Transient tachypnea of the newborn

Author:
Karen E Johnson, MD
Section Editor:
Joseph A Garcia-Prats, MD
Deputy Editor:
Melanie S Kim, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Apr 2019. | This topic last updated: Mar 29, 2018.

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, self-limited 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 "Infants of women with diabetes"). 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]. In addition, maternal obesity without chronic disease is
associated with neonatal adverse outcomes including an increased risk of TTN
[14,15]. (See "Obesity in pregnancy: Complications and maternal
management", section on 'Offspring'.)
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) [16]. 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 [17].

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 respiratory morbidity and mortality from preterm delivery", section on
'34+0 or more weeks'.)

There are preliminary data that suggest a relationship between TTN and thyroid
levels [18]. However, further evidence is needed to confirm this association.

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 [19]. However, more studies are needed to confirm these
findings before recommending ultrasound as a diagnostic imaging procedure
[20,21].

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 [22,23] or atrial natriuretic peptide [22], 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 [24,25].

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 [26]. 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 [27].
Ongoing research for therapies beyond supportive care for TTN continues.
However, limited data on the use of inhaled corticosteroid therapy or beta
agonists are inconclusive, and as a result these measures are not
recommended for routine use [28,29].

INFORMATION FOR PATIENTS UpToDate offers two types of

patient education materials, "The Basics" and "Beyond the Basics." The Basics
patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the
Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are
best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)

●Basicstopic (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.)
Neonatal pneumonia
Author:
Michael E Speer, MD
Section Editors:
Joseph A Garcia-Prats, MD
Morven S Edwards, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Apr 2019. | This topic last updated: Apr 04, 2019.

INTRODUCTION Pneumonia is an important cause of neonatal

infection and accounts for significant morbidity and mortality, especially in

developing countries [1,2].

The epidemiology, microbiology, clinical manifestations, diagnosis, and

treatment of neonatal pneumonia are reviewed here. Neonatal sepsis and
specific pathogens are discussed separately. (See "Clinical features, evaluation,
and diagnosis of sepsis in term and late preterm infants" and "Management and
outcome of sepsis in term and late preterm infants".)

PATHOGENESIS Neonatal pneumonia can have early or late onset.

Bacteria are the principal pathogens for both types. (See 'Microbiology' below.)

Routes of acquisition — The route of acquisition varies in part with the time of
onset of the pneumonia.

Early-onset pneumonia — Early-onset pneumonia is variably defined as within

48 hours to within six days of birth. For the purpose of this topic review, we
define early-onset as within six days of birth.

Early-onset pneumonia is acquired from the mother by one of three routes:

●Intrauterineaspiration of infected amniotic fluid.

●Transplacental transmission of organisms from the mother to the fetus
through the placental circulation.
●Aspiration during or after birth of infected amniotic fluid. The neonate can
aspirate vaginal organisms, leading to respiratory colonization and, in some
cases, pneumonia. Vaginal colonization with such organisms as group B
streptococcus (GBS) does not necessarily result in overt maternal infection.

Late-onset pneumonia — Late-onset pneumonia, which can occur during

hospitalization or after discharge, generally arises from organisms colonizing
the hospitalized newborn or is nosocomially acquired from infected individuals
or contaminated equipment. Microorganisms can invade through injured
tracheal or bronchial mucosa or through the bloodstream.

Mechanism of injury in GBS pneumonia — In GBS pneumonia, the level of

beta-hemolysin expression appears to correlate directly with the ability of the
organism to injure lung epithelial cells [3,4]. Studies suggest the hemolysin acts
as a pore-forming cytolysin. The injury results in increased permeability that
contributes to the development of alveolar edema and hemorrhage. This
mechanism also may be partially responsible for bloodstream extension.
Because surfactant phospholipid inhibits beta-hemolysin-associated lung
epithelial cell injury, preterm infants who are deficient in surfactant may be more
severely affected [3,4].

