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Prevention of Bronchopulmonary Dysplasia (BPD)

Authors 

Poets C, Zimmermann L, Hellström-Westas L, Buonocore G, Hallman M, Lista G, van Kaam A, Kramer B

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Target group

Very preterm and particularly extremely preterm infants, small for gestational age infants, and parents

User group

Healthcare professionals, neonatal units, hospitals, and health services

Statement of standard

Bronchopulmonary Dysplasia (BPD) is prevented using evidence-based strategies including avoiding mechanical ventilation, minimally invasive administration of exogenous surfactant, volume targeted ventilation and early caffeine, and administration of systemic steroids in infants still requiring ventilation during their 2nd postnatal week.

Rationale

Bronchopulmonary Dysplasia BPD results from the effects of non-physiologic stimuli (e.g. inflammation, ventilator induced lung injury, high supplemental oxygen levels) in an infant with underdeveloped lungs and defence mechanisms (e.g. anti-oxidant capacity). (1) Interventions that reduce inflammation (e.g. steroids) or any of these non-physiologic stimuli (e.g. mechanical ventilation) are likely to reduce BPD rates. Some of these interventions may additionally promote the survival of the target group; none decreases the chances of survival. (2)

BPD, defined as supplemental oxygen requirement at 36 weeks post-menstrual age, is a risk factor for later respiratory hospitalisation in infancy, compromised lung function in childhood, neurodevelopmental impairment, and a potential risk factor for chronic obstructive pulmonary disease in later life. (1,3)

Benefits

Short-term benefits

  • Reduced risk of BPD by avoiding invasive mechanical ventilation (risk ratio (RR), 0.91; 95% Confidence Interval 0.84-0.99) (2)
  • Reduced risk of BPD by use of minimally invasive surfactant administration (RR 0.75; 0.59-0.94) (4,5)
  • Reduced risk of BPD by use of volume targeted ventilation (as opposed to pressure targeting) (RR 0.61; 0.46-0.82) (6)
  • Reduced risk of BPD by starting caffeine on postnatal day one or two instead of later (RR 0.51; 0.40-0.64) (7,8)
  • Reduced risk of BPD by administration of vitamin A intramuscularly for the first four postnatal weeks (RR 0.87; 0.77-0.98) (9)
  • Reduced rate of death or BPD by administration of systemic steroids in ventilated infants (RR 0.72; 0.63-0.82) without increasing the risks of cerebral palsy (10)

Long-term benefits

  • Reduced adverse neurodevelopmental outcome if BPD can be prevented (3)

 

Components of the standard

Component Grading of evidence Indicator of meeting the standard
For parents and family    
1. Parents are informed by healthcare professionals about Bronchopulmonary Dysplasia (BPD) and strategies to minimise its risk. (1) A (High quality) Patient information sheet
       
For healthcare professionals    
2. A unit guideline on the management and prevention BPD is adhered to by all healthcare professionals, and includes the following advice:

  • Surfactant is administered via a thin intra-tracheal catheter if FiO2 is >0.30 or using INSURE (intubate surfactant extubate). (11)
  • Volume targeted ventilation (at 5-7 ml/kg) is used plus adequate PEEP level, if intubation cannot be avoided. (6)
  • Infants on n-CPAP are switched to synchronised nasal ventilation if respiratory distress visible while on CPAP. (12)
  • Caffeine is administered from day 1-2 after birth (10 mg/kg loading, 5 mg/kg/d maintenance for caffeine base). (7,8)
  • Vitamin A is considered (5000 IE i.m. three times/week for week 1-4 after birth). (9)
  • If mechanical ventilation is still necessary during postnatal week 2, postnatal steroid use is considered (dexame­tha­sone at the lowest effective dose possible. (13,14))
  • Efforts to reduce rates of nosocomial infection, as a risk factor for BPD, are made. (15)
A (High quality) Guideline
       
3. Training on the management and prevention of BPD is attended by all responsible healthcare professionals. B (High quality) Training documentation
       
For neonatal unit    
4. A unit guideline on prevention and management of BPD is available and regularly updated. B (High quality) Guideline
       
For hospital    
5. Training on management and prevention of BPD is ensured. B (High quality) Training documentation
       
6. Institutional BPD rates are monitored together with length of hospital stay and use of supplemental oxygen. B (High quality) Audit report
       
For health service    
7. A national guideline on management and prevention of BPD is available and regularly updated. B (High quality) Guideline
       

