Timing of Initial Surfactant Treatment for Infants 23 to 29 Weeks

Gestation: Is Routine Practice Evidence Based?

Jeffrey D. Horbar, MD*; Joseph H. Carpenter, MS; Jeffrey Buzas, PhD; Roger F. Soll, MD*;
Gautham Suresh, MD*; Michael B. Bracken, PhD; Laura C. Leviton, PhD; Paul E. Plsek, MS#; and
John C. Sinclair, MD**, for the members of the Vermont Oxford Network
ABSTRACT. Objective. To describe the timing of initial surfactant treatment for high-risk preterm infants in
routine practice and compare these findings with evidence from randomized trials and published guidelines.
Methods. Data from the Vermont Oxford Network
Database for infants who were born from 1998 to 2000
and had birth weights 401 to 1500 g and gestational ages
of 23 to 29 weeks were analyzed to determine the time
after birth at which the initial dose of surfactant was
administered. Multivariate models adjusting for clustering of cases within hospitals identified factors associated
with surfactant administration and its timing. Evidence
on surfactant timing from systematic reviews of randomized trials and from published guidelines was reviewed.
Results. A total of 47 608 eligible infants were cared
for at 341 hospitals in North America that participated in
the Vermont Oxford Network Database from 1998 to
2000. Seventy-nine percent of infants received surfactant
treatment (77.6% in 1998, 79.4% in 1999, and 79.6% in
2000). Factors that increased the likelihood of surfactant
treatment were outborn birth, lower gestational age,
lower 1-minute Apgar score, male gender, white race,
cesarean delivery, multiple birth, or birth later in the
study period. The first dose of surfactant was administered at a median time after birth of 50 minutes (60
minutes in 1998, 51 minutes in 1999, and 42 minutes in
2000). Over the 3-year study period, inborn infants received their initial dose of surfactant earlier than outborn
infants (median time: 43 minutes vs 79 minutes). Other
factors associated with earlier administration of the initial surfactant dose were gestational age, lower 1-minute
Apgar score, cesarean delivery, antenatal steroid treatment, multiple birth, and small size for gestational age.
In 2000, 27% of infants received surfactant in the delivery
room. There was wide variation among hospitals in the
proportion of infants who received surfactant treatment
in the delivery room (interquartile range: 0%75%), in the
median time of the initial surfactant dose (interquartile
range: 20-90 minutes), and in the proportion of infants
who received the first dose >2 hours after birth (interFrom the *Department of Pediatrics, University of Vermont College of
Medicine, Burlington, Vermont; Vermont Oxford Network, Burlington,
Vermont; Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont; Center for Perinatal, Pediatric and Environmental Epidemiology, Yale University, New Haven, Connecticut; Robert
Wood Johnson Foundation, Princeton, New Jersey; #Directed Creativity,
Atlanta, Georgia; **Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; and Center for Clinical Research and EvidenceBased Medicine, University of Texas Medical School, Houston, Texas.
Received for publication Sep 15, 2003; accepted Oct 23, 2003.
Reprint requests to (J.D.H.) Vermont Oxford Network, 33 Kilburn St, Burlington, VT 05401. E-mail: horbar@vtoxford.org
PEDIATRICS (ISSN 0031 4005). Copyright 2004 by the American Academy of Pediatrics.

quartile range: 7%34%). Six systematic reviews of randomized trials of surfactant timing were identified. No
national guidelines addressing the timing of surfactant
therapy were found.
Conclusion. Although the time after birth at which
the first dose of surfactant is administered to infants 23 to
29 weeks gestation decreased from 1998 to 2000, in 2000
many infants still received delayed treatment, and delivery room surfactant administration was not routinely
practiced at most units. We conclude that there is a gap
between evidence from randomized controlled trials that
supports prophylactic or early surfactant administration
and what is actually done in routine practice at many
units. Pediatrics 2004;113:15931602; surfactant, very low
birth weight, Vermont Oxford Network, evidence, respiratory distress syndrome, preterm delivery.
ABBREVIATIONS. RDS, respiratory distress syndrome; NICU,
neonatal intensive care unit; VON, Vermont Oxford Network; CI,
confidence interval; RR, relative risk.

early 50 years after the discovery that infants

with respiratory distress syndrome (RDS)
are deficient in pulmonary surfactant and
more than a decade after the introduction of exogenous surfactants for routine clinical use in neonates,
questions remain concerning the optimal treatment
strategy. There are 2 basic approaches to therapy.
Surfactant may be administered soon after birth as
prophylaxis to infants who are at risk for developing
RDS or later as rescue treatment to infants who have
developed signs of respiratory distress. Multiple randomized controlled trials have demonstrated that
both of these approaches to surfactant therapy are
safe and effective,1 yet controversy remains over
how to select infants for prophylactic treatment and
how soon after birth to initiate therapy. Many neonatal units lack standardized protocols for surfactant
treatment. As a result, there is likely to be considerable variation in surfactant treatment practices both
within and among neonatal intensive care units
(NICUs), but data on these practices are not currently
available.
In this article, we describe the timing of initial
surfactant treatment for high-risk preterm infants
and identify factors associated with variations in timing of initial treatment. The report includes data for
infants who were of 23 to 29 weeks gestation and
were born from 1998 to 2000 and cared for at the 341
NICUs in the United States that participated in the
PEDIATRICS Vol. 113 No. 6 June 2004

1593

Vermont Oxford Network (VON). These analyses

provide a detailed description of current surfactant
treatment practices and allow us to evaluate how the
available evidence has been translated into routine
practice.
METHODS
Vermont Oxford Network
The VON is a voluntary collaboration of health professionals
whose mission is to improve the quality and safety of medical care
for newborn infants and their families through a coordinated
program of research, education, and quality improvement.2 In
support of this mission, VON maintains a database for infants 401
to 1500 g. Members adhere to uniform definitions included in
VONs Database Manual of Operations.3 Infants with birth
weights 401 to 1500 g are eligible for inclusion in the database if
they were born at a VON center or were transferred to it within 28
days of birth. In addition to submitting data on eligible infants,
each member hospital completes an annual hospital survey, which
provides information on the types of services available.4

Study Sample
This report is based on an analysis of data for infants who were
born from 1998 to 2000 with gestational ages from 23 and 29 weeks
and birth weights from 401 to 1500 g. Infants with lethal or
life-threatening birth defects were excluded. All US and Canadian
VON hospitals that participated in the VON database in any of
those years were included in the analyses. Infants who were
transferred from a VON hospital to another VON hospital within
28 days of life were included only at the second VON hospital to
avoid data redundancy and to ensure that data were as complete
as possible.

