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Bronchopulmonary dysplasia (BPD): Management and outcome

Bronchopulmonary dysplasia (BPD): Management and outcome
Literature review current through: Jan 2024.
This topic last updated: Jul 17, 2023.

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 management and outcome of BPD are discussed here. Other related topics include:

(See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis".)

(See "Bronchopulmonary dysplasia (BPD): Prevention".)

(See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants".)

(See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia".)

(See "Pulmonary hypertension associated with bronchopulmonary dysplasia".)

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), 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'.)

BPD – BPD is a chronic lung disease characterized by disruption of pulmonary development and/or lung injury in the context of preterm birth. 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 BPD, as summarized in the (table 2) and discussed in detail separately. (See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Definitions and severity of BPD'.)

MANAGEMENT

General measures — In-hospital general measures that are applied to all infants with established BPD include ensuring adequate nutrition and modest fluid restriction.

Growth and nutrition — Nutrition is provided to meet the increased total energy needs of infants with BPD and to support lung growth and healing. Caloric demands are generally high to meet the metabolic requirements for growth and healing. Total energy needs are often >130 kcal/kg per day in some infants may increase to 150 kcal/kg per day; protein intake needs are generally in the range of 3.5 to 4 g/kg per day [1]. Because fluid intake is often restricted, the volume of feeding may need to be reduced and provided with high caloric density to meet the neonate's needs.

In our centers, fortified human milk that is supplemented to meet their needs for adequate growth is given to infants with BPD. Mother's milk is preferred, but if not available, donor milk should be used. If fluid restriction <140 mL/kg is needed, commercially available human milk fortifier can be added to increase caloric density to 24, 27, or 30 kcal/oz as needed. An alternative option is to alternate feeds between fortified human milk and preterm formula with a higher nutrient density [2]. (See "Human milk feeding and fortification of human milk for premature infants", section on 'Fortification of human milk' and "Growth management in preterm infants", section on 'Bronchopulmonary dysplasia'.)

Patients should be weighed two to three times per week while in the hospital, and length and head circumference should be measured weekly (figure 1 and figure 2). Additional monitoring includes measurements of blood urea nitrogen, calcium, phosphorus, and alkaline phosphatase concentrations. Serum electrolyte concentrations should be monitored in infants on diuretic therapy. (See "Growth management in preterm infants" and 'Diuretics' below.)

Infants with BPD are at risk for metabolic bone disease (MBD) and they require calcium, phosphorus, and vitamin D supplementation because of their rapid growth, loss of accretion of these nutrients during the third trimester of pregnancy, and, in some patients, renal losses from diuretic therapy. Management and prevention of MBD in preterm infants is discussed in detail separately. (See "Management of bone health in preterm infants".)

The nutritional prescription should be adjusted as needed based upon the infant's growth and laboratory results. Consultation with a dietitian experienced in the management of chronically ill infants is advised.

Infants with BPD may have oral motor dysfunction and feeding disorders that adversely affect growth and require specific intervention. Consultation with an experienced clinician (occupational and/or speech therapist) is useful to assess and manage these feeding difficulties. The evaluation and management of these patients are discussed separately. (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders".)

Fluid restriction — For most infants with BPD, we suggest modest fluid restriction (140 to 150 mL/kg per day). In severely affected infants, fluid restriction to 110 to 120 mL/kg per day may be necessary.

Based upon our clinical experience, modest fluid restriction appears to improve pulmonary function and reduces the risk of pulmonary edema. Limited clinical trial data support this practice [3,4]; however, the trials were largely performed in the 1980s and 1990s and may not be directly applicable to modern-day practice. In addition, most trials evaluated the impact of fluid restriction in the early postnatal course (before the neonate had established BPD). The one trial comparing restrictive versus liberal feeding volumes in neonates with established BPD did not detect a benefit of fluid restriction in any of the measured respiratory outcomes [5,6]. However, it was a small trial (60 infants) and may have been underpowered to detect a true difference.

As noted above, adequate nutrition must be provided to ensure proper growth regardless of the decision to restrict fluid intake. The caloric density of feeds may need to be increased in patients who are managed with a more restrictive fluid intake. (See 'Growth and nutrition' above.)

Respiratory support — Respiratory care is supportive. The goal is to maintain adequate gas exchange while minimizing further lung injury. Depending on the severity of lung disease, respiratory support may consist of supplemental oxygen (eg, via nasal cannula), noninvasive support (eg, nasal continuous positive airway pressure [nCPAP], noninvasive intermittent positive pressure ventilation [NIPPV], or high-flow nasal cannula [HFNC]), or invasive mechanical ventilation. (See "Approach to mechanical ventilation in very preterm neonates", section on 'Indications for invasive MV' and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)

Supplemental oxygen — The goal of supplemental oxygen therapy in neonates with BPD is to meet the metabolic needs of the neonate while avoiding high concentrations of oxygen, hyperoxia, and hypoxia. The initial target range for oxygen therapy is a peripheral oxygen saturation (SpO2) of 90 to 95 percent. This is discussed in detail separately. (See "Neonatal target oxygen levels for preterm infants", section on 'Oxygen target levels'.)

Once an infant with BPD reaches term and achieves mature retinal vascularization (as documented by ophthalmologic examination), the upper limit of the target SpO2 range can be increased to >95 percent [7].

