Respiratory distress occurs frequently in newborns and can be a presenting symptom of both benign and life-threatening diseases. Failure of any of a complex series of cardiovascular and pulmonary modifications that help the neonate transition to extrauterine life can manifest as neonatal respiratory distress. Clinical features of a newborn in respiratory distress include tachypnea of more than 60 breaths per minute; cyanosis; expiratory grunting; intercostal, subcostal, or supraclavicular retractions; and nasal flaring. Although the causes of respiratory distress are numerous, this chapter focuses on a relatively common cause of respiratory distress known as transient tachypnea of the newborn (TTN) and the identification of a more serious condition, persistent pulmonary hypertension of the newborn (PPHN).

PATHOPHYSIOLOGY

TTN is a benign, self-limited disorder that occurs during the transition from uterine to extrauterine life and results from the delayed clearance of excess lung fluid. TTN was first described in 1966 when it was observed that a subset of newborns exhibited respiratory distress, consisting primarily of tachypnea, at or shortly after birth. Although the tachypnea persisted for several days, it subsequently resolved completely without sequelae.¹

Inadequate or delayed clearance of fetal lung fluid results in TTN. This fluid fills the alveolar space and then moves into the extra-alveolar space subsequently surrounding the perivascular tissue and lung fissures. It remains there until resorption is completed by the lymphatic or vascular circulation. The initiation of gas exchange in the lungs requires onset of breathing, increased pulmonary blood, and decreased systemic vascular resistance and air displacing fetal fluids. Some have suggested that TTN is associated with a relative surfactant dysfunction,² but other studies found no association between TTN and surfactant mutation.³

Delivery via elective cesarean section increases the risk for TTN. Although the physiologic mechanisms are not understood, this risk is significantly decreased if the mother undergoes a trial of labor.⁴ Additional risk factors for TTN include male sex, late prematurity (34 to 37 weeks gestational age) and macrosomia.⁵ Although the mechanism is obscure, being born to an asthmatic mother appears to be a risk factor for TTN. Infants born to women with gestational diabetes also appear to be at increased risk. This observation may be related to a corresponding increase in the rate of cesarean sections among these mothers.

PPHN commonly occurs in full-term and near-term (late preterm) infants (>34 weeks) and has an estimated incidence of 0.2% of live births.⁶ After birth, PPHN occurs when there is an insufficient or delayed decrease in pulmonary vascular resistance, which results in right-to-left shunting of blood through the ductus arteriosus or foramen ovale and severe hypoxemia. PPHN typically arises in the setting of a structurally normal heart, either with or without associated pulmonary disease. Perinatal risk factors that increase pulmonary vasoconstriction include hypoxia, acidosis, alveolar atelectasis, sepsis, direct lung injury, hypoglycemia, and cold stress.^7,8 The most common causes are meconium aspiration syndrome (50%), idiopathic PPHN (20%), sepsis (20%), and respiratory distress syndrome (5%).⁷

Despite the array of conditions associated with PPHN, one common feature is an underlying abnormality of the pulmonary vasculature. This abnormality can be broadly categorized into three groups.^6,7 In the first group, the vasculature is abnormally constricted due to parenchymal lung disease. This group is the most common and includes meconium aspiration syndrome, sepsis, and respiratory distress. The second group is associated with structurally abnormal pulmonary vasculature and includes idiopathic PPHN. The pulmonary vasculature of these infants shows significant thickening and does not appropriately vasodilate in response to birth stimuli (particularly nitric oxide and endothelin-signaling pathways). The vasculature of the third group is hypoplastic, usually due to congenital diaphragmatic hernia or, much less commonly, a rare malformation of lung development known as alveolar-capillary dysplasia.⁶

TTN presents within the first few hours of life with respiratory rates greater than 60 breaths per minute. Infants typically have shallow respirations, which may be accompanied by mild cyanosis. Increased work of breathing, including subcostal retractions, expiratory grunting, and nasal flaring, may also be present. Auscultation of the chest generally reveals clear breath sounds without rales, rhonchi, or crackles. Most infants do not require high levels of exogenous oxygen to ensure adequate oxygenation. Although symptoms usually resolve within the first 24 hours, TTN can persist for as long as 72 hours.

Early signs of PPHN may overlap with those of TTN, but there are distinguishing features. As unoxygenated blood is shunted away from the high-pressure circuit of the lungs through the patent ductus arteriosus in PPHN, the blood that reaches postductal areas of the systemic circulation is mixed, or lower in saturation, than the blood that circulates to the preductal regions. Pulse oximeters placed on both a preductal (right upper) and a postductal (left upper, right or left lower) extremity yield discrepancies. If the preductal oxygen saturation exceeds the postductal oxygen saturation by more than 1 or 2 percentage points, a diagnosis of PPHN must be considered. These infants can present with cyanosis and may deteriorate rapidly, with systemic hypotension and severe respiratory distress, if their pulmonary arterioles cannot be dilated.