Surfactant Outcome Measures

Whether infants received surfactant at any time and the age in
hours and minutes at first dose were collected in the database for
infants who were born from January 1, 1998, to December 31, 2000.
The VON began collecting data on whether infants received surfactant in the delivery room for infants who were born in 2000. In
addition to these 3 measures, we constructed a dichotomous variable for infants who received surfactant to evaluate whether their
first dose was after 2 hours of age. Data on the number of doses or
type of surfactant administered were not collected.

Evidence Review
A search for systematic reviews and published guidelines was
conducted to ascertain what evidence was available to support
specific surfactant treatment strategies. Searches were made of the
Cochrane Library and Medline (key words: surfactant, pulmonary
surfactant; limits: guidelines, meta-analysis). Two systematic reviews published in the Cochrane Library address the issue of
timing of treatment.5,6 Four meta-analyses published in peer-reviewed journals addressed issues of treatment strategy including
timing of treatment.710 The 4 non-Cochrane reviews were limited
either by initial design (a review of only 1 surfactant product or
dosing regime) or incomplete literature review. We therefore
based our summary of the randomized trials evidence on the
Cochrane reviews that included all trials identified in any of the
other reviews. Two published guidelines were identified.11,12

Statistical Methods
Multivariate models were created to explore the relationship
between infant and hospital characteristics and the administration
and timing of surfactant treatment during the period 1998 to 2000.
All standard errors and significance tests reflect adjustment for
clustering of infants within hospitals.13
Dichotomous outcome measures (surfactant at any time, surfactant in the delivery room, and surfactant after 2 hours) were
modeled using logistic regression. Intrahospital correlation was
accounted for using generalized estimating equations. The exchangeable correlation structure was assumed in all logistic models, unless there was a problem with convergence, in which case
the independent correlation structure was used. A linear model
including infant and hospital characteristics was used to model

1594

time to first dose of surfactant, with random effects for hospital.

To minimize outlier effects, the natural log of time to first dose
was used as the dependent measure in this model.
Infant-level covariates in all models included gestational age in
completed weeks, small for gestational age (yes or no for birth
weight 10th percentile for infants gestational age and gender
and maternal race and multifetal gestation), birth location (inborn
or outborn), Apgar score at 1 minute after birth, multiple birth (yes
or no), mode of delivery (cesarean section or vaginal), antenatal
steroids (yes or no), gender, and maternal race or ethnicity (black,
Hispanic, white, or other). For the surfactant measures available
during the entire study period (all except delivery room surfactant), we included month of birth (1-36) to test for a time trend. For
improving the model fit, gestational age was modeled as a categorical variable.
Hospital characteristics specified in all models were geographic
region, teaching hospital (yes or no), annual volume of eligible
infants with birth weights between 401 and 1500 g (50, 50) and
level of service (type A, B, or C). Level of service was assigned on
the basis of the VON Annual Membership Survey. Type A hospitals are those that have restrictions on providing assisted ventilation or that provide only minor surgery. Type B hospitals perform
major surgery but not cardiac surgery and have no restrictions on
assisted ventilation. Type C hospitals perform major surgery, including cardiac surgery, and have no restrictions on assisted ventilation. Statistical analyses were performed using SAS statistical
software version 8.2 (SAS Institute, Cary, NC).

RESULTS

A total of 341 hospitals in the United States and

Canada contributed to the VON Database during the
period 1998 to 2000. Of these hospitals, 252 participated during all 3 years, 49 during 2 of the years, and
40 for only 1 of the years. The median average annual
number of infants contributed by an individual hospital was 43 with an interquartile range of from 24 to
71 infants. Characteristics of participating hospitals
are shown in Table 1.
A total of 47 608 infants who were 23 to 29 weeks
gestational age were cared for at the 341 hospitals
during the 3-year study period. Characteristics of
infants by birth location and overall are shown in
Table 2.
Seventy-nine percent of the infants received surfactant treatment at some time during their hospitalization. There were small increases in the proportions who received surfactant from 1998 to 2000
(77.6% in 1998, 79.4% in 1999, and 79.6% in 2000).
Outborn infants were more likely to receive surfacTABLE 1.

Characteristics of 341 Participating Hospitals

Region
New England
Atlantic
Central
Mountain
Pacific
Canada
NICU type
A
B
C
Member of Council of Teaching Hospitals
Yes
No
Missing
Annual volume, infants 4011500 g
50
50

SURFACTANT THERAPY FOR INFANTS 23 TO 29 WEEKS

14
105
131
16
69
6

4
31
38
5
20
2

64
195
82

19
57
24

118
214
9

35
63
3

108
233

32
68

TABLE 2.

Characteristics of Study Infants

Inborn

No. of infants
1998
1999
2000
Total
Female, %
Ethnicity and race, %
Hispanic
Black
White
Asian
Other
Multiple birth, %
SGA, %
Cesarean section, %
Antenatal steroids, %
Apgar score 3 at 1 min, %
Received surfactant at any time, %
Mechanical ventilation
Survived, %
Birth weight (g; mean [SD])
Gestational age (wk; mean [SD])
Total length of stay (d; mean [SD])
Survivors
Deaths

11
13
14
39

889
102
673
664
48

Outborn
2247
2726
2971
7944
45

All
14
15
17
47

136
828
644
608
47

12
30
53
3
2
26
11
59
80
30
77
89
83
920 (260)
27 (2)

19
26
49
3
3
20
7
52
43
37
87
95
80
937 (253)
26 (2)

13
30
52
3
2
25
10
58
74
31
79
90
83
923 (259)
27 (2)

77 (36)
19 (42)

79 (39)
21 (44)

77 (37)
19 (42)

SGA indicates small for gestational age; SD, standard deviation.

tant than inborn infants (87% vs 77%). Seventy-three

percent of infants at 23 weeks gestation received
surfactant, whereas 90% of infants at 24 weeks and
91% at 25 weeks received treatment. The proportion
of infants who received surfactant between 26 and 29
weeks gestation declined from 88% at 26 weeks to
62% at 29 weeks (P .001).
Multivariate logistic models that explored the relation between surfactant administration with infant
and hospital characteristics showed that infants were
more likely to receive surfactant when they were
born later in the study period or were outborn, had
lower gestational age, had lower 1-minute Apgar
score, were male, were white, were delivered by
cesarean section, or were 1 of multiple births (P
.001 for all) or were treated at hospitals that were
members of the Council on Teaching Hospitals (P
.02). The likelihood of surfactant treatment increased
from 1998 to 2000 (P .01). No treatment differences
were observed in type A, B, or C hospitals or in lower
versus higher volume hospitals, after adjusting for
other predictors.
The median time after birth at which the initial
dose of surfactant was administered to infants who
were of 23 to 29 weeks gestation and received surfactant is shown by gestational age and year in Fig 1.
Overall, the median time after birth at which the
initial dose of surfactant is given remains relatively
constant from 23 to 25 weeks gestation and then
increases steadily up to 29 weeks. Importantly, there
is a decrease in the median time of the initial dose
from 1998 to 2000 in every gestational age category.
At 23 weeks, the median time decreased from 41
minutes in 1998 to 30 minutes in 2000; at 29 weeks,
the median time decreased from 95 minutes in 1998
to 67 minutes in 2000.
The median time after birth at which the initial
dose of surfactant was administered also varied by

