Prevention of bronchopulmonary dysplasia
- Ann R Stark, MD
Ann R Stark, MD
- Professor of Pediatrics
- Vanderbilt University School of Medicine
- Eric C Eichenwald, MD
Eric C Eichenwald, MD
- Professor of Pediatrics
- Perelman School of Medicine, University of Pennsylvania
- Section Editors
- Richard Martin, MD
Richard Martin, MD
- Section Editor — Neonatology
- Professor, Pediatrics, Reproductive Biology, and Physiology & Biophysics
- Case Western Reserve University School of Medicine
- Gregory Redding, MD
Gregory Redding, MD
- Section Editor — Pediatric Pulmonology
- Professor of Pediatrics
- University of Washington School of Medicine
Bronchopulmonary dysplasia (BPD), also known as neonatal chronic lung disease (CLD), is an important cause of respiratory illness in preterm newborns. Factors implicated in the pathogenesis of BPD include prematurity, and inflammation caused by mechanical injury, oxygen toxicity, and infection. Many strategies have been attempted to prevent BPD. Success has been limited, in part, because the etiology of the disorder is multifactorial and multiple interventions are needed.
Potential strategies to prevent BPD are reviewed here. The pathogenesis, clinical features, management, and prognosis of this disorder are discussed separately. (See "Pathogenesis and clinical features of bronchopulmonary dysplasia" and "Management of bronchopulmonary dysplasia" and "Outcome of infants with bronchopulmonary dysplasia".)
Prematurity — Different degrees of prematurity are defined by gestational age (GA), which is calculated from the first day of the mother's last period, or birth weight (BW). Data on BPD is often based upon the following classification of preterm infants categorized by BW as follows:
●Low birth weight (LBW) − BW less than 2500 g
●Very low birth weight (VLBW) − BW less than 1500 g
- Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163:1723.
- Hascoët JM, Picaud JC, Ligi I, et al. Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age: A Randomized Clinical Trial. JAMA Pediatr 2016; 170:365.
- Laughon M, Bose C, Moya F, et al. A pilot randomized, controlled trial of later treatment with a peptide-containing, synthetic surfactant for the prevention of bronchopulmonary dysplasia. Pediatrics 2009; 123:89.
- Keller RL, Merrill JD, Black DM, et al. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res 2012; 72:613.
- Oh W, Poindexter BB, Perritt R, 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; 147:786.
- Kavvadia V, Greenough A, Dimitriou G, Hooper R. Randomised trial of fluid restriction in ventilated very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2000; 83:F91.
- Tammela OK, Lanning FP, Koivisto ME. The relationship of fluid restriction during the 1st month of life to the occurrence and severity of bronchopulmonary dysplasia in low birth weight infants: a 1-year radiological follow up. Eur J Pediatr 1992; 151:367.
- Carlo WA, Stark AR, Wright LL, et al. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants. J Pediatr 2002; 141:370.
- Mariani G, Cifuentes J, Carlo WA. Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 1999; 104:1082.
- Woodgate PG, Davies MW. Permissive hypercapnia for the prevention of morbidity and mortality in mechanically ventilated newborn infants. Cochrane Database Syst Rev 2001; :CD002061.
- Bhuta T, Henderson-Smart DJ. Elective high frequency jet ventilation versus conventional ventilation for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev 2000; :CD000328.
- Keszler M, Donn SM, Bucciarelli RL, et al. Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema. J Pediatr 1991; 119:85.
- Aly H. Is there a strategy for preventing bronchopulmonary dysplasia? Absence of evidence is not evidence of absence. Pediatrics 2007; 119:818.
- Kirpalani H, Millar D, Lemyre B, et al. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med 2013; 369:611.
- Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354:2112.
- Schmidt B, Roberts RS, Davis P, et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007; 357:1893.
- Schmidt B, Anderson PJ, Doyle LW, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA 2012; 307:275.
- Maitre NL, Stark AR. Neuroprotection for premature infants?: another perspective on caffeine. JAMA 2012; 307:304.
- Davis PG, Schmidt B, Roberts RS, et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr 2010; 156:382.
- Dobson NR, Patel RM, Smith PB, et al. Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants. J Pediatr 2014; 164:992.
- Tyson JE, Wright LL, Oh W, et al. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 1999; 340:1962.
- Darlow BA, Graham PJ. Vitamin A supplementation for preventing morbidity and mortality in very low birthweight infants. Cochrane Database Syst Rev 2000; :CD000501.
- Darlow BA, Graham PJ. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev 2011; :CD000501.
- Tolia VN, Murthy K, McKinley PS, et al. The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants. JAMA Pediatr 2014; 168:1039.
- Schreiber MD, Gin-Mestan K, Marks JD, et al. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med 2003; 349:2099.
- Van Meurs KP, Wright LL, Ehrenkranz RA, et al. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 2005; 353:13.
- Kinsella JP, Cutter GR, Walsh WF, et al. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med 2006; 355:354.
- Ballard RA, Truog WE, Cnaan A, et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 2006; 355:343.
- Mercier JC, Hummler H, Durrmeyer X, et al. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. Lancet 2010; 376:346.
- Patrianakos-Hoobler AI, Marks JD, Msall ME, et al. Safety and efficacy of inhaled nitric oxide treatment for premature infants with respiratory distress syndrome: follow-up evaluation at early school age. Acta Paediatr 2011; 100:524.
- Donohue PK, Gilmore MM, Cristofalo E, et al. Inhaled nitric oxide in preterm infants: a systematic review. Pediatrics 2011; 127:e414.
- Askie LM, Ballard RA, Cutter GR, et al. Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials. Pediatrics 2011; 128:729.
- Barrington KJ, Finer N. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev 2010; :CD000509.
- Kinsella JP, Cutter GR, Steinhorn RH, et al. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr 2014; 165:1104.
- Cole FS, Alleyne C, Barks JD, et al. NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants. Pediatrics 2011; 127:363.
- Kumar P, Committee on Fetus and Newborn, American Academy of Pediatrics. Use of inhaled nitric oxide in preterm infants. Pediatrics 2014; 133:164.
- Ballard RA, Keller RL, Black DM, et al. Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide. J Pediatr 2016; 168:23.
- Davis JM, Rosenfeld WN, Richter SE, et al. Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome. Pediatrics 1997; 100:24.
- Davis JM, Parad RB, Michele T, et al. Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. Pediatrics 2003; 111:469.
- Biniwale MA, Ehrenkranz RA. The role of nutrition in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 2006; 30:200.
- Bronchopulmonary dysplasia
- - Antenatal glucocorticoids
- - Postnatal glucocorticoids
- - Late surfactant therapy
- Fluid restriction
- Protective ventilation strategies
- - Minimal ventilation
- - Volume-targeted ventilation (VTV)
- - High frequency ventilation
- - Continuous positive airway pressure
- - Noninvasive mechanical ventilation
- - Target pulse oximetry saturation
- Vitamin A
- Ineffective or unproven interventions
- - Nitric oxide
- Our approach
- - Combination of surfactant and nitric oxide
- - Superoxide dismutase
- OUR APPROACH
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS