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OBSTETRICS

The efficacy of early amniotomy in nulliparous

labor induction: a randomized controlled trial
George A. Macones, MD; Alison Cahill, MD; David M. Stamilio, MD; Anthony O. Odibo, MD
OBJECTIVE: The purpose of this study was to assess whether early am-

niotomy reduces the duration of labor or increases the proportion of

subjects who are delivered within 24 hours in nulliparous patients who
undergo labor induction.
STUDY DESIGN: We performed a randomized controlled trial that com-

pared early amniotomy to standard management in nulliparous labor inductions. Inclusion criteria were nulliparity, singleton, term gestation,
and a need for labor induction. Subjects were assigned randomly to
early amniotomy (artificial rupture of membranes, 4 cm) or to standard treatment. There were 2 primary outcomes: (1) time from induc-

tion initiation to delivery and (2) the proportion of women who delivered
within 24 hours.
RESULTS: Early amniotomy shortens the time to delivery by 2 hours

(19.0 vs 21.3 hours) and increases the proportion of induced nulliparous

women who deliver within 24 hours (68% vs 56%). These improvements in
labor outcomes did not come at the expense of increased complications.
CONCLUSION: Early amniotomy is a safe and efficacious adjunct in nul-

liparous labor inductions.

Key words: amniotomy, nulliparous labor induction

Cite this article as: Macones GA, Cahill A, Stamilio DM, et al. The efficacy of early amniotomy in nulliparous labor induction: a randomized controlled trial. Am J
Obstet Gynecol 2012;207:403.e1-5.

ates of labor induction are rising.

Recent data from the National Center for Health Statistics demonstrate an
induction rate of 22% in 2006, which
was more than double what it was in
1990 and impacted 900,000 births in
the United States that year.1 Although
many recent studies have offered evidence for the improvement in methods
for labor induction, 2-7 the induction of
labor remains a significant risk factor for
cesarean delivery,8,9 which highlights the
critical need for additional tools to refine
induction practice.
Amniotomy, generally thought to be
low-tech, inexpensive, and safe, has received little research attention, and stud-

From the Department of Obstetrics and

Gynecology, Washington University in St. Louis
School of Medicine, St. Louis, MO.
Received Feb. 27, 2012; revised June 1, 2012;
accepted Aug. 21, 2012.
The authors report no conflict of interest.
Reprints: George A. Macones, MD, Professor
and Chair, Department of Obstetrics and
Gynecology, Washington University in St Louis,
School of Medicine, 4911 Barnes Jewish
Hospital Plaza, St. Louis, MO 63110.
maconesg@wustl.edu.
0002-9378/$36.00
2012 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2012.08.032

ies to date have neglected to investigate

the efficacy of amniotomy in nulliparous
women, despite the fact that more inductions are performed in nulliparous
women than their multiparous peers.1
Based on clinical trials from those in
spontaneous labor,10 early amniotomy
timing in labor inductions may shorten
the duration of labor. Clinical concern
for the rare complications of umbilical
cord prolapse and theoretic concerns
that rupturing the membranes earlier
will lead to a longer overall duration of
rupture of membranes with potentially
increased rates of chorioamnionitis,
neonatal sepsis, and neonatal intensive
care unit (NICU) admission have limited the empiric use of the practice of
amniotomy in nulliparous labor inductions without level I evidence to
support it.
The specific aim of this study was to
assess whether early amniotomy, defined
as artificial rupture of the membranes, at
4-cm dilation, reduces the duration of
labor or increases the proportion of subjects delivered within 24 hours in term
nulliparous patients who undergo labor
induction. We also sought to assess the
safety of early amniotomy, as measured
by adverse obstetric outcomes and measures of maternal and neonatal infectious morbidities.

M ETHODS
We performed an unblinded, randomized controlled trial at Washington University in St. Louis and the University of
Pennsylvania with approval from the Institutional Review Boards at both institutions. Inclusion criteria for this clinical
trial were nulliparity, singleton, term
gestation (defined as 37 weeks 0 days),
and a need for labor induction as determined by the treating physician. Exclusion criteria included HIV infection or
cervical dilation of 4 cm at admission
examination.
Eligible subjects were approached by
trained research nurses and were offered
enrollment into the clinical trial. Patients
who consented were then randomly assigned to early amniotomy, which was
defined as artificial rupture of the membranes at 4 cm or to standard management, which was amniotomy at 4 cm
dilation. In the early amniotomy group,
amniotomy was performed as early as
could be done safely. Decisions about the
exact timing of rupture (after random
assignment) were made by a team that
included residents, fellows, and attendings. There were no specific instructions
given regarding the timing of amniotomy
in the standard treatment group; this decision was left to the treating physicians. The

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FIGURE

Flowchart
749 assessed for eligibility

164 excluded
84 not meeting inclusion criteria
80 refused to participate
0 other reasons

