4/8/23, 1:56 Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis - UpToDate

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Síndrome de dificultad respiratoria (SDR) en el recién

nacido: características clínicas y diagnóstico
AUTOR: Dr. Richard Martín
REDACTOR DE SECCIÓN: Joseph A García-Prats, MD
REDACTOR ADJUNTO: Carrie Armsby, MD, MPH

Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso de revisión por
pares .

Revisión de la literatura actual hasta: julio de 2023.

Última actualización de este tema: 16 de febrero de 2023.

INTRODUCCIÓN

El síndrome de dificultad respiratoria (SDR), anteriormente conocido como enfermedad de la

membrana hialina, es un problema común en los bebés prematuros. Este trastorno es causado
principalmente por la deficiencia de agente tensioactivo pulmonar en un pulmón inmaduro. El
SDR es una causa importante de morbilidad y mortalidad en los recién nacidos prematuros.

La fisiopatología y las características clínicas del SDR se presentarán aquí. El manejo del SDR y
otros trastornos de la transición perinatal se analizan por separado. (Consulte "Síndrome de
dificultad respiratoria (SDR) en bebés prematuros: Manejo" y "Resumen de la dificultad
respiratoria neonatal y los trastornos de transición" .)

DESARROLLO PULMONAR

El conocimiento del desarrollo pulmonar fetal normal es fundamental para comprender la

fisiopatología del SDR neonatal, que se debe a una actividad inadecuada del surfactante como
resultado de la inmadurez pulmonar.

El desarrollo alveolar fetal normal ocurre en las siguientes etapas [ 1 ]:

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● Período embrionario: aproximadamente a los 26 días de gestación, la etapa embrionaria

comienza con la primera aparición del pulmón fetal, que aparece como una protuberancia
del intestino anterior. La ramificación inicial del pulmón ocurre a los 33 días de gestación
formando los posibles bronquios principales, que comienzan a extenderse hacia el
mesénquima. La ramificación adicional forma los bronquios segmentarios a medida que
el pulmón ingresa a la siguiente etapa de desarrollo.

● Etapa pseudoglandular: en la etapa pseudoglandular (5 a 16 semanas de gestación), ocurren

de 15 a 20 generaciones de ramificación de las vías respiratorias que comienzan en los
bronquios segmentarios principales y terminan como bronquiolos terminales. Al final de
la etapa pseudoglandular, las vías respiratorias están rodeadas por un mesénquima
laxamente empaquetado, que incluye algunos vasos sanguíneos y está revestido por
células epiteliales ricas en glucógeno y morfológicamente indiferenciadas con una forma
de columna a cuboide. En general, la diferenciación epitelial es centrífuga, por lo que las
vías respiratorias proximales están cubiertas por las células más diferenciadas, con una
diferenciación progresivamente menor en los túbulos más distales.

● Etapa canalicular: durante la etapa canalicular (semanas 16 a 25 de gestación), se produce

la transición de un pulmón previable a un pulmón potencialmente viable a medida que se
forman los bronquiolos respiratorios y los conductos alveolares de la región de
intercambio de gases del pulmón. El mesénquima circundante se vuelve más vascular y se
condensa alrededor de las vías respiratorias. La proximidad vascular más cercana
finalmente da como resultado la fusión de las membranas basales capilares y epiteliales.
Después de las 20 semanas de gestación, las células epiteliales cuboideas comienzan a
diferenciarse en células alveolares de tipo II con formación de cuerpos lamelares
citoplasmáticos [ 2 ]. La presencia de cuerpos lamelares indica la producción de
surfactante, que se produce a partir de glucógeno y se almacena en los cuerpos
lamelares.

● Etapa sacular: al comienzo de la etapa sacular (aproximadamente 24 semanas de

gestación), existe potencial de viabilidad porque el intercambio de gases es posible debido
a la presencia de formas grandes y primitivas de los futuros alvéolos. En esta etapa, la
formación de alvéolos (es decir, la alveolarización) ocurre por el crecimiento de tabiques
que subdividen los sáculos terminales en alvéolos anatómicos, donde ocurre el
intercambio de aire. El número de alvéolos en cada pulmón aumenta de cero a las 32
semanas de gestación a entre 50 y 150 millones de alvéolos en recién nacidos a término y
300 millones en adultos. El crecimiento alveolar continúa durante al menos dos años
después del nacimiento a término.

