Predictors of Bronchopulmonary Dysplasia
Introduction
Although significant advances in respiratory care have been made in neonatal medicine, bronchopulmonary dysplasia (BPD) remains the most common serious pulmonary morbidity in premature infants. Premature infants with BPD have a longer initial hospitalization than their peers without BPD.1 BPD remains a substantial lifelong burden. The costs of the disorder are both social and economic, and are measured in impaired childhood health and quality of life, family stress, economic hardship, and increased health care costs.2, 3, 4
Over the past 40 years, the definition, disease, and risk factors for BPD have changed.5, 6 BPD, as it was initially described by Northway and colleages7 in the 1960s, was based on clinical and radiographic evidence of pulmonary disease in moderately to late premature infants with a history of respiratory distress syndrome. The respiratory management of these infants included exposure to prolonged mechanical ventilation and oxygen exposure. On histologic samples, the characteristic areas of hyperinflation alternating with areas of focal collapse were often noted, and hyperplasia of the bronchial epithelium.8 Radiography of these infants showed areas of heterogeneity throughout the lung fields and coarse scattered opacities in the most severely affected of infants.9
The classical BPD described by Northway and colleagues has been replaced by a milder form of the disease. There is reason to believe that risk factors associated with the “new” BPD, compared with historical risk factors, may be distinct. This new BPD occurs in less mature infants exposed to antenatal steroids, who are often treated with exogenous surfactant therapy. They spend fewer days on positive pressure ventilation and have less exposure to supplemental oxygen. Animal studies suggest that the histology of new BPD shows more diffuse disease, fewer areas of hyperinflation, and a reduction in alveoli and capillaries, but little fibrosis.10, 11
The incidence of BPD varies widely between centers, even after adjusting for potential risk factors. Data from 2010 from the Vermont Oxford Network show that the rates of BPD vary from 12% to 32% among infants born at less than 32 weeks’ gestation. Although multiple trials have been aimed at reducing the incidence of BPD, the incidence seems to be stagnant, or even increasing. The rising absolute number of infants with BPD might be caused by the improvement in the survival of extremely low gestational age infants, the population most likely to have this diagnosis.5, 12, 13 Compared with the pathology described by Northway and colleagues, the most common type of BPD today may be a less severe form of the disease.
This article reviews the definitions of BPD and the predictors of BPD by time period (before, at, and after birth). Several of the estimators that are available to quantify the risk of BPD, and to explain how this might affect clinicians, families, and researchers, are also reviewed.
Section snippets
Defining BPD
The definition of BPD most often uses receipt of oxygen therapy or positive pressure for a duration of time (usually in days) or on a specific day (eg, postnatal day 28 or at postmenstrual age [PMA] 36 weeks). The original definition was based on receipt of oxygen at 28 days of age. However, this definition does not take into account the various developmental considerations of infants born across the spectrum of susceptible gestational ages. Thus, attempts have been made to improve the
Understanding and interpreting the predictors of BPD
Predictors of disease are more commonly known as risk factors. In epidemiologic studies, risk is most often used synonymously with probability of disease occurrence; however, it may represent a wide variety of statistical measures that include incidence, prevalence, rate, or odds. A risk factor often implies an increase in the outcome of interest with exposure, although risk measures may also represent protective effects.20
In many studies, risks are often compared through relative measures, as
Antenatal Steroids
Antenatal steroids are associated with a decrease in both severity of respiratory distress syndrome and neonatal mortality.28, 29 Therefore, antenatal steroids were initially believed to decrease the risk of BPD.30 In a multivariate analysis, Van Marter and colleagues31 examined the independent effect of antenatal steroids on the risk of BPD. They found that treatment with either a partial or full course of antenatal steroids did not convey any additional benefit in reducing the likelihood of
Infant Demographics: Gestational Age, Birth Weight, and Sex
Extreme prematurity and extremely-low-birth-weight have been well established as risk factors for BPD. Gestational age and birth weight are inversely proportional to the incidence of BPD and the severity of the disease. Among infants meeting the physiologic definition of BPD at 36 weeks’, 95% are very-low-birth-weight (VLBW).16 In the NICHD network, the incidence of BPD at 23 weeks’ PMA (as defined as oxygen at 36 weeks’ PMA) was 73%, with 56% of infants having severe BPD. In comparison, at 28
Respiratory Patterns
Describing the early respiratory patterns of extremely low gestational age newborns may provide insight into early risk factors for BPD. Among these infants, three distinct patterns of lung disease typically emerge in the first 2 weeks of life.43, 44, 45, 46, 47 The first pattern includes infants with little lung disease, who progressively recover. The second group of infants experiences early persistent pulmonary dysfunction and requires significant and prolonged respiratory support from
Predictive models of BPD
In the past decade, researchers have developed predictive models for long-term morbidities, such as neurodevelopmental impairment. Schmidt and colleagues92 examined the impact of BPD, brain injury, and severe retinopathy on 18-month outcomes and determined that the incidence of poor long-term outcomes increased with the presence of one, two, or all three neonatal morbidities. Tyson and colleagues93 examined infants in the Neonatal Research Network and determined that exposure to antenatal
Summary
The development of bronchopulmonary dysplasia is the result of the complex interactions between multiple perinatal and postnatal factors. Although predictive factors for BPD are easy to identify, they are often difficult to modify. Early identification of infants at the greatest risk of developing BPD through the use of estimators and models may allow a targeted approach for reducing BPD in the future.