Supplemental oxygen therapy can be beneficial to infants with BPD since it ensures adequate tissue oxygenation and avoids alveolar hypoxia, thereby reducing pulmonary vascular resistance [8,9]. However, increases in the inspired oxygen concentration, even small changes, may have a negative impact on the clinical course by exacerbating pulmonary inflammation or pulmonary edema. It also increases the risk of retinopathy of prematurity. (See "Retinopathy of prematurity (ROP): Risk factors, classification, and screening", section on 'Risk factors' and "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Oxygen toxicity'.)

Noninvasive support — Patients with moderate BPD (grade II) generally require noninvasive positive airway pressure support, which may be provided with nCPAP, NIPPV, or HFNC. The choice between these modalities is largely center dependent. Our centers most often use nCPAP. Details regarding these modalities are provided separately. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)

Mechanical ventilation

Approach — For patients with established BPD who require mechanical ventilation, our suggested approach is as follows:

We suggest a synchronized mode with both mandatory and spontaneous breaths (ie, synchronized intermittent mandatory ventilation plus pressure support or assist control ventilation). (See "Overview of mechanical ventilation in neonates", section on 'Synchronized modes'.)

We suggest volume-targeted ventilation with low tidal volumes (4 to 6 mL/kg). The rationale for low tidal volume ventilation in infants with BPD is to minimize volutrauma, which contributes to ventilator-induced lung injury and worsening BPD. However, infants with severe BPD may require higher tidal volumes over time to maintain effective ventilation because airway dilation and dead space to tidal volume ratio increase with chronic mechanical ventilation [1,10]. (See "Approach to mechanical ventilation in very preterm neonates", section on 'Volume-targeted versus pressure-limited ventilation' and "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Mechanical ventilation'.)

We initially use a standard inspiratory time setting (ie, 0.35 to 0.4 seconds). However, based on our clinical experience, a slightly prolonged inspiratory time (0.4 to 0.5 seconds) sometimes is needed to promote uniform lung inflation in patients who develop uneven airway obstruction.

Positive end-expiratory pressure (PEEP) is set to 5 to 7 cm H2O since this minimizes atelectasis and may reduce pulmonary edema. However, infants with bronchomalacia (narrowing of the bronchi due to diminished cartilage airway support) may require higher levels of PEEP to keep airways open during exhalation.

We suggest the following targets for gas exchange:

The peripheral oxygen saturation (SpO2) goal is 90 to 95 percent initially. Once the infant reaches term, the upper limit of the target SpO2 range can be increased to >95 percent. (See "Neonatal target oxygen levels for preterm infants".)

The partial pressure of carbon dioxide (PaCO2) goal is 55 to 65 mmHg and pH goal is 7.3 to 7.4. In patients with severe BPD, PaCO2 values up to 70 mmHg may be tolerated on occasion to avoid further escalation of ventilator support [7]. (See "Approach to mechanical ventilation in very preterm neonates", section on 'Gas exchange targets'.)

Endotracheal suctioning is performed only if needed and care should be used to ensure that the suction catheter does not pass beyond the distal end of the endotracheal tube ("calibrated suctioning"). This is because excessive suctioning is associated with tracheal and bronchial injury.

Additional details regarding mechanical ventilation in preterm neonates are provided separately. (See "Approach to mechanical ventilation in very preterm neonates".)

Monitoring and weaning — Ongoing assessment of ventilator-dependent infants includes continuous pulse oximetry and intermittent blood gas sampling to monitor pH and PaCO2. The frequency of blood gas sampling depends on the severity of illness and frequency of ventilator changes. We initially obtain daily or every other day blood gas samples and then decrease the frequency as the clinical condition stabilizes with fewer ventilator changes. A blood gas and chest radiograph should generally be obtained if the infant experiences an episode of respiratory decompensation. (See 'Acute exacerbations' below.)

As the infant grows and lung function improves, periodic attempts should be made to wean ventilator support as tolerated. Infants who can maintain acceptable PaCO2 levels with minimal ventilator support and without increased respiratory effort or tachypnea can be extubated to nCPAP and then to nasal cannula oxygen as needed based on SpO2 values.

Additional details regarding monitoring and weaning infants receiving mechanical ventilation are provided separately. (See "Approach to mechanical ventilation in very preterm neonates", section on 'Monitoring' and "Approach to mechanical ventilation in very preterm neonates", section on 'Weaning and discontinuation of MV'.)

Role of tracheostomy — In addition to ongoing lung injury, prolonged intubation and mechanical ventilation and may be associated with acquired subglottic stenosis and laryngeal injury, especially in infants who require multiple intubations. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Glottic and subglottic damage' and "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Tracheal and bronchial stenosis and granuloma formation'.)

Tracheostomy placement provides a stable and reliable airway, and diminishes acute events due to endotracheal tube displacement or obstruction [1]. The appropriate timing and indications of tracheostomy placement in ventilator-dependent infants remains poorly defined [1,11,12]. In our practice, tracheostomy is considered in infants who are 40 to 42 weeks postmenstrual age and are expected to need continued ventilator support. However, the optimal timing is uncertain and individualized decision-making is required.