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Surfactante pulmonar : la causa principal del SDR es la deficiencia de surfactante pulmonar,

que está regulado por el desarrollo. El pulmón fetal está lleno de líquido y no proporciona
ninguna función respiratoria hasta el nacimiento. En preparación para respirar aire, el
surfactante se expresa en el pulmón a partir de la semana 20 de gestación [ 3 ]. El surfactante
reduce la tensión superficial alveolar, lo que facilita la expansión alveolar y reduce la
probabilidad de atelectasia por colapso alveolar.

Debido a la regulación del desarrollo de la producción de surfactante, la causa más común de

deficiencia de surfactante es el parto prematuro. Además, las mutaciones en los genes que
codifican las proteínas del surfactante SP-B y SP-C [ 4,5 ] y el transportador A3 (ABCA3) del
casete de unión de trifosfato de adenosina (ATP) (ATP) [ 6-8 ] pueden causar deficiencia de
surfactante y /o disfunción e insuficiencia respiratoria hereditaria en recién nacidos a término.
(Consulte "Trastornos genéticos de la disfunción del surfactante", sección "Variantes de la
secuencia SFTPC" .)

El surfactante pulmonar es una mezcla compleja que se compone principalmente de lípidos (90
por ciento), principalmente fosfolípidos y aproximadamente 10 por ciento de proteínas.

● Lípido: aproximadamente el 70 por ciento de los lípidos en el surfactante son especies de

fosfatidilcolina. De esto, aproximadamente el 60 por ciento es palmitoilfosfatidilcolina
disaturada, el componente principal del surfactante que reduce la tensión superficial
alveolar [ 9 ].

● Proteína: se identificaron cuatro proteínas específicas de surfactante y sus funciones se

dilucidaron parcialmente [ 1,10-12 ]. Incluyen las proteínas tensioactivas hidrofóbicas SP-B
y SP-C, y las proteínas hidrofílicas SP-A y SP-D.

• SP-A, un miembro de la familia de proteínas de la colectina, es una proteína de defensa

del huésped innata y un regulador de la inflamación en el pulmón. Esta proteína facilita
la fagocitosis de patógenos y su eliminación del espacio aéreo por los macrófagos. No
se han identificado pacientes con deficiencia de SP-A. Los niveles de SP-A son bajos en
el surfactante de los pulmones prematuros y aumentan con la exposición a los
corticosteroides. Los ratones que carecen de SP-A tienen una función pulmonar y un
metabolismo del tensioactivo normales, lo que indica que la SP-A no es fundamental
para la regulación del metabolismo del tensioactivo. SP-A no está presente en los
tensioactivos actualmente disponibles utilizados para el tratamiento de RDS.

• SP-B facilita la absorción superficial de lípidos y, como resultado, contribuye a la

capacidad del surfactante para reducir la tensión superficial. Los animales con
anticuerpos contra SP-B desarrollan insuficiencia respiratoria. La deficiencia
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homocigota de SP-B es extremadamente rara y esencialmente letal en los bebés

humanos a término [ 4 ]. SP-B y SP-C son componentes que se encuentran en
preparaciones comerciales de tensioactivos.

• Los seres humanos con deficiencia de SP-C no tienen dificultad respiratoria al nacer,
pero desarrollan fibrosis pulmonar intersticial progresiva en la infancia y en la primera
infancia [ 5 ]. Los ratones deficientes en SP-C tienen una función pulmonar y de
surfactante normal al nacer. Sin embargo, los ratones desarrollan enfermedad
pulmonar intersticial progresiva y enfisema a medida que envejecen. En este modelo
animal, el SP-C mal procesado da como resultado una deficiencia de SP-C en los
espacios aéreos y lesiones en la célula de tipo II. SP-B y SP-C probablemente trabajen
de manera cooperativa para optimizar la adsorción rápida y la distribución de
fosfolípidos en una superficie y para facilitar la disminución de la tensión superficial y
la estabilidad alveolar en la compresión del área superficial con un volumen pulmonar
bajo.

