INTRODUCTION — Bronchopulmonary dysplasia (BPD; also known as neonatal chronic lung disease [CLD]) is a major cause of respiratory illness in preterm infants. It is an important contributing factor in the increased risk of mortality and morbidity in the preterm population.
The definition, pathogenesis, clinical features, and diagnosis of BPD are reviewed here. Other related topics include:
●Terms related to 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), as summarized in the table (table 1) and discussed in detail separately. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality", section on 'Definitions'.)
●Terms related to neonatal lung disease
•BPD – BPD is a chronic lung disease characterized by disruption of pulmonary development and/or lung injury in the context of preterm birth. As such, it applies only to preterm infants. Clinically, BPD is defined as an ongoing need for supplemental oxygen and/or respiratory support at either 28 days postnatal age or 36 weeks postmenstrual age (PMA) in a preterm neonate with radiographic evidence of parenchymal lung disease (image 1). Various criteria are used to define the severity of BPD, as summarized in the (table 2) and discussed below. (See 'Definitions and severity of BPD' below.)
•Chronic lung disease (CLD) – CLD is a broader term that overlaps with BPD. However, the term CLD is not restricted to preterm infants and is commonly used to describe lung disease in full-term infants who require respiratory support in the setting of various chronic pulmonary disorders (eg, pulmonary hypoplasia, congenital diaphragmatic hernia). (See "Congenital diaphragmatic hernia in the neonate".)
DEFINITIONS AND SEVERITY OF BPD — Clinically, BPD is defined as an ongoing need for supplemental oxygen and/or respiratory support at either 28 days postnatal age or 36 weeks postmenstrual age (PMA) in a preterm neonate (<32 weeks gestations age [GA]) with radiographic evidence of parenchymal lung disease (image 1).
Several definitions have been used since the first description of BPD by Northway in 1967. The severity classification schema in the 2019 definition (sometimes called the Jensen definition) (table 2) is based primarily on the mode of respiratory support rather than the required fraction of inspired oxygen (FiO2). This definition appears to be the most accurate for predicting long-term outcomes . However, many studies define BPD based solely upon whether the infant requires supplemental oxygen or other respiratory support either at 28 postnatal days or 36 weeks PMA [2-4]. This definition does not account for the severity of respiratory disease but it is commonly used in clinical trials because of its simplicity [4-8]. This simple definition is also frequently used in clinical practice. (See 'Clinical diagnosis' below.)
BPD definitions that have been used in clinical practice and research studies include (table 2):
●Simple clinical definition without severity classification – The simplest definition of BPD is based solely upon whether the infant requires oxygen therapy and/or respiratory support either at 28 postnatal days or 36 weeks PMA. Because of its simplicity, this definition is commonly used as an outcome measure in clinical trials [2,3,7]. However, it does not account for the severity of respiratory disease and it is therefore less reliable as a predictor of long-term pulmonary morbidity [4,6].
●Definitions that include severity classification – Various classification schemas have been used to characterize the severity of BPD. Most of these definitions require that the infant is preterm (GA <32 weeks), requires supplemental oxygen and/or respiratory support at 36 weeks PMA, and has radiographic evidence of parenchymal lung disease (image 1).
•2019 definition (Jensen definition) — Severity categories in the 2019 definition are based primarily on the mode of respiratory support administered at 36 weeks PMA, regardless of whether the infant requires supplemental oxygen :
-Mild BPD (grade I) – Requiring low-flow nasal cannula (<2 L/min) at 36 weeks PMA
-Moderate BPD (grade II) – Requiring high-flow nasal cannula flow (≥2 L/min), CPAP, or noninvasive intermittent positive pressure ventilation (NIPPV) at 36 weeks PMA
-Severe BPD (grade III) – Requiring invasive mechanical ventilation at 36 weeks PMA
These definitions come from a prospective study of 2677 very preterm (VPT) and extremely preterm (EPT) infants (90 percent of the cohort had GA <27 weeks) born between 2011 and 2015 . The study evaluated 18 different BPD definitions and found that the mode of respiratory support at 36 weeks PMA most accurately predicted death or serious respiratory morbidity through 18 to 26 months of corrected age.
