(See also Overview of Perinatal Respiratory Disorders 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... read more .)
Extensive physiologic changes Perinatal Physiology The transition from life in utero to life outside the womb involves multiple changes in physiology and function. See also Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more accompany the birth process (see also Neonatal pulmonary function Neonatal Pulmonary Function The transition from life in utero to life outside the womb involves multiple changes in physiology and function. See also Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more ), sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation Neonatal Resuscitation Extensive physiologic changes accompany the birth process, sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation... read more skills must attend each birth. Gestational age Gestational Age Gestational age and growth parameters help identify the risk of neonatal pathology. Gestational age is the primary determinant of organ maturity. Gestational age is usually defined as the number... read more and growth parameters Growth Parameters in Neonates Growth parameters and gestational age help identify the risk of neonatal pathology. Growth is influenced by genetic and nutritional factors as well as intrauterine conditions. Growth parameters... read more help identify the risk of neonatal pathology.
About 25% of preterm infants Preterm Infants An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more 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 Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more ). Risk of apnea of prematurity increases with earlier gestational age Gestational Age Gestational age and growth parameters help identify the risk of neonatal pathology. Gestational age is the primary determinant of organ maturity. Gestational age is usually defined as the number... read more .
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)
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 Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) Sudden unexpected infant death (SUID) is a term used to describe any unexpected and sudden death in a child less than 1 year of age, which often occurs during sleep or in the infant's sleep... read more ) had a history of prematurity Preterm Infants An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more , 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 preterm infants and is not considered apnea of prematurity and has little or no clinical significance.
Pearls & Pitfalls
Diagnosis of Apnea of Prematurity
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
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.
If apnea continues despite respiratory stimulants, the infant may be given CPAP Continuous Positive Airway Pressure (CPAP) Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more 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.
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
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 Cardiopulmonary Resuscitation (CPR) in Infants and Children Despite the use of cardiopulmonary resuscitation (CPR), mortality rates for out-of-hospital cardiac arrest are about 90% for infants and children. Mortality rates for in-hospital cardiac arrest... read more ]), 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 Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) Sudden unexpected infant death (SUID) is a term used to describe any unexpected and sudden death in a child less than 1 year of age, which often occurs during sleep or in the infant's sleep... read more or brief resolved unexplained events (BRUEs BRUE BRUE (brief, resolved, unexplained event) is an episode of cyanosis or pallor, abnormal breathing, abnormal muscle tone, or altered responsiveness in infants. A previous term for similar events... read more ).
Pearls & Pitfalls
(See also the American Academy of Pediatrics' updated 2022 recommendations for reducing infant deaths in the sleep environment.)
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.
Investigators often find that infants found dead in a sleep space died of suffocation. For additional measures that decrease the risk of SIDS, see Prevention of SUID and SIDS Prevention Sudden unexpected infant death (SUID) is a term used to describe any unexpected and sudden death in a child less than 1 year of age, which often occurs during sleep or in the infant's sleep... read more .
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 gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more before discharge.
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.
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
American Academy of Pediatrics: Sleep-Related Infant Deaths: Updated 2022 Recommendations for Reducing Infant Deaths in the Sleep Environment
Drugs Mentioned In This Article
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