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Transient tachypnea of the newborn

Author:
Karen E Johnson, MD
Section Editor:
Joseph A Garcia-Prats, MD
Deputy Editor:
Melanie S Kim, MD

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Dec 2016. | This topic last updated: Apr 07,
2016.
INTRODUCTION Transient tachypnea of the newborn (TTN) is a parenchymal lung
disorder characterized by pulmonary edema resulting from delayed resorption and
clearance of fetal alveolar fluid [1]. TTN is a common cause of respiratory distress in
the immediate newborn period. In a review of 33,289 term deliveries (37 to 42 weeks),
the incidence of TTN was 5.7 per 1000 births [2]. Although thought to be a benign, selflimited condition, there are increasing data to suggest that TTN increases a newborn's
risk for developing a wheezing syndrome early in life [3].
PATHOPHYSIOLOGY The process of clearing fetal alveolar fluid begins before term
birth and continues through labor and after delivery. During late gestation, in response
to increased concentrations of catecholamines and other hormones, the mature lung
epithelium switches from actively secreting chloride and liquid into the air spaces to
actively reabsorbing sodium and liquid (figure 1) [4,5]. Increased oxygen tension at
birth enhances the capacity of the epithelium to transport sodium and increases gene
expression of the epithelial sodium channel [5]. Reduced gene expression of this
channel contributes to the inability of immature lungs to switch from fluid secretion to
absorption and can be upregulated by glucocorticoids [5].
Passive resorption of liquid also occurs after birth because of differences among the
oncotic pressure of air spaces, interstitium, and blood vessels. The majority of water
transport across the apical membrane is thought to occur through aquaporin 5 (AQP5)
water channels [6].
Delayed resorption of fetal lung fluid is thought to be the underlying cause of TTN. Fluid
fills the air spaces and moves into the interstitium, where it pools in perivascular tissues
and interlobar fissures until it is eventually cleared by the lymphatics or absorbed into
small blood vessels. The excess lung water in TTN results in decreased pulmonary
compliance. Tachypnea develops to compensate for the increased work of breathing
associated with reduced compliance. In addition, accumulation of fluid in the
peribronchiolar lymphatics and interstitium promotes partial collapse of the bronchioles
with subsequent air trapping. Continued perfusion of poorly ventilated alveoli leads to

hypoxemia, and alveolar edema reduces ventilation, sometimes resulting in

hypercapnia.
In one study, the expression of AQP5 was greater in patients with TTN than in those
with respiratory distress syndrome (RDS) or controls. This finding suggests that
upregulation of AQP5 increases reabsorption of postnatal lung fluid, which contributes
to the quick resolution of symptoms in infants with TTN [6].
Decreased surfactant function has also been proposed as contributing to the
pathophysiology of TTN. In one small study of term infants delivered via elective
cesarean delivery, patients with TTN compared with age-matched controls were more
likely to have lower surfactant function as determined by gastric aspirate measurement
of lamellar body count and stable microbubble test [7]. However, further studies are
needed to confirm these findings.
The role of nitric oxide (NO) in TTN has been the focus of studies as well. Asymmetric
dimethylarginine (ADMA) is an endogenous NO synthase inhibitor. Increased ADMA
concentration may reduce NO synthesis, leading to increased pulmonary vascular
resistance associated with fetal lung fluid retention resulting in prolonged duration of
tachypnea. In one small study, ADMA levels were elevated in newborns with TTN
compared with healthy newborns [8].
RISK FACTORS TTN develops in infants born prematurely or after cesarean
delivery without labor because mechanisms to reabsorb alveolar fluid have not been
initiated, as illustrated by the following studies:
In a review of 29,669 deliveries from 1992 to 1999 from a single center in the
United States, TTN occurred in more infants after elective cesarean than after
vaginal delivery (3.1 versus 1.1 percent) [9].
In a German study that analyzed data from perinatal regional registries of almost
240,000 term deliveries from 2001 to 2005, the incidence of TTN was 5.9 cases
per 1000 singleton births [10]. Elective cesarean section was the most significant
risk factor associated with TTN compared with data from the national German
perinatal registry (42 versus 9 percent). Other risk factors associated with TTN
included being small for gestational age (SGA; 16 versus 10 percent), being large
for gestational age (LGA; 14 versus 11 percent), and male gender (60 versus 51
percent).
In a multicenter Norwegian study, there was a twofold higher risk for pulmonary
disorders (ie, TTN and neonatal respiratory distress syndrome [RDS]) for infants
born after planned cesarean delivery compared with those born after planned
vaginal delivery (1.6 versus 0.8 percent) [11].
TTN occurs two to three times more often in infants of diabetic mothers (IDM) [12]
(see "Infant of a diabetic mother"). The mechanism may be related to decreased fluid
clearance in the diabetic fetal lung, although cesarean delivery, which is more
frequently performed in pregnancies of diabetic mothers, is a contributing factor [13].

