eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Apnea of Prematurity: Treatment & Medication

Author: Dharmendra J Nimavat, MD, FAAP, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine
Coauthor(s): Michael P Sherman, MD, Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Director, Fellowship Training Program in Neonatal-Perinatal Medicine, NICU, Columbia Regional Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine; Rene L Santin, MD, Consulting Staff, Department of Pediatrics, Division of Neonatology, Primary Care Centers of Eastern Kentucky; 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
Contributor Information and Disclosures

Updated: Oct 26, 2009

Treatment

Medical Care

Goal of medical therapy

The principal goals of treating apnea of prematurity (AOP) are to address its cause and to provide appropriate medical management. For example, bacterial sepsis that causes apnea is treated with antibiotics and other supportive therapies, whereas seizures require anticonvulsants. The use of assisted ventilation to manage severe apnea, bradycardia, and O2 desaturation can be life saving, and assisted ventilation and O2 may be required to prevent injury to the CNS. The primary disease process must be identified and treated.

When all causes of apnea other than prematurity are excluded during the diagnostic work-up, apnea of prematurity is the presumptive etiology. Caregivers must decide which intervention is appropriate given the severity of the patient's apnea, bradycardia, and O2 desaturation. For example, an infant who has an inadequate response to tactile stimulation and O2 administration and who requires airway suctioning and bag-mask ventilation to recover suggests a serious problem.

A useful strategy is to have a protocol that defines escalating treatments for apnea of prematurity. Depending on the frequency and the severity of apnea, bradycardia, and O2 desaturation, common treatments include stimulation (usually tactile), methylxanthine, or assisted ventilation (eg, nasal continuous positive airway pressure [CPAP], mechanical ventilation).104

Pantalitschka et al compared 4 modes of nasal respiratory support for apnea of prematurity in very low birthweight infants: intermittent positive pressure ventilation (IPPV) via a conventional ventilator or a variable flow device and CPAP via a variable flow device or a constant flow underwater bubble system.105 In their randomized controlled trial with a crossover design, episodes of bradycardia or desaturation occurred at a rate of 6.7 per hour with the conventional ventilator in IPPV mode and at a rate of 2.8 and 4.4 per hour with the variable flow device in CPAP and IPPV mode, respectively (P<0.03 for both compared with IPPV/conventional ventilator). Pantalitschka et al concluded that a variable flow nasal CPAP may be more effective than a conventional ventilator in nasal IPPV mode for treating apnea of prematurity.

Stimulation

Tactile stimulation is usually sufficient to terminate an isolated apneic event caused by central apnea. Stimulation akin to that used during neonatal resuscitation (eg, a gentle tap to the sole of the foot or rubbing the back) is often enough to terminate a central apnea. However, other measures may be required to treat an obstructive event or an episode of airway obstruction followed by central apnea.

If the upper airway is obstructed, repositioning the patient's head and neck or gently elevating the infant's jaw may alleviate the occlusion.

Use of a high-flow nasal cannula may open the airway enough to reduce obstructive apnea. As an alternative, high-flow oxygenation through a nasal cannula may be an agonist for receptors in the airway. Nasal irritation due to the cannula may prevent central apnea by causing arousal. Additional research is needed to ascertain the usefulness of high-flow nasal cannulas for treating apnea of prematurity.

Administration of O2

Supplemental oxygenation or bag-mask ventilation is indicated in infants with signs of bradycardia or desaturation.

Medical treatment is indicated when apneic episodes number 6-10 or more per day; when the infant does not respond to tactile stimulation; or when an event requires O2 and/or bag-mask ventilation to terminate apnea, bradycardia, and/or desaturation.

Avoid hyperoxia, which may increase the risk of retinopathy of prematurity (ROP).

Use of CPAP

CPAP has been used to treat apnea in preterm neonates, and it is indicated when the infant continues to have apneic episodes despite achieving a therapeutic serum level of methylxanthine.

CPAP is delivered with nasal prongs, a nasal mask, or a face mask with 3-6 cm of water pressure.

CPAP effectively treats mixed and obstructive apnea, but it has little or no effect on central apnea. This limitation suggests that CPAP may reduce the frequency of apnea by means of several mechanisms, including stabilization of the partial pressure of O2 (PaO2) by increasing the functional residual capacity (FRC), by altering the influence of stretch receptors on respiratory timing, or by splinting the upper airway in an open position.