585 randomized

292 assigned to early amniotomy

270 received intervention as assigned
22 did not receive assigned intervention
(Clinical concern)

293 assigned to standard management

280 received intervention as assigned
13 did not receive assigned intervention
(Clinical concern)

0 lost to follow-up

0 lost to follow-up

292 included in analysis

0 excluded from analysis

293 included in analysis

0 excluded from analysis

Macones. Early amniotomy in nulliparous labor induction. Am J Obstet Gynecol 2012.

primary method of induction was at the

discretion of the treating physician, as were
all other intrapartum/postpartum decisions. Random assignment was accomplished centrally. A permuted block
randomization procedure was used to
formulate assignment lists to assure close
to equal numbers of subjects in each treatment group. A uniform block size of 4 was
used.
There were 2 primary outcomes. The
first was time from initiation of induction, defined as time at delivery of the
first induction method to delivery. The
second was the proportion of women delivered within 24 hours from the initiation of induction. Although it may seem
unusual to have 2 primary endpoints, we
believed that both were equally clinically
relevant and should be treated as primary outcomes. This decision was made
a priori. We also assessed a number of
403.e2

secondary endpoints that included cesarean delivery rates and indications for
cesarean delivery, chorioamnionitis (oral
temperature 38C during labor), postpartum fever (oral temperature 38C on
2 separate occasions 6 hours apart, 24
hours from delivery), wound infection
(defined as purulent discharge from the
incision), endomyometritis (defined as
fundal tenderness and fever that require
treatment with antibiotics), NICU admission, and suspected neonatal sepsis. Trained
research nurses collected all baseline information, information on the course of labor,
and information on maternal and neonatal
outcomes.
Statistical analyses were performed
with the intent-to-treat principle. Continuous outcomes were compared with
the use of the Student t test or MannWhitney U dependent on their distributions; dichotomous outcomes were as-

American Journal of Obstetrics & Gynecology NOVEMBER 2012

sessed with 2 tests or Fisher exact test

where appropriate. Time to delivery was
not normally distributed and was compared with the use of the Mann-Whitney
U test. Relative risks by group and 95%
confidence intervals (CIs) were estimated for the percent of women who delivered within 24 hours and each of the
secondary outcomes. Our sample size
estimate was based on 1 of our primary
outcomes: the proportion of women
who delivered within 24 hours. We assumed an alpha error of .05, a beta error
of .20 (or 80% power), an incidence of
delivery within 24 hours of 50% based on
published data, a minimum detectable
relative risk of 0.75, and a 1:1 allocation
ratio. With these assumptions in mind,
we estimated that we would need 290
subjects per group. This strategy for
sample size calculation gave us tremendous power for our second primary outcome, time to delivery (a continuous
measure). Specifically, we estimated a
priori that we had 95% power to detect a
2-hour reduction in time to delivery.

R ESULTS
Seven hundred forty-nine women were
screened for eligibility; 84 women (11.2%)
were deemed ineligible by exclusion criteria. Of the 635 eligible nulliparous women,
585 women (92%) consented and were assigned randomly (Figure); 292 women
were assigned to the early amniotomy
group, and 293 women were assigned to
standard treatment. Those who agreed to
participate and those who did not were
similar in terms of baseline characteristics
(age, gestational age, preexisting medical
conditions). The groups were well-balanced with regards to demographics and
maternal medical conditions; the mean
gestational age at induction was similar between the groups (Table 1). The admission
cervical dilation was also similar between
the groups. Likewise, the indications for labor induction were similar between the
groups. The 2 most common indications
for induction were 40-week gestations
and gestational hypertension/preeclampsia. The other category for indication for
induction had a variety of uncommon indications for induction, which included
maternal request/social factors (eg, dis-

Obstetrics

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tance from hospital) and oligohydramnios
(Table 2).
Methods for induction were similar
between the early amniotomy and standard treatment groups. Most women received misoprostol; approximately 30%
of the women received a Foley bulb. The
induction method categories are not mutually exclusive, because many women received multiple agents. In fact, 73% of
women in both groups received 1 agent
for induction. As expected, with regards to
timing of amniotomy, the early amniotomy group was ruptured earlier than
the standard treatment group. Twentytwo women who were assigned randomly
to early amniotomy were ruptured after 4
cm of dilation; 13 women who were assigned randomly to standard treatment
were ruptured at 4 cm.
The primary results of this study are
given in Table 3. The average time from
the start of induction to delivery was
shortened by slightly 2 hours in the
early amniotomy group (19.0 vs 21.3
hours, respectively; P .04) compared
with those with standard treatment. This
difference in length of labor occurred
mainly in the first stage of labor, which
was defined as time from random assignment to complete cervical dilation. A
higher proportion of women in the early
amniotomy group were delivered within
24 hours of the initiation of induction
(68% vs 56%, respectively; P .002).
Despite these differences in length of labor and delivery within 24 hours, there
was no difference in the rate of cesarean
deliveries. The rate of chorioamnionitis
was increased numerically in the early
amniotomy group (11.5% v. 8.5%, respectively; P .22), although this difference was not statistically significant.
Likewise, there were 2 cord prolapses in
the early amniotomy group, and none in
the standard treatment group.
Selected neonatal outcomes are shown
in Table 4. There was no increase in the rate
of confirmed or suspected neonatal sepsis
or admission to the special care nursery or
NICU in women who underwent early
amniotomy compared with those who experienced standard care. The infants born
to women with cord prolapse both did
well, with umbilical arterial pH 7.20 and
5-minute Apgar score.

