Tocolytics For Suspected Intrapartum Fetal Distress (Review)

Tocolytics for suspected intrapartum fetal distress (Review)
Kulier R, Hofmeyr GJ
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1
http://www.thecochranelibrary.com

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Tocolytics versus no treatment, Outcome 1 No improvement in fetal heart rate abnormality.
Analysis 1.2. Comparison 1 Tocolytics versus no treatment, Outcome 2 Apgar score < 7 at 1 minute. . . . . . .
Analysis 1.3. Comparison 1 Tocolytics versus no treatment, Outcome 3 Apgar score < 7 after 5 minutes. . . . . .
Analysis 1.4. Comparison 1 Tocolytics versus no treatment, Outcome 4 Perinatal mortality. . . . . . . . . .
Analysis 1.5. Comparison 1 Tocolytics versus no treatment, Outcome 5 Umbilical arterial pH. . . . . . . . .
Analysis 1.6. Comparison 1 Tocolytics versus no treatment, Outcome 6 Umbilical artery pH < 7.2. . . . . . .
Analysis 1.7. Comparison 1 Tocolytics versus no treatment, Outcome 7 Neonatal intensive care unit admission. . .
Analysis 2.1. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 1 No improvement in fetal heart rate
abnormality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.2. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 2 Failure to reduce uterine activity. .
Analysis 2.3. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 3 Mean uterine activity after treatment
(Montevideo units). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.4. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 4 Time (in minutes) to reduced uterine
activity in responders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.6. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 6 Umbilical arterial pH < 7.20. . .
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1
1
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2
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3
3
3
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12
12
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[Intervention Review]
Tocolytics for suspected intrapartum fetal distress

Regina Kulier1 , G Justus Hofmeyr2
1 Geneva
Foundation for Medical Education and Research, Geneva, Switzerland. 2 Department of Obstetrics and Gynaecology, East
London Hospital Complex, University of the Witwatersrand, University of Fort Hare, Eastern Cape Department of Health, East
London, South Africa
Contact address: Regina Kulier, Geneva Foundation for Medical Education and Research, Chemin Edouard Tavan 5, Geneva, CH1206, Switzerland. regina.kulier@bluewin.ch.
Editorial group: Cochrane Pregnancy and Childbirth Group.

Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 11 May 2006.
Citation: Kulier R, Hofmeyr GJ. Tocolytics for suspected intrapartum fetal distress. Cochrane Database of Systematic Reviews 1998,
Issue 2. Art. No.: CD000035. DOI: 10.1002/14651858.CD000035.
ABSTRACT
Background
Prophylactic tocolysis with betamimetics and other agents has become widespread as a treatment for fetal distress. Uterine relaxation
may improve placental blood flow and, therefore, fetal oxygenation. However, there may also be adverse maternal cardiovascular effects.
Objectives
The objective of this review was to assess the effects of tocolytic therapy for suspected fetal distress on fetal, maternal and perinatal
outcomes.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (May 2006)
Selection criteria
Randomised trials comparing tocolytic therapy with no treatment or treatment with another tocolytic agent for suspected fetal distress.
Data collection and analysis
Two review authors assessed trial quality and extracted data.
Main results
Three studies were included. Compared with no treatment, there were fewer failed improvements in fetal heart rate abnormalities with
tocolytic therapy (relative risk (RR) 0.26, 95% confidence interval (CI) 0.13 to 0.53). Betamimetic therapy compared with magnesium
sulphate showed a non-significant trend towards reduced uterine activity (RR 0.07, 95% CI 0.00 to 1.10).
Authors conclusions
Betamimetic therapy appears to be able to reduce the number of fetal heart rate abnormalities and perhaps reduce uterine activity.
However, there is not enough evidence based on clinically important outcomes to evaluate the use of betamimetics for suspected fetal
distress.
PLAIN LANGUAGE SUMMARY

