Article

pulmonology

Surfactant for Respiratory Distress Syndrome

Alan Jobe, MD, PhD*

Author Disclosure
Dr Jobe has disclosed
he is a consultant for
Fisher & Paykel
Healthcare, Chiesi

Educational Gaps
1. There is a lack of recognition of the limitations and confounders for the diagnosis of
respiratory distress syndrome (RDS).
2. Some practitioners lack experience with using continuous positive airway pressure
(CPAP) in the delivery room to transition infants to spontaneous breathing.
3. There may be a lack of confidence to treat infants with surfactant other than by
intubation.

Farmaceutici, AbbVie
Inc., and Sobi (Swedish

Abstract

Orphan Biovitrum AB).

Surfactant treatment is standard of care for infants who have respiratory distress syndrome (RDS). However, many practical questions remain about what RDS is, and who
should be treated and when. This review will attempt to answer these questions on the
basis of new clinical trials and a perspective on the goals of treatment. Clinical data now
support an initial use of continuous positive airway pressure to stabilize most infants
before treatment, but the optimal way to treat an infant is under intense investigation.
The best treatment option for an infant ultimately depends on gestational age, clinical
status, and the experience of the clinician. The differences in surfactants are minor
given the low rates of complications with any surfactant treatment. The clinical management of RDS is the greatest success story in neonatology.

This commentary does

contain a discussion of
an unapproved/
investigative use of
a commercial product/
device.

Objectives

After completing this article, readers should be able to:

1. Recognize the limitations of the clinical diagnosis of respiratory distress syndrome

(RDS);
2. Decide how to best initially support preterm infants in the delivery room;
3. Assess an infant for the need for surfactant therapy; and
4. Anticipate the development of new approaches for surfactant treatments.

Introduction

Abbreviations
BPD:
CPAP:
INSURE:
RDS:

Although surfactant for the treatment of respiratory distress syndrome (RDS) has been
widely available since 1990, the population of infants who have RDS has changed over
the last 24 years. Most infants now have been exposed to antenatal corticosteroids and
many are smaller and more immature. (1) Neonatologists also have changed their management of infants who have RDS since the trials to validate surfactant treatments. Recent trials
have asked the following questions: Who should be treated? When should an infant be treated? How should the surfactant be given? Which surfactant should be used? I will answer
these questions from the perspective of the clinical trials,
clinical practice, and my perspective on information about
how surfactant works for the treatment of RDS. (2)

bronchopulmonary dysplasia
continuous positive airway pressure
intubate, surfactant, and extubate
respiratory distress syndrome

Who Should Be Treated With Surfactant?

Surfactants were developed specically to replace surfactant
deciency, which is the initiating abnormality resulting in
progressive respiratory failure in preterm infants. (2) As

*Neonatology/Pulmonary Biology, Cincinnati Childrens Hospital, University of Cincinnati, Cincinnati, OH.

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pulmonology

a general guideline, any preterm infant who has signicant respiratory failure thought to be RDS should receive
surfactant. The two key words are signicant and
RDS. The clinical denitions of RDS are problematic
for both the individual infant and for population studies.
(3) Traditionally, RDS was diagnosed for preterm infants
who have clinical ndings of retractions, grunting, and
aring who needed supplemental oxygen and had chest
radiographic ndings of diffuse haziness and air bronchograms. More recently, the diagnosis for epidemiologic
purposes has been simplied to be simply oxygen use
for 6 hours for the rst 24 hours after birth, with or
without ventilatory support and without the need for radiologic ndings. (4) With this permissive diagnosis,
approximately 95% of infants younger than 28 weeks
gestational age will have RDS. Surfactant treatments at
birth further complicate any denition of RDS. The
change in management for low birthweight infants to allow initial respiratory adaptation without intubation in
the delivery room has uncovered the previously known
fact that many very preterm infants initially do not have
signicant RDS. Earlier Scandinavian experiences and the
transitioning of infants with continuous positive airway
pressure (CPAP) in the delivery room demonstrate that
many of these infants do not have surfactant deciency
(Table 1). (5)(6)(7)(8) An extreme example of the ability
to manage low birthweight infants was recently reported
from South Africa. In an neonatal intensive care unit
(NICU) without the resources to ventilate infants less
than 1 kg, 69% of 309 infants were managed with nasal
CPAP alone, and 31% received surfactant followed by
CPAP with 75% surviving to discharge (Fig 1). (9)
These experiences demonstrate that many very low
birthweight infants do not have RDS of sufcient severity
to receive surfactant treatment. As the normal fetus
would be expected to have RDS if delivered before
approximately 35 weeks gestational age, (10) the clinician should ask the question why a very preterm infant

