J. Obstet. Gynaecol. Res. Vol. 37, No.

7: 787791, July 2011

doi:10.1111/j.1447-0756.2010.01434.x

Comparison of success rate of nifedipine, progesterone,

and bed rest for inhibiting uterine contraction in
threatened preterm labor
jog_1434

787..791

Saifon Chawanpaiboon1, Kanjana Pimol2 and Ratre Sirisomboon2

1

Division of Maternal-Fetal Medicine, and 2Division of Obstetrics and Gynecology Nursing, Department of Obstetrics and
Gynaecology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

Abstract
Aim: To compare the success rates and gestational ages at delivery of nifedipine, proluton depot administration as a tocolytic agent and bed rest groups to pregnant women with threatened preterm labor.
Material and Methods: A total of 150 pregnant women with threatened preterm labor between 28 and
35 weeks of gestation were enrolled in the study. All women underwent contraction inhibition randomly
sorted into three groups. The rst and second groups were inhibited with nifedipine and proluton depot,
respectively. The third group was admitted for bed rest.
Results: Nifedipine, proluton depot and bed rest can be used to inhibit contraction in threatened preterm
labor. However, when time-to-event test was used, nifedipine took the shortest time for contraction inhibition
with statistical signicance.
Conclusion: Nifedipine, proluton depot and bed rest can be used successfully to inhibit contraction in
threatened preterm labor. However, nifedipine took the shortest time to inhibit uterine contraction in threatened preterm labor.
Key words: bed rest, nifedipine, proluton depot, threatened preterm labor.

Introduction
Preterm labor is the main etiology which causes high
perinatal morbidity and mortality. The prevalence of
preterm labor in Siriraj Hospital is 12.89%.1 Siriraj
Hospital is the tertiary center to which complicated
preterm pregnant women are referred. The limited
availability of neonatologists and newborn intensive
care units (NICU) nationwide has resulted in insufcient care of preterm births. Therefore, many trials
have been initiated to inhibit or prevent preterm birth.
Recent evidence from the Statistical Unit at Siriraj
Hospital showed that pregnant women with threatened preterm labor who had only bed rest developed
preterm labor at a rate of about 3050%.2,3 After bed

rest, 30% of women with threatened preterm labor proceeded to advanced stage of labor and underwent
delivery. Our study suspected that if threatened
preterm labor was stopped, the prevalence of preterm
birth could be minimized and perinatal mortality and
morbidity could be reduced. Therefore, nifedipine25
and proluton depot25 were of interest to be studied for
inhibiting contraction in threatened preterm labor
compared with bed rest.

Material and Methods

This study was approved by Siriraj Ethics Committee
of the Faculty of Medicine at Siriraj Hospital. The
sample size, using a power and precision analysis

Received: November 22 2009.

Accepted: July 21 2010.
Reprint request to: Dr Saifon Chawanpaiboon, Department of Obstetrics and Gynaecology, Faculty of Medicine, Siriraj Hospital,
Mahidol University, Bangkok 10700, Thailand. Email: siscw@mahidol.ac.th

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S. Chawanpaiboon et al.

formula, was calculated by the incidence of threatened

preterm labor at Siriraj Hospital, which was about 1.3%
per year.1 One hundred and fty pregnant women
with threatened preterm labor between 1 May 2007 and
31 December 2008 were enrolled in this study. All
women with singleton pregnancies presenting to the
labor ward with painful and regular uterine contractions at 2835 weeks of gestation were diagnosed with
threatened preterm labor. In all cases gestation was
calculated from the menstrual history and by an ultrasound scan in early pregnancy. Transvaginal ultrasound3,6,7 was performed in all patients.
Women in active labor, dened by the presence of
cervical dilatation 3 cm, those with cervical insufciency, and those with ruptured membranes were
excluded. Classic cervical insufciency is a diagnosis
based on an obstetric history of recurrent second trimester or early third trimester fetal loss following painless cervical dilatation, prolapse or rupture of the
membranes and expulsion of a live fetus, despite
minimal uterine activity.8
Patients with cervical length <3 cm were enrolled in
this study. If causes of threatened preterm labor,
including urinary tract infection and bacterial vaginosis, were found, the patients were treated according to
their causes. If threatened preterm labor occurred
spontaneously, contraction inhibition with nifedipine,
17-alpha-hydroxyprogesterone caproate (proluton
depot), or bed rest was administered randomly in three
groups. The patients were randomly allocated to each
group. Each group consisted of 50 patients.
The rst group was inhibited with a loading dose of
nifedipine 20 mg orally every 30 min, three times, then
maintained with nifedipine sustained release (SR)
20 mg every 12 h.25 The second group was inhibited
with proluton depot 250 mg intramuscularly on a
weekly basis.9 The third group was admitted for bed
rest. Contractions were recorded every hour for 12 h.
Successful cessation of uterine contraction was
dened as no contractions after inhibition for 12 h by
nifedipine, proluton depot or bed rest.

