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Apnea of Prematurity


Arcangela Lattari Balest

, MD, University of Pittsburgh, School of Medicine

Reviewed/Revised Jul 2023

Apnea of prematurity is defined as respiratory pauses > 20 seconds or pauses < 20 seconds that are associated with bradycardia (< 100 beats/minute; 1 General reference Apnea of prematurity is defined as respiratory pauses > 20 seconds or pauses < 20 seconds that are associated with bradycardia (< 100 beats/minute; 1), central cyanosis, and/or oxygen... read more ), central cyanosis, and/or oxygen saturation < 85% in neonates born at < 37 weeks gestation and with no underlying disorders causing apnea. Cause may be central nervous system immaturity (central apnea); if the episode of apnea is prolonged, there may be a component of airway obstruction as well. Diagnosis is clinical and by cardiorespiratory monitoring. Treatment is with respiratory stimulants for central apnea and head positioning for obstructive apnea. Prognosis is excellent; apnea resolves in most preterm neonates by 37 weeks postmenstrual age and in almost all preterm infants by 44 weeks postmenstrual age.

General reference

Pathophysiology of Apnea of Prematurity

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 (most common)

  • Obstructive

  • A mixed pattern

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. This is the most common type of apnea of prematurity.

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. Because bradycardia can also occur simultaneously with apnea, a central mechanism may be responsible for both.

Periodic breathing is repeated cycles of 5 to 20 seconds of normal breathing alternating with brief (< 20 seconds) periods of apnea. This phenomenon is common among preterm infants and is not considered apnea of prematurity and has little or no clinical significance.

Pearls & Pitfalls

  • Apneic episodes in preterm infants should not be attributed to prematurity until serious causes (eg, infectious, cardiac, metabolic, respiratory, central nervous system, thermoregulatory) have been ruled out.

Diagnosis of Apnea of Prematurity

  • Clinical evaluation

  • Cardiorespiratory monitoring

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

Although frequently attributable to immature respiratory control mechanisms, apnea in preterm infants can be a 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 Gastroesophageal Reflux in Infants Gastroesophageal reflux is the movement of gastric contents into the esophagus. It may be physiologic or pathologic. When pathologic, it is also known as gastroesophageal reflux disease (GERD)... read more ) is no longer thought to cause apnea in preterm infants, so the presence of GERD should not be considered an explanation for apneic episodes nor should treatment for GERD be started because of apnea of prematurity.

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.

Treatment of Apnea of Prematurity

  • Stimulation

  • Treatment of underlying disorder

  • Respiratory stimulants (eg, caffeine)

  • Continuous positive airway pressure (CPAP)

Patients are admitted to a monitored setting. 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 ventilation is provided (see Airway and Respiratory Devices Airway and Respiratory Devices If no spontaneous respiration occurs after airway opening and no respiratory devices are available, rescue breathing (mouth-to-mask or mouth-to-barrier device) is started; mouth-to-mouth ventilation... read more ).

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. Oral caffeine is the safest and most commonly used respiratory stimulant drug. 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 weeks gestation and free from apnea requiring physical intervention for at least 5 to 7 days. Monitoring continues after the last episode of apnea or after caffeine has been stopped until the infant has gone 5 to 10 more days without having apnea requiring intervention.

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.

Prognosis for Apnea of Prematurity

Most preterm infants stop having apneic spells by 37 weeks postmenstrual age, and apnea of prematurity resolves in almost all preterm infants by 44 weeks postmenstrual age. Apnea may continue for weeks in infants born at extremely early gestational ages (eg, 23 to 27 weeks).

Death is rare.

Prevention of Apnea of Prematurity

Home monitoring

Hospitalized high-risk infants who have not had clinically significant cardiopulmonary events (eg, apnea > 20 seconds, apnea accompanied by central cyanosis, apnea associated with heart rate < 80 beats/minute) 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, few infants are discharged home with an apnea monitor, and only those whose episodes resolve spontaneously and without intervention, including stimulation, should be considered for discharge from the hospital with a monitor.

Pearls & Pitfalls

  • Home cardiorespiratory monitors have not been shown to reduce the incidence of sudden infant death syndrome (SIDS) or brief resolved unexplained events (BRUEs).


Infants should always be placed on their back to sleep on a firm, flat, non-inclined sleep surface for every sleep unless other medical conditions prevent this. Side sleeping or propping is too unstable. 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 preterm infants, especially those with apnea of prematurity, are at risk of apnea, bradycardia, and oxygen desaturation while in a car seat and should undergo a car seat challenge test Later screening An infant born before 37 weeks of gestation is considered preterm. In 2021 in the United States, 10.48% of births were preterm ( 1), and in 2018, 26.53% of births were early term (significantly... read more before discharge.

Key Points

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

  • Until mature, preterm infants may have respiratory pauses > 20 seconds or pauses < 20 seconds combined with bradycardia (< 100 beats/minute) and/or oxygen saturation < 85%.

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

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

  • Give oral caffeine to neonates who have recurrent episodes.

  • Treatment for gastroesophageal reflux disease should not be started as an intervention for apnea of prematurity.

  • Few infants are discharged with an apnea monitor, and only those whose episodes resolve spontaneously and without stimulation should even be considered for discharge with a monitor.

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Drug Name Select Trade
Cafcit, NoDoz, Stay Awake, Vivarin
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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