Induction of Labor With Misoprostol For Premature Rupture of Membranes Beyond Thirty-Six Weeks' Gestation
Induction of Labor With Misoprostol For Premature Rupture of Membranes Beyond Thirty-Six Weeks' Gestation
Induction of Labor With Misoprostol For Premature Rupture of Membranes Beyond Thirty-Six Weeks' Gestation
2
tests or Fishers exact tests when appropriate. Apgar
and Bishop scores were analyzed with use of the Mann-
Whitney U test. Relative risk and corresponding 95%
confidence interval comparing misoprostol to oxytocin
treatments were also reported when necessary.
Results
The subjects were similar with respect to mean age,
gravidity, parity, height, weight, ethnicity, and estimated
gestational age at entry. Forty-one (41.8%) of the miso-
prostol subjects and 47 (48.0%) of the oxytocin subjects
were nulliparous (P = .35). The mean estimated gesta-
tional age for the misoprostol treatment group was 38.7
1.5 (SD) weeks and for the oxytocin treatment group
38.9 1.6 (SD) weeks (P = .46). The median preinduc-
tion Bishop score was 3 in the misoprostol group (range
0 to 10) and 4 in the oxytocin group (range 0 to 10) (P =
.57, Mann-Whitney U test).
A similar percentage of subjects in both treatment
groups had a treatment success. Seventy-five (75.8%) of
misoprostol-treated subjects and 73 (74.5%) of oxytocin-
treated women were delivered vaginally within 24 hours
of initiating induction (P = .87). There was no significant
difference in the mean time interval from start of induc-
tion to delivery between the two treatment groups. The
mean time from start of induction to delivery, regardless
of the route, was 900.8 558.1 minutes for the misopros-
Table I. Time intervals to delivery
Misoprostol (n = 98) Oxytocin (n = 99) Statistical significance
Initiation to delivery (min) 900.8 558.1 833.5 485.3 P = .99
*
Initiation to vaginal delivery (min) 811.5 511.4 747.0 448.0 P = .65
*
Vaginal delivery in 12 h 44 (44.4%) 49 (50%) P = .30
Vaginal delivery in 24 h 75 (75.8%) 73 (74.5%) P = .87
Data presented as mean SD or number and percent.
*
Based on log-transformed data.
Volume 179, Number 1 Wing and Paul 97
Am J Obstet Gynecol
tol-treated subjects and 833.5 485.3 minutes for the
oxytocin-treated subjects (P = .99, log-transformed data).
The mean time intervals from start of induction to vagi-
nal delivery were also similar. The mean time from start
of induction to vaginal delivery was 811.5 511.4 minutes
for misoprostol-treated women and 747.0 448.0 min-
utes for oxytocin-treated women (P = .65, log-trans-
formed data) (Table I).
Parity influenced the success of induction, regardless
of the treatment arm. In the misoprostol treatment
group 26 nulliparous (63%) and 49 multiparous (86%)
women were delivered vaginally within 24 hours after ini-
tiating induction, and in the oxytocin treatment group
29 nulliparous (60%) and 44 multiparous (86%) women
were delivered in this time period. Forty-one (41.8%) of
the misoprostol-treated subjects and 48 (48.4%) of the
oxytocin-treated subjects were nulliparous (P = .35). The
mean duration from induction to delivery in misopros-
tol-treated nulliparous women was 1116.3 546.1 min-
utes and in misoprostol-treated parous subjects it was
745.8 517.9 minutes, whereas the mean duration from
induction to delivery in oxytocin-treated nulliparous
women was 1080.1 489.3 minutes and in oxytocin-
treated multiparous women it was 601.3 350.90 min-
utes. These differences were not statistically different be-
tween the two treatment groups (nulliparous subjects P =
.87 and multiparous subjects P = .29, log-transformed
data).
The misoprostol-treated women required an average of
1.3 0.5 doses. Sixty-eight women received one dose of
misoprostol, and 30 received two doses. The average time
interval between doses was 469.7 182.2 minutes (range
330 to 1050 minutes). Thirty-seven (37.3%) women in
this group required oxytocin augmentation. The indica-
tions for oxytocin augmentation were failure to begin ac-
tive labor after two doses of misoprostol (14/37, 37.8%),
inadequate uterine activity in the active phase of labor
(13/37, 35.1%), and adequate cervical ripening after the
first dose of misoprostol (10/37, 27.0%).
Uterine tachysystole occurred in six subjects in each
treatment group. The time interval from the last dose of
misoprostol to the onset of tachysystole was 243.3 118.8
minutes and from initiation of oxytocin to onset of
tachysystole 417.0 209.6 minutes (P = .14). Hypertonus
was reported in only one misoprostol-treated subject.
There were no instances of uterine hyperstimulation.
Abnormal FHR tracings occurred in 29 (29.6%) and 28
(28.9%) of the misoprostol-treated and oxytocin-treated
women, respectively (P = .91) (Table II).
