Apnea of Prematurity Follow-up
- Author: Dharmendra J Nimavat, MD, FAAP; Chief Editor: Ted Rosenkrantz, MD more...
Further Inpatient Care
Apnea-free interval before discharge
Most neonatologists agree that babies should be apnea-free for 2-10 days before discharge. However, the interval between the last apneic event and a safe time for discharge is not clearly established. The minimum apnea-free period is debated among clinicians. Darnall et al concluded that otherwise healthy preterm neonates continue to have periods of apnea separated by as many as 8 days before the last episode of apnea before discharge.[126] Infants with long intervals between apneic event often have risk factors other than apnea of prematurity (AOP).
Home monitoring
Home monitoring after discharge is necessary for infants whose apneic episodes continue despite the administration of methylxanthine. Infants undergoing methylxanthine therapy rarely are sent home without a monitor because apnea may recur after they outgrow their therapeutic level. Without a monitor, caregivers may not know when apnea reappears.
Some families cannot manage monitoring in the home. In these cases, the administration of caffeine may be the only possible therapy. Infants in this situation need frequent follow-up visits, and they should be readmitted for further evaluation when their blood levels approach the subtherapeutic range.
Further Outpatient Care
Home monitoring
Various agencies and organizations have stated that home monitoring cannot prevent sudden infant death syndrome (SIDS), also called crib death or cot death, in preterm infants who have apnea of prematurity during their hospitalization.[9]
Indications for home monitoring
Home monitoring may be indicated in the situations described below.
- Historical evidence suggests the occurrence of clinically significant apnea or an apparent life-threatening event (ALTE).
- Recording monitoring or multichannel evaluation documents apnea.
- The patient has gastroesophageal reflux (GER) with apnea.
- A sibling or twin of the patient died from SIDS or another postneonatal cause of death (see Special Concerns).
The National Institutes of Health (NIH) consensus conference recommends monitoring for the siblings of infants with SIDS, but only after 2 SIDS-related deaths occur in a family. Physicians often begin monitoring after one sibling dies from SIDS; this practice may be related to a fear of litigation should another child in the family die from SIDS. Siblings of patients who died from SIDS are routinely monitored until one month past the patient's age at death.
Monitoring is not indicated to prevent SIDS in infants older than one year, though proponents believe that such monitoring reduces anxiety in the parents of high-risk infants. Opponents of monitoring cite a lack of evidence to show that monitoring reduces the rate of SIDS. They argue that monitors intrude on the family's life and that they are poorly tolerated by the family.[9]
Types of monitors
Several types of cardiorespiratory monitors are available for home use in the United States. The most common type combines impedance pneumography with an assessment of the patient's mean heart rate. The most notable drawback of impedance monitors is their inability to detect obstructive apnea. Newer monitors can minimize false alarms caused by motion artifact.
Standard home monitors detect respiratory signals and heart rates. Electrodes are placed directly on the infant's chest or inside an adjustable belt secured around his or her chest.
Monitoring units should be capable of recording cardiac and respiratory data because this information can help the physician in evaluating the need to stop medication or monitoring. These devices also record compliance with monitor use. The event recorder contains a computer chip that continuously records respiratory and cardiac signals. Normal signals are erased, but any event that deviates from preset parameters activates the monitor to save records of that event, as well as data 15-75 before and 15-75 seconds it. Additional channels are available to record pulse oximetry readings, nasal airflow, and body position (eg, prone vs supine). The records are downloaded within 24 hours after a parent reports an event or after excessive alarms occur.
Many units now have computer modems that instantly transmit data to the physician's office for evaluation. These easily installed devices are especially useful for families who have had problems with events or alarms.
Some devices, such as pulse oximeters, piezo belts, and pressure capsules, have been impractical to use or have had limited applications. Newer technologies and software programs may soon make such oximeters and similar devices more practical than they once were.
All monitoring devices are associated with false alarms, which are alerts without in the absent of a true cardiorespiratory event. False alarms worry parents. If they happen often, they may discourage use of the monitor. Excessive false alarms can usually be minimized by adjusting the placement of the electrodes and by educating the parents.
Details of monitoring depend on the frequency of events observed during neonatal hospitalization, the size and stability of the infant at the time of discharge, and the degree of parental anxiety.
