Practice Essentials
Transient tachypnea of the newborn (TTN) is a common etiology for respiratory distress in the immediate newborn period.
A common historical finding is a cesarean section done with the absence of limited labor.
Diagnosis of TTN is one of exclusion.
A chest X-ray may be useful in evaluating for TTN.
A worsening clinical course should alert clinicians to other etiologies for respiratory distress.
TTN usually resolves by 72 hours of life.
Management of TTN is supportive, with the main clinical finding being the need for respiratory support.
Background
Transient tachypnea of the newborn (TTN) is a self-limited disease commonly seen in neonates throughout the world and is encountered by physicians who care for hospitalized neonates. This condition is caused by delayed postpartum resorption of fetal lung fluid, resulting in ineffective gas exchange, respiratory distress, and tachypnea. [1] It is the most common etiology of perinatal respiratory distress, responsible for 40% of respiratory distress after birth. [2, 3]
Infants with transient tachypnea of the newborn present within the first few hours of life with tachypnea and other signs of respiratory distress, increased oxygen requirement, and arterial blood gases that do not reflect carbon dioxide retention. When managing transient tachypnea of the newborn, it is important to observe for the development of respiratory fatigue and signs of clinical deterioration that may suggest other diagnoses. The appearance of the chest radiograph below is consistent with a neonate having transient tachypnea of the newborn.
Transient Tachypnea of the Newborn. A supine anteroposterior chest radiograph of an infant with transient tachypnea of the newborn (TTN). Note the reticular appearance of the film with mild cardiomegaly and obvious interstitial fluid.
Pathophysiology
Studies have been done with respect to the catecholamine surge following birth. Fetal lung fluid clears by 35% a few days prior to birth, owing to changes in the epithelial sodium (Na+) channel (ENaC); by around 30% during active labor, owing to mechanical transpulmonary forces and catecholamine surge; and around 35% postnatally, during active crying and breathing.
Lack of an epinephrine surge in neonates born by cesarean compared with vaginal delivery often leads to decreased fetal lung fluid release. In the face of elevated epinephrine levels, the chloride (Cl-) pump responsible for lung liquid secretion is inhibited, and the sodium channels that absorb liquid are stimulated. As a result, net movement of fluid from the lung into the interstitium occurs. Therefore, cesarean delivery without labor and subsequent lack of this normal surge of counter-regulatory hormones limit the excursion of pulmonary fluid. Transient tachypnea of the newborn (TTN) is the result of a delay in clearance of fetal lung liquid. In the past, respiratory distress was thought to be a problem of relative surfactant deficiency but is now characterized by an airspace-fluid burden secondary to the inability to absorb fetal lung liquid.
In vivo experiments have demonstrated that lung epithelium secretes Cl- and fluid throughout gestation, but it develops the ability to actively reabsorb Na+ only during late gestation. At birth, the mature lung switches from active Cl- (fluid) secretion to active Na+ (fluid) absorption in response to circulating catecholamines. Evidence suggests glucocorticoids play a role in this switch. Changes in oxygen tension augment the Na+–transporting capacity of the epithelium and increase gene expression for the ENaC. The inability of the immature fetal lung to switch from fluid secretion to fluid absorption mainly occurs because of immaturity in the expression of ENaC, which may be upregulated by glucocorticoids. [4] Glucocorticoids induce lung Na+ reabsorption most likely through the fetal lung alveolar ENaC channel in late gestational age. [5]
Both pharmacologic blockade of the lung's ENaC channel and genetic knockout experiments using mice deficient in the ENaC pore-forming subunit have demonstrated the critical physiologic importance of lung Na+ transport at birth. When Na+ transport is ineffective, newborn animals develop respiratory distress; hypoxemia; fetal lung liquid retention; and, in the case of the ENaC knockout mice, death. Bioelectrical studies of human infants' nasal epithelia demonstrate that both transient tachypnea of the newborn and respiratory distress syndrome (RDS) involve defective amiloride-sensitive Na+ transport. [6, 7]
Mature newborns who have normal transitions from fetal to postnatal life have mature surfactant and lung epithelial systems. Transient tachypnea of the newborn occurs in mature newborns with mature surfactant pathways and poorly developed respiratory epithelial Na+ transport, whereas neonatal RDS occurs in infants with both premature surfactant pathways and immature Na+ transport. At the same time, full-term neonates may have lower lamellar body counts, suggesting diminished surfactant function and association with prolonged tachypnea of newborns. [8]
Fetal lung fluid clears by 35% a few days prior to birth, owing to changes in the ENaC; by around 30% during active labor owing to mechanical transpulmonary forces and catecholamine surge; and around 35% is cleared postnatally during active crying and breathing. An infant born by cesarean delivery is at risk of having excessive pulmonary fluid as a result of not having experienced all of the stages of labor and subsequent lack of appropriate catecholamine surge, which results in low release of counter-regulatory hormones at delivery. The result is alveoli with retained fluid that inhibit gas exchange.
