32 Transient Tachypnea of the Newborn Kirsten A. Kicnstra I. DEFINITION.

Transient tachypnea of the newborn (TTN), first described by Avery and coworkers in 1900, 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, which 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 basolatcral 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 ventilationperfusion mismatch. Because infants usually recover, a precise pathologic definition is lacking. III. EPIDEMIOLOGY. Risk factors for TTN include birth by cesarean section with or without labor, precipitous birth, and preterm birth. These have been attributed to delayed or abnormal fetal lung fluid clearance due to the absence of the hormonal changes that accompany spontaneous labor. For infants delivered by elective cesarean section. the presence of labor and the gestational age at delivery impact the risk of respiratory complications, with some degree of protection provided by onset of labor and term gestation. Delivery at lower gestational ages, including late preterm birth, increases the risk of TTN. Diagnosis at earlier gestations is complicated by the presence of other comorbidities such as respiratory distress syndrome (RDS). Other risk factors include male gender and family history of asthma(especially the mother). The mechanism underlying the gender- and asthma-associated risks is unclear but may be related to altered sensitivity to catecholarnines that play a role in lung fluid clearance. Genetic polymorphisms in -adrenergic receptors in alveolar type II cells have been associated with TIN and may influence lung fluid clearance by regulating epitheliaal sodium channel expression. Macrosomia. maternal diabetes, and multiple gestations also increase risk of TTN.The associations between TT nan other obstetric factors such as excessive maternal sedation, prolonged labor, and volume of rnaternal intravenous fluids have been less consistent. 1V. CLINICAL PRESENTATION. Affected term or late preterm infants usually present within (he first o hours of life with tachypnea: respiratory rates are typically 60 to 120 breaths

per minute. The tachypnea may be associated with mild to moderate respiratory distress with retractions, grunting, nasal flaring, and/or mild cyanosis that usually responds to supplemental oxygen at <0.40 FiO2. Respiratory failure and mechanical ventilation are rare. Infants may have an increased anteroposterior diameter of the chest (barrel-shaped) due to hyperinflation. which may also push down the liver and spleen, making them palpable. Auscultation usually reveals good air entry, and crackles may or may not be appreciated. Signs of TTN usually persist for 12 to 24 hours in cases of mild disease but can last up to 72 hours in more severe cases. V. DIFFERENTIAl. DIAGNOS1S. The diagnosis of TTN requires the exclusion of other potential etiologies for mild to moderate respiratory distress presenting in the first 6 hours of age. The differential diagnosis includes pneumonia/sepsis, RDS, pulmonary hypertension, meconiurn aspiration, cyanotic congenital heart disease, congenital malformations(e.g., congenital diaphragmatic hernia, cystic adenomatoid malformations), central nervous system (CNS) insults (subarachnoid hemorrhage. hypoxic-ischcrnic enccphalopathv) causing central hyperventilation, pneumothorax, polycythemia, and metabolic acidosis. VI. EVALUATION A. History and physical examilnation. A careful history identifies elements such as prematurity, infectious risk factors, meconium, or perinatal depression that may aid in directing the evaluation. Similarly, findings on physical examination such as cardiac or neurologic abnormalities may lead to a more targeted investigation. B. Radiographic evaluation. The chest radiograph of an infant with TTN is consistent with retained fetal lung fluid, with characteristic prominent perihilar streaking (sunburst pattern) due to engorgement of periarterial lymphatics that participate in the clearance of alveolar fluid, Coarse, fluffy densities may reflect alveolar edema. Hyperaeration with widening of intercostal spaces, mild cardiomegaly, widened and fluid-filled interlobar fissure, and mild pleural effusions may also be observed. The radiographic findings in TTN usually improve by 12 to 18 hours and resolve by 48 to 72 hours. This rapid resolution helps distinguish the process from pneumonia and meconium aspiration. The chest radiograph can also be used to exclude other diagnoses such as pneumothorax, RDS, and congenital malformations. Of note, the presence of increased pulmonary vascularity in the absence of cardiormegaly may represent total anomalous pulmonary venous return. C. Laboratoris evaluation. A complete blood count (CBC) and appropriate cultures can provide information concerning possible pneumonia or sepsis. If risk factors or laboratory data suggest infection, or if respiratory distress does not improve, broad-spectrum antibiotics should be initiated. An arterial blood gas may be used to determine the extent of hypoxemia and adequacy of ventilation. Infants with TTN may have mild hypoxemia and mild respiratory acidosis that typically resolve over 24 hours. With persistent or severe hypoxemia. a cardiac evaluation should be considered. Respiratory alkalosis may reflect central hyperventilation due to CNS pathology. VII. TREATMENT. Treatment is mainly supportive with provision of supplemental oxygen. as needed. More severe cases may respond to continuous positive airway pressure (CPAP) to improve lung recruitment. Infants often undergo an evaluation for infection are treated with antibiotics for 24 to 48 hours until blood cultures arc negative. If tachypnea persists and is associated with increased work of breathing, gavage feedings or intravenous fluids may be

needed. Strategies aimed to facilitate lung fluid absorption have not shown clinical efficacy. Oral furosemide has not been shown to improve the duration of tachypnea or length of hospitalization. In a study based on the hypothesis that infants with TTN have relatively low levels of catecholarnines that facilitate fetal lung fluid absorption, treatment with racemic epinephrine did not change the rate of resolution of tachypnea compared to placebo. COMPLICAIIONS. Although TIN is a self-limited process, supportive therapy may be accompanied by complications. CPAP is associated with increased risk of air leak. Delayed initiation of oral feeds may interfere with parental bonding and establishment of breastfeeding, and may prolong hospitalization. IX. PROGNOSIS. By definition, TIN is a self-limited process with no risk of recurrence and the prognosis is excellent. Generally, there are no significant long-term residual effects. However, there is an increasing body of literature describing a possible link between TTN and reactive airway disease; the correlation remains to be confirmed. Suggested Readings Guglani L. Lakshminrusimha S. Ryan RM. Transient tachypnea of the newborn. Pcdiatr Rev 2008;29:e59-c5. Tutdibi E, Ones K, Bucheler N. et al. Impact of labor on outcomes in transient tachypnea of the newborn. Pediatrics 2010:125:e577-e583.