Anemia of Prematurity - Portal Neonatal

pressure. Bradycardia may begin within 1.5-2 seconds of apnea onset. Apneic episodes
associated with bradycardia are characterized by heart rate decreases of more than 30%
below the baseline rates. This reflex bradycardia is secondary to hypoxic stimulation of the
carotid body chemoreceptor or a direct effect of hypoxia on the heart.
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 xanthineresistant
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.
DIFFERENTIALS Section 4 of 11
Anemia of Prematurity
Neonatal Sepsis
Respiratory Failure
Respiratory Syncytial Virus Infection