Apnea of Prematurity

No Results

No Results

processing….

Our understanding of the anatomy, physiology, biochemistry, and molecular biology of neonatal breathing has increased in recent years. [1, 2, 3, 4] For instance, emerging data are elucidating the genes involved in the embryonic development of central respiratory centers and their neural networks. [5] The central respiratory generator is essential for fetal breathing movements. It appears early in pregnancy and importantly contributes to pulmonary development. [6]

In the fetus, breathing is intermittent and occurs during the low-voltage electrocortical state (analogous to rapid eye movement [REM] sleep) and becomes continuous immediately after birth. The regulatory neurologic mechanisms that cause the transition from intermittent fetal breathing to continuous neonatal breathing are incompletely appreciated. [7, 8]

After birth, apnea of prematurity (AOP) is a major concern for caregivers in intensive care nurseries. The magnitude of this problem resulted in the National Institutes of Child Health and Human Development (NICHD) convening a workshop on apnea of prematurity. Summary Proceedings from the Apnea-of-Prematurity Group have been published.

The NICHD review group emphasized the following conclusions:

No consensus has been reached regarding the definition, diagnosis, or treatment of apnea of prematurity.

Systematic research has not been conducted to investigate the value of different interventions for apnea of prematurity.

Available technology is not routinely used to document real-time events associated with apnea.

The time required to demonstrate an improvement in apnea of prematurity with a specific treatment has not been established.

The observational period needed after therapy for apnea of prematurity is unknown, and an appropriate duration of surveillance off therapy is needed to reasonably prevent acute life-threatening events.

Important confounding conditions that influence the occurrence of apnea of prematurity are poorly recognized and/or integrated into care.

The relationship between gastroesophageal reflux (GER) and apnea of prematurity requires additional investigation because current knowledge suggests an infrequent association.

Improved characterization of the effects of apnea of prematurity on neurodevelopment during infancy and childhood is needed.

Other confounders associated with brain injury in preterm infants are difficult to separate from apnea of prematurity as meaningful causes of abnormal child development.

The NICHD review group also made recommendations about what issues associated with apnea of prematurity that need urgent attention, what research methods might be best for future studies, what outcomes are essential to our understanding of apnea of prematurity, and what ethical principles should govern future investigations of apnea of prematurity.

Given this discussion from the NICHD review group, the present article provides state-of-the-art information regarding what is and what is not known about apnea of prematurity.

Apnea is defined as the cessation of breathing for more than 20 seconds or apnea or the cessation of breathing for less than 20 seconds if it is accompanied by bradycardia or oxygen (O2) desaturation. [9] Note the following:

Bradycardia in a premature neonate is considered clinically significant when the heart rate slows by least 30 bpm from the resting heart rate.

An O2 saturation level of less than 85% is considered pathologic in this age group, as is a decrease in O2 saturation should it persist for 5 seconds or longer.

These definitions represent clinically significant changes in apnea, bradycardia, and O2 saturation changes and rarely occur in healthy preterm neonates older than 36 weeks after conception.

Apnea is classified as central, obstructive, or mixed. Note the following:

Central apnea is defined as complete cessation of respiration, which can be differentiated from obstructive apnea through a pneumogram, with cessation of airflow and respiratory effort (see the image below).

Obstructive apnea is the cessation of airflow in the presence of continued respiratory effort.

Mixed apnea contains elements of both central and obstructive apnea (see the image below), either within the same apneic pause or at different times during a period of respiratory recording.

Apnea of infancy (AOI) occurs when apnea persists in a neonate older than 37 weeks after conception. The physiologic aspects of apnea of prematurity and AOI coincide, though further studies are needed to determine their exact relationship.

Periodic breathing is defined as periods of regular respiration for as long as 20 seconds followed by apneic periods of 10 seconds or less that occur at least 3 times in succession (see the image below).

Periodic breathing may be observed for 2-6% of the breathing time in healthy term neonates and as much as 25% of the breathing time in preterm neonates. The occurrence of periodic breathing is directly proportional to the degree of prematurity.

Kelly and coworkers observed periodic breathing in 78% of neonates examined at 0-2 weeks of age. [10] The incidence substantially declined to 29% at the postconceptual ages of 39-52 weeks.

Periodic breathing typically does not occur in neonates during their first 2 days of life.

