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Apnea of Prematurity Clinical Presentation

  • Author: Dharmendra J Nimavat, MD, FAAP; Chief Editor: Ted Rosenkrantz, MD  more...
Updated: May 29, 2014


Initial identification and assessment of apnea

The bedside caregivers—namely, the nurse in the neonatal intensive care unit (NICU) the respiratory care practitioner—identify the problem for the physician. Apnea should be distinguished from periodic breathing and documented. Use of a cardiorespiratory monitor is essential for identifying apnea of prematurity (AOP) and for monitoring the patient's blood pressure. Events associated with apnea, such as bradycardia and cyanosis, must be quantified. For bradycardia, the magnitude of reduction in heart rate from baseline and the duration of the event should be recorded. The presence and duration of central cyanosis should also be noted.

Pulse oximetry may be helpful for measuring the severity and duration of central O2 desaturation. Caregivers should be aware of the problems associated with the use of pulse oximetry to evaluate O2 saturation.[57]

When apnea is observed, its duration must be established. Cardiorespiratory monitors can be used to quantify the duration. Caregivers should attempt to define the type and severity of the patient's apnea. The type of apnea is identified as central, obstructive, or mixed. A nasal thermistor may be needed in conjunction with pneumography to differentiate the type of apnea.

Classification of the severity of apnea

Criteria to classify the severity of apnea have not been well developed in clinical studies.

The University of Washington published indications for different treatments based on the severity of apnea of prematurity.[58] This classification for apnea of prematurity uses the terms spontaneous, mild, moderate, or severe.

  • A spontaneous event might be defined by apnea with minimal physiologic changes, an event of brief duration, one associated with self-recovery, or an event only occurring once or twice in 24 hours.
  • Mild or moderate events involve apnea, bradycardia, and/or O 2 desaturation of intermediate magnitude. These events require therapeutic interventions less rigorous than those needed for severe episodes.
  • A severe event entails prolonged apnea associated with clinically significant and persistent bradycardia, as well as O 2 desaturation (ie, central cyanosis). A severe event requires vigorous stimulation, administration of an increased concentration of inspired O 2, and/or assisted ventilation (eg, bag-mask ventilation).

Clinical centers must develop the classification system they wish to use to measure the severity of apnea. Factors often used to judge the need for future interventions include these:

  • Severity of the apnea
  • Number of events per day
  • Magnitude of the intervention required to alleviate the event

The therapeutic approach used in most NICUs involves a progression from tactile stimulation to methylxanthine therapy and then some form of assisted breathing (eg, nasal continuous airway pressure or assisted ventilation).

Exclusion of other causes of apnea

Before a diagnosis of apnea of prematurity is made, other causes of apnea in neonates must be excluded (see Differentials).

All forms of apnea may be difficult to detect visually, although obstructive apnea is usually most obvious to a trained observer.

Cardiorespiratory monitoring and pulse oximetry have improved bedside detection of apnea of prematurity.[59] Caregivers should familiarize themselves with the advantages and disadvantages of cardiorespiratory monitoring and pulse oximetry in neonates.

Published findings show that even highly trained observers miss more than 50% of apnea of prematurity episodes.

Precise diagnosis of apnea of prematurity requires multichannel recordings, which are most commonly measurements of nasal airflow, thoracic impedance, heart rate, and O2 saturation. Expanded testing may include electroencephalography and/or use of an esophageal pH probe with a high thoracic Clark electrode.

Hydrochloric acid may be added to the feedings to increase the gastric concentration of hydrogen ions.



Physical examination should include observation of the infant's breathing patterns while he or she is asleep and awake. The prone or supine sleeping positions and other lying postures may be important during this clinical observation.

Important to the assessment of neonatal apnea is the identification of airway abnormalities (eg, choanal obstruction, anomalies of the palate, jaw deformities, neck masses) and conditions in distant organs that influence breathing (eg, brain hemorrhages, seizures, pulmonary disorders, congenital heart disease).

Findings in the head and neck and other obvious major and minor anomalies identified may suggest chromosomal abnormalities or a malformation syndrome. Appropriate work-up must then follow.

Physical examination includes the elements described below:

  • Monitor the baby's cardiac, neurologic, and respiratory status.
  • Observe the infant for any signs of breathing difficulty, desaturation, or bradycardia during feeding.
  • Reflex effects of apnea include characteristic changes in heart rate, blood pressure, and pulse pressure.
    • Bradycardia may begin within 1.5-2 seconds of the onset of apnea.
    • Apneic episodes associated with bradycardia are characterized by decreases in heart rate of more than 30% below baseline rates.
    • This reflex bradycardia is secondary to hypoxic stimulation of the carotid body chemoreceptor or a direct effect of hypoxia on the heart.
    • Transient bradycardias also occur relatively often in very low birth weight infants who also have apnea of prematurity.[60] These events are not associated with apnea, but they are presumed to be mediated by an increase in vagal tone.
  • Pulse oximetry may reveal clinically significant desaturation. However, pulse oximeters typically have a delay in recording the event.


The physiology related to apnea of prematurity is reviewed in Pathophysiology. Aspects of causation are briefly reemphasized here.

