Dysplasia In Preterm Infants Research Articles

Effect of early vitamin A supplementation on bronchopulmonary dysplasia in premature infants.

Effect of early vitamin A supplementation on bronchopulmonary dysplasia in premature infants.

Epidemiology and risk factors for bronchopulmonary dysplasia in preterm infants born at or less than 32 weeks of gestation

ObjectivesTo describe risk factors of bronchopulmonary dysplasia in very preterm infants in the first weeks of life. Material and methodsRetrospective cohort study of preterm infants ≤ 32 weeks of gestational age and birth weight ≤ 1500 g. A multivariate logistic regression analysis was performed to identify independent risk factors for bronchopulmonary dysplasia in the first weeks of life. ResultsA total of 202 newborns were included in the study (mean gestational age 29.5 ± 2.1 weeks), 61.4% never received invasive mechanical ventilation. The incidence of bronchopulmonary dysplasia was 28.7%, and 10.4% of the patients were diagnosed with moderate-severe bronchopulmonary dysplasia. Bronchopulmonary dysplasia was independently associated with gestational age (P < 0.001; OR = 0.44 (95% CI = 0.30–0.65)), the need for mechanical ventilation on the first day of life (P = 0.001; OR = 8.13 ((95% CI = 2.41–27.42)), nosocomial sepsis (P < 0.001; OR = 9.51 ((95% CI = 2.99–30.28)) and FiO2 on day 14 (P < 0.001; OR = 1.39 ((95% CI = 1.16–1.66)). Receiving mechanical ventilation at the first day of life (P = 0.008; OR = 5.39 ((95% CI = 1.54–18.89)) and at the third day of life (P = 0.001; OR = 9.99 ((95% CI = 2.47–40.44)) and nosocomial sepsis (P = 0.001; OR = 9.87 ((95% CI = 2.58–37.80)) were independent risk factors for moderate-severe bronchopulmonary dysplasia. ConclusionsGestational age, mechanical ventilation in the first days of life and nosocomial sepsis are early risk factors for bronchopulmonary dysplasia. The analysis of simple and objective clinical data, allows us to select a group of patients at high risk of bronchopulmonary dysplasia in whom it could be justified to act more aggressively, and shows areas for improvement to prevent its development or reduce its severity.

Oral vitamin A for the prevention of bronchopulmonary dysplasia in preterm infants: a meta-analysis of randomized controlled trials.

article: Oral vitamin A for the prevention of bronchopulmonary dysplasia in preterm infants: a meta-analysis of randomized controlled trials - Minerva Pediatrics 2022 August;74(4):488-91 - Minerva Medica - Journals

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta-analysis.

Recombinant erythropoietin (rEPO) has erythropoiesis and anti-inflammatory properties that might help reduce lung injury in preterm infants. To conduct a systematic review and meta-analysis to evaluate the possible role of rEPO in altering the risk of bronchopulmonary dysplasia (BPD). PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that evaluated the effects of rEPO for the prevention of BPD in preterm infants. Fourteen studies (3199 infants) were included. Our results could not demonstrate a significant effect of rEPO on the incidence of BPD36 (risk ratio [RR]: 0.97, 95% confidence interval [CI]: 0.87-1.09, p = 0.63, I2 = 0, 12 RCTs, high-quality evidence), BPD28 (RR: 1.28, 95% CI: 0.91-1.79, p = 0.15, I2 = 17%, three RCTs, low-quality evidence) and oxygen dependence days. The test for subgroup analysis by administration route of rEPO showed similar outcomes above. Some of the included trials reported a significant effect of intravenous rEPO on reduction of sepsis (RR: 0.82, 95% CI: 0.70-0.96, p = 0.01, I2 = 0, high-quality evidence) and any stage necrotizing enterocolitis (NEC) (RR: 0.75, 95% CI: 0.59-0.94, p = 0.01, I2 = 0, moderate-quality evidence). The incidence of mortality and stage II or higher NEC was comparable in rEPO and control infants. Our results suggest that rEPO does not affect the risk of developing BPD in preterm infants. Adequately powered RCTs are required to further confirm these findings.