PATHOLOGY The pathologic changes vary with the type of organism:

bacterial or viral. Bacterial pneumonia is characterized by inflammation of the

pleura, infiltration or destruction of bronchopulmonary tissue, and leukocyte and
fibrinous exudate within alveoli and the bronchi/bronchioles [5,6]. Bacteria often
are seen within the interstitial spaces, alveoli, and bronchi/bronchioles [5].

Viruses typically cause an interstitial pneumonia. The pneumonia induced by

rubella, for example, is characterized by infiltration of mononuclear cells and
lymphocytes. Extensive inflammation occasionally occurs with hyaline
membrane formation, followed by varying degrees of interstitial fibrosis and
scarring [7-9].

EPIDEMIOLOGY In resource-rich settings, the estimated incidence of

pneumonia is <1 percent among full-term infants and approximately 10 percent

in preterm infants [10,11]. By contrast, the incidence of neonatal pneumonia at
autopsy ranges from 20 to 32 percent of liveborn and from 15 to 38 percent of
stillborn infants [11].

Congenital pneumonia is a common cause of mortality among extremely low

birth weight (ELBW) infants (ie, BW <1000 g), accounting for nearly 30 percent
of deaths in one series [12]. Pneumonia caused by maternal enteric organisms
frequently accompanies chorioamnionitis and/or funisitis in these congenital
infections.

In resource-limited settings, pneumonia is major contributor to infant mortality.

The World Health Organization estimated that in 2015 pneumonia caused
>900,000 deaths worldwide in children under five years old, with the majority of
deaths occurring in infants <1 year old [13]. In one study conducted in a rural
area in central India, mortality secondary to pneumonia in the first month was
29 per 1000 live births; more than one-half of all pneumonia deaths in children
occurred in newborns [14]. These figures may underestimate the burden of
neonatal pneumonia in resource-limited settings because many newborns do
not receive medical care.
 RISK FACTORS Risk factors associated with early-onset pneumonia

include prolonged rupture of the fetal membranes (>18 hours), maternal

amnionitis, preterm delivery, fetal tachycardia, and maternal intrapartum fever
[15,16].

Infants who require assisted ventilation are at highest risk for late-onset
pneumonia. Data from adults, which are thought to be applicable to neonates,
suggest that the risk of nosocomial pneumonia is approximately four times
higher in intubated than in nonintubated patients [17]. Other risk factors include:

●Anomalies of the airway (eg, choanal atresia, tracheoesophageal fistula,

and cystic adenomatoid malformations)
●Severe underlying disease
●Prolonged hospitalization
●Neurologic impairment resulting in aspiration of gastrointestinal contents

Nosocomial infections occasionally are traced to poor handwashing or

overcrowding [18].

MICROBIOLOGY Bacterial, viral, spirochetal, protozoan, and fungal

pathogens can cause pneumonia.

Early-onset pneumonia — Bacterial pathogens are the most common cause

of early- and late-onset pneumonia, although the specific organisms may differ
(table 1).

Bacterial infections — Most early-onset pneumonia is caused by aerobic

bacteria, although anaerobes such as Bacteroides spp. occasionally are
recovered. Group B streptococcus (GBS) is the most common cause of early-
onset pneumonia in the United States and other resource-rich countries,
although gram negative organisms are emerging cause [19]. (See "Group B
Streptococcus: Virulence factors and pathogenic mechanisms" and "Group B
streptococcal infection in neonates and young infants", section on 'Pneumonia'.)

In one study from the United Kingdom of 35 infants with early-onset pneumonia,
GBS was responsible for 57 percent of the cases [20]. Different organisms may
predominate in other locations, especially developing countries [2,21-23]. In a
review of neonatal pneumonia in developing countries, pathogens responsible
for early-onset neonatal sepsis and pneumonia included Escherichia coli,
GBS, Klebsiella spp, Staphylococcus aureus, and Streptococcus
pneumoniae [2].

