org
OBSTETRICS
Defining failed induction of labor
William A. Grobman, MD, MBA; Jennifer Bailit, MD, MPH; Yinglei Lai, PhD; Uma M. Reddy, MD, MPH;
Ronald J. Wapner, MD; Michael W. Varner, MD; John M. Thorp Jr, MD; Kenneth J. Leveno, MD; Steve N. Caritis, MD;
Mona Prasad, DO; Alan T. N. Tita, MD, PhD; George Saade, MD; Yoram Sorokin, MD; Dwight J. Rouse, MD;
Sean C. Blackwell, MD; Jorge E. Tolosa, MD, MSCE; for the Eunice Kennedy Shriver National Institute of Child Health
and Human Development Maternal-Fetal Medicine Units Network
BACKGROUND: While there are well-accepted standards for the RESULTS: A total of 10,677 women were available for analysis. In the
diagnosis of arrested active-phase labor, the definition of a “failed” vast majority (96.4%) of women, the active phase had been reached by
induction of labor remains less certain. One approach to diagnosing a 15 hours. The longer the duration of a woman’s latent phase,
failed induction is based on the duration of the latent phase. However, a the greater her chance of ultimately undergoing a cesarean delivery
standard for the minimum duration that the latent phase of a labor (P < .001, for time both as a continuous and categorical independent
induction should continue, absent acute maternal or fetal indications for variable), although >40% of women whose latent phase lasted 18
cesarean delivery, remains lacking. hours still had a vaginal delivery. Several maternal morbidities, such as
OBJECTIVE: The objective of this study was to determine the frequency postpartum hemorrhage (P < .001) and chorioamnionitis (P < .001),
of adverse maternal and perinatal outcomes as a function of the duration increased in frequency as the length of latent phase increased.
of the latent phase among nulliparous women undergoing labor induction. Conversely, the frequencies of most adverse perinatal outcomes were
STUDY DESIGN: This study is based on data from an obstetric cohort statistically stable over time.
of women delivering at 25 US hospitals from 2008 through 2011. CONCLUSION: The large majority of women undergoing labor in-
Nulliparous women who had a term singleton gestation in the cephalic duction will have entered the active phase by 15 hours after oxytocin has
presentation were eligible for this analysis if they underwent a labor started and rupture of membranes has occurred. Maternal adverse out-
induction. Consistent with prior studies, the latent phase was determined comes become statistically more frequent with greater time in the latent
to begin once cervical ripening had ended, oxytocin was initiated, and phase, although the absolute increase in frequency is relatively small.
rupture of membranes had occurred, and was determined to end once These data suggest that cesarean delivery should not be undertaken
5-cm dilation was achieved. The frequencies of cesarean delivery, as well during the latent phase prior to at least 15 hours after oxytocin and rupture
as of adverse maternal (eg, postpartum hemorrhage, chorioamnionitis) of membranes have occurred. The decision to continue labor beyond this
and perinatal (eg, a composite frequency of seizures, sepsis, bone or nerve point should be individualized, and may take into account factors such as
injury, encephalopathy, or death) outcomes, were compared as a function other evidence of labor progress.
of the duration of the latent phase (analyzed with time both as a continuous
measure and categorized in 3-hour increments). Key words: labor induction, latent phase, outcomes
(1.007e1.298)
(1.14e110.0)
Hysterectomy, Relative risk
(1.02e2.19)
(1.04e4.79)
(1.07e10.5)
(1.09e23.0)
(1.11e50.3)
(95% CI) dystocia. The frequency of neonatal
Referent
intensive care unit (NICU) admission
.039
1.144
1.50
2.24
3.34
5.00
7.48
11.2
increased with duration of the latent
phase (Table 5).