• SP-D es una proteína hidrófila y, como SP-A, un miembro de la familia de proteínas de

la colectina. También funciona como una molécula de defensa innata del huésped al
unirse a los patógenos y facilitar su eliminación. La ausencia de SP-D da como
resultado un aumento de las reservas de lípidos del surfactante en los espacios aéreos
y enfisema, pero ningún déficit importante en la función del surfactante en ratones [
13 ]. Se ha demostrado que el tratamiento de corderos prematuros con proteína D
recombinante del surfactante inhibe la inflamación pulmonar, lo que reduce la
inactivación del surfactante y puede ser prometedor para futuras investigaciones en
humanos [ 14 ].

Síntesis, secreción y absorción : el surfactante se sintetiza dentro de las células alveolares

tipo II comenzando con la síntesis de fosfolípidos en el retículo endoplásmico, luego se procesa
a través del aparato de Golgi hacia los cuerpos lamelares. Los fosfolípidos se combinan con las
proteínas tensioactivas SP-B y SP-C para formar el complejo de lipoproteínas tensioactivas
dentro de los cuerpos lamelares. Los cuerpos lamelares se localizan en la superficie apical de la
célula tipo II y se liberan en los alvéolos por exocitosis.

A medida que los cuerpos lamelares se deshacen dentro de los alvéolos, el complejo
surfactante forma una matriz de lipoproteínas (que incluye proteínas SP-A, SP-B y SP-C y
fosfolípidos) llamada mielina tubular que contribuye a la película superficial dentro de los
alvéolos y las vías respiratorias y reduce la tensión superficial alveolar [ 1 ]. El surfactante
secretado se mueve desde los espacios aéreos de vuelta a las células de tipo II, donde se recicla
nuevamente dentro de la célula mediante un proceso de endocitosis en cuerpos
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multivesiculares y, posteriormente, en cuerpos lamelares. El reciclaje de tensioactivos

endógenos y exógenos contribuye de manera importante a la reserva de tensioactivos [ 15 ].

Prematuridad : en el bebé prematuro, tanto una disminución en la cantidad como en la

calidad del surfactante contribuye a la disminución de la actividad del surfactante, lo que
resulta en SDR.

Además de la baja producción de surfactante observada con la disminución de la edad

gestacional, el surfactante producido en los bebés prematuros en comparación con el
surfactante de los bebés nacidos a término tiene una actividad reducida debido a las
diferencias en la composición de lípidos y proteínas [16 ] :

● El surfactante de pulmones inmaduros en comparación con el surfactante de pulmones

maduros contiene cantidades mayores de fosfatidilinositol (10 frente a 2 por ciento de la
composición del surfactante) y cantidades más pequeñas de fosfatidilglicerol (menos de 1
frente a 10 por ciento). La forma más madura de tensioactivo con mayor contenido de
fosfatidilglicerol tiene mayor actividad superficial. El contenido de fosfatidilglicerol
comienza a aumentar en el líquido amniótico después de las 35 semanas de gestación y
se utiliza como marcador de la madurez pulmonar fetal.

Varias otras técnicas están disponibles para evaluar la maduración pulmonar fetal. Estos
incluyen la relación lecitina/esfingomielina (L/S) y el recuento de cuerpos lamelares. Como
se discutió anteriormente, la producción de surfactante se observa por primera vez
alrededor de las 20 semanas de gestación con la aparición de cuerpos lamelares dentro
de las células epiteliales de las vías respiratorias. Clínicamente, los recuentos de cuerpos
lamelares en el líquido amniótico también se pueden usar para medir la madurez
pulmonar fetal y la producción de surfactante. (Ver "Evaluación de la madurez pulmonar
fetal", sección sobre 'Fosfatidilglicerol' ).