A subsequent retrospective cohort study from the Vermont Oxford Network applied the 2019 definition to a cohort of preterm infants (gestational age from 22 to 29 weeks) born in 2018 at 715 centers in the United States . Among the 24,896 infants included in the study, 37 percent met criteria for mild or moderate BPD and 4 percent met criteria for severe BPD. Approximately 10 percent died before reaching 36 weeks PMA. Patients with severe BPD were more likely to have major comorbidities, die during birth hospitalization, or require supplemental oxygen support at discharge compared with infants with mild or moderate BPD.
-2001 NICHD definition – In 2001, a consensus workshop of the National Institute of Child Health and Human Development (NICHD) developed a definitions for mild, moderate, and severe BPD that incorporated GA, oxygen and respiratory support requirement, and persistence of disease [10,11]. However, these definitions are limited by their inability to identify infants using respiratory interventions developed after the convening of the workshop and the inability to accurately predict long-term pulmonary morbidity.
-2018 definition (revised NICHD definition) – Since the 2001 definition did not account for interventions developed after 2001 (ie, respiratory support modes that provide positive pressure without supplemental oxygen) and it did not reliably predict long-term respiratory outcomes , an NICHD workshop was held in 2016 to revise the definition and identify research opportunities to address knowledge gaps . Suggested refinements to the definition included adding newer modes of noninvasive ventilation (eg, high-flow nasal cannula); reclassifying the severity categories, including a new category (grade IIIA) for early lethal BPD (ie, infants who die with lung disease between 14 days and 36 weeks postnatally); and adding the criterion for radiographic evidence of pulmonary parenchymal disease. This workshop yielded the revised 2018 NICHD definition, which is summarized in the table (table 2) .
When evaluating the literature, it is important to keep in mind that these definitions have changed over time and thus the definition used in one study may differ from that in another [5,14]. Many neonatal clinical trials have used BPD as a key outcome measure for evaluating a wide range of interventions. Despite the frequent reliance on this outcome in the design of clinical trials, it has been challenging to reach a lasting consensus definition as there have been changes in the population at risk (ie, greater number of surviving extremely preterm neonates) and advances in neonatal management (ie, increasing use of noninvasive ventilation modes such as continuous positive airway pressure [CPAP]). These factors have altered the pathology and clinical course of BPD and led to revisions in its definition.
The challenges of applying different definitions of BPD have been described in observational studies [5,15,16]. In a multicenter study including 765 preterm infants (GA 23 to <29 weeks), BPD was diagnosed in 30 to 60 percent of the cohort, depending on the definition used (of note, this study was conducted prior to the 2018 and 2019 revised definitions) :
●59 percent met the definition based upon supplemental oxygen requirement alone
●41 percent met the 2001 NICHD criteria
●32 percent were diagnosed based upon physiologic testing (see 'Physiologic testing' below)
Physiologic testing was the most difficult to apply, resulting in the largest number of unclassified patients. The number of unclassified patients was lowest (2 percent) using the 2001 NICHD criteria.
EPIDEMIOLOGY — Rates of BPD vary between institutions, likely reflecting differences in neonatal risk factors, care practices (eg, use of noninvasive ventilation, oxygen targets), and differences in the clinical criteria used to define BPD [5,17-20]. The risk of BPD increases with decreasing gestational age (GA For extremely preterm (EPT) infants (GA <28 weeks), the incidence of BPD is approximately 40 percent .
In a multicenter study from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network of 9575 EPT infants born between 2003 and 2007, the overall incidence of BPD (defined as requiring supplemental oxygen at 36 weeks postmenstrual age) according to GA was as follows :
●22 weeks – 85 percent
●23 weeks – 73 percent
●24 weeks – 69 percent
●25 weeks – 55 percent
●26 weeks – 44 percent
●27 weeks – 34 percent
●28 weeks – 23 percent
The severity of BPD also increases with decreasing GA. In a study from the Vermont Oxford Network of 24,896 infants <30 weeks GA, the risk of severe BPD (ie, grade III using the 2019 criteria (table 2)) increased tenfold from 0.8 percent for infants born at 29 weeks GA to 10 percent for those born at 22 weeks GA . Grade III BPD was associated with increased risk of death and other serious comorbidities.
It is unclear whether the incidence of BPD is changing.
●In a report from the NICHD Neonatal Research Network, the incidence of BPD had not changed over a 20-year period from 1993 and 2012 except for an increased rate among infants born at 26 to 27 weeks gestation between 2009 and 2012 .
