ARTICLES
Impact of Labor on Outcomes in Transient Tachypnea
of the Newborn: Population-Based Study
AUTHORS: Erol Tutdibi, MD,a Katharina Gries, MD,a
Monika Bucheler, MD,b Bjorn Misselwitz, MD, MPH,c
Rolf L. Schlosser, MD,d and Ludwig Gortner, MDa
aCenter of Pediatrics and Neonatology, Childrens University
Hospital of Saarland, Homburg, Germany; bInstitute of Quality
Assurance Saarland, Saarbrucken, Germany; cInstitute of Quality
Assurance Hesse, Eschborn, Germany; and dDepartment of
Neonatology, Childrens University Hospital, Frankfurt, Germany
KEY WORDS
transient tachypnea of the newborn, mode of birth, outcome,
population-based studies
ABBREVIATIONS
TTNtransient tachypnea of the newborn
ECS elective cesarean section
GA gestational age
CS cesarean section
OR odds ratio
CI condence interval
www.pediatrics.org/cgi/doi/10.1542/peds.2009-0314
doi:10.1542/peds.2009-0314
Accepted for publication Oct 5, 2009
Address correspondence to Erol Tutdibi, MD, Childrens
University Hospital of Saarland, Center of Pediatrics and
Neonatology, Kirrberger Strasse, 66421 Homburg/Saar,
Germany. E-mail: erol.tutdibi@uks.eu
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2010 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.
PEDIATRICS Volume 125, Number 3, March 2010
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WHATS KNOWN ON THIS SUBJECT: ECS is known as a main risk
factor for TTN, because of its crucial role in perinatal lung uid
clearance. Our study emphasizes and outlines the impact of labor
before birth on respiratory outcomes in TTN.
WHAT THIS STUDY ADDS: Our study indicates that TTN is
strongly related to ECS and low GA. Furthermore, the absence of
exposure to labor contractions is associated with increased risk
and severe course of TTN at term, with longer duration of oxygen
supplementation.
abstract
OBJECTIVE: Our aim was to assess the effect of labor on the risk and
course of transient tachypnea of the newborn (TTN) in term neonates
from a contemporary, population-based cohort.
METHODS: We analyzed perinatal characteristics of term singleton
newborns (gestational age [GA] of 37 completed weeks) who were
born between January 2001 and December 2005 in the federal states of
Hesse and Saarland (Germany). TTN was diagnosed on the basis of
International Classication of Diseases, 10th Revision codes.
RESULTS: Of a total of 275 459 births, 239 971 fullled the inclusion
criteria of GA of 37 completed weeks and singleton live birth. Among
those, 13 346 term infants were admitted for neonatal care and 1423
were diagnosed as having TTN. The overall incidence of TTN was 5.9
cases per 1000 singleton live births in our study cohort. Elective cesar-
ean section, low GA, male gender, and low birth weight were associated
with TTN. The duration of oxygen supplementation for newborns with
TTN was associated inversely with the duration of labor (r 0.151;
P .028).
CONCLUSIONS: Our study indicates that TTN is strongly related to elec-
tive cesarean section and low GA. Furthermore, the absence of expo-
sure to labor contractions is associated with increased risk and severe
course of TTN at term, with longer duration of oxygen supplementation.
Pediatrics 2010;125:e577e583
e577
Postnatal respiratory complications
among term infants are common. The
most commonly reported cause of
neonatal respiratory distress is tran-
sient tachypnea of the newborn (TTN),
with an estimated incidence of 1% to
2% of all newborns.1 The disorder is
reported to be benign and self-limiting,
with resolution usually occurring by 2
to 5 days of age. In severe courses of
TTN, complications such as pneumo-
thorax, need for extracorporeal mem-
brane oxygenation, and death have
been reported.2 Known risk factors for
TTN include lower gestational age (GA)
and birth weight, male gender, and
elective cesarean section (ECS).3
In recent decades, the rates of cesar-
ean section (CS), especially those per-
formed electively at term and partly at
maternal request, have shown an in-
creasing trend.4 In Germany, accord-
ing to data supplied by the Federal Of-
ce for Quality Assurance, the overall
CS rate for all singleton deliveries in-
creased constantly from 21.6% to
29.3% between 2001 and 2007.5 The
major clinical reasons for performing
a CS have not changed and include
breech presentation, suspected fetal
distress, failure to progress in labor,
and previous CS. The fth most com-
mon indication for a CS has changed
and now is reported to be maternal
request. In the literature, the risks
and benets of ECS are controversial.