surfactant for RDS

without RDS does not have RDS. The simple answer is

the miraculous potential of the human fetal lung for early
gestational lung maturation as early as 23 to 24 weeks.
(11) Although these very preterm saccular lungs are far
from anatomically mature, they can have sufcient surfactant and enough gas exchange surface to support adequate
ventilation. Two clinically relevant mediators of this early
maturation are antenatal corticosteroid treatments and
chronic, often asymptomatic chorioamnionitis (Table 2).
Many infants have both these exposures. (12) It is safe
to assume any pregnancy delivered before 30 weeks is
stressed and abnormal, but much remains to be learned
about this remarkable early lung maturation (that prominently includes increased amounts of surfactant).
The ip side of the question about why the infant does
not have RDS is to ask if the infant who has respiratory
failure really has RDS (Table 2). As noted, very preterm
infants are all abnormal in that delivery at early gestational ages are not normal. An increased percent of these
infants are growth restricted, which causes abnormal lung
development in animal models and substantially increases
the risks of bronchopulmonary dysplasia (BPD). (13) Despite fetal growth restriction (and presumed severe stress)
the incidence of RDS is not decreased. These infants may
have variable degrees of pulmonary hypoplasia or other
lung structural abnormalities and not simply RDS. Similarly, pulmonary hypoplasia of variable severity can result
from decreased volumes of amniotic uid and present as
RDS, often with pulmonary hypertension.
The greatest confounder to a pure diagnosis of RDS
is chorioamnionitis. Although often clinically silent, more
than 50% of infants delivered before 30 weeks gestational
age will have been exposed to chorioamnionitis. (14) In
animal models, intra-amniotic pro-inammatory mediators cause lung inammation. (15) That inammation
can induce lung maturation and decrease RDS, but the
inammation also can be a diffuse pneumonia that can
present as RDS. Surprisingly, a pure pneumonia syndrome

Incidence of Respiratory Distress Syndrome in Very Low

Birthweight Infants

Table 1.

Study

Infants Reported

% Treated With Surfactant

Ref. No.

Danish Experience
COIN Trial
NICHDSupport Trial
Vermont-Oxford CPAP Trial

27 2 weeks
950 g average
2427 weeks
2629 weeks

30%
38% (CPAP arm)
67% (CPAP arm)
45% (CPAP arm)

5
6
7
8

CPAPcontinuous positive airway pressure; COINcontinuous positive airway pressure or intubation at birth; NICHDNational Institute of Child Health
and Human Development.