Periodic breathing most frequently occurs during active sleep, but it can also happen when neonates are awake or quietly sleeping. This pattern, commonly observed in patients at high altitudes, is eliminated with supplemental oxygenation and/or with the use of continuous positive airway pressure (CPAP). Because the prognosis is excellent and because the infant is not compromised, no treatment is usually required.

Immaturity and/or depression of the central respiratory drive to the muscles of respiration have been accepted as key factors in the pathogenesis of apnea of prematurity. [1] Vulnerability of the ventral surface of the medulla and adjacent areas in the brainstem to inhibitory mechanisms is the likely explanation for why apneic episodes occur in prematurely born infants. This vulnerability involves diverse clinicopathologic events. [4, 11] Inhibitory events that affect the central respiratory generator and initiate apnea include hypoxia, hyperthermia and adenosine secretion. [12] Studies of preterm infants and in animals (especially genetically altered mice) have enhanced our understanding of the molecular and biochemical events leading to maturation of the central respiratory generator in preterm infants. [2, 3, 13, 14]

Using noninvasive techniques, Henderson-Smart and coworkers documented that brainstem conduction times of auditory-evoked responses were longer in infants with apnea than in matched premature infants without apnea. [15] This study elucidated apnea in preterm infants by indirectly showing that infants with apnea had greater-than-expected immaturity of brainstem function, which was based on postconceptional age. This finding supports the concept than an immature brainstem eventually develops control of breathing as dendritic spines and synaptic connections mature. An observation that emphasizes the importance of the central respiratory generator is the finding of increased apnea among preterm infants with bilirubin-encephalopathy diagnosed by using abnormal auditory brainstem-evoked responses. [16]

The absence of respiratory muscle activity during central apnea unequivocally implicates depression of respiratory center output. In support of this concept, Gauda and associates (1989) documented reduced electromyographic activity in the diaphragm during spontaneous obstructed inspiratory efforts. [17] Such efforts characterize combined central and obstructive apnea. [18] Therefore, episodes of both central and mixed apneic share an element of decreased respiratory center output to the respiratory muscles.

Apnea during infancy occurs most frequently during active or REM sleep. [19, 20] Apnea occurs relatively infrequently during quiet sleep, when respiration is characteristically regular, with little breath-to-breath variation in tidal volume and respiratory rate. However, periodic breathing may predominantly occur during non-REM sleep. During active sleep, respiration is mostly paradoxical due to spinal motoneural inhibition of the activity of intercostal muscles. [21]

In extremely preterm infants, the paucity of quiet sleep, together with an extremely compliant rib cage, makes paradoxical chest-wall movements almost a constant phenomenon. Paradoxical chest movement may predispose the baby to apnea by decreasing functional residual capacity (FRC) and limiting oxygenation. [22]

Complex relationships exist between respiratory control; several sites of central chemosensitivity to carbon dioxide (CO2) during sleep; and various neuromechanical factors originating in the lungs, chest wall, and upper airway that modify respiratory function during sleep. [23]

Responses of chemoreceptors in preterm and term neonates were recently reviewed. [24, 25, 26] The response to elevated CO2 concentrations was blunted in prematurely born infants. This diminished response may partly be due to decreased central chemosensitivity or mechanical factors that prevent an adequate ventilatory response. [27, 28]

The slope of the response curve for CO2 is decreased for preterm infants who have apnea. [29] However, a cause-and-effect relationship between decreased CO2 responsiveness and apnea of prematurity has not been clearly established. Administration of CO2 ameliorates periodic breathing, but inhalation of CO2 is not a therapeutic option for human infants.

For many years, scientists have known that preterm infants respond to a decrease in inspired O2 concentration with a transient increase in ventilatory response, followed by return to baseline or even depression of ventilation. [30] This response to low O2 in infants appears to result from initial stimulation of peripheral chemoreceptors then overriding depression of the respiratory center as a result of hypoxemia. [31] Consistent with these findings is the observation that a progressive decrease in inspired O2 concentrations causes a significant flattening of CO2 responsiveness in preterm infants. [32]

This unstable response to low inspired O2 levels may play an important role in the origin of neonatal apnea. It offers a physiologic rationale for the decrease in incidence of apnea observed when a slightly increased concentration of inspired O2 is administered to infants with apnea. [33]

The Hering-Breuer reflex also plays an important role in modulating respiratory timing in human neonates. Pulmonary stretch receptors send an afferent neural input to brain and mediate the Hering-Breuer reflex by means of the vagus nerve. Thereafter, they inhibit inspiration, prolong expiration, or both, while increasing lung volume. [22] Active shortening of expiratory duration with decreased lung volume may provide a breathing strategy for preserving FRC in a neonate with a highly compliant chest wall.

