Infection - Sepsis especially in the first day of life and nosocomial infections and/or necrotizing enterocolitis in the first weeks of life.

Temperature Regulation - Hypothermia or hyperthermia.

Gastrointestinal - NEC or gastroesophageal reflux.

Neurological - Intraventricular hemorrhage, intracranial hemorrhage, neonatal seizures, perinatal asphyxia or other pathology which could lead to increased intracranial pressure.

Drugs - Prenatal exposure with transplacental transfer to the neonate of various drugs (narcotics, beta-blockers). Postnatal exposure to sedatives, hypnotics or narcotics.

Metabolic - Hypercalcemia, hypoglycemia, hyponatremia or acidosis.

Cardiovascular - Impairment of oxygenation from congestive heart failure and pulmonary edema (PDA, coarctation, etc.) or from shunting (cyanotic heart disease).

Hematological - Anemia.

Pulmonary - Impairment of oxygenation and ventilation from lung disease (surfactant deficiency, pneumonia, etc.).

Central Apnea - A pause in alveolar ventilation due to a lack of diaphragmatic activity. In other words, there is no signal to breathe being transmitted from the central nervous system to the respiratory muscles. This is due to immaturity of brainstem control of central respiratory drive. The premature infant also manifests an immature response to peripheral vagal stimulation. For example, stimulation of laryngeal receptors in the adult results in coughing. However, stimulation of these same receptors in the premature infant results in apnea. Gavages feeds, aggressive pharyngeal suctioning and gastroesophageal reflux can induce this reflex apnea.

Obstructive Apnea - A pause in alveolar ventilation due to obstruction of airflow within the upper airway, particularly at the level of the pharynx. The pharynx collapses from negative pressure generated during inspiration, because the muscles responsible for keeping the airway open are too weak in the premature infant (ex. genioglossus and geniohyoid). Once collapsed, mucosal adhesive forces tend to prevent the reopening of the airway during expiration. Neck flexion will worsen this form of apnea.

Mixed Apnea - A combination of both types of apnea representing as much as 50% of all episodes. (5)

Central Apnea :

• Primary central respiratory center depression Decreased or inhibitory upper afferent input to the central respiratory center.Abnormal or hyperactive reflexes.Decreased or inhibitory lower afferent input to the central respiratory center.
• Hypoxemia.

Obstructive Apnea :

• Decreased or inhibitory upper afferent input to the central respiratory center.

Mixed Apnea :

• Decreased or inhibitory upper afferent input to the central respiratory center.
• Hypoxemia.

Decrease in arterial oxygen tension

Decrease in heart rate

Decrease in peripheral blood flow

EEG changes suggesting CNS depression if apnea is severe

Increase in venous pressure

Decrease in muscle tone