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pulmonology

surfactant for RDS

transient tachypnea of the newborn

includes low surfactant levels. (17)
Although essentially unstudied in
preterm infants, the delayed clearance of fetal lung uid from preterm
monkey lungs contributes to their
respiratory failure. (18) My interpretation of RDS in preterm infants
is as follows: the surfactant pool
sizes will be small, even for infants
who may not have RDS. The preterm sheep with approximately 5
mg/kg surfactant in the airspaces
(an amount comparable with the
healthy adult human) has minimal
respiratory distress on CPAP. (19)
Lung inammation, structural abnormalities, or excessive lung uid
Figure 1. Outcomes of infants treated with continuous positive airway pressure (CPAP). A
will compromise the function of
clinical experience with infants of birthweight 500 to1,000 g and 25 weeks gestational
age in a low resource academic neonatal intensive care unit (NICU) in South Africa that a small amount of surfactant, and
did not support infants with mechanical ventilation. The majority of the infants were poor respiratory effort will promote
managed with CPAP alone, and some infants were intubated and given surfactant and atelectasis. Any mechanical ventilathen extubated back to CPAP (intubate, surfactant, and extubate [INSURE]). Data from tion may be injurious and may further damage surfactant function.
Kirsten et al. (9)
BPD[bronchopulmonary dysplasia; GA[gestational age; NCPAP[nasal CPAP.
(20) The infant with marginal surfactant amounts might escape
RDS
if
transitioned
with
CPAP. In contrast, the same inis seldom diagnosed soon after very preterm birth. (4) Infant
may
end
up
with
a
preterm
version of adult RDS if
fants exposed to chorioamnionitis who have a fetal inamthe
lung
is
not
stabilized
or
if
ventilation
is excessive.
matory response have a poor response to surfactant. (16)
Thus,
many
very
preterm
infants
have
RDS
plus, and
Another confounder for a pure diagnosis of RDS is the
the
plus
is
various
combinations
of
the
confounders
listed
amount of fetal lung uid retained in the lung. Severe
in Table 2. Nevertheless, any preterm infant with a diagnosis of signicant respiratory failure, probably with
a RDS component, should be treated with surfactant.
There are no contraindications to surfactant treatment
Table 2.
for suspected RDS.

Confounders of Diagnosis
of Respiratory Distress
Syndrome
Possible Explanations for No RDS
Antenatal corticosteroids
Chorioamnionitis and induced lung maturation
Presently unknown mechanisms
Alternative Causes or Contributors to RDS
Pulmonary hypoplasia
Pulmonary hypertension
Lung inflammation/pneumonia
Retained fetal lung fluid
Failure of respiratory driveapnea
Injury from mechanical ventilation
RDSrespiratory distress syndrome.

When to Treat?
The decision of when to treat an infant who has surfactant deciency continues to evolve. The trials following
licensure of surfactant for general use strongly supported
the treatment of infants at high risk of RDS in the delivery
room after initial stabilization. (21) A trial of treatment at
delivery and preferably before the infant breathing versus
after initially stabilization of the infant revealed more
BPD in the very early treatment group, presumably because the surfactant treatment interfered with the initial
care of the infant. (22) Many clinicians prefer a delayed
treatment, often after several hours of age. The VermontOxford group reported a quality improvement initiative

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to decrease the interval from birth to treatment. (23) Although the educational intervention decreased the time
to treatment from 78 minutes to 21 minutes, there were
no differences in any outcome, including BPD or death.
Infants who have RDS often have a honeymoon period of
relatively good lung function before progression toward
severe RDS. My interpretation is that delayed treatments
reect reasonable clinical decisions to avoid unnecessary
treatments. The practical advantage for delaying treatment beyond the initial period of stabilization at delivery
is that treatment of the large number of infants without
RDS is avoided. There are no data to demonstrate any
benet of a surfactant treatment for an infant not destined to have RDS. Selective treatment of infants as they
progress toward RDS allows more controlled treatments in the NICU rather than the delivery room. The
counter argument is that any ventilation, even spontaneous breathing with RDS, will cause lung injury and result
in a less favorable response to surfactant, more acute
complications such as pneumothorax, and increased risks
of poor outcomes (death and BPD). These risks of delaying treatments with surfactant are supported by the studies of animal models of RDS.
From my perspective, this controversy has been resolved by the series of randomized controlled trials that
have recently been published and compiled into two
meta-analyses. (24)(25) The trials were designed to ask
this question: Will initial stabilization of breathing with
CPAP be better than early intubation and surfactant
treatment for very preterm infants? Although each of
the trials differ in patient population and choice of surfactant, the results of the four large trials including 2,782
patients compiled by Schmolzer et al (24) and the seven
trials evaluated by Fischer and Buhrer (25) that included
3,289 patients were similar. A CPAP strategy to avoid
early mechanical ventilation decreased death or BPD signicantly, odds ratio 0.83 (0.710.96), with a number
needed to treat of 35. (25) The meta-analysis that compared CPAP with early intubation and surfactant treatment revealed that the CPAP strategy decreased BPD
and death was decreased qualitatively from 12% to 11%
(Fig 2). (24) The combined outcome had a risk ratio
of 0.91 (0.840.99) that favored the CPAP strategy.
The Dunn et al (8) trial had three randomization arms
for infants of mean gestational age 28 weeks (early surfactant treatment with ventilation, early surfactant with
rapid extubation to CPAP or CPAP alone). Although
the trial was underpowered, the two groups that did
not receive more prolonged ventilation had lower mortality and BPD. Only 52% of the CPAP only group needed
mechanical ventilation during their hospitalization and

