The Premature Infant

Definitions

It is useful to review some common definitions. The premature infant is often defined as a viable newborn delivered after the 20th completed week of gestation and before full term, with an arbitrary weight of 500 to 2499 g at birth. The preterm infant is born at any time before the 37th completed week (259 days) of gestation (although most clinicians usually consider infants born any time in the 37th week to be full term). Preterm can be further subclassified into late preterm (34–36 weeks’ gestation), moderate preterm (32–34 weeks’ gestation), very preterm (28–32 weeks’ gestation), and extremely preterm (less than 28 weeks’ gestation). Low birth weight (LBW) is defined as less than 2500 g at birth. Very low birth weight (VLBW) is defined as less than 1500 g at birth. Extremely low birth weight (ELBW) is defined as less than 1000 g at birth.

Although the severity of the medical problems described in this chapter is directly correlated with decreasing gestational age, there is a growing recognition that the late preterm (LP) infants have associated risks. LP infants make up 74% of all preterm births and 8% to 9% of total births. The last 6 weeks of gestation are a critical period for neural and respiratory development. LP infants also have an increased risk for the need for resuscitation at birth, feeding difficulty, jaundice, hypoglycemia, temperature instability, apnea and respiratory distress. The mortality rate during infancy is tripled compared with full-term infants. LP infants are more vulnerable to brain injuries and have a tripled risk for developing cerebral palsy, adverse developmental outcomes and academic difficulties up to 7 years of age.

Respiratory Distress Syndrome

Premature infants are born with a deficiency of alveolar type 2 pneumocytes, which are responsible for surfactant production. Surfactant is mainly comprised of phosphatidylcholine, which lowers surface tension inside the alveoli, thus preventing alveolar collapse. Type 2 pneumocytes begin to appear in the fetus by the 22nd week of gestation, and surfactant is primarily produced during the second trimester of pregnancy. Fifty percent of surfactant is produced by the 28th week of gestation, and production is usually complete by 36 weeks.

Surfactant deficiency is associated with a clinical syndrome of pulmonary insufficiency known as respiratory distress syndrome (RDS), formerly termed hyaline membrane disease (HMD). The incidence and severity of RDS is inversely correlated with gestational age; it affects approximately one-half of infants born between 26 to 28 weeks’ gestation and 30% of infants born at 30 to 31 weeks’ gestation, and is infrequent in infants born after the 35th week of gestation. RDS contributes to a large portion of premature deaths. Approximately 50% of premature infant deaths from the age of 12 hours to 14 days can be attributed in part to RDS. Just over 40% of premature deaths in the first month of life can be attributed to complications of RDS. Conditions that decrease surfactant production and increase the incidence of RDS include perinatal asphyxia, maternal diabetes, multiple pregnancies, cesarean section delivery, precipitous delivery, cold stress and a history of affected siblings. Prenatal factors that increase fetal stress and, therefore, increase surfactant production and lower the risk for RDS include pregnancy-associated hypertension, maternal opiate addiction, prolonged rupture of the membranes and antenatal administration of corticosteroids.

Absence or deficiency of surfactant leads to widespread atelectasis, decreased lung compliance, and loss of functional residual capacity (FRC). This correlates with the clinical manifestations of RDS that usually appear shortly after birth and include tachypnea, nasal flaring, audible grunting, chest wall retractions, and use of accessory muscles of respiration. Severely affected infants with substantial ventilation-to-perfusion mismatch will demonstrate cyanosis and respiratory failure. Blood gas analysis will usually reveal hypoxemia, hypercarbia, and metabolic acidosis. The classic finding on chest radiography in infants with RDS is a bilateral diffuse ground-glass appearance and multiple air bronchograms. On occasion, these radiographic findings may not develop until the second day of life.

