThrough the sensitivity and specificity calculation formula, we calculated the diagnostic efficacy of the three definitions by taking the occurrence of adverse respiratory outcomes as a positive indicator. The susceptibility and specificity of the 2001 definition in the whole cohort were 0.85 and 0.43, respectively, and the negative predictive value and positive predictive value were 0.41 and 0.86, respectively. Compared to the 2019 and 2018 definitions, the 2001 definition had a high susceptibility but a low specificity for the prediction of severe respiratory outcomes, especially in the moderate and severe grades of BPD (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab6\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePerformance Evaluation\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003esensitivity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpecificity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003epredictive value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003epredictive value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2001 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2018 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eModerate and serve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2001 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2018 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019 definition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e*Regarded the occurrence of adverse respiratory outcomes as a positive indicator.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e*Compared the efficiency of predicting the occurrence of this outcome.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eWith the improvement of treatment technology for premature infants, an increasing number of critical premature infants have successfully survived. However, the incidence of BPD has not decreased, and the progress of relevant research is slow.\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e One of the primary reasons is that the definition of BPD is still not uniform, and its diagnosis and grading standards lack objectivity.\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIt is well known that BPD is a chronic lung disease that may have a serious impact on the later quality of life of surviving preterm infants.\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e However, the diagnostic criteria of BPD in various medical units have not been unified, so it is difficult to formulate a clinical application guide for early intervention of different degrees of BPD. As Faith Kim et al. reported,\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e even within a single institution, the discordance between BPD incidence based on different definitions was significant, highlighting the difficulty in comparing BPD among centres without consistent diagnostic criteria. Therefore, it is necessary to evaluate the existing diagnostic criteria of BPD and standardize the clinical diagnosis. Among the definitions of BPD, the accurate prediction of adverse outcomes is an important standard to measure the feasibility of the definition. An important avenue for exploration will be the relationship between different grades of BPD under different definitions and their long-term adverse outcomes.\u003c/p\u003e \u003cp\u003eIn this study, we compared the morbidity and grading of BPD and the occurrence of adverse outcomes under three different definitions. The results found that the incidence of adverse outcomes was low in infants with mild BPD and increased with the severity of BPD in all three definitions.\u003c/p\u003e \u003cp\u003eAs mentioned previously, BPD is a common chronic lung disease of preterm infants that is critically affected from prenatal to early childhood and that increases the burden of social medical care and expenditure of households.\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e Therefore, we are more focused on the long-term prognosis. Our results show that both the 2018 and 2019 definitions systematically classified respiratory support patterns in a way that was more cautious and rigorous in diagnosis, and they had better predictive value of long-term prognosis. They could be used to guide the focus of early intervention and rehabilitation treatment and improve the early treatment effect and long-term quality of life of critically ill infants. On the other hand, more infants were considered to have no BPD or mild BPD according to the 2018 and 2019 definitions, which can reduce unnecessary excessive intervention in mildly affected infants, such as shorter hospital stays and lower costs of treatment, due to the low incidence of adverse outcomes in infants with mild BPD.\u003c/p\u003e \u003cp\u003eComparison of the 2018 and 2019 definitions showed that both were good predictors of long-term adverse outcomes. The primary difference between these two definitions were the classification of respiratory support patterns and whether radiographic evidence of lung disease was required. The 2018 definition required radiographic evidence of lung disease and used oxygen concentration combined with a respiratory support model and was classified in more detail. The 2019 definition shows the optimal definition of BPD severity using only the mode of respiratory support, which is more convenient for clinical implementation.\u003c/p\u003e \u003cp\u003eThere are several limitations to this study. First, this study was a single-centre retrospective study with a small sample size, which could have affected the accuracy of the analysis. Second, in our study, few infants used the HFNC support mode alone, which limits our discussion of HFNC patterns. Third, all three definitions did not fully separate HFNC from NIV, but there was still controversy between the two in the effectiveness difference of early treatment of dyspnoea and reduction of extubation failure in premature infants, suggesting that different noninvasive respiratory support methods may play a certain role in differentiating the severity of BPD.\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e Further classification may be needed in the future.