surfactant for RDS

45% received surfactant. This trial suggests no benet to early

surfactant even if the infant is not subsequently ventilated.
The trials demonstrate that stabilization of spontaneous
breathing in the delivery room is marginally better than intubation and surfactant treatment for very preterm infants.
The contentious point is how low can you go (in birthweight/gestational age) with CPAP to support spontaneous ventilation. The experience from South Africa in
a resource-limited environment was that most infants less
than 1,000 g did well on CPAP alone, although they did
not support infants less than 500 g, and 38% of infants
were growth restricted. (9) At Columbia University,
69% infants who have gestational ages of 23 to 25 weeks
could be initially stabilized with CPAP, and 31% remained
on CPAP at 72 hours. (26) The Surfactant Positive Pressure and Pulse Oximetry Randomized Trial (SUPPORT)
enrolled a large number of infants at 240 to 256 weeks gestational age. (7) Although there were no signicant differences for outcomes for the overall trial that included more
mature infants, this very low gestational age group seemed
to benet from randomization to CPAP (Table 3).
The clinical message from these trials is that CPAP in
the delivery room is a reasonable strategy for any preterm
infant who can be coaxed (quickly) to breathe, independent of size or gestational age. Unfortunately, the benets of the CPAP/avoiding ventilation strategy are not as
great as might be anticipated from research with preterm
animals. The research emphasis is now on how best to recruit lung gas volumes immediately after birth. Perhaps
a CPAP plus strategy that might use higher pressures
or supplemental long initial breaths (sighs) will improve
outcomes. (27) A problem with converting information
from the trials into practice guidelines is the clinical reality
that these very fragile infants are not uniform at birth
(Fig 3). Each infant needs the equivalent of a 10-second

Figure 2. Outcomes for infants randomly assigned to continuous positive airway pressure (CPAP) initiated in the delivery room or intubation and surfactant treatment in the
delivery room. The combined outcome of death or bronchopulmonary dysplasia significantly favored the CPAP group.
Data from Schmolzer et al. (24)
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surfactant for RDS

Outcomes for Support Trial

Infants With Gestational Ages of
240 to 256 Weeks

Table 3.

BPD or death
BPD
Death
Use of postnatal
steroids

Relative Risk (95%

Confidence Interval)

0.96
1.06
0.68
0.66

.45
.46
.01
.02

(0.851.07)
(0.911.25)
(0.500.92)
(0.460.94)

BPDbronchopulmonary dysplasia. Data from Finer et al. (7)