Maternal asthma is a risk factor, although the mechanism is unknown. In one study,
infants of asthmatic mothers were more likely to have TTN than were controls (odds
ratio [OR] 1.8, 95% CI 1.4-2.4) [14]. Moreover, another study suggested that in male
infants, TTN may be a marker of deficient pulmonary function reflecting inherited
susceptibility to the development of asthma [15].
The administration of antenatal corticosteroid therapy appears to reduce the rate of
TTN in late preterm and term infants. However, it remains uncertain whether the benefit
of reducing TTN outweighs the potential adverse effects of corticosteroid therapy.
(See "Antenatal corticosteroid therapy for reduction of neonatal morbidity and mortality
from preterm delivery", section on 'After 34 weeks'.)
CLINICAL FEATURES The onset of TTN is usually at the time of birth and within
two hours after delivery. Tachypnea (respiratory rate greater than 60 breaths per
minute) is the most prominent feature. Infants with this condition typically have
cyanosis and increased work of breathing, manifested by nasal flaring, mild intercostal
and subcostal retractions, and expiratory grunting. The anterior-posterior diameter of
the chest may be increased.
Breath sounds in affected infants typically are clear, without rales or rhonchi. Infants
with mild to moderate TTN are symptomatic for 12 to 24 hours, but signs may persist
as long as 72 hours in severe cases. Infants rarely require a supplemental oxygen
concentration greater than 40 percent to achieve adequate oxygenation.
DIAGNOSIS TTN is a clinical diagnosis. Characteristic findings on chest radiograph
support the diagnosis. These include increased lung volumes with flat diaphragms, mild
cardiomegaly, and prominent vascular markings in a sunburst pattern originating at the
hilum. Fluid often is seen in the interlobar fissures, and pleural effusions may be
present. Alveolar edema may appear as fluffy densities.
It has been suggested that lung ultrasonography is an accurate and reliable tool for
diagnosing TTN [16]. However, more studies are needed to confirm these findings
before recommending ultrasound as a diagnostic imaging procedure.
Arterial blood gas measurements typically reveal mild to moderate hypoxemia and mild
hypercapnia, resulting in respiratory acidosis. Complete blood count and differential are
normal.
Differential diagnosis TTN is a benign disorder, and pathologic conditions must be
excluded. Because most of these disorders have overlapping clinical and radiological
features, studies have looked for biochemical markers, such as endothelin-1 [17,18] or
atrial natriuretic peptide [17], which may aid in the differential diagnosis.
Pneumonia or sepsis should be considered, especially in cases that persist
longer than 24 hours. (See "Neonatal pneumonia".)
TTN is unlikely in infants who require persistently high oxygen concentration
(greater than 60 percent) or mechanical ventilation.

