Prolonged Pregnancy: Induction of Labor and

Cesarean Births
JAMES M. ALEXANDER, MD, DONALD D. MCINTIRE, PhD, AND
KENNETH J. LEVENO, MD
Objective: To determine the effects of labor induction on
cesarean delivery in post-date pregnancies.
Materials and Methods: A total of 1325 women who
reached 41 weeks gestation between December 1, 1997, and
April 4, 2000, and who were scheduled for induction of labor
at 42 weeks were included in this prospective observational
study. Cesarean delivery rates were compared between those
women who entered spontaneous labor and those who
underwent induction. Women with any medical or obstetric
risk factors were excluded. A power analysis was performed
to determine how many patients would be required to show
no effect of labor induction on cesarean delivery with a of
.8 and an of .05. Approximately 5200 patients would be
required, taking an estimated 28 years to accrue at our
institution.
Results: Admission to delivery was longer (5.7 compared
with 11.1 hours, P .001) and more likely to extend beyond
10 hours (55 compared with 24%, P .001) in the induction
group. Cesarean deliveries were increased in the induced
group (19 compared with 14%, P <<< .001) due to cesarean for
failure to progress (14 compared with 8%, P <<< .001). Inde-
pendent risk factors for cesarean delivery included nullipar-
ity, undilated cervix prior to labor, and epidural analgesia.
Correction for these risk factors using logistic regression
analysis revealed that it was the risk factors, and not induc-
tion of labor per se, that increased cesarean delivery.
Conclusion: Risk factors intrinsic to the patient, rather
than labor induction itself, are the cause of excess cesarean
deliveries in women with prolonged pregnancies. (Obstet
Gynecol 2001;97:9115. 2001 by The American College of
Obstetricians and Gynecologists.)
The rate of labor induction has been rising steadily in
the United States since at least 1989 when data on this
obstetric practice rst became available on the birth
certicate.
1
Currently, about one in ve pregnant
women undergo labor induction, with the highest rates
of induction occurring in women with the longest
gestations (25% of women who reach 41 weeks). This
increase in induction has intensied a long-standing
obstetric concern that induction of labor leads to an
increase in cesarean births. During the 1990s, there were
at least eight published reports
29
that dealt specically
with the effects of labor induction on cesarean rates and
numerous other reports dealing with pharmacologic
methods of cervical ripening, primarily involving
prostins.
10
With few exceptions, these reports dealing
with the effects of labor induction on cesarean delivery
included a heterogeneous group of patients with many
potentially confounding risk factors for cesarean deliv-
ery. For example, most reports included a relatively
wide spectrum of gestational ages (eg, 3741 weeks),
multiple indications for induction such as preeclampsia
(which undoubtedly inuences the conduct of the in-
duction), and differing methods of labor stimulation
within a given study cohort. The multiplicity of these
factors makes it difcult to determine if it is the induc-
tion of labor per se, or the patient circumstances under
which induction is undertaken, that inuence the re-
sulting cesarean rate.
Our purpose was to measure the effects of labor
induction in a homogeneous cohort of women, all of
whom were scheduled for induction within a 6-day
gestational age window (41 to 41-
6
7 days) and in whom
the only complication was prolonged pregnancy. Im-
portantly, induction and labor management were uni-
form.
Materials and Methods
Between December 1, 1997, and April 4, 2000, women
whose pregnancies reached 41 completed weeks were
seen in a special post-term clinic held at Parkland
Hospital. Information about each patients pregnancy,
labor course, and neonatal outcome was prospectively
entered into a computerized database maintained by a
research nurse. This study was limited to women with
From the University of Texas Southwestern Medical Center at Dallas,
Dallas, Texas.
911 VOL. 97, NO. 6, JUNE 2001 0029-7844/01/$20.00
PII S0029-7844(01)01354-0
singleton cephalic presentations. Women with an
anomalous fetus, diabetes, prior cesarean delivery, or
other medical or obstetric indications for delivery were
excluded. Gestational age was conrmed to be 41 weeks
if the stated last menses agreed with an ultrasound
examination prior to 26 weeks or the last menses was
supported by fundal height measurements between 18
and 30 weeks gestation.