●A study using a United States national database (Nationwide Inpatient Sample) reported a decrease in the rate of BPD of 4.3 percent per year for the study period between 1993 and 2006 .
●However, a study in Japan of 19,370 EPT infants reported an increase in the incidence of BPD for the 17,126 survivors between 2003 and 2016 (46 versus 52 percent) . During the same period of time, there was an increase in survival rate (81 to 92 percent).
One study from the United States reported that Black infants had a lower risk of BPD compared with White infants even after adjusting for confounding risk factors (GA, antenatal steroid use, and intubation and surfactant administration at birth) .
Rates of BPD tend to be higher at hospitals at high altitude since infants managed at high altitude more often require supplemental oxygen therapy. However, the differences are less dramatic if adjustments are made to account for the barometric pressure [26,27].
RISK FACTORS — The etiology of BPD is multifactorial and involves disruption of lung development and injury due to antenatal (intrauterine growth restriction, maternal smoking) and/or postnatal factors (eg, mechanical ventilation, oxygen toxicity, infection) that cause inflammation and damage to the highly vulnerable premature lung . Numerous risk factors have been identified. Risk prediction models have been developed, but many are based upon single-center data from earlier eras and few have been externally validated in contemporary populations [29-31].
The following section discusses important risk factors that contribute to the development of BPD.
Prematurity — The premature lung is susceptible to damage because of its immature, underdeveloped airway-supporting structures, surfactant deficiency, decreased compliance, underdeveloped antioxidant mechanisms, and inadequate fluid clearance [32-34]. The premature lung's structural and functional immaturity increases the risk of injury and disruption of normal pulmonary microvascular and alveolar development from external antenatal and postnatal insults. As discussed above, the incidence of BPD increases with decreasing GA; the risk is greatest among extremely preterm (EPT) infants (gestational age [GA] <28 weeks). (See 'Epidemiology' above.)
Fetal growth restriction — Fetal (intrauterine) growth restriction in preterm infants is an independent risk factor for BPD [35-37]. Growth restriction may have a significant impact on the vulnerability of lung injury and vasculogenesis. In a case-control study of 2255 infants with <33 weeks GA, infants born small for GA had more than twice the risk of BPD (odds ratio [OR] 2.73, 95% CI 2.11-3.55) . (See "Infants with fetal (intrauterine) growth restriction".)
Maternal smoking — Maternal smoking negatively affects lung development in offspring and contributes to the risk of BPD [13,39,40]. In a prospective, longitudinal study of 587 preterm infants (GA <34 weeks and birth weight [BW] between 500 and 1250 g), maternal smoking was independently associated with risk of BPD (OR 2.02, 95% CI 1.09-3.74) . (See "Cigarette and tobacco products in pregnancy: Impact on pregnancy and the neonate", section on 'Postnatal'.)
Mechanical ventilation — Ventilator-induced lung injury in infants with BPD is primarily due to large tidal volumes (volutrauma) that overdistend airways and airspaces [41-43]. Barotrauma (exposure to high airway pressures) plays less of a role. For EPT infants who received mechanical ventilation at postnatal day 7, the risk of BPD is high . More aggressive ventilation (eg, large tidal volumes and/or low partial pressure of carbon dioxide [PaCO2] levels) is associated with increased risk of BPD [2,45].
Because aggressive mechanical ventilation plays a major role in the pathogenesis of BPD, management of preterm infants requiring respiratory support has shifted towards initial use of noninvasive modalities (eg, nasal continuous airway pressure [nCPAP]) to avoid mechanical ventilation, if possible. Between-center differences in the approach for respiratory support (including differences in criteria for intubation) may explain some of the variation among hospitals in BPD rates. (See "Bronchopulmonary dysplasia (BPD): Prevention", section on 'Ventilation strategies to minimize lung injury' and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)
Despite the use of noninvasive respiratory support, up to 50 percent of EPT infants require intubation and mechanical ventilation. If mechanical ventilation is needed, a more conservative approach of volume-targeted ventilation using small tidal volumes is utilized . The approach is summarized in the table (table 3) and discussed in detail separately. (See "Approach to mechanical ventilation in very preterm neonates".)