Affected infants also should be evaluated clinically for cardiac disease, and
further studies should be undertaken if it is suspected.
TTN may complicate respiratory distress syndrome (RDS) in preterm infants.
However, infants with RDS usually have a characteristic chest radiograph and
more significant requirements for respiratory support.
MANAGEMENT Because TTN is a benign, self-limited condition, management is
supportive. Supplemental oxygen is provided by hood or nasal cannula to maintain
oxygen saturation above 90 percent. Infants with TTN rarely require more than 40
percent inspired oxygen concentration. However, if the required supplemental oxygen
concentration is greater or the infant has increased work of breathing as well as
tachypnea, we sometimes use nasal continuous positive airway pressure (nCPAP).
Supportive measures include maintaining a neutral thermal environment and providing
nutrition. Respiratory rates greater than 60 to 80 breaths per minute or increased work
of breathing preclude oral feeding; orogastric tube feeding or intravenous fluids should
be provided in such patients. If tachypnea persists longer than four to six hours or if the
initial complete blood count and differential are abnormal, we obtain a blood culture
and begin antibiotic coverage with ampicillin and gentamicin while awaiting the
results. Furosemide does not affect the clinical course [19,20].
Fluid restriction may be beneficial in the management of severe TTN. In a trial of 73
late preterm and term infants with TTN, post-hoc analysis demonstrated fluid restriction
compared with standard therapy reduced the duration of respiratory support for the
subset of patients (n = 26) who had severe TTN (defined as requiring respiratory
support for 48 hours) without any adverse effects [21]. For preterm infants, the
standard fluid management consisted of an intake of 80 mL/kg and restricted fluid
therapy of 60 mL/kg for the first day of life. For term infants, standard therapy was
60 mL/kg and restricted fluid therapy was 40 mL/kg for the first day of life. However,
further studies are needed to confirm whether or not fluid restriction is a safe and
effective intervention for TTN.
There is no evidence that diuretic therapy is beneficial in patients with TTN. This was
illustrated in a systematic review that identified two trials in which diuretic therapy had
no effect on duration of symptoms or length of hospitalization [22].
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Basics topic (see "Patient education: Transient tachypnea of the newborn (The
Basics)")
SUMMARY
Transient tachypnea of the newborn (TTN), a common cause of respiratory
distress in the immediate newborn period, is a parenchymal lung disorder
characterized by pulmonary edema resulting from delayed resorption and
clearance of fetal alveolar fluid. (See 'Pathophysiology' above.)
Risk factors for TTN include prematurity, birth by cesarean delivery, maternal
diabetes, and maternal asthma. (See 'Risk factors' above.)
The typical presentation of TTN is onset of tachypnea within two hours after
delivery. Infants may also be cyanotic and have increased work of breathing (ie,
nasal flaring, intercostals and subcostal retractions, and expiratory grunting).
Symptoms generally resolve after 12 to 24 hours, but may persist as long as 72
hours in severe cases. (See 'Clinical features' above.)
TTN is a benign disorder and other causes of neonatal respiratory distress must
be excluded. The differential diagnosis of TTN includes pneumonia, sepsis,
cardiac disease, and respiratory distress syndrome (RDS).
(See 'Diagnosis' above.)
Because TTN is a benign, self-limited condition, management is supportive. It
includes maintaining a neutral thermal environment, providing nutrition, and, if
needed, administering supplemental oxygen. (See 'Management' above.)
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Topic 5066 Version 17.0

GRAPHICS
Resorption of alveolar fluid at birth: Cellular mechanisms

Na enters the cell through the apical surface of both ATI and ATII cells via amiloride-sensitive
epithelial Na channels (ENaC), both highly selective channels (HSC) and nonselective
channels (NSC), and via cyclic nucleotide gated channels (seen only in ATI cells).
Electroneutrality is conserved with chloride movement through cystic fibrosis transmembrane
conductance regulator (CFTR) or through chloride channels (CLC) in ATI and ATII cells,
and/or paracellularly through tight junctions. The increase in cell Na stimulates Na-K-ATPase
activity on the basolateral aspect of the cell membrane, which drives out three Na ions in
exchange for two K ions, a process that can be blocked by the cardiac glycoside ouabain. If
the net ion movement is from the apical surface to the interstitium, an osmotic gradient
would be created, which would in turn direct water transport in the same direction, either
through aquaporins or by diffusion.
Reprinted with permission from: Jain L. Respiratory morbidity in late-preterm infants: prevention
is better than cure. Am J Perinatol 2008; 25:75. Copyright 2008 Thieme Medical Publishers,
Inc.
Graphic 57746 Version 8.0

Contributor Disclosures
Karen E Johnson, MDNothing to discloseJoseph A Garcia-Prats, MDNothing to
discloseMelanie S Kim, MDNothing to disclose

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