Pulmonary Function and Bronchopulmonary Dysplasia Classification: Insights from the Spanish Registry

Pulmonary Function and Bronchopulmonary Dysplasia Classification: Insights from the Spanish Registry | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pulmonary Function and Bronchopulmonary Dysplasia Classification: Insights from the Spanish Registry Cristina Ramos-Navarro, Manuel Sánchez-Luna, Santiago Pérez-Tarazona, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4269926/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jun, 2024 Read the published version in European Journal of Pediatrics → Version 1 posted 8 You are reading this latest preprint version Abstract Background and Aims In 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36 weeks postmenstrual age (PMA). Methods The study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7 years of age. Statistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36 weeks PMA. Results The study involved 143 patients with a median gestational age (GA) of 27.3 weeks (range: 25.7-28.7) and a median weight of 880 grams (range: 740-1135). Pathological spirometry was observed in 39.2% (56) of the patients. Among patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36 weeks PMA exhibited an increased risk of pathological spirometry (OR 4.48; 95% CI: 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10,65; 95% IC 2,06-54,98) and BPD type 2 (OR 6,76; 95% IC 1,09-42,06). No significant differences were found in the incidence of an obstructive pattern between BPD types. Additionally, the study revealed distinct etiopathogenic mechanisms underlying the development of restrictive versus obstructive patterns. Conclusions: The requirement of more than 30% oxygen at 36 weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function. Figures Figure 1 Figure 2 INTRODUCTION Bronchopulmonary dysplasia (BPD) is the most common morbidity associated with prematurity, contributing to a significant impact on respiratory health throughout childhood and into adulthood [1]. The diagnosis of BPD is established at 36 weeks postmenstrual age (PMA) based on the respiratory support required up to that point. Traditionally, patients are classified as having BPD if they have required oxygen supplementation above 21% for more than 28 days, and is classified according to the respiratory support required at 36 weeks PMA as Type 1 (mild: no support), Type 2 (moderate: nasal cannula with < 30% oxygen), or Type 3 (severe: positive pressure or nasal cannula with ≥ 30% oxygen) [2]. Improvements in the care and management of preterm infants have had a profound impact on the pathophysiology of this condition [3]. The introduction of early minimally invasive surfactant administration, precise oxygen titration, and non-invasive ventilation strategies have attenuated the lung injury associated with mechanical ventilation and oxidative stress. Simultaneously, technological innovations and comprehensive antenatal and postnatal care have significantly enhanced the survival rates of infants born at gestational ages (GA) as low as 23–24 weeks, representing a substantially earlier stage of pulmonary development compared to historical cohorts [4]. These substantial advances have generated considerable debate regarding the efficacy of traditional BPD classification in predicting respiratory morbidity and long-term lung function abnormalities in contemporary BPD patients. Alternative classification criteria based on modern respiratory interventions have been proposed [5, 6], but consensus on the optimal criteria remains to be reached [7]. The Spanish Bronchopulmonary Dysplasia Research Group (GEIDIS), established in 2016 as a network comprising 66 hospitals, gathers data on the perinatal characteristics and long-term outcomes of patients diagnosed with BPD. Its purpose is to enhance the understanding of respiratory progression and impact during childhood and adulthood in patients who develop BPD today. In a previous study investigating perinatal risk factors among preterm infants included in the registry and their association with BPD severity, it was found that among patients with BPD type 3, the need for more than 30% oxygen at 36 weeks PMA was associated with increased morbidity both during hospitalization and at discharge, in contrast to those requiring positive pressure support with less than 30% oxygen [8]. The aim of this study is to evaluate pulmonary function at 5–7 years of age in premature infants diagnosed with BPD, and to examine their correlation with perinatal risk factors and the respiratory support and oxygen requirements at 36 weeks PMA. MATERIALS AND METHODS The study retrospectively analyzed data from infants who were prospectively enrolled in the GEIDIS registry and were born between January 2016 and December 2017. Inclusion criteria : Patients born at less than 32 weeks GA, diagnosed with BPD (more than 28 days on respiratory support or an FiO2 > 21% considered at 36 weeks PMA) [2], who had been entered into the GEIDIS registry database and has an acceptable forced spirometry recorded between 5 and 7 years of age. Definitions of the variables used in the study (specified in the database) (Appendix 1). Lung Function Parameters: The measurements were performed according to American Thoracic Society/European Respiratory Society guidelines [9]. The following parameters were recorded in the database: forced vital capacity (FVC); forced expiratory volume in the first second (FEV1) and FEV1/FVC. Z-scores for spirometry parameters were calculated using the Global Lung Function Initiative 2012 (GLI-2012) equations, allowing the determination of the percentage of children below the lower limit of normal (LLN) for each parameter (5th percentile or z-score of -1.64) [10]. These equations were recently validated in healthy Spanish Caucasian preschool children aged 3-6 years [11]. Pathologic spirometry was defined as FEV1/FVC z-score < -1.64 or FVC z-score < -1.64, while a normal pattern was defined as FEV1/FVC ≥ -1.64 z-score, FEV1 ≥ -1.64 z-score, and FVC ≥ -1.64 z-score. An obstructive pattern was defined by an FEV1/FVC < -1.64 z-score, a restrictive pattern by an FVC < -1.64 z-score, and a mixed pattern by a combination of the two patterns. Statistical Analysis: Statistical analyses were conducted using IBM SPSS Statistics software package, version 21 (IBM Corp., Armonk, NY, USA, 2012). Descriptive analysis summarized quantitative variables using measures of central tendency and dispersion, while qualitative variables were presented as percentage distributions. Comparative analysis of categorical variables employed the Chi-squared test (χ2) or Fisher’s exact test, with Bonferroni correction for multiple comparisons. The Kruskal-Wallis test, adjusted with Bonferroni correction, was used to analyze non-normally distributed quantitative variables. The significance level was set at p-value < 0.05. Binary logistic regression was used for multivariate analysis of binary response variables, while linear regression was employed for quantitative variables. Variables were selected based on theoretical relevance and significance observed in bivariate analysis. Gestational age (GA) was included in all models due to its clinical importance. Informed consent was obtained from the legal guardians of all participants. RESULTS A total of 989 patients diagnosed with BPD and born at less than 32 weeks GA between 2016 and 2017 were included in the registry. Of these, pulmonary function test data were available for 143 patients between 5 and 7 years of age constituting the study population. Perinatal characteristics and spirometry values according to the NIH 2001 Classification of BPD ( Table 1 ). Table 1 Perinatal characteristics of patients according to NIH 2001 Consensus Classification. BPD type 1 (51%; n73) BPD type 2 (20.3%; n29) BPD type 3 (28.7%; n41) p Total (143) Gestational age (weeks) Median (IQR) 27.4 (26-28.3) 27.5 (26-28.3) 26.6 (25.2–28.8) 0.536 27.3 (25.7–28.7) < 26 weeks GA (n,%) 32(43.8%) 9 (32.8%) 21 (51.2%) 0.292 62 (43.7%) Birth weight (grams) 910 (765–1150) 950 (700-1187.5) 796 (687.5-977.5) 0,053 880 (740–1135) Female sex (n,%) 34 (46.6%) 14 (48.3%) 13 (31.7%) 0.262 61 (42.7%) Oligohydramnios (n,%) 8 (11.1%) 8 (29.6%) 11 (28.2%) 0.032* 27 (19.6%) Histological chorioamnionitis (n,%) 10 (13.7%) 4 (13.8%) 5 (12.8%) 1 19 (13.3%) Intrauterine growth restriction (n,%) 14 (19.2%) 5 (20%) 10 (25%) 0.761 29 (21%) Prenatal corticosteroids (n,%) 68 (93.2%) 27(93.1%) 38 (92.7%) 0.995 133 (93%) - Complete course 52 (77.6%) 21(75%) 36 (87.8%) 0.301 103 (80.1%) Intubation in delivery room (n,%) 25 (34.2%) 12 (41.4%) 14 (34.1%) 0.772 51 (35.7%) FiO 2 ≥ 30% in delivery room (n,%) 43 (58.9%) 25 (89.3%) 33 (82.5%) 0.002* 101 (71.6%) Surfactant Therapy (%, n) 64.8% (46/71) 75% (21/28) 82.9% (34/41) 0.111 72.1% (101/140) Days of mechanical ventilation; Median (IQR) 1 (0–11) 7.5 (0.25–28.25) 11 (3.5–31.5) < 0.001* 6 (0–19) Nosocomial pneumonia (%,n) 6.9% (5/72) 14.3% (4/28) 35% (14/40) 0.001† 16.4% (23/140) Pulmonary hypertension (%,n) 5.6% (4/71) 17.9% (5/28) 15.4% (6/39) 0.115 10.9% (15/138) * Difference between BPD type 1 and BPD type 2, and between BPD type 1 and BPD type 3. † BPD type 1 and 3 No significant differences in perinatal characteristics were observed between patients with BPD types 2 and 3. However, patients with BPD type 1 had a lower incidence of oligohydramnios, a lower requirement for more than 30% oxygen at birth, and a shorter duration of exposure to mechanical ventilation compared with patients with BPD types 2 and 3. The analysis of spirometry values did not reveal any significant differences between patients with type 2 and type 3 BPD (Table 2 ). Table 2 Lung function parameters according to NIH 2001 Consensus Classification: BPD type 1 (n73) BPD type 2 (n29) BPD type 3 (n 41) p Total (143) Corrected age (years) 5.3 (5.0-6.4) 5.8 (5.3–6.2) 5.9 (5.2–6.5) 0.570 5.96 (5.28–6.39) FEV1% 95 (83–103) 85 (76.6–97.4) 83 (69.9–95) 0.001 * 89 (79–100) FEV1 Z-score -0.48 (-1.25-0.29) -1.02 (-1.72- -0.27) -1.14 (-1.99- -0.52) 0.005 * -0.86 (-1.47-0.01) FVC % 99 (89–109) 91.2 (84.5–103) 88 (76-100.6) 0.009 † 94 (82–105) FVC Z-score 0.01 (-0.92-0.64) -0.33 (-1.02-0.31) -0.7 (-1.59-0.26) 0.061 -0.29 (-0.05- -0.09) FEV1/FVC 90.9 (83.35–94.5) 86.7 (79–93) 85 (78–98) 0.190 88.7 (80.6–94.7) FEV1/FVC Z score -0.61 (-1.63-0.46) -0.45 (-2.04-0.82) -1.08 (-1.97-0.74) 0.761 -0.64 (-1.84-0.63) Pathological spirometry (FVC or FEV1/FVC z-score < -1.64) 23 (31.5%) 12 (41.4%) 21 (51.2%) 0.038 † 56 (39.2%) - < 26 weeks 12 (37.5%) 5 (55.6%) 10 (47.5%) NS 43.5% - ≥ 26 weeks 11 (26.8%) 7 (35%) 11 (52.4%) 35.8% Normal spirometry (FEV1, FEV1/FVC, and FVC Z-score ≥ -1.64) 49 (67.1%) 16 (55.2%) 17 (41.5%) 0.028 † 82 (57.3%) - < 26 weeks 20 (62.5%) 4 (44.4%) 9 (42.6%) NS ‡ 53.2% - ≥ 26 weeks 29 (70.7%) 12 (60%) 8 (40%) 60.5% Obstructive pattern (FEV1/FVC z-score < -1.64 and FVC Z-score ≥ -1.64) 18 (25%) 9 (32.1%) 12 (31.6%) 0.676 39/138 (28.3%) - < 26 weeks 9 (28.1%) 4 (44.4%) 5 (26.3%) NS ‡ 30% - ≥ 26 weeks 9 (22.5%) 5 (26.3%) 7 (36.8%) 26.9% Restrictive/mixed pattern (FVC Z-score < -1.64) 5 (6.9%) 3 (10.7%) 9 (23.7%) 0.043 † 17/138 (12.3%) - < 26 weeks 3 (9.4%) 1 (11.1%) 5(26.3%) NS ‡ 15% - ≥ 26 weeks 2 (5%) 2 (10.5%) 4 (21.1%) 10.3% * Differences between BPD type 1 and BPD type 2 and between BPD type 1 and BPD type 3. † Difference between BPD type 1 and BPD type 3. ‡ No significant differences between < 26weeks GA and ≥ 26 weeks GA Patients diagnosed with type 1 BPD exhibited higher predicted FVC and FEV1 values, as well as higher FEV1 Z scores. Additionally, a greater proportion of patients had spirometry values in the normal range. 