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  1. Definitions. Simply defined, apnea is the absence of respiratory shorter gas flow for a period of 20 s or more if associated with bradycardia or significant desaturation.

      1. Central apnea is of central nervous system (CNS) origin and characterized by the absence of gas flow with no respiratory effort.

      1. Obstructive apnea is continued respiratory effort not resulting in gas flow.

      1. Mixed apnea is a combination of the central and obstructive types.

      1. Periodic breathing, defined as three or more periods of apnea lasting ≥3 s within a 20 s period of otherwise normal respiration, is also common in the newborn period. Currently, it is not known whether an association exists between apnea and periodic breathing.

  2. Incidence. 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 is the most common type of apnea, followed by central and then obstructive. Another 30% have periodic breathing.

  3. Pathophysiology. Apnea and periodic breathing probably have a common pathophysiologic origin, apnea being a step further along the continuum than periodic breathing. Although the exact pathophysiology of these events has not yet been elucidated, there are many theories.

      1. Immaturity of respiratory control. Because apnea is seen most commonly in the premature infant, some type of immaturity of the respiratory control mechanism is thought to play a role in most cases.

          1. Hypoxic response. The preterm infant is known to have an abnormal biphasic response to hypoxia: a brief period of tachypnea followed by apnea. This response is unlike that seen in the adult or older child in whom hypoxia produces a state of prolonged tachypnea.

          1. Carbon dioxide response. The carbon dioxide response curve is shifted in the preterm infant, with higher levels of carbon dioxide required before respiration is stimulated.

      1. Sleep-related response. Sleep states may also play an important role in the development of apnea in the preterm infant. A shift from one sleep state to another is often characterized by instability of respiratory activity in the adult. The preterm infant is sleeping ~80% of the time and has difficulty making the transition between the sleeping and waking states. This may be associated with an increased risk for the development of apnea in the infants.

      1. Protective reflexes such as the apneic response to noxious substances in the airway may also play a role in the apneic episodes seen in the newborn infant.

      1. Muscle weakness. Overall muscle weakness (of both the muscles of respiration and the muscles that maintain airway patency) also plays an important role in pathophysiology.

      1. All of the preceding point to an immature respiratory control mechanism in the preterm infant. Whether the immaturity is operational at the level of the brainstem, the peripheral chemoreceptors, or the central receptors has yet to be determined. What is likely is that apnea results from a combination of immature afferent impulses to the respiratory control centers along with immature efferent pathways from these receptor sites, giving rise to the poor ventilation control.

      1. Pathologic states can also lead to apnea in the infant. The following disorders are all associated with apnea in the neonatal period: ...

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