Overview
Definition:
Apnea of prematurity (AOP) is defined as the cessation of breathing for 20 seconds or longer, or a shorter pause associated with cyanosis, pallor, or bradycardia in a preterm infant.
Epidemiology:
AOP affects approximately 85% of infants born before 28 weeks of gestation and 50% of those born between 30-34 weeks
The incidence decreases with increasing gestational age and postmenstrual age.
Clinical Significance:
AOP can lead to intermittent hypoxemia, bradycardia, and increased work of breathing, potentially causing long-term neurodevelopmental issues
Effective management is crucial for infant well-being and reducing hospital stay.
Clinical Presentation
Symptoms:
Episodic cessation of breathing
Episodes often characterized by a central pause in respiration
Accompanying cyanosis or pallor
Bradycardia
Sometimes desaturation (SpO2 < 80-85%).
Signs:
Observed apneic spells
Decreased respiratory effort during spells
Bradycardia (<100 bpm) and/or desaturation during spells
Increased work of breathing between spells.
Diagnostic Criteria:
Diagnosis is clinical, based on observing apneic spells in a preterm infant
No specific laboratory tests confirm AOP
Exclusion of other causes of apnea (e.g., sepsis, neurological injury, metabolic disorders) is essential.
Diagnostic Approach
History Taking:
Gestational age at birth
Gestational and postnatal age at onset of apnea
Frequency, duration, and type of apneic spells (central, obstructive, mixed)
Association with feeding, activity, or sleep
Any recent changes in care or medications.
Physical Examination:
General assessment of tone, color, and perfusion
Auscultation of lungs for any adventitious sounds
Cardiac auscultation for murmurs or irregular rhythm
Abdominal examination for distension or tenderness.
Investigations:
Rule out underlying causes: Complete blood count (CBC) to assess for infection
Blood gas analysis (if significant desaturation or respiratory distress)
Chest X-ray if pneumonia is suspected
Metabolic screen if indicated
Neurological assessment or imaging (e.g., cranial ultrasound) if neurological cause is suspected.
Differential Diagnosis:
Sepsis
Hypothermia
Hypoglycemia
Anemia
Gastroesophageal reflux
Neurological insult (e.g., intraventricular hemorrhage)
Airway obstruction
Congenital anomalies (e.g., choanal atresia)
Neonatal abstinence syndrome.
Management
Initial Management:
Mild spells: Gentle stimulation (e.g., tactile, auditory)
Moderate spells: Oxygen therapy (nasal cannula or mask)
Severe spells: Positive pressure ventilation (CPAP or bag-mask ventilation)
Identify and treat precipitating factors (e.g., fever, hypothermia, anemia).
Medical Management:
Pharmacological therapy with methylxanthines is the mainstay
Caffeine citrate is the preferred agent due to its wider therapeutic index and less frequent dosing
Loading dose: 20 mg/kg
Maintenance dose: 5 mg/kg once or twice daily (depending on institution protocol and infant response).
Caffeine Dosing Protocols:
Loading dose: 20 mg/kg IV or PO
Maintenance dose: 5 mg/kg/day (once daily) for infants >32 weeks postmenstrual age, or 7.5 mg/kg/day (divided into two doses) for infants <32 weeks postmenstrual age
Monitor drug levels if concerns for toxicity or efficacy (therapeutic range: 10-20 mcg/mL).
Supportive Care:
Cardiorespiratory monitoring is essential
Ensure adequate thermoregulation
Optimize feeding and fluid balance
Minimize handling and environmental stimuli during apneic spells
Consider prophylactic use of CPAP in very high-risk infants.
Weaning Strategies
Weaning Criteria:
Spells should be significantly reduced or absent for a defined period (e.g., 5-7 days) on current caffeine dose
Infant should be clinically stable with minimal or no need for respiratory support.
Weaning Protocol:
Gradually reduce the maintenance dose of caffeine citrate
Common approach: Reduce by 25% every 3-7 days
Monitor closely for recurrence of apnea during the weaning process
If spells recur, return to the previous effective dose and re-initiate weaning after stabilization.
Duration Of Therapy:
Typically continued until term postmenstrual age (40-42 weeks) or until infant has been off caffeine for 7-10 days without recurrent apnea
Duration varies based on infant's gestational age, response to therapy, and institutional guidelines.
Complications
Early Complications:
Gastrointestinal intolerance (vomiting, increased residuals)
Tachycardia
Irritability
Seizures (rare).
Late Complications:
Long-term neurodevelopmental impairment if severe or prolonged apnea is not managed
Increased risk of retinopathy of prematurity (ROP) or bronchopulmonary dysplasia (BPD) in very premature infants, though caffeine may have some protective effects.
Prevention Strategies:
Initiate caffeine therapy early in infants with significant apnea
Optimize environmental conditions to minimize triggers
Ensure adequate nutrition and hydration
Avoid overstimulation.
Prognosis
Factors Affecting Prognosis:
Gestational age at birth
Severity and frequency of apneic spells
Presence of other comorbidities (e.g., BPD, NEC, IVH)
Timeliness and effectiveness of treatment.
Outcomes:
With appropriate management, most infants achieve resolution of AOP
Long-term outcomes are primarily related to prematurity itself and associated complications rather than AOP alone
Aggressive management reduces the risk of hypoxemic injury.
Follow Up:
Regular clinical assessment of respiratory status
Monitoring for developmental milestones
Follow-up for prematurity-related issues such as ROP, BPD, and neurodevelopmental deficits.
Key Points
Exam Focus:
Caffeine citrate is the drug of choice for AOP
Loading dose: 20 mg/kg, Maintenance: 5 mg/kg/day (or 7.5 mg/kg/day for <32 wks)
Weaning involves gradual dose reduction.
Clinical Pearls:
Always consider and rule out other causes of apnea before initiating caffeine
Monitor for signs of toxicity (irritability, tachycardia)
Weaning should be slow and cautious, observing for spell recurrence.
Common Mistakes:
Not initiating therapy in infants with symptomatic apnea
Inadequate dosing or premature discontinuation of therapy
Failing to monitor for recurrence during weaning
Forgetting to rule out secondary causes of apnea.