28.2% of patients (39) exhibit an obstructive pattern, 10.1% (14) a restrictive pattern, and 2.1% (3) a mixed pattern. Patients with restrictive and mixed patterns have been grouped for comparison. There are no significant differences in the percentage of patients with an obstructive pattern among BPD types. However, a higher proportion of patients with a restrictive-mixed pattern is observed in BPD type 3 compared to those with BPD type 1 (OR 3.82; 95% IC 1.19–12.34). Of the 39 patients with an obstructive pattern, 26 (66.6%) had an FEV1 value within the normal range, with a higher rate between BPD type 1 patients, 16 (88.8%), compared to BPD type 2, 4 (44.4%), and BPD type 3, 6 (50%) (p = 0.02). Spirometry values grading type 3 BPD according to Respiratory and Oxygen support at 36 weeks PMA. Individuals requiring positive pressure support with equal or more than 30% oxygen at 36 weeks PMA, exhibit a significantly higher incidence of pathological spirometry (88.9%) compared to their counterparts relying on positive pressure support with less than 30% oxygen (38.5%) (p = 0.028). (Fig. 1 ). The need for ≥ 30% oxygen at 36 weeks PMA (with nasal canula or positive pressure) is associated with an increased risk of presenting pathological spirometry compared to requiring positive pressure with < 30% oxygen (OR 4.48; 95% CI: 1.11–18.13). None of the patients who required positive pressure support with ≥ 30% oxygen at 36 weeks PMA met criteria for normal spirometry, compared to 57.7% of those requiring positive pressure with < 30% oxygen (p = 0.04). The need for positive pressure with ≥ 30% oxygen at 36 weeks is associated with an increased incidence of restrictive-mixed patterns compared to BPD type 1 (OR 10,65; 95% IC 2,06–54,98) and BPD type 2 (OR 6,76; 95% IC 1,09–42,06). No significant differences in the incidence of obstructive patterns are observed (Fig. 2 ). Perinatal risk factors and respiratory morbidity associated with spirometry patterns ( Table 3 ). Table 3 Risk factors according to Lung function Patterns NORMAL PATTERN (n82) OBSTRUCTIVE PATTERN (n39) RESTRICTIVE-MIXED PATTERN (n17) P Gestational age (weeks) Median (IQR) 27.57 (25.82–28.71) 27.28 (25.71–28.86) 26.00 (25.21–28.71) 0.711 Birth weight (grams) Median (IQR) 905 (737.5-1136.25) 885.00 (750–1185) 790 (692.5–1045) 0.539 Female gender (n,%) 46.3% (38) 43.6% (17) 29.4% (5) 0.498 Oligohydramnios (n,%) 12.8% (10) 28.9% (11) 23.5% (4) 0.079 Intrauterine growth restriction (n,%) 17.7% (14) 21.1% (8) 25.0% (4) 0.165 Histological chorioamnionitis 11.0% (9) 23.1% (9) 5.9% (1) 0.216 Prenatal corticosteroids; - Complete course (n,%) 93.9% (77) 76.3% (58) 92.3% (36) 84.2% (32) 88.2% (15) 82.4% (14) 0.705 0.664 Intubation at birth (n,%) 34.1% (28) 41.0% (16) 29.4% (5) 0.485 FiO 2 ≥ 30% at birth (n,%) 60.5% (49/81) 87.2% (34) 94.1% (16) 0.003 * 0.009 † Exposure to more than 1 day of mechanical ventilation (n,%) 51.2% (41/80) 65.8% (25/38) 94.1% (16/17) 0.001 † 0.043 ‡ Days of mechanical ventilation Median (IQR) 2 (0-13.75) 4.5 (0-16.25) 19 (6.5–31.5) 0.001 † 0.01 ‡ Days of positive pressure support Median (IQR) 25 (13-36.5) 34 (16–47) 45 (21.7–68.2) 0.048 * 0.022 † Days of oxygen therapy Median (IQR) 42 (27.5–53.5) 59 (38–76) 40 (25.5–89) 0.009 * Nosocomial pneumonia (n,%) 11.1% (9/81) 10.5% (4/38) 47.1% (8/17) 0.005 ‡ 0.002 † Pulmonary hypertension (n,%) 6.3% (5/80) 13.5% (5/37) 29.4% (5/17) 0.014 † Oxygen at discharge (n,%) 17.1% (14) 23.1% (9) 41.2% (7) 0.046 † Postnatal corticosteroids (n,%) 23.2% (19) 35.9% (14) 41.2% (7) 0.157 Breastfeeding at discharge (n,%) 62.2% (51) 64.1% (25) 58.8% (10) 0.978 Respiratory hospitalizations (n,%) 42.2% (27/64) 62.1% (18/29) 42.9% (6/14) 0.207 Regular Asthma medications (n,%) 35.4% (29) 59.0% (23) 52.9% (9) 0.018 * *Obstructive pattern vs Normal Pattern. † Restrictive-Mixed Pattern vs Normal Pattern. ‡ Obstructive Pattern vs Restrictive-mixed Pattern. The characteristics of the excluded patients due to an altered spirometry pattern (FEV1 Z score < -1.64) without meeting criteria for obstructive or restrictive pattern are as follows: Median gestational age of 27.14 weeks (range: 25.3–27.5) and a weight of 780 grams (range: 753.5-989.5). Two of them (40%) were diagnosed with oligohydramnios, while the other 3 had intrauterine growth restriction (60%). Two patients required intubation at birth, and four patients (80%) required more than 1 day of mechanical ventilation during hospitalization, with a median duration of 39 days (range: 4.5–49). Four patients received postnatal corticosteroids, and three patients (60%) were discharged on oxygen. Five patients have an FEV1 z-score below − 1.64, without meeting criteria for pathological spirometry; four of them have an FVC z-score below the 10th percentile (<-1.25), and the other one has an FEV1/FVC z-score of -1.64 (5th percentile). Since they do not have a normal spirometry but do not strictly meet the criteria for restrictive, obstructive, or mixed patterns, they have been excluded from the comparative spirometry pattern table. Five patients have an FEV1 z-score below − 1.64, without meeting criteria for pathological spirometry; four of them have an FVC z-score below the 10th percentile (<-1.25), and the other one has an FEV1/FVC z-score of -1.64 (5th percentile). Since they do not have a normal spirometry but do not strictly meet the criteria for restrictive, obstructive, or mixed patterns, they have been excluded from the comparative spirometry pattern table (Table 3 ). The diagnosis of oligohydramnios is associated with a lower proportion of patients meeting criteria for normal spirometry (37% vs 61.3%, p = 0.03) being associated with a lower z-score value of FEV1/FVC, -0.17 (95% CI -1.26- -0.015). Histological chorioamnionitis is associated with a higher incidence of obstructive pattern (OR 3.19; 95% CI 1.13–8.95). There was no significant association between chorioamnionitis and the incidence of restrictive-mixed pattern. The requirement for more than or equal to 30% oxygen at birth, within the first 10 minutes, is associated with a higher proportion of pathological spirometry (45.9% vs 15%). When adjusted by BPD classification based on respiratory and oxygen support at 36 weeks PMA, the effect is only significant in type 1 BPD (OR 4; 95% CI: 1.25–12.81). This oxygen requirement at birth is associated with a higher incidence of an obstructive pattern (33.7% vs 12.5%: p = 0.012) (OR 3.55; 95% CI 1.27–9.88) and a restrictive-mixed pattern (15.8% vs 2.5%; p = 0.041). However, the association with the restrictive-mixed pattern loses statistical significance after adjusting for GA. Exposure to mechanical ventilation for more than 24 hours is also associated with an increased incidence of pathological spirometry (47.7% vs 25.9%), regardless of severity of BPD (OR 2.46; 95% CI 1.09–5.56). Patients exposed to mechanical ventilation exhibit a higher incidence of a restrictive pattern (18.6% vs 1.9%, p = 0.002) with no differences in the incidence of an obstructive pattern (29.1% vs 24.1%, p = 0.563). Each day of mechanical ventilation increases the risk of developing a restrictive-mixed pattern by 4.3% (OR 1.04; 95% CI 1.01–1.08) and decreases the z-score of FVC by -0.018 (95% CI -0.025- -0.011). The diagnosis of nosocomial pneumonia is associated with a higher incidence of restrictive mixed pattern, independently of the duration of mechanical ventilation in days (OR 4.57; 95% CI 1.09–19.13). DISCUSSION In our study of premature patients with BPD, we found a high incidence of pathologic spirometry (39.2%) between 5 and 7 years of age, exceeding the rates reported in patients less than 32 weeks of age without BPD (14.1%) and in term controls (5–10%) [12–15]. Although we observed a correlation between the severity of BPD, as defined by the NIH 2001 classification [2], and a decline in lung function values, our study did not find any significant differences between BPD type 2 and BPD type 3. However, upon examination of the requirement for oxygen exceeding 30% at 36 weeks PMA, an increase in the incidence of pathological spirometry became evident. It is noteworthy that none of the patients requiring positive pressure support with ≥ 30% oxygen at 36 weeks PMA met the criteria for normal lung function, in contrast to the 57.7% of patients requiring positive pressure support with < 30% oxygen. Consequently, in our population, the more severe forms of BPD, particularly those that exhibit parenchymal involvement as evidenced by a need for more than 30% oxygen at 36 weeks PMA, are associated with persistent impairment of lung function throughout the school-age years. One of the most debated aspects of BPD lies in its diagnostic criteria and classification, which depend on the respiratory support received at a specific time. This results in significant variation in long-term predictive capabilities for morbidity across different centers, which can be attributed to differences in respiratory support protocols and oxygen utilization [5, 16]. Furthermore, the diagnosis of BPD coincides with the early stage of alveolar development. This implies that factors encountered during infancy can significantly impact its lung function trajectory and affect the long-term prognosis of affected individuals. Although there have been several proposed classifications in recent years [5, 6], a unanimous consensus on the most suitable classification has yet to be reached [7]. In addition, the shift in the pathophysiology of this disease as a consequence of extremely premature birth adds complexity to determining the level of impairment that constitutes the diagnosis of BPD. Patients born during the canalicular or saccular phase of pulmonary development will inevitably experience some degree of alteration in lung development. This is particularly evident in studies of premature infants born before 27–28 weeks of gestation, where those who do not meet the diagnostic criteria for BPD still exhibit lung function abnormalities by school age, albeit to a lesser extent than their BPD-diagnosed counterparts. [17, 18]. Therefore, it's crucial to consider BPD not as a simple binary condition but as a spectrum of severity. Recent proposals for classification [5, 6, 19] suggest a transition towards considering only the need for respiratory support at 36 weeks of gestational age as a diagnostic criterion for BPD. This approach removes the notion of mild BPD (type 1) from the conventional classification, which previously included cases in which oxygen support > 21% was required for more than 28 days, even if no support was required at 36 weeks PMA. This classification practice has been adopted in many studies, often grouping these patients with those without BPD [19]. In several studies that differentiate Type 1 BPD, significant lung function alterations are observed in these patients compared to premature infants without BPD. However, when patient characteristics are examined, it is often found that the type 1 BPD group has a lower gestational age [20, 21]. As a result, distinguishing between the impact of prematurity and the effect of mild BPD diagnosis on long-term morbidity becomes challenging. The Spanish Research Group on Bronchopulmonary Dysplasia decided to include in the registry patients requiring more than 28 days of respiratory support, acknowledging the inherent heterogeneity in lung involvement within this population. This is because the need for respiratory support in premature infants can arise from factors beyond respiratory issues alone, including central or obstructive apnea, muscle weakness, coexisting conditions and is also influenced by the management protocols employed at each center. The rationale behind this decision is to enhance understanding of the pathophysiology of different phenotypes of BPD patients and analyze both perinatal and childhood risk factors affecting long-term lung function and respiratory morbidity. In our cohort, even though the differences in lung function abnormalities between those under and over 26 weeks in each BPD group do not reach statistical significance, patients born under 26 weeks had a similar proportion of pathological spirometry as those born over 26 weeks but with a higher grade in the BPD classification. For instance, patients classified as having type 1 BPD exhibited a similar proportion of pathological lung function (37.5%) as those with BPD type 2 born at or after 26 weeks (35%), highlighting the importance of follow-up and evaluation for patients with BPD type 1, particularly those with lower gestational age, to elucidate the impact of these milder forms of BPD on long-term outcomes. In premature patients with BPD, the most common pathological pattern observed is the obstructive pattern, as reported in previous studies [22–24]. Consistent with these findings, our study shows that 28.2% of cases have an obstructive pattern. In addition, 10.1% have a restrictive pattern and 2.1% have a mixed pattern. Notably, there is a progressive increase in the occurrence of the restrictive-mixed pattern with the severity of BPD, reaching its peak at 50% in the most severe cases when oxygen requirements are considered. This correlation between the restrictive pattern and severe forms of BPD has also been documented in recent studies [12, 20, 25]. In line with the findings reported by Lai et al. [25], a decline in FVC Z-score correlates with exposure to and duration of mechanical ventilation. Furthermore, within our cohort, the presence of a restrictive-mixed pattern is additionally associated with the administration of more than 30% oxygen at birth, diagnosis of pulmonary hypertension, nosocomial pneumonia, length of mechanical ventilation exposure and the necessity for oxygen therapy upon discharge. These correlations suggest an increased level of structural lung damage contributing to the development of a restrictive pattern. In our cohort, the use of oxygen exceeding 30% at birth correlates with a higher prevalence of compromised lung function in school age. However, due to the observational nature of our study, determining the precise influence of this variable presents challenges. It likely serves as an indicator of prenatal lung injury, exacerbated by known oxygen-related