References (104)
- et al.
General and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia: a systematic review
Chest
(2012) - et al.
Bronchopulmonary dysplasia
Pediatr Clin North Am
(1986) - et al.
Does labor influence neonatal and neurodevelopmental outcomes of extremely-low-birth-weight infants who are born by cesarean delivery?
Am J Obstet Gynecol
(2003) - et al.
Outcomes of extremely low birth weight infants with bronchopulmonary dysplasia: impact of the physiologic definition
Early Hum Dev
(2012) - et al.
Association between fluid intake and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants
J Pediatr
(2005) - et al.
Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease
J Pediatr
(1995) - et al.
Antenatal glucocorticoid treatment does not reduce chronic lung disease among surviving preterm infants
J Pediatrics
(2001) Preterm histologic chorioamnionitis: impact on cord gas and pH values and neonatal outcome
Am J Obstet Gynecol
(2006)Impact on neonatal outcome and anthropometric growth in very low birth weight infants with histological chorioamnionitis
J Formos Med Assoc
(2008)Increased risk of bronchopulmonary dysplasia in infants with patent ductus arteriosus
J Pediatr
(1979)
The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: reexamining a randomized controlled trial
J Pediatr
Prolonged hospital stay for extremely premature infants: risk factors, center differences, and the impact of mortality on selecting a best-performing center
J Perinatol
Early motor and mental development in very preterm infants with chronic lung disease
Arch Dis Child Fetal Neonatal Ed
Financial and emotional cost of bronchopulmonary dysplasia
Clin Pediatr
Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era
Arch Dis Child Fetal Neonatal Ed
Impact of improved survival of very low-birth-weight infants on incidence and severity of bronchopulmonary dysplasia
Biol Neonate
Pulmonary disease following respirator therapy of hyaline-membrane disease
N Engl J Med
Barotrauma to the lung
Decreased alveolarization in baboon survivors with bronchopulmonary dysplasia
Am J Respir Crit Care Med
The new BPD: an arrest of lung development
Pediatr Res
Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age <32 weeks): the Project On Preterm and Small for Gestational Age Infants 1983 and the Leiden Follow-Up Project on Prematurity 1996-1997
Pediatrics
Bronchopulmonary dysplasia
Am J Respir Crit Care Med
Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia
Pediatrics
Impact of a physiologic definition on bronchopulmonary dysplasia rates
Pediatrics
Diuretics for respiratory distress syndrome in preterm infants
Cochrane Database Syst Rev
Development of a proxy-reported pulmonary outcome scale for preterm infants with bronchopulmonary dysplasia
Health Qual Life Outcomes
Clinical epidemiology
Modern epidemiology
Identifiability, exchangeability, and epidemiological confounding
Int J Epidemiol
The environment and disease: association or causation?
Proc R Soc Med
Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association
Pediatrics
Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure
J Perinatol
The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials
Br J Obstet Gynaecol
Effect of corticosteroids for fetal maturation on perinatal outcomes
JAMA
Maternal glucocorticoid therapy and reduced risk of bronchopulmonary dysplasia
Pediatrics (Evanston)
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth
Cochrane Database Syst Rev
Histological chorioamnionitis and respiratory outcome in preterm infants
Arch Dis Child Fetal Neonatal Ed
Outcome of neonates less than 30 weeks gestation with histologic chorioamnionitis
Am J Perinatol
Histologic chorioamnionitis and severity of illness in very low birth weight newborns
Pediatr Crit Care Med
Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis
Arch Dis Child Fetal Neonatal Ed
Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation
Pediatrics
Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants
Am J Respir Crit Care Med
Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network
Pediatrics
Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996
Pediatrics
Atypical chronic lung disease patterns in neonates
Pediatrics
Atypical chronic lung disease in preterm infants
J Perinat Med
Clinical characteristics of chronic lung disease without preceding respiratory distress syndrome in preterm infants
Pediatr Int
Risk factors for the different types of chronic lung diseases of prematurity according to the preceding respiratory distress syndrome
Pediatr Int
The epidemiology of atypical chronic lung disease in extremely low birth weight infants
J Perinatol
Outcomes of extremely low birth weight (<1 kg) and extremely low gestational age (<28 weeks) infants with bronchopulmonary dysplasia: effects of practice changes in 2000 to 2003
Pediatrics
Cited by (0)
Dr Laughon receives support from the U.S. government for his work in pediatric and neonatal clinical pharmacology (government contract HHSN267200700051C, PI: Benjamin under the Best Pharmaceuticals for Children's Act), and from the National Institute of Child Health & Human Development (1K23HL092225-01).