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Apnea of Prematurity

by James W. Kendig, MD, Ursula Nawab, MD

Apnea of prematurity is defined as respiratory pauses > 20 sec or pauses < 20 sec that are associated with bradycardia (< 80 beats/min), central cyanosis, and/or O 2 saturation < 85% in neonates born at < 37 wk gestation and with no underlying disorders causing apnea. Cause may be CNS immaturity (central) or airway obstruction. Diagnosis is by multichannel respiratory monitoring. Treatment is with respiratory stimulants for central apnea and head positioning for obstructive apnea. Prognosis is excellent; apnea resolves in most neonates by 37 wk.

About 25% of preterm infants (see Premature Infant) have apnea of prematurity, which usually begins 2 to 3 days after birth and only rarely on the first day. Apnea that develops > 14 days after birth in an otherwise healthy infant signifies a serious illness other than apnea of prematurity (eg, sepsis [see Neonatal Sepsis]). Risk increases with earlier gestational age.

Pathophysiology

Apnea of prematurity is a developmental disorder caused by immaturity of neurologic and/or mechanical function of the respiratory system. Apnea may be characterized as

  • Central

  • Obstructive

  • A mixed pattern (most common)

Central apnea is caused by immature medullary respiratory control centers. The specific pathophysiology is not understood completely but appears to involve a number of factors, including abnormal responses to hypoxia and hypercapnia.

Obstructive apnea is caused by obstructed airflow, neck flexion causing opposition of hypopharyngeal soft tissues, nasal occlusion, or reflex laryngospasm.

Mixed apnea is a combination of central and obstructive apnea.

All types of apnea can cause hypoxemia, cyanosis, and bradycardia if the apnea is prolonged. Among infants dying of SIDS (see Sudden Infant Death Syndrome (SIDS)), 18% have a history of prematurity, but apnea of prematurity is not a precursor to SIDS.

Periodic breathing is repeated cycles of 5 to 20 sec of normal breathing alternating with brief (< 20 sec) periods of apnea. This phenomenon is common among premature infants and has little or no clinical significance.

Diagnosis

  • Clinical evaluation

  • Cardiorespiratory monitoring, physiologic parameter recordings

  • Other causes (eg, hypoglycemia, sepsis, intracranial hemorrhage) ruled out

Although frequently attributable to immature respiratory control mechanisms, apnea in premature infants can be sign of infectious, metabolic, thermoregulatory, respiratory, cardiac, or CNS dysfunction. Thorough history, physical assessment, and, when necessary, testing should be done before accepting prematurity as the cause of apnea. Gastroesophageal reflux disease (GERD—see Gastroesophageal Reflux in Infants) is no longer thought to cause apnea in preterm infants, so the presence of GERD should not be considered an explanation for apneic episodes.

Diagnosis of apnea usually is made by visual observation or by use of impedance-type cardiorespiratory monitors used continuously during assessment and ongoing care of preterm infants. Multichannel recordings of multiple physiologic parameters (eg, chest wall movement, airflow, O 2 saturation, heart rate, brain electric activity) taken for up to 24 h can be used as adjuncts for diagnosis and planning and monitoring treatment. However, these more advanced tests are not necessary for discharge planning.

Prognosis

Most preterm infants stop having apneic spells by the time they reach about 37 wk gestation. Apnea may continue for weeks in infants born at extremely early gestational ages (eg, 23 to 27 wk). Death is rare.

Treatment

  • Stimulation

  • Treatment of underlying disorder

  • Respiratory stimulants (eg, caffeine)

When apnea is noted, either by observation or monitor alarm, infants are stimulated, which may be all that is required; if breathing does not resume, bag-valve-mask or mouth-to-mouth-and-nose ventilation is provided (see Airway Establishment and Control : Airway and Respiratory Devices). For infants at home, the physician is contacted if apnea occurs but ceases after stimulation; if intervention beyond stimulation is required, the infant should be rehospitalized and evaluated.

Frequent or severe episodes should be quickly and thoroughly evaluated, and identifiable causes should be treated. If no infectious or other treatable underlying disorder is found, respiratory stimulants are indicated for treatment of frequent or severe episodes, characterized by hypoxemia, cyanosis, bradycardia, or a combination. Caffeine is the safest and most commonly used respiratory stimulant drug. It can be given as caffeine base (loading dose 10 mg/kg followed by a maintenance dose of 2.5 mg/kg po q 24 h) or caffeine citrate, a caffeine salt that is 50% caffeine (loading dose 20 mg/kg followed by a maintenance dose of 5 to 10 mg/kg q 24 h). Caffeine is preferred because of ease of administration, fewer adverse effects, larger therapeutic window, and less need to monitor drug levels. Treatment continues until the infant is 34 to 35 wk gestation and free from apnea requiring physical intervention for at least 5 to 7 days. Monitoring continues until the infant is free of apnea requiring intervention for 5 to 10 days.

If apnea continues despite respiratory stimulants, the infant may be given continuous positive airway pressure (CPAP—see Continuous positive airway pressure (CPAP)) starting at 5 to 8 cm H 2 O pressure. Intractable apneic spells require ventilator support. Discharge practices vary; some practitioners observe infants for 7 days after treatment has ended to ensure that apnea or bradycardia does not recur, whereas others discharge with caffeine if treatment seems effective.

Prevention

Home monitoring

Hospitalized high-risk infants who have not had clinically significant cardiopulmonary events (eg, apnea > 20 sec, apnea accompanied by central cyanosis, apnea associated with heart rate < 80 for > 5 sec) during 3 to 10 days of continuous cardiorespiratory monitoring can be discharged home safely without a monitor. Sometimes a home cardiorespiratory monitor and/or oral caffeine may be prescribed to shorten the hospital stay for infants who are otherwise ready for discharge but are still having cardiopulmonary events that reverse without intervention. However, infants who have events that require intervention, including stimulation, are not discharged from the hospital.

Parents should be taught how to properly use equipment, assess alarm situations, intervene (eg, CPR—see Cardiopulmonary Resuscitation in Infants and Children), and keep a log of events. Round-the-clock telephone support and triage as well as outpatient follow-up regarding the decision to stop using the monitor should be provided. Monitors that store event information are preferred. Parents should be informed that home cardiorespiratory monitors have not been shown to reduce the incidence of SIDS (see Sudden Infant Death Syndrome (SIDS)) or apparent life-threatening events (ALTE—see Apparent Life-Threatening Event (ALTE))

Pearls & Pitfalls

  • Home cardiorespiratory monitors have not been shown to reduce the incidence of SIDS or ALTEs.

Positioning

Infants should always be placed on their back to sleep. The infant’s head should be kept in the midline, and the neck should be kept in the neutral position or slightly extended to prevent upper airway obstruction. All premature infants, especially those with apnea of prematurity, are at risk of apnea, bradycardia, and O 2 desaturation while in a car seat and should undergo a car seat challenge test before discharge.

Key Points

  • Apnea of prematurity is caused by immaturity of neurologic and/or mechanical function of the respiratory system.

  • Infants have respiratory pauses >20 sec or pauses < 20 sec combined with bradycardia (< 80 beats/min) and/or O 2 saturation < 85%.

  • Diagnose by observation and exclude other, more serious causes of apnea (eg, infectious, metabolic, thermoregulatory, respiratory, cardiac, or CNS disorders).

  • Monitor respiration and give physical stimulation for apnea; if breathing does not resume, give bag-valve-mask or mouth-to-mouth-and-nose ventilation.

  • Give oral caffeine to neonates who have recurrent episodes.

Resources In This Article

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