damage and the established correlation between even brief oxygen exposures at birth and the development of BPD [26]. Regarding the obstructive pattern, it is observed in up to 25% of patients diagnosed with type 1 BPD. Although variations in FEV1 Z-score with the severity of BPD are apparent, differences in the occurrence of the obstructive pattern do not reach statistical significance. Interestingly, it is not correlated with exposure to mechanical ventilation, but rather associated with the use of oxygen exceeding 30% at birth, histological chorioamnionitis, and oligohydramnios. This suggest the presence of distinct etiopathogenic mechanisms underlying the development of obstructive versus restrictive-mixed patterns. Airflow obstruction is a common impairment associated with prematurity, particularly prevalent in patients diagnosed with BPD, and tends to persist into adulthood, as indicated by a recent meta-analysis [27]. This obstruction often arises from a mismatch between distal airway growth and lung volume, known as dysanapsis, resulting from disruptions in normal pulmonary development [28, 29]. In our study cohort, we found that over half of the cases with an obstructive pattern exhibited FEV1 values within the normal range. Notably, this proportion was significantly higher (88.8%) in patients diagnosed with BPD type 1 compared to those with BPD types 2 (44.4%) and 3 (50%). Thus, this pattern of mild obstruction appears to be particularly associated with milder forms of BPD. In several studies, a gradual improvement in lung function has been observed over time among premature infants with mild forms of BPD, suggesting a potential restoration of disrupted lung development during childhood. Conversely, preterm infants with more severe BPD often exhibit persistent abnormalities in lung function, with values not only lower than those of controls but also falling below the lower limit of normality (LLN) [15, 24, 25, 30]. These findings align with growing evidence suggesting that lung function follows a defined trajectory throughout life, characterized by an increase during childhood, stabilization in adulthood, and subsequent decline with age [31]. Alterations in lung function during childhood have been found to predict adult lung function and the onset of clinical pathology, including the development of chronic obstructive pulmonary disease (COPD). The fact that premature patients, particularly those with BPD, exhibit initial lung function abnormalities makes them particularly vulnerable to the early onset of respiratory failure in adulthood [32, 33]. Recent studies have indicated a higher incidence of COPD among individuals born at younger gestational ages [1], especially among those diagnosed with BPD [33]. While some studies suggest improved long-term respiratory outcomes in contemporary cohorts of preterm infants compared with earlier populations [18, 34]. others show no differences[27, 35, 36]. Advancements in technology and understanding of lung injury mechanisms have led to improved prenatal and postnatal management strategies, including less agressive respiratory support, early minimally invasive surfactant administration, optimized nutrition, and hemodynamic management. As a result of these modifications in treatment approaches, the etiopathogenesis and lung injury profiles associated with prematurity have experience significant changes. Premature infants who can be successfully treated with non-invasive support methods typically experience less structural damage, although varying degrees of pulmonary and vascular developmental impairment may persist depending on the degree of prematurity, leading to the development of milder forms of BPD. On the other hand, modern neonatal care has significantly increased the survival rates of infants who fail non-invasive respiratory support strategies due to extreme prematurity, prenatal pathology and/or genetic factors. These infants often require prolonged mechanical ventilation and have high oxygen requirements, resulting in added structural damage to the lung parenchyma, vasculature and airways. Such patients develop severe forms of BPD, which present a distinct pathophysiology and phenotype compared to milder forms. Therefore, conducting long-term follow-up studies of patients with severe BPD is imperative, given its potential association with the development of a restrictive lung pattern and the significant morbidity and mortality linked to this pattern in adulthood [37, 38]. Limitations This study is an observational analysis utilizing data sourced from a national database, which offers extensive coverage but also introduces certain constraints. One notable limitation is the low proportion of BPD patients with recorded lung function values within the database between 5 and 7 years of age, potentially leading to selection bias. Additionally, the limited number of patients further constrains the ability to detect statistically significant differences among the gestational age groups. Although spirometry values were carefully provided by pediatric pulmonology specialists at each participating center, the lack of available data on childhood secondhand smoke exposure, lung volumes, and bronchodilator response precluded their inclusion in the analysis. These limitations underscore the need for caution in interpreting the results and highlight areas for future research to address gaps in data availability and improve the comprehensiveness of analyses in this area. In conclusion , this study emphasizes the high prevalence of pulmonary function abnormalities in patients with BPD and highlights oxygen supplementation greater than 30% at 36 weeks postmenstrual age (PMA) as a valuable marker of disease severity. Of particular note is the identification of a significant association between a restrictive pattern and severe forms of BPD. These findings underscore the urgent need for close patient follow-up, given the significant morbidity and mortality associated with a restrictive pattern in adulthood. Further research is essential to refine management strategies to improve outcomes for this vulnerable population. Declarations Data availability : Data are available on the online GEIDIS registry platform. Ethics declarations Ethical approval : This study was conducted in accordance with the Declaration of Helsinki. The study was approved by local research ethics committees and by the Spanish Agency for Medicines and Medical Devices (AEMPS). All data were anonymized. Consent to participate: Informed consent was obtained from the legal guardians of participants included in the study. Consent for publication : All the authors revised and approved the final version of the text and consents its publication. Competing interest: The authors declare no competing interests. Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Corresponding author: Correspondence to Cristina Ramos-Navarro: [email protected] References Bui, D.S., et al., Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study. Lancet Respir Med, 2022. 10 (5): p. 478-484. Jobe, A.H. and E. Bancalari, Bronchopulmonary dysplasia. Am J Respir Crit Care Med, 2001. 163 (7): p. 1723-9. Coalson, J.J., Pathology of bronchopulmonary dysplasia. Semin Perinatol, 2006. 30 (4): p. 179-84. Stoll, B.J., et al., Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. Jama, 2015. 314 (10): p. 1039-51. Jensen, E.A., et al., The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants: An Evidence-Based Approach. Am J Respir Crit Care Med, 2019. Higgins, R.D., et al., Bronchopulmonary Dysplasia: Executive Summary of a Workshop. J Pediatr, 2018. Bancalari, E. and D. Jain, Bronchopulmonary Dysplasia: Can We Agree on a Definition? Am J Perinatol, 2018. 35 (6): p. 537-540. Ramos-Navarro, C., et al., Risk factors and bronchopulmonary dysplasia severity: data from the Spanish Bronchopulmonary Dysplasia Research Network. Eur J Pediatr, 2022. 181 (2): p. 789-799. Beydon, N., et al., An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med, 2007. 175 (12): p. 1304-45. Quanjer, P.H., et al., Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J, 2012. 40 (6): p. 1324-43. Martín de Vicente, C., et al., Validation of Global Lung Function Initiative and All Ages Reference Equations for Forced Spirometry in Healthy Spanish Preschoolers. Arch Bronconeumol (Engl Ed), 2018. 54 (1): p. 24-30. Rite, S., et al., The Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age. Front Pediatr, 2022. 10 : p. 830035. Chang, H.Y., et al., Reduced Lung Function at Preschool Age in Survivors of Very Low Birth Weight Preterm Infants. Front Pediatr, 2020. 8 : p. 577673. Fawke, J., et al., Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study. Am J Respir Crit Care Med, 2010. 182 (2): p. 237-45. Doyle, L.W., et al., Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data. Lancet Respir Med, 2019. 7 (8): p. 677-686. Jeon, G.W., M. Oh, and Y.S. Chang, Definitions of bronchopulmonary dysplasia and long-term outcomes of extremely preterm infants in Korean Neonatal Network. Sci Rep, 2021. 11 (1): p. 24349. Hurst, J.R., et al., Respiratory and Cardiovascular Outcomes in Survivors of Extremely Preterm Birth at 19 Years. Am J Respir Crit Care Med, 2020. 202 (3): p. 422-432. Bårdsen, T., et al., Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight. Thorax, 2022. 77 (8): p. 790-798. Hines, D., et al., Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus. Acta Paediatr, 2017. 106 (3): p. 366-374. Broström, E.B., et al., Obstructive lung disease in children with mild to severe BPD. Respir Med, 2010. 104 (3): p. 362-70. Vollsæter, M., et al., Lung function after preterm birth: development from mid-childhood to adulthood. Thorax, 2013. 68 (8): p. 767-76. Kotecha, S.J., et al., Effect of preterm birth on later FEV1: a systematic review and meta-analysis. Thorax, 2013. 68 (8): p. 760-6. Caskey, S., et al., Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia. Ann Am Thorac Soc, 2016. 13 (8): p. 1262-70. Moschino, L., et al., Longitudinal Assessment of Lung Function in BPD Survivors from Birth to Adulthood: The Padova BPD Study. Am J Respir Crit Care Med, 2018. Lai, S.H., et al., Evolution and Determinants of Lung Function until Late Infancy among Infants Born Preterm. Sci Rep, 2020. 10 (1): p. 490. Vento, M., et al., Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics, 2009. 124 (3): p. e439-49. Gibbons, J.T.D., et al., Increasing airway obstruction through life following bronchopulmonary dysplasia: a meta-analysis. ERJ Open Res, 2023. 9 (3). McGinn, E.A., et al., Dysanapsis as a Determinant of Lung Function in Development and Disease. Am J Respir Crit Care Med, 2023. 208 (9): p. 956-963. Duke, J.W., et al., Physiological aspects of cardiopulmonary dysanapsis on exercise in adults born preterm. J Physiol, 2022. 600 (3): p. 463-482. Northway, W.H., et al., Late pulmonary sequelae of bronchopulmonary dysplasia. N Engl J Med, 1990. 323 (26): p. 1793-9. Jordan, B.K. and C.T. McEvoy, Trajectories of Lung Function in Infants and Children: Setting a Course for Lifelong Lung Health. Pediatrics, 2020. 146 (4). Deolmi, M., et al., Early Origins of Chronic Obstructive Pulmonary Disease: Prenatal and Early Life Risk Factors. Int J Environ Res Public Health, 2023. 20 (3). Martinez, F.D., Early-Life Origins of Chronic Obstructive Pulmonary Disease. N Engl J Med, 2016. 375 (9): p. 871-8. Kotecha, S.J., et al., Geographical Differences and Temporal Improvements in Forced Expiratory Volume in 1 Second of Preterm-Born Children: A Systematic Review and Meta-analysis. JAMA Pediatr, 2022. 176 (9): p. 867-877. Simpson, S.J., et al., Lung function trajectories throughout childhood in survivors of very preterm birth: a longitudinal cohort study. Lancet Child Adolesc Health, 2018. 2 (5): p. 350-359. Doyle, L.W., et al., Increasing airway obstruction from 8 to 18 years in extremely preterm/low-birthweight survivors born in the surfactant era. Thorax, 2017. 72 (8): p. 712-719. Godfrey, M.S. and M.D. Jankowich, The Vital Capacity Is Vital: Epidemiology and Clinical Significance of the Restrictive Spirometry Pattern. Chest, 2016. 149 (1): p. 238-51. Dharmage, S.C., et al., Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study. Lancet Respir Med, 2023. 