Pediatric Apnea

Updated: Sep 28, 2018
  • Author: Joshua A Rocker, MD; Chief Editor: Kirsten A Bechtel, MD  more...
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Overview

Background

Apnea is defined by the cessation of respiratory airflow. The length of time necessary to be qualified as a true apneic event has changed dramatically over the last several decades: 2 minutes in 1956, [1]  1 minute in 1959, [2]  30 seconds in 1970, [3]  and then 20 seconds or shorter if associated with bradycardia or cyanosis in 1978. [4]  The reduction of the duration in the definition of apnea reveals doctors’ desire to intervene early enough to avoid systemic consequences.

The 3 main categories of apnea are central, obstructive, and mixed. Central apnea is a result of inadequate medullary responsiveness and thus results in no or poor muscle coordination for breathing. Obstructive apnea is when there is an obstruction of the airway passages and therefore poor to no air exchange. Often times with obstructive apnea, there is a vigorous inspiratory effort but it is ineffective against the obstruction. Mixed apnea refers to an episode where combinations of both central and obstructive forces are involved.

Infant apnea is defined by the American Academy of Pediatrics as "an unexplained episode of cessation of breathing for 20 seconds or longer, or a shorter respiratory pause associated with bradycardia, cyanosis, pallor, and/or marked hypotonia." [5]  Apnea is more common in preterm infants. Apnea of prematurity requires a specific assessment and treatment and is not discussed in full in this article. True apnea is rare among full-term healthy infants and, if present, may indicate an underlying pathology.

The ED physician may not experience many patients with pure apneic events but more likely will have an infant's caregiver come in and report that his or her child appeared to stop breathing, changed color, or became limp. This is a brief resolved unexplained event (BRUE), previously referred to as an apparent life threatening event (ALTE).

Previously, ALTE was defined as: "An episode that is frightening to the observer and is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking or gagging. In some cases, the observer fears that the infant has died. ALTE was meant to replace previous terminology, such as “near miss SIDS.”

ALTE was used as the description of an event or a presenting complaint. The potential underlying diagnoses were broad, and ranged from benign to extremely serious. The challenge with the assessment of the patient who experienced an ALTE often was determining via history if the event was in fact a true episode of apnea, cyanosis, or tone change, and to then use the physical examination findings and various diagnostic studies, if needed, to deduce the reason the event took place.

The American Academy of Pediatrics published a clinical practice guideline in 2016 recommending replacing the term apparent life threatening event (ALTE) with the new term brief resolved unexplained event (BRUE). [6]  The goal of this new guideline was to refine the diagnosis to better assess the risk of an underlying serious disorder, and to provide evidence based recommendations on the management of lower risk infants.  In an infant who presented with an ALTE, clinicians often times felt compelled to perform tests and hospitalize the patient even though this may have subjected him to unnecessary risk and was unlikely to lead to a treatable diagnosis or prevent future events. A study conducted in 200 analyzed 243 patients diagnosed with an ALTE on whom 3776 tests were performed. Only 5.9% of these tests contributed to reaching a diagnosis. [7]  

According to the clinical practice guidelines on BRUE, the term should be used when describing an event that occurs in an infant younger than 1 year, when the caregiver reports a sudden, brief, and now resolved (meaning that the patient has returned to it’s baseline state of health) episode of 1 or more of the following:

  • cyanosis or pallor
  • absent, decreased or irregular breathing
  • marked change in tone
  • altered level of consciousness

Where as previously, GERD and feeding issues were the most diagnosed cause for ALTE second to idiopathic, this is no longer the case. If the event is thought to be feeding related (with choking, gagging, or vomiting) the diagnosis should be specific to the feeding issue alone despite the apparent serious reaction it caused in the child. Therefore, there is no indication for a BRUE diagnosis. [8]  

The term BRUE is intended to better reflect the transient nature and lack of clear cause, and removes the “life threatening” label.