Some authors favor planned CS in at-
tempts to prevent the fear of childbirth
associated with labor and delivery, uri-
nary and fecal incontinence, and pelvic
prolapse. CS-related maternal morbid-
ity and mortality rates in the German
population have decreased markedly
in recent years. However, ECS remains
major surgery, with potential impor-
tant surgical complications for the
mother that lead to extended hospital
stays.6 The impact of ECS on neonatal
respiratory outcomes was summa-
rized recently.2 Epidemiological stud-
e578 TUTDIBI et al
ies reported that ECS increased the
risk of neonatal respiratory morbidity
and rates of admission to the NICU,
compared with GA-matched newborns
after spontaneous vaginal delivery.
The aim of this study was to assess
whether maternal characteristics,
mode of birth, labor before birth, and
perinatal factors were associated with
the risk and course of TTN among term
singleton newborns in a large, repre-
sentative, cohort study in Germany,
which has not yet been evaluated. Fur-
thermore, neonatal outcomes were
addressed with respect to the progno-
sis of respiratory failure in TTN, de-
pending on labor before birth. To the
best of our knowledge, no studies have
investigated the impact of labor on the
severity of TTN courses.
METHODS
Study Population and Data Sources
We analyzed perinatal databases re-
corded by the national neonatal audit
program of the federal states of Hesse
and Saarland in Germany, for single-
tons born at GA of 37 weeks between
January 2001 and December 2005. Re-
corded GAs were based on maternal
last menstrual period or early prena-
tal ultrasound examination ndings.
The register provides detailed infor-
mation for 98% of all infants born
alive in Hesse and Saarland. The peri-
natal birth registers include data
about the mother, the current preg-
nancy and delivery, and the postnatal
course, as documented by the obstetri-
cian in charge of the birth by using
an evaluated standardized question-
naire.7 We also used neonatal data sets
including data for all infants who were
admitted to a neonatal center in Hesse
or Saarland within the rst 10 postna-
tal days. Neonatal data were docu-
mented by the hospital to which the
infant was transferred and were re-
ported to the neonatal audit center
with another questionnaire. The neo-
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natal questionnaire includes informa-
tion on all diagnoses, on the basis of
International Classication of Diseases,
10th Revision codes. We excluded all sets
of data that did not coincide completely
in all of these variables and those that
were incomplete. Data from infants with
congenital malformations affecting the
cardiorespiratory system, chromosomal
aberrations, depression at birth (Ap-
gar score at 5 minutes of 7 or umbil-
ical artery pH of 7.10), fetal hydrops,
or mothers with alcohol or drug abuse
also were excluded from the study. CS
was dened as elective when surgery
was performed before the onset of la-
bor, with all other cases dened as
secondary CS.
Identication of TTN Cases
The data sets for all newborns who
were transferred to a NICU because of
respiratory problems were reviewed
thoroughly. TTN was dened on the ba-
sis of characteristic clinical signs pre-
senting within 24 hours after birth and
radiographic ndings, in agreement
with most authors.1,6,8 We identied
newborns with TTN on the basis of re-
spiratory distress diagnoses (Interna-
tional Classication of Diseases, 10th
Revision code P22), as reported to the
Federal Ofce for Quality Assurance
register by the responsible neonatolo-
gist. Cases with suspicion of TTN were
validated through the absence of other
morbidities affecting respiration, par-
ticularly perinatal infection, persistent
pulmonary hypertension, and meco-
nium aspiration syndrome. Finally, we
paired mother-infant data sets of all
eligible cases of TTN on the basis of
coinciding variables documented on
the perinatal and neonatal question-
naires, including date and time of
birth, zip code, gender, and birth
weight. Therefore, deliveries were di-
vided into groups without labor (no-
labor group) and with labor (labor
group). Outcome variables of interest
were diagnosis of TTN, oxygen therapy,
 ARTICLES

application of continuous positive

airway pressure therapy, mechani-
cal ventilation, antibiotic treatment,
extracorporeal membrane oxygen-
ation therapy, incidence of pulmonary
air leaks, duration of hospitalization,
and death. For qualitative comparison
with national data, the German Neona-
tal and Perinatal Database was used.5

Statistical Analyses
For statistical analyses, we used SPSS
15 (SPSS, Chicago, IL). Continuous vari-
ables were compared by using t tests
when data were distributed normally;
otherwise, the nonparametric Mann-
Whitney U test was used. Categorical
variables were analyzed by using Pear-
sons 2 test or Fishers exact test, as
appropriate. Correlation studies were
performed by using Pearsons correla-
tion coefcient. The statistical signi-
cance level was set at P .05 for all
analyses with 2-tailed comparisons.