Etiology
Transient tachypnea of the newborn (TTN) results from delayed absorption of fetal lung fluid following delivery. The disorder is commonly observed following birth by cesarean delivery.
Cesarean delivery
Cesarean delivery is associated with increased risk of transient tachypnea of the newborn regardless of whether the cesarean delivery was preceded by labor or not. Labor prior to cesarean delivery is not protective of transient tachypnea of the newborn. [9]
Studies using lung mechanical measurements were performed in infants born by either cesarean or vaginal delivery. Milner et al noted that the mean thoracic gas volume was 32.7 mL/kg in infants born vaginally and 19.7 mL/kg in infants born via cesarean delivery. [10] An important observation is that the chest circumferences were the same. Milner et al also noted that the infants born via cesarean delivery had higher volumes of interstitial and alveolar fluid compared with those born vaginally, despite the overall thoracic volumes being within the reference range. [10]
Epinephrine release during labor affects fetal lung fluid. In the face of elevated epinephrine levels, the chloride pump responsible for lung liquid secretion is inhibited, and the sodium channels that absorb liquid are stimulated. As a result, net movement of fluid from the lung into the interstitium occurs. [11, 12] Therefore, cesarean delivery without labor and subsequent lack of this normal surge of counter-regulatory hormones limit the excursion of pulmonary fluid.
Maternal asthma and smoking
Demissie et al performed a historical cohort analysis on singleton live deliveries in New Jersey hospitals from 1989 to 1992. [13] After controlling for confounding effects of important variables, infants of mothers with asthma were more likely to exhibit transient tachypnea of the newborn than infants of mothers in the control group.
Schatz et al studied a group of 294 pregnant women with asthma and a group of 294 pregnant women without asthma. [14] Both groups had normal pulmonary function test results and were matched for age and smoking status. Transient tachypnea of the newborn was found in 11 infants (3.7%) of mothers with asthma and in 1 infant (0.3%) of a mother from the control group. No significant differences between asthmatic and matched control subjects in other transient tachypnea of the newborn risk factors were observed.
Gundogdu studied the effect of sibling asthma on 1318 newborns with transient tachypnea of the newborn. [15] Prelabor cesarean section and maternal asthma were common risk factors for these newborns, and there was an association between sibling asthma and the development of transient tachypnea of the newborn in the infants, even when their mothers were nonasthmatic. [15]
Prematurity
Late preterm infants are at higher risk of developing transient tachypnea of the newborn compared with full-term infants, probably because of immaturity of ENaC transition, lack of lamellar bodies for surfactant production, and overall lung epithelium immaturity. [16, 17] The risk of adverse respiratory outcomes in late preterm infants is particularly higher for those delivered after 35 weeks' gestation and whose mothers did not receive antenatal steroids. [18]
Gestational diabetes in itself does not appear to be a major contributor to respiratory distress syndrome in infants born late preterm. [19] Independent factors that raise the risk of respiratory morbidity in these infants are prematurity and cesarean birth.
Other factors
Male sex and macrosomic infants born to diabetic mothers have been associated with increased risk of transient tachypnea of the newborn.
Maternal illicit drug use (especially narcotics), excessive maternal sedation or fluid overload, perinatal asphyxia, elective cesarean delivery without preceding labor, precipitous delivery, low Apgar scores, and prolonged rupture of membranes are frequently associated with transient tachypnea of the newborn.
