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doi:10.1111/j.1447-0756.2010.01434.x J. Obstet. Gynaecol. Res. Vol. 37, No.

7: 787791, July 2011

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 administra-
tion 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 threat-
ened preterm labor.
Key words: bed rest, nifedipine, proluton depot, threatened preterm labor.

Introduction rest, 30% of women with threatened preterm labor pro-


ceeded to advanced stage of labor and underwent
Preterm labor is the main etiology which causes high delivery. Our study suspected that if threatened
perinatal morbidity and mortality. The prevalence of preterm labor was stopped, the prevalence of preterm
preterm labor in Siriraj Hospital is 12.89%.1 Siriraj birth could be minimized and perinatal mortality and
Hospital is the tertiary center to which complicated morbidity could be reduced. Therefore, nifedipine25
preterm pregnant women are referred. The limited and proluton depot25 were of interest to be studied for
availability of neonatologists and newborn intensive inhibiting contraction in threatened preterm labor
care units (NICU) nationwide has resulted in insuf- compared with bed rest.
cient care of preterm births. Therefore, many trials
have been initiated to inhibit or prevent preterm birth. Material and Methods
Recent evidence from the Statistical Unit at Siriraj
Hospital showed that pregnant women with threat- This study was approved by Siriraj Ethics Committee
ened preterm labor who had only bed rest developed of the Faculty of Medicine at Siriraj Hospital. The
preterm labor at a rate of about 3050%.2,3 After bed 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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Journal of Obstetrics and Gynaecology Research 2011 Japan Society of Obstetrics and Gynecology
S. Chawanpaiboon et al.

formula, was calculated by the incidence of threatened Unsuccessful cessation of uterine contraction was
preterm labor at Siriraj Hospital, which was about 1.3% dened as continuing contraction during and after
per year.1 One hundred and fty pregnant women inhibition for 12 h.
with threatened preterm labor between 1 May 2007 and If the inhibition succeeded, the same intervention in
31 December 2008 were enrolled in this study. All each group was continued until 34 weeks of gestation.
women with singleton pregnancies presenting to the If the inhibition failed and there was no contraindica-
labor ward with painful and regular uterine contrac- tion to use bricanyl intravenously, then bricanyl was
tions at 2835 weeks of gestation were diagnosed with used.4 If any complication or contraindication of either
threatened preterm labor. In all cases gestation was nifedipine or proluton depot was found, the contrac-
calculated from the menstrual history and by an ultra- tion inhibition was changed to intravenous bricanyl
sound scan in early pregnancy. Transvaginal ultra- and the patient was excluded from the study. Maternal
sound3,6,7 was performed in all patients. vital signs and fetal heart rate monitoring were
Women in active labor, dened by the presence of recorded during the intervention.
cervical dilatation 3 cm, those with cervical insuf- SPSS version 13 was used to analyze data. One-way
ciency, and those with ruptured membranes were ANOVA, c2 and time-to-event test were used to
excluded. Classic cervical insufciency is a diagnosis compare the data. Results were reported as mean, stan-
based on an obstetric history of recurrent second tri- dard deviation (SD) or percentage. The level of statisti-
mester or early third trimester fetal loss following pain- cal signicance was <0.05.
less cervical dilatation, prolapse or rupture of the
membranes and expulsion of a live fetus, despite
minimal uterine activity.8 Results
Patients with cervical length <3 cm were enrolled in
this study. If causes of threatened preterm labor, From 1 May 2007 to 31 December, 2008, a total of 150
including urinary tract infection and bacterial vagino- pregnant women with a diagnosis of threatened
sis, were found, the patients were treated according to preterm labor were admitted to the labor room at
their causes. If threatened preterm labor occurred Siriraj Hospital. Each group consisted of 50 pregnant
spontaneously, contraction inhibition with nifedipine, women and their contractions were inhibited with
17-alpha-hydroxyprogesterone caproate (proluton nifedipine, proluton depot and bed rest, respectively.
depot), or bed rest was administered randomly in three There was no statistical signicance in maternal age,
groups. The patients were randomly allocated to each mean gestational age of admission, mean gravida,
group. Each group consisted of 50 patients. parity, abortion and cervical length among the patients
The rst group was inhibited with a loading dose of in the three groups (Table 1). Nifedipine, proluton
nifedipine 20 mg orally every 30 min, three times, then depot and bed rest were used to inhibit contractions
maintained with nifedipine sustained release (SR) with a success rate of 80%, 66% and 64%, respectively,
20 mg every 12 h.25 The second group was inhibited without statistical signicance (Table 2). However,
with proluton depot 250 mg intramuscularly on a when time-to-event test was used, nifedipine took the
weekly basis.9 The third group was admitted for bed shortest time for contraction inhibition in threatened
rest. Contractions were recorded every hour for 12 h. preterm labor with statistical signicance (Fig. 1,
Successful cessation of uterine contraction was Tables 2,3). Nifedipine took the shortest median time
dened as no contractions after inhibition for 12 h by to inhibit contraction (3.00 0.48 h with 95% CI of
nifedipine, proluton depot or bed rest. 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 26.4 6.6 (1443) 28.6 7.4 (1845) 26.4 6.6 (1739)
Mean gravida 2.4 1.8 (17) 1.9 1.1 (17) 2.0 1.2 (15)
Mean parity 0.7 0.8 (02) 0.7 0.8 (03) 0.6 0.9 (03)
Mean abortion 0.7 1.3 (05) 0.2 0.6 (03) 0.4 0.7 (02)
Mean gestational age of admission 31.8 1.5 (2835) 31.6 2.1 (2335) 31.8 2.3 (2635)
Mean cervical length (mm) 2.4 0.5 (1.53.0) 2.2 0.3 (1.33.0) 2.1 0.5 (1.63.0)

