Continuing Education Activity

Apnea in infants is the term used to describe episodes of cessation of breathing and may be due to many physiologic or pathophysiologic processes. Brief periods of apnea that occur in short cycles of 5 to 10 seconds is not pathologic and is referred to as periodic breathing. Periodic breathing is seen predominantly during the age of two to four weeks and resolves by age six months. Apnea is frequently seen in preterm infants but can occur at any age. Apnea of prematurity is defined as a sudden cessation of breathing that lasts for at least 20 seconds or is accompanied by bradycardia or oxygen desaturation (cyanosis) in an infant younger than 37 weeks gestational age. Apnea of infancy is defined as an unexplained episode of cessation of breathing lasting 20 seconds or longer, or a shorter respiratory pause associated with bradycardia, cyanosis, pallor, and/or marked hypotonia. This activity examines the differential diagnosis of infant apnea and how to properly evaluate these infants. This activity highlights the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Describe infant apnea.
• Review the presentation of infant apnea.
• Identify the etiology of infant apnea.
• Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for infants with apnea.

Introduction

Apnea in infants is the term used to describe episodes of cessation of breathing and may be due to many physiological and pathophysiological processes. Brief periods of apnea that occur in short cycles of 5 seconds to 10 seconds is not pathologic and is referred to as periodic breathing. Periodic breathing is seen predominantly during the age of two to four weeks and resolves by age six months.[1][2][2]

Apnea is frequently seen in preterm infants but can occur at any age.

Apnea of prematurity is defined as a sudden cessation of breathing that lasts for at least 20 seconds or is accompanied by bradycardia or oxygen desaturation (cyanosis) in an infant younger than 37 weeks’ gestational age.

Apnea of infancy is defined 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.”

Apnea may be central, obstructive, or mixed.

Central apnea is due to the depressed respiratory center where there is a cessation of output from the central respiratory centers, and there is no respiratory effort.

Obstructive apnea occurs when there is an obstruction to the airway, and respiratory efforts are inadequate to maintain ventilation.

Mixed apnea (a period of central apnea, typically followed by airway obstruction) is the most frequent type among preterm infants.

Etiology

The etiology of apnea in infants is broad and varies according to the age of the infant and the pathophysiological mechanism.[3][4][5]

Preterm infants, especially those under 28 weeks gestation are highly prone for apnea due to the poor development of mechanisms of respiratory control and have apnea of prematurity.

Apnea soon after birth can occur due to birth asphyxia, maternal drug use, infections, metabolic causes and congenital anomalies.

Causes of Central apnea include central nervous system (CNS) infections (meningitis, encephalitis), head trauma (birth asphyxia or abusive trauma), toxin exposure, pertussis, infant botulism, inborn errors of metabolism (mitochondrial disease, Pompe disease, Leigh syndrome, and the mucopolysaccharidoses), metabolic derangements (hypoglycemia, hypocalcemia, and acidosis) and congenital anomalies (congenital central hypoventilation, Down syndrome and Arnold-Chiari malformation).

Obstructive apnea can occur due to obstructive sleep apnea, infections (pneumonia, croup), vocal cord paralysis, and congenital upper airway anomalies (e.g., Pierre-Robin sequence)

Mixed apnea occurs predominantly among premature infants but can also be caused by gastroesophageal reflux, pertussis, and bronchiolitis. 

Epidemiology

The true prevalence and incidence of apnea in infants in unknown. Among preterm infants, the incidence of apnea is inversely related to gestational age with almost every infant younger than 28 weeks gestation having an episode and 50% of infants born between 33 weeks and 34 weeks. The incidence of apnea in the full-term infant is one per 1000.[6]

Pathophysiology

The relatively immature respiratory center among infants, particularly the preterm infants, makes them vulnerable to apneic episodes in the face of internal and external stressors. Unlike adults and older children, neonates respond to hypoxia and hypercarbia with a brief increase in respiratory rate followed by respiratory depression and apnea. When feeding, poor coordination of sucking and breathing affects ventilation, further accentuated by exaggerated laryngeal chemical reflexes that depress the respiratory center causing apnea. Infants are very sensitive to stressors such as anemia, hypoglycemia, hypothermia, and toxin exposure that can depress the respiratory center. The very pliable thoracic cage causes a collapse of the chest wall resulting in increased work of breathing and eventual tiring of chest muscles that lead to respiratory failure and apnea.