11
The management protocol for women who reach 41
weeks at our institution begins with referral to a spe-
cialized clinic staffed by a maternal-fetal medicine spe-
cialist (JA). Women identied to be 41 weeks based on
gestational age landmarks or ultrasound were sched-
uled for a two-stage induction attempt beginning at
41-
6
7 weeks. All women received a cervical examination
by either an MD or MD-supervised midwives and
nurse practitioners during the clinic visit. The rst stage
included installation of 0.5 mg prostaglandin E
2
gel into
the cervix the afternoon before scheduled induction of
labor with oxytocin (stage 2) the next morning. Women
who did not develop sustained uterine contractions
with intracervical prostaglandin received oxytocin ac-
cording to a previously published schedule.
12
Briey,
an oxytocin infusion was begun at 6 mU/min and
increased by 6 mU/min every 40 minutes to a maxi-
mum of 42 mU/min. Labor management was standard-
ized and included cervical examinations every 23
hours, with amniotomy when cervical dilatation
reached 34 cm, followed by internal uterine and fetal
heart rate (FHR) monitoring. The uterine activity goal
for labor stimulation was more than 200 Montevideo
units. Failure to progress was diagnosed and cesarean
delivery performed when cervical dilatation or fetal
descent ceased for 24 hours despite adequate uterine
activity.
Statistical analysis was by Pearson chi-square, Man-
telHaenszel chi-square for trend,
13
Student t test, and
multiple logistic regression. The variables entered into
the logistic regression model were selected a priori as
variables known to be related to cesarean delivery.
These included cervical dilation (modeled as zero or
larger), parity (nulliparity to multiparous), epidural
(present or absent), gestational age (a continuous vari-
able of completed integral weeks), and induction (in-
duced or spontaneous). Results are presented as
means standard deviation, number and percent, and
odds ratios (OR) with 95% condence intervals (CI).
Wilcoxon rank sum methods were used for non-
normally distributed data and are shown as median
values with quartiles. All P values are two-sided and
were considered statistically signicant if less than .05.
SAS version 8 (SAS Institute, Cary, NC) was used.
Results
A total of 1325 women with pregnancies 41 to 41-
6
7
weeks were prospectively enrolled in this observational
study. A total of 687 (52%) women entered spontaneous
labor before their scheduled inductions and the remain-
der underwent labor induction. Shown in Table 1 are
selected demographic characteristics for women who
had spontaneous labor compared with those whose
labor was induced. There were no signicant differ-
ences except for nulliparity, which was noted for 54% of
induced pregnancies compared with 49% of those with
spontaneous labor. As expected, gestational age at
delivery was approximately 4 days less, on average, in
women who entered spontaneous labor before their
scheduled inductions, compared with those who re-
quired labor induction (Table 2). Labor was longer and
epidural analgesia was more frequent in women who
underwent induction than in those with spontaneous
labor. Cesarean delivery was signicantly increased in
women with inductions; this increase was limited to
cesareans for failure to progress.
Table 1. Demographic Characteristics of Women Who
Entered Labor Before Scheduled Inductions
Compared With Those Who Actually Underwent
Induction of Labor at 42 Weeks Gestation
Characteristics
Spontaneous labor
n 687 (%)
Induction
n 638 (%) P
Maternal age (y)* 24.4 5.3 24.0 5.3 .16
Race .14
Hispanic 553 (80) 498 (78)
Black 97 (14) 85 (13)
White 27 (4) 41 (6)
Other 10 (1) 14 (2)
Nulliparity 336 (49) 347 (54) .05
* Mean standard deviation.
Table 2. Selected Intrapartum Characteristics of Women
Entering Spontaneous Labor Before Scheduled
Induction Compared With Those Undergoing
Scheduled Induction at 42 Weeks Gestation
Characteristics
Spontaneous labor
n 687 (%)
Induction
n 638 (%) P
Gestational age at delivery
(wk)
41-
3
7 42-
0
7 .001
Epidural analgesia 159 (23) 200 (31) .001
Admit to delivery (h)* 5.7 (2.8, 9.7) 11.05 (6.9, 16.4) .001
10 h 164 (24) 351 (55) .001
Second stage 2 h 39 (6) 33 (5) .69
Forceps delivery 51 (7) 53 (8) .55
Total cesarean births 97 (14) 124 (19) .001
Failure to progress 54 (8) 87 (14) .001
Fetal distress 25 (4) 30 (5) .33
* Median with 25th and 75th quartiles shown.
912 Alexander et al Cesarean, Induction Post-term Obstetrics & Gynecology
Table 3 shows the cesarean births stratied by cervi-
cal dilatation before the onset of labor. This examination
occurred at the clinic visit where the induction was
scheduled. Using trend analysis, cesarean deliveries
were related signicantly to cervical dilatation in both
study groups. Cervical dilatation was used in this
analysis because it was more predictive of cesarean
delivery than cervical effacement or fetal head station
when analyzed using receiver operator characteristic
curves. Further analysis, using chi-square, showed that
the increase in cesarean delivery associated with induc-
tion of labor was attributable to the subgroup of in-
duced women with undilated cervices.