Where to go

Further development Grading of evidence
For parents and family  
N/A  
For healthcare professionals  
  • Investigate in larger numbers whether using synchronised nasal ventilation rather than CPAP is the preferred mode of nasal respiratory support. (6)
A (Moderate quality)
  • Evaluate alternative anti-inflammatory strategies, e.g. hydrocortisone, inhaled budesonide, or tracheal instillation of budesonide together with exogenous surfactant to generate more data on their long-term effectiveness and safety. (10,16,17)
A (High quality)
  • Investigate the role of eradicating Ureaplasma urealyticum shortly after birth. (18)
A (Moderate quality)
  • Investigate oral Vitamin A administration as well as the role of other nutrients. (9,19)
A (High quality)
  • Find the optimal drug and dose for postnatal steroid application. (9)
A (Moderate quality)
  • Investigate the potential of mesenchymal stem cells in repairing the injured immature lung. (20,21)
A (High quality)
  • Investigate the effect of various delivery-room practices (e.g. sustained inflations) and of early enteral feeding on the prevention of BPD. (22)
A (Moderate quality)
For neonatal unit  
N/A  
For hospital  
N/A  
For health service  
N/A  
   

Getting started

Initial steps
For parents and family
  • Parents are verbally informed by healthcare professionals about BPD and strategies to minimise its risk. (1)
For healthcare professionals
  • Attend training on management and prevention of BPD.
  • Apply exogenous surfactant via less/minimally invasive administration via a thin catheter, i.e. without using an endotracheal tube, or via the INSURE method (intubate, surfactant, extubate).
  • Use nasal continuous positive airway pressure (n-CPAP) instead of intubation and mechanical ventilation. (22)
  • Start caffeine on postnatal day 1 or 2 instead of later.
For neonatal unit
  • Develop and implement a unit guideline on management and prevention of BPD.
  • Develop information material about BPD for parents.
For hospital
  • Support healthcare professionals to participate in training on management and prevention BPD.
For health service
  • Develop and implement a national guideline on management and prevention of BPD.
 

Sources

  1. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007 Nov 8;357(19):1946–55.
  2. Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F285–91.
  3. Schmidt B, Asztalos EV, Roberts RS, Robertson CMT, Sauve RS, Whitfield MF, et al. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124–9.
  4. Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2017 Jan;102(1):F17–23.
  5. Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003063.
  6. Peng W, Zhu H, Shi H, Liu E. Volume-targeted ventilation is more suitable than pressure-limited ventilation for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F158-165.
  7. Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2010 Mar;156(3):382–7.
  8. Park HW, Lim G, Chung S-H, Chung S, Kim KS, Kim S-N. Early Caffeine Use in Very Low Birth Weight Infants and Neonatal Outcomes: A Systematic Reviewand Meta-Analysis. J Korean Med Sci. 2015 Dec;30(12):1828–35.
  9. Darlow BA, Graham PJ, Rojas-Reyes MX. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2016 Aug 22;(8):CD000501.
  10. Doyle LW, Ehrenkranz RA, Halliday HL. Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 13;(5):CD001145.
  11. Kribs A, Roll C, Göpel W, Wieg C, Groneck P, Laux R, et al. Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2015 Aug;169(8):723–30.
  12. Lemyre B, Davis PG, De Paoli AG, Kirpalani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2014 Sep 4;(9):CD003212.
  13. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, DART Study Investigators. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics. 2006 Jan;117(1):75–83.
  14. Onland W, Offringa M, Jaegere APD, Kaam AH van. Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials. Pediatrics. 2009 Jan 1;123(1):367–77.
  15. Lapcharoensap W, Kan P, Powers RJ, Shaw GM, Stevenson DK, Gould JB, et al. The Relationship of Nosocomial Infection Reduction to Changes in Neonatal Intensive Care Unit Rates of Bronchopulmonary Dysplasia. J Pediatr. 2017 Jan;180:105–109.e1.
  16. Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet Lond Engl. 2016 Apr 30;387(10030):1827–36.
  17. Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, et al. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86–95.
  18. Smith C, Egunsola O, Choonara I, Kotecha S, Jacqz-Aigrain E, Sammons H. Use and safety of azithromycin in neonates: a systematic review. BMJ Open. 2015 Dec;5(12):e008194.
  19. Meyer S, Gortner L, NeoVitaA Trial investigators. Up-date on the NeoVitaA Trial: Obstacles, challenges, perspectives, and local experiences. Wien Med Wochenschr 1946. 2017 Sep;167(11–12):264–70.
  20. O’Reilly M, Thébaud B. Stem Cells for the Prevention of Neonatal Lung Disease. Neonatology. 2015;107:360–4.
  21. Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, et al. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014 May;164(5):966–972.e6.
  22. Schmölzer GM, Kumar M, Pichler G, Aziz K, O’Reilly M, Cheung P-Y. Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis. BMJ. 2013 Oct 17;347:f5980.

November 2018 / 1st edition / next revision: 2021

Recommended citation

EFCNI, Poets C, Zimmermann L et al., European Standards of Care for Newborn Health: Prevention of Bronchopulmonary Dysplasia (BPD). 2018.

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