Other less common bacterial pathogens include Listeria monocytogenes

and Mycobacterium tuberculosis, both of which can be transmitted
transplacentally. Although transplacental infection by M. tuberculosis often
results in primary liver involvement, pneumonia may be the sole manifestation
or may accompany hepatic disease [24]. Tuberculosis (TB) occurs with greater
frequency in human immunodeficiency virus (HIV)-infected patients, and
congenital TB also has become more common [25].

Possible link of Ureaplasma urealyticum to chronic lung disease — One

bacterial pathogen, Ureaplasma urealyticum, has been linked potentially to the
development of acute and chronic lung disease [26-30]. This connection has
been shown in both small series and a meta-analysis [27].

●In one study of 47 infants weighing <1500 g, radiographic features of

pneumonia were more frequent within seven days in those colonized
with U. urealyticum than in noncolonized infants (53 versus 21 percent)
[26]. Evidence of "precocious" chronic lung disease by radiography also
was more common in patients with a positive culture for the organism (23
versus 2 percent). Infants with a positive U. urealyticum culture had a
relative risk of 11.0 (95% CI 1.6-75.5) for oxygen dependence at 36
postmenstrual weeks [26].
●In another report, tracheal aspirates were obtained prior to administration
of surfactant or antibiotics from 105 very low birth weight (VLBW) infants
who required mechanical ventilation before 12 hours of age [28]. Infants
positive for U. urealyticum were more likely to have chronic lung disease at
28 days, but not at 36 postmenstrual weeks [28].

The efficacy of antimicrobial therapy is uncertain. Two small trials

of erythromycin therapy in colonized infants failed to show an effect on the
development of chronic lung disease [29,30]. In addition, there are data to
suggest that some isolates of Ureaplasma are not susceptible to erythromycin
[31-33].

Viral infections — Herpes simplex virus (HSV) is the most common viral agent
to cause early-onset pneumonia, usually following acquisition from the mother
at the time of birth [34]. HSV pneumonia occurs in 33 to 54 percent of
disseminated HSV infections and usually is fatal in spite of treatment [16,34].
(See "Neonatal herpes simplex virus infection: Clinical features and diagnosis",
section on 'Disseminated disease'.)

Other viruses can cause pneumonia, usually via transplacental transmission

from a mother who acquires the infection late in pregnancy. Examples include
adenovirus, enteroviruses, and mumps [16,35,36]. Interstitial pneumonitis can
also occur in congenital rubella infection and congenital cytomegalovirus (CMV)
infection [37]. (See "Congenital cytomegalovirus infection: Clinical features and
diagnosis", section on 'Symptomatic neonate'and "Congenital rubella syndrome:
Clinical features and diagnosis", section on 'In neonates'.)

Fungal infections — Candida spp. and other fungal pathogens also are
responsible for neonatal pneumonia [38,39]. In one prospective study,
approximately 25 percent of VLBW infants were colonized by Candida in the
gastrointestinal and respiratory tracts, presumably during labor and delivery
[40]. Pneumonia occurs in approximately 70 percent of infants with systemic
candidiasis [41].
Other pathogens — Occasionally, early-onset pneumonia is seen in patients
with congenital toxoplasmosis and syphilis [42].

Late-onset pneumonia — Hospitalized infants often are colonized with

organisms that are different from normal flora and these can cause late-onset
pneumonia.

