Anemia of Prematurity - Portal Neonatal

Periodic breathing :
Periodic breathing (PB) is defined as periods of regular respiration for as long as 20 seconds
followed by apneic periods no longer than 10 seconds that occur at least 3 times in succession (see
Image 3). In most cases, PB accounts for 2-6% of the breathing time in healthy term neonates and
as much as 25% of the breathing time in preterm neonates. PB occurrence is directly proportional to
the degree of prematurity. Kelly and coworkers found that PB occurred in 78% of patients examined
at age 0-2 weeks; the incidence declined significantly to 29% at age 39-52 weeks. This condition
does not occur in neonates during their first 2 days of life.
PB is more frequent during active sleep, but it can occur when neonates are awake or quietly
sleeping. This pattern, common at high altitudes, is eliminated with the administration of
supplemental oxygen and/or with the use of continuous positive airway pressure (CPAP). Because
the prognosis is excellent, no treatment is usually required.
Pathophysiology: Inspiration is controlled by an off switch. During inspiration, the augmenting
discharge of the central inspiratory activator to the inspiratory motor neurons and specialized right
bundle (Rb) neurons suddenly causes the off-switch neurons to discharge, transiently inhibiting the
central inspiratory activator and allowing passive exhalation. Pulmonary volume sensors and the
rostral pontine pneumotaxic center also control the off switch.
The pathophysiology of AOP has been attributed to abnormal breathing control caused by neuronal
immaturity of the brainstem. This immaturity probably is secondary to decreased afferent traffic from
peripheral receptors to the reticular formation. When dendritic and other synaptic interconnections
multiply, breathing control improves as the brain matures, and AOP tends to resolve. This resolution
typically occurs 34-52 weeks after conception.
Indomethacin stimulates phrenic neural output in an anesthetized piglet model; this finding supports
the concept that prostaglandins inhibit breathing early in neonatal life. The final output of the
respiratory control nuclei in the medulla may be a complex function of many inhibitory and
stimulatory inputs, both humoral and neural. The exact manner in which these are altered during
AOP remains unknown.
Sleep
Although determining the sleep state in neonates younger than 34 weeks is controversial, apnea
appears to occur predominantly during active (ie, rapid eye movement [REM]) and indeterminate or
transitional sleep in preterm and full-term neonates. Several mechanisms have been proposed to
explain the high incidence of apnea during active sleep. Chest-wall movements are predominantly
out of phase or paradoxical during active sleep, unlike their state during quiet sleep. A decrease in
the fractional catabolic rate (FCR) and a decrease of 6-10 mm Hg in PaO2 have been observed in
infants during active sleep, and both effects predispose an infant to apneic episodes. Moreover,
ventilatory responses to increased carbon dioxide and decreased oxygen concentrations attenuate
during active sleep.
Chemoreceptors
Preterm neonates respond to a decrease in the inspired oxygen concentration by transiently
increasing the ventilation rate for approximately 1 minute and then returning to baseline or even
depressed ventilation rates. A progressive decrease in the inspired oxygen concentration causes
significant flattening of carbon dioxide responsiveness in preterm neonates. This unstable response
to low concentrations of inspired oxygen may play an important role in the etiology of neonatal
apnea. Central chemoreceptor activity is less developed in immature neonates younger than 33
weeks after conception. The sensitivity of the central chemoreceptor to CO2 is reduced in premature
neonates and increases progressively with gestational age to adult levels by term. The sensitivity to
CO2 is increased with higher O2 concentrations and decreased in hypoxemia.