Upper airway obstruction substantially contributes to apneic episodes in preterm infants, and upper airway muscles show preferential reflex activation in response to airway obstruction in infants. [34]

Gerhardt and Bancalari compared the ability of preterm infants with and those without apnea to respond to end-expiratory airway occlusion. [29, 35] Prolongation of the occluded inspiratory effort was significantly prolonged in the group without apnea. This finding suggested that this group had a relatively mature respiratory reflex response that improved their ability to respond to airway obstruction.

In premature infants, complex changes in pulmonary mechanics and ventilatory timing accompany apnea. [36] Before apnea occurs, total pulmonary resistance may increase in association with a decrease in tidal volume and prolongation of the expiratory time. Such changes have been noted before episodes of mixed, obstructive, and central apnea.

In 1982, Waggener and coworkers showed that a diminution in respiratory drive precedes apnea, a finding reminiscent of the cyclic alterations in respiratory drive. [37] After apnea resolves and respiration resumes, the respiratory drive in premature infants initially increases, possibly because of a cumulative effect of hypoxia and hypercapnia. Total pulmonary and supraglottic resistance also increases, perhaps in response to a decrease in lung volume and collapse of the upper airway when respiratory drive declines during the apnea.

Of note, within 2 or 3 breaths after apnea, pulmonary resistance and respiratory drive is restored to normal pre-apnea values in premature infants. Therefore, the neural systems that restore respiratory homeostasis appear to be capable of mounting an adequate response, even in premature infants with apnea.

Premature infants have pharyngeal or laryngeal obstruction during spontaneous apnea.

Thach (1983) proposed a model in which the negative luminal pressures generated during inspiration in the upper airway predispose a compliant pharynx to collapse. [38]

Many muscles of the upper airway, especially the genioglossus muscles, have been widely implicated in mixed and obstructive apnea affecting both infants and adults. Carlo, Martin, and Difiore compared the activity of the genioglossus muscles with that of the diaphragm in response to hypercapnic stimulation. [39] In preterm infants, genioglossus activation was delayed for about one minute after CO2 rebreathing was begun, and it occurred only after a CO2 threshold of approximately 45 mm Hg was reached.

In neonates inspiratory time is often modestly prolonged when end-expiratory airway occlusion prevents lung inflation. As indicated earlier, this effect is a manifestation of the Hering-Breuer reflex.

Studies in animals demonstrated that this vagally mediated inhibition of normal lung inflation has more influence on the upper airway muscles than on the diaphragm. [40]

The upper airway contains many sensory nerve endings that may respond to various chemical and mechanical stimuli. Sensory input from these upper airway receptors travels to the CNS by means of cranial nerves V, VI, IX, X, XI, and XII. They may strongly affect respiratory rate and rhythm, heart rate, and vascular resistance. [41]

The chemoreceptor drive may augment the ability of the upper airway muscles to respond to increasing negative pressure, whereas input from pulmonary stretch receptors inhibits it. [42]

Swallowing during the respiratory pause is unique to apnea and does not occur during periodic breathing. [43]

Adenosine and its analogs cause respiratory depression. [44] Adenosine antagonism is proposed as a mechanism to explain the therapeutic effect of aminophylline. [45]

GER and apnea are common in preterm infants. Because they often coexist, a lively and ongoing debate persists among healthcare professionals about the role of GER in apnea of prematurity.

An extensive literature review was undertaken to justify arguments about the role of GER in apnea of prematurity. Monitoring studies demonstrated that, when a relationship between reflux and apnea is observed, apnea may precede rather than follow reflux. [46, 47] During an apneic episode, loss of respiratory neural output may be accompanied by a decrease in lower esophageal tone, and GER occurs.

This phenomenon is supported by data from a newborn piglet model, which showed that hypoxia and apnea were accompanied by a reduction in lower esophageal sphincter pressure, which was a predisposing factor for GER. [48]

GER and apnea are also discussed in Differentials and in Special Concerns.