● El contenido de proteínas del surfactante del pulmón prematuro es bajo en relación con la
cantidad de lípidos del surfactante. En general, las células de tipo II con cuerpos lamelares
aparecen en el pulmón humano después de 20 semanas con muy poca expresión de
ARNm de proteína surfactante hasta más tarde en la gestación. La expresión de las cuatro
proteínas surfactantes varía con la edad gestacional: SP-A aumenta después de las 32
semanas de gestación, SP-B aumenta después de las 34 semanas de gestación, el ARNm
de SP-C se expresa mucho en la punta de las vías respiratorias ramificadas durante el
desarrollo pulmonar temprano y la expresión El mRNA de SP-D es bajo hasta el final de la
gestación.

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The administration of antenatal glucocorticoids reduces the risk of RDS in preterm infants
because it improves neonatal lung function by enhancing maturational changes in lung
architecture and by inducing enzymes that stimulate phospholipid synthesis and release of
surfactant. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory
morbidity and mortality from preterm delivery", section on 'Mechanism of action' and
"Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality
from preterm delivery".)

PATHOPHYSIOLOGY

The primary abnormality in RDS is surfactant deficiency. In the premature lung, inadequate
surfactant activity results in high surface tension leading to instability of the lung at end-
expiration, low lung volume, and decreased compliance. These changes in lung function cause
hypoxemia due to a mismatch between ventilation and perfusion primarily due to collapse of
large portions of the lung (atelectasis), with additional contributions of ventilation/perfusion
mismatch from intrapulmonary and extrapulmonary right-to-left shunts.

Surfactant deficiency also leads to lung inflammation and respiratory epithelial injury, which
may result in pulmonary edema and increased airway resistance. These factors further
exacerbate lung injury and worsen lung function. At the same time, abnormal fluid absorption
results in inefficient clearing of liquid in the injured lung, leading to edema lung that also
impedes gas exchange.

Surfactant deficiency — In preterm infants, surfactant deficiency is the primary cause of RDS
because the loss of surfactant leads to an increase in the amount of pressure needed to open
alveoli, and alveolar instability at low volume resulting in alveolar collapse and diffuse
atelectasis. (See 'Prematurity' above.)

The relationship of the inflating pressure, surface tension, and radius of curvature is illustrated
by the model of a distal alveolus as a sphere connected to a distal airway described by LaPlace's
law. According to LaPlace's law, the pressure (P) necessary to keep the sphere open is
proportional to the surface tension (T) and inversely proportional to the radius (R) of the sphere,
as shown by the formula:

P = 2T/R

If the surface tension is high and the alveolar volume is small (ie, the radius is low), as occurs at
end-expiration, the pressure necessary to keep the alveolus open is high. If this increased

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pressure cannot be generated, the alveolus collapses. Diffuse atelectasis occurs when alveolar
collapse occurs throughout the lung, which leads to hypoxemia. Pulmonary surfactant reduces
the surface tension, even at low volumes, leading to a decrease in the required pressure, thus
maintaining alveolar volume and stability ( figure 1).

Inflammation and lung injury — The role of inflammation in the pathogenesis of RDS is
suggested by animal experiments in which surfactant deficiency was associated with the rapid
accumulation of neutrophils in the lung and evidence of pulmonary edema [17]. In this model,
depletion of neutrophils prevented pulmonary edema. In addition, as noted above, surfactant
deficiency causes atelectasis that may lead to injury of the respiratory epithelium and the
alveolar capillary endothelium, which can trigger a cytokine-mediated inflammatory response.
Further injury may be caused by positive pressure ventilatory support or excessive oxidant
exposure [18-23]. The inflammation and lung injury may, in turn, lead to accumulation of
protein-rich pulmonary fluid that can deactivate any surfactant that is present, thereby further
exacerbating the underlying surfactant deficiency [24].

Pulmonary edema — In infants with RDS, pulmonary edema often occurs because of the
following contributory factors:

● Inflammation and lung injury. (See 'Inflammation and lung injury' above.)

● Reduced pulmonary fluid absorption − In the fetus, lung fluid is actively transported into
the potential airspaces in a process mediated by chloride channels. In preparation for
birth and air-breathing, the lung shifts from a secretory to an absorptive mode. Fluid
absorption is mediated by sodium channels expressed on epithelial cells (ENaC). However,
ENaC expression increases with gestational age in parallel with the surge in surfactant
production. In preterm infants, an inadequate number of ENaC may result in fluid
retention, similar to what is seen in infants with transient tachypnea of the newborn
[25,26].