History and Physical

The initial history should be aimed to differentiate between a true apneic episode and periodic breathing or breath-holding spell. Once deemed as an apneic episode, a thorough review of the antenatal, perinatal, postnatal, and feeding history should be done. History of apneic episodes should be elicited as this indicates a life-threatening underlying cause and a higher probability of recurrence. The family history of seizures, infant deaths, and the presence of serious illnesses in family members should also be ascertained. Social history should ask about potentially toxic exposures, including drugs or medications in the home, tobacco smoke exposure, and potential carbon monoxide exposure. Associated symptoms such as sleep problems, snoring, mouth breathing should be inquired. A physical exam often provides valuable clues and aids to identify congenital anomalies, genetic syndromes or stigmata of inborn errors of metabolism and congenital infections.  Fever or hypothermia can raise the suspicion of sepsis or other infectious processes, tachypnea may indicate a lower respiratory tract infection or metabolic acidosis, and stridor indicates an upper airway obstruction. Unexplained skin bruises should raise a suspicion of child abuse.

Evaluation

The performance of lab and imaging studies should be guided by the history and physical exam findings. In neonates, complete blood count, serum glucose, calcium, and electrolyte measurement can be considered. If the infant is febrile or hypothermic and a serious infection is suspected, appropriate cultures of blood, urine, and possibly cerebrospinal fluid (CSF) should be obtained. An EKG can be done to rule out cardiac dysrhythmias, especially the Long QT syndrome. Neuroimaging, EEG, specialist consults are not routinely recommended unless specifically indicated by the clinical picture. If the patient meets low-risk criteria for a Brief Resolved Unexplained Event (BRUE), no lab studies are indicated.[7][8]

Treatment / Management

The initial step in the management of apnea in infants is to assess the need for immediate resuscitation and/or stabilization of the infant. Subsequent management consists of determining the underlying etiology and instituting targeted specific therapy to the identified cause. For neonates, a period of observation with cardiorespiratory and pulse oximetry monitoring in the neonatal intensive care unit (NICU) is recommended. For infants with apnea of prematurity, interventions are recommended if apneic spells are frequent, prolonged, need frequent stimulation, or are associated with bradycardia and hypoxia. These infants benefit from nasal continuous positive airway pressure (CPAP) and methylxanthine therapy. There is no evidence that methylxanthine therapy is effective in term infants. Speech or occupational therapy may be consulted for infants with feeding-related issues. Management of infants in the low-risk BRUE category consists of parental reassurance and education. [9][10][11]

Differential Diagnosis

• Aspiration syndrome

• Bacteremia

• Botulism

• Bronchiolitis

• Bronchopulmonary dysplasia

• Childhood sleep apnea

• Croup

• Heart failure, congestive

• Influenza

• Laryngomalacia

• Munchausen syndrome by proxy

Pearls and Other Issues

Apneic episodes may sometimes be categorized to have an Apparent Life Threatening Event (ALTE). The term ALTE describes an acute event that appears frightening to the caregiver and includes some combination of apnea, bradycardia, color change (usually cyanosis or pallor, occasionally plethora), and choking or gagging. In 2016, the American Academy of Pediatrics recommended discontinuing the use of ALTE as a diagnosis and recommended an alternate term. Brief Resolved Unexplained Event (BRUE).

Enhancing Healthcare Team Outcomes

There are many causes of apnea in infants and the condition may be intermittent in presentation, and if left untreated may have undesirable consequences. Hence, healthcare workers including nurses must be aware of apnea and its clinical presentation. In general, apnea is more common in low birth weight infants and affects anywhere from 1 to 7.5% of hospitalized infants. Untreated apnea can result in failure to thrive, loss of intellect and cor pulmonale. Apnea caused by sepsis or a neurological insult carries a very high mortality rate.[11][12][13] (Level V)

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References

1.