A premature neonate in whom all other causes of apnea have been excluded may be considered to have apnea of prematurity. Although the etiology of apnea of prematurity is not fully understood, several mechanisms have been proposed to explain this condition, including those described below.

  • Apnea of prematurity is the clinical phenomenon associated with incompletely organized and interconnected respiratory neurons in the brainstem and their response to a multitude of afferent stimuli. Therefore, the abnormal control of breathing seen in apnea of prematurity represents neuronal immaturity of the brain. (For an excellent review of this topic, see the article by Darnall et al. [1] )
  • In a premature neonate, protective respiratory reflex activity is decreased, and Hering-Breuer reflex activity is increased.
  • Dopaminergic receptors may have a role in inhibiting the responses of peripheral chemoreceptor and hypoxia-elicited central neural mechanisms. Evidence from studies of neonatal animals indicates that endogenous endorphin production may depress the central respiratory drive. Although endogenous opiates may modulate the ventilatory response to hypoxia in newborn animals, a competitive opiate receptor antagonist (naloxone) has no therapeutic role in apnea of prematurity.
  • Negative luminal pressures are generated during inspiration, and the compliant pharynx of the premature neonate is predisposed to collapse. Failure of genioglossus activation is most widely implicated in mixed and obstructive apnea among infants and adults.
  • The ability of medullary chemoreceptors to sense elevated CO 2 levels is impaired. Therefore, an absent, small, or delayed response of the upper airway muscles to hypercapnia might cause upper airway instability when a linear increase in chest-wall activity also occurs. This impairment may predispose the infant to obstructed inspiration after a period of central apnea.
  • Another important factor to consider is the excitation of chemoreceptors in the larynx due to acid reflux. Laryngeal receptors send afferent fibers to the medulla and can elicit apnea when stimulated.
  • Swallowing during a respiratory pause is unique to apnea and does not occur during periodic breathing. Accumulation of saliva in the pharynx could hypothetically prolong apnea by means of a chemoreflex mechanism.
  • Some practicing neonatologists believe that gastroesophageal reflux (GER) is associated with recurrent apnea and have, therefore, treated preterm neonates with antacid and/or antireflux drugs. However, this assumption has been vigorously challenged.
    • Booth suggested that apneic episodes were reduced when esophagitis resolved because apnea clinically improved 1 or 2 days after the start of antireflux therapy. Therefore, neonatologists have treated xanthine-resistant apnea with H2 blockers, metoclopramide, thickened formula, and/or upright positioning during feeding.
    • No controlled trials have demonstrated that antireflux drugs are effective in preventing apnea.
    • Findings from several studies have not demonstrated a relationship between episodes of apnea and episodes of acid reflux into the esophagus (see Pathophysiology and Differentials).
  • Menon, Schefft, and Thach observed that regurgitation of formula into the pharynx after feeding was associated with an increased incidence of apnea in premature infants. [61] As stated above, gastric fluids can possibly activate laryngeal chemoreflexes, leading to apnea.
  • Although well-designed, controlled clinical trials are few, scientists often say that aminophylline exacerbates reflux in infants with apnea. The relationship of GER to methylxanthines is based on the literature about asthma, and limited studies in neonatal only suggest its occurrence. [62] Some authors have not related the use of methylxanthine to severe GER disease. [63]
Contributor Information and Disclosures

Dharmendra J Nimavat, MD, FAAP Associate Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine

Dharmendra J Nimavat, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.


Michael P Sherman, MD, FAAP Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Neonatologist, Women’s and Children’s Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine

Michael P Sherman, MD, FAAP is a member of the following medical societies: American Pediatric Society, American Society for Microbiology, American Thoracic Society, Pediatric Infectious Diseases Society, American Association for the Advancement of Science, European Society for Paediatric Research, Western Society for Pediatric Research, Perinatal Research Society, American Academy of Pediatrics, American Association of Immunologists, Society for Pediatric Research

Disclosure: Nothing to disclose.

Rene L Santin, MD 

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Arun K Pramanik, MD, MBBS Professor of Pediatrics, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.


Rachel Porat, MD Director, Neonatal Apnea Monitoring Program, Assistant Director, Division of Neonatology, Albert Einstein Medical Center; Associate Professor, Department of Pediatrics, Thomas Jefferson University

Rachel Porat, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

  1. Darnall RA, Ariagno RL, Kinney HC. The late preterm infant and the control of breathing, sleep, and brainstem development: a review. Clin Perinatol. 2006 Dec. 33(4):883-914; abstract x. [Medline].

  2. Gaultier C, Gallego J. Development of respiratory control: evolving concepts and perspectives. Respir Physiol Neurobiol. 2005 Nov 15. 149(1-3):3-15. [Medline].

  3. Gozal D. New concepts in abnormalities of respiratory control in children. Curr Opin Pediatr. 2004 Jun. 16(3):305-8. [Medline].

  4. Martin RJ, Abu-Shaweesh JM. Control of breathing and neonatal apnea. Biol Neonate. 2005. 87(4):288-95. [Medline].

  5. Chatonnet F, Dominguez del Toro E, Thoby-Brisson M, et al. From hindbrain segmentation to breathing after birth: developmental patterning in rhombomeres 3 and 4. Mol Neurobiol. 2003 Dec. 28(3):277-94. [Medline].