● Low urine output − Infants with RDS typically have low urine output contributing to fluid
retention in the first few days, which may exacerbate pulmonary edema. Some infants
have hyponatremia due to increased free water. Infants recovering from RDS typically
have a spontaneous diuresis on the second to fourth day, followed by improved
pulmonary function.

Surfactant inactivation — In addition to decreased surfactant production and synthesis of a

less active surfactant, surfactant inactivation further reduces the effective surfactant pool size.
Factors that contribute to surfactant inactivation include:

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● Meconium and blood in the alveoli can inactivate surfactant activity, which is more
typically an issue in term infants with meconium aspiration than in preterm infants with
surfactant deficiency.

● Proteinaceous edema and inflammatory products increase the conversion rate of

surfactant into its inactive vesicular form. This conversion can be accelerated by oxidant
and mechanical stress associated with mechanical ventilation, especially if high tidal
volumes and lack of positive end-expiratory pressure (PEEP) are used [21,27].

Pulmonary function and gas exchange — The major negative effects of surfactant deficiency
on pulmonary function are low compliance and low lung volume (functional residual capacity),
and are primarily due to atelectasis, although both pulmonary edema and inflammation may be
contributing factors. Total lung resistance is slightly increased, probably as a result of airway
compression by interstitial edema and damage to the airways by the increased pressure
needed to expand the poorly compliant alveoli [28-31].

Exogenous surfactant therapy prevents or corrects these pulmonary functional abnormalities

(ie, low lung compliance and volume, and increased lung resistance). (See "Respiratory distress
syndrome (RDS) in preterm infants: Management", section on 'Surfactant therapy'.)

The hypoxemia that occurs in RDS is due primarily to mismatch of ventilation and perfusion
with intrapulmonary right-to-left shunting of blood past substantial regions of the lung that are
poorly ventilated. Extrapulmonary shunting also occurs typically across the foramen ovale and
patent ductus arteriosus.

The proportion of hypoxemia due to shunting versus poor alveolar ventilation depends upon
the extent of hypoxic pulmonary vasoconstriction and the relative size of the underventilated
region. Although minute ventilation may be increased, alveolar ventilation is decreased as most
of the lung is collapsed and poorly ventilated. Poor ventilation is reflected in elevated values of
arterial partial pressure of carbon dioxide (PaCO2), and a resultant respiratory acidosis.
Metabolic acidosis also may be present due to lactic acid production from anaerobic
metabolism, in response to hypoxemia and compromised tissue perfusion.

INCIDENCE

The incidence of RDS increases with decreasing gestational age (GA). The risk is highest in
extremely preterm infants, as illustrated by a study from the National Institute of Child Health
and Human Development Neonatal Research Network that found a 93 percent incidence of RDS

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in a cohort of 9575 extremely preterm infants (GA 28 weeks or below) born between 2003 and
2007 [32].

Although the incidence is lower, RDS still occurs in a significant number of late preterm infants
(GA between 34 weeks and 36 weeks and 6 days). In a report from the Safe Labor Consortium of
233,844 deliveries from 2002 and 2008, RDS was diagnosed in 10.5, 6, 2.8, 1, and 0.3 percent for
infants born at 34, 35, 36, 37, and ≥38 weeks gestation, respectively [33]. In late preterm and
term infants, male sex is associated with an increased risk of RDS (adjusted odds ratio [AOR] 1.7,
95% CI 1.45-1.93), and being White is also associated with increased risk, as opposed to being of
Asian (AOR 0.57, 95% CI 0.47-0.7), Black (AOR 0.66, 95% CI 0.5-0.87), or Hispanic race/ethnicity
(AOR 0.76, 95% CI 0.64-0.9) [34].

CLINICAL MANIFESTATIONS

The clinical manifestations of RDS result primarily from abnormal pulmonary function and
hypoxemia. Because RDS is primarily a developmental disorder of deficient surfactant
production, it presents within the first minutes or hours after birth. If untreated, RDS
progressively worsens over the first 48 hours of life. In some cases, infants may not appear ill
immediately after delivery, but develop respiratory distress and cyanosis within the first few
hours of age. These infants may have a borderline amount of surfactant that is consumed or
becomes inactivated.