Medication

Methylxanthines

Methylxanthines may help reduce the incidence of events in a neonate with central apnea, though apnea in 15-20% of infants does not respond to methylxanthines.

Questions have been raised regarding short- and long-term adverse effects in preterm infants.106 The relationship of methylxanthine therapy to neurodevelopmental outcomes over time is especially of concern. For this reason, a clinical trial related to the safety of caffeine in preterm infants with apnea of prematurity (AOP) is in progress.107

For the purpose of this review, pharmacotherapy is based on the 2006 NeoFax.104 This is the source for information regarding the administration, adverse effects, and interactions of methylxanthines (eg, drug and solution compatibility).

Caffeine

Caffeine is the preferred drug for treating apnea of prematurity.80 Caffeine is also the most acceptable prophylactic agent to facilitate successful extubation in preterm infants.108 Caffeine therapy may reduce the rate of bronchopulmonary dysplasia in very low-birth-weight infants.109

In addition, caffeine has a therapeutic margin wider than that of other methylxanthines, such as theophylline. Therefore, an overdose is less likely to occur with caffeine than with other drugs in its class.

Aminophylline

Aminophylline is the alternative methylxanthine. Aminophylline may be preferred when the physician wants to enhance contractility in the thoracic musculature or if the infant might benefit from the bronchodilator properties of aminophylline.110,111 This latter effect may be desired in infants with bronchopulmonary dysplasia.

One concern is that aminophylline may decrease cerebral blood flow.112,113,114,115,116

Early reports in the literature also indicate a concern about the role that aminophylline may play in the occurrence or severity of necrotizing enterocolitis.117,118,119

Doxapram

Doxapram is excluded as a therapy for apnea of prematurity because it is associated with reduced cerebral blood flow.120,121 Use of doxapram was not strongly recommended in a Cochrane Review.122 Doxapram should be reserved for infants in whom appropriate methylxanthine therapy and continuous positive airway pressure (CPAP) fail to control severe apneic events. If the caregiver wishes to use this agent, they should consult other resources regarding its administration.

Home Monitoring

Home monitoring after discharge is always necessary for infants whose apneic episodes continue despite the administration of methylxanthine. Infants undergoing methylxanthine therapy should rarely be sent home without a monitor because apnea may recur when they outgrow their therapeutic level.

Some families cannot manage monitoring in the home. In these cases, caffeine may be the only possible therapy.

For more information about follow-up care, see Follow-up.

Methylxanthines

Aminophylline appears to stimulate skeletal and diaphragmatic muscle contraction, increase the sensitivity of the ventilatory center to CO2, and stimulate the central respiratory drive.

Aminophylline, theophylline, and caffeine act as nonspecific inhibitors of adenosine A1 and adenosine A2a receptors.106 It is this last effect that raises concerns about the safety of methylxanthine therapy in preterm infants.


Aminophylline (Aminophyllin)

Indications include AOP (eg, apnea after extubation from assisted ventilation, apnea after general anesthesia, apnea during use of prostaglandin E1 to treat ductal-dependent heart defects).
Stimulates central respiratory drive and peripheral chemoreceptor activity; may increase diaphragmatic contractility.
Aminophylline salt is 78.9% theophylline; theophylline PO is 80% bioavailable. May need to adjust dose when changing from IV aminophylline to PO theophylline. In neonates, aminophylline significantly (30-80%) interconverted to caffeine.
IV and PO forms effective in about 80-85% of infants with central apnea.

Adult

Pediatric

Based on aminophylline (ie, not theophylline equivalent)
Loading dose: 4-8 mg/kg PO or IV over 30 min
Maintenance dose: 1.5-3 mg/kg/dose PO q8-12h or slow IV bolus q8-12h; start 8-12 h after loading dose
Therapeutic theophylline serum concentration (trough) for AOP is 7-12 mcg/mL; target theophylline serum concentration is 10-20 mcg/mL for bronchospasm in older infants (ie, some infants with bronchopulmonary dysplasia)

Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects of theophylline; allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon may increase effects of theophylline
May be associated with renal calcifications when used concurrently with furosemide and/or dexamethasone
IV incompatible with amiodarone, cefotaxime, ceftriaxone, clindamycin, dobutamine, epinephrine, hydralazine, insulin, isoproterenol, methadone, methylprednisolone, penicillin G, and phenytoin
Solution compatible with 5% or 10% dextrose in water and normal saline
Terminal injection site compatible with dextrose and amino acid solutions, lipid emulsions, acyclovir, ampicillin, amikacin, aztreonam, calcium gluconate, cefazolin, ceftazidime, dexamethasone, dopamine, enalaprilat, erythromycin lactobionate, famotidine, fluconazole, furosemide, heparin, hydrocortisone succinate, isoproterenol, lidocaine, methicillin, meropenem, metronidazole, midazolam, morphine, nafcillin, nitroglycerin, nitroprusside, pancuronium bromide, pentobarbital, phenobarbital, piperacillin, potassium chloride, prostaglandin E1, ranitidine, sodium bicarbonate, ticarcillin/clavulanate, tobramycin, vancomycin, and vecuronium

Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Emphasize slow IV infusion because changes in cerebral blood flow may occur
Caution with peptic ulcers, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; increased risk of toxicity in pulmonary edema or liver dysfunction because of reduced clearance; periodically monitor heart rate and blood glucose; consider withholding next dose if heart rate >180 bpm; may produce GI irritation, hyperglycemia, CNS irritability, and sleeplessness; signs of toxicity include sinus tachycardia, failure to gain weight, vomiting, jitteriness, hyperreflexia, and seizures


Caffeine citrate (Cafcit)

Indications include AOP (eg, apnea after extubation from assisted ventilation, apnea after general anesthesia). Therapeutic index more favorable than that of aminophylline.
Increases output of respiratory center, sensitivity of chemoreceptor to CO2, smooth muscle relaxation, and cardiac output.
Serum half-life 40-230 h, which declines until 60-wk postmenstrual age.

Adult

Pediatric

Loading dose: 20-40 mg/kg PO or IV over 30 min (equivalent to 10-20 mg/kg caffeine base)
Maintenance dose: 5-8 mg/kg PO qd or slow IV bolus starting 24 h after loading dose (equivalent to 2.5-4 mg/kg caffeine base)
Therapeutic trough serum concentrations 5-25 mcg/mL; measure trough levels 5 d after start of therapy; serum concentration >40-50 mcg/mL is toxic

Antagonizes actions of adenosine; may reduce clearance of theophylline by 25% and cause additive pharmacologic effects (decrease dose); additive positive inotropic and chronotropic effects may occur with beta-adrenergic agonists; cimetidine and fluconazole decrease clearance, increasing serum levels; phenytoin induces hepatic metabolism, decreasing half-life and increasing clearance; increases metabolism of phenobarbital and increases own metabolism
Incompatible with acyclovir, furosemide, lorazepam, oxacillin, and nitroglycerin
Solution compatible with 5% or 10% dextrose in water and normal saline
Terminal injection site compatible with dextrose and amino acid solutions, lipid emulsions, calcium gluconate, cefotaxime, cimetidine, clindamycin, dexamethasone, dobutamine, dopamine, epinephrine, fentanyl, gentamicin, heparin (<1 U/mL), isoproterenol, lidocaine, morphine, nitroprusside, pancuronium, penicillin G, phenobarbital, sodium bicarbonate, and vancomycin

Documented hypersensitivity; products containing sodium benzoate

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May increase O2 consumption and decrease weight gain; do not administer dose if heart rate persistently >180 bpm; functional cardiac symptoms (eg, extrasystoles) possible; restlessness and vomiting can be signs of toxicity; cholestatic hepatitis may prolong serum half-life

More on Apnea of Prematurity

Overview: Apnea of Prematurity
Differential Diagnoses & Workup: Apnea of Prematurity
Treatment & Medication: Apnea of Prematurity
Follow-up: Apnea of Prematurity
Multimedia: Apnea of Prematurity
References
[ CLOSE WINDOW ]

References

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

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

  3. Gozal D. New concepts in abnormalities of respiratory control in children. Curr Opin Pediatr. Jun 2004;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. Dec 2003;28(3):277-94. [Medline].

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

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

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

  9. [Guideline] Finer NN, Higgins R, Kattwinkel J, Martin RJ. Summary proceedings from the apnea-of-prematurity group. Pediatrics. Mar 2006;117(3 Pt 2):S47-51. [Medline]. [Full Text].

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

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

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

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

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

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

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

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

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

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

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

  21. 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. Nov 1 2005;28(11):1428-36. [Medline].