Fig 1. Median time (minutes) at administration of the first dose of

surfactant by gestational age and year of birth for infants who
were 23 to 29 weeks gestation and received surfactant (VON
1998-2000).

location of birth (Fig 2). During the 3-year period,

inborn infants received the initial dose of surfactant
earlier than outborn infants (median time: 43 minutes vs 79 minutes; P .001). The median time after
birth at which the initial dose of surfactant was administered decreased from 1998 to 2000 for both
inborn and outborn infants. The median time for
outborn infants remained higher in all 3 years.
Multivariate linear models of the log of the time of
the first surfactant dose with infant and hospital
characteristics showed that infants who had lower
gestational ages, had lower 1-minute Apgar scores,
were delivered by cesarean section, were born to
mothers who were treated with antenatal steroids, or
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1595

Fig 2. Median time (minutes) at administration of

the first dose of surfactant by location of birth
(inborn, outborn) and year of birth for infants who
were 23 to 29 weeks gestation and received surfactant (VON 1998-2000).

were 1 of multiple births are treated earlier with

surfactant (P .001 for all). The time of first surfactant treatment decreased from 1998 to 2000 (P
.001). There was no statistically significant association between gender, race, geographic region, NICU
type, annual patient volume, or teaching hospital
and the time of the first surfactant dose.
The VON collected information on delivery room
administration of surfactant for the first time in the
year 2000. For that reason, we focus on the timing of
initial surfactant treatment for infants who were born
in that year. In these analyses, the denominator is all
infants rather than infants who received surfactant to
identify overall differences in prophylactic treatment
practices among centers.
Overall, 26.6% of infants who were 23 to 29 weeks
gestation and born in 2000 were treated with surfactant in the delivery room. The values of the mean
hospital percentages and quartiles for infants who
received surfactant at the 323 hospitals that participated in 2000 are shown by location of birth and
gestational age in Table 3. There is wide variation
among hospitals in the proportion of infants who
receive surfactant treatment in the delivery room.
For example, although overall 38% of all inborn infants of 24 weeks gestation received surfactant in the
delivery room in 2000, the interquartile range among
hospitals was from 0% to 75%. This indicates that in
25% of hospitals, no 24-week inborn infants received
surfactant in the delivery room, whereas at the 25%
of hospitals with the highest rates, 75% of 24-week
inborn infants received surfactant in the delivery
room. There is less variation in treatment practice for

outborn infants at 28 or 29 weeks gestation when no

infants received delivery room surfactant at 75% of
hospitals.
The cumulative proportions of all infants who
were treated with surfactant in 2000 at specific times
after birth are shown in Fig 3. Of the 17 614 infants
who were 23 to 29 weeks gestation and born in 2000
for whom data were available, 28% received the initial dose within 15 minutes of birth, 44% within 30
minutes, 60% within 60 minutes, 79% within 120
minutes, and 92% within 240 minutes after birth.
Twenty percent of the infants who were born in 2000
never received any surfactant. Time data were missing for 216 (1.5%) of the infants who received surfactant.
There was marked variation in 2000 among the 323
hospitals with respect to delivery room surfactant
treatment and delayed treatment (2 hours). Among
the hospitals in the lowest quartile for delivery room
treatment, 0% of the infants received surfactant in the
delivery room, whereas at hospitals in the upper
quartile, 40% of infants received surfactant in the
delivery room. Of infants who received surfactant in
2000, 21% received the first dose 2 hours after birth.
There was also marked variation in the frequency of
delayed treatment among hospitals (interquartile
range: 7%34%).
Because all infants who are intubated in the delivery room are potentially eligible to receive surfactant
in the delivery room, it is of interest to determine
what proportion of these infants actually received
surfactant in the delivery room and what proportion
were treated with surfactant at a later time. These

TABLE 3.
Delivery Room Surfactant Treatment by Gestational Age and Location of Birth for 17 614 Infants 23 to 29 Weeks Gestation
Born in 2000 and 323 Participating Centers*
Gestational Age
(Weeks)
23
24
25
26
27
28
29

Inborn

Outborn

All

IQR

IQR

IQR

263
279
281
289
299
307
299

27
36
36
30
25
19
14

(050)
(075)
(075)
(058)
(050)
(033)
(020)

111
142
156
161
163
179
188

31
27
31
20
23
12
9

(075)
(050)
(059)
(033)
(038)
(00)
(00)

283
298
298
305
314
320
318

28
35
36
29
25
19
13

(050)
(063)
(071)
(050)
(043)
(033)
(020)

N indicates number of hospitals reporting infants at each gestational age; IQR, interquartile range.
* Values are calculated on the basis of average and IQR of hospital percentages.

1596

SURFACTANT THERAPY FOR INFANTS 23 TO 29 WEEKS

Fig 3. Cumulative percentage of all infants who

were 23 to 29 weeks gestation and received the
first dose of surfactant at specific time intervals
after birth. The vertical bars represent the interquartile ranges for the percentages at the 341 participating units (VON 1998-2000).

data are shown by gestational age in Fig 4, in which

the total height of the vertical bar represents the
proportion of infants who were intubated in the delivery room. The proportion of infants who were
intubated in the delivery room increases from 78% at
23 weeks to 93% at 24 weeks and 92% at 25 weeks
and then decreases with advancing gestational age.
Although a high proportion of infants who are intubated in the delivery room ultimately are treated
with surfactant, 36% of the infants who are intubated in the delivery room receive surfactant in the
delivery room.
DISCUSSION