In a multicenter cohort study of 8683 surviving infants <30 weeks gestational age (GA) born between 2001 and 2011, tracheostomy was performed in 3.5 percent (n = 304) [12]. Requiring tracheostomy was an independent risk factor for long-term neurodevelopmental impairment (NDI).In this study, outcomes differed depending on the timing of tracheostomy with a lower risk of NDI among infants who underwent earlier (at age <120 days) versus later (at age ≥120 days of age) tracheostomy.

Pharmacologic therapy — Pharmacologic therapy is typically reserved for infants with moderate to severe BPD.

Diuretics — Diuretic therapy has been shown to improve short-term pulmonary mechanics in infants with BPD, but there is little evidence that the long-term use of diuretics improves clinical outcomes [13]. Thus, diuretic therapy is not used routinely in all neonates with BPD, but it is commonly used to improve pulmonary function in patients with moderate to severe BPD.

Indications – We use diuretic therapy in the following settings:

For patients who remain ventilator-dependent or dependent on noninvasive positive pressure support (eg, nCPAP) despite modest fluid restriction, we suggest a trial of diuretic therapy. We typically use a thiazide diuretic in this setting, as discussed below.

For patients with acute pulmonary exacerbations attributed to pulmonary edema, we use single or intermittent doses of diuretics (typically furosemide).

When patients with BPD receive red blood cell (RBC) transfusions, we provide a single dose of diuretic (typically furosemide) during or immediately after the transfusion.

Choice of agent

Chronic therapy – For infants with moderate to severe BPD who require diuretic therapy, we generally begin with a thiazide, such as chlorothiazide or hydrochlorothiazide. We do not routinely use a combination of spironolactone with thiazide as spironolactone does not add any further benefit in our experience [14]. However, other centers may add spironolactone for its potassium-sparing effect. For infants who remain unstable despite modest fluid restriction and daily thiazide therapy, it is reasonable to add furosemide for a limited duration. However, we avoid the chronic use of furosemide, if possible, because of its potential complications of ototoxicity and nephrocalcinosis.

Acute exacerbations – For management of acute exacerbations attributed to pulmonary edema, we generally use oral or intravenous (IV) furosemide. We do not use combination therapy with furosemide plus a thiazide diuretic since this increases the risk of adverse effects. If the infant is receiving chronic thiazide therapy, it is discontinued when initiating furosemide.

Infants receiving RBC transfusions – For infants receiving RBC transfusions, we typically provide a single dose of IV furosemide.

Dosing

Chlorothiazide is typically given orally at a dose of 20 to 40 mg/kg per day divided in two doses, The published maximum oral dose of chlorothiazide is 375 mg; however, in our experience, we have never approached this maximum dose. Chlorothiazide can also be given IV at a dose of 2 to 8 mg/kg per day in two divided doses.

Hydrochlorothiazide is given orally at a dose of 3 to 4 mg/kg per day divided to two doses (maximum dose of 37.7 mg per day).

Furosemide can be given IV at a dose of 1 mg/kg per or orally at a dose of 2 mg/kg per dose.

Duration of treatment

Chronic therapy – We typically continue diuretic therapy until the infant is no longer receiving positive airway pressure and the fraction of inspired oxygen (FiO2) is <0.3. Weaning strategies include decreasing the daily diuretic dose in a step-wise fashion every 3 to 4 days, or not adjusting the dose for growth.

Acute exacerbations – The duration of diuretic therapy for infants with acute exacerbations depends on the severity of the exacerbation and the response to treatment. Some infants may improve with one to two doses. For infants with more severe respiratory decompensation, a trial of furosemide may be continued for two to three days. A longer course of furosemide may be considered for ventilator-dependent infants with severe BPD who had a short-term positive response to furosemide during an acute exacerbation. However, we generally avoid chronic use of furosemide, if possible, because of its potential complications of ototoxicity and nephrocalcinosis.

Electrolyte monitoring and supplementation – Serum electrolytes should be measured one to two days after initiating diuretic therapy and after dose increases. During chronic therapy, electrolytes should be monitored at least weekly. Electrolyte supplements should be administered to compensate for increased urinary losses. We usually start with 2 to 4 mEq/kg per day of potassium chloride and adjust as needed based on laboratory values and changes in diuretic dosing.

Adverse effects – The most common adverse effects of diuretic therapy are electrolyte abnormalities (hyponatremia, hypokalemia, and hypochloremic alkalosis) [13,15]. Dietary supplementation with potassium chloride usually is needed to prevent these abnormalities. As noted above, some centers will add spironolactone as a potassium-sparing diuretic.

Little data are available regarding effect of diuretics on long-term bone growth and mineralization.

Other complications associated with loop diuretics (eg, furosemide) include:

Nephrocalcinosis and/or nephrolithiasis due to increased urinary calcium excretion [16,17]. (See "Nephrocalcinosis in neonates", section on 'Loop diuretics'.)

Ototoxicity, especially with chronic high-dose IV furosemide therapy. (See "Loop diuretics: Dosing and major side effects", section on 'Ototoxicity'.)