Bacterial infections — There is limited information on the bacterial etiology for

community-acquired, late-onset pneumonia [2]. There appears to be a
predominance of gram-positive bacteria including S. pyogenes, S. aureus,
and S. pneumoniae. Other bacterial pathogens have been implicated in late-
onset pneumonia, some of which have characteristic features:

●S. aureus and Klebsiella pneumoniae are notable for inducing extensive
tissue damage, abscess formation, and empyema [43].
●These and other pathogens (eg, Escherichia coli, Serratia
marcescens, Enterobacter cloacae, S. pneumoniae, and Pseudomonas
aeruginosa) may cause pneumatoceles [44-46].
●Citrobacter diversus, frequently associated with brain abscesses in
neonates, can also cause lung abscess [44].
●Bacillus cereus has been associated with necrotizing pneumonia in
preterm infants [47] and with pneumonia secondary to contaminated
ventilator circuits [48].
●Chlamydia trachomatis has a long incubation period and typically is
associated with pneumonia occurring between two and four weeks of age
[49]. A possible association between early lung disease and a positive
tracheal culture for C. trachomatis has been reported [50]. In developing
countries where untreated sexually transmitted disease is common, C.
trachomatis nasal carriage rate is between 15 and 20 percent and is a risk
factor for pneumonia [2,22,51].

Viral infections — Numerous viruses, including adenovirus, parainfluenza,

rhinovirus, enteroviruses, influenza, and respiratory syncytial virus (RSV), cause
pneumonia in the neonatal period [16,52,53]. Most infants initially are healthy,
but have ill family members. In a series of 40 newborns with viral pneumonia,
nine were born at less than 37 weeks gestation, and RSV accounted for 55
percent of the cases [52]. RSV is most prevalent during the winter months and
results in significant morbidity and mortality. Viral pathogens are also a common
cause of hospital-acquired respiratory infections in the neonatal intensive care
unit. (See "Nosocomial viral infections in the neonatal intensive care unit",
section on 'Respiratory viruses'.)

Fungal infections — Candida spp. occasionally cause late-onset pneumonia,

particularly in extremely low birth weight (ELBW) infants who have received
prolonged antibiotic therapy and have respiratory tract colonization [21,54-56].
Corticosteroid administration may increase the risk of systemic infection
from Candida spp. in preterm infants [57,58], potentially increasing the risk of
pneumonia.

A rare cause of pneumonia is aspergillosis, which frequently is fatal [59].

Aspergillus infection can occur in clusters, particularly during hospital
renovations [60].
 CLINICAL MANIFESTATIONS Early-onset pneumonia commonly

presents with respiratory distress beginning at or soon after birth. Infants may
have associated lethargy, apnea, tachycardia, and poor perfusion, sometimes
progressing to septic shock. Some infants develop pulmonary hypertension.
Other signs include temperature instability, metabolic acidosis, and abdominal
distension. None of these signs is specific for pneumonia, and respiratory
distress also can be caused by noninfectious causes (table 2).

Late-onset pneumonia is marked by changes in the overall condition of the

newborn and can include nonspecific signs of apnea, tachypnea, poor feeding,
abdominal distention, jaundice, emesis, respiratory distress, and circulatory
collapse. Ventilator-dependent infants may have increased oxygen and
ventilator requirements or purulent tracheal secretions.

DIAGNOSIS The diagnosis of neonatal pneumonia is based on a

combination of clinical, radiographic, and microbiologic findings. Because signs

of pneumonia are nonspecific, neonates with sudden onset of respiratory
distress or other signs of illness should be evaluated for pneumonia, including a
complete sepsis evaluations. The evaluation for neonatal sepsis is discussed in
greater detail separately. (See "Clinical features, evaluation, and diagnosis of
sepsis in term and late preterm infants", section on 'Evaluation and initial
management'.)

Cultures — Cultures of blood and cerebrospinal fluid should be obtained. In

infants who are intubated, Gram stain and culture of tracheal aspirates may
help identify the pathogen [61-64]. In patients with pleural effusions, if pleural
fluid is sampled for therapeutic reasons, it can be sent for Gram stain and
culture. If viral or other nonbacterial infection is suspected, specific studies
should be obtained including polymerase chain reaction (PCR) and viral
cultures.