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

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

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

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

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

  27. 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].

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  43. 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. Jun 1994;76(6):2656-62. [Medline].

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

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

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

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

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

  49. 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. Jul 2002;52(1):50-5. [Medline].

  50. 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. Jul 1982;126(1):103-7. [Medline].

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

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

  53. 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. Oct 1985;60(10):953-8. [Medline].

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

  55. 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. Feb 2006;160(2):203-10. [Medline].

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

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

  58. 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). Mar 2005;62(3):266-81. [Medline].

  59. Mayock DE. Apnea. Revised February 24, 2000. University of Washington Division of Neonatology Web site. NICU-WEB. Available at http://depts.washington.edu/nicuweb/NICU-WEB/apnea.stm.

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

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

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

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

  64. 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. Jan 2001;32(1):45-9. [Medline].

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

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

  67. 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. Jul 1998;17(7):593-8. [Medline].

  68. 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].

  69. 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. Dec 2005;24(12):1040-4. [Medline].

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

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

  72. Rasch DK, Huber PA, Richardson CJ, et al. Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr. Feb 1982;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. Jul 2003;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. [Best Evidence] Bell EF, Strauss RG, Widness JA, et al. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics. Jun 2005;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. Dec 2004;24(12):757-62. [Medline].

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

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

  79. 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].

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

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

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

  83. 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. Jul 2004;145(1):58-66. [Medline].

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

  85. 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].

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

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

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

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

  90. 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. Oct 1991;145(10):1132-6. [Medline].

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

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

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

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

  95. 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. Jun 1990;13(6):303-8. [Medline].

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

  97. 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. May-Jun 2004;23(3):39-48. [Medline].

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

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

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

  101. 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. Aug 2004;75(2):122-5. [Medline].

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

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

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

  105. [Best Evidence] 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. Jul 2009;94(4):F245-8. [Medline].

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

  107. 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].

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

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

  110. 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. Oct 1992;73(4):1425-31. [Medline].

  111. 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. Mar 1991;80(3):308-15. [Medline].

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

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

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

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

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

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

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

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

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

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

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

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

  124. 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. Nov 2005;116(5):1245-55. [Medline]. [Full Text].

  125. [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. Jul 2003;112(1 Pt 1):199-202. [Medline].

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

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

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

  129. 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. Oct 1999;104(4 Pt 1):986-7. [Medline].

  130. 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].

  131. 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].

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

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

  134. 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. Jul 24 2004;329(7459):193-8. [Medline].

  135. 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. May 2006;26(5):306-12. [Medline].

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

  137. 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. Oct 1997;100(4):613-21. [Medline].

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

  139. Al-Matary A, Kutbi I, Qurashi M, et al. Increased peripheral chemoreceptor activity may be critical in destabilizing breathing in neonates. Semin Perinatol. Aug 2004;28(4):264-72. [Medline].

  140. Brooks JG. Apparent life-threatening events and apnea of infancy. Clin Perinatol. Dec 1992;19(4):809-38. [Medline].

  141. Chardon K, Bach V, Telliez F, et al. Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages. J Appl Physiol. Jun 2004;96(6):2161-6. [Medline].

  142. Chardon K, Telliez F, Bach V, et al. Effects of warm and cool thermal conditions on ventilatory responses to hyperoxic test in neonates. Respir Physiol Neurobiol. May 20 2004;140(2):145-53. [Medline].

  143. Decker MJ, Rye DB. Neonatal intermittent hypoxia impairs dopamine signaling and executive functioning. Sleep Breath. Dec 2002;6(4):205-10. [Medline].

  144. Eichenwald EC, Aina A, Stark AR. Apnea frequently persists beyond term gestation in infants delivered at 24 to 28 weeks. Pediatrics. Sep 1997;100(3 Pt 1):354-9. [Medline].

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

  146. 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. Jul 2006;48(7):589-94. [Medline].

  147. Henderson-Smart DJ, Butcher-Puech MC, Edwards DA. Incidence and mechanism of bradycardia during apnoea in preterm infants. Arch Dis Child. Mar 1986;61(3):227-32. [Medline].

  148. Henderson-Smart DJ, Ponsonby AL, Murphy E. Reducing the risk of sudden infant death syndrome: a review of the scientific literature. J Paediatr Child Health. Jun 1998;34(3):213-9. [Medline].