Follow-up of home monitoring and patient education
Careful follow-up is needed with all cases of home monitoring in prematurely born neonates. Physicians who have limited experience with home monitoring or who cannot interpret the downloaded recordings should seek assistance from a center or program with expertise in these areas.
The most important issue with monitoring is that Neonatal Resuscitation Program (NRP) instructors should educate parents, guardians, and other caregivers about neonatal resuscitation by using a mannequin before their child is discharged from the NICU.
Parents should also be educated about prenatal and postnatal factors associated with an increased risk of SIDS, namely, the following:[127, 25]
- Prenatal and postnatal tobacco use
- Opiate abuse during pregnancy
- Baby's prone sleeping position
- Pacifier use
- Use of soft bedding
- Shared sleeping with children and adults
- Illnesses in infants with bronchopulmonary dysplasia
- Genetic factors
Parents must also be aware that postural skull deformities have occurred after the AAP offered positioning recommendations in its Back to Sleep campaign.[128] Prematurely born infants are probably at increased risk. Ways to avoid or minimize skull deformities should be discussed with parents.
Parents of infants with home monitors must have a clearly designated person who they can contact on a regular basis and during emergencies. Many programs or centers provide 24-hour assistance for families of children with home monitors.
The mean duration of home monitoring for prematurely born neonates is often more than 6 weeks. Extended monitoring is reserved for infants whose recordings show notable cardiorespiratory abnormalities. Monitoring beyond age 1 year is uncommon. Most often, children who require such monitoring have other conditions that require the use of additional technology. An example is an infant with bronchopulmonary dysplasia who requires mechanical ventilation at home.
For infants who require therapy with a methylxanthine, drug therapy is typically stopped after 8 weeks without true events, but monitoring is continued for an additional 4 weeks.[129, 130] If no events are noted in this period, monitoring can be discontinued. These recommendations regarding discontinuing methylxanthines or home monitoring are not based on data from controlled studies; these investigations are badly needed.
Complications
Infants born prematurely are at increased risk for apnea and bradycardia after undergoing general anesthesia or sedation with ketamine, regardless of their history of apnea. Because of this increased risk, defer elective surgery, if possible, until approximately 52-60 weeks after conception to allow the infant's respiratory control mechanism to mature.
Prognosis
Regarding the natural history of apnea in infants born prematurely, the frequencies of all types of apnea gradually decreases during the first months of postnatal life. However, in some infants, apnea may persist until the age of 44 weeks after conception.
Patient Education
Family members and others involved in the care of an infant with apnea of prematurity should be well trained in cardiopulmonary resuscitation (CPR).
Many of the pitfalls of home monitoring can be avoided by providing 24-hour telephone access (the ideal level of service) to a designated physician or nurse who is involved in the infant's care. In addition to this access, families should receive frequent, regularly scheduled telephone calls from healthcare providers, as well as home visits by a nurse or respiratory technician or follow-up appointments in a clinic familiar with this field of care.
For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Sudden Infant Death Syndrome (SIDS).
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].
Gaultier C, Gallego J. Development of respiratory control: evolving concepts and perspectives. Respir Physiol Neurobiol. Nov 15 2005;149(1-3):3-15. [Medline].
Gozal D. New concepts in abnormalities of respiratory control in children. Curr Opin Pediatr. Jun 2004;16(3):305-8. [Medline].
Martin RJ, Abu-Shaweesh JM. Control of breathing and neonatal apnea. Biol Neonate. 2005;87(4):288-95. [Medline].
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].
Kotecha S. Lung growth for beginners. Paediatr Respir Rev. Dec 2000;1(4):308-13. [Medline].
Givan DC. Physiology of breathing and related pathological processes in infants. Semin Pediatr Neurol. Dec 2003;10(4):271-80. [Medline].
Sinha SK, Donn SM. Fetal-to-neonatal maladaptation. Semin Fetal Neonatal Med. Jun 2006;11(3):166-73. [Medline].
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].
Kelly DH, Shannon DC. Periodic breathing in infants with near-miss sudden infant death syndrome. Pediatrics. Mar 1979;63(3):355-60. [Medline].
