Transient Tachypnea of the Newborn

Etiology

Delayed clearance of fetal lung fluid after birth is the underlying cause of TTN. Residual fluid within the alveoli and interstitium impairs gas exchange, resulting in tachypnea and respiratory distress. Normally, this fluid is cleared through a physiologic shift in the pulmonary epithelium from chloride secretion to active sodium reabsorption, a process stimulated by the release of catecholamines during labor. Well-established maternal risk factors for TTN are gestational diabetes, asthma, and cesarean delivery without labor.[5][6] Fetal and neonatal risk factors include gestational age younger than 39 weeks, male sex, small or large size for gestational age, and perinatal asphyxia.[7]

Epidemiology

TTN is the most common cause of neonatal respiratory distress, affecting approximately 7% to 10% of neonates. This condition occurs twice as frequently as respiratory distress syndrome, although incidence rates vary across studies due to differences in population characteristics and associated risk factors.[8] The incidence is inversely proportional to gestational age, affecting approximately 10% of neonates born at 33 to 34 weeks, 5% between 35 and 36 weeks, and fewer than 1% of those born at 37 weeks or greater.[9][10][11] While individual risk is highest in preterm and early term infants, most cases occur in term neonates simply because the majority of births occur at term.[12]

Cesarean delivery, particularly when performed before the onset of labor, is a well-established predisposing factor for TTN. The risk is primarily attributed to the absence of hormonal and physiological changes associated with labor, most notably a catecholamine surge, which facilitates the absorption of alveolar fluid into the lymphatic and vascular systems.[13] Although thoracic compression during vaginal delivery may also aid in expelling some alveolar fluid, this mechanism likely plays a secondary role compared to hormonally driven clearance. Reflecting these concerns, the American College of Obstetricians and Gynecologists (ACOG) issued guidelines in 2013 advising against nonmedically indicated cesarean deliveries before 39 weeks' gestation, in part to reduce respiratory morbidity, including TTN.[14] Other risk factors for TTN include maternal obesity, maternal diabetes, fetal male sex, and being small or large for gestational age.[7]

Pathophysiology

Fetal lung fluid plays a crucial role in the normal development of the lungs. As early as 6 weeks of gestation, the fetal pulmonary epithelium secretes fluid into the alveolar space at a rate of approximately 2 mL/kg per hour, which increases to about 5 mL/kg per hour by term.[12] Initially, chloride ions enter the alveolar epithelial cells by active transport and are secreted into the alveoli. Sodium ions passively follow, due to the electrochemical gradient. Osmosis then draws water into the alveoli, keeping them filled with fluid, which helps maintain normal lung expansion and contributes to the overall volume of amniotic fluid.[15][16]

A few days before the onset of spontaneous labor, fetal lung fluid production decreases. During labor, a maternal surge in catecholamines and glucocorticoids stimulates fluid clearance by activating epithelial sodium channels (ENaC) on alveolar cell membranes.[17] Sodium is absorbed through the ENaC and transported into the pulmonary interstitium, creating an osmotic gradient that allows chloride and water to follow and enter the pulmonary and lymphatic circulations.[18] This transport mechanism is the principal means of clearing fetal lung fluid. While mechanical factors, such as Starling forces and the thoracic "squeeze" during vaginal delivery, may aid in expelling fluid, they likely play a lesser role than hormonally mediated absorption.[19] TTN occurs when the transition from chloride secretion to sodium reabsorption, via activated ENaC, is delayed or immature, resulting in the failure to clear alveolar fluid. The excess fluid remaining in the alveoli causes decreased pulmonary compliance and impaired gas exchange, leading to signs of respiratory distress.[20]

History and Physical

Clinicians should maintain a high index of suspicion for TTN in neonates with risk factors discussed in the epidemiology and etiology sections above, including cesarean delivery without labor, late prematurity, and maternal diabetes. Neonates with TTN typically present with signs of mild respiratory distress within the first 2 hours after birth. Tachypnea (a respiratory rate of greater than 60 breaths per minute) is the hallmark feature that gives the condition its name. Additional findings include mild to moderate subcostal and intercostal retractions, nasal flaring, and expiratory grunting.