Unsuccessful cessation of uterine contraction was

dened as continuing contraction during and after
inhibition for 12 h.
If the inhibition succeeded, the same intervention in
each group was continued until 34 weeks of gestation.
If the inhibition failed and there was no contraindication to use bricanyl intravenously, then bricanyl was
used.4 If any complication or contraindication of either
nifedipine or proluton depot was found, the contraction inhibition was changed to intravenous bricanyl
and the patient was excluded from the study. Maternal
vital signs and fetal heart rate monitoring were
recorded during the intervention.
SPSS version 13 was used to analyze data. One-way
ANOVA, c2 and time-to-event test were used to
compare the data. Results were reported as mean, standard deviation (SD) or percentage. The level of statistical signicance was <0.05.

Results
From 1 May 2007 to 31 December, 2008, a total of 150
pregnant women with a diagnosis of threatened
preterm labor were admitted to the labor room at
Siriraj Hospital. Each group consisted of 50 pregnant
women and their contractions were inhibited with
nifedipine, proluton depot and bed rest, respectively.
There was no statistical signicance in maternal age,
mean gestational age of admission, mean gravida,
parity, abortion and cervical length among the patients
in the three groups (Table 1). Nifedipine, proluton
depot and bed rest were used to inhibit contractions
with a success rate of 80%, 66% and 64%, respectively,
without statistical signicance (Table 2). However,
when time-to-event test was used, nifedipine took the
shortest time for contraction inhibition in threatened
preterm labor with statistical signicance (Fig. 1,
Tables 2,3). Nifedipine took the shortest median time
to inhibit contraction (3.00 0.48 h with 95% CI of
4.185.83) (Table 4). Mode and gestational age of

Table 1 Demographic data of pregnant patients in three groups who received nifedipine, proluton depot and bed rest for
inhibiting uterine contraction in threatened preterm labour
Data

Nifedipine (n = 50)

Proluton depot (n = 50)

Bed rest (n = 50)

Maternal age
Mean gravida
Mean parity
Mean abortion
Mean gestational age of admission
Mean cervical length (mm)

26.4 6.6
2.4 1.8
0.7 0.8
0.7 1.3
31.8 1.5
2.4 0.5

28.6 7.4
1.9 1.1
0.7 0.8
0.2 0.6
31.6 2.1
2.2 0.3

26.4 6.6
2.0 1.2
0.6 0.9
0.4 0.7
31.8 2.3
2.1 0.5

788

(1443)
(17)
(02)
(05)
(2835)
(1.53.0)

(1845)
(17)
(03)
(03)
(2335)
(1.33.0)

(1739)
(15)
(03)
(02)
(2635)
(1.63.0)

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Contraction inhibition in preterm labor

Table 2 Number of patients and mean time of successful inhibition of uterine

contraction between pregnant patients in three groups (nifedipine, proluton
depot and bed rest)
Data after inhibition

Nifedipine
(n = 50)

Proluton depot
(n = 50)

Bed rest
(n = 50)

Number of succession
(%)
Mean time of
succession
P-value

40 (80)

33 (66)

32 (64)

2.9 2.1(112)

4.6 3.3 (112)

6.2 3.8 (112)

0.152

0.164

0.828

Figure 1 Time of succession between nifedipine, proluton depot and bed rest for inhibiting uterine contraction in threatened preterm labor by time-to-event test.

delivery, mean neonatal body weight and mean Apgar

score between the patients in three groups were not
statistically signicant (Table 5).

Discussion
Many interventions have long been used to prevent
preterm labor.10 Some interventions, including good
antenatal care, bed rest, and intravenous uid hydration seem to improve outcome, but there has been no
strong evidence supporting those interventions in the
prevention of preterm labor.10 Only fetal bronectin in
cervical mucus and cervical length are used to predict
preterm birth with well supported evidence.11,12
However, threatened preterm labor, which is classied
as regular uterine contraction, can progress to preterm
birth in about 30% of cases.2,5 Therefore, if this process
can be stopped the chances of both preterm birth and
perinatal morbidity and mortality can be reduced.
Terbutaline (bricanyl) is the rst-line drug which has
been used intravenously or subcutaneously to inhibit

preterm labor for over 20 years.13,14 However, evidence

has recently supported that the oral form of salbutamol
failed to inhibit contraction.13,14 Magnesium sulfate has
not been approved by the Food and Drug Administration for inhibition of contraction due to a higher risk of
maternal and fetal morbidity.15 Nifedipine was studied
and was strongly recommended for administration to
inhibit contraction.1618 The side-effects and complications of nifedipine to mother and fetus are fewer than
for beta-agonist and magnesium sulfate.1416 The study
showed that intramuscular progesterone was associated with a reduction in the risk of preterm birth at less
than 37 weeks of gestation, and of infant birth weight
of less than 2500 g in patients who had a previous
history of preterm birth.9 However, no study has supported its use in threatened preterm labor patients.
Therefore, proluton depot and nifedipine were still the
most promising medications with minimal side-effects.
There was, however, neither a study nor strong evidence which supported the use of both drugs to inhibit
uterine contraction in threatened preterm labor. Therefore, proluton depot and nifedipine to inhibit threatened preterm labor are studied here and compared to
bed rest intervention.
In the present study, nifedipine, proluton depot and
bed rest interventions were successful in inhibiting
contraction in threatened preterm labor at about 80%,
66% and 64%, respectively. There was no statistically
signicant difference among those interventions.
However, the present study had only a limited sample
size. When using a post hoc power analysis at 80% to
detect the success rate of intervention, each group must
include at least 157 patients. Further study should be
considered for precise interpretation.
However, when time-to-event test was used, nifedipine took the shortest time to inhibit contraction in
threatened preterm labor with a median time of
3.00 0.48 h. If the studied population was larger, the
signicance could be more clearly detected. Mean

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S. Chawanpaiboon et al.