11 (3): p. 273-282. Additional Declarations No competing interests reported. Supplementary Files Appendix1and2.docx Cite Share Download PDF Status: Published Journal Publication published 10 Jun, 2024 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 07 May, 2024 Reviews received at journal 02 May, 2024 Reviewers agreed at journal 29 Apr, 2024 Reviewers agreed at journal 28 Apr, 2024 Reviewers invited by journal 28 Apr, 2024 Editor assigned by journal 24 Apr, 2024 Submission checks completed at journal 24 Apr, 2024 First submitted to journal 15 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4269926","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":296434237,"identity":"1ef82349-9052-4825-9684-f91acf6f149d","order_by":0,"name":"Cristina Ramos-Navarro","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYBADOQYG5gYGHhDzAGODBDFajBkYGEnUktiA0MLAgFcL/+zDTzd8+HMnfX77wTaJNwzb5PluH268wVBxz64BhxaJc2lmN2e2PcvdcCaxTXIOw23DmecSmy0YzhQn49JiwMNgdpu34XDuBobENmkehtuMG84wtkkwtiUk43KYAQ/7t9s8fw6ny/c/BGuxJ0ILj9ltHrbDCQw3ILYkwrTY4dIicYanDOiXw4YbbjxstpxjcDt55hnGZouEMwkJuLTw97Bvu/Hhz2F5+f7kgzfeVNy27TvD/vDGh4oEe1xa0N0JpRPAMUUqINaWUTAKRsEoGP4AAIEgXwmP9ytLAAAAAElFTkSuQmCC","orcid":"","institution":"Gregorio Marañón University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Ramos-Navarro","suffix":""},{"id":296434238,"identity":"b3d545e8-b91a-4104-8e81-20a857786795","order_by":1,"name":"Manuel Sánchez-Luna","email":"","orcid":"","institution":"Gregorio Marañón University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Manuel","middleName":"","lastName":"Sánchez-Luna","suffix":""},{"id":296434239,"identity":"77426f15-e711-4090-9f8c-88d571174265","order_by":2,"name":"Santiago Pérez-Tarazona","email":"","orcid":"","institution":"La Fe University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Santiago","middleName":"","lastName":"Pérez-Tarazona","suffix":""},{"id":296434240,"identity":"905fc690-7925-4904-9085-78a08c42f8bb","order_by":3,"name":"Ester Sanz-López","email":"","orcid":"","institution":"Gregorio Marañón University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ester","middleName":"","lastName":"Sanz-López","suffix":""},{"id":296434241,"identity":"81cc15ca-ad13-4b9f-b8cc-393347fec64b","order_by":4,"name":"Elena Maderuelo-Rodriguez","email":"","orcid":"","institution":"Gregorio Marañón University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Maderuelo-Rodriguez","suffix":""},{"id":296434243,"identity":"3f84b491-fb57-444e-8d6f-ac4a4dfd8e05","order_by":5,"name":"Santiago Rueda-Esteban","email":"","orcid":"","institution":"San Carlos University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Santiago","middleName":"","lastName":"Rueda-Esteban","suffix":""},{"id":296434245,"identity":"e140cb59-111e-4298-8375-2c520c6a8c0d","order_by":6,"name":"Ana Sánchez-Torres","email":"","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Sánchez-Torres","suffix":""},{"id":296434247,"identity":"af4ddea6-9575-4ff5-9426-f4ec28073a17","order_by":7,"name":"Ana Concheiro-Guisán","email":"","orcid":"","institution":"Alvaro Cunqueiro University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Concheiro-Guisán","suffix":""},{"id":296434249,"identity":"faaf0050-8c3d-4770-b33b-34ba0b510896","order_by":8,"name":"Manuel Sánchez-Solís","email":"","orcid":"","institution":"Virgen Arrixaca University Hospital Murcia","correspondingAuthor":false,"prefix":"","firstName":"Manuel","middleName":"","lastName":"Sánchez-Solís","suffix":""},{"id":296434251,"identity":"1acfa92f-6d70-4fd8-bdf1-f115b5c7150b","order_by":9,"name":"GEIDIS Research Network","email":"","orcid":"","institution":"GEIDIS Research Network","correspondingAuthor":false,"prefix":"","firstName":"GEIDIS","middleName":"Research","lastName":"Network","suffix":""}],"badges":[],"createdAt":"2024-04-15 13:03:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4269926/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4269926/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-024-05629-w","type":"published","date":"2024-06-10T14:51:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55633435,"identity":"d621ef12-d260-4134-870d-3ae1394a75d3","added_by":"auto","created_at":"2024-04-30 20:04:16","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56709,"visible":true,"origin":"","legend":"\u003cp\u003eThis graph illustrates the percentage of pathological spirometry across different types of Bronchopulmonary Dysplasia (DBP), subdividing BPD type 3 according to respiratory support and oxygen required at 36 weeks PMA.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4269926/v1/a08e5530b01bdba298aa330c.jpg"},{"id":55633436,"identity":"e453ec5f-0203-4719-af34-fe000bd07f1b","added_by":"auto","created_at":"2024-04-30 20:04:16","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":85511,"visible":true,"origin":"","legend":"\u003cp\u003eThis graph illustrates the spirometry patterns based on the different types of Bronchopulmonary Dysplasia (DBP), subdividing BPD type 3 according to respiratory support and oxygen required at 36 weeks PMA. (At 36 weeks PMA, two patients were on mechanical ventilation. One patient, who required less than 30% oxygen, presented with a normal spirometry pattern. The other patient, who required equal to or more than 30% oxygen, developed a restrictive pattern)\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4269926/v1/8caf28919c8b96592e66ed37.jpg"},{"id":58822466,"identity":"b94babc9-0bed-4f1b-adff-5218df380ba3","added_by":"auto","created_at":"2024-06-21 16:44:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":919506,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4269926/v1/2c7e0676-839f-459d-9d92-1567ff51d0d7.pdf"},{"id":55633437,"identity":"402cc388-ffa9-4c4b-8aae-8a44867dfd3d","added_by":"auto","created_at":"2024-04-30 20:04:16","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":17750,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix1and2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4269926/v1/f87d6ea9e208e838948b5317.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pulmonary Function and Bronchopulmonary Dysplasia Classification: Insights from the Spanish Registry","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBronchopulmonary dysplasia (BPD) is the most common morbidity associated with prematurity, contributing to a significant impact on respiratory health throughout childhood and into adulthood [1].\u003c/p\u003e \u003cp\u003eThe diagnosis of BPD is established at 36 weeks postmenstrual age (PMA) based on the respiratory support required up to that point. Traditionally, patients are classified as having BPD if they have required oxygen supplementation above 21% for more than 28 days, and is classified according to the respiratory support required at 36 weeks PMA as Type 1 (mild: no support), Type 2 (moderate: nasal cannula with \u0026lt;\u0026thinsp;30% oxygen), or Type 3 (severe: positive pressure or nasal cannula with \u0026ge;\u0026thinsp;30% oxygen) [2].\u003c/p\u003e \u003cp\u003eImprovements in the care and management of preterm infants have had a profound impact on the pathophysiology of this condition [3]. The introduction of early minimally invasive surfactant administration, precise oxygen titration, and non-invasive ventilation strategies have attenuated the lung injury associated with mechanical ventilation and oxidative stress. Simultaneously, technological innovations and comprehensive antenatal and postnatal care have significantly enhanced the survival rates of infants born at gestational ages (GA) as low as 23\u0026ndash;24 weeks, representing a substantially earlier stage of pulmonary development compared to historical cohorts [4].\u003c/p\u003e \u003cp\u003eThese substantial advances have generated considerable debate regarding the efficacy of traditional BPD classification in predicting respiratory morbidity and long-term lung function abnormalities in contemporary BPD patients. Alternative classification criteria based on modern respiratory interventions have been proposed [5, 6], but consensus on the optimal criteria remains to be reached [7].\u003c/p\u003e \u003cp\u003eThe Spanish Bronchopulmonary Dysplasia Research Group (GEIDIS), established in 2016 as a network comprising 66 hospitals, gathers data on the perinatal characteristics and long-term outcomes of patients diagnosed with BPD. Its purpose is to enhance the understanding of respiratory progression and impact during childhood and adulthood in patients who develop BPD today. In a previous study investigating perinatal risk factors among preterm infants included in the registry and their association with BPD severity, it was found that among patients with BPD type 3, the need for more than 30% oxygen at 36 weeks PMA was associated with increased morbidity both during hospitalization and at discharge, in contrast to those requiring positive pressure support with less than 30% oxygen [8].\u003c/p\u003e \u003cp\u003eThe aim of this study is to evaluate pulmonary function at 5\u0026ndash;7 years of age in premature infants diagnosed with BPD, and to examine their correlation with perinatal risk factors and the respiratory support and oxygen requirements at 36 weeks PMA.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThe study retrospectively analyzed data from infants who were prospectively enrolled in the GEIDIS registry and were born between January 2016 and December 2017.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eInclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Patients born at less than 32 weeks GA, diagnosed with BPD (more than 28 days on respiratory support or an FiO2 \u0026gt; 21% considered at 36 weeks PMA)\u0026nbsp;[2], who had been entered into the GEIDIS registry database and has an acceptable forced spirometry recorded between 5 and 7 years of age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDefinitions of the variables\u003c/em\u003e\u003c/strong\u003eused in the study (specified in the database) (Appendix 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eLung Function Parameters:\u003c/em\u003e\u003c/strong\u003e The measurements were performed according to American Thoracic Society/European Respiratory Society guidelines\u0026nbsp;[9].\u0026nbsp;The following parameters were recorded in the database: forced vital capacity (FVC); forced expiratory volume in the first second (FEV1) and FEV1/FVC. Z-scores for spirometry parameters were calculated using the Global Lung Function Initiative 2012 (GLI-2012) equations, allowing the determination of the percentage of children below the lower limit of normal (LLN) for each parameter (5th percentile or z-score of -1.64)\u0026nbsp;[10]. \u0026nbsp; These equations were recently validated in healthy Spanish Caucasian preschool children aged 3-6 years\u0026nbsp;[11]. \u003cem\u003ePathologic spirometry\u003c/em\u003e was defined as FEV1/FVC z-score \u0026lt; -1.64 or FVC z-score \u0026lt; -1.64, while a \u003cem\u003enormal pattern\u0026nbsp;\u003c/em\u003ewas defined as FEV1/FVC ≥ -1.64 z-score, FEV1 ≥ -1.64 z-score, and FVC ≥ -1.64 z-score. \u003cem\u003eAn\u003c/em\u003e\u003cem\u003eobstructive pattern\u003c/em\u003e was defined by an FEV1/FVC \u0026lt; -1.64 z-score, a \u003cem\u003erestrictive pattern\u003c/em\u003e by an FVC \u0026lt; -1.64 z-score, and a \u003cem\u003emixed pattern\u003c/em\u003e by a combination of the two patterns.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis:\u003c/strong\u003e Statistical analyses were conducted using IBM SPSS Statistics software package, version 21 (IBM Corp., Armonk, NY, USA, 2012). Descriptive analysis summarized quantitative variables using measures of central tendency and dispersion, while qualitative variables were presented as percentage distributions. Comparative analysis of categorical variables employed the Chi-squared test (χ2) or Fisher’s exact test, with Bonferroni correction for multiple comparisons. The Kruskal-Wallis test, adjusted with Bonferroni correction, was used to analyze non-normally distributed quantitative variables. The significance level was set at p-value \u0026lt; 0.05. Binary logistic regression was used for multivariate analysis of binary response variables, while linear regression was employed for quantitative variables. Variables were selected based on theoretical relevance and significance observed in bivariate analysis. Gestational age (GA) was included in all models due to its clinical importance.\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the legal guardians of all participants.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 989 patients diagnosed with BPD and born at less than 32 weeks GA between 2016 and 2017 were included in the registry. Of these, pulmonary function test data were available for 143 patients between 5 and 7 years of age constituting the study population.\u003c/p\u003e \u003cp\u003e \u003cb\u003ePerinatal characteristics and spirometry values according to the NIH 2001 Classification of BPD (\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePerinatal characteristics of patients according to NIH 2001 Consensus Classification.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBPD type 1\u003c/p\u003e \u003cp\u003e(51%; n73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBPD type 2\u003c/p\u003e \u003cp\u003e(20.3%; n29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBPD type 3 (28.7%; n41)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTotal (143)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (weeks) Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.4 (26-28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.5 (26-28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.6 (25.2\u0026ndash;28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27.3 (25.7\u0026ndash;28.