Logistic regression was used to adjust for cervical
dilatation, gestational age, nulliparity, and epidural
analgesia (Figure 1). The OR for cesarean delivery
associated with labor induction was 1.1 (95% CI 0.9,
1.2). Unlike labor induction, an undilated cervix, nulli-
parity, and epidural analgesia remained signicantly
associated with cesarean delivery. A power analysis
was performed to determine how many patients would
be required to show no effect of labor induction on
cesarean delivery with a of .8 and an of .05.
Approximately 5200 patients would be required, taking
an estimated 28 years to accrue at our institution.
Discussion
There are three central ndings in this analysis of the
role labor induction plays in cesarean delivery. Induc-
tion of labor, compared with spontaneous labors in
demographically comparable study groups, was asso-
ciated with a 40% increase in overall cesarean delivery
rates (from 14% to 19%) and an increase in cesarean
deliveries for failure to progress, but not fetal distress.
Associated risk factors for cesarean delivery included
an undilated cervix, epidural analgesia, more advanced
gestational age, and nulliparity. Most importantly,
when the analysis was corrected for these confounding
risk factors, labor induction per se was not related to
excess cesarean delivery. This result suggests that it is
the patients circumstances, for example, undilated cer-
vix, that increase the risk of cesarean delivery rather
than the induction itself.
It has long been accepted that induction of labor
increases the risk of cesarean delivery. We were able to
nd eight reports published in the last decade that
specically deal with the effects of labor induction on
cesarean delivery.
29
Two of these reports described
randomized trials and the others were retrospective
studies. Hannah et al
3
randomized 3407 women with
uncomplicated pregnancies at 41 weeks gestation or
longer to induction of labor or expectant management.
Induction resulted in a lower cesarean rate. However,
the increase in cesarean births in the expectantly man-
aged group was primarily due to abnormal FHR pat-
terns during antepartum fetal testing, making it difcult
to isolate the effect of labor induction, per se, on
cesarean rates. In the other randomized trial, 440 preg-
Figure 1. Odds ratios for overall cesarean delivery related to induc-
tion of labor corrected for nulliparity, cervical dilatation, gestational
age, and epidural analgesia. CI condence interval.
Table 3. Cesarean Birth Rates Stratied by Cervical Dilatation in Women Who Entered Spontaneous Labor Before Scheduled
Induction Compared With Those Who Underwent Induction at 42 Weeks Gestation
Spontaneous labor
cervical dilatation, cm (%)
Induction
cervical dilatation, cm (%)
0
n 142
1
n 233
2 or greater
n 322 P for trend
0
n 260
1
n 244
2 or greater
n 134 P for trend
Cesarean, all 28 (20) 41 (18) 28 (9) 0.001 79 (30)* 34 (14) 11 (8) .001
Failure to progress 14 (10) 22 (10) 18 (6) 0.07 60 (23)

21 (9) 6 (4) .001

Fetal distress 7 (5) 13 (6) 5 (2) 0.03 17 (7) 9 (4) 4 (3) .09
* Signicant, P .02 when compared with overall cesareans in women with zero cervical dilatation and spontaneous labor.

Signicant, P .001 for zero cervical dilatation.

VOL. 97, NO. 6, JUNE 2001 Alexander et al Cesarean, Induction Post-term 913
nancies at 41 weeks gestation were randomized, and
induction of labor had no signicant effect on cesarean
delivery but the sample size was deemed insufcient to
measure this outcome.
2
Shown in Table 4 is a summary
of the six retrospective studies published during the
1990s specically addressing the effect of labor induc-
tion on cesarean delivery.
49
Induction was linked to
excess cesarean births in four reports and unrelated in
two others. The populations studied were heteroge-
neous in terms of medical and obstetric complications
as well as demographic factors. Frequently identied
risk factors for induction-related cesarean births in-
cluded nulliparity,
4 9
unfavorable cervical dilata-
tion,
47,9
and epidural analgesia.
4,6
Our results are sim-
ilar to those of Prysak and Castronova,
6
who performed
a case-control study involving 461 pairs of women. The
increased rate of cesarean delivery in women undergo-
ing labor induction was explained by nulliparity and
undilated cervices and not by induction per se.