Huang YS, Hsu JF, Paiva T, Chin WC, Chen IC, Guilleminault C. Sleep-disordered breathing, craniofacial development, and neurodevelopment in premature infants: a 2-year follow-up study. Sleep Med. 2019 Aug;60:20-25. [PubMed: 30466820]

2.

Kelly CE, Ooi WL, Yang JY, Chen J, Adamson C, Lee KJ, Cheong JLY, Anderson PJ, Doyle LW, Thompson DK. Caffeine for apnea of prematurity and brain development at 11 years of age. Ann Clin Transl Neurol. 2018 Sep;5(9):1112-1127. [PMC free article: PMC6144456] [PubMed: 30250867]

3.

Miura Y, Watanabe T, Uchida T, Nawa T, Endo N, Fukuzawa T, Ohkubo R, Takeyama J, Sasaki A, Hayasaka K. A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. Eur J Med Genet. 2019 Sep;62(9):103541. [PubMed: 30227298]

4.

Ramos-Fernández JM, Sánchez-Pérez M, Sánchez-González JM, Calvo-Cillán A, Moreno-Pérez D. Apnea in infants hospitalized with pertussis: Incidence and gestational smoking association. Pediatr Int. 2018 Oct;60(10):943-947. [PubMed: 30074664]

5.

McFarlin A. What to Do when Babies Turn Blue: Beyond the Basic Brief Resolved Unexplained Event. Emerg Med Clin North Am. 2018 May;36(2):335-347. [PubMed: 29622326]

6.

Regenbogen E, Zhang S, Yang J, Shroyer A, Zhu C, DeCristofaro J. Epidemiological trends among preterm infants with apnea. A twelve-year database review. Int J Pediatr Otorhinolaryngol. 2018 Apr;107:86-92. [PubMed: 29501318]

7.

Choi HJ, Kim YH. Apparent life-threatening event in infancy. Korean J Pediatr. 2016 Sep;59(9):347-354. [PMC free article: PMC5052132] [PubMed: 27721838]

8.

Sen K, Agarwal R. More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy. BMJ Case Rep. 2018 Apr 05;2018 [PMC free article: PMC5893988] [PubMed: 29622709]

9.

Piumelli R, Davanzo R, Nassi N, Salvatore S, Arzilli C, Peruzzi M, Agosti M, Palmieri A, Paglietti MG, Nosetti L, Pomo R, De Luca F, Rimini A, De Masi S, Costabel S, Cavarretta V, Cremante A, Cardinale F, Cutrera R. Apparent Life-Threatening Events (ALTE): Italian guidelines. Ital J Pediatr. 2017 Dec 12;43(1):111. [PMC free article: PMC5728046] [PubMed: 29233182]

10.

Patrinos ME, Martin RJ. Apnea in the term infant. Semin Fetal Neonatal Med. 2017 Aug;22(4):240-244. [PubMed: 28438477]

11.

Arane K, Claudius I, Goldman RD. Brief resolved unexplained event: New diagnosis in infants. Can Fam Physician. 2017 Jan;63(1):39-41. [PMC free article: PMC5257218] [PubMed: 28115439]

12.

Vliegenthart R, Miedema M, Hutten GJ, van Kaam AH, Onland W. High versus standard dose caffeine for apnoea: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2018 Nov;103(6):F523-F529. [PubMed: 29437799]

13.

Hong HS, Lee JY. Intracranial hemorrhage in term neonates. Childs Nerv Syst. 2018 Jun;34(6):1135-1143. [PMC free article: PMC5978839] [PubMed: 29637304]

Disclosure: Noah Kondamudi declares no relevant financial relationships with ineligible companies.

Disclosure: Lewis Krata declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Wilt declares no relevant financial relationships with ineligible companies.