Evidence of intraamniotic infection occurred in simi-
lar frequencies in the two treatment groups. Twenty-eight
(28.6%) misoprostol-treated women and 26 (26.3%) oxy-
tocin-treated women had intraamniotic infection (P =
.71, relative risk 1.06, 95% confidence interval 0.78 to
1.45). Clinical suspicion of neonatal sepsis occurred in
21 (21.4%) infants born to misoprostol-treated women
and 27 (27.3%) infants of oxytocin-treated women (P =
.34, relative risk 0.85, 95% confidence interval 0.60 to
1.19). There were 2 cases of confirmed neonatal sepsis,
both born to mothers treated with oxytocin.
Eighty-five (85.9%) misoprostol-treated women were
delivered vaginally and 82 (83.7%) oxytocin-treated
women were delivered vaginally (relative risk 1.17, 95%
confidence interval 0.78 to 1.78). Of the 13 cesarean
births in women assigned to the misoprostol treatment
arm, 9 were for arrest disorders of labor and 4 were for
abnormal FHR tracings. Of the 17 cesarean deliveries in
the women treated with oxytocin, there were 10 for arrest
disorders, 4 for abnormal FHR tracings, and 3 for failed
inductions.
Neonatal outcomes were also similar between the two
treatment groups (Table III). The mean birth weights
did not differ between the two groups (3214 428 g in
the misoprostol-treated patients and 3250 480 g in
the oxytocin-treated patient (P = .59) The percentage of
infants requiring resuscitation at delivery, demonstrating
meconium passage, assigned Apgar scores <7 at 1 and 5
minutes, and requiring admission to the intensive care
Table II. Intrapartum complications
Misoprostol (n = 98) Oxytocin (n = 99) Statistical significance
Abnormal FHR patterns 29 (29.6%) 28 (28.9%) P = .91
Repetitive moderate-severe variable decelerations 17 10
Late decelerations 3 1
Prolonged decelerations 6 9
Other 0 1
Combinations 3 7
Meconium passage 8 (8.1%) 9 (9.1%) P = .82
Thin 5 9
Thick 3 0
Chorioamnionitis/intrauterine infection 28 (28.6%) 26 (26.3%) P = .71
Data presented as number and percent.
98 Wing and Paul July 1998
Am J Obstet Gynecol
unit were similar between the treatment groups.
Comment
There was no significant difference in the percentage
of subjects having success of induction, defined as vagi-
nal delivery within 24 hours after initiation of induction,
with use of vaginally administered misoprostol or oxy-
tocin infusion. There was also no significant difference in
the mean time intervals from start of induction to deliv-
ery in women with spontaneous rupture of membranes
beyond 36 weeks of gestation when treated with either
misoprostol or oxytocin. There was a trend toward a
higher number of failed inductions in the oxytocin treat-
ment group, because all three cesarean deliveries per-
formed for this indication occurred in oxytocin-treated
subjects. However, this difference was not statistically sig-
nificant.
We were unable to reduce the cesarean delivery rate in
women with premature rupture of membranes by admin-
istering misoprostol rather than oxytocin for labor in-
duction. Because the majority of cesarean sections in
misoprostol-treated women were performed for labor
dystocia, rather than failed induction, misoprostol ap-
pears to be effective for causing cervical dilatation and ef-
facement and inducing labor in patients with premature
rupture of membranes. We were also unable to reduce
the numbers of women receiving antimicrobial therapy
for the diagnosis of chorioamnionitis by administering
misoprostol rather than oxytocin. Intravaginal misopros-
tol administration may have contributed to the relatively
high frequency of chorioamnionitis in this treatment
arm.
We did not meet our assumptions for our power calcu-
lation, because the numbers of subjects achieving a suc-
cessful induction did not differ between the two groups.
However, it would appear that misoprostol can be used
with similar efficacy and safety in patients with premature
rupture of membranes beyond 36 weeks gestation.
The dosing regimen of misoprostol used in this investi-
gation was chosen on the basis of our past experience
with this medication for cervical ripening and labor in-
duction
18
and reflects a degree of conservatism in our ap-
proach to this subset of patients.
In our efforts to create the safest dosing regimen possi-
ble for misoprostol, we designed this protocol to reflect
the most conservative dosing regimen we had had expe-
rience with to date, that of misoprostol 25 g every 6
hours. It would seem from extrapolation from our most
recent investigation in which we compared giving miso-
prostol every 4 hours to a 24-hour exposure to the dino-
prostone vaginal insert Cervidil that a similar dosing fre-
quency could also be used safely in patients with
ruptured membranes.
23
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Table III. Neonatal outcomes
Misoprostol (n = 98) Oxytocin (n = 99) Statistical significance
Birth weight (g) 3214 428 3250 480 p = .59
Apgar score <7
1 min 11 (11.1%) 10 (10.2%) p = .84
5 min 2 (2.0%) 2 (2.0%) p = .99
*
Neonatal resuscitation 24 (24.5%) 27 (27.6%) p = .63
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Days in NICU 9.2 6.4 7.7 3.3 p = .29
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*
Data presented as mean SD or number and percent. NICU, Neonatal intensive care unit.
*
Fishers exact test.
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