Anemia of Prematurity - Portal Neonatal

o Comparisons of these studies are difficult secondary to the ventilator strategy
employed and the definition of BPD used. After surfactant administration, infants in the
Provo multicenter HFOV trial were randomized to CV or HFOV with a lung recruitment
strategy. This study found that patients randomized to HFOV had no CLD at age 30
days and needed less oxygen at discharge. Similarly, in 1997, Keszler and colleagues
studied HFJV versus CV in preterm infants with RDS who were treated with surfactant.
Although the study was terminated early, secondary to neurologic complications of
another HFV trial using a different ventilator strategy, infants treated with HFJV had
less BPD (ie, oxygen requirement at 36 weeks corrected age), less need for
supplemental home oxygen therapy, and had no difference in severe neurologic injury
(eg, grade III or IV intraventricular hemorrhage or periventricular leukomalacia [PVL]).
o Regardless of the HFV strategy that was used, avoidance of hypocarbia and
optimization of alveolar recruitment may decrease the risk of BPD development and
CNS abnormalities.
• Oxygen and antioxidants: Oxygen (O2) can accept electrons in its outer ring to form oxygen
free radicals. Oxygen free radicals can cause cell membrane destruction and DNA
abnormalities. Neonates live in an oxygen-rich environment as compared to the fetus.
Oxygen is ubiquitous and necessary for extrauterine survival. All mammals have
antioxidant (AO) defense to mitigate oxygen free radical injury. Neonates are relatively AO
deficient. The major AOs in humans are superoxide dismutase (SOD), glutathione
peroxidase, and catalase. Antioxidant enzyme (AOE) levels tend to increase during the last
trimester of pregnancy, similar to surfactant production. Increases in alveolar size and
number, surfactant production, and AOEs prepare the fetus for transition from a relatively
hypoxic placental respiratory environment to a relatively hyperoxic extrauterine life. Preterm
birth exposes the neonate to high oxygen concentrations with low AO reserves, thereby
increasing the risk of oxygen free radical injury.
Animal and human studies of supplemental SOD and catalase supplementation have
shown reduced cell damage, increased survival, and possible prevention of lung
barotrauma. Lipid peroxidation is increased in neonates who develop BPD. Lipid
peroxidation can be measured in vivo by measurement of expired pentane and ethane. In
2000, Davis and others studied SOD supplementation in ventilated preterm infants with
RDS.
• Inflammation
o Activation of inflammatory mediators has been demonstrated in humans and
animal models of acute lung injury. Activation of leukocytes perhaps by oxygen free
radicals, barotrauma, infection, and other stimuli may begin the process of
destruction and abnormal lung repair that results in acute lung injury followed by
development of BPD.
o Radiolabeled activated leukocytes have been recovered by bronchoalveolar lavage
(BAL) in preterm neonates receiving oxygen and PPV. These leukocytes, as well
as lipid byproducts of cell membrane destruction, activate the inflammatory
cascade and are metabolized to arachidonic acid (AA) and lysoplatelet factor. AA is
catabolized by lipoxygenase, resulting in cytokines and leukotrienes. These
byproducts may also be metabolized by cyclooxygenase to produce thromboxane,
prostaglandin, or prostacyclin. All of these substances have potent vasoactive and
inflammatory properties and are elevated in tracheal aspirates of newly ventilated
preterm infants who subsequently develop BPD.
o Metabolites of AA, lysoplatelet factor, prostaglandin, and prostacyclin may cause
vasodilatation, increased capillary permeability with subsequent albumin leakage,
and inhibition of surfactant function, thereby potentiating barotrauma.
o Collagenase and elastase are released from activated neutrophils and may destroy
lung tissue directly. Hydroxyproline and elastin (breakdown products of collagen
and elastin) have been recovered in the urine of preterm infants who develop BPD.
Alpha1-proteinase inhibitor mitigates the action of elastases and is activated by
oxygen free radicals. Increased activity as well as decreased alpha1-proteinase
inhibitor function may worsen lung injury in neonates. A decrease in the prevalence