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Apnea of Prematurity

Richard J. Martin, Christopher G. Wilson

10.1002/cphy.c100021

Source: Volume 2, Issue 4, October 2012

Published online: October 2012

Full Article on Wiley Online Library



Abstract

Apnea of prematurity is a significant problem due to immaturity of the central neural control circuitry responsible for integrating afferent input and central rhythm. In this review, we provide an overview of the pathogenesis of apnea of prematurity—including our current understanding of the role that afferent input to the brain stem plays in synergy with the central pattern generation circuitry in the emergence of apnea of prematurity. We then discuss the interplay of apnea, bradycardia, desaturation, as well as the genesis of central, mixed, and obstructive apnea. Finally, we provide a summary of the physiological basis for current therapeutic approaches to treating apnea of prematurity, and conclude with an overview of proposed long‐term consequences of the resultant intermittent hypoxic episodes. © 2012 American Physiological Society. Compr Physiol 2:2923‐2931, 2012.

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Figure 1. Figure 1.

Specific contributory causes of apnea. CNS, central nervous system.
Figure 2. Figure 2.

Diagram of the relationship between inputs and integration at the brain stem in relation to autonomic “stability.” The role that phasic inputs from the lung stretch receptors and other “noisy” inputs play in coordinating and producing robust rhythm depends on the central integration at the brain stem that changes dramatically in early development. Greater respiratory stability should decrease the resultant morbidities that may be a consequence of intermittent hypoxia.
Figure 3. Figure 3.

Proposed physiologic mechanisms whereby apnea induces reflex bradycardia. This can occur secondary to hypoxemia in the absence of lung inflation or by stimulation of upper airway inhibitory afferents.
Figure 4. Figure 4.

The interplay of gas exchange depends on oxygen carrying capacity as well as hemoglobin affinity. Since premature children have a higher oxygen consumption, the relative carrying capacity and significance of neonatal hemoglobin kinetics may play a significant role in the evolution of apnea of prematurity.
Figure 5. Figure 5.

Evidence that adenosine A2A receptors modulate breathing rhythm in a developmentally dependent manner. (A) Integrated diaphragm electromyography in rats at P14, P21, and Adult (P35) showing the inhibitory effect of the adenosine A2A agonist, CGS21680, upon breathing. (B) Staining for A2A receptor protein in pre‐Bötzinger complex on the left, and GAD67 in Bötzinger complex (Bc) on the right, at ages P4, P7, P14, and P21 in rat. Scale bar = 100 microns.


Figure 1.

Specific contributory causes of apnea. CNS, central nervous system.



Figure 2.

Diagram of the relationship between inputs and integration at the brain stem in relation to autonomic “stability.” The role that phasic inputs from the lung stretch receptors and other “noisy” inputs play in coordinating and producing robust rhythm depends on the central integration at the brain stem that changes dramatically in early development. Greater respiratory stability should decrease the resultant morbidities that may be a consequence of intermittent hypoxia.



Figure 3.

Proposed physiologic mechanisms whereby apnea induces reflex bradycardia. This can occur secondary to hypoxemia in the absence of lung inflation or by stimulation of upper airway inhibitory afferents.



Figure 4.

The interplay of gas exchange depends on oxygen carrying capacity as well as hemoglobin affinity. Since premature children have a higher oxygen consumption, the relative carrying capacity and significance of neonatal hemoglobin kinetics may play a significant role in the evolution of apnea of prematurity.



Figure 5.

Evidence that adenosine A2A receptors modulate breathing rhythm in a developmentally dependent manner. (A) Integrated diaphragm electromyography in rats at P14, P21, and Adult (P35) showing the inhibitory effect of the adenosine A2A agonist, CGS21680, upon breathing. (B) Staining for A2A receptor protein in pre‐Bötzinger complex on the left, and GAD67 in Bötzinger complex (Bc) on the right, at ages P4, P7, P14, and P21 in rat. Scale bar = 100 microns.

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Richard J. Martin, Christopher G. Wilson. Apnea of Prematurity. Compr Physiol 2012, 2: 2923-2931. doi: 10.1002/cphy.c100021