  6. Kotecha S. Lung growth for beginners. Paediatr Respir Rev. 2000 Dec. 1(4):308-13. [Medline].

  7. Givan DC. Physiology of breathing and related pathological processes in infants. Semin Pediatr Neurol. 2003 Dec. 10(4):271-80. [Medline].

  8. Sinha SK, Donn SM. Fetal-to-neonatal maladaptation. Semin Fetal Neonatal Med. 2006 Jun. 11(3):166-73. [Medline].

  9. American Academy of Pediatrics, Committee on Fetus and Newborn. Apnea, sudden infant death syndrome, and home monitoring. Pediatrics. 2003 Apr. 111(4 Pt 1):914-7. [Medline]. [Full Text].

  10. Kelly DH, Shannon DC. Periodic breathing in infants with near-miss sudden infant death syndrome. Pediatrics. 1979 Mar. 63(3):355-60. [Medline].

  11. Martin RJ, Miller MJ, Carlo WA. Pathogenesis of apnea in preterm infants. J Pediatr. 1986 Nov. 109(5):733-41. [Medline].

  12. Lagercrantz H. Improved understanding of respiratory control--implications for the treatment of apnoea. Eur J Pediatr. 1995. 154(8 Suppl 3):S10-2. [Medline].

  13. Putnam RW, Conrad SC, Gdovin MJ, et al. Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity. Respir Physiol Neurobiol. 2005 Nov 15. 149(1-3):165-79. [Medline].

  14. Simakajornboon N, Kuptanon T. Maturational changes in neuromodulation of central pathways underlying hypoxic ventilatory response. Respir Physiol Neurobiol. 2005 Nov 15. 149(1-3):273-86. [Medline].

  15. Henderson-Smart DJ, Pettigrew AG, Campbell DJ. Clinical apnea and brain-stem neural function in preterm infants. N Engl J Med. 1983 Feb 17. 308(7):353-7. [Medline].

  16. Amin SB, Charafeddine L, Guillet R. Transient bilirubin encephalopathy and apnea of prematurity in 28 to 32 weeks gestational age infants. J Perinatol. 2005 Jun. 25(6):386-90. [Medline].

  17. Gauda EB, Miller MJ, Carlo WA, et al. Genioglossus and diaphragm activity during obstructive apnea and airway occlusion in infants. Pediatr Res. 1989 Dec. 26(6):583-7. [Medline].

  18. Martin RJ, Abu-Shaweesh JM, Baird TM. Apnoea of prematurity. Paediatr Respir Rev. 2004. 5 Suppl A:S377-82. [Medline].

  19. Gould JB, Lee AF, James O, et al. The sleep state characteristics of apnea during infancy. Pediatrics. 1977 Feb. 59(2):182-94. [Medline].

  20. Hoppenbrouwers T, Hodgman JE, Rybine D, et al. Sleep architecture in term and preterm infants beyond the neonatal period: the influence of gestational age, steroids, and ventilatory support. Sleep. 2005 Nov 1. 28(11):1428-36. [Medline].

  21. Bryan AC, Bryan MH. Control of respiration in the newborn. Clin Perinatol. 1978 Sep. 5(2):269-81. [Medline].

  22. Martin RJ, Okken A, Rubin D. Arterial oxygen tension during active and quiet sleep in the normal neonate. J Pediatr. 1979 Feb. 94(2):271-4. [Medline].

  23. Krimsky WR, Leiter JC. Physiology of breathing and respiratory control during sleep. Semin Respir Crit Care Med. 2005 Feb. 26(1):5-12. [Medline].

  24. Cohen G, Katz-Salamon M. Development of chemoreceptor responses in infants. Respir Physiol Neurobiol. 2005 Nov 15. 149(1-3):233-42. [Medline].

  25. Hunt CE, Hauck FR. Sudden infant death syndrome. CMAJ. 2006 Jun 20. 174(13):1861-9. [Medline].

  26. Koons A, Hegyi T, Mehta R, et al. Cerebral vascular responses to changes in carbon dioxide tension in term and preterm infants with apnea. Biol Neonate. 2003. 84(2):115-8. [Medline].

  27. Carlo WA, DiFiore JM. Respiratory muscle responses to changes in chemoreceptor drive in infants. J Appl Physiol. 1990 Mar. 68(3):1041-7. [Medline].

  28. Noble LM, Carlo WA, Miller MJ, et al. Transient changes in expiratory time during hypercapnia in premature infants. J Appl Physiol. 1987 Mar. 62(3):1010-3. [Medline].

  29. Gerhardt T, Bancalari E. Apnea of prematurity: II. Respiratory reflexes. Pediatrics. 1984 Jul. 74(1):63-6. [Medline].

  30. Cross KW, Oppe TE. The effect of inhalation of high and low concentrations of oxygen on the respiration of the premature infant. J Physiol. 1952 May. 117(1):38-55. [Medline].

