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J Matern Fetal Neonatal Med, Early Online: 15
! 2015 Informa UK Ltd. DOI: 10.3109/14767058.2015.1018171
ORIGINAL ARTICLE
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Chad K. Klauser1, Christian M. Briery2, Ann R. Tucker3, Rick W. Martin3, Everett F. Magann4, Suneet P. Chauhan5, and
John C. Morrison3
1
Departments of Obstetrics and Gynecology, The Mount Sinai Medical Center, New York City, NY, USA, 2Departments of Obstetrics and Gynecology,
Regional Perinatal Group, Shreveport, LA, USA, 3Departments of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS,
USA, 4Departments of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA, and 5Departments of Obstetrics
and Gynecology, Lyndon B. Johnson General Hospital, Houston, TX, USA
Abstract
Keywords
Objective: To compare the efficacy of tocolytic treatment with indomethacin (I), magnesium
sulfate (M) and nifedipine (N) for acute tocolysis in women with advanced cervical dilation
(46 cm).
Methods: A single center, randomized trial was carried out involving patients in preterm labor
(cervix 16 cm). Secondary analysis of women with advanced cervical dilation (cervix 46 cm)
at 2432 weeks gestation who received intravenous M, oral N or I suppositories comprised this
study population.
Results: Over 38 months, 92 women with advanced cervical dilation were randomized to one
tocoloytic type. Days gained in utero (11.7) and percent remaining undelivered at 48 h (60.8%),
72 h (53.1%) and 47 days (38.3%) were similar regardless of tocolytic employed (p 0.923,
0.968, 0.791, 0.802, respectively). Likewise, gestational age at delivery (30.7 3.2) was similar
between groups (p 0.771). Finally, neonatal statistics were not different when stratified by
tocolytic treatment.
Conclusion: There were no statistical differences between tocolytics in treating women with
advanced cervical dilation. All offered significant days gained in utero after therapy, a high
percentage remaining undelivered after 48 or 72 h and after 7 days. It would appear from data
that there may be advantages to tocolytic treatment even in women with advanced cervical
dilation.
Introduction
In spite of all the advances in perinatal medicine, preterm
delivery continues to be the leading serious complication of
pregnancy, affecting as many as 10% of all gestations and
accounting for the vast majority of perinatal morbidity and
mortality [1]. Preterm labor with or without early rupture of
the membranes is responsible for up to 70% of the cases of
preterm delivery [2]. Several tocolytic drugs (such as
magnesium sulfate, terbutaline, nifedipine, indomethacin)
have been demonstrated to postpone delivery for several
days or up to a week following acute preterm labor but their
success is inversely related to cervical dilation when tocolysis
is begun [3].
The success rate of tocolytic treatment when the cervix is
dilated to 3 cm is assumed to be very poor [4]. Indeed, many
practitioners choose not to administer tocolytic drugs in such
History
Received 24 November 2014
Revised 4 February 2015
Accepted 9 February 2015
Published online 9 March 2015
cases due to the presumed high failure rate [5]. For example,
Cordero et al. [6] found that the primary reason women in
preterm labor were not appropriately referred to tertiary
centers was advanced cervical dilation. While the literature on
this subject is sparse, a few studies over the past decades have
shown significant prolongation of pregnancy for 23 days or
even 47 days [35,7].
The purpose of this study was to compare intravenous
magnesium sulfate, rectal indomethacin and oral nifedipine in
a group of women with advanced cervical dilation to assess
the efficacy of such treatment in these patients.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 04/10/15
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C. K. Klauser et al.
Results
In this study, 276 subjects were randomized and 87 received
indomethacin while 85 were treated with magnesium sulfate
and 104 were tocolized with nifedipine over a 38 month
period (Figure 1). Of these, 32 receiving indomethacin (37
infants), 33 treated with magnesium sulfate (36 infants) and
27 who received the tocolytic nifedipine (32 infants) were
4 cm to 6 cm and comprised this study population. As
shown in Table 1, the demographics of age, race, gravidity
and parity as well as women having had a prior preterm
delivery were not different between the three groups.
Similarly, the cervical dilation on admission was similar
between the three groups (p 0.521), as was the gestational
age (all 2829 weeks) at randomization (p 0.129).
Table 2 shows the various obstetric factors. All deliveries
were due to spontaneous labor and none were indicated for
maternal/fetal complications. The gestational age at delivery
(30.7 3.2 weeks) was similar between groups (p 0.771).
Magnesium had more births in the 3034 week group,
whereas indomethacin was associated with more women
delivering at 530 weeks but neither was statistically
DOI: 10.3109/14767058.2015.1018171
n 92
Indomethacin
32
MgSO4
33
Nifedipine
27
p value
Age (yrs)
Race (AA/C/H)*
Gravity
Parity
Prior preterm birth
Cervical exam (cm) at randomization
Gestational age at entry weeks
23.1 5.3
27/3/2
2.3 1.2
0.9 1.1
7 (21.8%)
4.3 0.6
28.2 2.4
22.7 4.7
30/3/0
2.7 1.9
1.3 1.5
12 (36.4%)
4.3 0.5
29.3 2.1
23.6 4.1
24/3/0
2.8 1.3
1.2 1.3
8 (29.6%)
4.3 0.5
28.1 2.4
0.483
0.419
0.374
0.173
0.439
0.521
0.129
*African American/Caucasian/Hispanic.
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n 92
GA at del
3034 weeks
530 weeks
Days gained
448 h
472 h
47 days
Indomethacin
32
MgSO4
33
Nifedipine
27
p value
30.3 3.6
11
21
30.8 2.9
17
16
30.1 3.1
11
16
0.771
0.368
0.296
15.7 20.6
20 (62.5%)
17 (53.1%)
14 (43.7%)
9.9 13.1
20 (60.6%)
15 (45.4%)
12 (36.4%)
9.5 10.9
16 (59.3%)
15 (55.5%)
10 (37.0%)
0.923
0.968
0.791
0.802
MgSO4
36
Nifedipine
32
p value
n 104
Indomethacin
37
Birth weight (g) 1585.7 693.2 1643.3 595.7 1496.0 513.9 0.696
APGAR 5
8.4 1.6
8.6 1.3
8.8 0.5
0.760
Cord pH
7.31 0.06
7.30 0.06
7.29 0.06 0.705
Neonatal morbidity
RDS
22
PDA
6
Sepsis
5
NEC
4
IVH
1
Total hosp. days 37.3 25.2
16
5
4
0
4
30.5 19.6
12
4
3
1
3
40.5 36.7
0.180
0.908
0.866
0.087
0.348
0.683
Discussion
There is a dearth of studies about acute preterm labor
and advanced cervical dilation treated with tocolytic drugs.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 04/10/15
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C. K. Klauser et al.
Declaration of interest
The authors report no conflicts of interest. The
authors alone are responsible for the content and writing of
this article.
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DOI: 10.3109/14767058.2015.1018171
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 04/10/15
For personal use only.
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