Chest radiography — The chest radiograph can confirm the clinical diagnosis
of pneumonia. Bilateral alveolar densities with air bronchograms are
characteristic [65], but irregular patchy infiltrates or occasionally a normal
pattern also occur [66]. Pneumonia caused by group B streptococcus (GBS) or
other pathogens is difficult to distinguish from respiratory distress syndrome
(RDS) in preterm infants [67-69]. The presence of pleural effusions may be
helpful because they occur in up to 67 percent of patients with pneumonia, but
are rarely found in RDS. However, pleural effusions also can be seen in
patients with transient tachypnea of the newborn, congenital heart disease,
hydrops fetalis, and congenital lymphangiectasia [66].
 TREATMENT Successful treatment depends upon the pathogen, early

recognition of the infection, and early therapy prior to the development of

irreversible injury.

Depending on the severity of respiratory distress, initial management may

include oxygen supplementation and mechanical ventilation, in addition to
empirical antibiotic therapy. (See "Overview of neonatal respiratory distress:
Disorders of transition", section on 'Initial management'.)

Bacterial infection — The choice of empiric regimens is based upon whether

the infection is early or late onset.

Early-onset pneumonia — For early-onset pneumonia (ie, age ≤6 days),

empiric parenteral antibiotic treatment is started until culture results are
available. Once a specific organism is identified, therapy is modified according
to the susceptibility pattern.

For most neonates, we suggest initial empiric coverage

with ampicillin and gentamicin (dosing is based upon weight, renal function,
postnatal age, and postmenstrual age) [70]. Ampicillin is effective against group
B streptococcus (GBS), most other strains of streptococci, L. monocytogenes,
and some gram-negative bacteria. Ampicillin plus gentamicin also has
synergistic activity against many of these organisms [71]. In communities in
which a substantial proportion of gram-negative bacilli are resistant to
gentamicin, another aminoglycoside (eg, amikacin) should be substituted.

Third-generation cephalosporins, although active against many gram-negative

organisms, should not generally be used for suspected early-onset sepsis or
pneumonia. Gram-negative bacilli can rapidly develop resistance to
cephalosporins by either inducible or chromosomally mediated beta-lactamase
activity [71,72]. In addition, a large observational study found that the risk of
death from early-onset sepsis was increased in neonates who
received cefotaxime as initial empiric treatment compared with those who
received gentamicin [73].

Late-onset pneumonia — The choice of empiric therapy for late-onset

pneumonia depends upon the prevalence and sensitivity of bacteria in both the
community and the hospital. For most term infants >6 days old, we
suggest vancomycin plus an aminoglycoside for initial therapy because of the
high prevalence of staphylococcal species resistant to penicillins
(eg, Staphylococcus epidermidis and methicillin-resistant S. aureus [MRSA]).
Dosing of these medications is based upon the infant's weight, renal function,
postnatal age, and postmenstrual age. Because of the emergence of
vancomycin-resistant enterococci (VRE) and S. aureus with reduced
susceptibility to vancomycin, vancomycin should be continued only if there is no
alternative [74].

Isolation of extended spectrum beta-lactamase (ESBL)-producing organisms is

increasing. A carbapenem (eg, meropenem) is the drug of choice for treatment
of infections caused by these organisms [75]. Consultation with an infectious
disease specialist is advised. Meropenem is active against gram-negative
aerobic organisms with chromosomally mediated ampC beta-lactamases or
ESBL-producing strains, except carbapenemase-producing
strains. Amikacin has the most activity against ESBL-producing strains among
the aminoglycosides.

The duration of therapy is guided by the infecting pathogen and the response of
the patient. The usual treatment course for uncomplicated pneumonia is 10 to
14 days.

Viral infections — Specific agents for the treatment of viral pneumonia are
limited. For most viral infections acquired in the perinatal or postnatal period,
therapy remains supportive.

Herpes simplex virus — If herpes simplex virus (HSV) pneumonia is

suspected, intravenous acyclovir (60 mg/kg per day in 3 divided doses for 21
days) is recommended [76]. HSV pneumonia usually is fatal despite treatment
[16,34]. (See "Neonatal herpes simplex virus infection: Clinical features and
diagnosis", section on 'Disseminated disease' and "Neonatal herpes simplex
virus infection: Management and prevention", section on 'Acyclovir therapy'.)