The affected infant is almost always preterm and exhibits signs of respiratory distress that
include:

● Tachypnea.

● Nasal flaring, which reflects the use of accessory respiratory muscles and lowers total
respiratory system resistance.

● Expiratory grunting, which results from exhalation through a partially closed glottis and
slows the decrease in end-expiratory lung volume.

● Intercostal, subxiphoid, and subcostal retractions, which occur because the highly
compliant rib cage is drawn in during inspiration by the high intrathoracic pressures
required to expand the poorly compliant lungs.

● Cyanosis due to right-to-left intra- and extra-pulmonary shunting. (See 'Pulmonary

function and gas exchange' above.)

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On physical examination, auscultated breath sounds are decreased, and infants may be pale
with diminished peripheral pulses. The urine output often is low in the first 24 to 48 hours and
peripheral edema is common.

Clinical course — Prior to surfactant use, uncomplicated RDS typically progressed for 48 to 72
hours. This was associated with an improvement in respiratory function as endogenous
surfactant production increased. RDS typically resolves by one week of age. A marked diuresis
typically preceded the improvement in lung function. The natural history of RDS is greatly
modified by treatment with exogenous surfactant, which dramatically improves pulmonary
function, leading to the resolution of symptoms, and shortens the clinical course. In addition,
the use of continuous positive airway pressure (CPAP) has also improved the clinical course of
RDS, even in infants who do not receive surfactant therapy. (See "Respiratory distress syndrome
(RDS) in preterm infants: Management", section on 'Surfactant therapy' and "Respiratory
distress syndrome (RDS) in preterm infants: Management", section on 'Nasal continuous
positive airway pressure (nCPAP)'.)

Laboratory findings — Chest radiography is generally obtained for all neonates with
respiratory distress. The radiographic features of neonatal RDS (low lung volume and the classic
diffuse reticulogranular ground glass appearance with air bronchograms) in a preterm infant
with respiratory distress fulfill the clinical diagnosis criteria for RDS ( image 1). (See
'Diagnosis' below.)

Other laboratory findings associated with, but not diagnostic for, RDS include:

● Arterial blood gas measurements typically show hypoxemia that responds to

administration of supplemental oxygen. The partial pressure of carbon dioxide (PCO2)
initially is normal or slightly elevated, but usually increases as the disease worsens.

● As the disease progresses, infants may develop hyponatremia. This results from water
retention, and usually improves with fluid restriction. Attentive fluid management
prevents hyponatremia, and as a result, this finding is less commonly observed.

Chest imaging

Chest radiography — Radiographic features of RDS include:

● Low lung volumes

● Diffuse reticulogranular ground glass appearance with air bronchograms ( image 1)
● Pulmonary edema may contribute to the diffuse appearance

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● Pneumothorax and air leaks are uncommon findings in the initial chest radiography, and
are more frequently observed when lung compliance improves (see "Pulmonary air leak in
the newborn")

This radiographic pattern results from alveolar atelectasis contrasting with aerated airways.

Chest ultrasound — Neonatal chest ultrasonography is increasingly used in neonatology

practice to evaluate lung disease [35-38]. The characteristic ultrasound findings of RDS include
[37,39,40]:

● Lung consolidation with air bronchograms – Consolidated areas show an uneven

hypoechoic quality, and the boundary with surrounding lung tissue is clear and easy to
distinguish. Air bronchograms may appear as dense, speckled, or snowflake-like shapes.
There is usually bilateral involvement and posterior lung regions are commonly involved.
The amount of consolidation correlates with disease severity. In mild RDS, consolidations
may be limited to the subpleural lung parenchyma. Severe RDS generally has diffuse
involvement ("white lung"). The presence of lung consolidations is the key feature that
distinguishes the ultrasound appearance of RDS from that of transient tachypnea of the
newborn (TTN).

● Pleural line abnormalities – The pleural line has an abnormal appearance and the A-lines
disappear.