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 CO2 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; on the contrary, recent data suggest that it may be harmful. [49]

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. [50] 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. [51] Some authors have not related the use of methylxanthine to severe GER disease. [52]

Although not always apparent, apnea of prematurity is the most common problem in premature neonates. Approximately 70% of babies born before 34 weeks of gestation have clinically significant apnea, bradycardia, or O2 desaturation during their hospital stay. The more immature the infant, the higher his or her risk of apnea of prematurity. Apnea may occur during the postnatal period in 25% of neonates who weighed less than 2500 g at birth and in 84% of neonates who weigh less than 1000 g.

Carlo and Barrington showed that apnea may begin on the first day of life in neonates without respiratory distress syndrome. [53, 54] However, apnea of prematurity is always a diagnosis of exclusion. Many diseases manifest with apnea on the day of birth; examples are intrapartum magnesium exposure, systemic infections or the fetal inflammatory response syndrome, pneumonia, intracranial pathology, seizures, hypoglycemia, and other metabolic disturbances.

Approximately 50% or more of surviving infants who weighed less than 1500 g at birth have episodes of apnea that must be managed with pharmacologic intervention or ventilatory support. Mixed apnea accounts for about 50% of all cases of apnea in premature neonates; about 40% are central apneas, and 10% are obstructive apneas. [55] These percentages vary in different reports. In 50% of all apneic episodes, an obstructive component precedes or follows central apnea, which leads to mixed apnea.

To the authors’ knowledge, no investigators have compared the incidence of apnea of prematurity in the United States with those of other countries.

The authors know of no systematic, prospective clinical study that has been conducted to evaluate the role of a person’s race/ethnic background or sex on the incidence of apnea of prematurity.

A young gestational age at birth is associated with an increased incidence of apnea of prematurity. The age at which apnea of prematurity resolves depends on several factors. The mean time for severe apnea of prematurity to resolve is approximately 43 weeks after conception, but a prolonged duration of risk is not uncommon. [9]

In one report, about 6-22% of babies with a very low birth weight had apnea at term. [56] Approximately 91% of premature neonates had apnea of longer than 12 seconds at the time of hospital discharge. Of these babies, 31% also had bradycardia, and 6.5% required prolonged hospitalization because of the severity of their apnea and bradycardia.

These findings show that apnea of prematurity does not resolve at term in many low birth weight infants and that it may persist for some time after hospital discharge.

Butcher-Puech and coworkers found that infants in whom obstructive apnea exceeded 20 seconds had an increased incidence of intraventricular hemorrhage, hydrocephalus, prolonged mechanical ventilation, and abnormal neurologic development after their first year of life. [57]

In 1985, Perlman and Volpe described a decrease in the cerebral blood flow velocity that accompanies severe bradycardia (heart rate < 80 bpm). [58] Infants with clinically significant apnea of prematurity do not perform as well as prematurely born infants without recurrent apneas during neurodevelopmental follow-up testing. [59, 60]

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 patient education resources, see Children’s Health Center, as well as 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. 2006 Dec. 33(4):883-914; abstract x. [Medline].

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

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

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

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

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

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].

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

Martin RJ, Miller MJ, Carlo WA. Pathogenesis of apnea in preterm infants. J Pediatr. 1986 Nov. 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. 2005 Nov 15. 149(1-3):165-79. [Medline].

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].

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].

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].

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].

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. 1977 Feb. 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. 2005 Nov 1. 28(11):1428-36. [Medline].

Bryan AC, Bryan MH. Control of respiration in the newborn. Clin Perinatol. 1978 Sep. 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. 1979 Feb. 94(2):271-4. [Medline].

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

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

Hunt CE, Hauck FR. Sudden infant death syndrome. CMAJ. 2006 Jun 20. 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. 1990 Mar. 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. 1987 Mar. 62(3):1010-3. [Medline].

Gerhardt T, Bancalari E. Apnea of prematurity: II. Respiratory reflexes. Pediatrics. 1984 Jul. 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. 1952 May. 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. 2004 Jun. 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. 1975 Dec. 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. 2002 Nov. 110(5):884-8. [Medline].

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].

Gerhardt T, Bancalari E. Apnea of prematurity: I. Lung function and regulation of breathing. Pediatrics. 1984 Jul. 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. 1993 Aug. 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. 1982 May. 52(5):1288-95. [Medline].

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.

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].

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].

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

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].

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].

