Transient Tachypnea of the Newborn

Transient tachypnea of the newborn (TTN) is a self-limited disease commonly seen in neonates throughout the world and is encountered by all physicians who take care of newborn infants. 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 ABGs that do not reflect carbon dioxide retention. When managing transient tachypnea of the newborn, it is imminent to observe for development of respiratory fatigue and signs of clinical deterioration that may suggest some other diagnoses. See the image below.

Noninfectious acute respiratory disease develops in approximately 1% of all newborn infants and results in admission to a critical care unit. 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 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 epithelial Na⁺ channel (ENaC). The inability of the immature fetal lung to switch from fluid secretion to fluid absorption results, mainly because of immaturity in the expression of ENaC, which can be up-regulated by glucocorticoids. ^[1] Glucocorticoids induce lung Na⁺ reabsorption most likely through the fetal lung alveolar ENaC channel in late gestational age. ^[2]

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. ^{[3, 4]}

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. Although, full-term neonates may have lower lamellar body counts, suggesting diminished surfactant function and association with prolonged tachypnea of newborns. ^[5]

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.

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. ^[6]

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. ^[7] Important to note is that chest circumferences were the same. Milner et al noted that the infants born via cesarean delivery had higher volumes of interstitial and alveolar fluid compared with those born vaginally, even though the overall thoracic volumes were within the reference range.

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. ^{[8, 9]} Therefore, cesarian 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 1989-1992. ^[10] 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. ^[11] 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. ^[12] 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 nonasthmatics. ^[12]

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. ^{[13, 14]}  The risk of adverse respiratory outcomes in late preterm infants is particularly higher for those delivered after 35 weeks' gestatoin and whose mothers did not receive antenatal steroids. ^[15]

Gestational diabetes in itself does not appear to be a major contributor to respiratory distress syndrome in infants born late preterm. ^[16] ​ Independent factors that raise the risk of respiratory morbidity in these infants are prematurity and cesarean birth.

Male sex and macrosomia

Male sex and macrosomic infants born to diabetic mothers have been associated with increased risk of transient tachypnea of the newborn.

Other factors

Excessive maternal sedation, perinatal asphyxia, and elective cesarean delivery without preceding labor, low Apgar scores, and prolonged rupture of membranes are frequently associated with transient tachypnea of the newborn.

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. Of this 1%, approximately 33-50% have transient tachypnea of the newborn (TTN).

Race-, sex-, and age-related demographics

No racial predilection has been reported,  and male neonates are more affected than females.

Clinically, transient tachypnea of the newborn presents as respiratory distress in full-term or near-term infants.

Morbidit/mortality

Transient tachypnea of the newborn (TTN) is generally a self-resolving disorder with excellent prognosis. It frequently resolves over a 24-hour to 72-hour period.

However, this condition has been associated with subsequent respiratory morbidity, with a significantly increased risk of a wheezing disorder in childhood.

Complications

Some infants may develop hypoxia, respiratory fatigue, and acidosis. Occasionally, air leaks (eg, a small pneumothorax or pneumomediastinum) may be seen in infants who have increased work of breathing. Hence, any infant who does not follow the typical course of transient tachypnea of the newborn and develops any concerning symptoms must be re-evaluated.

Infants delivered by elective cesarean section prior to 39 weeks' gestation may develop pulmonary hypertension and may require extracorporeal membrane oxygenation (ECMO). ^[17]

Several reports suggest that transient tachypnea of the newborn is a risk factor for future wheezing syndromes in childhood and may not be as transient as previously thought. Although Liem et al hypothesize that genetic and environmental interactions synergistically predispose these children for future wheeze, prospective studies are required to better define this association. ^[18]

Inform parents that transient tachypnea of the newborn (TTN) is usually a self-limited disorder and is not life threatening.

New data link transient tachypnea of the newborn 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. ^[19] 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.