Supporting evidence

Thiazide diuretics – Acute and chronic administration of diuretics that act on the distal renal tubule (thiazide and/or spironolactone) produce short-term improvement in lung mechanics in preterm infants with BPD [18]. However, in a systematic review, data were inadequate to show that distal diuretic administration improved long-term clinical outcome in infants with established or developing BPD [18]. Further clinical trials are needed to determine which infants are likely to benefit from chronic use of thiazide diuretics.

Loop diuretics – The most commonly used and best studied loop diuretic is furosemide. In a systematic review, chronic administration of furosemide either enterally or intravenously to infants with BPD older than three weeks of age improved pulmonary mechanics and oxygenation [19]. Pulmonary mechanics were also improved after a single intravenous dose of furosemide (1 mg/kg). However, no benefit was demonstrated in clinical outcomes, including need for ventilator support, length of hospital stay, survival, or long-term outcome. No consistent effects were found when intravenous furosemide was given to preterm infants younger than three weeks of age with developing BPD.

In a large retrospective study of 3252 preterm infants (GA <32 weeks) cared for in 43 neonatal intensive care units in children's hospitals, there was a six-fold difference in the proportion of days of loop diuretic exposure for infants with severe BPD between the lowest-use and highest-use centers (7 versus 49 percent, respectively) [20]. However, despite this marked variation in loop diuretic usage, mortality rates were similar between low- and high-use centers (9.7 versus 9.5 percent) as was the median postmenstrual age at discharge (45 versus 47 weeks).

Bronchodilators — We do not routinely use bronchodilators in the management of infants with BPD. Bronchodilator therapy is generally reserved for infants who have episodes of acute pulmonary decompensation with evidence of airway reactivity.

In patients with acute bronchoconstriction, inhaled beta agonists (eg, albuterol [salbutamol] or levalbuterol) decrease airway resistance and improve lung aeration [17,21,22]. Based on the available clinical trial evidence, chronic beta agonist therapy does not appear to improve outcomes for infants with BPD and these agents have known adverse effects (tachycardia, increased blood pressure, increased risk of tachyarrhythmias).

However, in some infants with severe BPD, especially older infants who remain ventilator-dependent, acute episodes of bronchoconstriction can occur. In this setting, inhaled beta agonist therapy (eg, albuterol [salbutamol] or levalbuterol) can be trialed and may improve short-term lung function [22,23].

When beta agonist therapy is used, it can be administered with a nebulizer or a metered-dose inhaler with a spacer. The infant should be observed for clinical benefit, as evidenced by decreased respiratory effort, improved lung aeration, and improved gas exchange (eg, improved oxygen saturation). If the infant has a good response, the beta agonist can be used up to a 48-hour period, then progressively weaned. If no benefit is seen, treatment should be discontinued. For patients with clinical signs of airway obstruction (ie, wheezing and/or prolonged exhalation) who have no response to bronchodilator therapy, it is more likely that the airway obstruction is due to bronchomalacia rather than bronchoconstriction. Large airway collapse from acquired tracheobronchomalacia is a known complication of severe BPD [24]. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia'.)

The use of bronchodilator therapy in infants with BPD has been investigated in observational studies and a few small clinical trials [25-28]. In a trial that included 87 infants randomly assigned to albuterol (given every 4 hours beginning at age 10 days and continued through 28 days of age and then tapered over 8 days) or placebo, mortality was the same in both groups (9 percent each) as were rates of severe BPD (5 percent each) [25].

Glucocorticoids — We use glucocorticoids in the following settings:

For extremely preterm (EPT) infants (ie, GA <28 weeks) who remain ventilator-dependent and/or require oxygen supplementation >50 percent at two to four weeks postnatal age. In this high-risk population, we use systemic glucocorticoids to prevent development of severe BPD and other pulmonary morbidity. This is discussed separately. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants", section on 'Our approach'.)

In selected older infants with established severe BPD who are dependent upon substantial respiratory support (eg, mechanical ventilation and high FiO2 requirement) or have evidence of airway reactivity. In these infants we use inhaled glucocorticoid therapy with the aim of reducing lung inflammation and facilitating ventilator weaning. If the infant continues to have significant respiratory compromise despite beta agonist therapy and an inhaled glucocorticoid, we provide a short (7 to 10 days) tapering course of systemic hydrocortisone (initial dose 5 mg/kg). We generally limit this treatment to ventilator-dependent infants >40 weeks postmenstrual age because of concerns for adverse effects on long-term neurodevelopment when used in more premature infants.

Additional details regarding glucocorticoid therapy in the neonates, including the supporting evidence and concerns about adverse effects on neurodevelopment, are discussed in greater detail separately. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants".)

ACUTE EXACERBATIONS — Infants with BPD may experience episodes of acute pulmonary decompensation, manifested by worsening gas exchange (eg, increased oxygen requirement) and/or respiratory distress. These may be precipitated by acute bronchospasm or excessive fluid retention in the lung. Other causes of acute pulmonary decompensation in infants with BPD include pulmonary air leak, displacement of the endotracheal tube, or the development of symptomatic tracheobronchomalacia. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia'.)

Evaluation

Assessment of fluid status – Excessive weight gain may suggest fluid retention in the lung, which is a common cause for pulmonary decompensation.

Respiratory assessment – The clinician should assess infant's work of breathing and lung aeration, including assessing for evidence of airway obstruction and bronchoconstriction (prolonged expiratory phase and wheezing). Specific findings on lung auscultation may be a clue to an underlying pulmonary complication:

Wheezing, poor air movement, and/or prolong exhalation may be indicative of bronchoconstriction.

