1. APNOEA OF
PREMATURITY
Avikesh Chand
20160449
Year 6

2. INTRODUCTION
Apnea of prematurity is defined
1. as sudden cessation of breathing that lasts for at least 20 seconds or
2. is accompanied by bradycardia or oxygen desaturation (cyanosis) in an infant
younger than 37 weeks' gestational age.
• It usually ceases by 43 weeks' postmenstrual age but may persist for several
weeks beyond term, especially in infants born before 28 weeks' gestation with
this risk decreasing with time.
• The frequency of symptoms is inversely proportional to gestational age (GA).

3. INCIDENCE
• The incidence of apnea increases with decreasing gestational age (GA).
• Term infants – The incidence of apnea in term infants is quite low. As a
result, the cause of apnea in term infants should be assumed to be
pathologic and can include hypoglycemia, seizure disorder, infection,
severe birth asphyxia, intracranial hemorrhage or stroke, drug depression,
and micrognathia with obstruction of the airway.
• Very preterm infants – Apnea occurs in virtually all infants born at less than
28 weeks gestation based on review of cardiorespiratory recordings from
pneumography and cardiac and pulse oximetry monitoring.
Infants born at 24 to 28 weeks gestation may continue to exhibit apnea
beyond 38 weeks postconception, which prolongs their hospitalization,
although resolution of apnea is typically complete by around 43 to 44 weeks
postmenstrual age (PMA).

4. • About 25% of preterm infants have apnoea of prematurity beginning at 2-3
days after birth and only rarely on the 1st day.
• Apnoea on the 1st day of life  indicates a CNS malformation or injury
• Apnoea that develops > 14 days after birth in an otherwise healthy infant 
signifies a serious illness other than apnoea of prematurity.
• Incidence of recurrent apnoea ↑ with ↓GA.
• infants born at less than 35 weeks’ gestation generally require cardiorespiratory
monitoring after birth because of their risk of apnoea.

5. PATHOGENESIS
• In fetal life, placenta does the gas exchange with intermittent breathing
• In postnatal life, a continuous respiratory muscle activity is required to
maintain gas exchange.
• In AOP, the ventilation control processes are disrupted and thus proper
exchange is not possible
• Ventilation control processes
- CO2 Chemosensitivity
- Response to hypoxia and hyperoxia
- Sensitivity to neurotransmitters
- Laryngeal reflex

6. Types
• Central: which is caused by decreased central nervous system (CNS) stimuli to
respiratory muscles, results in both airflow and chest wall motion being absent.
Gestational age is the most important determinant of respiratory control, with the
frequency of central apnea being inversely related to gestational age. The
immaturity of the brainstem respiratory centers is manifest by an attenuated
response to CO2 and a paradoxical response to hypoxia that results in
central apnea rather than hyperventilation.
• Obstructive: pharyngeal instability, neck flexion) is characterized by absence of
airflow but persistent chest wall motion. Pharyngeal collapse may follow the
negative airway pressures generated during inspiration, or it may result from
incoordination of the tongue and other upper airway muscles involved in
maintaining airway patency.
• Mixed: most common type Upper airway obstruction with inspiratory efforts that
precedes or follows central apnea

7. Etiology
Symptomatic of underlying problems;
• Respiratory conditions  RDS, pneumothorax, airway obstruction, pulmonary
haemorrhage
• Sepsis
• Hypoxaemia
• Hypothermia
• CNS abnormalities  asphyxia, seizures, ↑ICP, IVH
• Metabolic disturbance  hypoglycaemia, hyponatremia, hypocalcaemia
• Cardiac failure, CHD, anaemia
• NEC
• Vagal response  NGT, suctioning, feeding