Oxygen toxicity — High concentrations of inspired oxygen can damage the lungs, although the exact level or duration of exposure that is unsafe is not known. The risk of BPD for EPT infants rises with increasing accumulation of supplemental oxygen during the first two weeks after delivery . It is thought that cellular damage is caused by the overproduction of cytotoxic reactive oxygen metabolites (ie, superoxide free radical, hydrogen peroxide, hydroxyl free radical, and singlet oxygen), which overwhelm the neonate's immature antioxidant system, resulting in inflammation and lung injury . Preterm infants are most susceptible to oxygen toxicity compared with term infants due to their more immature antioxidant enzyme systems (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase) [49,50].
Because of the adverse effects of high oxygen concentration, supplemental oxygen therapy in preterm neonates should aim to meet the metabolic needs of the infant while avoiding hyperoxia and high oxygen concentrations. This is discussed in detail separately. (See "Neonatal target oxygen levels for preterm infants", section on 'Oxygen target levels'.)
Infection — Both antenatal and postnatal infections are associated with increased risk of BPD:
●Antenatal infections – Studies have reached variable conclusions regarding the association between BPD and maternal intraamniotic infection (IAI; also called chorioamnionitis) [51-54]. A systematic review identified 158 studies examining this association; however, the definitions of IAI and BPD varied considerably between studies . The association between maternal IAI and BPD was strongest in studies that defined IAI based on histology and defined BPD as oxygen requirement at 28 postnatal days (pooled OR 2.58, 95% CI 1.99-3.34; based on 43 studies). The association was least pronounced in studies that defined IAI clinically and defined BPD as oxygen requirement at 36 weeks PMA (pooled OR 1.24, 95% CI 1.03-1.49; based on 31 studies).
Since IAI is known to substantially increase the risks of preterm birth and neonatal sepsis, it remains unclear whether IAI is an independent risk factor for BPD. It is possible that the association with BPD is indirect and largely due to the impact of prematurity and postnatal infection. However, it is hypothesized that IAI plays a direct role due to inflammatory changes that may contribute to development of BPD. This is supported by studies that have demonstrated increased concentrations of proinflammatory cytokines (interleukin [IL]-6, IL-1 beta, and IL-8) in the amniotic fluid of infants who subsequently develop BPD compared with those who did not . (See 'Pathogenesis' below.)
●Postnatal infections – The risk of BPD is increased in infants who develop postnatal bacterial or fungal infections. This was illustrated in an observational study from a single tertiary center of 798 preterm infants (mean GA 27.4 weeks) born between 1992 and 2004 that reported neonatal sepsis was associated with a nearly three-fold increased risk of BPD (OR 2.71, 95% CI 1.64-4.51) . Infants with candidemia had the highest risk of developing BPD (OR 8.68, 95% CI 1.65-45.63).
Infection with Ureaplasma urealyticum has been reported to cause a sustained dysregulated inflammatory response that impairs lung development, resulting in BPD [57,58]. A systematic review of the literature noted that infants with pulmonary colonization with Ureaplasma were more likely to develop BPD than those without colonization at 36 weeks postmenstrual age (OR 2.22, 95% CI 1.42-3.47) or at 28 days of life (OR 3.04, 95% CI 2.41-3.83) . Whether eradication of Ureaplasma respiratory colonization acquired in utero by preterm infants reduces the incidence of BPD requires testing in clinical trials [60,61] In a randomized trial of azithromycin to improve Ureaplasma free-survival in 121 preterm infants (GA <29 weeks), subgroup analysis found that physiological BPD-free survival was 50 percent (95% CI 19 - 81 percent) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonization versus 18 percent (95% CI 2 - 52 percent) in placebo-treated infants .
Patent ductus arteriosus — The role of the patent ductus arteriosus (PDA) in the development of BPD is uncertain. Although clinical trials conducted before 2000 consistently reported that PDA was associated with BPD, the accuracy of these results has been questioned due to study design issues . Subsequent studies of prophylactic indomethacin to prevent PDA resulted in conflicting results on the risk of BPD [63,64]. Ongoing research efforts are focused on comparing early versus no or late treatment of PDA and hope to address whether a persistent PDA contributes to the development of BPD. (See "Patent ductus arteriosus (PDA) in preterm infants: Clinical features and diagnosis", section on 'Consequences of a PDA'.)
Genetic factors — It remains uncertain whether there is a genetic predisposition that may influence the development of BPD as illustrated in the difference in results between twin cohort studies of preterm infants [65,66].