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;26 weeks GA (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(43.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (32.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (51.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62 (43.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (grams)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e910 (765\u0026ndash;1150)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e950 (700-1187.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e796 (687.5-977.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e880 (740\u0026ndash;1135)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (46.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (48.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (31.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e61 (42.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligohydramnios (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.032*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistological chorioamnionitis (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (13.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrauterine growth restriction (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (19.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 (21%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrenatal corticosteroids (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (93.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(93.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (92.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.995\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e133 (93%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Complete course\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (77.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (87.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e103 (80.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation in delivery room (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (34.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (41.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (34.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFiO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026ge;\u0026thinsp;30% in delivery room (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (58.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (89.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (82.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101 (71.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurfactant Therapy (%, n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.8% (46/71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75% (21/28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.9% (34/41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72.1% (101/140)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of mechanical ventilation; Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.5 (0.25\u0026ndash;28.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (3.5\u0026ndash;31.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (0\u0026ndash;19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNosocomial pneumonia (%,n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.9% (5/72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.3% (4/28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35% (14/40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.4% (23/140)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary hypertension (%,n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6% (4/71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.9% (5/28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.4% (6/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.9% (15/138)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e* Difference between BPD type 1 and BPD type 2, and between BPD type 1 and BPD type 3.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u0026dagger; BPD type 1 and 3\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNo significant differences in perinatal characteristics were observed between patients with BPD types 2 and 3. However, patients with BPD type 1 had a lower incidence of oligohydramnios, a lower requirement for more than 30% oxygen at birth, and a shorter duration of exposure to mechanical ventilation compared with patients with BPD types 2 and 3.\u003c/p\u003e \u003cp\u003eThe analysis of spirometry values did not reveal any significant differences between patients with type 2 and type 3 BPD (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLung function parameters according to NIH 2001 Consensus Classification:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBPD type 1 (n73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBPD type 2 (n29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBPD type 3 (n 41)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTotal (143)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrected age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.3 (5.0-6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.8 (5.3\u0026ndash;6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.9 (5.2\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.570\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.96 (5.28\u0026ndash;6.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFEV1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (83\u0026ndash;103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (76.6\u0026ndash;97.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (69.9\u0026ndash;95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89 (79\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFEV1 Z-score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.48 (-1.25-0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.02 (-1.72- -0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.14 (-1.99- -0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.86 (-1.47-0.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFVC %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (89\u0026ndash;109)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.2 (84.5\u0026ndash;103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88 (76-100.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e94 (82\u0026ndash;105)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFVC Z-score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.01 (-0.92-0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.33 (-1.02-0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.7 (-1.59-0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.29 (-0.05- -0.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFEV1/FVC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.9 (83.35\u0026ndash;94.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86.7 (79\u0026ndash;93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85 (78\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e88.7 (80.6\u0026ndash;94.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFEV1/FVC Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.61 (-1.63-0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.45 (-2.04-0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.08 (-1.97-0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.64 (-1.84-0.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological spirometry (FVC or FEV1/FVC z-score \u0026lt; -1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (31.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (41.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (51.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56 (39.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026lt;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (55.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026ge;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (26.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (52.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal spirometry (FEV1, FEV1/FVC, and FVC Z-score \u0026ge; -1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (67.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (55.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82 (57.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026lt;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (42.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNS\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e53.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026ge;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (70.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstructive pattern (FEV1/FVC z-score \u0026lt; -1.64 and FVC Z-score \u0026ge; -1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (32.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.676\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39/138 (28.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026lt;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNS\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026ge;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (22.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRestrictive/mixed pattern (FVC Z-score \u0026lt; -1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (23.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17/138 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026lt;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNS\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- \u0026ge;\u0026thinsp;26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e* Differences between BPD type 1 and BPD type 2 and between BPD type 1 and BPD type 3.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u0026dagger; Difference between BPD type 1 and BPD type 3.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u0026Dagger; No significant differences between \u0026lt;\u0026thinsp;26weeks GA and \u0026ge;\u0026thinsp;26 weeks GA\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients diagnosed with type 1 BPD exhibited higher predicted FVC and FEV1 values, as well as higher FEV1 Z scores. Additionally, a greater proportion of patients had spirometry values in the normal range.\u003c/p\u003e \u003cp\u003e28.2% of patients (39) exhibit an obstructive pattern, 10.1% (14) a restrictive pattern, and 2.1% (3) a mixed pattern. Patients with restrictive and mixed patterns have been grouped for comparison. There are no significant differences in the percentage of patients with an obstructive pattern among BPD types. However, a higher proportion of patients with a restrictive-mixed pattern is observed in BPD type 3 compared to those with BPD type 1 (OR 3.82; 95% IC 1.19\u0026ndash;12.34).\u003c/p\u003e \u003cp\u003eOf the 39 patients with an obstructive pattern, 26 (66.6%) had an FEV1 value within the normal range, with a higher rate between BPD type 1 patients, 16 (88.8%), compared to BPD type 2, 4 (44.4%), and BPD type 3, 6 (50%) (p\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e \u003cp\u003e \u003cb\u003eSpirometry values grading type 3 BPD according to Respiratory and Oxygen support at 36 weeks PMA.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIndividuals requiring positive pressure support with equal or more than 30% oxygen at 36 weeks PMA, exhibit a significantly higher incidence of pathological spirometry (88.9%) compared to their counterparts relying on positive pressure support with less than 30% oxygen (38.5%) (p\u0026thinsp;=\u0026thinsp;0.028). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe need for \u0026ge;\u0026thinsp;30% oxygen at 36 weeks PMA (with nasal canula or positive pressure) is associated with an increased risk of presenting pathological spirometry compared to requiring positive pressure with \u0026lt;\u0026thinsp;30% oxygen (OR 4.48; 95% CI: 1.11\u0026ndash;18.13).\u003c/p\u003e \u003cp\u003eNone of the patients who required positive pressure support with \u0026ge;\u0026thinsp;30% oxygen at 36 weeks PMA met criteria for normal spirometry, compared to 57.7% of those requiring positive pressure with \u0026lt;\u0026thinsp;30% oxygen (p\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003cp\u003eThe need for positive pressure with \u0026ge;\u0026thinsp;30% oxygen at 36 weeks is associated with an increased incidence of restrictive-mixed patterns compared to BPD type 1 (OR 10,65; 95% IC 2,06\u0026ndash;54,98) and BPD type 2 (OR 6,76; 95% IC 1,09\u0026ndash;42,06). No significant differences in the incidence of obstructive patterns are observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePerinatal risk factors and respiratory morbidity associated with spirometry patterns (\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors according to Lung function Patterns\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNORMAL PATTERN (n82)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOBSTRUCTIVE PATTERN (n39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRESTRICTIVE-MIXED PATTERN (n17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (weeks) Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.57 (25.82\u0026ndash;28.