8. Potential Causes of Neonatal Apnea and Bradycardia
Central nervous
system
Intraventricular hemorrhage, drugs, seizures, hypoxic injury, herniation, neuromuscular
disorders, Leigh syndrome, brainstem infarction or anomalies (e.g., olivopontocerebellar
atrophy), spinal cord injury after general anesthesia
Respiratory Pneumonia, obstructive airway lesions, upper airway collapse, atelectasis, extreme
prematurity, laryngeal reflex, phrenic nerve paralysis, pneumothorax, hypoxia
Infectious Sepsis, meningitis (bacterial, fungal, viral), respiratory syncytial virus, pertussis
Gastrointestinal Oral feeding, bowel movement, necrotizing enterocolitis, intestinal perforation
Metabolic ↓ Glucose, ↓ calcium, ↓/↑ sodium, ↑ ammonia, ↑ organic acids, ↑ ambient
temperature, hypothermia
Cardiovascular Hypotension, hypertension, heart failure, anemia, hypovolemia, vagal tone
Other Immaturity of respiratory center, sleep state

9. AOP Versus Periodic breathing
• Regular sequence of respiratory pauses of 10-20 sec interspersed
with periods of hyperventilation (4-15 sec) and occurring at least 3x/
minute, not associated with cyanosis or bradycardia.
• Benign respiratory pattern for which no treatment is required.
• Respiratory pauses appear self-limited, and ventilation continues
cyclically. Periodic breathing typically does not occur in neonates in
the first 2 days of life

10. DIFFERENTIAL DIAGNOSIS
• Although apnea of prematurity is the most common cause of apnea in preterm infants, it is a diagnosis of
exclusion. The following etiologies that may present with apnea in preterm infants need to be considered
and eliminated before the diagnosis of apnea of prematurity can be conclusively made.
 Anemia
 Infection, including sepsis.
 Metabolic disorders including hypoglycemia.
 Unstable thermal environment (especially warming).
 Antepartum administration of magnesium sulphate or opiates to the mother.
 Administration of opiates or general anesthesia to the infant.
 Neurologic disorders, including intracranial hemorrhage and neonatal encephalopathy
 Necrotizing enterocolitis (NEC).
 Congenital anomalies of the upper airway.
 Seizures.
 Dysphagia and feeding difficulties.

11. EVALUATION TO DETERMINE CAUSE OF APNEA
The goal of the diagnostic evaluation is to differentiate apnea of prematurity from other causes of neonatal apnea.
The diagnostic evaluation includes the following:
• Maternal and neonatal history:
• Maternal administration of magnesium sulfate or opioids
• Neonatal administration of opioid therapy
• Risk factors for neonatal sepsis
• Traumatic delivery and/or perinatal asphyxia
• Infant of a diabetic mother
Assessment of the infant for other signs of an underlying etiology:
• Signs and symptoms of hypoglycemia (eg, jitteriness, hypotonia, and lethargy)
• Signs and symptoms of sepsis (eg, temperature instability, lethargy, and poor feeding)
• Signs and symptoms of neurologic impairment due to intraventricular hemorrhage, posthemorrhagic hydrocephalus, or
neonatal encephalopathy
• Signs and symptoms of necrotizing enterocolitis (NEC) (eg, abdominal distension, feeding intolerance, and bloody stools)
• Although less likely, consider assessment of the airway to detect congenital anomalies of the upper airway.

12. Laboratory evaluation includes the following tests that may be helpful
in identifying an underlying diagnosis. Testing is typically reserved for
patients with significant or abrupt increases in events based on clinical
judgement:
• Complete blood count: anemia and sepsis
• Blood culture: sepsis
• Measurements of blood glucose: hypoglycemia
• Blood gas: hypoxemia and acidosis, which may be present in patients
with inborn errors of metabolism, sepsis, or NEC

13. Management
1. Immediate resuscitation
surface stimulation
Flick soles, touch baby
Gentle suctioning
CAUTION may prolong apnoea
ventilate with bag and mask on previous FiO2
 be careful not to use supplementary oxygen if infant has been in room air as
child's lungs are likely normal, ↑Pa02 can result in retinopathy of prematurity
intubate, IPPV if child cyanosed or apnoea is recurrent/persistent
 try CPAP in milder cases