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

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].

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].

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].

Terrin G, Passariello A, De Curtis M, et al. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics. 2012 Jan. 129(1):e40-5. [Medline].

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

Newell SJ, Booth IW, Morgan ME, et al. Gastro-oesophageal reflux in preterm infants. Arch Dis Child. 1989 Jun. 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. 2001 Jan. 32(1):45-9. [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. 1982 Jul. 126(1):103-7. [Medline].

Barrington KJ, Finer NN. Periodic breathing and apnea in preterm infants. Pediatr Res. 1990 Feb. 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. 1992 Dec. 121(6):943-50. [Medline].

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].

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].

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].

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].

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].

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].

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. 2004 Jun. 9(3):195-203. [Medline].

Powell MB, Ahlers-Schmidt CR, Engel M, Bloom BT. Clinically significant cardiopulmonary events and the effect of definition standardization on apnea of prematurity management. J Perinatol. 2016 Sep 29 [Epub ahead of print]. [Medline].

Eichenwald EC, Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of prematurity. Pediatrics. 2016 Jan. 137(1):[Medline].

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

Andrade EO, Arain A, Malow BA. Partial epilepsy presenting as apneic seizures without posturing. Pediatr Neurol. 2006 Nov. 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. 2002 Mar-Apr. 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. 1998 Jul. 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. 2005 Dec. 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. 1984 Feb. 59(2):120-5. [Medline].

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

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].

Rasch DK, Huber PA, Richardson CJ, et al. Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr. 1982 Feb. 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. 2003 Jul. 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].

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].

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].

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].

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].

Kurth CD, Spitzer AR, Broennle AM, Downes JJ. Postoperative apnea in preterm infants. Anesthesiology. 1987 Apr. 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. 1993 Jun. 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. 1998 Mar. 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. 2005 Aug. 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. 2004 Jul. 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. 2007 Jan 22. 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 Jun 19. 6:20. [Medline].

Reid B, Wang H, Guillet R. Apnea after routine eye examinations inpremature infants. Am J Perinatol. 2016 Jul 11 [Epub ahead of print]. [Medline].

Thach BT. Reflux associated apnea in infants: evidence for a laryngeal chemoreflex. Am J Med. 1997 Nov 24. 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. 2005 Apr. 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. 1990 Jul. 25(7):755-7. [Medline].

Justo RN, Gray PH. Fundoplication in preterm infants with gastro-oesophageal reflux. J Paediatr Child Health. 1991 Aug. 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. 1991 Oct. 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. 2005 Nov. 116(5):1059-63. [Medline].

Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnea in premature infants. J Pediatr. 2001 Mar. 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. 2004 Oct. 145(4):499-502. [Medline].

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].

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].

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].

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].

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].

Arnon SS, Midura TF, Clay SA, et al. Infant botulism. Epidemiological, clinical, and laboratory aspects. JAMA. 1977 May 2. 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. 1983 Feb. 58(2):92-100. [Medline].

Cademartiri F, Luccichenti G, Lagana 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].

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].

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].

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

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].

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].

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].

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].

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].

[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].

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

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

Millar D, Schmidt B. Controversies surrounding xanthine therapy. Semin Neonatol. 2004 Jun. 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].

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].

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

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

Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for prevention of apnoea in preterm infants. Cochrane Database Syst Rev. 2010 Dec 8. 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. 2012 Jan 18. 307(3):275-82. [Medline].

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].

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].

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].

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].

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].

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].

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

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].

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].

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].

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].

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. 2004 Apr. 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].

Hymel KP. Distinguishing sudden infant death syndrome from child abuse fatalities. Pediatrics. 2006 Jul. 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. 1999 Oct. 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. 2007 Mar. 150(3):224-8. [Medline].

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].

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].

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].

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].

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].

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].

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].

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].

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].

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].

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

Dharmendra J Nimavat, MD, FAAP Associate Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine; Staff Neonatologist, Clinical Director, NICU Regional Perinatal Center, HSHS St John’s Children’s Hospital

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 Academy of Pediatrics, American Association for the Advancement of Science, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, American Thoracic Society, European Society for Paediatric Research, Pediatric Infectious Diseases Society, Perinatal Research Society, Society for Pediatric Research, Western 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.

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.

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.

Apnea of Prematurity

Research & References of Apnea of Prematurity|A&C Accounting And Tax Services
Source