Research

TABLE 1

Baseline characteristics
Early amniotomy
(n 292)

Variable

Standard therapy
(n 293)

P value

Maternal age, y

22.7 5.8

23.3 6.2

.17

African American race, %

72

68

.30

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

Diabetes mellitus, %

3.9

3.5

.81

5.2

.32

..............................................................................................................................................................................................................................................

Chronic hypertension, %

7.2

..............................................................................................................................................................................................................................................
2a

Body mass index, kg/m

28 4.2

28 3.9

.90

GBS, %

29

30

.66

Pitocin, %

93

93

.87

Misoprostol, %

67

69

.70

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

Cervidil, %

6.8

8.4

.45

..............................................................................................................................................................................................................................................

Foley bulb, %

27

30

.43

More than 1 agent, %

73

73

.80

Epidural anesthesia, %

92

94

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

.88

..............................................................................................................................................................................................................................................
a

Admission dilation, cm

1.1 1.03

1.1 0.97

.54

Dilation at rupture of membranes, cm

3.2

7.4

.001

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
a

Station at rupture of membranes

1 1.2

1 1.5

.50

..............................................................................................................................................................................................................................................
a

6.2 3.0

Cervical examinations, n

5.9 3.4

.67

..............................................................................................................................................................................................................................................
a

3323 516

Birthweight, g

3311 566

.78

..............................................................................................................................................................................................................................................
a

39.7 1.4

Gestational age, wk

39.5 1.4

.16

..............................................................................................................................................................................................................................................

GBS, Group B streptococcus.

a

Data are given as mean SD.

Macones. Early amniotomy in nulliparous labor induction. Am J Obstet Gynecol 2012.

C OMMENT

Although these differences in duration

of labor and proportion of women delivered within 24 hours may seem to be intermediate outcomes, we would argue
that these are good surrogates for both
maternal and neonatal outcomes. For
example, it has been well-documented
that the length of labor is correlated directly with maternal chorioamnionitis,
postpartum fever, and neonatal infec-

The goal of our study was to assess the

efficacy and safety of early amniotomy in
nulliparous women who undergo labor
induction. The results of this clinical trial
indicate that early amniotomy shortens
labor by approximately 2 hours, increases the proportion of women delivered within 24 hours, but does not impact the rate of cesarean deliveries.
TABLE 2

Indications for induction

Variable

Early
amniotomy, %

Standard, %

P value

40 wk

40

39

.83

Maternal medical indication

13

14

.72

Gestational hypertension/preeclampsia

29

27

.63

.63

12

13

.63

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

Intrauterine growth restriction

..............................................................................................................................................................................................................................................

Other

..............................................................................................................................................................................................................................................

Macones. Early amniotomy in nulliparous labor induction. Am J Obstet Gynecol 2012.

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TABLE 3

Maternal and labor outcomes

Outcome

Early
amniotomy
(n 292)

Standard
(n 293)

Randomization at delivery, hra

19.0 9.1

21.3 10.1

Delivery at 24 hr, %

68

56

0.72

0.590.89

.002

Cesarean delivery, %

41

40

1.03

0.850.25

.75

Amnioinfusion, %

19

19

1.02

0.731.42

.87

Chorioamnionitis, %

11.5

1.35

0.832.21

.22

Cord prolapsed, %

0.7

Abruption, %

0.4

0.6

0.55

0.056.03

.62

Postpartum hemorrhage, %

8.2

10.1

0.81

0.481.36

.44

Relative
risk

95% CI

P
value
.04

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

8.5

..............................................................................................................................................................................................................................................

.13

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

CI, confidence interval.

a

Data are given as mean SD.

