Hypoxic Respiratory Failure in the Late Preterm Infant

Late preterm infants (LPTI), born between 34 and 37 weeks gestation are a significant proportion of preterm births in developed countries. LPTI are often passed off as mature infants, but manifest signs of physiologic immaturity or delayed transition in the neonatal period and therefore are often requiring intensive care. In fact, LPTI present a high incidence of respiratory distress syndrome (RDS), as well as transient tachypnea of the newborn (TTNB), persistent pulmonary hypertension of the newborn (PPHN), and hypoxemic respiratory failure (HRF). The incidence of these conditions is even higher in infants delivered by caesarean section. Therefore, an appropriate management of these conditions is required.
For instance, HRF is associated with high mortality. About 85% of LPTI may fail to respond to conventional ventilation with high fractional oxygen concentrations and will develop neonatal HRF. Newer techniques and adjuvant treatments have improved survival rates in this population by addressing the pathophysiology of HRF. These include administration of exogenous surfactant, iNO, high-frequency ventilation and extracorporeal life support (ECMO).
Mechanical ventilation with high inspired oxygen concentration is the main support modality for the treatment of neonates with HRF. However, it has become apparent that mechanical ventilation can lead to numerous serious complications, including initiation or exacerbation of underlying lung injury. Conversely, high-frequency ventilation can be used as a lung protective strategy in neonates who have HRF. In fact, if adequate mean airway pressure is used to recruit and maintain alveolar patency, the small magnitude of volume oscillations will neither cause overdistension of alveoli.
The physiologic rationale for iNO therapy for treating neonatal HRF is based on its ability to achieve potent and sustained pulmonary vasodilation without decreasing systemic vascular tone. A recent meta-analysis of six randomized controlled trials showed that about 50% of infants will have clinically significant increases in oxygenation within 60 minutes after initiating iNO.
Exogenous surfactant therapy is another promising adjunctive treatment for late preterm and term neonates who have severe HRF. In fact, there is evidence that surfactant deficiency contributes to decreased lung compliance and atelectasis in some patients who have PPHN. Recent studies have suggested that exogenous surfactant therapy can cause sustained clinical improvement in LPTI and term infants with pneumonia and meconium aspiration syndrome. Moreover, in a randomized multi-center trial, it has been demonstrated that treatment with surfactant decreased the need for extracorporeal life support (ECMO) in LPTI and term newborns with respiratory failure. In addition, by improving lung inflation, surfactant treatment may augment the response to inhalational vasodilators such as iNO.
In summary, a significant number of babies each year are delivered at late preterm gestations, and up to 50% of these deliveries occur by cesarean section. Of these, a significant number of infants develop severe HRF, resulting in need for additional treatments, like ventilation, surfactant, inhaled nitric oxide, and ECMO. In particular, surfactant therapy determines a significant clinical improvement in LPTI and, in addition, may decrease the need for ECMO and enhances the response to iNO.

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