Delivery room interventions to prevent bronchopulmonary dysplasia in extremely preterm infants


Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory complication of preterm birth. Preterm infants are at risk for acute lung injury immediately after birth, which predisposes to BPD. In this article, we review the current evidence for interventions applied during neonatal transition (delivery room and first postnatal hours of life) to prevent BPD in extremely preterm infants: continuous positive airway pressure (CPAP), sustained lung inflation, supplemental oxygen use during neonatal resuscitation, and surfactant therapy including less-invasive surfactant administration. Preterm infants should be stabilized with CPAP in the delivery room, reserving invasive mechanical ventilation for infants who fail non-invasive respiratory support. For infants who require endotracheal intubation and mechanical ventilation soon after birth, surfactant should be given early (<2 h of life). We recommend prudent titration of supplemental oxygen in the delivery room to achieve targeted oxygen saturations. Promising interventions that may further reduce BPD, such as sustained inflation and non-invasive surfactant administration, are currently under investigation.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2


  1. 1

    Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314: 1039–1051.

  2. 2

    Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF, Morrow KA et al. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics 2012; 129: 1019–1026.

  3. 3

    Laughon MM, Langer JC, Bose CL, Smith PB, Ambalavanan N, Kennedy KA et al. Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants. Am J Respir Crit Care Med 2011; 183: 1715–1722.

  4. 4

    Klinger G, Sokolover N, Boyko V, Sirota L, Lerner-Geva L, Reichman B et al. Perinatal risk factors for bronchopulmonary dysplasia in a national cohort of very-low-birthweight infants. Am J Obstet Gynecol 2013; 208: 115.e1–9.

  5. 5

    Doyle LW, Faber B, Callanan C, Freezer N, Ford GW, Davis NM . Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence. Pediatrics 2006; 118: 108–113.

  6. 6

    Fawke J, Lum S, Kirkby J, Hennessy E, Marlow N, Rowell V et al. Lung function and respiratory symptoms at 11 years in children born extremely preterm: the Epicure study. Am J Respir Crit Care Med 2010; 182: 237–245.

  7. 7

    Sanchez-Solis M, Garcia-Marcos L, Bosch-Gimenez V, Pérez-Fernandez V, Pastor-Vivero MD, Mondéjar-Lopez P . Lung function among infants born preterm, with or without bronchopulmonary dysplasia. Pediatr Pulmonol 2012; 47: 674–681.

  8. 8

    Vollsæter M, Røksund OD, Eide GE, Markestad T, Halvorsen T . Lung function after preterm birth: development from mid-childhood to adulthood. Thorax 2013; 68: 767–776.

  9. 9

    Natarajan G, Pappas A, Shankaran S, Kendrick DE, Das A, Higgins RD et al. Outcomes of extremely low birth weight infants with bronchopulmonary dysplasia: impact of the physiologic definition. Early Hum Dev 2012; 88: 509–515.

  10. 10

    Wang L-Y, Luo H-J, Hsieh W-S, Hsu C-H, Hsu H-C, Chen P-S et al. Severity of bronchopulmonary dysplasia and increased risk of feeding desaturation and growth delay in very low birth weight preterm infants. Pediatr Pulmonol 2010; 45: 165–173.

  11. 11

    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; 289: 1124–1129.

  12. 12

    Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA et al. Validation of the national institutes of health consensus definition of bronchopulmonary dysplasia. Pediatrics 2005; 116: 1353–1360.

  13. 13

    Short EJ, Klein NK, Lewis BA, Fulton S, Eisengart S, Kercsmar C et al. Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. Pediatrics 2003; 112: e359.

  14. 14

    Björklund LJ, Ingimarsson J, Curstedt T, John J, Robertson B, Werner O et al. Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs. Pediatr Res 1997; 42: 348–355.

  15. 15

    Hillman NH, Moss TJM, Kallapur SG, Bachurski C, Pillow JJ, Polglase GR et al. Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep. Am J Respir Crit Care Med 2007; 176: 575–581.

  16. 16

    Albertine KH, Jones GP, Starcher BC, Bohnsack JF, Davis PL, Cho SC et al. Chronic lung injury in preterm lambs. Disordered respiratory tract development. Am J Respir Crit Care Med 1999; 159: 945–958.

  17. 17

    Wallace MJ, Probyn ME, Zahra VA, Crossley K, Cole TJ, Davis PG et al. Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs. Respir Res 2009; 10: 19.

  18. 18

    Heldt GP, McIlroy MB . Distortion of chest wall and work of diaphragm in preterm infants. J Appl Physiol (1985) 1987; 62: 164–169.

  19. 19

    Heldt GP, McIlroy MB . Dynamics of chest wall in preterm infants. J Appl Physiol (1985) 1987; 62: 170–174.