Low birthweight, pregnancy-induced hypertension, and multiparity have also been noted as significant predisposing factors for transient tachypnea of the newborn. [2]
Based on possible complications, cholestasis of pregnancy in mothers is a finding that may prompt early delivery. A 2021 study showed severe maternal intrahepatic cholestasis and elevated serum bile-acid levels to be positively correlated with an increased risk for transient tachypnea of the newborn. [20]
Boskabadi et al found that serum vitamin D levels of infants with transient tachypnea of the newborn and their mothers were significantly lower than the control group. [21]
Epidemiology
United States data
Approximately 1% of infants have some form of respiratory distress that is not associated with infection. Respiratory distress includes both respiratory distress syndrome (RDS) (ie, hyaline membrane disease) and transient tachypnea of the newborn (TTN). Of this 1%, approximately 33-50% have transient tachypnea of the newborn (TTN). [22]
Race-, sex-, and age-related demographics
No racial predilection has been reported. Male neonates are more affected than females.
Clinically, transient tachypnea of the newborn presents as respiratory distress in full-term or near-term infants.
Prognosis
Transient tachypnea of the newborn (TTN) is generally a self-resolving disorder, most often resolving over a 24- to 72-hour period. Rapid clinical recovery within 6 to 12 hours and the absence of radiographic findings characteristic of other lung disorders supports the diagnosis. As the retained lung fluid is absorbed by the infant's lymphatic system, the pulmonary status improves: The degree of tachypnea lessens, the oxygen requirement decreases and chest X-ray findings normalize.
Longer durations of tachypnea are generally associated with prolonged hospitalization and a greater severity of transient tachypnea of the newborn. Kasap et al reported that a peak respiratory rate of more than 90 breaths per minute during the first 36 hours of life was associated with prolonged tachypnea lasting more than 72 hours. [23] Elevated levels of the partial pressure of carbon dioxide (PCO2) and base excess have also been associated with longer stays in the neonatal intensive care unit. [24]
Morbidity/mortality
With the exception of complications that may occur, transient tachypnea of the newborn is usually self-limited, with a duration of approximately 2 days. A future factor may be the development of wheezing or asthma (see Complications, below).
The most common background with respect to transient tachypnea of the newborn consists of cesarean delivery without labor or precipitous delivery. Tachypnea occurs shortly after birth and often with other signs of respiratory distress, such as grunting, nasal flaring, retractions, hypoxia, and cyanosis.
Complications
Respiratory issues while hospitalized
Infants who exhibit an increased work of breathing may also develop air leaks, such as a pneumothorax, particularly with those on continuous positive airway pressure (CPAP) support. In rare instances, some infants may have prolonged tachypnea (>72 hours) or worsening respiratory distress requiring increased respiratory support. These infants may develop hypoxia, acidosis, and respiratory failure with the need for mechanical ventilation. Less commonly, infants delivered by elective cesarean section prior to 39 weeks' gestation may develop pulmonary hypertension and may even require extracorporeal membrane oxygenation (ECMO). [25]
Future wheezing and asthma
Several reports suggest that transient tachypnea of the newborn is a risk factor for future wheezing syndromes in childhood. The rate of respiratory syncytial virus (RSV) hospitalization is higher in children with transient tachypnea of the newborn compared to those without. When Birnkrant et al studied the association between childhood asthma and transient tachypnea of the newborn in a cohort of 2137 term newborns who were subsequently diagnosed with asthma and a similar number of matched controls, transient tachypnea of the newborn was significantly associated with the diagnosis of childhood asthma. [26] This association of transient tachypnea of the newborn and asthma was statistically strongest among non-White male infants whose mothers lived at an urban address and did not have asthma. In another study, Liem et al suggested that genetic and environmental interactions synergistically predispose these children for future wheezing. [27]
Patient Education
Data links transient tachypnea of the newborn (TTN) to the later development of childhood asthma. Birnkrant et al studied the association between childhood asthma and transient tachypnea of the newborn in a nested cohort of 2137 term newborns who were subsequently diagnosed with asthma and a similar number of birthday-matched controls. [26] After adjustment for confounding factors, transient tachypnea of the newborn was significantly associated with the diagnosis of childhood asthma. The adjusted odds ratio was 1.5 (95% CI, 1.13-1.99; P = .005). The association of transient tachypnea of the newborn and asthma was statistically strongest among nonwhite male infants whose mothers lived at an urban address and did not have asthma. Thus, parents should be made aware that their child has a small risk of subsequently developing childhood asthma, especially if the child is male.
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Transient Tachypnea of the Newborn. A supine anteroposterior chest radiograph of an infant with transient tachypnea of the newborn (TTN). Note the reticular appearance of the film with mild cardiomegaly and obvious interstitial fluid.
