INTRODUCTION — Despite important advances in perinatal care and a steady decline in mortality rates among very low birth weight (VLBW) infants (<1500 grams), bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant mortality and morbidity. The increasing rates of survival among the smallest of premature infants due to changes in antenatal and postnatal respiratory management, such as antenatal steroids and surfactant replacement, contribute to an overall increase in the incidence of BPD despite advances in the care of premature infants that reduce the risk or severity of BPD. (See "Bronchopulmonary dysplasia: Prevention".)
The outcome of infants with BPD is reviewed here. Pathogenesis and clinical features, management, and potential strategies to prevent BPD are discussed separately. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features" and "Bronchopulmonary dysplasia: Management" and "Bronchopulmonary dysplasia: Prevention".)
TERMINOLOGY
Prematurity — Different degrees of prematurity are defined by gestational age (GA), which is calculated from the first day of the mother's last period, or birth weight (BW). Data on BPD are often based upon the following classification of preterm infants categorized by BW or GA (table 1).
These terms are used throughout this discussion.
Bronchopulmonary dysplasia — It has been challenging to maintain a consistent definition of BPD because of changes in the population at risk (ie, greater number of patients at earlier GAs) and advances in neonatal management (ie, surfactant and antenatal glucocorticoid therapy and less aggressive mechanical ventilation) have altered the pathology and clinical course of BPD and led to revisions in its definition (table 2).
When evaluating the literature, it is important to have an appreciation of the definitions used and their limitations, especially if comparing data across different studies and to ensure that results are applicable to the clinical setting at hand [1,2]. Most of the evidence cited in this topic has used one of the following definitions:
●Oxygen requirement either at 28 postnatal days or 36 weeks postmenstrual age (PMA) [3-5].
●2001 National Institute of Child Health and Human Development (NICHD) definition, which added criteria that included GA, severity of disease, and timing of assessment based on GA [6]. Further revisions were suggested at a subsequent 2016 NICHD workshop that renamed categories and added newer modes of noninvasive ventilation (eg, nasal cannula flow) not included in the previous definition, radiologic evidence of disease as a criterion, and a new category (IIIA) of early lethal BPD [7].
The discussion that reviews the ongoing challenge of establishing a consensus definition is reviewed separately. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features", section on 'Definitions'.)
TRENDS OVER TIME — The pathology and clinical course of bronchopulmonary dysplasia (BPD) has been altered by the widespread use of surfactant after its introduction in 1980, and the increased survival rate of extremely low birth weight infants. As a result, the long-term outcome of BPD continues to change along with these factors. In particular, results vary depending upon whether the study was performed prior to or after the introduction of surfactant in the 1980s. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features".)
In addition, the definition of BPD has also evolved over time. Studies that were performed prior to the 2001 National Institute of Child Health and Human Development (NICHD) modified consensus definition may have used definitions that are less accurate at predicting outcome, because of the increasing survival rate of extremely low birth weight (ELBW) infants and the increased prevalence of milder forms of BPD due to improved treatment of RDS. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features", section on 'Definitions'.)
MORTALITY — Infants with severe bronchopulmonary dysplasia (BPD) (defined as those that require respiratory support that typically includes mechanical ventilation and/or FiO2 >0.30) have a higher risk of mortality than unaffected infants or those with mild disease at the same gestational age (GA) [8-10]. Death usually is caused by respiratory failure, unremitting pulmonary hypertension with cor pulmonale, or acquired infection (pneumonia or sepsis).
Although the prevalence of pulmonary artery hypertension in infants with BPD is unclear, infants with BPD and severe pulmonary artery hypertension (PAH) have a high mortality rate [11,12].
PAH as a long-term complication of BPD is discussed separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Pulmonary hypertension' and "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Epidemiology and natural history'.)
READMISSION — Readmission to the hospital is common amongst survivors of BPD. In an analysis of data from the Pediatric Hospital Information System of 3574 infants (gestational age <32 weeks) with BPD, one-third of patients were hospitalized by one year corrected age [13]. In this study, risk factors based on multivariable modeling for readmission included severity of BPD, earlier gestational age, male sex, gastrostomy tube placement, and surgical NEC. Of note, home oxygen was not associated with readmission.
PULMONARY OUTCOME — Respiratory illnesses contribute to high rates of rehospitalization for survivors of bronchopulmonary dysplasia (BPD), especially in the first year and for extremely preterm survivors (gestational age <29 weeks) [14-17].
Respiratory infection — Infants with BPD are at increased risk for respiratory infections, including respiratory syncytial virus (RSV), which may be life-threatening [18]. Palivizumab is a humanized monoclonal antibody against the RSV F glycoprotein. It is licensed for use in selected infants and children including infants and young children younger than 24 months with BPD. We suggest that palivizumab be administered to these patients if they have required medical therapy for their pulmonary disease within six months of the anticipated RSV season to reduce their risk of RSV infection. (See "Respiratory syncytial virus infection: Clinical features and diagnosis" and "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Palivizumab immunoprophylaxis'.)
Asthma-like disease — Episodes of wheezing suggest bronchiolitis or asthma and are common in preterm survivors with BPD before two years of age. Asthma-like disease in patients who had BPD is discussed in detail separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Asthma-like symptoms'.)
Pulmonary function — Persistent abnormalities in pulmonary function, particularly expiratory airflow obstruction, are common in patients who had BPD as infants and depend upon the severity of BPD. Many also exhibit episodes of reactive airway disease. The long-term pulmonary function and abnormalities in preterm survivors with BPD are discussed separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Pulmonary function'.)