Tocolytic drugs to help babies who have a shortage of oxygen during labour.
Most healthy babies cope well with the contractions of labour. However, some babies become short of oxygen, or cannot seem to
get sufficient oxygen for their needs during labour. It can be difficult to identify these babies accurately, but they usually show some
irregularity in their heartbeat patterns. If the mother lies on her back during labour, the weight of the uterus compresses her major
blood vessels thus inhibiting the blood flow to the placenta and baby. If the mother is upright and moving around in labour, this can
help to prevent such problems. However, the drug, syntocinon, given to push labour on more quickly, can contribute to such problems
for the baby. Drugs that relax the uterus are thought to improve the blood circulation round the placenta and uterus. The review looked
at the effectiveness of tocolytic drugs (drugs that relax the uterus) for helping babies in such situations prior to caesarean section. The
review of trials found three studies involving just over 100 women. The studies seemed to show a benefit in terms of the acidity of the
babys blood at birth, and so showed a possible benefit in terms of buying time and helping the baby whilst waiting for a caesarean
section. However, the possibility of contributing to haemorrhage for the mother by relaxing the uterus needs proper investigation. So
further research is needed.
BACKGROUND
The use of acute tocolysis with betamimetic and other agents has
become widespread in clinical practice in recent years on the basis
of the presumption that uterine relaxation improves uteroplacental blood flow and, therefore, fetal oxygenation, and that this advantage outweighs adverse cardiovascular effects of the treatment
on the mother. Surprisingly few well-controlled studies have addressed this question.
Types of participants
Women with suspected fetal distress in labour.
Types of interventions
Tocolysis versus no treatment (placebo or nothing).
Comparison of different tocolytics.
Types of outcome measures
Fetal heart rate patterns, maternal and neonatal morbidity.
OBJECTIVES
To assess the effects on fetal heart rate abnormalities and perinatal
mortality and morbidity of tocolytic therapy during labour for
fetal distress diagnosed by electronic fetal heart rate monitoring or
fetal scalp pH measurement.
METHODS
Criteria for considering studies for this review
Types of studies
All acceptable randomized trials which address the objectives of
the review were considered.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Pregnancy and Childbirth Group Trials
Register by contacting the Trials Search Co-ordinator (May 2006).
The Cochrane Pregnancy and Childbirth Groups Trials Register
is maintained by the Trials Search Co-ordinator and contains trials
identified from:
1. quarterly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. monthly searches of MEDLINE;
3. handsearches of 30 journals and the proceedings of major
conferences;
4. weekly current awareness search of a further 37 journals.
Details of the search strategies for CENTRAL and MEDLINE,
the list of handsearched journals and conference proceedings, and

the list of journals reviewed via the current awareness service can be
found in the Search strategies for identification of studies section
within the editorial information about the Cochrane Pregnancy
and Childbirth Group.
Trials identified through the searching activities described above
are given a code (or codes) depending on the topic. The codes are
linked to review topics. The Trials Search Co-ordinator searches
the register for each review using these codes rather than keywords.
We did not apply any language restrictions.
Data collection and analysis

Trials under consideration were evaluated for methodological quality and appropriateness for inclusion, without consideration of
their results. Included trial data were processed as described in
Mulrow 1997.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies.
See table of Characteristics of included studies.
Risk of bias in included studies

In the trial of Patriarco 1987, allocation of participants was by
randomly generated numbers. Blinding by placebo injections was
not employed. No withdrawals after randomization were recorded.
The assessment of fetal heart rate response may have been biased
as evaluation of the tracings was not noted to have been blinded.
In the trial of Magann 1993, allocation was by a random number table using sealed opaque envelopes. The treatments were not
blinded, but evaluation of the fetal heart rate traces and uterine
contraction records were performed blind to the group allocation.
In the trial of Kulier 1997, allocation was by numbered, sealed,
opaque envelopes. Randomization was done by computer-generated random numbers in blocks of ten. There were no withdrawals
after randomization. The treatment was not blinded. The fetal
heart rate tracings were analysed blinded with regard to group allocation.
in one of the 11 women treated with subcutaneous terbutaline,