Lastly, for sensitivity analyses, we
examined whether results differed after
6 (0.06)
1 (0.03)
2 (0.53)
1 (0.52)
2 (0.06)
N (%)
.035
phase duration were reduced (leaving
0
0
(1.044e1.104)
(1.14e1.35)
(1.30e1.81)
(1.48e2.43)
(1.69e3.27)
(1.92e4.40)
(2.19e5.92)
missing), or after adjustment for
(95% CI)
Referent
<.001
1.074
1.24
1.53
1.90
2.35
2.91
3.60
the induction was undertaken without a
medical indication (ie, an elective in-
duction), or PROM had occurred. In all
175 (1.6)
39 (1.1)
54 (1.6)
36 (1.8)
16 (1.7)
13 (3.4)
7 (3.7)
10 (5.2)
<.001
sensitivity analyses, the associations be-
Blood
N (%)
(0.90e1.01)
(0.81e1.03)
(0.73e1.04)
(0.66e1.06)
(0.60e1.07)
(0.54e1.09)
of the primary analysis (data not shown).
(95% CI)
.138
199 (5.7) 0.96
42 (4.6) 0.87
13 (3.4) 0.84
10 (5.2) 0.80
7 (3.6) 0.76
Comment
This study described several aspects of
3rd/4th
.252
(1.30e1.70)
(1.48e2.22)
(1.69e2.89)
(1.92e3.77)
(2.19e4.91)
66 (1.9) Referent
<.001
268 (2.6) 1.068
51 (2.6) 1.49
26 (2.9) 1.81
23 (6.2) 2.21
11 (5.8) 2.69
12 (6.3) 3.28
<.001
N (%)
PPH,
(1.43e1.60)
(1.70e2.03)
(2.03e2.56)
(2.43e3.24)
(2.90e4.10)
Referent
<.001
1.071
1.51
1.86
2.28
2.81
3.45
160 (17.4)
84 (22.1)
47 (24.5)
32 (16.5)
(1.14e1.16)
(1.29e1.35)
(1.46e1.57)
(1.66e1.83)
(1.88e2.13)
(2.14e2.47)
<.001
10,677 3608 (33.8) 1.047
380
192
194
3523
1997
15e17.9
9e11.9
P value
0e2.9
3e5.9
6e8.9
18
TABLE 4
Frequency of indications for cesarean delivery, stratified by phase and stage of labor
Latent phase Active phase Second stage
Latent phase, h NRFS Dystocia NRFS Dystocia NRFS Dystocia
0e2.9 [N ¼ 932] 144 (15.5) 41 (4.4) 178 (19.1) 369 (40.1) 50 (5.4) 148 (15.9)
3e5.9 [N ¼ 1025] 114 (11.1) 144 (14.0) 129 (12.6) 385 (37.6) 46 (4.5) 206 (20.1)
6e8.9 [N ¼ 787] 77 (9.8) 234 (29.7) 74 (9.4) 271 (34.4) 19 (2.4) 109 (13.9)
9e11.9 [N ¼ 433] 39 (9.0) 139 (32.1) 38 (8.8) 151 (34.9) 9 (2.1) 57 (13.2)
12e14.9 [N ¼ 207] 25 (12.1) 71 (34.3) 16 (7.7) 65 (31.4) 4 (1.9) 24 (11.6)
15e17.9 [N ¼ 115] 9 (7.8) 55 (47.8) 9 (7.8) 31 (27.0) 3 (2.6) 8 (7.0)
18 [N ¼ 109] 9 (8.3) 48 (44.0) 5 (4.6) 33 (30.3) 2 (1.8) 12 (11.0)
Data presented as N (%).
NRFS, nonreassuring fetal status.
