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INTRODUCTION

Apnea is common and a significant clinical problem in preterm neonates. It is manifested by an unstable respiratory rhythm, reflecting the immaturity of the respiratory control system. Apnea can also be secondary to other pathologic conditions that need to be excluded before the diagnosis of apnea of prematurity (AOP) is assumed. In contrast, periodic breathing is a benign condition and does not merit any treatment. (See also on-call problem Apnea and Bradycardia in Chapter 52.)

I. DEFINITION

AOP is most widely defined as cessation of breathing for >20 seconds or a shorter respiratory pause if associated with hypoxemia and/or bradycardia in infants who are younger than 37 weeks’ gestation. Apnea that lasts for <10 seconds is considered “significant” if it is associated with a decrease in oxygen saturation (SpO2) to ≤80% or 85%, whereas “significant” bradycardia has been defined as a decrease in heart rate to <80 beats/min or less than two-thirds of baseline.

  1. Central apnea: Related to immaturity of the central nervous system, central apnea is characterized by total cessation of inspiratory effort with no evidence of obstruction to airflow.

  2. Obstructive apnea: Presents clinically with the preservation of chest wall movement while airflow is obstructed. The primary site of airway obstruction is the pharynx. Lack of coordination of respiratory musculature, neck flexion, or nasal obstruction may further enhance the severity of this impairment of airway airflow.

  3. Mixed apnea: Consists of both obstructive and central apnea, with 1 type triggering the onset of the second type of apnea.

  4. Periodic breathing: Periodic breathing is a normal breathing pattern characterized by ventilatory cycles of 10 to 15 seconds followed by respiratory pause for 5 to 10 seconds without change in heart rate or skin color. It is due to an imbalance between the opposite response of peripheral and central chemoreceptors on ventilatory drive stimuli. Periodic breathing in premature infants is often due to excessive stimulation by the peripheral chemoreceptors promoting a breathing instability. Prevalence of periodic breathing approaches 100% in preterm infants <1000 g. It is more frequent during active sleep. The prognosis is good, although severe hypoxic events are noted to be often preceded by hypoventilation or arterial oxygen saturations of ≤90% associated with a short apneic pause or periodic breathing.

II. INCIDENCE

The incidence of apnea increases with decreasing gestational age. Practically all infants born at <29 weeks will develop apnea, whereas by 30 weeks, this proportion will decrease to 85% and is further reduced to 20% among those born at 34 weeks. Mixed is the most common type of apnea (50%), followed by central (40%) and then obstructive (10%).

III. PATHOPHYSIOLOGY

AOP is a developmental disorder and generally resolves by 36 to 37 weeks in infants born beyond 27 weeks’ gestation. Among more immature infants, apnea can often persist past term gestation. It reflects a “physiologic” rather than “pathologic” immature state of respiratory control.

  1. Fetal to neonatal transition. Peripheral chemoreceptors are active only at the low oxygen levels in the fetal life and thus become essentially silent in the immediate postnatal period following the increase in partial pressure of oxygen from <30 mm Hg to 50 to 70 mm Hg. Peripheral chemoreceptors undergo a progressive reset postnatally, and chemoreceptor drive is significant at the relatively hypoxic level of 50 to 70 mm Hg. This postnatal adjustment may be delayed when neonates are exposed to 100% oxygen during resuscitation. These infants can become apneic when their inspired oxygen is increased sufficiently to produce a physiologic denervation of peripheral chemoreceptors, resulting in a brief delay in the onset of spontaneous breathing.

  2. Ventilatory response to hypoxia. In contrast to adults who show a sustained increase in ventilation in response to hypoxia, preterm infants exhibit a biphasic ventilatory response where the initial increase in ventilation is transient (approximately 1 minute) and is followed by ...

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