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 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 premature neonates by 37 weeks postmenstrual age and in almost all premature infants by 44 weeks postmenstrual age.
(See also Overview of Perinatal Respiratory Disorders.)
Extensive physiologic changes accompany the birth process (see also Neonatal pulmonary function), sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation skills must attend each birth. Gestational age and growth parameters help identify the risk of neonatal pathology.
About 25% of preterm infants have apnea of prematurity, which usually begins 2 to 3 days after birth and only rarely on the first day. Apnea on the first day of life may indicate a central nervous system (CNS) malformation or injury. Apnea that develops > 14 days after birth in an otherwise healthy infant may signify a serious illness other than apnea of prematurity (eg, sepsis). Risk of apnea of prematurity increases with earlier gestational age.
- 1. Eichenwald EC, Committee on Fetus and Newborn, American Academy of Pediatrics: Apnea of prematurity. Pediatrics 137(1), 2016. doi: 10.1542/peds.2015-3757
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)
- 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. About 18% of infants who have died of sudden infant death syndrome (SIDS) had a history of prematurity, but apnea of prematurity is not a precursor to SIDS.
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 premature infants and is not considered apnea of prematurity and has little or no clinical significance.
Pearls & Pitfalls
- Clinical evaluation
- Cardiorespiratory monitoring
- Other causes (eg, hypoglycemia, sepsis, intracranial hemorrhage) ruled out
Although frequently attributable to immature respiratory control mechanisms, apnea in premature 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) 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.
Most preterm infants stop having apneic spells by 37 weeks postmenstrual age, and apnea of prematurity resolves in almost all premature 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.
- Treatment of underlying disorder
- Respiratory stimulants (eg, caffeine)
- Continuous positive airway pressure (CPAP)
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).
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. It can be given as caffeine base (loading dose 10 mg/kg followed by a maintenance dose of 2.5 mg/kg every 24 hour) 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 every 24 hour). 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.
If apnea continues despite respiratory stimulants, the infant may be given CPAP starting at 5 to 7 cm H2O 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.
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.
Parents should be taught how to properly use equipment, assess alarm situations, intervene (eg, cardiopulmonary resuscitation [CPR]), 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 or brief resolved unexplained events (BRUEs).
Pearls & Pitfalls
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 oxygen desaturation while in a car seat and should undergo a car seat challenge test before discharge.
- Apnea of prematurity is caused by immaturity of neurologic and/or mechanical function of the respiratory system.
- Until mature, premature 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.