Results of multivariate regression FIGURE 1
analyses (including the confounders Cohort design of study, with deliveries from 2001 to 2005 in the federal states of Hesse and Saarland
(Germany).
maternal age, parity, smoking, diabe-
tes mellitus, mode of delivery, GA, birth
weight, and gender) were expressed
as odds ratios (ORs) and 95% con- with maternal data. Variables within summarized in Table 1. Compared with
dence intervals (CIs). the maternal and neonatal data sets the national German perinatal data for
coincided for 6843 (73.2%) of those term singletons born between 2001
RESULTS 9352 infants. There were no signicant and 2005, study infants with TTN were
During the study period, the perinatal differences between all term infants more likely to have an inappropriate
birth registers included data for and those with matched perinatal data birth weight for GA (small for GA: 15.8%
275 459 deliveries, including 259 312 in sets, with respect to basic maternal vs 9.6%; large for GA: 13.5% vs 10.6%;
Hesse between 2001 and 2005 and and neonatal variables (data not P .001) and more often were male
16 147 in Saarland between 2004 and shown). Of the 9352 admitted neo- (60.3% vs 51.4%; P .001).
2005 (Fig 1). Among these deliveries, nates, postnatal respiratory problems The mode of birth was closely related
239 971 (87%) fullled the inclusion were found as leading causes for neo- to GA. Nearly 70% of all ECSs were per-
criteria of GA of 37 weeks and single- natal admission for a total of 2984 new- formed at GAs of 37 to 38 completed
ton live birth. Of these term newborns, borns (31.9%), including TTN (n weeks. The main indications for ECSs
13 346 (5.6%) were transferred to a 1423), meconium aspiration syndrome were as follows: previous CS (31.7%),
neonatal ward. After application of the (n 223), persistent pulmonary hy- breech presentation (17.6%), cephalo-
exclusion criteria (congenital anoma- pertension of the newborn (n 24), pelvic disproportion (13.8%), and ma-
lies affecting the cardiorespiratory and infection (n 1314). The overall ternal disorders (11.7%). For 11.6% of
system or chromosomal aberrations, incidence of TTN was 5.9 cases per ECSs, the indications for surgery in-
n 1871; asphyxia, n 1603; fetal hy- 1000 singleton live births in our study cluded other malpresentations, pla-
drops, n 8; mothers with alcohol or cohort. cental and umbilical cord complica-
drug abuse, n 512), data for the re- The main characteristics of the study tions, and pregnancy disorders. In
maining 9352 newborns were matched cohort and newborns with TTN are 13.6% of cases, however, the indication

PEDIATRICS Volume 125, Number 3, March 2010 e579

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TABLE 1 Basic Perinatal Characteristics of Study Cohort and Newborns with TTN
GA, mean SD, wk
Birth weight
Mean SD, g
10th percentile, %
90th percentile, %
Apgar score at 5 min, median (range)
Umbilical artery pH, mean SD
Male, %
ECS, %
a
Data on term singletons obtained from Federal Ofce for Quality Assurance reports from 2001 to 2005.
b 2 test between TTN group and German population.
for ECS was not dened, and we might
have evidence to suggest that CS at
maternal request may account for this
gure.
The TTN rate was linked inversely to GA
and decreased with advancing GA from
37 completed weeks onward (Fig 2).
The overall frequency of ECS was 42.2%
among newborns with TTN, compared
with 9.2% among term singletons in
FIGURE 2
Relative risk of TTN from 37 to 42 weeks of gestation for newborns delivered vaginally or through
secondary CS (labor group) or ECS (no-labor group). *Crude relative risk of TTN in newborns delivered
through ECS (no-labor group), compared with GA-matched newborns after spontaneous vaginal de-
livery and secondary CS (labor group).
from week 42 to week 37; in the no-
Total TTN Germany Pb labor group, there was a signicant in-
(N 13 346) (N 1423) (N 2 675 841)a
crease in the incidence of TTN with de-
39.1 1.4 38.8 1.4
creasing GA from 40 to 37 weeks (P for
3340 598 3351 556 trend .01). ECSs at GAs of 40 weeks
19.6 15.8 9.2 .001 showed signicantly greater risk for
12.5 13.5 10.6 .001
9 (710) 9 (710)
TTN, compared with those at GAs of
7.28 0.07 7.27 0.07 41 weeks (37 weeks of gestation: OR:
56.4 60.3 51.4 .001 4.8 [95% CI: 3.7 6.3]; 38 weeks of ges-
20.7 42.2 9.2 .001
tation: OR: 3.7 [95% CI: 2.9 4.8]; 39
weeks of gestation: OR: 3.4 [95% CI:
2.3 4.7]; 40 weeks of gestation: OR: 2.0
[95% CI: 1.33.0]). Infants born vagi-
the German population (P .001) (Ta- nally or through secondary CS showed
ble 1). When data were analyzed ac- no increased risk for TTN.
