Apnea Of Prematurity: Symptoms, Types, Causes and Treatment

Apnea of Prematurity (AOP) is a common and sometimes alarming condition affecting newborns born before 34 weeks of gestation. For families and caregivers, understanding this condition is the first step toward providing the best care and support for these vulnerable infants. In this article, we’ll explore the symptoms, types, underlying causes, and the latest evidence-based treatments for AOP, helping you navigate this complex neonatal challenge with clarity and confidence.

Symptoms of Apnea Of Prematurity

Apnea of Prematurity reveals itself through a spectrum of cardiorespiratory signs. The condition is defined by pauses in breathing, but it rarely occurs in isolation. Often, these events are accompanied by changes in heart rate and oxygen levels, which can be distressing for both infants and those caring for them. Early identification of symptoms is crucial for timely intervention and optimal outcomes.

Symptom	Description	Typical Onset	Source(s)
Apnea	Breathing pause ≥20 seconds or shorter if symptomatic	First 24 hours	2 10
Bradycardia	Slowed heart rate, often <100 beats per minute	During apneic event	1 2 5 10
Hypoxemia	Low blood oxygen saturation, visible as cyanosis	During/after apnea	1 2 5 10
Color Change	Pallor or bluish skin (cyanosis)	During/after apnea	1 5

Table 1: Key Symptoms

What Happens During an Apneic Event?

When a premature infant experiences apnea, the most common and recognizable sign is a pause in breathing lasting at least 20 seconds. However, shorter pauses may also be clinically significant if they result in bradycardia (a marked drop in heart rate) or hypoxemia (a drop in oxygen saturation) 2 10. These episodes may be dramatic, with infants appearing limp, pale, or bluish, or they may be subtle and only detected by monitors in the neonatal intensive care unit (NICU) 1 5.

Symptom Progression and Variability

• Timing: Apneic spells are often seen within the first 24 hours after birth, especially in infants born before 34 weeks of gestation 2.
• Frequency: The frequency is highest in the initial days and gradually decreases as the infant matures 2.
• Severity: Some infants may have brief, self-resolving episodes, while others experience frequent and prolonged events that require intervention 1 2.
• Associated Signs: In addition to apnea, bradycardia and hypoxemia are common and often used to define the clinical significance of an event 1 5 10.

Clinical Importance

Recognizing these symptoms early is essential. Prolonged or frequent apneic episodes, especially those associated with bradycardia and hypoxemia, can have both immediate and long-term consequences, including potential impacts on neurodevelopment 1 5.

Types of Apnea Of Prematurity

Not all apneic events in preterm infants are the same. Understanding the different types helps clinicians tailor management strategies and anticipate potential complications. The types are classified based on the underlying mechanism and the pattern of respiratory compromise.

Type	Key Features	Prevalence/Timing	Source(s)
Central	Absence of respiratory effort	Most common, esp. early	2 3 5 6
Obstructive	Upper airway blockage, effort present	Early days, less common	2 4 5 8
Mixed	Combination of central & obstructive	Most frequent overall	5 10

Table 2: Types of Apnea

Central Apnea

Central apnea arises from a lack of respiratory effort due to immature or depressed central respiratory control. There is no movement of the chest or airflow because the brain's respiratory centers fail to send signals to the breathing muscles 3 5 6. This type is especially common in the earliest days of life among very premature infants 2.

Obstructive Apnea

Obstructive apnea occurs when there is ongoing respiratory effort, but airflow is blocked due to collapse or obstruction of the upper airway. Preterm infants are particularly vulnerable because of their weak pharyngeal muscles and immature airway reflexes 4 5 8. Interestingly, obstructive apnea is more frequent in the first two days of life but becomes less common as the infant matures 2.

Mixed Apnea

Mixed apnea, as the name suggests, involves elements of both central and obstructive apnea. An episode often begins as a central apnea (no effort), then transitions into obstructive apnea (effort resumes but airway is blocked) 5 10. Mixed events are, in fact, the most frequently observed pattern in preterm infants 5.

Why Does the Type Matter?

Different subtypes may respond differently to therapies. For example, interventions that stimulate the central nervous system may be more effective for central apnea, whereas strategies that maintain airway patency (like positive airway pressure) are crucial for obstructive or mixed events 4 5 11.

Causes of Apnea Of Prematurity

Delving into the causes of AOP uncovers a mix of physiological immaturity and various modulating factors. Understanding these root causes is vital for both prevention and effective intervention.

Cause	Mechanism/Description	Influence on AOP	Source(s)
Immature Respiratory Control	Underdeveloped brainstem centers	Primary cause	1 3 4 5 6
Immature Reflexes	Poor airway protection and load compensation	Exacerbates apnea	8
Genetic Predisposition	Family/hereditary factors	Risk modifier	6 7
Perinatal Complications	CNS injury, metabolic disease, infection, etc.	Increase risk	7
Environmental Factors	Maternal smoking, drugs, alcohol	Increase risk	7

Table 3: Causes of AOP

Immaturity of Respiratory Control

The root cause of AOP is the immaturity of the central nervous system, particularly the brainstem centers responsible for generating and regulating breathing rhythms. In preterm infants, these control centers have not fully developed the ability to respond to changes in blood oxygen and carbon dioxide levels 1 3 4 5 6. This leads to unstable breathing and a blunted response to hypoxia (low oxygen) or hypercapnia (high carbon dioxide) 6.