Apnea is a symptom that has large possibility of etiologies. In this article, some of the major etiologies of apneic events that an ED physician or primary care physician will encounter are discussed, namely, apnea of prematurity, BRUE, obstructive sleep apnea, and miscellaneous forms of apnea that are toxin mediated, secondary to head trauma, or caused by infections.

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Pathophysiology

Apnea refers to a cessation of respiratory airflow and has 3 major types.

Central apnea

Central apnea occurs when there is a lack of respiratory effort due to either a cessation of output from the central respiratory centers or the inability of the efferent peripheral nerves and respiratory muscles required for oxygenation and ventilation to receive or process the signals from the brain. This can be due to immaturity of the system, as seen in certain premature infants, who have a decreased response to hypercapnia (increased carbon dioxide levels). Patients with central apnea have no respiratory effort. This can be seen by a lack of chest wall movement and no breath sounds will be appreciated on auscultation. [9]

Another cause of central apnea is head trauma, as it may interfere with the afferent and efferent signals of the central respiratory center. Head trauma may be the result of abuse and must always be considered in the apneic pediatric patient without an obvious cause. Toxin-mediated apnea is another form of central apnea, as it may cause central nervous system depression and decrease the respiratory drive.

Obstructive apnea

Obstructive apnea, as the name suggests, results from attempts to breathe through an occluded airway. Obstructive sleep apnea (OSA) is the most common form of obstructive apnea in children. Obstructive sleep apnea is on the sleep-disordered breathing (SDB) spectrum. The sleep-disordered breathing spectrum includes snoring, upper airway resistance syndrome, obstructive hypoventilation and, at its extreme, obstructive sleep apnea.

Mixed apnea

Mixed apnea has characteristics of both central apnea and obstructive apnea. Examples can include a patient with a partial obstructive apnea (due to adenotonsillar hypertrophy) who has undergone sedation (causing central apnea), or a premature infant with central apnea who has an obstruction due to nasal congestion brought on by a viral illness. Gastroesophageal reflux is thought to cause this mixed picture as regurgitated gastric contents may occlude the airway and block laryngeal chemoreceptors to send signals for dilation to the brain.

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Epidemiology

Frequency

United States

An inverse relationship is found with apnea of prematurity for both birth weight and gestational age. Because advances in NICU care are steadily improving, the number of infants who are surviving ultra-premature births has expanded and therefore the number of children experiencing apnea of prematurity is also growing.  Approximately 70% of babies born before 34 weeks gestation have clinically significant apnea, bradycardia, or oxygen desaturation during their hospital stay.

Prior to the new classification of BRUE, the true incidence of apparent life-threatening event (ALTE) was unknown but was thought to account for 2.3% of hospitalized children, and to occur in between 0.5% and 0.6% of all newborns. [10]  

Since brief resolved unexplained event (BRUE) is a fairly new term having only been described since 2016, there are no reports to describe its epidemiology. In one recent study, BRUEs accounted for approximately 0.6% to 1.7% of all emergency department visits and 7.5% of calls to the emergency medical services system for infants younger than one year of age. [6]

Obstructive sleep apnea (OSA) has been previously shown to occur in almost 2% of the pediatric population, but that number is rapidly increasing secondary to the explosive incidence of obesity in the United States. In older pediatric textbooks, the classic picture of a patient with obstructive sleep apnea was of a patient who was thin and may have even been considered to have failure to thrive. However, currently, the typical patient with obstructive sleep apnea is significantly overweight. Recent evidence now suggests that sleep disordered breathing, which ranges from primary snoring to OSA, is more common among boys than girls, and among children who are heavier than others, with emerging data to suggest a higher prevalence among African Americans. [11]  

There are certain conditions that classically have a high rate of OSA. These conditions include mucopolysaccharidosis, Trisomy 21, craniofacial anomalies, and obesity. Other causes of obstructive apnea are an aspirated foreign body and vocal cord paralysis.