14. 2. Review possible causes and initiate specific therapy + check CBG
• Management to prevent recurrence
• Nurse baby in thermoneutral environment
• Nursing baby prone  improves thoraco-abdominal wall synchrony  ↓ apnoea
• Variable flow NCPAP ↓work of breathing & ↓ risk of apnoea
• Monitoring  pulse oximetry, cardio-respiratory
• Drug therapy  methyl xanthine compounds
Caffeine citrate , if N/A then IV Aminophylline or Theophylline
• Prophylaxis  started for babies <32wks. >32 weeks give if babies have apnoea

15. To stop methylxanthines if
1. gestation > 35 weeks
2. Apnoea free for 1 week when the patient is no longer on NCPAP
3. Monitor for at least 1 week once the methylxanthines are stopped
4. After discharge, parents should be given advice for prevention of
SIDS:
• Supine sleep position.
• Safe sleeping environments.
• Elimination of prenatal and postnatal exposure to tobacco smoke.

16. • Give caffeine citrate and aminophylline to prevent apnoea in premature
infants. Caffeine is preferred if it is available.
• The loading dose of caffeine citrate is 20 mg/kg orally or IV (given slowly
over 30 min). A maintenance dose of 5 mg/kg per day should be prescribed
24 h later and can be increased by 5 mg/kg every 24 h to a maximum of 20
mg/kg per day, unless side-effects develop. Continue 4–5 days after
cessation of apnoea.
• If caffeine is not available, give a loading dose of aminophylline at 6 mg/kg
IV over 20 min, followed by a maintenance dose of 2.5 mg/kg every 12 h

17. Prognosis
• In 92% of infants by 37 wk PMA and in 98% of infants by 40 wk
PMA, apnea of prematurity resolves spontaneously. However, infants
born well before 28 wk GA may experience apnea and bradycardic
events until 44 wk PMA. Beyond 44 wk PMA, extreme events
(apnea >30 sec and/or bradycardia <60 beats/min for >10 sec) are
very rare.
• Despite its high frequency in preterm infants, the harm associated
with apnea of prematurity is unknown. However, apnea of
prematurity does not appear to alter an infant’s prognosis unless it is
severe, recurrent, and refractory to therapy. Prompt, effective therapy
and careful monitoring are vital to avoid prolonged, severe hypoxia,
which may increase the risk of death and neurodevelopmental
impairment.

18. Apnea of Prematurity andSudden Infant Death Syndrome
• Although preterm infants are at higher risk for sudden infant death
syndrome (SIDS), apnea of prematurity does not further increase that risk.
The peak incidence of SIDS occurs earlier in infants born at 24-28 wk GA
• The epidemiologic evidence that placing babies supine during sleep
reduces the rate of SIDS deaths by >50% suggests that positioning, and not
prematurity, primarily influences the incidence of SIDS. Supine positioning
on a firm sleep surface separate from the parents’ bed, promotion of
breastfeeding, and pacifier use during sleep reduce the incidence of SIDS.
• Avoidance of cigarette smoke exposure and no parental use of alcohol or
illicit drugs during pregnancy and after birth are also important in the
prevention of SIDS.

19. REFERENCES
• Nelsons Paediatrics 21st Edition
• WHO Pocket Handbook Hospital Care For Children
• NICU Guideline Fiji
• Pathogenesis, clinical manifestations, and diagnosis of apnea of
prematurity https://www.uptodate.com/contents/pathogenesis-clinical-
manifestations-and-diagnosis-of-apnea-of-
prematurity?search=apnoea%20of%20prematurity&topicRef=5048&source
=see_link
• Pathogenesis, clinical manifestations, and diagnosis of apnea of
prematurity https://www.uptodate.com/contents/management-of-apnea-
of-
prematurity?search=apnoea%20of%20prematurity&topicRef=5052&source
=see_link