Apgar score (a physiologic assessment) for the clinician to

decide what will be best for that infant. Severe depression
requires assistance with positive pressure ventilation (PPV),
whereas the larger vigorous infant needs no ventilatory support and the smaller infant may benet from CPAP to assist
with transition. The problem is the large number of infants between these extremes. Units that routinely use
CPAP in the delivery room can coax most of these infants
to breathe and transition on CPAP. A standard of care for
delivery room management for all infants less than 1 kg is
problematic. Intubation may harm the vigorous infant. In
contrast, a CPAP standard could harm the depressed infant by delaying ventilation.
The next decision point for the clinician is the evaluation of the infant for RDS and surfactant treatment. The

evaluation of the infant involves a balanced clinical judgment of the abnormalities. Signicant apnea requires intervention. The larger infant in 30% oxygen with
a normal PCO2 may be distressed with radiologic ndings
of RDS, but the infant is compensating because of his
ability to increase respiratory effort. The very small infant
may have only modest distress, but elevated PCO2 values
and need surfactant treatment. Bahadue and Soll (28) reported a benet for early treatment within 1 to 2 hours
relative to treatment at more than 2 hours with signicant
risk ratios of 0.84 (0.720.95) for death, 0.61 (0.48
0.78) for air leak, and 0.69 (0.550.86) for BPD. The
European Consensus Guidelines for the management
of RDS are to treat infants younger than 26 weeks gestation with RDS with surfactant early in the clinical
course when oxygen requirements are more than 30%
and to use more than 40% oxygen for infants older than
26 weeks gestation. (29) The recently published guidelines from the American Academy of Pediatrics Committee on Fetus and Newborn are less specic, but suggest
early rather than later treatment on the basis of a recent
meta-analysis. (30) Surfactant treatment can be avoided
in some infants by strategies such as the use of higher
pressure for CPAP or noninvasive ventilation. Failure
of CPAP increased as gestational age decreased and increased for higher oxygen requirements in the rst hours
after birth. (31) CPAP failure was associated with a higher
risk of BPD and pneumothorax. If an infant has progressive RDS, there is a specic therapy that should be given,
surfactant.

How Should Surfactant Be

Given?

Figure 3. A flow diagram for an action plan following a 10-second Apgar (physiologic
assessment of a very low birthweight infant). Based on appearance and breathing activity the
clinician must decide how to initially support respiratory transition. Subsequently, all infants
will need an evaluation for respiratory distress syndrome (RDS) and surfactant treatment.
CPAP[continuous positive airway pressure; PPV[positive pressure ventilation.

Surfactant was the rst drug approved

by the Food and Drug Administration (FDA) for direct instillation into
the lungs through an endotracheal
tube. All the early trials for testing
the value of surfactant treatment used
instillation via an endotracheal tube.
At the time the standard management for RDS was mechanical ventilation of intubated infants. With the
interest in avoiding intubation at delivery and the management of RDS
with CPAP or noninvasive ventilation, strategies to give surfactant
without intubation with an endotracheal tube have been developed. Another concern has been the acute