Martin RJ, Miller MJ, Carlo WA. Pathogenesis of apnea in preterm infants. J Pediatr. Nov 1986;109(5):733-41. [Medline].
Lagercrantz H. Improved understanding of respiratory control--implications for the treatment of apnoea. Eur J Pediatr. 1995;154(8 Suppl 3):S10-2. [Medline].
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].
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].
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].
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].
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].
Martin RJ, Abu-Shaweesh JM, Baird TM. Apnoea of prematurity. Paediatr Respir Rev. 2004;5 Suppl A:S377-82. [Medline].
Gould JB, Lee AF, James O, et al. The sleep state characteristics of apnea during infancy. Pediatrics. Feb 1977;59(2):182-94. [Medline].
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].
Bryan AC, Bryan MH. Control of respiration in the newborn. Clin Perinatol. Sep 1978;5(2):269-81. [Medline].
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].
Krimsky WR, Leiter JC. Physiology of breathing and respiratory control during sleep. Semin Respir Crit Care Med. Feb 2005;26(1):5-12. [Medline].
Cohen G, Katz-Salamon M. Development of chemoreceptor responses in infants. Respir Physiol Neurobiol. Nov 15 2005;149(1-3):233-42. [Medline].
Hunt CE, Hauck FR. Sudden infant death syndrome. CMAJ. Jun 20 2006;174(13):1861-9. [Medline].
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].
Carlo WA, DiFiore JM. Respiratory muscle responses to changes in chemoreceptor drive in infants. J Appl Physiol. Mar 1990;68(3):1041-7. [Medline].
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].
Gerhardt T, Bancalari E. Apnea of prematurity: II. Respiratory reflexes. Pediatrics. Jul 1984;74(1):63-6. [Medline].
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].
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].
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].
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].
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].
Gerhardt T, Bancalari E. Apnea of prematurity: I. Lung function and regulation of breathing. Pediatrics. Jul 1984;74(1):58-62. [Medline].
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].
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].
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.
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].
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].
Harding R. Function of the larynx in the fetus and newborn. Annu Rev Physiol. 1984;46:645-59. [Medline].
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].
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].
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].
Darnall RA Jr. Aminophylline reduces hypoxic ventilatory depression: possible role of adenosine. Pediatr Res. Jul 1985;19(7):706-10. [Medline].
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].
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].
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].
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].
Barrington KJ, Finer NN. Periodic breathing and apnea in preterm infants. Pediatr Res. Feb 1990;27(2):118-21. [Medline].
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].
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].
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].
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].
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].
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].
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].
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.
Di Fiore JM. Neonatal cardiorespiratory monitoring techniques. Semin Neonatol. Jun 2004;9(3):195-203. [Medline].
Gamble YD, Lutin WP, Mathew OP. Non-sinus bradyarrhythmias in very low birth weight infants. J Perinatol. Jan 2007;27(1):65-7. [Medline].
Menon AP, Schefft GL, Thach BT. Apnea associated with regurgitation in infants. J Pediatr. Apr 1985;106(4):625-9. [Medline].
Newell SJ, Booth IW, Morgan ME, et al. Gastro-oesophageal reflux in preterm infants. Arch Dis Child. Jun 1989;64(6):780-6. [Medline].
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].
Andrade EO, Arain A, Malow BA. Partial epilepsy presenting as apneic seizures without posturing. Pediatr Neurol. Nov 2006;35(5):359-62. [Medline].
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].
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].
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].
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].
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].
Cheromcha DP, Hyman PE. Neonatal necrotizing enterocolitis. Inflammatory bowel disease of the newborn. Dig Dis Sci. Mar 1988;33(3 Suppl):78S-84S. [Medline].
Rasch DK, Huber PA, Richardson CJ, et al. Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr. Feb 1982;100(2):272-6. [Medline].
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].
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].
[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].
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].
Kurth CD, Spitzer AR, Broennle AM, Downes JJ. Postoperative apnea in preterm infants. Anesthesiology. Apr 1987;66(4):483-8. [Medline].
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].
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].
Henderson-Smart DJ, Steer P. Methylxanthine treatment for apnea in preterm infants. Cochrane Database Syst Rev. 2001;(3):CD000140. [Medline].
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].
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].
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].
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].
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].