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.28 (25.71\u0026ndash;28.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26.00 (25.21\u0026ndash;28.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (grams) Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e905 (737.5-1136.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e885.00 (750\u0026ndash;1185)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e790 (692.5\u0026ndash;1045)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.539\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale gender (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46.3% (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.6% (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29.4% (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.498\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligohydramnios (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.8% (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.9% (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23.5% (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrauterine growth restriction (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.7% (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.1% (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.0% (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistological chorioamnionitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.0% (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1% (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.9% (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrenatal corticosteroids;\u003c/p\u003e \u003cp\u003e- Complete course (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93.9% (77)\u003c/p\u003e \u003cp\u003e76.3% (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.3% (36)\u003c/p\u003e \u003cp\u003e84.2% (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e88.2% (15)\u003c/p\u003e \u003cp\u003e82.4% (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.705\u003c/p\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation at birth (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34.1% (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.0% (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29.4% (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.485\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFiO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026ge;\u0026thinsp;30% at birth (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60.5% (49/81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.2% (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e94.1% (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003 \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.009 \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExposure to more than 1 day of mechanical ventilation (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51.2% (41/80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.8% (25/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e94.1% (16/17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001 \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.043 \u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of mechanical ventilation Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0-13.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5 (0-16.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19 (6.5\u0026ndash;31.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.01\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of positive pressure support Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25 (13-36.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (16\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45 (21.7\u0026ndash;68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.048\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.022\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of oxygen therapy Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42 (27.5\u0026ndash;53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (38\u0026ndash;76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40 (25.5\u0026ndash;89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNosocomial pneumonia (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.1% (9/81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5% (4/38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.1% (8/17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005 \u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.002\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary hypertension (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.3% (5/80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.5% (5/37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29.4% (5/17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxygen at discharge (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.1% (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1% (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e41.2% (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.046\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostnatal corticosteroids (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23.2% (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.9% (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e41.2% (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreastfeeding at discharge (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62.2% (51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.1% (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58.8% (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory hospitalizations (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42.2% (27/64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.1% (18/29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.9% (6/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegular Asthma medications (n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35.4% (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.0% (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52.9% (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.018\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Obstructive pattern vs Normal Pattern.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e Restrictive-Mixed Pattern vs Normal Pattern.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e Obstructive Pattern vs Restrictive-mixed Pattern.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eThe characteristics of the excluded patients due to an altered spirometry pattern (FEV1 Z score \u0026lt; -1.64) without meeting criteria for obstructive or restrictive pattern are as follows: Median gestational age of 27.14 weeks (range: 25.3\u0026ndash;27.5) and a weight of 780 grams (range: 753.5-989.5). Two of them (40%) were diagnosed with oligohydramnios, while the other 3 had intrauterine growth restriction (60%). Two patients required intubation at birth, and four patients (80%) required more than 1 day of mechanical ventilation during hospitalization, with a median duration of 39 days (range: 4.5\u0026ndash;49). Four patients received postnatal corticosteroids, and three patients (60%) were discharged on oxygen.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFive patients have an FEV1 z-score below \u0026minus;\u0026thinsp;1.64, without meeting criteria for pathological spirometry; four of them have an FVC z-score below the 10th percentile (\u0026lt;-1.25), and the other one has an FEV1/FVC z-score of -1.64 (5th percentile). Since they do not have a normal spirometry but do not strictly meet the criteria for restrictive, obstructive, or mixed patterns, they have been excluded from the comparative spirometry pattern table. Five patients have an FEV1 z-score below \u0026minus;\u0026thinsp;1.64, without meeting criteria for pathological spirometry; four of them have an FVC z-score below the 10th percentile (\u0026lt;-1.25), and the other one has an FEV1/FVC z-score of -1.64 (5th percentile). Since they do not have a normal spirometry but do not strictly meet the criteria for restrictive, obstructive, or mixed patterns, they have been excluded from the comparative spirometry pattern table (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnosis of oligohydramnios is associated with a lower proportion of patients meeting criteria for normal spirometry (37% vs 61.3%, p\u0026thinsp;=\u0026thinsp;0.03) being associated with a lower z-score value of FEV1/FVC, -0.17 (95% CI -1.26- -0.015).\u003c/p\u003e \u003cp\u003eHistological chorioamnionitis is associated with a higher incidence of obstructive pattern (OR 3.19; 95% CI 1.13\u0026ndash;8.95). There was no significant association between chorioamnionitis and the incidence of restrictive-mixed pattern.\u003c/p\u003e \u003cp\u003eThe requirement for more than or equal to 30% oxygen at birth, within the first 10 minutes, is associated with a higher proportion of pathological spirometry (45.9% vs 15%). When adjusted by BPD classification based on respiratory and oxygen support at 36 weeks PMA, the effect is only significant in type 1 BPD (OR 4; 95% CI: 1.25\u0026ndash;12.81).\u003c/p\u003e \u003cp\u003eThis oxygen requirement at birth is associated with a higher incidence of an obstructive pattern (33.7% vs 12.5%: p\u0026thinsp;=\u0026thinsp;0.012) (OR 3.55; 95% CI 1.27\u0026ndash;9.88) and a restrictive-mixed pattern (15.8% vs 2.5%; p\u0026thinsp;=\u0026thinsp;0.041). However, the association with the restrictive-mixed pattern loses statistical significance after adjusting for GA.\u003c/p\u003e \u003cp\u003eExposure to mechanical ventilation for more than 24 hours is also associated with an increased incidence of pathological spirometry (47.7% vs 25.9%), regardless of severity of BPD (OR 2.46; 95% CI 1.09\u0026ndash;5.56). Patients exposed to mechanical ventilation exhibit a higher incidence of a restrictive pattern (18.6% vs 1.9%, p\u0026thinsp;=\u0026thinsp;0.002) with no differences in the incidence of an obstructive pattern (29.1% vs 24.1%, p\u0026thinsp;=\u0026thinsp;0.563).\u003c/p\u003e \u003cp\u003eEach day of mechanical ventilation increases the risk of developing a restrictive-mixed pattern by 4.3% (OR 1.04; 95% CI 1.01\u0026ndash;1.08) and decreases the z-score of FVC by -0.018 (95% CI -0.025- -0.011).\u003c/p\u003e \u003cp\u003eThe diagnosis of nosocomial pneumonia is associated with a higher incidence of restrictive mixed pattern, independently of the duration of mechanical ventilation in days (OR 4.57; 95% CI 1.09\u0026ndash;19.13).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn our study of premature patients with BPD, we found a high incidence of pathologic spirometry (39.2%) between 5 and 7 years of age, exceeding the rates reported in patients less than 32 weeks of age without BPD (14.1%) and in term controls (5\u0026ndash;10%) [12\u0026ndash;15].\u003c/p\u003e \u003cp\u003eAlthough we observed a correlation between the severity of BPD, as defined by the NIH 2001 classification [2], and a decline in lung function values, our study did not find any significant differences between BPD type 2 and BPD type 3. However, upon examination of the requirement for oxygen exceeding 30% at 36 weeks PMA, an increase in the incidence of pathological spirometry became evident. It is noteworthy that none of the patients requiring positive pressure support with \u0026ge;\u0026thinsp;30% oxygen at 36 weeks PMA met the criteria for normal lung function, in contrast to the 57.7% of patients requiring positive pressure support with \u0026lt;\u0026thinsp;30% oxygen. Consequently, in our population, the more severe forms of BPD, particularly those that exhibit parenchymal involvement as evidenced by a need for more than 30% oxygen at 36 weeks PMA, are associated with persistent impairment of lung function throughout the school-age years.\u003c/p\u003e \u003cp\u003eOne of the most debated aspects of BPD lies in its diagnostic criteria and classification, which depend on the respiratory support received at a specific time. This results in significant variation in long-term predictive capabilities for morbidity across different centers, which can be attributed to differences in respiratory support protocols and oxygen utilization [5, 16]. Furthermore, the diagnosis of BPD coincides with the early stage of alveolar development. This implies that factors encountered during infancy can significantly impact its lung function trajectory and affect the long-term prognosis of affected individuals.