Further, auscultation may reveal clear or slightly decreased breath sounds, but rales and wheezing are generally absent. Cyanosis and tachycardia may occur if significant hypoxemia is present, but improve with supplemental oxygen administration.[Hermansen CL, Lorah KN. Transient tachypnea of the newborn. NeoReviews. 2017;18(3):e141–e148. https://doi.org/10.1542/neo.18-3-e141] The severity of respiratory distress in TTN is generally less than in other neonatal respiratory disorders. Additionally, patients with TTN typically lack findings suggestive of sepsis, such as temperature instability, lethargy, or poor perfusion.

Evaluation

Early evaluation helps distinguish TTN, delayed transition, and other conditions that cause neonatal respiratory distress, such as respiratory distress syndrome (RDS), pneumonia, meconium aspiration, pneumothorax, and sepsis. Although the 6-hour mark is an arbitrary cutoff to distinguish delayed transition from TTN, clinicians should not delay initiating a diagnostic workup in a newborn with tachypnea. A timely evaluation is essential to identify and treat more serious respiratory conditions. The diagnostic workup begins with pulse oximetry to assess oxygenation, including preductal and postductal oxygen saturations to screen for critical congenital heart disease. 

Next, imaging plays a vital role in diagnosing TTN. Typical radiographic features include hyperinflated lungs, prominent vascular markings, fluid in interlobar fissures, and occasionally small pleural effusions—features differentiate it from RDS, which shows air bronchograms and diffuse ground-glass opacities.[2] In TTN, x-ray findings often resolve within 24 hours.  

Lung ultrasound (LUS) is increasingly used to diagnose TTN. The American Academy of Pediatrics states that this modality is safe, highly sensitive, and specific for identifying TTN, helping to distinguish TTN from RDS and pneumonia.[21] Obtaining a point-of-care ultrasound (POCUS) can reduce the time to diagnosis compared to performing a chest x-ray and avoid exposure to ionizing radiation.[22] Neonatal units in academic and tertiary care settings frequently use POCUS as a first-line imaging modality; however, chest x-rays remain more accessible and reliable in level 1 nurseries, which usually lack the equipment and expertise to perform and interpret ultrasound results. 

Characteristic LUS findings in TTN include the "double lung point," which demonstrates the upper lung with air and the lower lung with signs of extra fluid. Additionally, mild to moderate pulmonary edema from retained lung fluid, known as interstitial syndrome, may occur in TTN, and lung consolidation with air bronchograms is absent.[23] Venous or arterial blood gas analysis can identify hypoxemia or hypoventilation with acidosis. If an infection is suspected, laboratory studies, including a complete blood count, C-reactive protein, and blood cultures, should be obtained.[2]

Treatment / Management

Although TTN is a self-limited condition, treatment optimizes the infant's breathing and provides comfort while the condition resolves. The primary approach is supportive care, focusing on monitoring, maintaining adequate oxygenation, and minimizing the work of breathing.[24] In some cases, noninvasive respiratory support, such as an oxygen hood, nasal continuous positive airway pressure, or a high-flow nasal cannula, can reduce respiratory distress and maintain adequate oxygenation. These interventions may also aid in clearing retained lung fluid, thereby reducing the effort required to breathe and potentially shortening the duration of tachypnea.[1] (A1)

When infants fail to improve, worsen, or need an fraction of inspired oxygen greater than 0.40, clinicians should consider transferring them to a facility that offers a higher level of neonatal care.[25] Routine support includes continuous cardiopulmonary monitoring, maintaining a neutral thermal environment, maintaining fluid balance, obtaining blood glucose levels, securing intravenous (IV) access, and monitoring for signs of infection. Because TTN may be challenging to distinguish from pneumonia and early sepsis, clinicians should consider using empiric antibiotic therapy (eg, ampicillin and gentamicin) while awaiting the results of blood cultures.

