The fetus and newborn infant are susceptible to a large number of diseases. Because many disorders have a different presentation and course in term as compared with preterm infants, they are considered separately (see Chap. 36, Mortality Rates of Preterm Infants). Disorders that are the direct consequence of maternal disease are discussed in chapters pertinent to specific maternal conditions. Because most perinatal infections arise as a result of maternal infection or colonization, they are considered in Chapters 58 and 59.
Respiratory Distress Syndrome
To provide blood gas exchange immediately following delivery, the lungs must rapidly fill with air while being cleared of fluid. Concurrently, pulmonary arterial blood flow must increase remarkably. Some of the fluid is expressed as the chest is compressed during vaginal delivery, and the remainder is absorbed through the pulmonary lymphatics. Sufficient surfactant, synthesized by type II pneumocytes, is essential to stabilize the air-expanded alveoli. It lowers surface tension and thereby prevents lung collapse during expiration (see Chap. 4, Lungs). If surfactant is inadequate, hyaline membranes form in the distal bronchioles and alveoli, and respiratory distress develops.
Although respiratory distress syndrome (RDS) is generally a disease of preterm neonates, it does develop in term newborns, especially in the setting of sepsis or meconium aspiration. In recent years, mortality rates from RDS have decreased because of antenatal corticosteroid and newborn surfactant therapy (Jobe, 2004; Martin, 2004). Male infants are more likely to develop RDS than females, and white infants are more frequently and severely affected than black infants.
In typical RDS, tachypnea develops, the chest wall retracts, and expiration is accompanied by grunting and nostril flaring. Shunting of blood through nonventilated lung contributes to hypoxemia and metabolic and respiratory acidosis. Poor peripheral circulation and systemic hypotension may be evident. The chest radiograph shows a diffuse reticulogranular infiltrate and an air-filled tracheobronchial tree—air bronchogram.
Respiratory insufficiency also can be caused by sepsis, pneumonia, meconium aspiration, pneumothorax, persistent fetal circulation, heart failure, and malformations involving thoracic structures, such as diaphragmatic hernia. Evidence is also accruing that there may be common mutations in surfactant protein production that cause RDS (Garmany and colleagues, 2008; Shulenin and associates, 2004).
With inadequate surfactant, alveoli are unstable, and low pressures cause collapse at end expiration. Pneumocyte nutrition is compromised by hypoxia and systemic hypotension. There may be partial persistence of the fetal circulation that leads to pulmonary hypertension and a relative right-to-left shunt. Eventually, there is ischemic necrosis of alveolar cells. When oxygen therapy is initiated, the pulmonary vascular bed dilates, and the shunt reverses. Protein-filled fluid leaks into the alveolar ducts, and the cells lining the ducts slough. Hyaline membranes composed of fibrin-rich protein and cellular debris line the dilated alveoli and terminal bronchioles. The epithelium underlying the membrane becomes necrotic. Following hematoxylin-eosin staining, these membranes appear amorphous and eosinophilic, like hyaline cartilage. Because of this, respiratory distress in the newborn is also termed hyaline membrane disease.
The most important factor influencing survival is neonatal intensive care. Although hypoxemia is indicative of the need for oxygen, excess oxygen can damage the pulmonary epithelium and the retina. Advances in mechanical ventilation technology have improved neonatal survival. For example, continuous positive airway pressure (CPAP) prevents the collapse of unstable alveoli and allows high inspired-oxygen concentrations to be reduced, thereby minimizing toxicity. Disadvantages include disturbance of the endothelium and epithelium—caused by overstretching, which results in barotrauma and impaired venous return (Verbrugge and Lachmann, 1999). High-frequency oscillatory ventilation may reduce the risk of barotrauma by using a constant, low-distending pressure and small variations or oscillations to promote alveolar patency. This technique allows optimal lung volume to be maintained and carbon dioxide to be cleared without damaging alveoli. Although mechanical ventilation has undoubtedly improved survival, it is also an important factor in the genesis of chronic lung disease—bronchopulmonary dysplasia.
Treatment of the ventilator-dependent neonate with glucocorticoids was used for many years to prevent chronic lung disease. The American Academy of Pediatrics (2002) now recommends against their use because of limited benefits and increased adverse neuropsychological effects. Yeh and colleagues (2004) described significantly impaired motor and cognitive function and school performance in exposed neonates. The results of a Cochrane Review by Halliday and co-workers (2009) support late postnatal corticosteroid treatment only for infants who could not be weaned from mechanical ventilation.
In some studies, inhaled nitric oxide was shown to be associated with improved outcomes for infants undergoing mechanical ventilation (Ballard, 2006; Kinsella, 2006; Mestan, 2005; Schreiber, 2003, and all their colleagues). Another study done by van Meurs and associates (2005) showed no benefits. Currently, such treatment is considered investigational (Chock and co-workers, 2009; Stark, 2006).
Exogenous surfactant products can prevent hyaline membrane disease. They contain biological or animal surfactants such as bovine—Survanta, calf—Infasurf, porcine—Curosurf, or synthetic—Exosurf. In a Cochrane Review, Pfister and associates (2007) found that animal-derived and synthetic surfactant were comparable. Lucinactant—Surfaxin R—is a synthetic form that contains sinulpeptide KL4 to diminish lung inflammation (Zhu and co-workers, 2008).
Surfactant therapy has been credited for the largest drop in infant mortality rates observed in 25 years (Jobe, 1993). It has been used for prophylaxis of preterm at-risk infants and for rescue of those with established disease. Antenatal corticosteroids and surfactant given together result in an even greater reduction in the overall death rate. In a Cochrane Review, Seger and Soll (2009) found that infants who receive prophylactic surfactant had a decreased risk of pneumothorax, pulmonary interstitial emphysema, ...