  31. Gauda EB, McLemore GL, Tolosa J, et al. Maturation of peripheral arterial chemoreceptors in relation to neonatal apnoea. Semin Neonatol. 2004 Jun. 9(3):181-94. [Medline].

  32. Rigatto H, De La Torre Verduzco R, Gates DB. Effects of O2 on the ventilatory response to CO2 in preterm infants. J Appl Physiol. 1975 Dec. 39(6):896-9. [Medline].

  33. Simakajornboon N, Beckerman RC, Mack C, et al. Effect of supplemental oxygen on sleep architecture and cardiorespiratory events in preterm infants. Pediatrics. 2002 Nov. 110(5):884-8. [Medline].

  34. Carlo WA, Miller MJ, Martin RJ. Differential response of respiratory muscles to airway occlusion in infants. J Appl Physiol. 1985 Sep. 59(3):847-52. [Medline].

  35. Gerhardt T, Bancalari E. Apnea of prematurity: I. Lung function and regulation of breathing. Pediatrics. 1984 Jul. 74(1):58-62. [Medline].

  36. Miller MJ, Petrie TG, Difiore JM. Changes in resistance and ventilatory timing that accompany apnea in premature infants. J Appl Physiol. 1993 Aug. 75(2):720-3. [Medline].

  37. Waggener TB, Frantz ID 3rd, Stark AR, Kronauer RE. Oscillatory breathing patterns leading to apneic spells in infants. J Appl Physiol. 1982 May. 52(5):1288-95. [Medline].

  38. Thach BT. The role of pharyngeal airway obstruction in prolonging infantile apneic spells. Tilden JT, Roeder JM, Steinschneide A, eds. Sudden Infant Death Syndrome. New York: Academic Press; 1983. 279.

  39. Carlo WA, Martin RJ, Difiore JM. Differences in CO2 threshold of respiratory muscles in preterm infants. J Appl Physiol. 1988 Dec. 65(6):2434-9. [Medline].

  40. van Lunteren E, Strohl KP, Parker DM, et al. Phasic volume-related feedback on upper airway muscle activity. J Appl Physiol. 1984 Mar. 56(3):730-6. [Medline].

  41. Harding R. Function of the larynx in the fetus and newborn. Annu Rev Physiol. 1984. 46:645-59. [Medline].

  42. Gauda EB, Carroll TP, Schwartz AR, et al. Mechano- and chemoreceptor modulation of respiratory muscles in response to upper airway negative pressure. J Appl Physiol. 1994 Jun. 76(6):2656-62. [Medline].

  43. Miller MJ, DiFiore JM. A comparison of swallowing during apnea and periodic breathing in premature infants. Pediatr Res. 1995 Jun. 37(6):796-9. [Medline].

  44. Zaidi SI, Jafri A, Martin RJ, Haxhiu MA. Adenosine A2A receptors are expressed by GABAergic neurons of medulla oblongata in developing rat. Brain Res. 2006 Feb 3. 1071(1):42-53. [Medline].

  45. Darnall RA Jr. Aminophylline reduces hypoxic ventilatory depression: possible role of adenosine. Pediatr Res. 1985 Jul. 19(7):706-10. [Medline].

  46. Arad-Cohen N, Cohen A, Tirosh E. The relationship between gastroesophageal reflux and apnea in infants. J Pediatr. 2000 Sep. 137(3):321-6. [Medline].

  47. Peter CS, Sprodowski N, Bohnhorst B, et al. Gastroesophageal reflux and apnea of prematurity: no temporal relationship. Pediatrics. 2002 Jan. 109(1):8-11. [Medline].

  48. Kiatchoosakun P, Dreshaj IA, Abu-Shaweesh JM, et al. Effects of hypoxia on respiratory neural output and lower esophageal sphincter pressure in piglets. Pediatr Res. 2002 Jul. 52(1):50-5. [Medline].

  49. Carlo WA, Martin RJ, Versteegh FG, et al. The effect of respiratory distress syndrome on chest wall movements and respiratory pauses in preterm infants. Am Rev Respir Dis. 1982 Jul. 126(1):103-7. [Medline].

  50. Barrington KJ, Finer NN. Periodic breathing and apnea in preterm infants. Pediatr Res. 1990 Feb. 27(2):118-21. [Medline].

  51. Finer NN, Barrington KJ, Hayes BJ, Hugh A. Obstructive, mixed, and central apnea in the neonate: physiologic correlates. J Pediatr. 1992 Dec. 121(6):943-50. [Medline].

  52. Butcher-Puech MC, Henderson-Smart DJ, Holley D, et al. Relation between apnoea duration and type and neurological status of preterm infants. Arch Dis Child. 1985 Oct. 60(10):953-8. [Medline].

  53. Perlman JM, Volpe JJ. Episodes of apnea and bradycardia in the preterm newborn: impact on cerebral circulation. Pediatrics. 1985 Sep. 76(3):333-8. [Medline].

  54. Emancipator JL, Storfer-Isser A, Taylor HG, et al. Variation of cognition and achievement with sleep-disordered breathing in full-term and preterm children. Arch Pediatr Adolesc Med. 2006 Feb. 160(2):203-10. [Medline].