\u003c/p\u003e \u003cp\u003eAlthough there have been several proposed classifications in recent years [5, 6], a unanimous consensus on the most suitable classification has yet to be reached [7].\u003c/p\u003e \u003cp\u003eIn addition, the shift in the pathophysiology of this disease as a consequence of extremely premature birth adds complexity to determining the level of impairment that constitutes the diagnosis of BPD. Patients born during the canalicular or saccular phase of pulmonary development will inevitably experience some degree of alteration in lung development. This is particularly evident in studies of premature infants born before 27\u0026ndash;28 weeks of gestation, where those who do not meet the diagnostic criteria for BPD still exhibit lung function abnormalities by school age, albeit to a lesser extent than their BPD-diagnosed counterparts. [17, 18]. Therefore, it's crucial to consider BPD not as a simple binary condition but as a spectrum of severity.\u003c/p\u003e \u003cp\u003eRecent proposals for classification [5, 6, 19] suggest a transition towards considering only the need for respiratory support at 36 weeks of gestational age as a diagnostic criterion for BPD. This approach removes the notion of mild BPD (type 1) from the conventional classification, which previously included cases in which oxygen support\u0026thinsp;\u0026gt;\u0026thinsp;21% was required for more than 28 days, even if no support was required at 36 weeks PMA. This classification practice has been adopted in many studies, often grouping these patients with those without BPD [19]. In several studies that differentiate Type 1 BPD, significant lung function alterations are observed in these patients compared to premature infants without BPD. However, when patient characteristics are examined, it is often found that the type 1 BPD group has a lower gestational age [20, 21]. As a result, distinguishing between the impact of prematurity and the effect of mild BPD diagnosis on long-term morbidity becomes challenging.\u003c/p\u003e \u003cp\u003eThe Spanish Research Group on Bronchopulmonary Dysplasia decided to include in the registry patients requiring more than 28 days of respiratory support, acknowledging the inherent heterogeneity in lung involvement within this population. This is because the need for respiratory support in premature infants can arise from factors beyond respiratory issues alone, including central or obstructive apnea, muscle weakness, coexisting conditions and is also influenced by the management protocols employed at each center. The rationale behind this decision is to enhance understanding of the pathophysiology of different phenotypes of BPD patients and analyze both perinatal and childhood risk factors affecting long-term lung function and respiratory morbidity.\u003c/p\u003e \u003cp\u003eIn our cohort, even though the differences in lung function abnormalities between those under and over 26 weeks in each BPD group do not reach statistical significance, patients born under 26 weeks had a similar proportion of pathological spirometry as those born over 26 weeks but with a higher grade in the BPD classification. For instance, patients classified as having type 1 BPD exhibited a similar proportion of pathological lung function (37.5%) as those with BPD type 2 born at or after 26 weeks (35%), highlighting the importance of follow-up and evaluation for patients with BPD type 1, particularly those with lower gestational age, to elucidate the impact of these milder forms of BPD on long-term outcomes.\u003c/p\u003e \u003cp\u003eIn premature patients with BPD, the most common pathological pattern observed is the obstructive pattern, as reported in previous studies [22\u0026ndash;24]. Consistent with these findings, our study shows that 28.2% of cases have an obstructive pattern. In addition, 10.1% have a restrictive pattern and 2.1% have a mixed pattern. Notably, there is a progressive increase in the occurrence of the restrictive-mixed pattern with the severity of BPD, reaching its peak at 50% in the most severe cases when oxygen requirements are considered. This correlation between the restrictive pattern and severe forms of BPD has also been documented in recent studies [12, 20, 25].\u003c/p\u003e \u003cp\u003eIn line with the findings reported by Lai et al. [25], a decline in FVC Z-score correlates with exposure to and duration of mechanical ventilation. Furthermore, within our cohort, the presence of a restrictive-mixed pattern is additionally associated with the administration of more than 30% oxygen at birth, diagnosis of pulmonary hypertension, nosocomial pneumonia, length of mechanical ventilation exposure and the necessity for oxygen therapy upon discharge. These correlations suggest an increased level of structural lung damage contributing to the development of a restrictive pattern.\u003c/p\u003e \u003cp\u003eIn our cohort, the use of oxygen exceeding 30% at birth correlates with a higher prevalence of compromised lung function in school age. However, due to the observational nature of our study, determining the precise influence of this variable presents challenges. It likely serves as an indicator of prenatal lung injury, exacerbated by known oxygen-related damage and the established correlation between even brief oxygen exposures at birth and the development of BPD [26].\u003c/p\u003e \u003cp\u003eRegarding the obstructive pattern, it is observed in up to 25% of patients diagnosed with type 1 BPD. Although variations in FEV1 Z-score with the severity of BPD are apparent, differences in the occurrence of the obstructive pattern do not reach statistical significance. Interestingly, it is not correlated with exposure to mechanical ventilation, but rather associated with the use of oxygen exceeding 30% at birth, histological chorioamnionitis, and oligohydramnios. This suggest the presence of distinct etiopathogenic mechanisms underlying the development of obstructive versus restrictive-mixed patterns.\u003c/p\u003e \u003cp\u003eAirflow obstruction is a common impairment associated with prematurity, particularly prevalent in patients diagnosed with BPD, and tends to persist into adulthood, as indicated by a recent meta-analysis [27]. This obstruction often arises from a mismatch between distal airway growth and lung volume, known as dysanapsis, resulting from disruptions in normal pulmonary development [28, 29]. In our study cohort, we found that over half of the cases with an obstructive pattern exhibited FEV1 values within the normal range. Notably, this proportion was significantly higher (88.8%) in patients diagnosed with BPD type 1 compared to those with BPD types 2 (44.4%) and 3 (50%). Thus, this pattern of mild obstruction appears to be particularly associated with milder forms of BPD.\u003c/p\u003e \u003cp\u003eIn several studies, a gradual improvement in lung function has been observed over time among premature infants with mild forms of BPD, suggesting a potential restoration of disrupted lung development during childhood. Conversely, preterm infants with more severe BPD often exhibit persistent abnormalities in lung function, with values not only lower than those of controls but also falling below the lower limit of normality (LLN) [15, 24, 25, 30]. These findings align with growing evidence suggesting that lung function follows a defined trajectory throughout life, characterized by an increase during childhood, stabilization in adulthood, and subsequent decline with age [31]. Alterations in lung function during childhood have been found to predict adult lung function and the onset of clinical pathology, including the development of chronic obstructive pulmonary disease (COPD). The fact that premature patients, particularly those with BPD, exhibit initial lung function abnormalities makes them particularly vulnerable to the early onset of respiratory failure in adulthood [32, 33]. Recent studies have indicated a higher incidence of COPD among individuals born at younger gestational ages [1], especially among those diagnosed with BPD [33].\u003c/p\u003e \u003cp\u003eWhile some studies suggest improved long-term respiratory outcomes in contemporary cohorts of preterm infants compared with earlier populations [18, 34]. others show no differences[27, 35, 36].\u003c/p\u003e \u003cp\u003eAdvancements in technology and understanding of lung injury mechanisms have led to improved prenatal and postnatal management strategies, including less agressive respiratory support, early minimally invasive surfactant administration, optimized nutrition, and hemodynamic management. As a result of these modifications in treatment approaches, the etiopathogenesis and lung injury profiles associated with prematurity have experience significant changes. Premature infants who can be successfully treated with non-invasive support methods typically experience less structural damage, although varying degrees of pulmonary and vascular developmental impairment may persist depending on the degree of prematurity, leading to the development of milder forms of BPD. On the other hand, modern neonatal care has significantly increased the survival rates of infants who fail non-invasive respiratory support strategies due to extreme prematurity, prenatal pathology and/or genetic factors. These infants often require prolonged mechanical ventilation and have high oxygen requirements, resulting in added structural damage to the lung parenchyma, vasculature and airways. Such patients develop severe forms of BPD, which present a distinct pathophysiology and phenotype compared to milder forms. Therefore, conducting long-term follow-up studies of patients with severe BPD is imperative, given its potential association with the development of a restrictive lung pattern and the significant morbidity and mortality linked to this pattern in adulthood [37, 38].\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLimitations\u003c/strong\u003e \u003cp\u003eThis study is an observational analysis utilizing data sourced from a national database, which offers extensive coverage but also introduces certain constraints. One notable limitation is the low proportion of BPD patients with recorded lung function values within the database between 5 and 7 years of age, potentially leading to selection bias. Additionally, the limited number of patients further constrains the ability to detect statistically significant differences among the gestational age groups. Although spirometry values were carefully provided by pediatric pulmonology specialists at each participating center, the lack of available data on childhood secondhand smoke exposure, lung volumes, and bronchodilator response precluded their inclusion in the analysis. These limitations underscore the need for caution in interpreting the results and highlight areas for future research to address gaps in data availability and improve the comprehensiveness of analyses in this area.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eIn conclusion\u003c/b\u003e, this study emphasizes the high prevalence of pulmonary function abnormalities in patients with BPD and highlights oxygen supplementation greater than 30% at 36 weeks postmenstrual age (PMA) as a valuable marker of disease severity. Of particular note is the identification of a significant association between a restrictive pattern and severe forms of BPD. These findings underscore the urgent need for close patient follow-up, given the significant morbidity and mortality associated with a restrictive pattern in adulthood. Further research is essential to refine management strategies to improve outcomes for this vulnerable population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eData availability\u003c/em\u003e: Data are available on the online GEIDIS registry platform.\u003c/p\u003e\n\u003cp\u003eEthics declarations\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthical approval\u003c/em\u003e: This study was conducted in accordance with the Declaration of Helsinki. The study was approved by local research ethics committees and by the Spanish Agency for Medicines and Medical Devices (AEMPS). \u0026nbsp;All data were anonymized.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent to participate:\u0026nbsp;\u003c/em\u003e Informed consent was obtained from the legal guardians of participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e: All the authors revised and approved the final version of the text and consents its publication.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interest:\u003c/em\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding:\u003c/em\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCorresponding author:\u0026nbsp;\u003c/em\u003eCorrespondence to Cristina Ramos-Navarro: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBui, D.S., et al., \u003cem\u003eAssociation between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study.