Effects of early vitamin D supplementation on the prevention of bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD) is a respiratory dysfunction caused by poor lung bronchial development, which may lead to long-term lung disease, threatening the lives of children. Studies have shown that premature infants with low vitamin D are highly associated with BPD. In this study, we aim to obtain insights into whether early vitamin D supplementation could prevent BPD in preterm infants. A total of 112 preterm infants were randomly divided into two groups: the control and vitamin D supplementation (VD) group. The VD group received vitamin D (800 IU/day) within 48 h at birth for consecutively 28 days. The serum levels of 25(OH)D3 and C-reactive protein (CRP), IL6, and TNF-α were measured using ELISA assay. The arterial partial pressure of oxygen (PaO2 ) and carbon dioxide (PaCO2 ) wasmeasured using an i-STAT analyzer. The occurrence of BPD was decreased in the VD group compared with the control. The decreased serum 25(OH)D3 was significantly elevated by supplementation with vitamin D. In addition, the serum inflammation factors (CRP, IL6, and TNF-α) were significantly reduced by vitamin D supplementation. We demonstrated that early vitamin D supplementation could significantly reduce BPD incidence in preterm infants. We showed that early vitamin D supplementation could significantly increase serum level of 25(OH)D3 and reduce inflammatory response thereby preventing and reducing neonatal BPD. Firstly, a larger sample size will be needed to be included to gain a comprehensive understanding of the protective effects of vitamin D and BPD mechanistically in preterm infants. Secondly, the pathophysiological process of BPD will need to be studied. In addition, the pathways that vitamin D is responsible for, needto be further researched.

Changes in definition and pathogenesis of bronchopulmonary dysplasia in preterm infants: A review

Bronchopulmonary dysplasia (BPD) is a common complication in preterm neonates, especially extremely preterm. However, effective prevention strategies and treatment methods are still being explored. Although the concept of BPD emerged a few decades ago, a consensus definition has not been established globally yet. The syndrome of BPD was introduced by Northway in 1967. With constant changes and improvements in newborn care and understanding about its pathogenesis, the definition of BPD has been changing and updated accordingly. NICHD (National Institute of Child Health and Human Development) first published the classification of BDP severity based on the level of required oxygen in 2001. Seventeen years later, in 2018, a new grading system was proposed to include new ventilation support methods. Unified diagnosis criteria and severity classification are important to facilitate consistent diagnosis between centers. Besides, understanding of BPD pathogenesis suggests antenatal risk factors such as genetic factors, intrauterine growth restriction, pre-eclampsia, inflammation, smoking during pregnancy; as well as postnatal risk factors such as oxygen toxicity, inflammation, moderate to large patent ductus arteriosus. Identification of these risk factors provides evidence for more effective treatment methods. This review describes the evolution of definitions, influence of lung development on BPD, and pathogenesis factors associated with BPD.

胎龄&lt;34周呼吸窘迫综合征早产儿发生支气管肺发育不良危险因素分析

胎龄&lt;34周呼吸窘迫综合征早产儿发生支气管肺发育不良危险因素分析

Can serum periostin predict bronchopulmonary dysplasia in premature infants?

Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD. A total of 98 preterm Japanese infants born at <32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay. Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P < 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006). Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants. This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.

Early diagnostic value of C-reactive protein as an inflammatory marker for moderate-to-severe bronchopulmonary dysplasia in premature infants with birth weight less than 1500 g

