I. DEFINITION. Transient tachypnea of the newborn (TTN), first described by Avery and coworkers in 1966, results from delayed clearance of fetal lung fluid. As the name implies, it is usually a benign, self-limited process. It generally affects infants born at late preterm or term gestation. The disorder is characterized by tachypnea with signs of mild respiratory distress including retractions and cyanosis; decreased oxygen saturation is usually alleviated by supplemental oxygen with FiO₂ <0.04.

II. PATHOPHYSIOLOGY. To accommodate the transition to breathing air at birth, the lungs must switch from a secretory mode that provides the fetal lung fluid required for normal lung growth and development in utero, to an absorptive mode. This transition is thought to be facilitated by changes in the maternal-fetal hormonal milieu, including a surge in glucocorticoids and catecholamines, associated with physiologic events near the end of pregnancy and during spontaneous labor. Amiloride-sensitive sodium channels expressed in the apical membrane of the alveolar epithelium play an important role in lung fluid clearance. Adrenergic stimulation and other changes near birth lead to passive transport of sodium through the epithelial sodium channels, followed by transport into the interstitium via basolateral Na⁺/K⁺-ATPase, and passive movement of chloride and water through paracellular and intracellular pathways. Interstitial lung fluid pools in perivascular cuffs of tissue and in the interlobar fissures and is then cleared into pulmonary capillaries and lung lymphatics. Disruption or delay in clearance of fetal lung fluid results in the transient pulmonary edema that characterizes TTN. Compression of the compliant airways by fluid accumulated in the interstitium can lead to airway obstruction, air trapping, and ventilation-perfusion mismatch. Functional residual capacity may be reduced due to obstruction, whereas thoracic gas volume may increase secondary to air trapping. Because infants usually recover, a precise pathologic definition is lacking.

III. EPIDEMIOLOGY. The incidence of TTN is 0.3% to 0.6% of term deliveries and 1% of preterm deliveries. Risk factors for TTN include cesarean delivery with or without labor, precipitous birth, and preterm birth. These conditions are thought to result in delayed or abnormal fetal lung fluid clearance due to the absence of the hormonal changes that accompany spontaneous labor. The presence of labor and the gestational age at delivery impact the risk of respiratory complications for infants delivered by elective cesarean section; onset of labor and term gestation provide some degree of protection. Delivery at lower gestational ages, including late preterm birth, increases the risk of TTN. Diagnosis at earlier gestations is complicated by the presence of comorbidities such as respiratory distress syndrome (RDS). Other risk factors include male gender and family history of asthma (especially mother). The mechanism underlying the gender- and asthma-associated risks is unclear but may be related to altered sensitivity to catecholamines that play a role in lung fluid clearance. Genetic polymorphisms in β-adrenergic receptors in alveolar type II cells have been associated with TTN and may influence lung fluid clearance by regulating epithelial sodium channel expression as well as explain the correlation between TTN and wheezing in the first years of life. Macrosomia, maternal diabetes, and multiple gestations also increase the risk of TTN. The associations between TTN and other obstetric factors such as excessive maternal sedation, prolonged labor, and volume of maternal intravenous fluids have been less consistent. Several small trials suggest that antenatal corticosteroids prior to cesarean section at 37 to 38 weeks may also decrease risk.