This report describes surfactant treatment practices from 1998 to 2000 for infants who were born at
23 to 29 weeks gestation at a broad range of NICUs
in North America. During this time period, the proportion of infants who were treated with surfactant
increased slightly (2%), and the median time after
birth at which the first dose of surfactant was administered decreased by 10 to 30 minutes, depending on
gestational age and location of birth (inborn, outborn). Inborn infants received the first dose of surfactant much sooner after birth than outborn infants
throughout the study period. The large number of
units included in the study allowed us to identify
wide variation in surfactant treatment practices
among units. For example, at 25% of the units, no
inborn infants of 24 or 25 weeks gestation received
surfactant in the delivery room in 2000, whereas at
the 25% of units with the highest delivery room

treatment rates, more than three quarters of infants

at 24 and 25 weeks gestation received surfactant in
the delivery room.
It is instructive to consider these findings in light
of available evidence regarding administration and
timing of surfactant therapy. Substantial evidence
demonstrates that surfactant therapy is beneficial for
high-risk preterm infants,1 and our data show that
for infants of 23 to 29 weeks gestation, surfactant
therapy is widely used. Furthermore, there is a
strong rationale to support the preference for prophylactic over rescue surfactant administration. Prophylactic administration of surfactant offers the theoretical advantage of replacing surfactant before the
onset of respiratory disease, decreasing the need for
ventilator support and avoiding secondary barotrauma that may result from even short periods of
assisted ventilation.14,15 In animal models, surfactant
is distributed more homogeneously when given immediately after birth into lungs that are still fluid
filled.16 Eight randomized, controlled trials that evaluated the benefits of prophylactic surfactant therapy
compared with treatment of infants with established
RDS were included in the systematic reviews of the
Cochrane Collaboration.5 In these trials, infants who
were at high risk of developing RDS were randomized to either intubation in the delivery room and
administration of natural surfactant extract or to natural surfactant extract treatment of established RDS
(surfactant treatment for infants on assisted ventilation with clinical signs of RDS). In these trials, prophylactic surfactant was administered within 10

Fig 4. Administration and timing of surfactant treatment for infants who were 23 to 29 weeks gestation
and intubated in the delivery room. The total height
of the stacked bar at each gestational age represents
the percentage of infants at that gestational age who
were intubated in the delivery room. Each bar is
divided into 3 categories: infants who received the
first dose of surfactant in the delivery room (black),
infants who received the first dose of surfactant after
leaving the delivery room (dark gray), and infants
who never received surfactant (light gray) (VON,
1998-2000).

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1597

minutes of birth, whereas rescue treatment was administered at mean times ranging from 90 minutes to
7 hours based on each individual studys prespecified criteria for the threshold severity of respiratory
distress. Meta-analysis of the 8 trials demonstrates
that prophylactic administration of natural surfactant extract leads to a significant reduction in the risk
of pneumothorax (typical relative risk: 0.62; 95% confidence interval [CI]: 0.42-0.89; typical risk reduction:
2%, 95% CI 4% to 1%) and a significant reduction in the risk of mortality (typical relative risk: 0.61;
95% CI: 0.48-0.77; typical risk reduction: 5%; 95%
CI: 7% to 2%).2 Because of the greater risk of RDS
and mortality with decreasing gestational age, the
benefits of prophylactic surfactant administration are
most pronounced in infants of 30 weeks gestation.
Four randomized, controlled trials that compared
early surfactant administration within 2 hours of
birth with delayed therapy are included in the systematic review of the Cochrane Collaboration.6 Early
surfactant administration leads to decreased risks of
pneumothorax (typical relative risk [RR]: 0.70; 95%
CI: 0.59-0.82), pulmonary interstitial emphysema
(typical RR: 0.63; 95% CI: 0.43-0.93), neonatal mortality (typical RR: 0.87; 95% CI: 0.77-0.99), and chronic
lung disease (typical RR: 0.70; 95% CI: 0.55-0.88).
Guidelines from the Canadian Pediatric Society
and the American Academy of Pediatrics were available during the time period covered by this
study.11,12 Although these guidelines suggest the
need for institutionally approved protocols to govern
surfactant administration, they did not include specific recommendations regarding the timing of the
first dose.
Are the practices that we observed at 341 North
American neonatal units in this study consistent with
this evidence? Prophylactic surfactant therapy was
not widely practiced in 2000 by either of the 2 measures available to us: administration of the first dose
of surfactant within 15 minutes of birth and administration of surfactant in the delivery room. Fewer
than 30% of infants received the first dose of surfactant within 15 minutes of birth. At many units, no
infants were treated within this time frame, and no
infants received treatment in the delivery room. Furthermore, the first dose of surfactant is often delayed
beyond 2 hours after birth. At 25% of neonatal
units in our study, 30% of the infants who were
treated with surfactant received the first dose 2
hours after birth. Thus, current surfactant treatment
practices at many units are inconsistent with the
evidence favoring prophylactic and early surfactant
treatment. Although delivery room treatment is 1
strategy for achieving prophylactic therapy, in those
units where the NICU is directly adjacent to the
delivery room, it may be possible to achieve treatment in the NICU within a few minutes.
A concern about interpreting the evidence from
randomized trials is that these trials were conducted
at a time when the use of antenatal corticosteroid
therapy was much lower than it is today.17 Therefore, potential benefits of prophylactic and early surfactant treatment in the current practice environment
may be less than that reported in the original trials.
1598

Nonetheless, infants who go on to develop RDS are

still likely to benefit from earlier rather than delayed
therapy. It is interesting to note that we observed
that infants who were delivered by cesarean section
and those whose mothers received antenatal corticosteroids were more likely to receive the first dose of
surfactant sooner after birth. This suggests that the
decision to provide early surfactant treatment is
more common in cases in which an antenatal decision has been made to provide full obstetric intervention.
Location of birth was a major determinant of the
timing of the first dose of surfactant. As expected, the
first dose of surfactant was delayed considerably for
outborn as compared with inborn infants. Outborn
infants have a higher risk for mortality and morbidity than inborn infants.18 Surfactant treatment before
transport or more rapidly after arrival at the referral
center are potential opportunities for improving the
outcomes of outborn infants.
Evidence from randomized, controlled trials, as
summarized in the Cochrane systematic reviews,
demonstrates that prophylactic or early surfactant as
compared with delayed rescue surfactant treatment
results in improved outcomes for high-risk preterm
infants.5,6 However, the trials have not provided a
definitive answer to the question, How early is
early enough? because no trial has yet compared
prophylactic therapy with early rescue therapy administered at 20 or 60 minutes after birth. This uncertainty may account for some of the marked variation in practice that we observed.
Another factor that may contribute to the variation
in practice is the recent interest in using nasal continuous positive airway pressure shortly after delivery to avoid endotracheal intubation, surfactant
administration, and mechanical ventilation. Observational studies have reported that this approach
may decrease the incidence of chronic lung disease
and the need for mechanical ventilation as well as
surfactant use.1921 The efficacy of this approach has
not yet been tested in randomized, controlled trials.22
Our data indicate considerable opportunity for improvement. The high proportion of infants who receive delayed treatment at some NICUs suggests that
there are in fact unintended delays in surfactant
treatment that are amenable to change. Furthermore,
delays in treating outborn infants suggest that substantial opportunities for improvement exist in this
population.
We recommend that each NICU create a multidisciplinary team to review the available evidence and
to assess their own units practices. This exercise will
involve reviewing the administration and timing of
surfactant therapy, developing a unit-based strategy
and measurable goals for surfactant treatment, identifying change ideas to achieve those goals, and monitoring the success of the changes. This approach is
being applied by units in the VON Neonatal Intensive Care Quality Improvement Collaboratives.23 We
are also currently conducting a cluster randomized
trial with hospitals as the units of randomization to
assess the efficacy of a multifaceted quality improve-

SURFACTANT THERAPY FOR INFANTS 23 TO 29 WEEKS

ment intervention designed to promote evidencebased surfactant therapy.