Grobman et al. Defining failed induction of labor. Am J Obstet Gynecol 2018.
the present analysis to try to determine which 6 cm was used to define the end of If this missingness is not random, but
the association between duration of the latent labor, admission to the NICU (but related systematically to the outcome
latent phase and obstetric complications not mechanical ventilation or sepsis) was and exposure, bias may be introduced.
in the setting of labor induction. Their statistically more frequent (8.7% at 12 However, in a sensitivity analysis in
study included 509 women of mixed hours vs 6.7% at 9 hours) once 12 hours which the number of missing times was
parity and demonstrated that of the latent phase had been reached.6 reduced by >75%, the results remained
“continued labor induction allowed While that study used 6 cm to define unchanged. Also, these findings are for
some women to have vaginal deliveries,” the end of the latent phase, the results are nulliparous women and cannot be
that chorioamnionitis rose with longer similar to our study (in which 5 cm was generalized to parous women. Never-
times of the latent phase, and that major used as the terminal dilation for the theless, we believe nulliparous women
maternal and perinatal complications latent phase). are the population most in need of study,
were uncommon. They did not, howev- There are several strengths of this given their much greater chance of pro-
er, have sufficient sample size to compare study, including the size of the popula- longed labor and cesarean delivery.
more uncommon neonatal complica- tion, the quality of the data (which were Because this study was concerned with
tions, such as umbilical artery pH <7.0, abstracted by trained research personnel the length of the latent phase during
according to latent phase duration or from each chart), and the diversity of a induction, it provides no insight into the
reliably estimate the outcomes after 12 nationwide cohort. Women were latent phase during spontaneous labor.
hours of the latent phase. included with a variety of indications for Although this study occurred at many
Subsequent analyses by Simon and labor induction and with differing needs institutions, most were academic centers
Grobman4 (n ¼ 397) and Rouse et al5 for cervical ripening, and the associa- with training programs, and thus
(n ¼ 1347) included more nulliparous tions observed remained present even generalizability to community hospitals
women with latent phase durations >12 after taking these factors into account. cannot be certain. Yet, it is not evident
hours and concluded that even after 12 Conversely, factors such as maternal age why the presence of associations between
hours in the latent phase, vaginal de- or body mass index were not adjusted duration of a phase of labor and obstetric
livery occurred with reasonable fre- for, given that these may not be mere outcomes should differ based on com-
quency and complications remained covariates but causally related to both munity or academic setting. And, one
uncommon. For example, in the analysis exposure and outcome.12 could consider the many institutions and
by Simon and Grobman,4 67% of Despite these strengths, its limitations the lack of a single protocol for induction
women who had a latent phase of 12-18 should be acknowledged. Because of its or labor management as a strength of the
hours after the completion of any cer- observational nature, the associations study, as these characteristics increase
vical ripening, oxytocin initiation, and observed cannot be known to imply the applicability of the findings to other
ROM had a vaginal delivery without a causality. Even with good data quality institutions, which similarly lack a single
discernible increase in perinatal com- and control processes, particular types of standard for all aspects of labor man-
plications. In a recent analysis of data data (eg, times for multiple events agement. Other studies of labor stan-
from 9763 nulliparous women in the throughout labor) may be missing in the dards, such as those from the
Consortium of Safe Labor study, in chart and thus not able to be abstracted. Consortium of Safe Labor, also have
1.034 (1.021e1.047)
settings and not after imposition of a
1.10 (1.06e1.15)
199 (10.0) 1.22 (1.13e1.31)
98 (10.6) 1.35 (1.20e1.51)
44 (11.6) 1.49 (1.28e1.73)
29 (15.1) 1.64 (1.36e1.98)
33 (17.0) 1.81 (1.45e2.27)
standard study protocol.13 Nevertheless,
Relative risk
we cannot know with certainty whether
NICU, N (%) (95% CI)
Referent
these findings are generalizable to all
<.0001
health care settings.