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Journal of Obstetrics and Gynaecology Research 2011 Japan Society of Obstetrics and Gynecology
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 Proluton depot Bed rest
(n = 50) (n = 50) (n = 50)
Number of succession 40 (80) 33 (66) 32 (64)
(%)
Mean time of 2.9 2.1(112) 4.6 3.3 (112) 6.2 3.8 (112)
succession
P-value 0.152 0.164 0.828

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 Administra-
tion 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 complica-
tions of nifedipine to mother and fetus are fewer than
for beta-agonist and magnesium sulfate.1416 The study
showed that intramuscular progesterone was associ-
ated with a reduction in the risk of preterm birth at less
than 37 weeks of gestation, and of infant birth weight
Figure 1 Time of succession between nifedipine, prolu- of less than 2500 g in patients who had a previous
ton depot and bed rest for inhibiting uterine contrac- history of preterm birth.9 However, no study has sup-
tion in threatened preterm labor by time-to-event test. ported its use in threatened preterm labor patients.
Therefore, proluton depot and nifedipine were still the
most promising medications with minimal side-effects.
delivery, mean neonatal body weight and mean Apgar There was, however, neither a study nor strong evi-
score between the patients in three groups were not dence which supported the use of both drugs to inhibit
statistically signicant (Table 5). uterine contraction in threatened preterm labor. There-
fore, proluton depot and nifedipine to inhibit threat-
Discussion ened preterm labor are studied here and compared to
bed rest intervention.
Many interventions have long been used to prevent In the present study, nifedipine, proluton depot and
preterm labor.10 Some interventions, including good bed rest interventions were successful in inhibiting
antenatal care, bed rest, and intravenous uid hydra- contraction in threatened preterm labor at about 80%,
tion seem to improve outcome, but there has been no 66% and 64%, respectively. There was no statistically
strong evidence supporting those interventions in the signicant difference among those interventions.
prevention of preterm labor.10 Only fetal bronectin in However, the present study had only a limited sample
cervical mucus and cervical length are used to predict size. When using a post hoc power analysis at 80% to
preterm birth with well supported evidence.11,12 detect the success rate of intervention, each group must
However, threatened preterm labor, which is classied include at least 157 patients. Further study should be
as regular uterine contraction, can progress to preterm considered for precise interpretation.
birth in about 30% of cases.2,5 Therefore, if this process However, when time-to-event test was used, nife-
can be stopped the chances of both preterm birth and dipine took the shortest time to inhibit contraction in
perinatal morbidity and mortality can be reduced. threatened preterm labor with a median time of
Terbutaline (bricanyl) is the rst-line drug which has 3.00 0.48 h. If the studied population was larger, the
been used intravenously or subcutaneously to inhibit signicance could be more clearly detected. Mean

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Journal of Obstetrics and Gynaecology Research 2011 Japan Society of Obstetrics and Gynecology
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 P < 0.05* P < 0.05*
Proluton depot P < 0.05* P = 0.219
Bed rest 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 Median
Estimate Standard error 95% CI
Nifedipine (n = 50) 3.00 0.48 4.185.83
Proluton depot (n = 50) 5.00 0.42 2.073.93
Bed rest (n = 50) 10.00 3.08 3.9716.03
Over all 5.00 0.34 4.345.66

Table 5 Delivery and newborn data between the patients in three groups (nifedipine, proluton depot and bed rest)
Data Nifedipine (n = 50) Proluton depot (n = 50) Bed rest (n = 50)
Mode of delivery (P > 0.05)
Normal delivery 36 40 42
Vacuum extraction 1 0 0
Cesarean section 13 10 8
Mean gestational age of delivery (weeks) 37.1 1.7 (3240) 36.9 2.1 (3040) 36.3 3.0 (2741)
(P > 0.05)
Mean neonatal body weight (grams) (P > 0.05) 2780 351 (20503640) 2856 456 (13203490) 2685 533 (11203640)
Mean Apgar score (P > 0.05)
1 min 9 0.8 (710) 8.7 1.0 9.1 0.6
5 min 10 0.4 (810) 9.8 0.4 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, intrau-
terine 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 to inhibit uterine contraction than proluton depot,
mean Apgar score between the patients in the three which took longer time until the desired action
groups were also not signicant. Complications of nife- occurred. Even though much strong evidence prima-
dipine and proluton depot was not detected. rily suggested the use of proluton depot in patients
Nifedipine and proluton depot can be used to with a history of previous preterm birth, from the
inhibit uterine contraction in threatened preterm present study proluton depot seemed to be effective
labor, which could prevent or stop the process of to inhibit uterine contraction. Pregnant patients in the
preterm delivery. Proluton depot (250 mg) can be nifedipine group mostly delivered at a gestational age
used intramuscularly on a weekly basis, while a nife- after 37 weeks, which indicated the efcacy of nife-
dipine 20 mg loading dose was given orally every dipine when compared to other interventions.
30 min (three times), then maintained with nifedipine No signicant or denite risk was detected in the
SR (20 mg) every 12 h. Proluton depot is easier to use failure group of patients with bed rest, which was
than nifedipine due to the injection frequency being about 36%. This incidence was higher than the previ-
once a week. However, nifedipine took a shorter time ous 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 6. Leitich H, Brunbauer M, Kaider A, Egarter C, Hosslein P.
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detected by vaginal utrasonography as markers for preterm
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