Table 3 P-value between nifedipine, proluton depot and bed rest for inhibiting
uterine contraction in threatened preterm labour by time to event and c2 test
Type of intervention

Nifedipine

Proluton depot

Bed rest

Nifedipine
Proluton depot
Bed rest

P < 0.05*
P < 0.05*

P < 0.05*

P = 0.219

P < 0.05*
P = 0.219

*Statistical signicance when P < 0.05.

Table 4 Median time and condence interval of successful inhibition of uterine

contraction between pregnant patients in three groups (nifedipine, proluton
depot and bed rest)
Intervention
Nifedipine (n = 50)
Proluton depot (n = 50)
Bed rest (n = 50)
Over all

Estimate

Median
Standard error

95% CI

3.00
5.00
10.00
5.00

0.48
0.42
3.08
0.34

4.185.83
2.073.93
3.9716.03
4.345.66

Table 5 Delivery and newborn data between the patients in three groups (nifedipine, proluton depot and bed rest)
Data
Mode of delivery (P > 0.05)
Normal delivery
Vacuum extraction
Cesarean section
Mean gestational age of delivery (weeks)
(P > 0.05)
Mean neonatal body weight (grams) (P > 0.05)
Mean Apgar score (P > 0.05)
1 min
5 min

Nifedipine (n = 50)

Proluton depot (n = 50)

Bed rest (n = 50)

36
1
13
37.1 1.7 (3240)

40
0
10
36.9 2.1 (3040)

42
0
8
36.3 3.0 (2741)

2780 351 (20503640)

2856 456 (13203490)

2685 533 (11203640)

9 0.8 (710)
10 0.4 (810)

8.7 1.0
9.8 0.4

9.1 0.6
9.8 0.4

Indication of procedure:
Non-reassuring fetal heart rate pattern.
Previous cesarean section 4, non-reassuring fetal status 2, breech presentation 2, cephalopelvic disproportion 3, placenta previa 1, intrauterine growth restriction 1.
Previous cesarean section 4, non-reassuring fetal status 2, CPD 4.
Previous cesarean section 2, non-reassuring fetal status 2, placenta previa 2, unfavorable cervix 2.

gestational age at delivery, neonatal body weight and

mean Apgar score between the patients in the three
groups were also not signicant. Complications of nifedipine and proluton depot was not detected.
Nifedipine and proluton depot can be used to
inhibit uterine contraction in threatened preterm
labor, which could prevent or stop the process of
preterm delivery. Proluton depot (250 mg) can be
used intramuscularly on a weekly basis, while a nifedipine 20 mg loading dose was given orally every
30 min (three times), then maintained with nifedipine
SR (20 mg) every 12 h. Proluton depot is easier to use
than nifedipine due to the injection frequency being
once a week. However, nifedipine took a shorter time

790

to inhibit uterine contraction than proluton depot,

which took longer time until the desired action
occurred. Even though much strong evidence primarily suggested the use of proluton depot in patients
with a history of previous preterm birth, from the
present study proluton depot seemed to be effective
to inhibit uterine contraction. Pregnant patients in the
nifedipine group mostly delivered at a gestational age
after 37 weeks, which indicated the efcacy of nifedipine when compared to other interventions.
No signicant or denite risk was detected in the
failure group of patients with bed rest, which was
about 36%. This incidence was higher than the previous study which was found to be only 30%.2 Even

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Journal of Obstetrics and Gynaecology Research 2011 Japan Society of Obstetrics and Gynecology

Contraction inhibition in preterm labor

though the incidence was low, if contraction can be

stopped, then preterm birth can be minimized.
According to many randomized controlled trials all
tocolytic agents were more effective than placebo or no
therapy for delaying delivery by 48 h or 7 days, but
those interventions were not associated with signicant reduction in overall rates of respiratory distress
syndrome or neonatal death.19 Even though, the results
of the present study could not present the validity of
these interventions to reduce the risk of preterm labor
and to improve neonatal outcome, proper intervention
to stop uterine contraction was associated with the best
time for steroid therapy and the referral system of the
patient to the appropriate center for neonatal care.
In conclusion, nifedipine, proluton depot and bed
rest interventions can be used to inhibit uterine contraction in threatened preterm labor. This was only a
preliminary study; 50 cases in each group were still not
enough to reach to the correct result. Using a larger
population, greater varieties of proper doses and
timing of interventions should be studied.

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