Neonates with significant tachypnea or those requiring respiratory support often need IV fluids or nasogastric feeding to ensure adequate hydration and minimize the risk of aspiration. Oral feeding can be initiated or resumed once the respiratory rate is consistently below 60 breaths per minute, the work of breathing is minimal, and the infant can coordinate sucking, swallowing, and breathing. However, care should be individualized, as some clinically stable infants with respiratory rates above 60 may be able to tolerate oral feeding. Breast milk or formula volumes can be gradually advanced as respiratory symptoms improve.

Medications do not play a routine role in the treatment of TTN, as it is a self-limited condition that typically resolves with supportive care alone within 72 hours. Inhaled beta-agonists, including salbutamol and albuterol, have been investigated for their potential to enhance lung fluid clearance by stimulating sodium reabsorption through ENaC channels.[26] Salbutamol administration may slightly decrease the duration of symptoms and hospital stay, but further clinical trials are needed to confirm its efficacy and safety.[27][28] Current evidence does not support the routine use of diuretics, racemic epinephrine, or postnatal corticosteroids in the management of TTN.[29][30] (A1)

Differential Diagnosis

When evaluating a neonate with respiratory distress and tachypnea, the differential diagnosis must prioritize ruling out more serious conditions that require prompt and specific treatment, in contrast to the typically self-limited course of TTN.

• RDS, due to surfactant deficiency, is more common in preterm infants, who present with tachypnea, grunting, retractions, and hypoxemia. Chest x-ray shows hypoinflation and a reticulogranular appearance.
• Pneumonia and sepsis present with respiratory distress, often with temperature instability, poor perfusion, or hypotension. A chest x-ray may show patchy infiltrates or consolidation. Positive blood cultures, abnormal complete blood count, and inflammatory markers support the diagnosis.[2]
• Meconium aspiration syndrome occurs in term or post-term infants with meconium-stained amniotic fluid. Patients present with respiratory distress, coarse breath sounds, hypoxemia, and patchy infiltrates or hyperinflation on chest x-ray.[31]
• Congenital diaphragmatic hernia presents with severe respiratory distress, scaphoid abdomen, and decreased breath sounds on the affected side. Chest x-ray shows bowel loops in the thorax and a mediastinal shift.[2]
• Pneumothorax presents with sudden respiratory distress and decreased breath sounds. Chest x-ray, transillumination, or ultrasound confirms the diagnosis.[32]
• Critical congenital heart disease is a consideration in neonates with cyanosis, shock, or refractory hypoxemia. Pulse oximetry screening, including preductal and postductal oxygen saturations and echocardiography, is an essential diagnostic tool for evaluating neonatal respiratory distress.[33]
• Persistent pulmonary hypertension of the newborn presents with severe hypoxemia, a difference between preductal and postductal oxygen saturations, and may be associated with underlying parenchymal lung disease. Echocardiography is a diagnostic tool that confirms elevated pulmonary pressures and rules out structural heart disease.

Prognosis

The prognosis for infants with TTN is excellent, as this is a self-limited condition that typically resolves within 24 to 72 hours with supportive care alone; most infants recover without invasive respiratory treatment or long-term sequelae. A short admission to a neonatal unit for monitoring and supportive care is often sufficient. Complications are rare; however, case reports describe a form of “malignant” transient tachypnea of the newborn in which affected neonates develop persistent pulmonary hypertension, possibly related to elevated pulmonary vascular resistance secondary to retained lung fluid.[34] While some evidence suggests an increased risk of wheezing or asthma later in childhood, the vast majority of neonates with TTN experience complete resolution of symptoms and normal long-term pulmonary function.[3][35]

Complications

The most common complications of TTN are short-term and related to the need for supportive care. These include prolonged hospitalization and transfer to a neonatal unit, with subsequent maternal-infant separation that contributes to delayed initiation of breastfeeding and may interfere with early bonding.[3] Infants may be exposed to intravenous antibiotics while awaiting blood culture results. Rarely, TTN progresses to severe hypoxemia necessitating mechanical ventilation, with a risk of air leak and pneumothorax.[1]