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surfactant for RDS

physiologic effects of surfactant treatments on the cardiovasbased treatment resulted in less BPD than INSURE.
cular system of the infant. For example, Miedema et al (32)
(40) The outcomes from these different approaches to getrecently reported that infants treated with surfactant while
ting surfactant into the lungs are highly operator and detail
supported on an oscillator had a 61% increase in lung gas
dependent. For example, the use of sedatives or analgesics
volume within 4 minutes. Such changes probably explain
for the laryngoscopy will change the responses of the infant
the increases in systemic blood ow as infants respond to
to treatment. Infants treated by using the INSURE apsurfactant treatments. (33) The combined procedure of inproach can be ventilated briey while a catheter technique
tubation followed by surfactant treatment can alter brain
requires vigorous spontaneous breathing. Ultimately, the
perfusion and suppress the normal electroencephalography.
clinician must decide how much control of the airway will
(34) Further, surfactant treatments can obstruct the airways
be needed for a safe surfactant treatment for each infant.
and cause hypoxia and increase the PCO2 unless sufcient
Important variables are the respiratory effort of the infant,
pressures are used to distribute the surfactant into the distal
the size of the infant, and the severity and progression of
lung. (35)
the RDS.
Surfactant has been given into amniotic uid in the
The holy grail of surfactant treatment is to aerosolize
hope that the infant will aspirate the surfactant and be
surfactant while supporting the infant with CPAP. Such
treated before birth. Surfactant has been instilled into
an approach would avoid intubation and mechanical venthe nasopharynx before delivery of the shoulders with
tilation and avoid the acute cardiovascular changes that octhe anticipation that the infant will aspirate the surfactant
cur when an infant responds quickly to surfactant. The
with the initiation of breathing. (36) Another noninvaproblems with a successful Aerosolization strategy are subsive approach is to use a laryngeal mask airway to give surstantial: surfactant doses and volumes are large, aerosolfactant. (37) A laryngeal mask airway small enough for
izers could inactivate the surfactant, the surfactant tends
infants less than 1,200 g is not available. These apto deposit where the lung is being ventilated and not to
proaches have not been extensively tested.
atelectatic or air trapped regions, and much of the aerosol
An effective approach to minimize mechanical ventilawill get deposited in the nose and pharynx. (41) A Cotion for surfactant treatment for an infant on CPAP is inchrane Neonatal Review in 2012 concluded that there
tubate, surfactant, and extubate (INSURE) to CPAP.
were insufcient data to evaluate aerosolized surfactant
This technique may decrease the
need for mechanical ventilation and
BPD in larger infants. (38) Very preterm infants may not have sufcient
respiratory reserve to cope with the
intubation and surfactant instillation
if quickly extubated to CPAP. The
European Consensus Guidelines support considering INSURE for larger
infants needing surfactant, whereas
the American Academy of Pediatrics
Guidance document makes no recommendation. (29)(30)
Another option is to avoid traditional intubation by passing a ne
catheter into the trachea of the infant
with direct visualization by laryngoscopy while maintaining some CPAP
with high ow. Once the catheter is
positioned, the laryngoscope is reFigure 4. Decrease in death from respiratory distress syndrome (RDS) from 1970 to 2010.
moved and the infant is treated dur- Infant mortality has decreased by 95%, although the infants coded as having RDS have
ing spontaneous breathing while on gotten smaller and more immature. The years for introduction of the interventions into
CPAP. (39) This approach can re- clinical practice are indicated on the graph. Figure redrawn from data in Lee et al (49)
duce the need for mechanical venti- with additional data for 2010 to 2011 from Hamilton et al. (50)
lation, and in one trial the catheter CPAP[continuous positive airway pressure; PEEP[positive end-expiratory pressure.
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surfactant for RDS

for clinical use. (42) One trial concluded only that aerosolized surfactant for infants on CPAP appeared to be safe.
(43) However, there are new innovations in nebulizer design that greatly improve efciency of aerosol delivery.
(44) Recent reports in animal models also support the feasibility of aerosol strategies. (45) Aerosolization of surfactant is being actively developed for infants with RDS.

Which Surfactant Should Be Used?

In the United States, three surfactants sourced from animal lungs (beractant, calfactant, and poractant) and one
synthetic containing a surfactant protein analog (lucinactant)
are available for clinical use. Elsewhere in the world, locally produced surfactants, often of unvalidated quality,
are available at lower cost. The choice of a surfactant
by the physician is likely to be inuenced by advertising
claims that may not be relevant to the primary outcomes
of interest, which should be major complications of prematurity that can be improved with surfactant therapy.
Those outcomes are death and pneumothorax. Contrary
to popular belief, surfactant treatments have not decreased the incidence of BPD, rather the increased survival results in more very preterm infants at risk for
BPD. Surfactant and better ventilation support strategies
have decreased the severity of BPD. Trembath et al (46)
reported the comparative effectiveness for the animal lung
derived surfactants in 51,282 infants. There were no consistent differences for pneumothorax, BPD, or death between the surfactants.
New synthetic surfactants that contain full length Surfactant Protein C and analogs of Surfactant Protein B are
being developed for treatment of RDS. (47) These surfactants perform well in animal models of RDS and likely
would be effective clinically. Synthetic surfactants have
the advantages of more quality control for manufacture
and they have no risk of animal derived disease (although
this has not been a problem). But will any new surfactant
result in better outcomes than the surfactants currently
available? The variability of clinical responses and the
low incidences of death and pneumothorax in all but
the most premature infants make the demonstration of
clinically relevant differences most difcult. (46) The
neonatal community is fortunate to have effective surfactants for the treatment of RDS.

