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Management of apnea of prematurity

Richard Martin, MD
Section Editors
Joseph A Garcia-Prats, MD
George B Mallory, MD
Deputy Editor
Melanie S Kim, MD


Apnea of prematurity is a developmental disorder in preterm infants, which occurs as a direct consequence of immature respiratory control. In an infant less than 37 weeks gestational age (GA), apneic spells are considered clinically significant if the episodes are greater than 20-second duration or when shorter episodes are accompanied by hypoxemia and/or bradycardia [1]. The frequency and severity of symptoms is inversely proportional to GA, and almost all extremely low birth weight (ELBW) infants (BW below 1000 g) are affected.

The management of apnea of prematurity will be reviewed here. The pathogenesis, clinical features, and diagnosis of apnea of prematurity are discussed separately. (See "Pathogenesis, clinical presentation, and diagnosis of apnea of prematurity".)


Preterm infants with a gestational age (GA) less than 35 weeks should be monitored for apnea because of the high prevalence of apnea in this group of patients. In most neonatal intensive care units (NICUs), cardiac monitors, pulse oximeters, and impedance pneumography are used to monitor for apnea of prematurity and its associated bradycardia and hypoxemia. The accuracy of pneumography is limited by movement artifacts and the inability to detect obstructive apnea episodes, and is generally not used as the sole technique. (See "Pathogenesis, clinical presentation, and diagnosis of apnea of prematurity", section on 'Incidence' and "Oxygen monitoring and therapy in the newborn" and "Oxygen monitoring and therapy in the newborn", section on 'Pulse oximetry'.)

There are no data on the optimal threshold settings to determine significant apnea events. In our practice, we use the following threshold settings to detect episodes of apnea and its associated bradycardia and hypoxemia. The lower thresholds are used when the decision is being made to discontinue caffeine therapy or discharge the infant home. Other centers utilize different parameters.

Apnea ≥15 or 20 seconds


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Literature review current through: Dec 2016. | This topic last updated: Fri Apr 01 00:00:00 GMT+00:00 2016.
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  1. Eichenwald EC, Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics 2016; 137.
  2. Miller MJ, Carlo WA, Martin RJ. Continuous positive airway pressure selectively reduces obstructive apnea in preterm infants. J Pediatr 1985; 106:91.
  3. Stark AR, Goldman MD, Frantz ID 3rd. Lung volume changes, occlusion pressure and chest wall configuration in human infants. Pediatr Res 1979; 13:250.
  4. Durand M, McCann E, Brady JP. Effect of continuous positive airway pressure on the ventilatory response to CO2 in preterm infants. Pediatrics 1983; 71:634.
  5. Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-flow nasal cannulae in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure. Pediatrics 2001; 107:1081.
  6. Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev 2010; :CD000140.
  7. Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354:2112.
  8. Davis PG, Schmidt B, Roberts RS, et al. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr 2010; 156:382.
  9. Bancalari E. Caffeine for apnea of prematurity. N Engl J Med 2006; 354:2179.
  10. 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.
  11. 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.
  12. Doyle LW, Schmidt B, Anderson PJ, et al. Reduction in developmental coordination disorder with neonatal caffeine therapy. J Pediatr 2014; 165:356.
  13. Lodha A, Seshia M, McMillan DD, et al. Association of early caffeine administration and neonatal outcomes in very preterm neonates. JAMA Pediatr 2015; 169:33.
  14. Abu Jawdeh EG, O'Riordan M, Limrungsikul A, et al. Methylxanthine use for apnea of prematurity among an international cohort of neonatologists. J Neonatal Perinatal Med 2013; 6:251.
  15. Abu-Shaweesh JM, Martin RJ. Neonatal apnea: what's new? Pediatr Pulmonol 2008; 43:937.
  16. Kraaijenga JV, Hutten GJ, de Jongh FH, van Kaam AH. The Effect of Caffeine on Diaphragmatic Activity and Tidal Volume in Preterm Infants. J Pediatr 2015; 167:70.
  17. Supcun S, Kutz P, Pielemeier W, Roll C. Caffeine increases cerebral cortical activity in preterm infants. J Pediatr 2010; 156:490.
  18. Martin RJ, Wang K, Köroğlu O, et al. Intermittent hypoxic episodes in preterm infants: do they matter? Neonatology 2011; 100:303.
  19. Köroğlu OA, MacFarlane PM, Balan KV, et al. Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis. Neonatology 2014; 106:235.
  20. Weichelt U, Cay R, Schmitz T, et al. Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by caffeine. Eur Respir J 2013; 41:966.
  21. Steer PA, Henderson-Smart DJ. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev 2000; :CD000273.
  22. Gounaris A, Kokori P, Varchalama L, et al. Theophylline and gastric emptying in very low birthweight neonates: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2004; 89:F297.
  23. Bauer J, Maier K, Linderkamp O, Hentschel R. Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea. Pediatrics 2001; 107:660.
  24. Aranda JV, Cook CE, Gorman W, et al. Pharmacokinetic profile of caffeine in the premature newborn infant with apnea. J Pediatr 1979; 94:663.
  25. Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev 2010; :CD000273.
  26. Natarajan G, Botica ML, Thomas R, Aranda JV. Therapeutic drug monitoring for caffeine in preterm neonates: an unnecessary exercise? Pediatrics 2007; 119:936.
  27. Darnall RA, Kattwinkel J, Nattie C, Robinson M. Margin of safety for discharge after apnea in preterm infants. Pediatrics 1997; 100:795.
  28. Rhein LM, Dobson NR, Darnall RA, et al. Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial. JAMA Pediatr 2014; 168:250.
  29. Doyle J, Davidson D, Katz S, et al. Apnea of prematurity and caffeine pharmacokinetics: potential impact on hospital discharge. J Perinatol 2016; 36:141.
  30. Zagol K, Lake DE, Vergales B, et al. Anemia, apnea of prematurity, and blood transfusions. J Pediatr 2012; 161:417.
  31. Abu Jawdeh EG, Martin RJ, Dick TE, et al. The effect of red blood cell transfusion on intermittent hypoxemia in ELBW infants. J Perinatol 2014; 34:921.
  32. Ramanathan R, Corwin MJ, Hunt CE, et al. Cardiorespiratory events recorded on home monitors: Comparison of healthy infants with those at increased risk for SIDS. JAMA 2001; 285:2199.
  33. Lorch SA, Srinivasan L, Escobar GJ. Epidemiology of apnea and bradycardia resolution in premature infants. Pediatrics 2011; 128:e366.