  55. Janvier A, Khairy M, Kokkotis A, et al. Apnea is associated with neurodevelopmental impairment in very low birth weight infants. J Perinatol. 2004 Dec. 24(12):763-8. [Medline].

  56. Barrington KJ, Finer N, Li D. Predischarge respiratory recordings in very low birth weight newborn infants. J Pediatr. 1996 Dec. 129(6):934-40. [Medline].

  57. Sola A, Chow L, Rogido M. Pulse oximetry in neonatal care in 2005. A comprehensive state of the art review [in Spanish]. An Pediatr (Barc). 2005 Mar. 62(3):266-81. [Medline].

  58. Mayock DE. Apnea. Revised February 24, 2000. University of Washington Division of Neonatology Web site. NICU-WEB. Available at

  59. Di Fiore JM. Neonatal cardiorespiratory monitoring techniques. Semin Neonatol. 2004 Jun. 9(3):195-203. [Medline].

  60. Gamble YD, Lutin WP, Mathew OP. Non-sinus bradyarrhythmias in very low birth weight infants. J Perinatol. 2007 Jan. 27(1):65-7. [Medline].

  61. Menon AP, Schefft GL, Thach BT. Apnea associated with regurgitation in infants. J Pediatr. 1985 Apr. 106(4):625-9. [Medline].

  62. Newell SJ, Booth IW, Morgan ME, et al. Gastro-oesophageal reflux in preterm infants. Arch Dis Child. 1989 Jun. 64(6):780-6. [Medline].

  63. Khalaf MN, Porat R, Brodsky NL, Bhandari V. Clinical correlations in infants in the neonatal intensive care unit with varying severity of gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2001 Jan. 32(1):45-9. [Medline].

  64. Andrade EO, Arain A, Malow BA. Partial epilepsy presenting as apneic seizures without posturing. Pediatr Neurol. 2006 Nov. 35(5):359-62. [Medline].

  65. Robles P, Poblano A, Hernandez G, et al. Cortical, brainstem and autonomic nervous system dysfunction in infants with post-hemorrhagic hydrocephalus. Rev Invest Clin. 2002 Mar-Apr. 54(2):133-8. [Medline].

  66. Fanaroff AA, Korones SB, Wright LL, et al. Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network. Pediatr Infect Dis J. 1998 Jul. 17(7):593-8. [Medline].

  67. Gonzalez BE, Mercado CK, Johnson L, et al. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med. 2003. 31(1):60-8. [Medline].

  68. Halasa NB, Williams JV, Wilson GJ, et al. Medical and economic impact of a respiratory syncytial virus outbreak in a neonatal intensive care unit. Pediatr Infect Dis J. 2005 Dec. 24(12):1040-4. [Medline].

  69. Rudd PT, Carrington D. A prospective study of chlamydial, mycoplasmal, and viral infections in a neonatal intensive care unit. Arch Dis Child. 1984 Feb. 59(2):120-5. [Medline].

  70. Cheromcha DP, Hyman PE. Neonatal necrotizing enterocolitis. Inflammatory bowel disease of the newborn. Dig Dis Sci. 1988 Mar. 33(3 Suppl):78S-84S. [Medline].

  71. Gauda EB, Shirahata M, Mason A, Pichard LE, Kostuk EW, Chavez-Valdez R. Inflammation in the carotid body during development and its contribution to apnea of prematurity. Respir Physiol Neurobiol. 2013 Jan 1. 185(1):120-31. [Medline].

  72. Rasch DK, Huber PA, Richardson CJ, et al. Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr. 1982 Feb. 100(2):272-6. [Medline].

  73. Ali A, Walentik C, Mantych GJ, et al. Iatrogenic acute hypermagnesemia after total parenteral nutrition infusion mimicking septic shock syndrome: two case reports. Pediatrics. 2003 Jul. 112(1 Pt 1):e70-2. [Medline].

  74. Westkamp E, Soditt V, Adrian S, et al. Blood transfusion in anemic infants with apnea of prematurity. Biol Neonate. 2002. 82(4):228-32. [Medline].

  75. Bell EF, Strauss RG, Widness JA, et al. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics. 2005 Jun. 115(6):1685-91. [Medline].

  76. Armony-Sivan R, Eidelman AI, Lanir A, et al. Iron status and neurobehavioral development of premature infants. J Perinatol. 2004 Dec. 24(12):757-62. [Medline].

  77. Zagol K, Lake DE, Vergales B, et al. Anemia, apnea of prematurity, and blood transfusions. J Pediatr. 2012 Sep. 161(3):417-421.e1. [Medline].

  78. Kurth CD, Spitzer AR, Broennle AM, Downes JJ. Postoperative apnea in preterm infants. Anesthesiology. 1987 Apr. 66(4):483-8. [Medline].

  79. Malviya S, Swartz J, Lerman J. Are all preterm infants younger than 60 weeks postconceptual age at risk for postanesthetic apnea?. Anesthesiology. 1993 Jun. 78(6):1076-81. [Medline].

  80. Craven PD, Badawi N, Henderson-Smart DJ, O'Brien M. Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. Cochrane Database Syst Rev. 2003. (3):CD003669. [Medline].