The Future
Innovation for the treatment of RDS presently is focused
on strategies for noninvasive respiratory support with new
devices for CPAP, noninvasive ventilation, and high ow
nasal cannulas. More sophisticated noninvasive ventilation

with synchronization to spontaneous breathing by using

techniques such as neural adjusted ventilator assist with
triggering from the electrical signal of the diaphragm are
being evaluated. (48) Surfactant treatment strategies are
being integrated into these respiratory support strategies.
Aerosols of surfactant may be another approach to improving treatment strategies and outcomes. In 2014, we must
recognize that the multifaceted treatments for preterm infants with RDS are the major success story in neonatology.
Mortality from RDS decreased by 95% from 1970 to 2011
(Fig 4). (49)(50) Over this period the infants diagnosed
with RDS are more immature, such that infants who have
RDS who died with RDS in 1970 no longer die. The infants who die of RDS now are the most immature infants
who have multiple other complications of prematurity.
Improved neonatal care plus surfactant has essentially
eliminated mortality from RDS for infants more than 1
kg unless they have other complicating problems.

American Board of Pediatrics Neonatal-Perinatal

Content Specifications
Know the pathophysiology and risk factors
for respiratory distress syndrome (RDS).
Know the clinical strategies and therapies
used to decrease the risk and severity of
RDS.
Know the management of RDS, including
surfactant replacement.

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20. Hillman NH, Kemp MW, Noble PB, Kallapur SG, Jobe AH.
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2013;347:f5980
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NeoReviews Quiz Requirements

To successfully complete 2014 NeoReviews articles for AMA PRA Category 1 CreditTM, learners must demonstrate a minimum performance level of
60% or higher on this assessment, which measures achievement of the educational purpose and/or objectives of this activity. If you score less than
60% on the assessment, you will be given additional opportunities to answer questions until an overall 60% or greater score is achieved. NOTE:
Learners can take NeoReviews quizzes and claim credit online only at: http://neoreviews.org.

1. A female infant is born at 27 weeks gestational age and is admitted to the neonatal intensive care unit (NICU).
The mother received antenatal steroids 3 days before delivery. The infant is brought to the unit on continuous
positive airway pressure (CPAP) and has increasing oxygen requirement, worsening signs of respiratory distress,
and is placed on mechanical ventilation and given surfactant by endotracheal tube. She remains on the
ventilator for 24 hours and is then extubated. Which of the following descriptions best matches this clinical
scenario and respiratory distress syndrome (RDS)?
A. Considering the clinical course, this patient cannot be considered to have RDS by standard definitions.
B. Although antenatal steroids may have assisted in alveolar development, all infants at this gestational age
have surfactant deficiency, which would ultimately benefit from replacement.
C. The presence of chorioamnionitis, even when asymptomatic, can potentially lead to early maturation of the
lungs, including increased surfactant.
D. As the infant was initially maintained on continuous positive airway pressure, the diagnoses of pulmonary
hypoplasia or problems of anatomic lung development can be excluded.
E. Recent studies indicate that optimal management for patients in this clinical situation should have
included nitric oxide treatment starting in the delivery room.
2. Upon examination of the placenta of the patient in the above question, there is evidence of histologic
chorioamnionitis. Which of the following is true regarding the relationship between chorioamnionitis and
respiratory development in the premature infant?
A. Although there may be evidence on pathologic examination, chorioamnionitis is a clinical diagnosis and
unless the mother exhibited symptoms such as fever and tachycardia, there would be no consequence to
the newborn infant.
B. Chorioamnionitis can induce lung maturation and decrease RDS, but may also lead to symptoms of diffuse
pneumonia presenting as respiratory distress.
C. Premature infants exposed to chorioamnionitis tend to have a particularly positive response to surfactant.
D. The majority of premature infants born after chorioamnionitis will present with a classic pneumonia
syndrome, but with negative radiographic findings.
E. In growth restricted infants, the incidence of RDS and respiratory distress in general is approximately 25%
of that of similar gestational age infants.