  20. 20

    Barker PM, Gowen CW, Lawson EE, Knowles MR . Decreased sodium ion absorption across nasal epithelium of very premature infants with respiratory distress syndrome. J Pediatr 1997; 130: 373–377.

  21. 21

    Obladen M . Factors influencing surfactant composition in the newborn infant. Eur J Pediatr 1978; 128: 129–143.

  22. 22

    Jensen EA, Foglia EE, Schmidt B . Evidence-based pharmacologic therapies for prevention of bronchopulmonary dysplasia: application of the grading of recommendations assessment, development, and evaluation methodology. Clin Perinatol 2015; 42: 755–779.

  23. 23

    Shinwell ES, Portnov I, Meerpohl JJ, Karen T, Bassler D . Inhaled corticosteroids for bronchopulmonary dysplasia: a meta-analysis. Pediatrics 2016; 138: e20162511.

  24. 24

    Lemyre B, Laughon M, Bose C, Davis PG . Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants. Cochrane Database Syst Rev 2016; 12: CD005384.

  25. 25

    Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987; 79: 26–30.

  26. 26

    Lindner W, Vossbeck S, Hummler H, Pohlandt F . Delivery room management of extremely low birth weight infants: spontaneous breathing or intubation? Pediatrics 1999; 103: 961–967.

  27. 27

    Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB et al. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008; 358: 700–708.

  28. 28

    Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010; 362: 1970–1979.

  29. 29

    Dunn MS, Kaempf J, de Klerk A, de Klerk R, Reilly M, Howard D et al. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics 2011; 128: e1069–e1076.

  30. 30

    Fischer HS, Bührer C . Avoiding endotracheal ventilation to prevent bronchopulmonary dysplasia: a meta-analysis. Pediatrics 2013; 132: e1351–e1360.

  31. 31

    Schmolzer M, Kumar M, Pichler G, Aziz K, O'Reilly M, Cheung -Y . Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis. BMJ 2013; 347: f5980.

  32. 32

    Subramaniam P, Ho JJ, Davis PG . Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database Syst Rev 2016; 6: CD001243.

  33. 33

    Committee on fetus and newborn. Respiratory support in preterm infants at birth. Pediatrics 2014; 133: 171–174.

  34. 34

    Vyas H, Milner AD, Hopkin IE, Boon AW . Physiologic responses to prolonged and slow-rise inflation in the resuscitation of the asphyxiated newborn infant. J Pediatr 1981; 99: 635–639.

  35. 35

    Harling AE, Beresford MW, Vince GS, Bates M, Yoxall CW . Does sustained lung inflation at resuscitation reduce lung injury in the preterm infant? Arch Dis Child Fetal Neonatal Ed 2005; 90: F406–F410.

  36. 36

    Lindner W, Högel J, Pohlandt F . Sustained pressure—controlled inflation or intermittent mandatory ventilation in preterm infants in the delivery room? A randomized, controlled trial on initial respiratory support via nasopharyngealtube. Acta Paediatr 2005; 94: 303–309.

  37. 37

    te Pas AB, Walther FJ . A randomized, controlled trial of delivery-room respiratory management in very preterm infants. Pediatrics 2007; 120: 322–329.

  38. 38

    Lista G, Boni L, Scopesi F, Mosca F, Trevisanuto D, Messner H et al. Sustained lung inflation at birth for preterm infants: a randomized clinical trial. Pediatrics 2015; 135: e457–e464.

  39. 39

    Jiravisitkul P, Rattanasiri S, Nuntnarumit P . Randomised controlled trial of sustained lung inflation for resuscitation of preterm infants in the delivery room. Resuscitation 2017; 111: 68–73.

  40. 40

    Schmölzer GM, Kumar M, Aziz K, Pichler G, O'Reilly M, Lista G et al. Sustained inflation versus positive pressure ventilation at birth: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2014; 100: F361–F368.

  41. 41

    Foglia EE, Owen LS, Thio M, Ratcliffe SJ, Lista G, Te Pas A et al. Sustained aeration of infant lungs (SAIL) trial: study protocol for a randomized controlled trial. Trials 2015; 16: 95.

  42. 42

    Assessment of Lung Aeration at Birth. Clinicaltrials.Gov Identifier NCT01739114. Available at Accessed 31 March 2017.

  43. 43

    Dawson JA, Kamlin CO, Vento M, Wong C, Cole TJ, Donath SM et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics 2010; 125: e1340–e1347.

  44. 44

    Vento M, Cubells E, Escobar JJ, Escrig R, Aguar M, Brugada M et al. Oxygen saturation after birth in preterm infants treated with continuous positive airway pressure and air: assessment of gender differences and comparison with a published nomogram. Arch Dis Child Fetal Neonatal Ed 2013; 98: F228–F232.