BackgroundBronchopulmonary dysplasia (BPD) is a serious respiratory complication in premature infants and moderate-to-severe BPD may affect the long-term quality of life and lack of specific treatment once it happened. Therefore, it is necessary to identify early diagnostic biomarkers for moderate-to-severe BPD. MethodsThis retrospective cohort study included all premature infants with birth weight <1500 g from March 1, 2015 to June 30, 2017. Patients were categorized into mild BPD, moderate-to-severe BPD and non BPD groups. Data collected included patient characteristics, C-reactive protein (CRP) tested at six time points, including 1d (2 h after birth and before the first feeding), 3d, 7d, 2w, 3w, and 4w after birth, and maternal factors. Ordinal regression analysis was used to identify independent predictors of moderate-to-severe BPD and receiver operating characteristic (ROC) curve was used to evaluate the value of CRP as an early diagnostic marker for moderate-to-severe BPD. ResultsA total of 831 patients were recruited. BPD occurred in 156/831 premature infants with birth weight less than 1500 g. Lower birth weight (OR = 0.998, 95% CI 0.997–0.999, P = 0.004), higher CRP level 3 days after birth (OR = 1.287, 95% CI 1.195–1.384, P = 0.000), and hemodynamically significant patent ductus arteriosus (HsPDA) (OR = 12.256, 95% CI 3.766–39.845, P = 0.000) were independent risk factors for moderate-to-severe BPD. The area under curve of the CRP level 3 days after birth for diagnosing moderate-to-severe BPD was 0.867 (95% CI, 0.823–0.912, P = 0.000). The sensitivity was 83.0% and the specificity was 78.3% when the cut-off value was set at 4.105 mg/L. ConclusionThe CRP level 3 days after birth may be used as an early diagnostic marker for moderate-to-severe BPD in preterm infants who have the risk factors for BPD with birth weight less than 1500 g.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome

The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. anzctr.org.au Identifier: ACTRN12611000916943.

Respiratory Tract Microecology and Bronchopulmonary Dysplasia in Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a severe respiratory complication in preterm infants. Although the etiology and pathogenesis of BPD are complex and remain to be clarified, recent studies have reported a certain correlation between the microecological environment of the respiratory tract and BPD. Changes in respiratory tract microecology, such as abnormal microbial diversity and altered evolutional patterns, are observed prior to the development of BPD in premature infants. Therefore, research on the colonization and evolution of neonatal respiratory tract microecology and its relationship with BPD is expected to provide new ideas for its prevention and treatment. In this paper, we review microecological changes in the respiratory tract and the mechanisms by which they can lead to BPD in preterm infants.

A RETROSPECTIVE OBSERVATIONAL STUDY TO ASSESS THE ROLE OF FUROSEMIDE IN PREVENTION OF BRONCHO-PULMONARY DYSPLASIA IN PRETERM INFANTS(28-32WKS).

1. BACKGROUND OF THE STUDY: Bronchopulmonary dysplasia (BPD) is the most common pulmonary morbidity associated with prematurity and pre- mature infants with BPD are at an increased risk of death and severe developmental disability .Despite the devastating impact of BPD on premature infants, there are currently no therapies labeled by the US Food and Drug Administration to prevent BPD. Neonatologists commonly use furosemide as off-label in premature infants. 2. OBJECTIVE: A. To evaluate the role of Furosemide in prevention of Bronchopulmonary Dysplasia in preterm infants. 3. METHODOLOGY: Details of total 350 babies admitted to SNCU and NICU of BMCH with gestational age between 28-32 weeksare included in this study for last 2 years (Nov,2019—Nov 2021). The data regarding exposure to Furosemide are searched retrospectively from medical records of the hospital. 4. RESULTS: Details of total 350 babies are taken in this study and among the total study population 47 babies died within 36 weeks of PMAof any cause . The percentage of BPD was found to be higher in non exposed group which is 43% in comparison to exposed group With 17% and which is statistically signicant(p-0.0028).Odds of furosemide exposure among BPD cases is less than non BPD cases.(OR=0.26).83% babies weaned off th from oxygen/CPAP/ventilator from 7 day to 36 weeks of PMAin exposed group in comparison to non exposed group(57%). 5. CONCLUSIONS: We found that a lesser percentage of Broncho-Pulomonary Dysplasia in the babies exposed to furosemide between birth to 36 weeks of PMA in premature infants. These results provide important preliminary data to support the development of prospective studies to evaluate the safety and efcacy of furosemide for the prevention of BPD in premature infant.

The effects of early vitamin A supplementation on the prevention and treatment of bronchopulmonary dysplasia in premature infants: a systematic review and meta-analysis.