\u003c/em\u003e Lancet Respir Med, 2022. \u003cstrong\u003e10\u003c/strong\u003e(5): p. 478-484.\u003c/li\u003e\n\u003cli\u003eJobe, A.H. and E. Bancalari, \u003cem\u003eBronchopulmonary dysplasia.\u003c/em\u003e Am J Respir Crit Care Med, 2001. \u003cstrong\u003e163\u003c/strong\u003e(7): p. 1723-9.\u003c/li\u003e\n\u003cli\u003eCoalson, J.J., \u003cem\u003ePathology of bronchopulmonary dysplasia.\u003c/em\u003e Semin Perinatol, 2006. \u003cstrong\u003e30\u003c/strong\u003e(4): p. 179-84.\u003c/li\u003e\n\u003cli\u003eStoll, B.J., et al., \u003cem\u003eTrends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012.\u003c/em\u003e Jama, 2015. \u003cstrong\u003e314\u003c/strong\u003e(10): p. 1039-51.\u003c/li\u003e\n\u003cli\u003eJensen, E.A., et al., \u003cem\u003eThe Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants: An Evidence-Based Approach.\u003c/em\u003e Am J Respir Crit Care Med, 2019.\u003c/li\u003e\n\u003cli\u003eHiggins, R.D., et al., \u003cem\u003eBronchopulmonary Dysplasia: Executive Summary of a Workshop.\u003c/em\u003e J Pediatr, 2018.\u003c/li\u003e\n\u003cli\u003eBancalari, E. and D. Jain, \u003cem\u003eBronchopulmonary Dysplasia: Can We Agree on a Definition?\u003c/em\u003e Am J Perinatol, 2018. \u003cstrong\u003e35\u003c/strong\u003e(6): p. 537-540.\u003c/li\u003e\n\u003cli\u003eRamos-Navarro, C., et al., \u003cem\u003eRisk factors and bronchopulmonary dysplasia severity: data from the Spanish Bronchopulmonary Dysplasia Research Network.\u003c/em\u003e Eur J Pediatr, 2022. \u003cstrong\u003e181\u003c/strong\u003e(2): p. 789-799.\u003c/li\u003e\n\u003cli\u003eBeydon, N., et al., \u003cem\u003eAn official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children.\u003c/em\u003e Am J Respir Crit Care Med, 2007. \u003cstrong\u003e175\u003c/strong\u003e(12): p. 1304-45.\u003c/li\u003e\n\u003cli\u003eQuanjer, P.H., et al., \u003cem\u003eMulti-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.\u003c/em\u003e Eur Respir J, 2012. \u003cstrong\u003e40\u003c/strong\u003e(6): p. 1324-43.\u003c/li\u003e\n\u003cli\u003eMart\u0026iacute;n de Vicente, C., et al., \u003cem\u003eValidation of Global Lung Function Initiative and All Ages Reference Equations for Forced Spirometry in Healthy Spanish Preschoolers.\u003c/em\u003e Arch Bronconeumol (Engl Ed), 2018. \u003cstrong\u003e54\u003c/strong\u003e(1): p. 24-30.\u003c/li\u003e\n\u003cli\u003eRite, S., et al., \u003cem\u003eThe Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age.\u003c/em\u003e Front Pediatr, 2022. \u003cstrong\u003e10\u003c/strong\u003e: p. 830035.\u003c/li\u003e\n\u003cli\u003eChang, H.Y., et al., \u003cem\u003eReduced Lung Function at Preschool Age in Survivors of Very Low Birth Weight Preterm Infants.\u003c/em\u003e Front Pediatr, 2020. \u003cstrong\u003e8\u003c/strong\u003e: p. 577673.\u003c/li\u003e\n\u003cli\u003eFawke, J., et al., \u003cem\u003eLung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study.\u003c/em\u003e Am J Respir Crit Care Med, 2010. \u003cstrong\u003e182\u003c/strong\u003e(2): p. 237-45.\u003c/li\u003e\n\u003cli\u003eDoyle, L.W., et al., \u003cem\u003eExpiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data.\u003c/em\u003e Lancet Respir Med, 2019. \u003cstrong\u003e7\u003c/strong\u003e(8): p. 677-686.\u003c/li\u003e\n\u003cli\u003eJeon, G.W., M. Oh, and Y.S. Chang, \u003cem\u003eDefinitions of bronchopulmonary dysplasia and long-term outcomes of extremely preterm infants in Korean Neonatal Network.\u003c/em\u003e Sci Rep, 2021. \u003cstrong\u003e11\u003c/strong\u003e(1): p. 24349.\u003c/li\u003e\n\u003cli\u003eHurst, J.R., et al., \u003cem\u003eRespiratory and Cardiovascular Outcomes in Survivors of Extremely Preterm Birth at 19 Years.\u003c/em\u003e Am J Respir Crit Care Med, 2020. \u003cstrong\u003e202\u003c/strong\u003e(3): p. 422-432.\u003c/li\u003e\n\u003cli\u003eB\u0026aring;rdsen, T., et al., \u003cem\u003eTracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight.\u003c/em\u003e Thorax, 2022. \u003cstrong\u003e77\u003c/strong\u003e(8): p. 790-798.\u003c/li\u003e\n\u003cli\u003eHines, D., et al., \u003cem\u003eScoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus.\u003c/em\u003e Acta Paediatr, 2017. \u003cstrong\u003e106\u003c/strong\u003e(3): p. 366-374.\u003c/li\u003e\n\u003cli\u003eBrostr\u0026ouml;m, E.B., et al., \u003cem\u003eObstructive lung disease in children with mild to severe BPD.\u003c/em\u003e Respir Med, 2010. \u003cstrong\u003e104\u003c/strong\u003e(3): p. 362-70.\u003c/li\u003e\n\u003cli\u003eVolls\u0026aelig;ter, M., et al., \u003cem\u003eLung function after preterm birth: development from mid-childhood to adulthood.\u003c/em\u003e Thorax, 2013. \u003cstrong\u003e68\u003c/strong\u003e(8): p. 767-76.\u003c/li\u003e\n\u003cli\u003eKotecha, S.J., et al., \u003cem\u003eEffect of preterm birth on later FEV1: a systematic review and meta-analysis.\u003c/em\u003e Thorax, 2013. \u003cstrong\u003e68\u003c/strong\u003e(8): p. 760-6.\u003c/li\u003e\n\u003cli\u003eCaskey, S., et al., \u003cem\u003eStructural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia.\u003c/em\u003e Ann Am Thorac Soc, 2016. \u003cstrong\u003e13\u003c/strong\u003e(8): p. 1262-70.\u003c/li\u003e\n\u003cli\u003eMoschino, L., et al., \u003cem\u003eLongitudinal Assessment of Lung Function in BPD Survivors from Birth to Adulthood: The Padova BPD Study.\u003c/em\u003e Am J Respir Crit Care Med, 2018.\u003c/li\u003e\n\u003cli\u003eLai, S.H., et al., \u003cem\u003eEvolution and Determinants of Lung Function until Late Infancy among Infants Born Preterm.\u003c/em\u003e Sci Rep, 2020. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 490.\u003c/li\u003e\n\u003cli\u003eVento, M., et al., \u003cem\u003ePreterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease.\u003c/em\u003e Pediatrics, 2009. \u003cstrong\u003e124\u003c/strong\u003e(3): p. e439-49.\u003c/li\u003e\n\u003cli\u003eGibbons, J.T.D., et al., \u003cem\u003eIncreasing airway obstruction through life following bronchopulmonary dysplasia: a meta-analysis.\u003c/em\u003e ERJ Open Res, 2023. \u003cstrong\u003e9\u003c/strong\u003e(3).\u003c/li\u003e\n\u003cli\u003eMcGinn, E.A., et al., \u003cem\u003eDysanapsis as a Determinant of Lung Function in Development and Disease.\u003c/em\u003e Am J Respir Crit Care Med, 2023. \u003cstrong\u003e208\u003c/strong\u003e(9): p. 956-963.\u003c/li\u003e\n\u003cli\u003eDuke, J.W., et al., \u003cem\u003ePhysiological aspects of cardiopulmonary dysanapsis on exercise in adults born preterm.\u003c/em\u003e J Physiol, 2022. \u003cstrong\u003e600\u003c/strong\u003e(3): p. 463-482.\u003c/li\u003e\n\u003cli\u003eNorthway, W.H., et al., \u003cem\u003eLate pulmonary sequelae of bronchopulmonary dysplasia.\u003c/em\u003e N Engl J Med, 1990. \u003cstrong\u003e323\u003c/strong\u003e(26): p. 1793-9.\u003c/li\u003e\n\u003cli\u003eJordan, B.K. and C.T. McEvoy, \u003cem\u003eTrajectories of Lung Function in Infants and Children: Setting a Course for Lifelong Lung Health.\u003c/em\u003e Pediatrics, 2020. \u003cstrong\u003e146\u003c/strong\u003e(4).\u003c/li\u003e\n\u003cli\u003eDeolmi, M., et al., \u003cem\u003eEarly Origins of Chronic Obstructive Pulmonary Disease: Prenatal and Early Life Risk Factors.\u003c/em\u003e Int J Environ Res Public Health, 2023. \u003cstrong\u003e20\u003c/strong\u003e(3).\u003c/li\u003e\n\u003cli\u003eMartinez, F.D., \u003cem\u003eEarly-Life Origins of Chronic Obstructive Pulmonary Disease.\u003c/em\u003e N Engl J Med, 2016. \u003cstrong\u003e375\u003c/strong\u003e(9): p. 871-8.\u003c/li\u003e\n\u003cli\u003eKotecha, S.J., et al., \u003cem\u003eGeographical Differences and Temporal Improvements in Forced Expiratory Volume in 1 Second of Preterm-Born Children: A Systematic Review and Meta-analysis.\u003c/em\u003e JAMA Pediatr, 2022. \u003cstrong\u003e176\u003c/strong\u003e(9): p. 867-877.\u003c/li\u003e\n\u003cli\u003eSimpson, S.J., et al., \u003cem\u003eLung function trajectories throughout childhood in survivors of very preterm birth: a longitudinal cohort study.\u003c/em\u003e Lancet Child Adolesc Health, 2018. \u003cstrong\u003e2\u003c/strong\u003e(5): p. 350-359.\u003c/li\u003e\n\u003cli\u003eDoyle, L.W., et al., \u003cem\u003eIncreasing airway obstruction from 8 to 18 years in extremely preterm/low-birthweight survivors born in the surfactant era.\u003c/em\u003e Thorax, 2017. \u003cstrong\u003e72\u003c/strong\u003e(8): p. 712-719.\u003c/li\u003e\n\u003cli\u003eGodfrey, M.S. and M.D. Jankowich, \u003cem\u003eThe Vital Capacity Is Vital: Epidemiology and Clinical Significance of the Restrictive Spirometry Pattern.\u003c/em\u003e Chest, 2016. \u003cstrong\u003e149\u003c/strong\u003e(1): p. 238-51.\u003c/li\u003e\n\u003cli\u003eDharmage, S.C., et al., \u003cem\u003eLifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study.\u003c/em\u003e Lancet Respir Med, 2023. \u003cstrong\u003e11\u003c/strong\u003e(3): p. 273-282.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4269926/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4269926/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Aims\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 2016, the Spanish Research Group on Bronchopulmonary Dysplasia (BPD) (GEIDIS) established a national registry with participation of 66 hospitals to collect information on clinical characteristics and long-term outcomes of BPD infants into adulthood. The aim of this study is to examine forced spirometry data in early childhood and to assess their correlation with the respiratory support required at 36 weeks postmenstrual age (PMA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study analyzed data from preterm infants with BPD born between January 2016 and December 2017 who underwent forced spirometry at 5-7 years of age.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were conducted to investigate the relationships between spirometry results, perinatal factors, and the required respiratory support at 36 weeks PMA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study involved 143 patients with a median gestational age (GA) of 27.3 weeks (range: 25.7-28.7) and a median weight of 880 grams (range: 740-1135). Pathological spirometry was observed in 39.2% (56) of the patients.\u003c/p\u003e\n\u003cp\u003eAmong patients diagnosed with BPD type 3, those requiring over 30% oxygen at 36 weeks PMA exhibited an increased risk of pathological spirometry (OR 4.48; 95% CI: 1.11-18.13) compared to those requiring positive pressure with less than 30% oxygen. In addition, this subgroup had a higher risk of developing a restrictive-mixed pattern compared to those with BPD type 1 (OR 10,65; 95% IC 2,06-54,98) and BPD type 2 (OR 6,76; 95% IC 1,09-42,06). No significant differences were found in the incidence of an obstructive pattern between BPD types. Additionally, the study revealed distinct etiopathogenic mechanisms underlying the development of restrictive versus obstructive patterns.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe requirement of more than 30% oxygen at 36 weeks PMA serves as a risk indicator for pulmonary function impairment in school-aged children with BPD. These findings suggest persistent airway and parenchymal injury in this specific patient population, and highlight the importance of careful monitoring to evaluate their long-term effects on lung function.\u003c/p\u003e","manuscriptTitle":"Pulmonary Function and Bronchopulmonary Dysplasia Classification: Insights from the Spanish Registry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-30 20:04:12","doi":"10.21203/rs.3.rs-4269926/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-07T14:25:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-02T18:39:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"123445278188818464910457539721496892512","date":"2024-04-29T19:35:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15328059569494270233723272129827610145","date":"2024-04-29T03:11:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-28T20:03:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-24T14:15:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-24T14:14:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2024-04-15T13:01:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f4d943aa-91e2-4429-b005-2e81a472e007","owner":[],"postedDate":"April 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-06-21T14:51:43+00:00","versionOfRecord":{"articleIdentity":"rs-4269926","link":"https://doi.org/10.1007/s00431-024-05629-w","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2024-06-10 14:51:42","publishedOnDateReadable":"June 10th, 2024"},"versionCreatedAt":"2024-04-30 20:04:12","video":"","vorDoi":"10.1007/s00431-024-05629-w","vorDoiUrl":"https://doi.org/10.1007/s00431-024-05629-w","workflowStages":[]},"version":"v1","identity":"rs-4269926","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4269926","identity":"rs-4269926","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}