Rhonchi or decreased breath sounds are suggestive of a consolidated process, such as pneumonia.

Crackles may indicate pulmonary edema.

Absent breath sounds may be due to pneumothorax or displaced endotracheal tube in ventilator-dependent infants.

Chest radiography – A chest radiograph should be obtained to detect pulmonary parenchymal changes, which may be suggestive of infection or increased pulmonary interstitial fluid, or detect pulmonary air leak or displacement of the endotracheal tube (see "Pulmonary air leak in the newborn"). The chest film may also detect hyperinflation or collapse, diaphragm position, and any changes in heart size.

Laboratory testing

Complete blood count to detect leukocytosis, which may indicate an infectious process.

Capillary or arterial blood gas sample to monitor partial pressure of carbon dioxide (PaCO2) and pH levels, and to decide if changes in respiratory support are needed: ventilator changes in ventilator-dependent patients, increased pressure support in patients dependent on continuous airway pressure, or intubation and ventilation in infants who are not intubated.

Evaluation for possible ventilator-associated pneumonia (VAP) – Although there is a lack of consensus on the definition of VAP in infants with BPD, acquired pulmonary infection is always a concern in patients receiving invasive mechanical ventilation. In our practice, a tracheal aspirate for culture and Gram stain should be obtained if secretions have become purulent, changed in volume or quality, or a new consolidated area (suggestive of an infectious process) is detected on chest radiography. If bacterial pneumonia is suspected, blood culture should also be obtained. Rapid tests for viral pathogens may also be considered, depending on season and possible exposures.

Evaluation for tracheobronchomalacia – Tracheobronchomalacia is characterized by abnormally compliant and collapsing trachea and bronchi presumably due to barotrauma, prolonged intubation, or injury from infection. Infants with tracheobronchomalacia will have episodes of apnea with absent airflow and chronic wheezing that does not improve with bronchodilators. A presumptive diagnosis can be made clinically; dynamic airway endoscopy is required for definitive diagnosis. This is discussed separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia'.)

Management — Management is directed towards the suspected underlying cause of acute exacerbations:

Infection – If bacterial infection is suspected, antibiotic treatment is initiated while awaiting culture results. Clinical findings suggestive of infection include a new localized consolidation on chest radiography or physical examination, leukocytosis, or the presence of fever. (See "Neonatal pneumonia".)

Pulmonary air leak – Management of the various forms of pulmonary air leak in the neonate is discussed separately. (See "Pulmonary air leak in the newborn".)

Displaced endotracheal tube – The endotracheal tube is correctly repositioned above the carina of the trachea.

Airway reactivity – Episodes of severe airway reactivity in infants with BPD should be treated immediately in a step-wise approach. Our general approach is as follows:

We begin treatment with levalbuterol (45 mcg per puff), administered as one to two puffs by metered dose inhaler with a spacer (MDI-S) every four to six hours. If there is severe airway obstruction, levalbuterol can be initially given as one to two puffs every 20 minutes for three doses. Albuterol (salbutamol) is a reasonable alternative beta agonist agent. Beta agonist therapy is weaned by decreasing the dosing frequency as airflow improves and is withheld if the heart rate exceeds 200 beats per minute. (See 'Bronchodilators' above.)

If acute bronchospasm occurs in an infant already receiving inhaled glucocorticoids, the dose is doubled for five to seven days. If the infant continues to have significant respiratory compromise despite beta agonist therapy and an inhaled glucocorticoid, we provide a short (7 to 10 days) tapering course of systemic hydrocortisone (initial dose 5 mg/kg). However, we generally limit this treatment to ventilator-dependent infants who are older than 40 weeks postmenstrual age (PMA) because of concern of adverse effects on long-term developmental outcome. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants", section on 'Systemic glucocorticoids'.)

Tracheobronchomalacia – For infants with significant respiratory compromise due to tracheobronchomalacia, we provide high positive end-expiratory pressure (PEEP) to maintain airway patency during expiration. In severe cases of tracheobronchomalacia that require long-term high PEEP (9 to 14 cm H2O) to maintain an open airway, tracheostomy may be required. (See 'Role of tracheostomy' above and "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Tracheostomy'.)

SCREENING FOR COMPLICATIONS — All infants with BPD should routinely be screened for the following complications:

High blood pressure – Blood pressure (BP) should be monitored at least weekly in infants who remain hospitalized and at each outpatient visit after discharge. For infants with elevated BP, an evaluation should be performed to determine the underlying cause. Persistent hypertension may require treatment. (See 'Cardiovascular complications' below and "Etiology, clinical features, and diagnosis of neonatal hypertension" and "Management of hypertension in neonates and infants".)

Pulmonary hypertension – The approach to echocardiographic screening for pulmonary hypertension in infants with BPD is summarized in the figure (algorithm 1) and discussed in detail separately. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Screening'.)

Neurodevelopmental impairment (NDI) – The approach to screening for NDI in high-risk preterm neonates, including those with BPD, is discussed separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Approach for follow-up care'.)