Our purpose was to attempt to separate the effects of
labor induction on cesarean delivery from the patient
characteristics that intrinsically impact cesarean births.
As previous studies have shown, this objective is dif-
cult to achieve. The complication for which induction is
performed may greatly affect the effectiveness of labor
stimulation and have an impact on the associated
cesarean rate. For example, in the case of hypertensive
disorders due to pregnancy, the clinical exigencies
concerning the severity of this disease would undoubt-
edly inuence the obstetricians readiness to proceed or
abandon labor induction in favor of cesarean delivery.
Similarly, gestational age is a signicant modier of the
success of labor induction with greater success linked to
advancing gestational age. The multiplicity of con-
founding factors such as these makes it difcult to
ascertain whether induction of labor based on the
patients characteristics account for the associated in-
crease in cesarean deliveries. Our study cohort was
chosen to exclude as many of these confounding factors
as possible and was mostly but not entirely successful.
For example, a 3-day difference in gestational age was
statistically linked to the cesarean delivery rate in our
study groups, even though their maximum gestational
age difference could not exceed 6 days. Such small
incremental differences make it difcult to separate the
effects of intrinsic patient characteristics on cesarean
delivery distinct from the induction of labor itself. We
are of the view, however, that the study cohort we
selected was as homogeneous as possible short of a
likely unfeasible randomized trial. Specically, to per-
form a randomized trial of induction compared with
expectant management in women with important risk
factors for cesarean delivery including undilated cervix,
nulliparity, and epidural analgesia would require 1728
women. This represents less than 5% of our prolonged
pregnancy study population and would require ascer-
tainment of over 30,000 pregnancies, a 40-year study at
our institution. In the absence of such a randomized
trial, we are left to conclude that patient circumstance,
as opposed to labor induction itself, leads to increased
cesarean delivery in prolonged pregnancy.
References
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Final data for 1998. National Vital Statistics Reports, vol. 48 no. 3.
Hyattsville, MD: National Center for Health Statistics, 2000.
2. The National Institute of Child Health and Human Development
Network of Maternal-Fetal Medicine Units. A clinical trial of
induction of labor versus expectant management in postterm
pregnancy. Am J Obstet Gynecol 1994;170:71623.
3. Hannah ME, Hannah WJ, Hellmann J, Hewson A, Milner R, Willan
A, et al. Induction of labor as compared with serial antenatal
monitoring in postterm pregnancy. N Engl J Med 1992;326:1587
92.
4. Macer JA, Macer CL, Chan LS. Elective induction versus sponta-
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Am J Obstet Gynecol 1992;166:16907.
5. Xenakis EM, Poper JM, Conway DL, Langer O. Induction of labor
in the nineties: Conquering the unfavorable cervix. Obstet Gynecol
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6. Prysak M, Castronova FC. Elective induction versus spontaneous
labor: A case-control analysis of safety and efcacy. Obstet Gynecol
1998;92:4752.
7. Seyb ST, Berka RJ, Socol ML, Dooley SL. Risk of cesarean delivery
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ship to cesarean delivery: A review of 7001 consecutive inductions.
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Table 4. Summary of Retrospective Studies Published
During the 1990s Dealing Specically With the
Effects of Labor Induction on Cesarean Delivery
Author(s) Year
Women
studied
(N)
Does induction
increase
cesarean rate?
Macer et al
4
1992 506 No
Xenakis et al
5
1997 597 Yes
Prysak and Castronova
6
1998 922 No
Seyb et al
7
1999 1561 Yes
Yeast et al
8
1999 7224 Yes
Maslow and Sweeney
9
2000 1135 Yes
914 Alexander et al Cesarean, Induction Post-term Obstetrics & Gynecology
13. Mantel N, Haenszel W. Statistical aspects of the analysis of data
from retrospective studies of disease. J Natl Cancer Inst 1959;22:
71948.
Address reprint requests to:
James M. Alexander, MD
Department of Obstetrics and Gynecology
University of Texas Southwestern Medical Center at Dallas
5323 Harry Hines Boulevard
Dallas, TX 75235-9032
E-mail: jalexa@mednet.swmed.edu
Received September 21, 2000.
Received in revised form January 9, 2001.
Accepted January 31, 2001.
Copyright 2001 by The American College of Obstetricians and
Gynecologists. Published by Elsevier Science Inc.
VOL. 97, NO. 6, JUNE 2001 Alexander et al Cesarean, Induction Post-term 915