  45. 45

    Mian QN, Pichler G, Binder C, O'Reilly M, Aziz K, Urlesberger B et al. Tidal volumes in spontaneously breathing preterm infants supported with continuous positive airway pressure. J Pediatr 2014; 165: 702–706.

  46. 46

    Lundstrom E, Pryds O, Greisen G . Oxygen at birth and prolonged cerebral vasoconstriction in preterm infants. Arch Dis Child Fetal Neonatal Ed 1995; 73: F81–F86.

  47. 47

    Harling AE, Beresford MW, Vince GS, Bates M, Yoxall CW . Does the use of 50% oxygen at birth in preterm infants reduce lung injury? Arch Dis Child Fetal Neonatal Ed 2005; 90: F401–F405.

  48. 48

    Wang CL, Anderson C, Leone TA, Rich W, Govindaswami B, Finer NN . Resuscitation of preterm neonates by using room air or 100% oxygen. Pediatrics 2008; 121: 1083–1089.

  49. 49

    Vento M, Moro M, Escrig R, Arruza L, Villar G, Izquierdo I et al. Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics 2009; 124: e439–e449.

  50. 50

    Rabi Y, Singhal N, Nettel-Aguirre A . Room-air versus oxygen administration for resuscitation of preterm infants: the ROAR study. Pediatrics 2011; 128: e374–e381.

  51. 51

    Armanian AM, Badiee Z . Resuscitation of preterm newborns with low concentration oxygen versus high concentration oxygen. J Res Pharm Pract 2012; 1: 25–29.

  52. 52

    Kapadia VS, Chalak LF, Sparks JE, Allen JR, Savani RC, Wyckoff MH . Resuscitation of preterm neonates with limited versus high oxygen strategy. Pediatrics 2013; 132: e1488–e1496.

  53. 53

    Rook D, Schierbeek H, Vento M, Vlaardingerbroek H, van der Eijk AC, Longini M et al. Resuscitation of preterm infants with different inspired oxygen fractions. J Pediatr 2014; 164: 1322–1326.

  54. 54

    Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P et al. Targeted oxygen in the resuscitation of preterm infants, a randomized clinical trial. Pediatrics 2017; 139: e20161452.

  55. 55

    Saugstad OD, Aune D, Aguar M, Kapadia V, Finer N, Vento M . Systematic review and meta-analysis of optimal initial fraction of oxygen levels in the delivery room at ≤32 weeks. Acta Paediatr 2014; 103: 744–751.

  56. 56

    Oei JL, Vento M, Rabi Y, Wright I, Finer N, Rich W et al. Higher or lower oxygen for delivery room resuscitation of preterm infants below 28 completed weeks gestation: a meta-analysis. Arch Dis Child Fetal Neonatal Ed 2017; 102: F24–F30.

  57. 57

    Rabi Y, Lodha A, Soraisham A, Singhal N, Barrington K, Shah PS . Outcomes of preterm infants following the introduction of room air resuscitation. Resuscitation 2015; 96: 252–259.

  58. 58

    Guyatt GH, Briel M, Glasziou P, Bassler D, Montori VM . Problems of stopping trials early. BMJ 2012; 344: e3863.

  59. 59

    Perlman JM, Wyllie J, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R et al. Part 7: Neonatal resuscitation: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2015; 132: S204–S241.

  60. 60

    Study of room air versus 60% oxygen for resuscitation of premature infants (PRESOX). Identifier NCT01773746. Available at: Accessed 31 March 2017.

  61. 61

    Soll RF . Prophylactic natural surfactant extract for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2000; 2: CD000511.

  62. 62

    Soll RF . Prophylactic synthetic surfactant for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2000; 2: CD001079.

  63. 63

    Soll RF . Synthetic surfactant for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev 2000; 2: CD001149.

  64. 64

    Bahadue FL, Soll R . Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2012; 11: CD001456.

  65. 65

    Ardell S, Pfister RH, Soll R . Animal derived surfactant extract versus protein free synthetic surfactant for the prevention and treatment of respiratory distress syndrome. Cochrane Database Syst Rev 2015; 5: CD000144.

  66. 66

    Singh N, Halliday HL, Stevens TP, Suresh G, Soll R, Rojas-Reyes MX . Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev 2015; 12: CD010249.

  67. 67

    Moya F, Sinha S, Gadzinowski J, D'Agostino R, Segal R, Guardia C et al. One-year follow-up of very preterm infants who received lucinactant for prevention of respiratory distress syndrome: results from 2 multicenter randomized, controlledtrials. Pediatrics 2007; 119: e1361–e1370.