Treatment of RDS initially includes supplemental oxygen to achieve a target PaO ₂ between 55 and 70 mm Hg. Ideal oxygen targets are still unknown, but an oxygen saturation of 90% to 94% is typically the goal in most institutions. Oxygen therapy is a balance between too much (hyperoxia can lead to increase incidence of retinopathy of prematurity) or not quite enough (hypoxia can lead to increased incidence of necrotizing enterocolitis and higher mortality risk). The optimal first mode of respiratory support for suspected RDS is continuous positive-pressure support, often delivered as nasal CPAP. Ideally, the oxygen should be heated and humidified and the pressures delivered, measured, and controlled. CPAP, between 6 to 9 cm H ₂ O, with early administration of surfactant is considered optimal management of RDS. In prematurely born infants at risk for developing RDS, artificial surfactant is administered into the lungs via an endotracheal tube shortly after delivery. More recently, less invasive means of delivery have made it possible to avoid intubation up front and potentially altogether. A small catheter advanced into the trachea while the child spontaneously ventilates, with CPAP support, is used to deliver surfactant directly into the trachea. Studies have shown that this less invasive method is just as beneficial as endotracheal administration but may have an indirect benefit considering intubation can potentially be avoided. Nebulized surfactant and pharyngeal deposition of surfactant are even less invasive means of administration which are currently under investigation.

If RDS is suspected at birth, the child is placed initially on CPAP. A high-flow nasal cannula has been shown to be inferior to CPAP because most infants often require escalation to CPAP as a rescue therapy. Any sign of worsening oxygen requirements is indication for artificial surfactant therapy. Early administration of surfactant using a low treatment threshold (Fio ₂ <0.45) is preferable to selective surfactant therapy at a higher threshold (Fio ₂ >0.45) and results in less pulmonary air leak, chronic lung disease, and decreased need for mechanical ventilation in the first week of life. Instituting mechanical ventilation is indicated if the infant on CPAP cannot maintain an arterial oxygen tension above 50 mm Hg while breathing inspired concentrations of oxygen up to 100%. Additional indications for mechanical ventilation include persistent pH less than 7.2, and central apnea that is unresponsive to pharmacologic therapy.

Because oxygen toxicity and pulmonary barotrauma/volutrauma are thought to be responsible for the development of neonatal chronic lung disease, the goals of mechanical ventilation in the infant with RDS are to achieve relative normoxemia (PaO ₂ >50 mm Hg), mild (permissive) hypercapnia (PaCO ₂ in the range 40–65 mm Hg), and a normal pH (>7.2), depending on the infant’s clinical status, while minimizing the concentration of inspired oxygen and the level of artificially maintained lung pressures. A modest amount of positive end-expiratory pressure (PEEP) may be used (3–5 cm H ₂ O) and ventilatory settings are weaned aggressively as the infant improves.

The majority of infants with RDS who require mechanical ventilation are placed on conventional ventilators that deliver continuous breathing cycles, usually at a rate between 30 and 50 breaths/min. Some studies suggest synchronous intermittent mandatory ventilation may shorten the duration of intubation and decrease oxygen requirements compared with conventional ventilation. Infants who are unresponsive to conventional ventilation may be switched to high frequency jet ventilation (HFJV), which can attain respiratory rates of 150 to 600 breaths/min, or an oscillating type ventilator that can deliver 300 to 1800 breaths/min. The main advantage of these unconventional ventilators is the ability to decrease mean airway pressure and tidal volumes while maintaining the ability to oxygenate and eliminate carbon dioxide.

Some methods used to decrease duration of mechanical ventilation include caffeine therapy and postnatal steroids in the form or systemic or inhaled corticosteroids. Additional doses of surfactant can be administered at regular intervals if respiratory distress persists and may also result in less RDS-related morbidity and mortality. Extremely premature neonates administered surfactant in the delivery room may have improvement in short-term outcomes and milder bronchopulmonary dysplasia (BPD). Some have recommended the prophylactic use of surfactant after resuscitation in extremely premature neonates to further protect the immature lung (<27 weeks’ gestation).