Respiratory syncytial virus — Management of respiratory syncytial virus

(RSV) pneumonia is supportive. Ribavirin is the only available specific treatment
for RSV pneumonia; however, it is generally not recommended in infants and
young children because efficacy in this population has not clearly been proven.
RSV prophylaxis is suggested for high-risk infants (eg, those with chronic lung
disease and/or born at <29 weeks gestation). (See "Respiratory syncytial virus
infection: Treatment", section on 'Ribavirin' and "Respiratory syncytial virus
infection: Prevention", section on 'Indications for palivizumab'.)

OUTCOME The prognosis of neonatal pneumonia depends upon the

severity of the disease, the gestational age of the patient, underlying medical
conditions, and the infecting organism. Increased mortality is associated with
preterm birth, preexisting chronic lung disease, or immune deficiencies. Most
term neonates managed in resource-rich settings recover well without long-term
sequelae.

SOCIETY GUIDELINE LINKS Links to society and government-

sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Sepsis in
neonates" and "Society guideline links: Pediatric pneumonia".)

SUMMARY AND RECOMMENDATIONS

●Pneumonia is an important cause of neonatal infection and is a major
contributor to infant mortality worldwide. In resource-rich countries, the
estimated incidence of pneumonia in full-term infants is <1 percent and
increases to 10 percent in preterm infants. (See 'Introduction' above
and 'Epidemiology' above.)
●Neonatal pneumonia can be classified by the infant's age as follows:
•Early-onset pneumonia (≤3 days), which is generally acquired from
the mother during labor or delivery. (See 'Early-onset
pneumonia' above.)
•Late-onset pneumonia (>3 days of age) is typically due to nosocomial
organisms from previous colonization of the infant or transmission from
care providers or contaminated equipment. (See 'Late-onset
pneumonia' above.)
●There are a large number of viral, bacterial, and fungal pathogens that
cause neonatal pneumonia (table 1). Early-onset bacterial pneumonia is
most commonly caused by group B streptococcus.
(See 'Microbiology' above.)
●Risk factors associated with early-onset pneumonia include prolonged
rupture of the fetal membranes (>18 hours), maternal amnionitis, preterm
delivery, fetal tachycardia, and maternal intrapartum fever. Late-onset
disease is associated with mechanical ventilation, airway anomalies,
prolonged hospitalization, and aspiration of gastrointestinal contents due to
neurologic impairment. (See 'Risk factors' above.)
●Early-onset pneumonia commonly presents with respiratory distress
beginning at or soon after birth. Other clinical manifestations, also seen in
late-onset disease, are nonspecific and include temperature instability,
apnea, lethargy, tachycardia, poor perfusion, tachypnea, and poor feeding.
(See 'Clinical manifestations' above.)
●The diagnosis of neonatal pneumonia is based on a combination of
clinical, radiographic, and microbiologic findings. (See 'Diagnosis' above.)
●Infants with pneumonia should be treated with empirical antibiotic therapy
that provides broad coverage for the most likely pathogens. The choice of
antibiotic regimen depends on timing of disease onset (early- versus late-
onset) and local antibiotic resistance patterns. For most full-term neonates
with early-onset pneumonia, we suggest initial empiric coverage
with ampicillin and gentamicin (Grade 2C). For most full-term neonates
with late-onset pneumonia, we suggest initial empiric coverage
with vancomycin plus an aminoglycoside (eg, gentamicin) (Grade 2C).
When results of microbiologic tests are available, antibiotic therapy is
directed toward the specific pathogen. (See 'Treatment' above.)
●The prognosis of neonatal pneumonia depends upon the severity of the
disease, the gestational age of the patient, underlying medical conditions,
and the infecting organism. (See 'Outcome' above.)