Macones. Early amniotomy in nulliparous labor induction. Am J Obstet Gynecol 2012.

tion.11-13 In addition, a 2-hour difference in labor length has important implications for resource utilization at the
hospital level. For example, a 2-hour difference in time to delivery across many
inductions could lead to a decrease in
staffing of a labor and delivery unit. Last,
there is likely enhanced patient satisfaction with shorter labors as well.
The shorter duration of labor must be
weighed against both maternal and neonatal safety concerns. There were a
greater number of cases of maternal chorioamnionitis in the early amniotomy
group, although this difference was not
statistically significant. For this study,
chorioamnionitis was defined purely on
the basis of fever in labor. Given that fever is an objective measure, we do not
believe that unblinding differentially affected the ascertainment of this outcome. Importantly, this numeric difference in chorioamnionitis did not lead to
an increase in the rate of suspected neo-

natal sepsis or NICU admission, and

there were no serious maternal consequences as a result of chorioamnionitis.
Still, future studies should focus on the
occurrence of chorioamnionitis with
early amniotomy. There were also 2 cord
prolapses in the early amniotomy group
and none in the standard treatment
group. Interestingly, one of the cord prolapses occurred in a patient in the early
amniotomy group who actually was ruptured after 4 cm of dilation. Still, the occurrence of cord prolapse is concerning
and warrants further study.
Although there has been work on the
role of amniotomy in spontaneous labor,14 surprisingly, there has been little
previous work on the role of early amniotomy in the context of labor induction. There have been several clinical trials that have compared the combination
of amniotomy and oxytocin with other
methods of induction,15 but no studies
that we are aware of that focus exclu-

TABLE 4

Neonatal outcomes
Outcome

Early
Relative
amniotomy Standard risk
95% CI

P value

5-minute Apgar score

8.6

8.6

Suspected neonatal sepsis, %

9.7

11.1

0.87

0.541.41 .58

.72

Special care nursery admission, % 13.6

15.0

0.90

0.611.35 .63

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

CI, confidence interval.

Macones. Early amniotomy in nulliparous labor induction. Am J Obstet Gynecol 2012.

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American Journal of Obstetrics & Gynecology NOVEMBER 2012

sively on the timing of amniotomy in labor induction. Amniotomy has been

well-studied in the context of those
women in spontaneous labor, which included the active management of labor;
however, the work on active management of labor may not be generalized
necessarily to those women whose labor
is induced.16,17 Fraser et al10 performed a
randomized clinical trial of amniotomy
in nulliparous women in spontaneous
labor. In that study, early amniotomy reduced the occurrence of dystocia (defined as 4 hours of cervical dilation of
0.5 cm/hr) and shortened the first
stage of labor by 136 minutes. The benefit of amniotomy was greatest in women
with 3-cm initial dilation. A recent Cochrane review summarized the available
information on early amniotomy in
spontaneous labor.14 This pooled analysis did not support the notion that early
amniotomy shortened the first stage of
labor or reduced the rate of cesarean deliveries. The authors of this Cochrane review did suggest that additional research
was needed.
Our study has some notable strengths
and limitations. First, our randomization strategy effectively balanced the
study groups with respect to potentially
confounding effects and, more importantly, maximally balanced them on
unmeasured confounders. Second, the
study is relatively large in size compared
with many other studies of labor induction, which allowed us to reach an adequate sample to test our primary hypothesis. Third, we included a diverse
group of patients with various indications for induction and various methods
for induction, lending to the generalizability of the results. Last, our simple
trial design with broad inclusion/exclusion criteria and treating physician decision-making should enhance both generalizability and the translation from
efficacy in a study setting to real world
effectiveness. There are some potential
weaknesses that we believe deserve careful consideration. For practical reasons,
this study was unblinded, which could
have impacted the study results both
with the potential for unequal distribution of cointerventions and the assessment of the secondary outcomes. We

Obstetrics

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were reassured that the potential impact
of cointerventions from practitioners
because of group assignment based on
the primary outcomes were likely minimal; there were no differences between
the groups in rates of any of the induction agents that were used alone or in
combination. With regard to the secondary outcomes, it is possible that the
knowledge of treatment assignment may
have influenced our somewhat subjective newborn infant outcomes. We believe that this potential bias, if present,
would have resulted in more neonates in
the early amniotomy group being admitted to the special care nursery, thus inflating the relative risk for NICU admission. The fact that we did not observe a
difference in admissions is reassuring.
Our sample size, although sufficiently
large to test our hypothesis and compared with many studies of labor induction, was limited with respect to the confident assessment of differences in rare
outcomes, such as cord prolapse. Approximately 10% of subjects in the early
amniotomy group were ruptured after 4
cm; likewise, some women were assigned
randomly to standard treatment were
ruptured earlier. This misclassification is
likely random and would therefore likely
bias our results towards the null.
With these strengths and limitations in
mind, this study supports the following
conclusions. First, relative to standard

treatment with later amniotomy, early amniotomy shortens the time to delivery by
2 hours and increases the proportion of
induced nulliparous women who were delivered within 24 hours. Based on these
data, early amniotomy, when deemed
safe by the practitioner, may be a useful
adjunct in nulliparous labor inductions and may be incorporated into induction algorithms.
f
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