APNEA OF PREMATURITY CAUSES

apnea of prematurity causes: A premature neonate in whom all other causes of apnea have been excluded may be considered to have true idiopathic apnea. Although the etiology of AOP is not fully understood, several mechanisms have been proposed to explain this condition, including the following:
• AOP is considered the final response of incompletely organized and interconnected respiratory neurons to a multitude of afferent stimuli. Abnormal control of breathing is secondary to neuronal immaturity of the brain.

• In a premature neonate, protective respiratory reflex activity is decreased, and Hering-Breuer reflex activity is increased.

• Dopaminergic receptors may have an inhibitory role in peripheral chemoreceptor responses and central neural mechanisms elicited by hypoxia. Evidence from neonatal animal studies indicates that endogenous endorphins may depress the central respiratory drive. Although endogenous opiates may modulate the ventilatory response to hypoxia in newborn animals, a competitive opiate receptor antagonist, naloxone, has no benefit in the resuscitation of an asphyxiated human neonate. Naloxone appears to have no therapeutic role in AOP.

• Negative luminal pressures are generated during inspiration, and the compliant pharynx of the premature neonate is predisposed to collapse. Genioglossus activation failure has been most widely implicated in mixed and obstructive apnea in adults and infants. The ability of medullary chemoreceptors to sense elevated CO2 levels is impaired; thus, an absent, small, or delayed upper airway muscle response to hypercapnia can possibly cause upper airway instability when accompanied by a linear increase in chest-wall activity. This impairment may predispose the infant to obstructed inspiratory efforts after a period of central apnea.

• Another important factor to consider is the excitation of chemoreceptors in the larynx by acid reflux. Laryngeal receptors send afferent fibers to the medulla and can elicit apnea when stimulated.

• Swallowing during a respiratory pause is unique to apnea and does not occur during PB. Accumulation of saliva in the pharynx hypothetically could prolong apnea with a chemoreflex mechanism and also elicit swallowing movements.

• Gastroesophageal reflux (GER) has been associated with recurrent apnea. Menon et al observed that regurgitation of formula into the pharynx after feeding is associated with an increased incidence of apnea in premature infants. Gastric fluids can possibly activate laryngeal chemoreflexes, leading to apnea. Aminophylline may also exacerbate reflux in patients with apnea. On the other hand, findings from several studies have not demonstrated a relationship between episodes of apnea and episodes of acid reflux into the esophagus.

• However, Newell et al demonstrated that effective control of GER in infants with xanthine-resistant AOP was associated with a significant decrease in number of apneas. In 1992, Booth suggested that the reduction of apneic episodes was due to the resolution of esophagitis because clinical improvement of apnea occurred 1-2 days after initiation of antireflux therapy.

• Many clinicians treat xanthine-resistant apnea with H2 blockers, metoclopramide, thickened formula, and upright positioning during feeding. However, to the author's knowledge, no controlled trials have demonstrated that antireflux medications are effective in preventing apnea.