  81. Henderson-Smart DJ, Steer P. Methylxanthine treatment for apnea in preterm infants. Cochrane Database Syst Rev. 2001. (3):CD000140. [Medline].

  82. Pourcyrous M, Korones SB, Crouse D, Bada HS. Interleukin-6, C-reactive protein, and abnormal cardiorespiratory responses to immunization in premature infants. Pediatrics. 1998 Mar. 101(3):E3. [Medline].

  83. Ellison VJ, Davis PG, Doyle LW. Adverse reactions to immunization with newer vaccines in the very preterm infant. J Paediatr Child Health. 2005 Aug. 41(8):441-3. [Medline].

  84. Pfister RE, Aeschbach V, Niksic-Stuber V, et al. Safety of DTaP-based combined immunization in very-low-birth-weight premature infants: frequent but mostly benign cardiorespiratory events. J Pediatr. 2004 Jul. 145(1):58-66. [Medline].

  85. Faldella G, Galletti S, Corvaglia L, et al. Safety of DTaP-IPV-HIb-HBV hexavalent vaccine in very premature infants. Vaccine. 2007 Jan 22. 25(6):1036-42. [Medline].

  86. Lee J, Robinson JL, Spady DW. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. BMC Pediatr. 2006. 6:20. [Medline].

  87. Thach BT. Reflux associated apnea in infants: evidence for a laryngeal chemoreflex. Am J Med. 1997 Nov 24. 103(5A):120S-124S. [Medline].

  88. Vermeylen D, Franco P, Hennequin Y, et al. Laryngeal oedema in neonatal apnoea and bradycardia syndrome (a pilot study). Early Hum Dev. 2005 Apr. 81(4):361-7. [Medline].

  89. Jolley SG, Halpern CT, Sterling CE, Feldman BH. The relationship of respiratory complications from gastroesophageal reflux to prematurity in infants. J Pediatr Surg. 1990 Jul. 25(7):755-7. [Medline].

  90. Justo RN, Gray PH. Fundoplication in preterm infants with gastro-oesophageal reflux. J Paediatr Child Health. 1991 Aug. 27(4):250-4. [Medline].

  91. de Ajuriaguerra M, Radvanyi-Bouvet MF, Huon C, Moriette G. Gastroesophageal reflux and apnea in prematurely born infants during wakefulness and sleep. Am J Dis Child. 1991 Oct. 145(10):1132-6. [Medline].

  92. Di Fiore JM, Arko M, Whitehouse M, et al. Apnea is not prolonged by acid gastroesophageal reflux in preterm infants. Pediatrics. 2005 Nov. 116(5):1059-63. [Medline].

  93. Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnea in premature infants. J Pediatr. 2001 Mar. 138(3):355-60. [Medline].

  94. Bohnhorst B, Gill D, Dordelmann M, et al. Bradycardia and desaturation during skin-to-skin care: no relationship to hyperthermia. J Pediatr. 2004 Oct. 145(4):499-502. [Medline].

  95. Bohnhorst B, Heyne T, Peter CS, Poets CF. Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation. J Pediatr. 2001 Feb. 138(2):193-7. [Medline].

  96. Berterottiere D, D'Allest AM, Dehan M, Gaultier C. Effects of increase in body temperature on the breathing pattern in premature infants. J Dev Physiol. 1990 Jun. 13(6):303-8. [Medline].

  97. Tirosh E, Bader D, Hodgins H, et al. Apnoea-associated heart rate changes among preterm and full-term infants exposed to hyperthermia. Clin Physiol. 1998 Jul. 18(4):331-5. [Medline].

  98. Ludington-Hoe SM, Anderson GC, Swinth JY, et al. Randomized controlled trial of kangaroo care: cardiorespiratory and thermal effects on healthy preterm infants. Neonatal Netw. 2004 May-Jun. 23(3):39-48. [Medline].

  99. Sontheimer D, Fischer CB, Scheffer F, et al. Pitfalls in respiratory monitoring of premature infants during kangaroo care. Arch Dis Child Fetal Neonatal Ed. 1995 Mar. 72(2):F115-7. [Medline].

  100. Arnon SS, Midura TF, Clay SA, et al. Infant botulism. Epidemiological, clinical, and laboratory aspects. JAMA. 1977 May 2. 237(18):1946-51. [Medline].

  101. Jeffery HE, Rahilly P, Read DJ. Multiple causes of asphyxia in infants at high risk for sudden infant death. Arch Dis Child. 1983 Feb. 58(2):92-100. [Medline].

  102. Cademartiri F, Luccichenti G, Laganà F, et al. Effective clinical outcome of a mandibular distraction device using three-dimensional CT with volume rendering in Pierre-Robin sequence. Acta Biomed. 2004 Aug. 75(2):122-5. [Medline].

  103. Denny A, Amm C. New technique for airway correction in neonates with severe Pierre Robin sequence. J Pediatr. 2005 Jul. 147(1):97-101. [Medline].

  104. Wittenborn W, Panchal J, Marsh JL, et al. Neonatal distraction surgery for micrognathia reduces obstructive apnea and the need for tracheotomy. J Craniofac Surg. 2004 Jul. 15(4):623-30. [Medline].