BackgroundBronchopulmonary dysplasia (BPD) is a common and unique chronic disease of premature infants with a high mortality rate. A large number of studies have shown that vitamin A supplementation has a better effect on the prevention and treatment of BPD.MethodsRandomized controlled trials (RCTs) on early vitamin A supplementation for the prevention and treatment of BPD were searched in PubMed, EMBASE, and the Cochrane Library database. The search time was from the establishment of the database to July 28, 2021. Two investigators performed standard independent screening trials of the literature according to the inclusion and exclusion criteria. The methodology of the included articles was evaluated, and the data were extracted. If the opinions of the 2 investigators were not consistent, a third party could be consulted. The Cochrane systematic review manual was used to analyze the bias of the included studies, and the RevMan 5.3 software was used to perform the meta-analysis.ResultsIn the experimental group, the BPD incidence [−0.71, 95% confidential interval (CI): −0.34 to −0.00; Z=1.98; P=0.05], 28-day oxygen uptake rate (0.81, 95% CI: 0.38–1.730; Z=0.53; P=0.59), 36-week survival rate (1.08, 95% CI: 0.80–1.46; Z=0.49; P=0.62), incidence of patent ductus arteriosus (0.77, 95% CI: 0.27–2.21; Z=0.48; P=0.63), days of mechanical ventilation (0.02, 95% CI: −1.46–1.49; Z=0.02; P=0.98), and 28-day ventilator use (0.77, 95% CI: 0.31–1.92; Z=0.55; P=0.58) were lower than those in the control group, especially the incidence of BPD.DiscussionEarly supplementation of vitamin A showed good efficacy and safety in the prevention and treatment of BPD in premature infants, and can also improve the survival rate of infants. Therefore, it is worthy of clinical application.

Late (≥ 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Late (≥ 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Early (&lt; 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Early (&lt; 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Construction of early risk prediction models for bronchopulmonary dysplasia in preterm infants.

To construct risk prediction models for bronchopulmonary dysplasia (BPD) in preterm infants on postnatal days 3, 7, and 14. A retrospective analysis was performed on the medical data of 414 preterm infants, with a gestational age of <32 weeks and a birth weight (BW) of <1 500 g, who were admitted to the neonatal intensive care unit from July 2019 to April 2021. According to the diagnostic criteria for BPD revised in 2018, they were divided into a BPD group with 98 infants and a non-BPD group with 316 infants. The two groups were compared in terms of general status, laboratory examination results, treatment, and complications. The logistic regression model was used to identify the variables associated with BPD. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of models. The logistic regression analysis showed that BW, asphyxia, grade III-IV respiratory distress syndrome (RDS), acute chorioamnionitis, interstitial pneumonia, fraction of inspired oxygen (FiO2), and respiratory support mode were the main risk factors for BPD (P<0.05). The prediction models on postnatal days 7 and 14 were established as logit (P7) =-2.049-0.004×BW (g) +0.686×asphyxia (no=0, yes=1) +1.842×grade III-IV RDS (no=0, yes=1) +0.906×acute chorioamnionitis (no=0, yes=1) +0.506×interstitial pneumonia (no=0, yes=1) +0.116×FiO2 (%) +0.816×respiratory support mode (no=0, nasal tube=1, nasal continuous positive airway pressure=2, conventional mechanical ventilation=3, high-frequency mechanical ventilation=4) and logit (P14) =-1.200-0.004×BW (g) +0.723×asphyxia+2.081×grade III-IV RDS+0.799×acute chorioamnionitis+0.601×interstitial pneumonia+0.074×FiO2 (%) +0.800×respiratory support mode, with an area under the ROC curve (AUC) of 0.876 and 0.880, respectively, which was significantly larger than the AUC of the prediction model on postnatal day 3 (P<0.05). BW, asphyxia, grade III-IV RDS, acute chorioamnionitis, interstitial pneumonia, FiO2, and respiratory support mode are the main risk factors for BPD and can be used to construct risk prediction models. The prediction models on postnatal days 7 and 14 can effectively predict BPD.

Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD".

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.