There are important tradeoffs to be considered in
developing a surfactant treatment strategy. Prophylactic surfactant administration will likely result in
more infants being exposed to surfactant and to endotracheal intubation, both of which are associated
with specific risks and financial costs. Unit-based
teams should assess these tradeoffs carefully. As our
observations have shown, at some gestational ages, a
high proportion of infants are intubated in the delivery room and ultimately receive surfactant, yet the
first dose of surfactant is delayed, often beyond 2
hours. These infants could be treated sooner after
birth, realizing the potential benefits of earlier treatment with little additional risk or cost.
Several strategies of surfactant therapy are consistent with the available evidence. After reviewing the
evidence, assessing local practices, and addressing
the tradeoffs, some units may decide to implement a
strategy of prophylactic surfactant for selected
groups of high-risk infants on the basis of gestational
age, tests of fetal lung maturity, or other factors.
Some units may choose to focus on the unintended
delays that occur between the decision to administer
surfactant and its actual delivery. Still others may
identify opportunities for modifying practices related to the stabilization and transport of outborn
infants to achieve earlier treatment of these infants.
We do not claim that there is a single correct policy
or guideline. We do suggest that there is a gap between what the evidence suggests should be done
and what is actually done in routine practice at many
units. It is the responsibility of each unit to review
and modify its own practices in light of its interpretation of the evidence and how it applies in its unit.
Between 1998 and 2000, the trend toward earlier
administration of the first dose of surfactant that
we have documented suggests that this process has
already begun.
APPENDIX: PARTICIPATING HOSPITALS

Abington Memorial Hospital, Abington, Pennsylvania; Adventist Center for Children, Rockville,
Maryland; Advocate Lutheran General Hospital,
Park Ridge, Illinois; Albany Medical Center, Albany, New York; All Saints Episcopal Hospital, Fort
Worth, Texas; Alta Bates Medical Center, Berkeley,
California; Anne Arundal Medical Center, Annapolis, Maryland; Antelope Valley Hospital, Lancaster,
California; Arnot Ogden Medical Center, Elmira,
New York; Aultman Hospital, Canton, Ohio; Aurora
Sinai Medical Center, Milwaukee, Wisconsin; Avera
McKennan, Sioux Falls, South Dakota; Ball Memorial Hospital, Muncie, Indiana; Baptist Childrens
Hospital, Miami, Florida; Baptist Medical Center,
Montgomery, Alabama; Baptist Memorial Hospital
for Women, Memphis, Tennessee; Baptist St. Anthonys Health System, Amarillo, Texas; Barbara Bush
Childrens at Maine Medical, Portland, Maine; Baylor University Medical Center, Dallas, Texas; Baystate Medical Center, Springfield, Massachusetts;
Bellevue Hospital-NYU Medical Center, New York,
New York; Benefis Healthcare, Great Falls, Mon-

tana; Beth Israel Deaconess Medical Center, Boston,

Massachusetts; Bethesda Memorial Hospital, Boynton Beach, Florida; Blank Childrens Hospital, Des
Moines, Iowa; Brandon Regional Hospital, Brandon, Florida; Brookdale Hospital Medical Center,
Brooklyn, New York; The Brooklyn Hospital Center, Brooklyn, New York; Broward General Medical
Center, Fort Lauderdale, Florida; Bryn Mawr Hospital, Bryn Mawr, Pennsylvania; C.R.C.H, Roanoke,
Virginia; CA Pacific Medical Center, San Francisco,
California; Cape Fear Valley Medical Center, Fayetteville, North Carolina; Cardinal Glennon Childrens Hospital, St. Louis, Missouri; Wake Medical
Center, Raleigh, North Carolina; Carle Foundation
Hospital, Urbana, Illinois; Cedars-Sinai Medical
Center, Los Angeles, California; Centennial Medical
Center, Nashville, Tennessee; Central Dupage Hospital, Winfield, Illinois; Central Mississippi Medical
Center, Jackson, Mississippi; Charleston Area Medical Center, Charleston, West Virginia; Childrens at
Cooper U. Medical Center, Camden, New Jersey;
Childrens Hospital Omaha, Omaha, Nebraska;
Childrens Hospital & Research Center at Oakland,
Oakland, California; Childrens Hospital at Bronson, Kalamazoo, Michigan; Childrens Hospital at
Providence Alaska, Anchorage, Alaska; Childrens
Hospital Central CA, Madera, California; Childrens
Hospital Medical Center Akron, Akron, Ohio; Childrens Hospital of Greenville, Greenville, South
Carolina; Childrens Hospital of Iowa, Iowa City,
Iowa; Childrens Hospital of Orange County, Orange, California; Childrens Hospital of WI - Fox
Valley, Neenah, Wisconsin; Childrens Hospital of
Wisconsin, Milwaukee, Wisconsin; Childrens Hospital-Lee Memorial, Ft. Myers, Florida; Childrens
Hospitals & Clinics, Minneapolis, Minnesota; Childrens Hospitals and Clinics, St Paul, Minnesota;
Childrens Hospital-San Diego, San Diego, California; Childrens Medical Center-Dayton, Dayton,
Ohio; Childrens Mercy Hospital, Kansas City, Missouri; CHKD/Sentara Norfolk, Norfolk, Virginia;
CHOA/Brackenridge Campus, Austin, Texas; CHOI
at OSF St. Francis Medical Center, Peoria, Illinois;
Christ Hospital & Medical Center, Oak Lawn, Illinois; Christiana Care Health Services, Newark,
Delaware; Christus Santa Rosa Healthcare, San Antonio, Texas; Citrus Valley-Inter-Community Campus/CA, Covina, California; Citrus Valley-Queen of
the Valley Campus, W. Covina, California; City Avenue/Allegheny University Hospital, Philadelphia,
Pennsylvania; Columbia East Ridge Hospital, Chattanooga, Tennessee; Columbia Hospital for Women,
Washington, District of Columbia; Columbia Medical Center of Plano TX, Dallas, Texas; Columbia
Womens Hospital, Indianapolis, Indiana; Columbus Regional Medical Center, Columbus, Georgia;
Community Medical Center, Missoula, Montana;
Connecticut Childrens Medical Center, Hartford,
Connecticut; Cook Childrens Medical Center, Fort
Worth, Texas; Coral Springs Medical Center, Coral
Springs, Florida; Crozer-Chester Medical Center,
Upland, Pennsylvania; Dameron Hospital, Stockton,
California; Danbury Hospital, Danbury, Connecticut; Dartmouth-Hitchcock Medical Center, LebaARTICLES