cording to the presence or absence of Data on clinical outcomes of new-
labor and GA separately, the rate of
borns with TTN were compared be-
TTN was greatly increased at each GA
tween the labor and no-labor groups,
from 37 to 40 weeks for the no-labor
as summarized in Table 2. Nearly one
group, compared with the labor group
half of the infants with TTN needed
(Fig 2). In the labor group, the preva-
supplemental oxygen, irrespective of
lence of TTN remained nearly un-
the mode of delivery. However, the
changed between 10.6% and 13.0%
absence of labor before birth was
signicantly associated with longer
duration of oxygen supplementation
(P .02) and higher rates of contin-
uous positive airway pressure ther-
apy (P .05) and mechanical venti-
lation (P .002). Infants with TTN
after ECS were more likely to develop
pulmonary air leaks, compared with
newborns after previous labor (2.8%
vs 1.0%; P .05). No cases of extra-
corporeal membrane oxygenation
therapy and no neonatal deaths were
recorded.
The duration of oxygen supplementa-
tion also was correlated inversely with
the duration of labor before birth (r
0.151; P .028). This correlation
remained signicant with controlling
for GA, birth weight, and gender of
the newborn (P .046). Multivariate
regression analysis of outcome vari-
ables, controlled for perinatal con-
founders, conrmed a signicant im-
pact on duration of oxygen therapy for
ECS (OR: 2.2 [95% CI: 1.117.9]; P
.05). Other outcome variables were

e580 TUTDIBI et al
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TABLE 2 Therapy and Outcomes of Infants With TTN and Role of Labor
All Infants With TTN
Oxygen supplementation, n (%)
Duration of oxygen supplementation,
mean SD, d
Mechanical ventilation, n (%)
Continuous positive airway pressure
therapy, n (%)
Pulmonary air leaks, n (%)
Antibiotic therapy, n (%)
Duration of hospital stay, median
(5th to 95th percentile range), d
Obstetric data were available for 76% of newborns with TTN (1081 of 1423 newborns) after maternal-neonatal data
matching. NS indicates not signicant.
a Pearson 2 test.
b Nonparametric Mann-Whitney U test.
found not to be inuenced by con-
founders and mode of birth.
DISCUSSION
The present study indicates the posi-
tive impact of labor on respiratory out-
comes among infants with TTN, in
agreement with previous studies; the
absence of labor in infants with TTN
was associated with higher rates of
continuous positive airway pressure
therapy, mechanical ventilation, and
complications from pulmonary air
leaks and longer duration of oxygen
supplementation, in comparison with
infants with TTN who were delivered
after having been exposed to uterine
contractions. Multivariate regression
analyses, with correction for perinatal
confounders, established that the ab-
sence of labor increased the duration
of oxygen supplementation by a factor
of 2. The duration of labor was linked
signicantly to the duration of oxygen
supplementation (r 0.151; P
.028). The length of hospital stay for
infants presenting with TTN did not dif-
fer on the basis of labor.