Similarly, conflicting results were reported in studies trying to identify genetic factors associated with BPD:
●A genome-wide association study (GWAS) that included 899 cases of BPD and 827 controls did not identify any single-nucleotide polymorphisms (SNPs) associated with BPD . These negative findings may have missed a genetic risk due to epigenetic effects, copy number variations, or joint effects of multiple SNPs or interaction among them.
●In a retrospective study of 157 preterm infants who developed respiratory distress syndrome requiring mechanical ventilation, two specific SNPs of a gene encoding for endothelial nitric oxide synthase (eNOS) were independent predictors of an increased risk of developing BPD .
●In another study of 751 infants of whom 428 developed BPD or died, pathway analysis of a GWAS identified involvement of several known pathways of lung development and repair that were significant for severe BPD or death and indicated specific molecules that were increased in patients with BPD .
Further studies are required to determine whether or not there is a genetic predisposition, and if so, what the underlying genetic factors are.
Pathology — The characteristic pathologic finding of BPD is disruption of the late canalicular or saccular phases of lung development [10,32,70]. The following pathologic findings occur:
●Decreased septation and alveolar hypoplasia lead to fewer and larger alveoli with a reduction in the surface area available for gas exchange.
●Dysregulation of pulmonary vasculature development with abnormal distribution of alveolar capillaries and thickening of the muscle layer of the pulmonary arterioles, which results in an increase in pulmonary resistance. Early disruption of vasculogenesis leading to pulmonary vascular disease results in pulmonary hypertension and contributes to morbidity and mortality .
●Increased elastic tissue formation and thickening of the interstitium. These tissue deformations may, in turn, compromise septation and capillary development. In one autopsy study, the amount of elastic tissue, septal thickness, and alveolar and duct diameters increased with the severity of BPD .
In older studies (before the 1980s), which generally included more mature infants (GA ≥28 weeks) cared for prior to the availability of surfactant replacement therapy and before widespread use of antenatal steroids, the prominent pathologic findings were airway injury, inflammation, and parenchymal fibrosis due to mechanical ventilation and oxygen toxicity [10,70]. Similar changes may rarely be seen in the contemporary era in surfactant-treated infants who develop severe BPD. In these severely affected infants, fibrosis, bronchial smooth muscle hypertrophy, and interstitial edema may be superimposed on the characteristic reduced numbers of alveoli and capillaries. Pulmonary vascular changes, such as abnormal arterial muscularization and obliteration of vessels, may also occur.
Pathogenesis — The pathogenesis of BPD is multifactorial. It results from lung injury and disruption of lung development due to antenatal and/or postnatal factors that cause inflammation and damage to the highly vulnerable premature lung . (See 'Risk factors' above.)
●Inflammation – The development of BPD may begin before birth in some newborns through intrauterine exposure to proinflammatory cytokines, possibly due to chorioamnionitis. However, this relationship remains controversial. Inflammation is a common pathway for many injuries that may disrupt late lung development. Evidence for a role for lung inflammation in the pathogenesis is based on the elevated concentration of proinflammatory and chemotactic factors in the tracheal aspirates of infants who subsequently develop BPD compared with those without BPD [48,73-75]. The presence of these mediators is associated with complement activation, increased vascular permeability, protein leakage, and mobilization of neutrophils into the interstitial and alveolar compartments. Release of reactive oxygen radicals, elastase, and collagenase by activated neutrophils results in lung damage . Interaction between macrophages and other cell types (eg, endothelial and epithelial cells) perpetuates the production of proinflammatory mediators and sustains the cycle of lung injury. Persistence of factors (eg, macrophage inflammatory protein-1 and IL-8) and decreases of counterregulatory cytokines (eg, IL-10, IL-17) may lead to unregulated and persistent inflammation .
●Late surfactant deficiency – Delayed recovery or late deficiency of postnatal surfactant may play a role in the pathogenesis of BPD. In a study of 68 ventilator-dependent preterm infants (GA between 23 and 30 weeks), 75 percent of tracheal aspirates exhibited abnormally low surface tension . In these samples, surfactant proteins A, B, and C were reduced by 50, 80, and 72 percent, respectively. There also appears to be a temporal association between samples with low surface tension and episodes of infection and respiratory deterioration. These results suggest that preterm infants who require continued respiratory support have transient surfactant dysfunction or deficiency, which may affect their clinical status. However, it appears that late administration of surfactant does not appear to reduce the risk of BPD, as discussed separately. (See "Respiratory distress syndrome (RDS) in preterm infants: Management", section on 'Timing'.)