1599

non, New Hampshire; Deaconess Medical Center,

Spokane, Washington; Desert Regional Medical
Center, Palm Springs, California; DeVos Childrens/
Spectrum Health, Grand Rapids, Michigan; Doctors
Medical Center, Modesto, California; Driscoll Childrens Hospital, Corpus Christi, Texas; East Tennessee Childrens Hospital, Knoxville, Tennessee; Eastern Maine Medical Center, Bangor, Maine; Encino
Tarzana Regional Medical Center, Tarzana, California; Evanston Hospital, Evanston, Illinois; Exempla
St. Joseph Hospital, Denver, Colorado; Fairview
University Medical Center, Minneapolis, Minnesota; Fitzgerald Mercy Medical Center, Darby, Pennsylvania; Florida Hospital, Orlando, Florida; Forrest
General Hospital, Hattiesburg, Mississippi; Forsyth
Memorial Hospital, Winston-Salem, North Carolina;
Forum Health - Tod Childrens, Youngstown, Ohio;
Frankford Torresdale Hospital, Philadelphia, Pennsylvania; Freeman Hospital & Health System, Joplin, Missouri; Geisinger Medical Center, Danville,
Pennsylvania; Glendale Memorial Hospital &
Health Center, Glendale, California; Good Samaritan HCA, San Jose, California; Good Samaritan Hospital, Los Angeles, California; Good Samaritan Hospital, West Palm Beach, Florida; Good Samaritan
Hospital, Cincinnati, Ohio; Grant Medical Center,
Columbus, Ohio; Greater Baltimore Medical Center,
Baltimore, Maryland; Gundersen Lutheran, LaCrosse, Wisconsin; Hackensack University Medical
Center, Hackensack, New Jersey; Hahnemann University Hospital, Philadelphia, Pennsylvania; Harbor UCLA Medical Center, Torrance, California;
Harris Methodist, Fort Worth, Texas; Hennepin
County Medical Center, Minneapolis, Minnesota;
Henrico Doctors Hospital, Richmond, Virginia;
Henry Ford Hospital, Detroit, Michigan; Holy Cross
Hospital, Silver Spring, Maryland; Hospital of University of Pennsylvania, Philadelphia, Pennsylvania; Houston NW Medical Center, Houston, Texas;
Howard County General Hospital, Columbia,
Maryland; Huntington Memorial Hospital, Pasadena, California; Huntsville Hospital, Huntsville,
Alabama; Hurley Medical Center, Flint, Michigan;
Illinois Masonic Medical Center, Chicago, Illinois;
Inova Alexandria Hospital, Alexandria, Virginia;
Inova Fairfax Hospital for Children, Falls Church,
Virginia; IWK Health Centre, Halifax, Nova Scotia,
Canada; Jackson-Madison County General Hospital, Jackson, Tennessee; Janeway Childrens Hospital Centre, St. John, Newfoundland, Canada; Joe
DiMaggio Childrens Hospital, Hollywood, Florida;
John Peter Smith Hospital, Fort Worth, Texas;
Kadlec Medical Center NICU, Richland, Washington; Kaiser Foundation, Bellflower, California; Kaiser Foundation, Fontana, California; Kaiser Foundation, Los Angeles, California; Kaiser FoundationOrange County, Anaheim, California; Kaiser
Foundation-Riverside Medical Center, Riverside,
California; Kaiser Foundation, San Diego, California; Kaiser Foundation-West Los Angeles, Los Angeles, California; Kaiser Foundation, Woodland
Hills, California; Kaiser Permanente, Baldwin Park,
California; Kennedy Memorial Hospital, Stratford,
New Jersey; Kosair Childrens Hospital, Louisville,
1600

Kentucky; Lancaster General Hospital, Lancaster,

Pennsylvania; Lankenau Hospital, Bryn Mawr,
Pennsylvania; LDS Hospital, Salt Lake City, Utah;
Legacy Emanuel Childrens Hospital, Portland, Oregon; Lehigh Valley Hospital, Allentown, Pennsylvania; Lenox Hill Hospital, New York, New York;
Little Company of Mary Hospital, Torrance, California; Loma Linda University Childrens, Loma
Linda, California; Loyola University Medical Center, Maywood, Illinois; LPCH-Stanford University,
Palo Alto, California; Maimonides Medical Center,
Brooklyn, New York; Mary Washington Hospital,
Fredericksburg, Virginia; McKay-Dee Hospital Center, Ogden, Utah; McLeod Regional Medical Center,
Florence, South Carolina; Mease Hospital, Dunedin,
Florida; Medical City, Dallas, Texas; Medical College of Georgia, Augusta, Georgia; Medical University of South Carolina, Charleston, South Carolina;
Memorial Hermann Southwest, Houston, Texas;
Memorial Hospital, South Bend, Indiana; Memorial
Hospital, Gulfport, Mississippi; Memorial Hospital
West, Pembroke Pines, Florida; Memorial Medical
Center, New Orleans, Louisiana; Mercer Medical
Center, Trenton, New Jersey; Mercy Childrens Hospital, Toledo, Ohio; Mercy Health Center, Oklahoma City, Oklahoma; Mercy Hospital & Medical
Center, Chicago, Illinois; Mercy Hospital of Pittsburgh, Pittsburgh, Pennsylvania; Mercy Hospital
South, Charlotte, North Carolina; Mercy San Juan
Hospital, Carmichael, California; Meridia Hillcrest
Hospital, Mayfield Heights, Ohio; Meritcare Childrens Hospital, Fargo, North Dakota; Methodist
Childrens Hospital, San Antonio, Texas; Methodist
Hospital of Indiana, Indianapolis, Indiana; Methodist Hospitals, Inc., Gary, Indiana; MHUMC, Savannah, Georgia; Miami Childrens Hospital, Miami,
Florida; Miami Valley Hospital, Dayton, Ohio; Midwest Neoped Associates, Oak Brook, Illinois; Miller
Childrens Hospital, Long Beach, California; Milton
S. Hershey Medical Center, Hershey, Pennsylvania;
Mission Hospitals, Asheville, North Carolina; Mississippi Baptist Health Systems, Jackson, Mississippi; Monmouth Medical Center, Long Branch,
New Jersey; Morristown Memorial Hospital, Morristown, New Jersey; Mt. Sinai Hospital, Toronto,
Ontario, Canada; Mt. Sinai Hospital Medical Center, Chicago, Illinois; Munson Medical Center, Traverse City, Michigan; National Naval Medical Center, Bethesda, Maryland; Naval Medical Center, San
Diego, California; Neonatology Associates, Kingsport, Tennessee; New Hanover Regional Medical
Center, Wilmington, North Carolina; New York
Presbyterian Hospital, New York, New York; Newark Beth Israel Medical Center, Newark, New Jersey; Newborn Specialists of Tulsa, Tulsa, Oklahoma; North Memorial Medical Center, Robbinsdale,
Minnesota; North Oaks Medical Center, Hammond,
Louisiana; North Shore U. Hospital Manhasset,
Manhasset, New York; Northbay Medical Center,
Fairfield, California; Northridge Hospital, Northridge, California; Northside Hospital, Atlanta, Georgia; Northwestern Memorial, Chicago, Illinois; Norton Suburban Hospital, Louisville, Kentucky;
Oakwood Hospital & Medical Center, Dearborn,