● Interstitial involvement – Nonconsolidated regions of the lungs may show signs of

interstitial involvement (eg, comet tail B lines and alveolar interstitial syndrome pattern).

● Pleural effusions – Unilateral or bilateral pleural effusions are seen in 15 to 20 percent of

cases [40].

These findings can be used to establish the diagnosis of RDS and to grade the severity [41,42].

DIAGNOSIS

The diagnosis of RDS is based on a clinical picture of a preterm infant with the onset of
progressive respiratory failure shortly after birth (manifested by an increase in the work of
breathing and an increase in the oxygen requirement), in conjunction with a characteristic chest
imaging findings (eg, diffuse reticulogranular ground glass appearance with air bronchograms)
( image 1). (See 'Clinical manifestations' above and "Pulmonary air leak in the newborn".)

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DIFFERENTIAL DIAGNOSIS

The differential diagnosis for RDS includes other causes of respiratory distress, which are
distinguished from RDS by their clinical features, radiographic features, and course. The initial
evaluation and management of neonates with respiratory distress are discussed separately.
(See "Overview of neonatal respiratory distress and disorders of transition".)

● Transient tachypnea of the newborn (TTN) – TTN is generally seen in more mature infants
(ie, term or late preterm infants) compared with RDS. Patients with TTN have milder
respiratory distress and improve more quickly than those with RDS. Only extremely severe
cases of TTN, which are rare, require mechanical ventilation. (See "Transient tachypnea of
the newborn".)

● Bacterial pneumonia – It is often difficult to differentiate between infants with RDS and
those with bacterial pneumonia because of overlap of both clinical and radiographic
findings. As a result, blood cultures and, possibly, tracheal cultures should be obtained in
all preterm infants who present with respiratory distress. Empirical antibiotics are given to
infants at risk for infection pending culture results and clinical course. (See "Neonatal
pneumonia".)

● Air leak – Air leak (eg, pneumothorax) may be a complication of RDS, an isolated problem,
or associated with another underlying disorder. It is detected by chest radiography. (See
"Pulmonary air leak in the newborn".)

● Cyanotic congenital heart disease – Most patients with cyanotic congenital heart disease
(CCHD) have milder respiratory distress than that seen in patients with RDS. In addition,
CCHD is usually differentiated from RDS by the absence of the characteristic diffuse
reticulogranular ground glass appearance with air bronchograms on chest radiograph. If
lung function and the chest radiograph do not improve with respiratory support and
surfactant administration, an echocardiogram should be performed to rule out structural
heart disease or persistent pulmonary hypertension of the newborn (PPHN) in infants with
severe arterial hypoxemia. (See "Cardiac causes of cyanosis in the newborn".)

● Interstitial (diffuse) lung disease – A number of interstitial and diffuse lung diseases may
present in the neonatal period, including genetic disorders of surfactant dysfunction, lung
growth abnormalities, and pulmonary interstitial glycogenosis. (See "Classification of
diffuse lung disease (interstitial lung disease) in infants and children".)

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● Non-pulmonary systemic disorders, such as hypothermia, hypoglycemia, anemia,

polycythemia, or metabolic acidosis, may present with respiratory distress. Differentiation
from RDS is based on the history, physical findings and appropriate laboratory evaluation.

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.)

● Basics topics (see "Patient education: When a baby is born premature (The Basics)" and
"Patient education: Transient tachypnea of the newborn (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Definition and pathophysiology – Respiratory distress syndrome (RDS), formerly also

known as hyaline membrane disease, is caused primarily by deficiency of pulmonary
surfactant in an immature lung. Other contributing factors to lung injury include
inflammation and pulmonary edema. (See 'Pulmonary surfactant' above and
'Pathophysiology' above.)

● Surfactant deficiency – Surfactant deficiency causes alveolar collapse, which leads to low
lung compliance and volume. The resulting ventilation and perfusion mismatch causes
hypoxemia. (See 'Pulmonary function and gas exchange' above.)

● Incidence – The incidence of RDS increases with decreasing gestational age (GA).
Extremely preterm infants (GA 28 weeks or below) are at the greatest risk for RDS, with an
incidence of over 90 percent. (See 'Incidence' above.)