Immature Reflexes and Airway Protection

Preterm infants also have immature airway protective reflexes. This means their bodies are less capable of compensating for airway resistance or obstruction, making them more susceptible to obstructive and mixed apneic events 8. The reduced ability to maintain inspiratory effort during airway stress further predisposes to apnea.

Genetic and Environmental Factors

Emerging evidence suggests that genetics may play a role, with some infants inheriting a predisposition to disordered breathing 6 7. Additionally, maternal habits such as smoking or alcohol use during pregnancy can further compromise respiratory control and increase the risk 7.

Perinatal and Postnatal Complications

Several complications can exacerbate or unmask AOP:

• Central Nervous System (CNS) Injury: Conditions like intraventricular hemorrhage or birth trauma can depress respiratory centers 7.
• Metabolic and Infectious Disorders: Sepsis, metabolic imbalances, and congenital defects may all precipitate or worsen apneic episodes 7.
• Lung Disease: While not the primary cause, lung immaturity or injury (e.g., from inflammation or infection) can interact with central mechanisms to increase the frequency and severity of apnea 1.

Complex Interplay

It is important to note that while physiologic immaturity is the main driver, the interplay of these additional factors can significantly influence both the presentation and outcome of AOP 1 5 6.

Treatment of Apnea Of Prematurity

Treating AOP requires a nuanced, individualized approach that balances efficacy with safety. Both non-pharmacologic and pharmacologic interventions are used, and ongoing research continues to refine best practices.

Treatment	Mechanism/Approach	Indication	Source(s)
Methylxanthines (Caffeine)	Stimulate CNS and respiratory muscles	Central/mixed apnea	4 6 9 10
CPAP/NIPPV	Maintains airway patency, supports breaths	Obstructive/mixed	4 11
Positioning	Prone or side positioning, head alignment	Obstructive apnea	4 5
Supportive Care	Gentle stimulation, oxygen therapy	Mild/infrequent cases	4 5 10

Table 4: Treatment Options

Pharmacologic Therapy: Methylxanthines

Methylxanthines, particularly caffeine citrate, are the cornerstone of pharmacologic management for AOP. They stimulate both the central respiratory drive and the contractility of respiratory muscles, reducing the frequency of apneic episodes and the need for mechanical ventilation 4 6 9. Caffeine has demonstrated short-term benefits, including earlier discontinuation of positive airway pressure and reduced rates of bronchopulmonary dysplasia, though it may temporarily slow weight gain 9. Long-term safety is still being studied, but no increase in serious adverse outcomes has been observed in large trials 9.

Non-Pharmacologic Interventions

• Continuous Positive Airway Pressure (CPAP): By delivering a constant flow of air, CPAP helps keep the airway open, especially useful for obstructive or mixed apnea. It’s commonly used alone or in conjunction with methylxanthines 4 11.
• Nasal Intermittent Positive Pressure Ventilation (NIPPV): This technique provides intermittent breaths via nasal prongs and may further reduce apneic episodes compared to CPAP alone, although more research is needed on its safety and efficacy 11.
• Positioning: Placing infants in the prone or side-lying position can reduce airway obstruction and the frequency of apnea, but must be balanced with safe sleep practices 4 5.
• Supportive Measures: Gentle tactile stimulation or supplemental oxygen may be sufficient for mild or infrequent episodes. More severe or recurrent apnea may require escalation to the above interventions 4 5 10.

Other and Emerging Therapies

• Red Blood Cell Transfusions: Sometimes used if anemia is contributing, though the evidence is mixed 4.
• Kangaroo Care (Skin-to-skin contact): May help regulate breathing patterns, but more research is needed 4.
• Future Directions: New research is targeting specific inhibitory neurotransmitters (e.g., adenosine, GABA, prostaglandins) for potential novel therapies 6.

Tailored, Individualized Care

Since no single approach works for all infants, treatment is tailored to the specific type and severity of apnea, as well as the infant’s overall health and risk factors 4 5. Regular monitoring and reassessment are essential.

Conclusion

Apnea of Prematurity is a multifaceted condition that reflects the unique vulnerabilities of preterm infants. Prompt recognition, accurate differentiation of types, understanding the underlying causes, and selecting the best evidence-based treatments can dramatically improve outcomes for these infants and offer peace of mind to their families.

Key Takeaways:

• AOP presents with apnea, bradycardia, and hypoxemia—often within the first day of life 2 10.
• There are three main types: central, obstructive, and mixed apnea, each with distinct mechanisms and implications 2 3 4 5.
• The central cause is immaturity of the respiratory control centers, but genetic, environmental, and perinatal factors also play roles 1 3 4 5 6 7 8.
• Treatment is multifaceted, including methylxanthines (like caffeine), respiratory support (CPAP/NIPPV), positioning, and supportive care 4 6 9 10 11.
• Ongoing research continues to shape our understanding and management of this challenging neonatal problem, aiming for safer and more effective interventions 6.

With continued advances in neonatal care, the outlook for infants with AOP is increasingly hopeful, highlighting the importance of early detection, individualized intervention, and family-centered support.