SURFACTANT THERAPY FOR INFANTS 23 TO 29 WEEKS

Michigan; OH-CHEO, Ottawa, Ontario, Canada; Oregon Health & Sciences University, Portland, Oregon; P.C.M.H., Greenville, North Carolina; Parkview
Hospital, Fort Wayne, Indiana; Parkway Regional
Medical Center, N. Miami Beach, Florida; Pennsylvania Hospital, Philadelphia, Pennsylvania; Phoenix
Childrens Hospital, Phoenix, Arizona; Pinnacle/
Harrisburg Campus, Harrisburg, Pennsylvania;
Presbyterian Hospital, Albuquerque, New Mexico;
Presbyterian Hospital of Dallas, Dallas, Texas; Presbyterian Intercommunity Hospital, Whittier, California; Presbyterian-St. Lukes Medical Center,
Denver, Colorado; Primary Childrens Medical Center, Salt Lake City, Utah; Promina Gwinnett Health,
Lawrenceville, Georgia; Provena Covenant Medical
Center, Urbana, Illinois; Providence St. Joseph Medical Center, Burbank, California; Providence St. Vincent Medical Center, Portland, Oregon; Rainbow
Babies & Childrens Hospital, Cleveland, Ohio;
Reading Hospital & Medical Center, Reading,
Pennsylvania; Redlands Community Hospital, Redlands, California; Regional Medical Center at Memphis, Memphis, Tennessee; Riverside Hospital, Toledo, Ohio; Riverside Methodist Hospital,
Columbus, Ohio; Rockford Memorial Hospital,
Rockford, Illinois; Rogue Valley Medical Center,
Medford, Oregon; Rose Medical Center, Denver,
Colorado; Royal Victoria Hospital, Montreal, Quebec, Canada; Sacred Heart Health System,
Pensacola, Florida; Sacred Heart Medical Center,
Eugene, Oregon; Sacred Heart Medical Center, Spokane, Washington; San Francisco General Hospital,
San Francisco, California; Scott & White Hospital,
Temple, Texas; Seton Medical Center, Austin, Texas;
Sharp Mary Birch Hospital for Women, San Diego,
California; Sheridan Childrens, Plantation, Florida;
Sinai Hospital of Baltimore, Baltimore, Maryland;
Sioux Valley Childrens Hospital, Sioux Falls, South
Dakota; Sisters of Charity, Staten Island, New York;
South Fulton Medical Center, East Point, Georgia;
Southern Regional Medical Center, Riverdale,
Georgia; Sparrow Hospital, Lansing, Michigan; St.
Agnes Hospital, Baltimore, Maryland; St. Barnabas
Medical Center, Livingston, New Jersey; St. Charles
Medical Center, Bend, Oregon; St. Cloud Hospital,
St Cloud, Minnesota; St. Davids Medical Center,
Austin, Texas; St. Elizabeth Hospital Center,
Youngstown, Ohio; St. Elizabeth Regional Medical
Center, Lincoln, Nebraska; St. Elizabeths Medical
Center, Boston, Massachusetts; St. Francis Hospital,
Hartford, Connecticut; St. Francis Hospital, Tulsa,
Oklahoma; St. Francis Medical Center, Lynwood,
California; St. John Hospital & Medical Center, Detroit, Michigan; St. Johns Hospital, Santa Monica,
California; St. Johns Hospital, Springfield, Illinois;
St. Johns Mercy Medical Center, St. Louis, Missouri; St. Johns Regional Medical Center, Oxnard,
California; St. Joseph Hospital & Medical Center,
Paterson, New Jersey; St. Joseph Hospital/TX, Houston, Texas; St. Joseph Hospital-Marshfield Clinic,
Marshfield, Wisconsin; St. Joseph Mercy Oakland,
Pontiac, Michigan; St. Josephs Health Center, Syracuse, New York; St. Josephs Hospital, Milwaukee,
Wisconsin; St. Josephs Hospital & Medical Center,

Phoenix, Arizona; St. Lukes Hospital, Kansas City,

Missouri; St. Lukes Hospital, Bethlehem, Pennsylvania; St. Lukes Hospital, Racine, Wisconsin; St.
Lukes Regional Medical Center, Boise, Idaho; St.
Mary Medical Center, Long Beach, California; St.
Marys Hospital, Milwaukee, Wisconsin; St. Marys
Hospital & Medical Center, Grand Junction, Colorado; St. Marys Hospital Medical Center, Madison,
Wisconsin; St. Marys Hospital, West Palm Beach,
Florida; St. Marys Medical Center, Evansville, Indiana; St. Marys Medical Center, Duluth, Minnesota;
St. Paul Medical Center, Dallas, Texas; St. Peters
Hospital, Albany, New York; St. Peters Medical
Center, New Brunswick, New Jersey; St. Vincent
Hospital, Indianapolis, Indiana; St. Vincent Hospital, Green Bay, Wisconsin; St. Vincent Hospital &
Health Center, Billings, Montana; Stamford Hospital, Stamford, Connecticut; Sunnybrook & Womens
College Health Sciences Center, Toronto, Ontario,
Canada; Sunrise Childrens Hospital, Las Vegas,
Nevada; Sutter Memorial Hospital, Sacramento,
California; Swedish American Hospital, Rockford,
Illinois; Swedish Medical Center, Englewood, Colorado; T.C. Thompson Childrens Hospital, Chattanooga, Tennessee; Tacoma General Hospital, Tacoma, Washington; Temple University Hospital,
Philadelphia, Pennsylvania; Texas Tech U. Health
Science Center, Amarillo, Texas; Thomas Jefferson
University Hospital, Philadelphia, Pennsylvania;
Tisch Hospital-NYU Medical Center, New York,
New York; Toledo Childrens Hospital, Toledo,
Ohio; Truman Medical Center, Kansas City, Missouri; Tufts-New England Medical Center, Boston,
Massachusetts; Tulane Medical Center, New Orleans, Louisiana; U. Mass Memorial Health Care,
Worcester, Massachusetts; U. of TN Medical Center,
Knoxville, Tennessee; UC Irvine Medical Center,
Orange, California; UCDMC, Sacramento, California; UCHSC, Denver, Colorado; UCSD Medical
Center, San Diego, California; UCSF Medical Center, San Francisco, California; University Medical
Center, Las Vegas, Nevada; University of Chicago,
Chicago, Illinois; University of Illinois at Chicago,
Chicago, Illinois; University of Kentucky Childrens
Hospital, Lexington, Kentucky; University of Louisville Hospital, Louisville, Kentucky; University of
Michigan-Holden NICU, Ann Arbor, Michigan;
University of Washington Medical Center, Seattle,
Washington; UPMC Lee Regional, Johnstown,
Pennsylvania; Utah Valley Regional Medical Center, Provo, Utah; Vassar Brothers Hospital, Poughkeepsie, New York; Ventura County Medical Center, Ventura, California; Via Christi-St. Francis
Campus, Wichita, Kansas; Virginia Beach General
Hospital, Virginia Beach, Virginia; VT Childrens at
Fletcher-Allen Health Care, Burlington, Vermont;
Wake Forest University Baptist Medical Center,
Winston-Salem, North Carolina; Waukesha Memorial Hospital, Waukesha, Wisconsin; Weiler Hospital-Montefiore, Bronx, New York; Wellstar Cobb
Hospital, Kennesaw, Georgia; Wellstar Kennestone
Hospital, Marietta, Georgia; Wesley Medical Center, Wichita, Kansas; Western Medical Center, Santa
Ana, California; Western Pennsylvania Hospital,
ARTICLES