DISCHARGE PLANNING — Infants with moderate to severe BPD typically have a prolonged and complicated birth hospitalization and require considerable supportive management after discharge to home. Optimal discharge planning is provided by a multidisciplinary team that includes a neonatologist, pediatric pulmonologist, nurses, respiratory therapists, a social worker, a child life specialist, a nutritionist, physical and occupational therapists, and an audiologist [1,29]. The team should meet regularly to monitor the patient's clinical course and to review and refine goals and criteria for discharge. The transition from hospital to home may require substantial preparation. In many cases, a step-down unit or rehabilitation facility is an intermediate step before discharge home. (See "Discharge planning for high-risk newborns", section on 'NICU discharge planning'.)

Discharge criteria – Discharge criteria for oxygenation include having a stable oxygen requirement with average pulse oximetry measurements ≥95 percent without frequent episodes of desaturation. At discharge, cardiorespiratory parameters (respiratory and heart rate, blood pressure, oxygen requirement, chest radiograph, and most recent echocardiogram to assess for pulmonary hypertension) should be communicated to the primary care provider responsible for the care of the infant. A more detailed discussion of discharge criteria for preterm neonates is provided separately. (See "Discharge planning for high-risk newborns", section on 'Medical readiness'.)

Parent/caregiver training – Training the parents/caregivers to care for the infant is critical. Prior to discharge, the parents need to demonstrate competency in the daily care of their infant and they should be able to recognize signs of respiratory distress and acute illnesses. Often, parents/caregivers require special training to learn complex medical care skills (use of medical equipment, drug administration, tracheostomy care). Parents/caregivers should learn cardiopulmonary resuscitation. Arrangements should be made for the necessary equipment for home care and nursing support, if needed. Education of the parents about the use of this equipment should begin well before anticipated discharge. (See "Discharge planning for high-risk newborns", section on 'Caregiver preparation and support'.)

Follow-up care – As is true for all infants discharged from the neonatal intensive care unit (NICU), comprehensive continuity of care that addresses the needs of the NICU graduates and their families is required. The neonatal team should communicate to the identified primary care provider who will be responsible for the medical management of the infant after discharge. In some cases, this includes ongoing subspecialty care and follow-up with other health care professionals. (See "Care of the neonatal intensive care unit graduate", section on 'Role of the primary care provider'.)

The initial follow-up visit is scheduled within 48 to 72 hours after discharge from the hospital, during which the infant's hospital course is reviewed, current medical status is evaluated, and parental/caregiver questions and concerns are addressed. (See "Care of the neonatal intensive care unit graduate", section on 'Initial visit'.)

Subsequent visits focus on routine primary care (eg, immunization and growth), general care targeted for NICU graduates (ie, hearing, vision, and neurodevelopment screening), and specific management issues for infants with BPD [1]. These include prophylaxis against respiratory syncytial virus (RSV) infection, ongoing assessment for pulmonary hypertension, and management of chronic complications, including systemic hypertension. (See 'Morbidities' below and "Care of the neonatal intensive care unit graduate", section on 'Subsequent visits'.)

RSV infection can be life-threatening in infants with BPD. All affected infants should receive RSV prophylaxis, as discussed in detail separately. (See "Respiratory syncytial virus infection: Prevention in infants and children".)

OUTCOME

Mortality — Infants with severe BPD are at higher risk of mortality compared with infants of the same gestational age (GA) without BPD or with only mild disease [30-32]. Reported mortality rates vary depending on the criteria used to define severe BPD. In a study that included 564 infants with BPD, hospital mortality after 36 weeks postmenstrual age (PMA) was 3 percent for the entire cohort [30]. Among those with severe BPD (defined as requiring invasive mechanical ventilation at 36 weeks PMA (table 2)), hospital mortality was 10 percent.

The risk of mortality is particularly high in infants with BPD-associated pulmonary hypertension [33,34]. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia".)

The most common causes of death in infants with severe BPD are primary respiratory failure, refractory pulmonary hypertension, and acquired infection (pneumonia or sepsis).

Morbidities

Hospital readmissions — Readmission to the hospital is common among survivors of BPD. In an analysis of data from the Pediatric Hospital Information System of 3574 infants with BPD, 34 percent required at least one hospital readmission by one year corrected age [35]. Risk factors for readmission included more severe BPD, earlier gestational age, male sex, gastrostomy tube placement, and surgical NEC. Use of home oxygen was not independently associated with readmission in this study. (See "Care of the neonatal intensive care unit graduate", section on 'Hospital readmissions'.)

Pulmonary outcomes — Infants with BPD are at risk for the following complications, which are discussed in greater detail separately:

Recurrent pulmonary infections, particularly during the first two years of life. Respiratory syncytial virus (RSV) infection can be life-threatening in this population. (See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children" and "Respiratory syncytial virus infection: Prevention in infants and children".)

Asthma-like symptoms. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Asthma-like symptoms'.)

Abnormal pulmonary function and reduced exercise capacity. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Pulmonary function'.)

Pulmonary hypertension. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia".)

Acquired airway abnormalities (tracheobronchomalacia, subglottic stenosis). (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia' and "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Glottic and subglottic damage'.)