Correlation of Early Nutritional Supply and Development of Bronchopulmonary Dysplasia in Preterm Infants

Background: Bronchopulmonary dysplasia (BPD) has multifactorial origins and is characterized by distorted physiological lung development. The impact of nutrition on the incidence of BPD is less studied so far.Methods: A retrospective single center analysis was performed on n = 207 preterm infants <1,000 g and <32 weeks of gestation without severe gastrointestinal complications to assess the impact of variations in nutritional supply during the first 2 weeks of life on the pulmonary outcome. Infants were grouped into no/mild and moderate/severe BPD to separate minor and major limitations in lung function.Results: After risk adjustment for gestational age, birth weight, sex, multiples, and antenatal steroids, a reduced total caloric intake and carbohydrate supply as the dominant energy source during the first 2 weeks of life prevailed statistically significant in infants developing moderate/severe BPD (p < 0.05). Enteral nutritional supply was increased at a slower rate with prolonged need for parenteral nutrition in the moderate/severe BPD group while breast milk provision and objective criteria of feeding intolerance were equally distributed in both groups.Conclusion: Early high caloric intake is correlated with a better pulmonary outcome in preterm infants <1,000 g. Our results are in line with the known strong impact of nutrient supply on somatic growth and psychomotor development. Our data encourage paying special attention to further decipher the ideal nutritional requirements for unrestricted lung development and promoting progressive enteral nutrition in the absence of objective criteria of feeding intolerance.

Systematic Evaluation of Early Inhalation of Nitric Oxide for Prevention and Treatment of Bronchopulmonary Dysplasia in Premature Infants

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, which seriously affects the quality of life of premature infants and may even lead to death of premature infants. At present, there is no unified opinion on the prevention and treatment of BPD, and the mechanism of its occurrence and development is not completely clear in clinical practice. Therefore, finding a better way to prevent and treat BPD is one of the hot spots in clinical practice. The safety of nitric oxide in premature infants with BPD is a focus of clinical attention, but its systematic evaluation has not been reported. In this study, meta-analysis method was used to analysis. The results demonstrated that there were no obvious differences in the incidence, survival, BPD-free survival, and mortality between the inhaled nitric oxide group (iNO group) and the placebo group. The common complications such as toxemia, necrotizing enterocolitis, and visual impairment between the iNO group and the placebo group were not obvious. This suggests that the use of NO to prevent BPD in premature infants has no obvious effect.

Association between Intermittent Hypoxemia and Severe Bronchopulmonary Dysplasia in Preterm Infants.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may play a role in this relationship. Objectives: To determine the association between prolonged episodes of intermittent hypoxemia and severe bronchopulmonary dysplasia. Methods: A post hoc analysis of extremely preterm infants in the Canadian Oxygen Trial who survived to 36 weeks' postmenstrual age was performed. Oxygen saturations <80% for ⩾1 minute and the proportion of time per day with hypoxemia were quantified using continuous pulse oximetry data that had been sampled every 10 seconds from within 24 hours of birth until 36 weeks' postmenstrual age. The study outcome was severe bronchopulmonary dysplasia as defined in the 2001 NIH Workshop Summary. Measurements and Main Results: Of 1,018 infants, 332 (32.6%) developed severe bronchopulmonary dysplasia. The median number of hypoxemic episodes ranged from 0.8/day (interquartile range, 0.2-1.1) to 60.2/day (interquartile range, 51.4-70.3) among the least and most affected 10% of infants. Compared with the lowest decile of exposure to hypoxemic episodes, the adjusted relative risk of severe bronchopulmonary dysplasia increased progressively from 1.72 (95% confidence interval, 1.55-1.90) at the 2nd decile to 20.40 (95% confidence interval, 12.88-32.32) at the 10th decile. Similar risk gradients were observed for time in hypoxemia. Significant differences in the rates of hypoxemia between infants with and without severe bronchopulmonary dysplasia emerged within the first week after birth. Conclusions: Prolonged intermittent hypoxemia beginning in the first week after birth was associated with an increased risk of developing severe bronchopulmonary dysplasia among extremely preterm infants. Clinical trial registered with www.isrctn.com (ISRCTN62491227) and www.clinicaltrials.gov (NCT00637169).