Thach BT. Reflux associated apnea in infants: evidence for a laryngeal chemoreflex. Am J Med. Nov 24 1997;103(5A):120S-124S. [Medline].
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].
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].
Justo RN, Gray PH. Fundoplication in preterm infants with gastro-oesophageal reflux. J Paediatr Child Health. Aug 1991;27(4):250-4. [Medline].
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].
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].
Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnea in premature infants. J Pediatr. Mar 2001;138(3):355-60. [Medline].
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].
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].
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].
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].
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].
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].
Arnon SS, Midura TF, Clay SA, et al. Infant botulism. Epidemiological, clinical, and laboratory aspects. JAMA. May 2 1977;237(18):1946-51. [Medline].
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].
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].
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].
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].
Young TE, Mangum B. Methylxanthines. In: NeoFax. 19th ed. Raleigh, NC: Acorn; 2006:200-3.
[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].
Millar D, Schmidt B. Controversies surrounding xanthine therapy. Semin Neonatol. Jun 2004;9(3):239-44. [Medline].
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].
Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for extubation in preterm infants. Cochrane Database Syst Rev. 2003;(1):CD000139. [Medline].
[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].
Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants. Cochrane Database Syst Rev. Dec 8 2010;CD000139. [Medline].
Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev. Dec 8 2010;CD000140. [Medline].
Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for prevention of apnoea in preterm infants. Cochrane Database Syst Rev. Dec 8 2010;CD000432. [Medline].
Schmidt B, Anderson PJ, Doyle LW, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA. Jan 18 2012;307(3):275-82. [Medline].
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].
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].
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].
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].
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].
Robel-Tillig E, Vogtmann C. Aminophylline influences cerebral hyperperfusion after severe birth hypoxia. Acta Paediatr. Aug 2000;89(8):971-4. [Medline].
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].
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].
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].
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].
Dani C, Bertini G, Pezzati M, et al. Brain hemodynamic effects of doxapram in preterm infants. Biol Neonate. 2006;89(2):69-74. [Medline].
Roll C, Horsch S. Effect of doxapram on cerebral blood flow velocity in preterm infants. Neuropediatrics. Apr 2004;35(2):126-9. [Medline].
Henderson-Smart D, Steer P. Doxapram treatment for apnea in preterm infants. Cochrane Database Syst Rev. 2004;(4):CD000074. [Medline].
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].
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].
[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].
Spitzer AR, Fox WW. Infant apnea. Pediatr Clin North Am. Jun 1986;33(3):561-81. [Medline].
Spitzer AR, Gibson E. Home monitoring. Clin Perinatol. Dec 1992;19(4):907-26. [Medline].
Hymel KP. Distinguishing sudden infant death syndrome from child abuse fatalities. Pediatrics. Jul 2006;118(1):421-7. [Medline].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Brooks JG. Apparent life-threatening events and apnea of infancy. Clin Perinatol. Dec 1992;19(4):809-38. [Medline].
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].
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].
Decker MJ, Rye DB. Neonatal intermittent hypoxia impairs dopamine signaling and executive functioning. Sleep Breath. Dec 2002;6(4):205-10. [Medline].
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].
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].
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].
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].
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].
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].
Herschel M, Mittendorf R. Tocolytic magnesium sulfate toxicity and unexpected neonatal death. J Perinatol. Jun 2001;21(4):261-2. [Medline].
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].
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].
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].
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].
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].
Molloy EJ, Di Fiore JM, Martin RJ. Does gastroesophageal reflux cause apnea in preterm infants?. Biol Neonate. 2005;87(4):254-61. [Medline].
Perlman JM. Brain injury in the term infant. Semin Perinatol. Dec 2004;28(6):415-24. [Medline].
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].
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].
Rigatto H. Maturation of breathing. Clin Perinatol. Dec 1992;19(4):739-56. [Medline].
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].
Sanchez PJ, Laptook AR, Fisher L, et al. Apnea after immunization of preterm infants. J Pediatr. May 1997;130(5):746-51. [Medline].
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].
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].
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].
Tamim H, Khogali M, Beydoun H, et al. Consanguinity and apnea of prematurity. Am J Epidemiol. Nov 15 2003;158(10):942-6. [Medline].
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].