Rosen et al ascertain the prevalence of and risk factors for obstructive sleep apnea syndrome in children with sickle cell anemia. The study concluded that the prevalence of obstructive sleep apnea syndrome in children with sickle cell anemia is higher than in the general pediatric population. [12]

One study has shown that the incidence of apnea can range from 1.2-23.8% in hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis; however, the populations in the studies included premature and neuromuscularly impaired infants. [13]

When assessing apnea in non- RSV viral infections, one study showed that out of 51 apneic infants admitted with bronchiolitis, 13.7% had rhinovirus, while 23.5% had more than one viral infection. Another study analyzed 108 infants with apnea hospitalized at 16 sites spanning 3 winters, and found that apnea risk was similar across the major viral pathogens. [14]  Still, RSV was the predominant virus in 33.3% of infants. [15]

International

Prior to the new BRUE classification, the worldwide incidence of ALTE was unknown. One report from Sweden places the incidence of apnea during the first 4 days of life at 0.35 case per 1,000 population. [16]  Another study from Italy suggests a cumulative incidence of 4.1 per 1,000 live births in the study area.

A Taiwanese population-based cohort study by Chen et al reported that children who are hospitalized due to enterovirus infection were at increased risk for obstructive sleep apnea (adjusted hazard ratio = 1.62, 95% CI: 1.18-2.21, p = 0.003). Allergic rhinitis was an additional factor that increased the risk. [17]

Mortality/Morbidity

As previously discussed, there are different types of apnea, and each has its own unique set of possible causes. The outcome may vary significantly from one cause to another.

Apnea of prematurity frequently persists beyond term gestation in infants delivered at prior to 28 weeks' gestational age. These persistent apnea events may contribute to prolonged hospitalization and mortality. Clearly, if a premature infant with apnea is not taken care of in an appropriate medical setting, the morbidity and mortality can be significant.

The morbidity and mortality rates for the patient who has had a BRUE is difficult to assess. A recent meta-analysis by Brand et al determined that the risk of death after a BRUE is about the same as the baseline risk of death during the first year of life. [7]

Untreated obstructive sleep apnea can result in failure to thrive, cor pulmonale, and loss of intellectual quotient points. In a study performed in first grade children, OSA was found to be disproportionally high in children whose school performance was in the lowest 10% of their class. When children were treated for OSA, they showed significant academic improvement, where as children who did not receive treatment did not improve academically. [18]

Apnea from miscellaneous sources, such an overwhelming sepsis, various infectious agents (RSV, influenza, pertussis, human metapneumovirus), toxic agents, or trauma, all carry very significant morbidity and mortality rates.

Sex

Most studies do not show a gender difference in the incidence of apnea of prematurity.

For BRUEs the male-to-female ratio is variable, but, in some studies, it has been as high as 2:1.

Sleep-disordered breathing continuum, of which OSA is on, appears to have a male predilection. The male to female ratio is estimated to range anywhere from 3:1 to 5:1 in the general population. [19]

Age

The risk for apnea of prematurity is clearly linked to a younger gestational age at birth as well as lower birth weights. Almost all infants born less than 28 weeks’ gestation suffer from apnea. For infants born at 30-31 weeks, the risk is approximately 50%, and, for those born at 32-33 weeks, the risk is about 14%. The risk for those born at 34-35 weeks is 7%. [20]

The typical infant presenting after a BRUE is 8-14 weeks. Approximately 7% of these infants were born prematurely.

OSA can occur at any age; however, its incidence is bimodal. It has its first peak at age 2-6 years and then again later in adulthood.

Infections such as bronchiolitis, classically caused by RSV but also influenza, rhinovirus, human metapneumovirus, or any other viral pathogen can cause apnea. Acquiring the respiratory illness at a younger age puts the patient at much higher risk for apnea. [21]

A bimodal distribution exists for apnea caused by ingestions. Accidental ingestions most commonly occur after children are capable of a pincer grasp, approximately 9 months, until early childhood, whereas both non-accidental ingestions and illicit drug behavior occurs during adolescence.

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