Tracheostomy and chronic ventilator dependence – Most infants who require home ventilation are successfully weaned from the ventilator [36,37]. This was demonstrated in a report of 83 surviving preterm infants cared for in one home ventilator program from 1984 to 2010 [36]. In this cohort, 69 of the 83 survivors no longer required positive pressure ventilation, most had been weaned off before their first birthday; 60 were decannulated, mostly before their sixth birthday. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Tracheostomy' and "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Home ventilators'.)

Long-term pulmonary outcomes in infants with BPD are discussed in detail separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia".)

Cardiovascular complications — In addition to pulmonary hypertension, other cardiovascular complications seen in infants with BPD include:

Systemic hypertension – Systemic hypertension is common in infants with BPD [38-40]. It is usually a transient finding in the first year of life and lasts approximately four months [38,41-44]. Approximately one-half of patients with BPD will have received medical therapy for blood pressure control. The pathogenesis for hypertension is uncertain and may be caused by increased levels of catecholamines, angiotensin, or antidiuretic hormone, or altered neurohumoral regulation [45]. Glucocorticoid therapy also can contribute to hypertension.

Ventricular hypertrophy – Left ventricular hypertrophy (LVH) may be associated with BPD, although this appears to be rare in the modern era. LVH is usually found during screening echocardiography for pulmonary hypertension and may be associated with systemic hypertension. Patients with persistent LVH or those with signs of LV dysfunction should be evaluated by a pediatric cardiologist.

Pulmonary vein stenosis – Stenosis of the pulmonary veins has been reported in approximately 5 to 10 percent of infants with severe BPD [46,47]. It is an acquired lesion distinct from pulmonary vein stenosis seen in certain forms of congenital heart disease. It is usually diagnosed on echocardiography performed to evaluate pulmonary hypertension. The pathogenesis is uncertain but may be related to persistent lung inflammation in infants with severe BPD. Infants with BPD-associated pulmonary vein stenosis have higher morbidity and mortality than other patients with BPD [46].

Neurodevelopmental outcomes — Preterm survivors with BPD compared with those without BPD are at increased risk for neurodevelopmental impairment (NDI), which can include cognitive impairment, motor impairment (including cerebral palsy), hearing loss, vision loss, and/or behavioral and mental health problems (eg, attention deficit hyperactivity disorder). (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Definitions'.)

In studies performed after the introduction of routine surfactant therapy, BPD was associated with poorer motor and cognitive performance in toddlers and preschool children [48-52]. The association between BPD and NDI persists through school age [53,54]. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Risk factors for NDI'.)

The severity of BPD correlates with NDI risk as illustrated by a study from the NICHD Neonatal Research Network [55]. In this study of 5364 ELBW infants born between 1995 and 1998, NDI was documented in 76 percent of surviving infants who were ventilated for ≥60 days, 93 percent of those ventilated for ≥90 days, and all infants 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 [56-59]. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia".)

Although changes in neonatal practice have the potential to affect neurodevelopment outcomes for infants with BPD, limited data suggest that the rates if NDI in infants with BPD have largely remained unchanged since the early 2000s [60]. There has been a reduction in the use of postnatal glucocorticoids for prevention of BPD (a practice that is associated with cerebral palsy). This is discussed in detail elsewhere. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants".)

When interpreting studies on neurodevelopmental outcomes in preterm infants, it is important to recognize that many factors influence neurodevelopment [61]. These include neonatal morbidities (eg, intraventricular hemorrhage, sepsis, necrotizing enterocolitis), neurosensory problems (eg, retinopathy of prematurity, hearing impairment), hospital course including the use of glucocorticoid therapy, postdischarge 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 — Infants with BPD often display poor growth during and after their neonatal intensive care unit (NICU) hospitalization. (See "Growth management in preterm infants", section on 'After discharge'.)

Poor growth in this population is likely multifactorial, including the increased energy expenditure associated with respiratory disease and the challenges of maintaining adequate nutrient and mineral intake in the setting of fluid restriction. (See 'Growth and nutrition' above and 'Fluid restriction' above.)

Studies reporting on long-term growth trajectories in patients with BPD have reached variable conclusions. Some studied found significant growth delays compared with patients without BPD [62,63] while other studies reported no difference after adjusting for confounding variables [64-66].

Poor growth of survivors with BPD was noted in a study that followed 20 preterm infants with BPD for two years [62]. 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 [63].

In a study of preterm 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 [65].

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 generally 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 (table 2). BPD is an important contributing factor in the increased risk of mortality and morbidity in preterm infants. (See 'Outcome' above and "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality", section on 'Definitions'.)

General supportive measures – General supportive measures for all patients with established BPD include (see 'General measures' above):

Providing adequate nutrition to promote lung growth and healing. Fortified human milk is used whenever possible because of the intrinsic benefits of human milk. (See 'Growth and nutrition' above and "Human milk feeding and fortification of human milk for premature infants" and "Growth management in preterm infants".)

For most infants with BPD, we suggest modest fluid restriction (140 to 150 mL/kg per day) rather than more liberal fluid administration (Grade 2C). Fluid restriction may help to improve pulmonary function by preventing excess pulmonary fluid accumulation. Caloric density of feeds may need to be increased to maintain fluid restriction. (See 'Fluid restriction' above.)

