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I. DEFINITION

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Apnea is common in preterm neonates and is a significant clinical problem. It is manifested by an unstable respiratory rhythm, reflecting the immaturity of the respiratory control system. Apnea can also be secondary to other pathological conditions, which need to be excluded before the diagnosis of apnea of prematurity is assumed. In contrast, periodic breathing is a benign condition and does not merit any treatment. Apnea is defined as cessation of breathing that lasts for at least 20 seconds and is accompanied by bradycardia, oxygen desaturation, or cyanosis.

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  1. Central apnea. Characterized by total cessation of inspiratory effort with no evidence of obstruction.

  2. Obstructive apnea. Infant tries to breathe against an obstructed airway resulting in chest wall motion without air flow throughout the entire apneic episode.

  3. Mixed apnea. Consists of obstructed respiratory efforts usually followed by central apnea. Purely obstructive apnea in the absence of a positional problem is probably uncommon.

  4. Periodic breathing. Periodic breathing is a normal breathing pattern followed by apnea for 5 to 10 seconds without change in heart rate or skin color. Periodic breathing consists of breathing for 10 to 15 seconds followed by apnea for 5 or 10 seconds, without change in heart rate or skin color, and the net effect may be hypoventilation. It is due to an imbalance between the effect of peripheral and central chemoreceptors on ventilatory drive. Periodic breathing in premature infants is often due to excessive stimulation by the chemoreceptors, thus promoting an imbalance. Prevalence of periodic breathing approaches 100% in preterm infants <1000 g. It is more frequent during active sleep. The prognosis is good, and it is controversial whether periodic breathing is associated with an increased risk for apnea of prematurity.

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II. INCIDENCE

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The incidence of apnea and periodic breathing in the term infant has not been adequately determined. More than 50% of infants weighing <1500 g and 90% of infants weighing <1000 g have apnea. Mixed apnea is the most common type (50%), followed by central (40%), and then obstructive (10%).

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III. PATHOPHYSIOLOGY

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Apnea of prematurity is a developmental disorder and reflects a “physiological” rather than “pathological” immature state of respiratory control.

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  1. Fetal to neonatal transition. The postnatal rise in Pao2 somewhat diminishes the response of peripheral chemoreceptors, resulting in a brief delay in the onset of spontaneous breathing. This effect is increased when neonates are exposed to 100% oxygen during resuscitation. The immature respiratory pattern and chemoreceptor function in premature infants may delay this postnatal adjustment, given fewer synaptic connections and less myelination of the immature brainstem.

  2. Ventilatory response to hypoxia. A transient increase in respiratory rate and tidal volume that lasts for 1–2 minutes followed by a late sustained decrease in spontaneous breathing. This unique response to hypoxia may last for several weeks in response to hypoxic episodes after birth. This late hypoventilatory depression associated with delayed postnatal respiratory adjustment occurs in premature infants. Peripheral chemoreceptor stimulation secondary to hypocapnia after hyperventilation may also contribute to apnea.

  3. Ventilatory response to laryngeal chemoreflex. The laryngeal chemoreflex is mediated through the superior laryngeal nerve afferents and is assumed to be ...

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