●Impaired angiogenesis — There is increasing evidence suggesting that growth of pulmonary blood vessels actively promotes alveolar growth. Disruption of angiogenesis has been proposed as a mechanism that impairs alveolarization, thereby contributing to the new form of BPD . (See 'Pathology' above.)
Support for the potential role of impaired angiogenesis in the pathogenesis of BPD includes:
•In one study, elevated cord plasma levels of endostatin, an antiangiogenic growth factor, was associated with an increased risk of BPD in very low birth weight (VLBW) infants (BW <1500 g) .
•In a study of preterm infants less than 35 weeks gestation, cord blood level of placenta growth factor (PlGF), but not vascular endothelial growth factor or soluble fms-like tyrosine kinase-1, was elevated in infants who subsequently developed BPD .
•Observational studies have shown that the risk of BPD is twofold greater in infants born to mothers with preeclampsia compared with those born to mothers without preeclampsia [81,82]. These findings suggest factors that trigger maternal endothelial dysfunction (impaired angiogenesis), resulting in preeclampsia, are transferred to infants, which may contribute to the pathogenesis of BPD. (See "Preeclampsia: Pathogenesis", section on 'Role of systemic endothelial dysfunction in clinical findings'.)
●Abnormal pulmonary function — Patients with severe BPD typically have both hypoxemia and hypercapnia and often require positive pressure ventilatory support (either with noninvasive ventilation or invasive mechanical ventilation). Abnormalities in pulmonary function include decreased tidal volume and poor lung compliance (ie, restrictive lung physiology). However, the lung disease can be either restrictive or obstructive and some patients may have a mixed picture . Lung compliance is dynamic and there may be intermittent airway obstruction resulting in gas trapping and hyperinflation with abnormal distribution of overventilated and underventilated areas of the lung . Infants with BPD-associated tracheobronchomalacia can have obstruction due to airway collapse during expiration. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia'.)
●Hemodynamic effects – Severely affected patients may develop pulmonary hypertension. Pulmonary vascular resistance is increased in these patients because of disruption of pulmonary vascular growth and/or reduced cross-sectional area of pulmonary vessels. Alveolar hypoxia in underventilated areas of the lung induces local vasoconstriction. The high microvascular pressure promotes increased fluid filtration into the perivascular interstitium. Elevated right atrial pressure inhibits pulmonary lymphatic drainage, further promoting pulmonary edema. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia".)
CLINICAL FEATURES — BPD is associated with multiple risk factors, including prematurity, mechanical ventilation, oxygen toxicity, and infection. It occurs most frequently in extremely preterm (EPT) infants (gestational age [GA] <28 weeks) [13,85]. (See 'Risk factors' above.)
Infants who require supplemental oxygen with a fraction of inspired oxygen (FiO2) >0.25 at two weeks of age are at increased risk for developing BPD; however, early need for supplemental oxygen does not necessarily predict subsequent development of BPD .
Physical examination — The physical examination is variable. Infants with BPD usually are tachypneic. Depending upon the extent of pulmonary edema and/or atelectasis, they may have mild to severe retractions, and scattered rales may be audible. Intermittent expiratory wheezing may be present in infants with airway narrowing from scar formation, constriction, mucus retention, collapse, and/or edema.
Chest radiograph — As BPD evolves, the chest radiograph also changes from clear lung fields to findings that include diffuse haziness and a coarse interstitial pattern, which reflect atelectasis, inflammation, and/or pulmonary edema (image 1). Lung volumes are normal or low. With further evolution of the disease, there may be areas of atelectasis that alternate with areas of gas trapping, related to airway obstruction from secretions or bronchiolar injury.
The chest radiograph in infants who develop severe BPD shows hyperinflation. Streaky densities or cystic areas may be prominent, corresponding to fibrotic changes (image 1). During acute exacerbations, pulmonary edema may be apparent.
Clinical diagnosis — Clinically, BPD is defined as a need for supplemental oxygen and/or respiratory support at either 28 days postnatal age or 36 weeks postmenstrual age (PMA) in a preterm neonate with radiographic evidence of parenchymal lung disease (image 1). The severity of BPD is classified according to the amount of respiratory support required at 36 weeks PMA, as summarized in the table (table 2) and discussed above. (See 'Definitions and severity of BPD' above.)