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surfactant for RDS

3. A male infant is born at 33 weeks gestational age and has symptoms of respiratory distress including
tachypnea, subcostal retractions, and nasal flaring. Chest radiograph reveals what appears to be retained lung
fluid. Which of the following considerations is appropriate regarding the further evaluation and treatment of
this patient?
A. This may be a presentation of severe transient tachypnea of the newborn with retained lung fluid, which
may be associated with low surfactant levels.
B. Mechanical ventilation by itself without surfactant replacement in primate and human studies has been
shown to be a potent stimulator of endogenous surfactant function.
C. Recent studies have demonstrated that preterm infants at this gestational age are unlikely to benefit from
surfactant, and should be treated with supportive care until lung maturation occurs in the first few days.
D. Because infants at this gestational age do not typically have surfactant deficiency, the treatment plan
should not include surfactant therapy unless the infant is growth restricted.
E. The main problem in infants with respiratory distress at this gestational age is a lack of lung fluid leading to
a decreased activation of surfactant, rather than the amount of surfactant available.
4. Your team is preparing for an infant who will be delivered at 27 weeks gestational age because of severe
maternal preeclampsia. The mother has received antenatal steroids, magnesium sulfate, and antibiotics. Which
of the following is correct regarding current understanding of appropriate treatment for the infant after birth?
A. Although previous studies have revealed that continuous positive airway pressure is sufficient for care for
most infants at this gestational age, recent studies reveal that prophylactic surfactant leads to reduced
incidence of bronchopulmonary dysplasia.
B. Quality improvement projects aimed at reducing the time to surfactant therapy have demonstrated
a reduction in mortality, bronchopulmonary dysplasia, and length of hospital stay.
C. Because RDS occurs in 100% of infants at this age, surfactant should be given unless the infant is able to
breathe in room air.
D. The decision of when to treat an infant at this gestational age is not amenable to one approach, because
treatment for patients who do not have RDS is not beneficial, but a delay in treatment for a patient with
RDS could lead to complications.
E. The most recent studies have not revealed any difference in the incidence of bronchopulmonary dysplasia,
regardless of initial treatments in the delivery room or first several hours in the neonatal intensive care
unit.
5. Which of the following statements is correct regarding the delivery of surfactant to premature infants?
A. Although surfactant has been shown in clinical trials to have efficacy for RDS, it is not officially approved
by the Food and Drug Administration (FDA) for premature infants.
B. Studies have demonstrated that the optimal use of surfactant is facilitated by at least 6 hours of
subsequent mechanical ventilation.
C. Intubation followed by surfactant treatment has been shown to alter cerebral perfusion and
electroencephalography activity.
D. The most promising alternative to intubation for surfactant is delivery by laryngeal mask airway,
particularly for infants more than 500 g who may be difficult to intubate.
E. Synthetic surfactant mimics the phospholipid component of natural surfactant, lacks protein, and has
proven to be ineffective in animal models.

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Surfactant for Respiratory Distress Syndrome

Alan Jobe
NeoReviews 2014;15;e236
DOI: 10.1542/neo.15-6-e236

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Surfactant for Respiratory Distress Syndrome

Alan Jobe
NeoReviews 2014;15;e236
DOI: 10.1542/neo.15-6-e236

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://neoreviews.aappublications.org/content/15/6/e236

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