Respiratory support – Respiratory support is tailored to the needs of the infant. The goal is to maintain adequate gas exchange while minimizing further lung injury. Depending on the severity of lung disease, respiratory support may consist of supplemental oxygen (eg, via nasal cannula), noninvasive support (eg, nasal continuous positive airway pressure [nCPAP], noninvasive intermittent positive pressure ventilation [NIPPV], or high-flow nasal cannula [HFNC]), or invasive mechanical ventilation. (See 'Respiratory support' above and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices' and "Approach to mechanical ventilation in very preterm neonates".)

Gas exchange targets

The peripheral oxygen saturation (SpO2) goal is 90 to 95 percent initially. Once the infant reaches term, the upper limit of the target SpO2 range can be increased to >95 percent. (See "Neonatal target oxygen levels for preterm infants".)

The partial pressure of carbon dioxide (PaCO2) goal is 55 to 65 mmHg and pH goal is 7.3 to 7.4. In patients with severe BPD, PaCO2 values up to 70 mmHg may be tolerated on occasion to avoid further escalation of ventilator support. (See "Approach to mechanical ventilation in very preterm neonates", section on 'Gas exchange targets'.)

Pharmacologic therapy – Pharmacologic therapy is generally reserved for infants with moderate to severe BPD.

Diuretics – Our suggest approach to diuretic therapy in infants with BPD is as follows (See 'Diuretics' above.):

-For patients who remain ventilator-dependent or dependent on noninvasive positive pressure support (eg, nCPAP) despite modest fluid restriction, we suggest a trial of diuretic therapy (Grade 2C). We typically use a thiazide diuretic in this setting (eg, chlorothiazide or hydrochlorothiazide).

-For patients with acute pulmonary exacerbations attributed to pulmonary edema, we suggest diuretic therapy (typically single or intermittent doses of furosemide). (See 'Acute exacerbations' above.)

-For patients with BPD who require red blood cell (RBC) transfusions, we suggest a single dose of diuretic (typically furosemide) during or immediately after the transfusion (Grade 2C).

Bronchodilator therapy – For infants who have episodes of acute pulmonary decompensation with evidence of bronchoconstriction (eg, wheezing, prolonged exhalation), we suggest a trial of beta agonist therapy (eg, albuterol [salbutamol] or levalbuterol) (Grade 2C). If no benefit is seen, treatment should be discontinued. Bronchodilator therapy does not play a routine role in the management of infants with BPD in the absence of clinical signs of bronchoconstriction. (See 'Bronchodilators' above and 'Acute exacerbations' above.)

Glucocorticoids

-For prevention of BPD – The role of glucocorticoids for prevention of BPD is discussed separately. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants".)

-For treatment of established BPD – For older infants with established severe BPD who are dependent upon substantial respiratory support (eg, mechanical ventilation and high FiO2 requirement) or have evidence of airway reactivity, we suggest treatment with an inhaled glucocorticoid (Grade 2C). The rationale is that this may reduce lung inflammation and facilitate ventilator weaning. If the infant continues to have significant respiratory compromise despite beta agonist therapy and an inhaled glucocorticoid, we suggest a short (7 to 10 days) tapering course of systemic hydrocortisone (Grade 2C). We generally limit this treatment to ventilator-dependent infants >40 weeks PMA because of concerns for adverse effects on long-term neurodevelopment when used in more premature infants. (See 'Glucocorticoids' above and "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants", section on 'Adverse effects'.)

Screening for complications – All infants with BPD should routinely be screened for the following complications:

High blood pressure – Blood pressure (BP) should be monitored at least weekly in infants who remain hospitalized and at each outpatient visit after discharge. For infants with elevated BP, an evaluation should be performed to determine the underlying cause. Persistent hypertension may require treatment. (See 'Cardiovascular complications' above and "Etiology, clinical features, and diagnosis of neonatal hypertension" and "Management of hypertension in neonates and infants".)

Pulmonary hypertension – The approach to echocardiographic screening for pulmonary hypertension in infants with BPD is summarized in the figure (algorithm 1) and discussed in detail separately. (See "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Screening'.)

Neurodevelopmental impairment (NDI) – The approach to screening for NDI in high-risk preterm neonates, including those with BPD, is discussed separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Approach for follow-up care'.)

Outcome

Mortality – Infants with BPD are at higher risk of mortality compared with infants of the same GA without BPD. Among infants with severe BPD (defined as requiring invasive mechanical ventilation at 36 weeks PMA (table 2)), hospital mortality is approximately 10 percent. (See 'Mortality' above.)

Morbidities – Infants with BPD are at risk for the following complications, which are discussed in separate topic reviews:

-Hospital readmissions (see 'Hospital readmissions' above and "Care of the neonatal intensive care unit graduate", section on 'Hospital readmissions')

-Long-term pulmonary compromise (ranging from mildly reduced exercise capacity to chronic ventilator dependence) (see "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia")

-Pulmonary hypertension (see "Pulmonary hypertension associated with bronchopulmonary dysplasia")

-Systemic hypertension (see 'Cardiovascular complications' above and "Etiology, clinical features, and diagnosis of neonatal hypertension")

-NDI (See 'Neurodevelopmental outcomes' above and "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)

-Poor growth (see 'Growth' above and "Growth management in preterm infants", section on 'Long-term outcome')

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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References

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