Physiologic testing — If there is uncertainty about the diagnosis, physiologic testing (oxygen reduction test) can be performed to define the true need for supplemental oxygen at 28 days postnatal age or 36 weeks PMA.
Infants are classified as having BPD if the oxygen saturation falls below 90 percent within 60 minutes of being placed in room air. When performing physiologic testing at high altitudes, corrections for altitude are necessary.
CLINICAL COURSE — Most infants improve gradually in the two to four months after the diagnosis of BPD is made. As pulmonary function improves with growth, they can be weaned to continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) with supplemental oxygen, then supplemental oxygen alone, until they can maintain adequate oxygenation when breathing room air. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)
Some infants develop severe BPD with prolonged ventilator dependence . These infants typically have substantial clinical instability during the first few weeks after birth with swings in oxygen saturation and intermittent episodes of acute deterioration requiring increased ventilator support . The instability typically improves slowly after four to six weeks. However, some infants require long-term ventilator support or supplemental oxygen beyond six months of age. (See "Bronchopulmonary dysplasia (BPD): Management and outcome", section on 'Pharmacologic therapy' and "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia".)
Infants with severe BPD are more likely to have other comorbid neonatal conditions (sepsis, intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity) . In addition, they are at risk for other chronic complications, including pulmonary hypertension, acquired tracheobronchomalacia, subglottic stenosis, asthma-like symptoms, poor growth, and neurodevelopmental impairment. These complications are discussed in detail separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia" and "Bronchopulmonary dysplasia (BPD): Management and outcome", section on 'Morbidities'.)
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 about 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 AND RECOMMENDATIONS
●Importance – Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by disruption of pulmonary development and/or lung injury in the context of preterm birth. It remains a major complication of prematurity, resulting in significant mortality and morbidity. (See 'Pathophysiology' above and "Bronchopulmonary dysplasia (BPD): Management and outcome", section on 'Outcome'.)
●Epidemiology – The risk of BPD increases with decreasing gestational age (GA). For extremely preterm (EPT) infants (GA <28 weeks), the incidence of BPD is approximately 40 percent. (See 'Epidemiology' above.)
●Risk factors –Risk factors that contribute to the development of BPD include (see 'Risk factors' above):
•Prematurity (see 'Prematurity' above)
•Fetal growth restriction (see 'Fetal growth restriction' above)
•Maternal smoking (see 'Maternal smoking' above)
•Infections (see 'Infection' above)
•Patent ductus arteriosus (see 'Patent ductus arteriosus' above)
•Genetic factors (see 'Genetic factors' above)
•Physical examination – Physical findings of BPD vary. Most affected infants are tachypneic. Other findings include retractions, rales, and wheezes. (See 'Physical examination' above.)
•Chest radiograph – The chest radiograph in infants with BPD changes with evolution of the disease from clear lung fields to findings that include diffuse haziness and a coarse interstitial pattern, which reflect atelectasis, inflammation, and/or pulmonary edema (image 1). (See 'Chest radiograph' above.)
•The infants is preterm (<32 weeks GA), and
•There is radiographic evidence of parenchymal lung disease (image 1), and
•The infant requires supplemental oxygen and/or respiratory support at either 28 days postnatal age or 36 weeks postmenstrual age (PMA)
If there is uncertainty, the diagnosis can be confirmed by physiologic testing (oxygen reduction test), which involves placing the infant in room air to document the need for supplemental oxygen. (See 'Physiologic testing' above.)
•Mild BPD (grade I) – Requiring low-flow nasal cannula (<2 L/min) at 36 weeks PMA
•Moderate BPD (grade II) – Requiring high-flow nasal cannula flow (≥2 L/min), continuous positive airway pressure, or noninvasive intermittent positive pressure ventilation (NIPPV) at 36 weeks PMA
•Severe BPD (grade III) – Requiring invasive mechanical ventilation at 36 weeks PMA
●Clinical course – Most infants with BPD improve gradually during the first two to four months. Those with severe disease (grade III BPD) may require prolonged mechanical ventilation and are at risk for developing pulmonary hypertension and other complications. (See 'Clinical course' above and "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia" and "Pulmonary hypertension associated with bronchopulmonary dysplasia".)
ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge James Adams, Jr., MD, who contributed to an earlier version of this topic review.
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