1601

Pittsburgh, Pennsylvania; Willis-Knighton South,

Shreveport, Louisiana; Womans Hospital, Baton
Rouge, Louisiana; Womens & Childrens Hospital,
Lafayette, Louisiana; Womens Hospital of Greensboro, Greensboro, North Carolina; Woodhull Medical Center, Brooklyn, New York; Wyckoff Heights
Medical Center, Brooklyn, New York; Yakima Valley Memorial Hospital, Yakima, Washington; YaleNew Haven Childrens Hospital, New Haven, Connecticut; York Hospital, York, Pennsylvania

9.
10.

11.
12.

13.

ACKNOWLEDGMENTS
This study was funded by a grant from the Agency for Healthcare Research and Quality (R01 HS 10528 to Dr Horbar, principal
investigator)

14.

15.

REFERENCES
1. Suresh GK, Soll RF. Current surfactant use in premature infants. Clin
Perinatol. 2001;28:671 694
2. Horbar JD, Plsek P, Leahy K. NIC/Q 2000: establishing habits for
improvement in neonatal intensive care units. Pediatrics 2003;111(4
suppl). Available at: www.pediatrics.org/cgi/content/full/111/4/
SE1/e397
3. Vermont Oxford Network Database Manual of Operations for Infants Born in
2000 (Release 4.0). Burlington, VT: Vermont Oxford Network; 2001
4. Horbar JD, Carpenter J (eds). Vermont Oxford Network Annual Database
Summary for 2000. Burlington, VT: Vermont Oxford Network; 2001
5. Soll RF, Morley CJ. Prophylactic versus selective use of surfactant in
preventing morbidity and mortality in preterm infants Cochrane Database Syst Rev. 2001;(2):CD000510
6. Yost CC, Soll RF. Early versus delayed selective surfactant treatment for
neonatal respiratory distress syndrome. Cochrane Database Syst Rev.
2000;(2):CD001456
7. Hennes HM, Lee MB, Rimm AA, Shapiro DL. Surfactant replacement
therapy in respiratory distress syndrome. Meta-analysis of clinical trials
of single-dose surfactant extracts. Am J Dis Child. 1991;145:102104
8. Egberts J, Brand R, Walti H, Bevilaqua G, Breart G, Gardini F. Mortality,
severe respiratory distress syndrome, and chronic lung disease of the
newborn are reduced more after prophylactic than after therapeutic

16.

17.

18.

19.

20.
21.
22.
23.

administration of the surfactant Curosurf. Pediatrics. 1997;100(1). Available at: www.pediatrics.org/cgi/content/full/100/1/e4

Morley CJ. Systematic review of prophylactic vs rescue surfactant. Arch
Dis Child Fetal Neonatal Ed. 1997;77:F70 F74
Kresch MJ, Clive JM. Meta-analyses of surfactant replacement therapy
of infants with birth weights less than 2000 grams. J Perinatol. 1998;18:
276 283
Neonatal surfactant replacement therapy. Fetus and Newborn Committee, Canadian Paediatric Society. CMAJ. 1992;146:1309 1312
Surfactant replacement therapy for respiratory distress syndrome.
American Academy of Pediatrics. Committee on Fetus and Newborn.
Pediatrics. 1999;103:684 685
Donner A, Klar N. Design and Analysis of Cluster Randomization Trials in
Health Research. London, UK: Arnold; 2000
Jobe A, Ikegami M, Glatz T, et al. Duration and characteristics of
treatment of premature lambs with natural surfactant. J Clin Invest.
1981;67:13731375
Nilsson R, Grossman G, Robertson B. Lung surfactant and the pathogenesis of neonatal bronchiolar lesions induced by artificial ventilation.
Pediatr Res. 1978;12:249 255
Jobe A, Ikegami M, Jacobs H, Jones S. Surfactant and pulmonary blood
flow distributions following treatment of premature lambs with natural
surfactant. J Clin Invest. 1984;73:848 856
NIH Consensus Development Panel on the Effect of Corticosteroids for
Fetal Maturation on Perinatal Outcomes. Effect of corticosteroids for
fetal maturation on perinatal outcomes. JAMA. 1995;273:413 418
Lee SK, McMillan DD, Ohlsson A, et al. The benefit of preterm birth at
tertiary care centers is related to gestational age. Am J Obstet Gynecol.
2003;188:617 622
Avery ME, Tooley WH, Keller JB, et al. Is chronic lung disease in low
birth weight infants preventable? A survey of eight centers. Pediatrics.
1987;79:26 30
Sahni R, Wung JT. Continuous positive airway pressure (CPAP). Indian
J Pediatr. 1998;65:265271
De Klerk AM, De Klerk RK. Nasal continuous positive airway pressure
and outcomes of preterm infants. J Paediatr Child Health. 2001;37:161167
Dunn MS, Reilly MC. Approaches to the initial respiratory management
of preterm neonates. Paediatr Respir Rev. 2003; 2-8
Horbar JD, Plsek P, Leahy K, Schriefer J (eds). Evidence-based quality
improvement in neonatal and perinatal medicine: the NIC/Q 2000
experience. Pediatrics. 2003;111(4). Available at: www.pediatrics.org/
content/vol111/issue4/index.shtml#SUPPLSE1

THE NEWLY PROMINENT THUMB

The Japanese have invented the word dyayubizoku, the thumb tribe, named for
the digit we so compulsively poke at our tiny keypads.

Gleick J. What Just Happened. New York, NY: Pantheon; 2002

Submitted by Student

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SURFACTANT THERAPY FOR INFANTS 23 TO 29 WEEKS