This study presents one, but certainly
299 (8.5)
302 (8.7)
1.032 (0.995e1.072) 1004 (9.4) not the only approach, to assessing the
<.0001
extent to which the latent phase should
continue, in the absence of acute indi-
cation for delivery, during labor induc-
tion. Other approaches, for example,
1.10 (0.98e1.23)
1.21 (0.97e1.52)
1.33 (0.95e1.87)
1.47 (0.94e2.30)
1.61 (0.92e2.83)
1.78 (0.91e3.48)
include determination of inflection
Relative risk
Referent
ANC, adverse neonatal composite (seizures, sepsis, bone or nerve injury, encephalopathy, death); CI, confidence interval; NICU, neonatal intensive care unit admission; UA, umbilical artery.
.094
population-level percentiles.13-16 This
presently applied approach, however,
has several advantages, including that it
38 (1.1)
37 (1.1)
20 (1.0)
16 (1.8)
1.034 (0.975e1.097) 243 (2.2) 0.985 (0.955e1.016) 125 (1.2)
4 (1.1)
8 (4.2)
2 (1.0)
.041
standardizes the duration as a function
of several aspects of management to
establish a common “clock” and directly
assesses the relationship between dura-
86 (2.5) 0.96 (0.87e1.05)
46 (2.3) 0.91 (0.76e1.10)
16 (1.7) 0.87 (0.66e1.15)
7 (1.9) 0.83 (0.58e1.21)
4 (2.1) 0.80 (0.50e1.26)
3 (1.6) 0.76 (0.44e1.32)
81 (2.3) Referent
Referent
.264
Data are missing for 6666 neonates; b Cochran-Armitage or exact trend test.
UA
Referent
latent phase.
Converting these data into a discrete
Time as a continuous variable
2 (1.0)
.158
5-min
N (%)
0
0
192
194
However, given that the vast majority of Campbell, C. Collins, N. Jackson, M. Dinsmoor Eunice Kennedy Shriver National Institute of
women will progress to the active phase (NorthShore University HealthSystem), J. Senka Child Health and Human Development,
(NorthShore University HealthSystem), K. Pay- Bethesda, MDeC. Spong, S. Tolivaisa.
by 15 hours, that most women who do chek (NorthShore University HealthSystem), A. Maternal-Fetal Medicine Units Network
will progress to a vaginal delivery, and Peaceman. Steering Committee Chair (Medical University of
that relatively few will have adverse Columbia University, New York, NYeM. South Carolina, Charleston, SC)eJ. P. Van
outcomes, we believe that our results are Talucci, M. Zylfijaj, Z. Reid (Drexel University), Dorsten, MD.
consistent with prior recommenda- R. Leed (Drexel University), J. Benson (Chris-
tiana Hospital), S. Forester (Christiana Hospital),
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taneous labor at term. Cochrane Database Syst sity of Utah Health Sciences Center, Salt Lake City, UT Health and Human Development (HD21410, HD27869,
Rev 2013;7:CD005461. (Dr Varner); University of North Carolina at Chapel Hill, HD27915, HD27917, HD34116, HD34208, HD36801,
19. Rhinehart-Ventura J, Eppes C, Sangi- Chapel Hill, NC (Dr Thorp); University of Texas South- HD40500, HD40512, HD40544, HD40545, HD40560,
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after implementation of an induction-of-labor of Pittsburgh, Pittsburgh, PA (Dr Caritis); Ohio State Uni- for Research Resources (UL1 RR024989; 5UL1
protocol. Am J Obstet Gynecol 2014;211:301. versity, Columbus, OH (Dr Prasad); University of Alabama RR025764). Comments and views of the authors do not
e1-7. at Birmingham, Birmingham, AL (Dr Tita); University of necessarily represent views of the National Institutes of
Texas Medical Branch, Galveston, TX (Dr Saade); Wayne Health.
Author and article information State University, Detroit, MI (Dr Sorokin); Brown University, The authors report no conflict of interest.
From the Departments of Obstetrics and Gynecology of Providence, RI (Dr Rouse); University of Texas Health Corresponding author: William A. Grobman, MD,
Northwestern University, Chicago, IL (Dr Grobman); Science Center at Houston-Children’s Memorial Hermann MBA. w-grobman@northwestern.edu