We suggest that both the incidence and
severity of TTN are affected by labor
before birth. TTN is the most common
cause of neonatal respiratory distress
in term neonates. Delayed resorption
of fetal lung uid after delivery is con-
sidered the main pathophysiological
PEDIATRICS Volume 125, Number 3, March 2010
Labor Group No-Labor Group
(N 1423) (N 625) (N 456)
580 (40.7) 258 (41.1) 208 (45.7)
1.3 0.9 1.1 0.6 1.3 1.1
60 (4.2) 22 (3.5) 36 (7.9)
58 (4.1) 17 (2.7) 26 (5.7)
22 (1.5) 6 (1.0) 13 (2.8)
307 (21.6) 177 (28.3) 112 (24.5)
5 (115) 5 (111) 5 (114)
factor in TTN.8,9 Defects in active pulmo-
nary epithelial sodium transport,10
mild pulmonary immaturity and tran-
sient surfactant deciency,11 and myo-
cardial left-heart failure attributable
to asphyxia have been discussed as the
main potential pathogenic factors op-
erative in dysfunction of postnatal lung
liquid clearance and TTN pathophysio-
logical processes.12 Studies on genetic
risk factors for TTN demonstrated that
certain functional polymorphisms in
the -adrenergic receptor encoding
genes are associated with higher TTN
risk.1315 Rapid clearance of fetal lung
uid during postnatal lung adaptation
is largely correlated with the onset of
labor before birth.16 Labor enhances
the release of catecholamines in ma-
ternal and fetal circulation, resulting
in -adrenergic receptormediated
upregulation of surfactant synthesis
and transepithelial sodium ion trans-
port, with subsequent uid reabsorp-
tion, in the neonatal lung. Infants deliv-
ered through ECS often are deprived of
this labor-related physiological stress
response pattern at birth and conse-
quently experience failure of postnatal
respiratory transition.17 According
to our study results from a large,
population-based, birth cohort, the
rate of TTN was 0.59% (1423 cases per
239 971 infants), which is comparable
to the previous reports by Morrison
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ARTICLES
et al18 (5.7 cases per 1000 infants) and
P Riskin et al19 (7.2 cases per 1000 in-
fants). The inclusion of neonates with
.141a
.02b
TTN with GAs of 35 weeks might ex-
plain the higher incidence of TTN in the
.01a study by Riskin et al.19
.05a
We found that TTN risk was associ-
.05a ated strongly with the mode of deliv-
NSa
NSb
ery and GA. The overall rate of ECS
was substantially higher in new-
borns with TTN, compared with term
singletons in the German population
(42.2% vs 9.2%; P .001). Other risk
factors for TTN were male gender
and inappropriate birth weight for
GA. Our results agree with previously
reported studies that demonstrated
the association of ECS with higher
risk for neonatal respiratory mor-
bidity and the importance of timing
of ECS to GA of 39 weeks, to de-
crease the TTN risk.18,2025 In line with
the report by Richardson et al,26 how-
ever, ECS performed even at a GA of
40 completed weeks was associated
with a signicant increase in the TTN
rate in our study, which demon-
strates the benecial effects of labor
in the mechanisms mediating post-
natal lung liquid clearance.
Our study has several limitations.
The main limitation is that the peri-
natal registers used for this study
may contain coding inaccuracies and
data entry errors, which are inher-
ent in all population-based analyses.
In our study, 26.8% of all data sets for
infants who were admitted to the
neonatal ward could not be con-
nected with maternal data (for new-
borns with TTN, the matching rate
was 76%). We are aware of the pos-
sibility that the results might be bi-
ased by the high loss rate. However,
basic validation analyses of the main
maternal and neonatal characteris-
tics and outcome variables for all
9352 neonates and the 6843 matched
newborns demonstrated no signi-
e581
cant differences, which indicated
that the ndings are robust.
Despite these limitations, the strengths
of our study are the large number
of term newborns from a 5-year,
population-based cohort, the maternal
and obstetric variables available for
analysis, and the fact that infants with
TTN were selected accurately after exclu-
sion of other predetermined causes of
respiratory distress, such as perinatal
infection, meconium aspiration syn-
drome, asphyxia, and congenital anoma-
lies. Our main concern was the compara-
bility of a large number of newborns with
validated TTN differentiated according to
the mode of delivery.
CONCLUSIONS
The main nding of the present study
is that the mode of birth and the ab-
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According to the analyses of our data
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that awaiting the onset of labor before
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and an uneventful delivery without
complications. Therefore, a growing
number of mothers tend toward ECS.
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women should be given reliable in-
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clear medical indication or benet to
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is planned, we suggest, on the basis
of our ndings, that CS be postponed
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 Impact of Labor on Outcomes in Transient Tachypnea of the Newborn:
Population-Based Study
Erol Tutdibi, Katharina Gries, Monika Bcheler, Bjorn Misselwitz, Rolf L. Schlosser
and Ludwig Gortner
Pediatrics 2010;125;e577; originally published online February 15, 2010;
DOI: 10.1542/peds.2009-0314
Updated Information & including high resolution figures, can be found at:
Services /content/125/3/e577.full.html
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
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 Impact of Labor on Outcomes in Transient Tachypnea of the Newborn:
Population-Based Study
Erol Tutdibi, Katharina Gries, Monika Bcheler, Bjorn Misselwitz, Rolf L. Schlosser
and Ludwig Gortner
Pediatrics 2010;125;e577; originally published online February 15, 2010;
DOI: 10.1542/peds.2009-0314

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/125/3/e577.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2010 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on May 15, 2017