BPD: Complication of prematurity

March 1, 2017

Despite improvements in obstetric and neonatal care leading to increased survival of premature infants, little progress has been made in the prevention of bronchopulmonary dysplasia. Pediatricians need to be aware of changing definitions, risk factors, prevention, and long-term health outcomes of this disease in their premature patients.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease usually following mechanical ventilation and oxygen therapy in premature infants requiring treatment for acute respiratory distress. Despite improvements in obstetric and neonatal care leading to increased survival of premature infants, little progress has been made in the prevention of BPD. Pediatricians need to be aware of changing definitions, risk factors, prevention, and long-term health outcomes of this disease in their premature patients.

Definition of BPD

The definition of BPD has undergone multiple changes since Northway’s1 original description in 1967. A 2001 workshop sponsored by the National Institute of Child Health and Human Development (NICHD) proposed to define BPD in the following manner based on severity:2-5

The NICHD definition was shown to better predict pulmonary outcomes (eg, requirement for pulmonary medication, rehospitalization) and neurodevelopment outcomes at age 18 to 22 months (eg, lower development index scores, cerebral palsy, hearing loss, blindness) compared with previous definitions.6 The definition is still under significant debate and research. More recent investigations found that significant respiratory morbidity is best predicted by oxygen use and respiratory support at 40 weeks PMA. Also, more recent studies find the prediction of neurosensory impairment to be less strong.5

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In terms of pathology of the lung disease, airway injury, inflammation, and fibrosis were seen prior to development of surfactant as a treatment in the 1980s. In the “new” postsurfactant BPD, the more prominent pathology is reduced surface area availability for gas exchange from alveolar hypoplasia and fewer and larger alveoli. Dysregulation of the pulmonary vasculature also contributes.7-9

Risk factors

Bronchopulmonary dysplasia is a multifactorial disease, including both antenatal and postnatal factors, leading to a disruption in pulmonary development, inflammation, and damage to the lungs.10 

Higher levels of inflammatory markers are noted in infants that develop BPD. However, whether this inflammation is attributed to another disease process such as chorioamnionitis, the exact role of inflammation in the pathogenesis remains a significant area of study.20 Likewise, whether there is a genetic predisposition to BPD remains controversial as recent research has demonstrated mixed results.21-23

 

NEXT: Prevention

 

Prevention

Current strategies for prevention of and treatment for BPD include:

Antenatal steroids

Decreasing the number of premature infants by advancing obstetric care will decrease the number of infants at risk for BPD. Antenatal steroids given to pregnant women from 23 to 34 weeks GA who are at risk for preterm delivery decreases the risk of respiratory distress syndrome, intraventricular hemorrhage, and overall mortality related to preterm delivery.24 However, this has not resulted in a decreased incidence of BPD. Although multifactorial, the reason is possibly that more infants are surviving and thus at increased risk for BPD.25,26

Postnatal glucocorticoids

Postnatal steroids for the prevention of BPD is an area of great debate in neonatology. Although there is evidence that administration of steroids decreases the incidence of BPD, adverse effects appear to diminish any benefit. In addition to short-term adverse events such as hyperglycemia, hypertension, and increased infection risk, long-term follow-up has demonstrated poor neurodevelopment outcomes including cerebral palsy.2 There are some instances in which steroids may be beneficial, but the type of steroid and which patients to consider need to be individualized.27-29 Similarly, inhaled steroids are not routinely recommended and have not been found to prevent BPD, but may be useful in certain limited scenarios.30-33

Surfactant

Surfactant, as mentioned previously, has changed the pathophysiology of BPD. However, it has not decreased the incidence of BPD for reasons similar to those for antenatal steroids. A strategy called the INSURE (Intubation-Surfactant-Extubation) approach combining brief intubation after birth for administration of surfactant and followed by extubation/use of nasal continuous positive airway pressure (CPAP) has demonstrated a decreased risk of BPD.2,34

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Mechanical ventilation

A number of different ventilation strategies have been employed to attempt to decrease rates of BPD. In addition to the INSURE approach, volume targeted strategies have decreased BPD compared with pressure-limited strategies of ventilation.35 Other ventilatory modes that demonstrate possible decreases in BPD include nasal intermittent mandatory ventilation, while permissive hypercapnia and jet ventilation have not decreased rates of BPD.36-39

Vitamin A

Low vitamin A levels are associated with development of BPD, and vitamin A is part of the internal processes for lung development and repair. Whereas administration of vitamin A decreases risk of BPD, there has not been a decrease in neurodevelopment complications associated with BPD.2

Azithromycin

Although this antibiotic has not decreased BPD rates overall, its administration decreases BPD in the previously mentioned group at higher risk because of Ureaplasma urealyticum infection.2

Nutrition and fluid restriction

Preterm infants at risk of BPD are often fluid restricted as volume overload in the first 10 days of life is hypothesized (and supported by retrospective research) as a risk factor for the development of BPD.40 However trials of fluid restriction have been small and produced mixed results.41,42 Given the outcomes associated with BPD, modest fluid restriction may be warranted, especially in the setting of patients with patent ductus arteriosus (PDA).