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eCompared to the 2001 definition, the 2018 and 2019 definitions are more accurate in predicting BPD-related adverse outcomes, especially respiratory outcomes, in critical infants. Early prediction of chronic lung disease through BPD diagnosis can help early preventive intervention accurately, which can improve prognosis and reduce medical burden. Therefore, we suggest that clinical treatment and research for BPD choose an appropriate definition based on the actual situation. For example, for infants with BPD diagnosed by the 2001 definition, we suggest screening for moderate and severe BPD again using the 2019 definition (which is easier to define than 2018) and carrying out early preventive intervention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e None declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e This study was approved by the Ethics Committee of the Children\u0026rsquo;s Hospital of Chongqing Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent:\u003c/strong\u003e Obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData sharing:\u003c/strong\u003e No additional data are available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuan Shi: Prof. Shi conceptualized and designed the study, drafted the manuscript, and approved the final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eLi Wang and Ruiwen Li: Drs. Wang, et al designed the data collection instruments, coordinated and supervised the data collection, carried out the initial analyses, drafted the manuscript, and approved the final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003eJianhui Wang and Hui Liu: Dr Wang,et al coordinated and supervised the data collection, and approved the final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Source:\u003c/strong\u003e Funding was from Key R \u0026amp; D projects in the field of health in the special project for technological innovation and application development of Chongqing Bureau of science and technology, China. [(2021)168].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003eNone of the authors have conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosure:\u0026nbsp;\u003c/strong\u003eNone of the authors have financial relationships relevant to this article to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration:\u003c/strong\u003e Number: NCT04184648；Date of first registration：29/11/2019.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials:\u003c/strong\u003e All data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNorthway WH, Jr., Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. 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Int J Pediatr Adolesc Med. 2020;7(1):9\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim SH, Han YS, Chun J, Lee MH, Sung TJ. Risk factors that affect the degree of bronchopulmonary dysplasia: Comparison by severity in the same gestational age. PLoS One. 2020;15(7):e0235901.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTracy MK, Berkelhamer SK. Bronchopulmonary Dysplasia and Pulmonary Outcomes of Prematurity. Pediatr Ann. 2019;48(4):e148-e53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavidson LM, Berkelhamer SK. Bronchopulmonary Dysplasia: Chronic Lung Disease of Infancy and Long-Term Pulmonary Outcomes. J Clin Med. 2017;6(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoindexter BB, Feng R, Schmidt B, Aschner JL, Ballard RA, Hamvas A, et al. Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program. Ann Am Thorac Soc. 2015;12(12):1822\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahni M, Bhandari V. Recent advances in understanding and management of bronchopulmonary dysplasia. F1000Res. 2020;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaith Kim, David A, Bateman, Nimrod Goldshtrom, Rakesh Sahni, Jen Tien Wung, Aaron Wallman-Stokes. Revisiting the definition of bronchopulmonary dysplasia in premature infants at a single center quaternary neonatal intensive care unit. Journal of Perinatology. 2021; 41: 756\u0026ndash;763.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurihara C, Zhang L, Mikhael M. Newer bronchopulmonary dysplasia definitions and prediction of health economics impacts in very preterm infants. Pediatr Pulmonol. 2021;56(2):409\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Y, Muniraman H, Biniwale M, Ramanathan R. A Review on Non-invasive Respiratory Support for Management of Respiratory Distress in Extremely Preterm Infants. Front Pediatr. 2020;8:270.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bronchopulmonary Dysplasia, Definition, Adverse Outcomes, 18-24 Months Corrected Age","lastPublishedDoi":"10.21203/rs.3.rs-1935674/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1935674/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn clinical work, the BPD definition has not been clearly unified and standardized, which limits clinical progress. A BPD diagnostic screening standard that can effectively predict the prognosis, as well as standardize the clinical early diagnosis and treatment of BPD, is needed.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We conducted an ambispective cohort study to compare the effects of the three different definitions of BPD on clinical diagnosis and the predictive ability of prognosis (followed to 18\u0026ndash;24 months corrected age).\u003c/p\u003e\u003ch2\u003eFindings:\u003c/h2\u003e \u003cp\u003eThe diagnostic rate of BPD defined in 2001 was significantly higher than that created in 2018 or 2019 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while the probability of adverse outcomes in infants with moderate and severe BPD diagnosed by the 2018 and 2019 definitions was significantly higher than those diagnosed by the 2001 definition (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eInterpretation:\u003c/h2\u003e \u003cp\u003eThe 2018 and 2019 diagnostic definitions are more accurate in predicting BPD-related adverse outcomes, especially respiratory outcomes. We suggest that for infants with BPD diagnosed via the 2001 definition, moderate and severe BPD should be screened again using the 2019 definition (which is easier to define than 2018), and early preventive intervention should be carried out.\u003c/p\u003e","manuscriptTitle":"Comparison of different definitions of bronchopulmonary dysplasia based on the prediction of adverse outcomes: Followed up to 18-24 months corrected age","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-29 13:53:50","doi":"10.21203/rs.3.rs-1935674/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6b027523-2792-4105-a294-6e8e68931586","owner":[],"postedDate":"August 29th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-09-26T06:44:29+00:00","versionOfRecord":[],"versionCreatedAt":"2022-08-29 13:53:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1935674","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1935674","identity":"rs-1935674","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}