Pulmonary artery hypertension — Pulmonary artery hypertension (PAH) is a serious sequela affecting 12 to 25 percent of infants with BPD. PAH [19] and the resultant right heart failure (cor pulmonale) associated with severe BPD are caused by both structural and functional changes within the lung. It is one of the most severe complications of BPD and is an important risk factor for mortality. The pathogenesis of PAH, its course, and its management are discussed in detail elsewhere. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Pulmonary hypertension' and "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Epidemiology and natural history'.)
Prolonged ventilation — Historically, prolonged mechanical ventilation among preterm infants with severe BPD was associated with reduced chance of survival. In a large retrospective study from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network in extremely low birth weight (ELBW) infants born from 1995 to 1998, the survival rate was lower for infants who received ventilator support for more than four months compared those who received ventilation for less than 28 days (50 versus 85 percent) [20]. However, data on the effect of subsequent changes in ventilatory management focused on reducing mortality and morbidity needs to be collected and evaluated to determine whether prolonged ventilation remains a risk factor for mortality.
Home ventilator care may be associated with improved survival [21,22]. In a retrospective review of 102 children with severe BPD and no other comorbidities that could contribute to chronic respiratory failure cared for in a university medical center home ventilator program from 1984 to 2010, 83 patients (81.4 percent) were alive at the time of review; the remainder had died [21]. In this cohort, 69 of the 83 survivors no longer required positive pressure ventilation, mostly before their first birthday, and 60 were decannulated, mostly before their sixth birthday.
NEURODEVELOPMENT OUTCOME — Preterm survivors who had bronchopulmonary dysplasia (BPD) compared with those without BPD are at increased risk for neurodevelopmental impairment. In studies performed after the routine introduction of surfactant therapy, BPD was associated with poorer motor and cognitive performance in toddlers and preschool children [23-27]. The association of BPD with impaired neurodevelopmental outcome persists through school age [28,29].
The severity of BPD is associated with an increased risk of neurodevelopmental impairment, as illustrated by a study from the NICHD Neonatal Research Network [20]. In this study of 5364 ELBW infants born between 1995 and 1998, abnormal neurodevelopmental outcomes were documented in 76 percent of surviving infants who were ventilated for ≥60 days, 93 percent of those ventilated for ≥90 days, and all of those who were ventilated for ≥120 days. In addition, neurodevelopmental outcomes are poorer with increasing severity of BPD, and in those who have associated pulmonary hypertension [30-33]. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia".)
Although changes in neonatal practice have the potential to affect the neurodevelopment outcome of infants with BPD, limited data suggest that the overall neurodevelopmental outcome of infants with BPD remains unchanged over the last two decades [34]. There has been a reduction in the use of postnatal glucocorticoid (which has been associated with cerebral palsy) treatment to prevent or treat BPD and is discussed in detail elsewhere.
In interpreting follow-up studies such as those cited above, it is important to recognize that many factors influence neurodevelopmental outcome [35]. These include the incidence of neurologic risk factors (eg, cranial ultrasound abnormalities), neurosensory problems (eg, retinopathy of prematurity, hearing impairment), hospital course including the use of glucocorticoid therapy, or poor social environment and parental educational attainment. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Limitations of the data'.)
GROWTH — It is clear that poor growth is observed in infants with bronchopulmonary dysplasia (BPD) during their neonatal intensive care unit (NICU) hospitalization and after discharge. This is due to the increased energy expenditure associated with their respiratory disease, and the difficulty of maintaining full nutrient and mineral intake in patients receiving fluid restriction and diuretics. However, the effect of BPD on long-term growth is uncertain. In some follow-up studies performed in the presurfactant era, poorer growth was reported in infants with BPD compared with unaffected infants through two years of age [36,37]. In contrast, other studies of patients treated from the same period found no difference in growth after adjustment for confounding variables in older children and adults [38-40].
Poor growth of survivors with BPD was noted in a study that followed 20 preterm infants with BPD for two years [36]. At term-adjusted age, infants were severely growth-restricted with average weight and height ≤3rd percentile. Growth accelerated as respiratory symptoms improved. By two years of age, the average weight for both boys and girls was between the 3rd and 10th percentile. The average height for boys was between the 10th and 25th percentile, and for girls, the average height was at the 25th percentile. In another series of 16 affected children evaluated at two years of age, height and weight were <10th percentile in 37 and 25 percent, respectively [37].
In a study of premature survivors at 8 and 10 years of age, although survivors with BPD were significantly smaller than unaffected children, after adjustment for confounding variables, no significant differences in growth were detected [39].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchopulmonary dysplasia".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Bronchopulmonary dysplasia (The Basics)")
SUMMARY
●Introduction – Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity resulting in significant mortality and morbidity.
●Mortality – Infants with severe BPD have a higher risk of mortality than unaffected infants or those with mild disease of the same gestational age (GA). Death usually is caused by respiratory failure, unremitting pulmonary hypertension with cor pulmonale, or sepsis. Increased mortality is associated with longer duration of mechanical ventilation, episodes of sepsis, and pulmonary artery hypertension (PAH). (See 'Mortality' above.)
●Pulmonary outcome – Survivors of prematurity and BPD are at increased risk for respiratory disease, including respiratory infection, asthma-like disease, and pulmonary artery hypertension. Persistent abnormalities in pulmonary function are also common in patients who had BPD as infants, and depend upon the severity of BPD. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia".)
●Neurodevelopmental outcome – BPD is associated with an increased risk for neurodevelopmental impairment, which affects both motor and cognitive function. The severity of BPD increases both the risk and severity of neurodevelopmental disability. (See 'Neurodevelopment outcome' above.)
●Growth – It remains uncertain whether BPD has a direct impact on long-term growth. After adjusting for confounding factors, no significant differences were detected in growth at school age in children who had BPD compared with those who did not have BPD. (See 'Growth' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges James Adams, Jr., MD, who contributed to an earlier version of this topic review.