Caffeine

Even though the mechanism is not known, administration of caffeine for the treatment of apnea of prematurity demonstrated a decrease in BPD.43,44

Nitric oxide

Nitric oxide has not demonstrated a benefit in the prevention of BPD, unlike its use for treating persistent pulmonary hypertension. Although some studies have demonstrated a benefit, no systematic review shows advantages related to pulmonary outcomes, survival, or neurodevelopment outcomes. Neither the National Institute of Health consensus conference45 or a 2014 AAP clinical report46 recommend routine administration of nitric oxide for the prevention of BPD.

 

 

NEXT: Long-term health consequences

 

 

Long-term health consequences

Bronchopulmonary dysplasia also can lead to health problems for these infants later in life, such as:

Asthma-like symptoms

Asthma-like symptoms and recurrent wheezing are extremely common in children with BPD. However the pathophysiology is different in that airway hyperresponsiveness is less common and symptoms are less responsive to bronchodilators and inhaled corticosteroids.47,48

Pulmonary arterial hypertension (PAH)

Whereas PAH generally resolves as the infant gets older, it is a significant cause of mortality in patients with BPD.49,50 Optimal timing for screening has not yet been established, however, guidelines from the American Heart Association and the American Thoracic Society recommend screening all infants with BPD for PAH and continue serial echocardiograms until the clinical picture is stabilized if PAH is present.51

Central airway disease

A number of problems with the central airways can complicate BPD and can persist as an infant ages. Acquired tracheobronchomalacia is more common in the presurfactant treatment period of BPD and is associated with both barotrauma and infection. Because the airway is more compliant and collapsible, the infant is at risk for “BPD spells” or abrupt episodes of apnea that may lead to a cyanotic episode (that can be life threatening) or chronic wheezing that does not respond to treatment.52

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Subglottic stenosis and laryngeal injury manifested as postextubation stridor may be seen in infants requiring prolonged or frequent intubations. Infants may experience chronic symptoms or only experience symptoms with upper respiratory tract infections.53 Tracheal and bronchial stenosis also are reported but are more likely a result of intubation and suctioning rather than from lung disease. Nevertheless, lobar emphysema, atelectasis, and overdistension can result.

Upper airway problems

Chronic snoring and sleep apnea are more common among premature infants as they get older.54,55 Untreated sleep apnea is associated with decreased intelligence quotient (IQ) and executive function, as well as possible neuronal injury.56

Hypoventilation and hypoxemic episodes during sleep are more likely to occur in infants with a history of BPD and may persist as children get older.57,58 This can result in further narrowing of airways as well as problems with pacemaker activities of the heart,59 growth delay,60 and cognitive development.56

Respiratory infections

Hospitalization during the first 2 years of life is common among patients with BPD.61 Mostly attributed to viral infections that can further impair respiratory function, respiratory syncytial virus (RSV) infections can be particularly severe, especially for infants still with an oxygen requirement.61,62 An RSV infection in a BPD patient during the first 2 years of life is associated with worse long-term health outcomes (eg, increased costs and decreased lung function) compared with a BPD patient not having an RSV infection.62

Neurodevelopment outcomes

Infants with BPD are at risk for long-term neurodevelopment impairment as evidenced by decreased scores on the mental and motor scales of the Bayley Scales of Infant Development.63

These low scores have been found to persist at 3 years of age in addition to lower expressive and receptive language skills.64,65 Other reports have demonstrated that these poor neurodevelopment outcomes persist through age 10 years.66,67 In general, the severity of the BPD is associated with the severity of the neurodevelopment disability.

NEXT: Summary

 

Summary

Bronchopulmonary dysplasia is a chronic disease that can impact the pediatric patient well beyond early life. The pediatrician needs to be aware of both strategies for prevention as well as the long-term consequences that need to be managed to improve the health and outcomes of these patients.

Next: Neonate with acute respiratory distress

 

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Dr Bass is chief medical information officer and associate professor of medicine and of pediatrics, Louisiana State University Health Sciences Center–Shreveport. The author has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.