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● Clinical manifestations – The clinical manifestations of RDS are primarily due to

abnormal pulmonary function and hypoxemia in a preterm infant. RDS presents within the
first minutes or hours of birth with signs of respiratory distress, such as tachypnea, nasal
flaring, expiratory grunting, cyanosis, and intercostal, subcostal, and subxiphoid
retractions. Additional findings may include decreased ausculatory breath sounds, pallor,
and diminished perfusion. (See 'Clinical manifestations' above.)

● Clinical course – RDS typically progresses over the first 48 to 72 hours of life with
increased respiratory distress and begins to resolve after 72 hours. Subsequent
improvement is coincident with increased production of endogenous surfactant, with
resolution of symptoms by one week of age. The use of antenatal steroids, exogenous
surfactant, and/or continuous positive airway pressure dramatically improves pulmonary
function and shortens the clinical course. (See 'Clinical course' above.)

● Diagnosis – The diagnosis of RDS is based on clinical findings of a preterm infant with
onset of progressive respiratory failure shortly after birth and a characteristic chest
imaging. Typical findings on chest radiograph include low lung volume and a diffuse
reticulogranular ground glass appearance with air bronchograms ( image 1). (See
'Diagnosis' above.)

● Differential diagnosis – The differential diagnosis of RDS includes other causes of

respiratory distress in the newborn including transient tachypnea of the newborn (TTN),
bacterial pneumonia, air leak, cyanotic congenital heart disease (CCHD), interstitial
(diffuse) lung disease, and non-pulmonary systemic disorders. These disorders are
distinguished from RDS based on differences in clinical presentation, chest radiograph
findings, and clinical course. (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Stephen E Welty, MD, and Firas Saker, MD, FAAP,
who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Terms of Use.

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Topic 5055 Version 34.0

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GRAPHICS

Efecto del surfactante sobre la presión-volumen

pulmonar en conejos prematuros

Pressure-volume relationships for the inflation and deflation of

surfactant-deficient and surfactant-treated preterm rabbit lungs.
The control lungs are from 27-day preterm rabbits. Rabbits with
surfactant deficiency have high opening pressure, low maximal
volume at a distending pressure of 35 cm H2O, and the lack of
deflation stability at low pressures on deflation (orange squares). In
contrast, treatment of 27-day preterm rabbits with a natural
surfactant alters the pressure-volume relationships with lower
opening pressure, improved maximal volume at a distending
pressure of 35 cm H2O, and deflation stability at low deflating
pressures (green circles).

Reproducido de: Jobe AH. Desarrollo y maduración pulmonar. En: Fanaroff &
Martin's Neonatal-Perinatal Medicine - Diseases of the Fetus and Infant, 9th ed,
Martin RJ, Fanaroff AA, Walsh MC (Eds), Elsevier, St. Louis 2011. Ilustración utilizada
con autorización de Elsevier Inc. Todos los derechos reservado.

Gráfico 70666 Versión 3.0

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Radiografía de tórax del síndrome de dificultad

respiratoria neonatal

Dos radiografías que demuestran síndrome de dificultad respiratoria

neonatal grave (A) y moderado (B). Ambos muestran los volúmenes
pulmonares bajos característicos y la apariencia de vidrio deslustrado
reticulogranular difuso con broncogramas aéreos.

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Contributor Disclosures
Richard Martin, MD No hay relación(es) financiera(s) relevante(s) con compañías no elegibles para
revelar. Joseph A Garcia-Prats, MD No hay relación(es) financiera(s) relevante(s) con compañías no
elegibles para revelar. Carrie Armsby, MD, MPH No hay relación(es) financiera(s) relevante(s) con
compañías no elegibles para revelar.

El grupo editorial revisa las divulgaciones de los contribuyentes en busca de conflictos de intereses.
Cuando se encuentran, estos se abordan mediante la investigación a través de un proceso de revisión de
múltiples niveles y mediante los requisitos para que se proporcionen referencias para respaldar el
contenido. Todos los autores deben tener referencias adecuadas de contenido y deben cumplir con los
estándares de evidencia de UpToDate.

Política de conflicto de intereses

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