  105. Young TE, Mangum B. Methylxanthines. NeoFax. 19th ed. Raleigh, NC: Acorn; 2006. 200-3.

  106. Pantalitschka T, Sievers J, Urschitz MS, et al. Randomised crossover trial of four nasal respiratory support systems for apnoea of prematurity in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2009 Jul. 94(4):F245-8. [Medline].

  107. Alvaro RE, Khalil M, Qurashi M, et al. CO(2) inhalation as a treatment for apnea of prematurity: a randomized double-blind controlled trial. J Pediatr. 2012 Feb. 160(2):252-257.e1. [Medline].

  108. Millar D, Schmidt B. Controversies surrounding xanthine therapy. Semin Neonatol. 2004 Jun. 9(3):239-44. [Medline].

  109. Schmidt B. Methylxanthine therapy for apnea of prematurity: evaluation of treatment benefits and risks at age 5 years in the international Caffeine for Apnea of Prematurity (CAP) trial. Biol Neonate. 2005. 88(3):208-13. [Medline].

  110. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for extubation in preterm infants. Cochrane Database Syst Rev. 2003. (1):CD000139. [Medline].

  111. Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18. 354(20):2112-21. [Medline].

  112. Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev. 2010 Dec 8. CD000139. [Medline].

  113. Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev. 2010 Dec 8. CD000140. [Medline].

  114. Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for prevention of apnoea in preterm infants. Cochrane Database Syst Rev. 2010 Dec 8. CD000432. [Medline].

  115. 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 Jan 18. 307(3):275-82. [Medline].

  116. Banni S, Evans RW, Salgo MG, Corongiu FP, Lombardi B. Conjugated diene and trans fatty acids in a choline-devoid diet hepatocarcinogenic in the rat. Carcinogenesis. 1990 Nov. 11(11):2047-51. [Medline].

  117. Eichenwald EC, Howell RG 3rd, Kosch PC, et al. Developmental changes in sequential activation of laryngeal abductor muscle and diaphragm in infants. J Appl Physiol. 1992 Oct. 73(4):1425-31. [Medline].

  118. Heyman E, Ohlsson A, Heyman Z, Fong K. The effect of aminophylline on the excursions of the diaphragm in preterm neonates. A randomized double-blind controlled study. Acta Paediatr Scand. 1991 Mar. 80(3):308-15. [Medline].

  119. Chang J, Gray PH. Aminophylline therapy and cerebral blood flow velocity in preterm infants. J Paediatr Child Health. 1994 Apr. 30(2):123-5. [Medline].

  120. Dani C, Bertini G, Reali MF, et al. Brain hemodynamic changes in preterm infants after maintenance dose caffeine and aminophylline treatment. Biol Neonate. 2000 Jul. 78(1):27-32. [Medline].

  121. Pryds O, Schneider S. Aminophylline reduces cerebral blood flow in stable, preterm infants without affecting the visual evoked potential. Eur J Pediatr. 1991 Mar. 150(5):366-9. [Medline].

  122. Robel-Tillig E, Vogtmann C. Aminophylline influences cerebral hyperperfusion after severe birth hypoxia. Acta Paediatr. 2000 Aug. 89(8):971-4. [Medline].

  123. Rosenkrantz TS, Oh W. Aminophylline reduces cerebral blood flow velocity in low-birth-weight infants. Am J Dis Child. 1984 May. 138(5):489-91. [Medline].

  124. Cikrit D, Mastandrea J, Grosfeld JL, et al. Significance of portal vein air in necrotizing entercolitis: analysis of 53 cases. J Pediatr Surg. 1985 Aug. 20(4):425-30. [Medline].

  125. Cikrit D, Mastandrea J, West KW, et al. Necrotizing enterocolitis: factors affecting mortality in 101 surgical cases. Surgery. 1984 Oct. 96(4):648-55. [Medline].

  126. Hufnal-Miller CA, Blackmon L, Baumgart S, Pereira GR. Enteral theophylline and necrotizing enterocolitis in the low-birthweight infant. Clin Pediatr (Phila). 1993 Nov. 32(11):647-53. [Medline].

  127. Dani C, Bertini G, Pezzati M, et al. Brain hemodynamic effects of doxapram in preterm infants. Biol Neonate. 2006. 89(2):69-74. [Medline].

  128. Roll C, Horsch S. Effect of doxapram on cerebral blood flow velocity in preterm infants. Neuropediatrics. 2004 Apr. 35(2):126-9. [Medline].

  129. Henderson-Smart D, Steer P. Doxapram treatment for apnea in preterm infants. Cochrane Database Syst Rev. 2004. (4):CD000074. [Medline].

  130. Darnall RA, Kattwinkel J, Nattie C, Robinson M. Margin of safety for discharge after apnea in preterm infants. Pediatrics. 1997 Nov. 100(5):795-801. [Medline].

  131. Anderson J, Noori K, Morris SA. Apnoea after the 2-month immunisation in extremely preterm infants: what happens with the 4-month immunisation?. J Paediatr Child Health. 2013 Mar. 49(3):E217-20. [Medline].