  68. 68

    Sinha SK, Lacaze-Masmonteil T, Valls i Soler A, Wiswell TE, Gadzinowski J, Hajdu J et al. A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome. Pediatrics 2005; 115: 1030–1038.

  69. 69

    Victorin LH, Deverajan LV, Curstedt T, Robertson B . Surfactant replacement in spontaneously breathing babies with hyaline membrane disease - a pilot study. Biol Neonate 1990; 58: 121–126.

  70. 70

    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; 4: CD003063.

  71. 71

    Isayama T, Chai-Adisaksopha C, McDonald SD . Noninvasive ventilation with vs without early surfactant to prevent chronic lung disease in preterm infants: a systematic review and meta-analysis. JAMA Pediatr 2015; 169: 731–739.

  72. 72

    More K, Sakhuja P, Shah PS . Minimally invasive surfactant administration in preterm infants: a meta-narrative review. JAMA Pediatr 2014; 168: 901–908.

  73. 73

    Verder H, Robertson B, Greisen G, Ebbesen F, Albertsen P, Lundstrøm K et al. Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish multicenter study group. N Engl J Med 1994; 331: 1051–1055.

  74. 74

    Göpel W, Kribs A, Härtel C, Avenarius S, Teig N, Groneck P et al. Less invasive surfactant administration is associated with improved pulmonary outcomes in spontaneously breathing preterm infants. Acta Paediatr 2015; 104: 241–246.

  75. 75

    Mirnia K, Heidarzadeh M, Hosseini MB, Sadeghnia A, Balila M, Ghojazadeh M . Comparison outcome of surfactant administration via tracheal catheterization during spontaneous breathing with insure. Med J Islamic World Acad Sci 2013; 21: 143–148.

  76. 76

    Kanmaz HG, Erdeve O, Canpolat FE, Mutlu B, Dilmen U . Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics 2013; 131: e502–e509.

  77. 77

    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; 169: 723–730.

  78. 78

    Bao Y, Zhang G, Wu M, Ma L, Zhu J . A pilot study of less invasive surfactant administration in very preterm infants in a chinese tertiary center. BMC Pediatr 2015; 15: 342.

  79. 79

    Göpel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011; 378: 1627–1634.

  80. 80

    Mohammadizadeh M, Ardestani AG, Sadeghnia AR . Early administration of surfactant via a thin intratracheal catheter in preterm infants with respiratory distress syndrome: feasibility and outcome. J Res Pharm Pract 2015; 4: 31–36.

  81. 81

    Rigo V, Lefebvre C, Broux I . Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis. Eur J Pediatr 2016; 175: 1933–1942.

  82. 82

    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; 102: F17–F23.

  83. 83

    Isayama T, Iwami H, McDonald S, Beyene J . Association of noninvasive ventilation strategies with mortality and bronchopulmonary dysplasia among preterm infants: a systematic review and meta-analysis. JAMA 2016; 316: 611–624.

  84. 84

    Dargaville PA, Kamlin CO, De Paoli AG, Carlin JB, Orsini F, Soll RF et al. The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation. BMC Pediatr 2014; 14: 213.

  85. 85

    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; 193: 86–95.

  86. 86

    Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A et al. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354: 2112–2121.

  87. 87

    Kribs A, Hummler H . Ancillary therapies to enhance success of non-invasive modes of respiratory support - approaches to delivery room use of surfactant and caffeine? Semin Fetal Neonatal Med 2016; 21: 212–218.

  88. 88

    Kua KP, Lee SW . Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates. Br J Clin Pharmacol 2017; 83: 180–191.

  89. 89

    Dekker J, Hooper SB, van Vonderen JJ, Witlox R, Lopriore E, te Pas AB . Caffeine to improve breathing effort of preterm infants at birth; a randomized controlled trial. Pediatr Res 2017 (epub ahead of print 17 May 2017; doi:10.1038/pr.2017.45).

  90. 90

    Sauberan J, Akotia D, Rich W, Durham J, Finer N, Katheria A . A pilot randomized controlled trial of early versus routine caffeine in extremely premature infants. Am J Perinatol 2015; 32: 879–886.

  91. 91

    Tataranno ML, Oei JL, Perrone S, Wright IM, Smyth JP, Lui K et al. Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air. Acta Paediatr 2015; 104: 759–765.

Download references


EEF is supported by a Career Development Award, NICHD K23HD084727. No other funding sources supported this manuscript.

Author information

Correspondence to E E Foglia.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Foglia, E., Jensen, E. & Kirpalani, H. Delivery room interventions to prevent bronchopulmonary dysplasia in extremely preterm infants. J Perinatol 37, 1171–1179 (2017).

Download citation

Further reading