Causes of A's and B's can be classified according to diseases and disorders of various organ systems, gestational age, or postnatal age. Apnea of prematurity is a diagnosis of exclusion; therefore, it is important to diagnose and treat any secondary cause.
Diseases and disorders of various organ systems
Head and central nervous system
Perinatal asphyxia.
Intraventricular/intracranial or subarachnoid hemorrhage.
Meningitis.
Hydrocephalus with increased intracranial pressure.
Cerebral infarct with seizures.
Seizures (apnea is an uncommon presentation of a subtle seizure). Consider a seizure if apnea occurs without bradycardia; tachycardia can be seen before or during the apneic attack.
Birth trauma.
Congenital myopathies or neuropathies.
Congenital malformations.
Congenital central hypoventilation syndrome.
Encephalopathy.
Respiratory system
Hypoxia
Airway obstruction/malformation
Lung disease/pneumonia/respiratory distress syndrome (RDS)/aspiration
Inadequate ventilation or performing extubation too early
Surfactant deficiency
Pulmonary hemorrhage
Pneumothorax
Hypercarbia
Cardiovascular system
Congestive heart failure.
Patent ductus arteriosus.
Cardiac disorders such as cyanotic congenital heart disease, congenital heart block, hypoplastic left heart syndrome, and transposition of the great vessels.
Hypovolemia/hypotension/hypertension.
Increased vagal tone. There is increased vagal tone in newborns especially in the postdelivery period. Vagal hyperreactivity has been described in sudden infant death syndrome (SIDS).
Gastrointestinal (GI) tract
Necrotizing enterocolitis (NEC). Apnea has been associated with the onset of NEC.
Gastroesophageal reflux (GER). Thought by some investigators to be related to AOP; however, to date, no research has shown a relationship between the two. Some studies suggest that antireflux surgery can reduce apnea in preterm infants at highest risk. It is a rare/infrequent cause of apnea in a full-term infant.
Feeding intolerance.
Oral feeding.
Abdominal distension.
Bowel movement.
Non-rotavirus infection causes apnea in a premature infant.
Esophageal hematoma. Rare.
Hematologic system
Anemia. There is no specific hematocrit at which apnea and bradycardia occur and can be seen in infants with anemia of prematurity. These infants show improvement after transfusion; it has been shown that liberal blood transfusion may reduce apnea compared with more restrictive blood transfusion.
Polycythemia. More common in term infants.
Other diseases and disorders
Temperature instability. Especially hyperthermia, but also hypothermia, can cause apnea and bradycardia. Note the incubator temperature; the infant may have a normal body temperature but may have a rise in incubator temperature (the infant is hypothermic) or may require a lower incubator temperature (the infant is hyperthermic). Any rapid fluctuation of temperature can cause apnea. Cold stress can occur after birth or during transport or a procedure, and it may produce apnea.
Infection (sepsis). Check for bacterial, fungal, and viral infections. Respiratory syncytial virus, Ureaplasma urealyticum, and botulism can all cause apnea in preterm infants.
Metabolic/electrolyte imbalance and inborn errors of metabolism. Hypoglycemia, hypo-/hypernatremia, hypermagnesemia (during parenteral nutrition), hyperkalemia, hyperammonemia, and hypo-/hypercalcemia can cause apnea and bradycardia. Hypothyroidism and inborn errors of metabolism can also cause apnea and bradycardia.
Vagal reflex. May occur secondary to nasogastric tube insertion, feeding, and suctioning.
Acute/chronic pain.
Head/body position (neck flexion).
Drugs/drug withdrawal. Oversedation from maternal drugs such as magnesium sulfate, narcotics such as opiates, and general anesthesia can cause apnea in the newborn. Apnea can be seen in drug withdrawal of infants born to drug-addicted mothers. In the infant, high levels of phenobarbital or other narcotics or sedatives, such as diazepam and chloral hydrate, may cause apnea and bradycardia. Topical eye drops for routine eye examinations can sometimes cause changes in apnea pattern. Prostaglandin E1, γ-aminobutyric acid (GABA), and adenosine therapy can cause apnea.
Immunization. Apnea increases in preterm infants after immunization with the whole-cell pertussis component. New studies have shown an increase in apnea/bradycardia/desaturation after the DTaP-IPV-HIb and DTaP-IPV-HIb-HBV in premature infants with chronic disease. It is recommended to give these at 8 weeks if still hospitalized, with close observation. Infants with significant lung disease or sepsis can experience apnea after immunization. There is a risk of recurrence of apnea in premature infants who had apnea with their first immunization. Monitoring for a minimum of 24 hours after their next immunization is recommended.
Kangaroo care. Early studies showed a relationship, but recent studies have found no adverse effects. Observe head positioning during holding.
Surgery. This can cause postoperative apnea in premature infants.
Retinopathy of prematurity (ROP). ROP examination has been reported as a cause.
Gestational age. See Table 47–1.
Full-term infants. Usually do not have apnea and bradycardia from physiologic causes; the disease or disorder must be identified. The onset of apnea in a term infant at any time is a critical event that requires immediate investigation.
Preterm infants. The most common cause is AOP, usually presenting between days 2 and 7 of life (usually <34 weeks' gestation, <1800 g, and no other identifiable cause) and is a diagnosis of exclusion.
Postnatal age can be a clue to the cause of apnea
Onset within hours after birth. Oversedation from maternal drugs, asphyxia, seizures, hypermagnesemia.
Apnea on day 1. Usually pathologic; consider sepsis or respiratory failure.
Apnea on days 1–2. Sepsis, hypoglycemia, respiratory failure, polycythemia.
Onset <1 week. Patent ductus arteriosus, periventricular-intraventricular hemorrhage, sepsis, respiratory failure, or AOP.
Onset >1 week of age. Posthemorrhagic hydrocephalus with increased intracranial pressure or seizures, postextubation atelectasis, outgrown dose of caffeine or theophylline.
Onset after 2 weeks in a previously well premature infant. Something new is going on that needs an immediate evaluation, usually indicative of a serious illness such as sepsis, meningitis, or other causes.
Onset 4–6 weeks. Respiratory syncytial virus (RSV) infection.
Variable onset. Sepsis, NEC, meningitis, aspiration, GER, cardiac disorder, pneumonia, cold stress, or fluctuations in temperature.