  132. American Academy of Pediatrics, Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics. 2005 Nov. 116(5):1245-55. [Medline]. [Full Text].

  133. [Guideline] Persing J, James H, Swanson J, Kattwinkel J. Prevention and management of positional skull deformities in infants. American Academy of Pediatrics Committee on Practice and Ambulatory Medicine, Section on Plastic Surgery and Section on Neurological Surgery. Pediatrics. 2003 Jul. 112(1 Pt 1):199-202. [Medline].

  134. Spitzer AR, Fox WW. Infant apnea. Pediatr Clin North Am. 1986 Jun. 33(3):561-81. [Medline].

  135. Spitzer AR, Gibson E. Home monitoring. Clin Perinatol. 1992 Dec. 19(4):907-26. [Medline].

  136. Hymel KP. Distinguishing sudden infant death syndrome from child abuse fatalities. Pediatrics. 2006 Jul. 118(1):421-7. [Medline].

  137. Bull M, Agran P, Laraque D, et al. American Academy of Pediatrics. Committee on Injury and Poison Prevention. Safe transportation of newborns at hospital discharge. Pediatrics. 1999 Oct. 104(4 Pt 1):986-7. [Medline].

  138. Ojadi VC, Petrova A, Mehta R, Hegyi T. Risk of cardio-respiratory abnormalities in preterm infants placed in car seats: a cross-sectional study. BMC Pediatr. 2005. 5:28. [Medline].

  139. Pilley E, McGuire W. Pre-discharge "car seat challenge" for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2006. (1):CD005386. [Medline].

  140. Salhab WA, Khattak A, Tyson JE, et al. Car seat or car bed for very low birth weight infants at discharge home. J Pediatr. 2007 Mar. 150(3):224-8. [Medline].

  141. Mitchell EA, Blair PS, L'Hoir MP. Should pacifiers be recommended to prevent sudden infant death syndrome?. Pediatrics. 2006 May. 117(5):1755-8. [Medline].

  142. Collins CT, Ryan P, Crowther CA, et al. Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial. BMJ. 2004 Jul 24. 329(7459):193-8. [Medline].

  143. Ariagno RL, van Liempt S, Mirmiran M. Fewer spontaneous arousals during prone sleep in preterm infants at 1 and 3 months corrected age. J Perinatol. 2006 May. 26(5):306-12. [Medline].

  144. Bhat RY, Hannam S, Pressler R, et al. Effect of prone and supine position on sleep, apneas, and arousal in preterm infants. Pediatrics. 2006 Jul. 118(1):101-7. [Medline].

  145. Oyen N, Markestad T, Skaerven R, et al. Combined effects of sleeping position and prenatal risk factors in sudden infant death syndrome: the Nordic Epidemiological SIDS Study. Pediatrics. 1997 Oct. 100(4):613-21. [Medline].

  146. Mattia FR, deRegnier RA. Chronic physiologic instability is associated with neurodevelopmental morbidity at one and two years in extremely premature infants. Pediatrics. 1998 Sep. 102(3):E35. [Medline].

  147. Gewolb IH, Vice FL. Abnormalities in the coordination of respiration and swallow in preterm infants with bronchopulmonary dysplasia. Dev Med Child Neurol. 2006 Jul. 48(7):595-9. [Medline].

  148. Gewolb IH, Vice FL. Maturational changes in the rhythms, patterning, and coordination of respiration and swallow during feeding in preterm and term infants. Dev Med Child Neurol. 2006 Jul. 48(7):589-94. [Medline].

  149. Hunt CE. Ontogeny of autonomic regulation in late preterm infants born at 34-37 weeks postmenstrual age. Semin Perinatol. 2006 Apr. 30(2):73-6. [Medline].

  150. Khan A, Qurashi M, Kwiatkowski K, et al. Measurement of the CO2 apneic threshold in newborn infants: possible relevance for periodic breathing and apnea. J Appl Physiol. 2005 Apr. 98(4):1171-6. [Medline].

  151. Molloy EJ, Di Fiore JM, Martin RJ. Does gastroesophageal reflux cause apnea in preterm infants?. Biol Neonate. 2005. 87(4):254-61. [Medline].

Central apnea is defined as the cessation of both airflow and respiratory effort. ECG = electrocardiogram; HR = heart rate; THO = thoracic impedance; FLOW = air flow; ACT = ; SpO2 = peripheral oxygen saturation; STAGE = sleep stage.
Polysomnogram. Mixed apnea contains elements of both central and obstructive apnea. ECG = electrocardiogram; HR = heart rate (bpm); THO = thoracic movement; FLOW = flow the from nose and mouth; ACT = gross body movement; SpO2 = peripheral oxygen saturation (%); STAGE = sleep stage, where AT = active sleep.
Polysomnogram. Periodic breathing is defined as periods of regular respiration for as long as 20 seconds followed by apneic periods no longer than 10 seconds that occur at least 3 times in succession. ECG = electrocardiogram; HR = heart rate (bpm); THO = thoracic movement; FLOW = flow the from nose and mouth; ACT = gross body movement.
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