  149. Henderson-Smart DJ, Steer P. Prophylactic caffeine to prevent postoperative apnea following general anesthesia in preterm infants. Cochrane Database Syst Rev. 2001;(4):CD000048. [Medline].

  150. Herschel M, Mittendorf R. Tocolytic magnesium sulfate toxicity and unexpected neonatal death. J Perinatol. Jun 2001;21(4):261-2. [Medline].

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

  152. 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. Apr 2005;98(4):1171-6. [Medline].

  153. Kugelman A, Bilker A, Bader D, et al. Sidestream end-tidal capnometry as related to infant's position and maturation. Acta Paediatr. 2002;91(8):869-73. [Medline].

  154. Lipsky CL, Gibson E, Cullen JA, et al. The timing of SIDS deaths in premature infants in an urban population. Clin Pediatr (Phila). Aug 1995;34(8):410-4. [Medline].

  155. Martin RJ, Okken A, Katona PG, Klaus MH. Effect of lung volume on expiratory time in the newborn infant. J Appl Physiol. Jul 1978;45(1):18-23. [Medline].

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

  157. Perlman JM. Brain injury in the term infant. Semin Perinatol. Dec 2004;28(6):415-24. [Medline].

  158. Pichler G, Urlesberger B, Müller W. Impact of bradycardia on cerebral oxygenation and cerebral blood volume during apnoea in preterm infants. Physiol Meas. Aug 2003;24(3):671-80. [Medline].

  159. Razi NM, DeLauter M, Pandit PB. Periodic breathing and oxygen saturation in preterm infants at discharge. J Perinatol. Sep 2002;22(6):442-4. [Medline].

  160. Rigatto H. Maturation of breathing. Clin Perinatol. Dec 1992;19(4):739-56. [Medline].

  161. Rigatto H, Brady JP. Periodic breathing and apnea in preterm infants. I. Evidence for hypoventilation possibly due to central respiratory depression. Pediatrics. Aug 1972;50(2):202-18. [Medline].

  162. Sanchez PJ, Laptook AR, Fisher L, et al. Apnea after immunization of preterm infants. J Pediatr. May 1997;130(5):746-51. [Medline].

  163. Sawnani H, Jackson T, Murphy T, et al. The effect of maternal smoking on respiratory and arousal patterns in preterm infants during sleep. Am J Respir Crit Care Med. Mar 15 2004;169(6):733-8. [Medline].

  164. Southall DP, Levitt GA, Richards JM, et al. Undetected episodes of prolonged apnea and severe bradycardia in preterm infants. Pediatrics. Oct 1983;72(4):541-51. [Medline].

  165. Stefano JL, Anday EK, Davis JM, et al. Pneumograms in premature infants: a study of longitudinal data. Am J Perinatol. May 1991;8(3):170-3. [Medline].

  166. Tamim H, Khogali M, Beydoun H, et al. Consanguinity and apnea of prematurity. Am J Epidemiol. Nov 15 2003;158(10):942-6. [Medline].

  167. Yamamoto A, Yokoyama N, Yonetani M, et al. Evaluation of change of cerebral circulation by SpO2 in preterm infants with apneic episodes using near infrared spectroscopy. Pediatr Int. Dec 2003;45(6):661-4. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

apnea of prematurity, AOP, fetal breathing, pathologic apnea, central apnea, obstructive apnea, mixed apnea, apnea of infancy, AOI, neonatal apnea, sudden infant death syndrome, SIDS, crib death, cot death

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Dharmendra J Nimavat, MD, FAAP, Assistant 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 and American Association of Physicians of Indian Origin
Disclosure: Nothing to disclose.

Coauthor(s)

Michael P Sherman, MD, Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Director, Fellowship Training Program in Neonatal-Perinatal Medicine, NICU, Columbia Regional Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine
Michael P Sherman, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, European Society for Paediatric Research, Perinatal Research Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Rene L Santin, MD, Consulting Staff, Department of Pediatrics, Division of Neonatology, Primary Care Centers of Eastern Kentucky
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.

Medical Editor

Steven M Donn, MD, Professor of Pediatrics, University of Michigan Medical School; Director, Division of Neonatal-Perinatal Medicine, Department of Pediatrics, CS Mott Children's Hospital, University of Michigan Health System
Steven M Donn, MD is a member of the following medical societies: American Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, 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, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and 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 Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.