compared with all the randomly selected control group (Part 1).
At birth, terbutaline-treated babies were less likely to be acidotic
(mean pH 7.25 (SEM 0.03) versus 7.17 (0.02), p < .025). Low
Apgar scores also tended to be less common in the treatment group,
though the 95% confidence intervals included the possibility of
anything between a large benefit and no effect. There were no
perinatal deaths in either group. Terbutaline was reported to have
no adverse effects, other than transient maternal tachycardia.
Magann 1993 compared magnesium sulphate 4 g intravenous bolus with terbutaline 0.25 mg subcutaneously in women awaiting
caesarean section for fetal distress. Mean uterine activity after, compared with before, treatment was not significantly reduced with
magnesium sulphate (200.45 Montevideo units, SD 36.9 versus
228.6, SD 49.35), but was with terbutaline (115.81, SD 57.5 versus 255.4, SD 108). Fewer women responded to magnesium sulphate than to terbutaline, and the response time for those who did
respond was longer with magnesium sulphate. There was a trend
towards persistent fetal heart rate abnormalities in more women
treated by magnesium sulphate, and more had umbilical arterial
pH values below 7.20.
Kulier 1997 enrolled 37 women who had developed persistent fetal heart rate abnormalities consistent with fetal distress. The fetal
heart rate pattern improved in more women after hexoprenaline
10 microgram intravenously than in the control group (8/13 or
61.6% versus 1/10 or 10%) and this difference reached statistical
significance. Fewer babies in the hexoprenaline group had umbilical artery pH values of <7.2 and base excess of < -10, but this is
not statistically significant. There were two stillbirths in the control group: one had gross hydrocephalus, which was discovered
only at delivery; the second woman was referred for fetal distress
from a peripheral hospital and delivered a stillborn baby after 55
minutes while waiting for caesarean section. Although there was
a statistically significant increase in maternal pulse rate after treatment (89.4 versus 102.1 beats/minute before and 5 minutes after
the injection respectively, p = 0.04), no maternal complaints were
reported.
DISCUSSION
The conclusions of this review need to be tentative in view of the
fact that they are based on two small trials comparing treatment
with no treatment.
AUTHORS CONCLUSIONS
Effects of interventions
Patriarco 1987 studied 20 women with labours characterised by
both ominous fetal heart rate changes and a fetal scalp blood pH
of less than 7.25. Persistence of the heart rate pattern occurred
Implications for practice

The limited evidence available suggests that intravenous betamimetics are a useful treatment for buying time when fetal

distress is diagnosed during labour. Such time may be useful for

preparing for caesarean section or operative delivery, setting up
regional analgesia, transferring a woman at home or in a unit without the necessary surgical or neonatal facilities, to an appropriate
hospital, or reviewing the need for urgent delivery. Whether the
need for operative delivery can in fact be reduced by this treatment remains to be demonstrated. On the basis of the one trial
comparing magnesium sulphate with terbutaline as a tocolytic
(Magann 1993), it appears that terbutaline (and presumably other
betamimetics) are more likely to be effective than magnesium sulphate.
Implications for research

Because of the small sample sizes of the two trials comparing betamimetics with no treatment, evaluated in the primary comparison in this review, it is important that larger randomized trials be
carried out to confirm these findings and to evaluate the effect of
the treatment on meaningful measures of clinical outcome such
as need for operative delivery and serious neonatal morbidity.
ACKNOWLEDGEMENTS
None.
REFERENCES
References to studies included in this review

Kulier 1997 {published data only}
Kulier R, Gulmezoglu AM, Hofmeyr GJ. Betamimetics for
fetal distress: a randomized trial. Proceedings of the 14th
conference on priorities in perinatal care in South Africa;
1995 March 7-10; South Africa. 1995:1903.
Kulier R, Glmezoglu AM, Hofmeyr GJ, Van Gelderen CJ.
Betamimetics in fetal distress: a randomised controlled trial.
Journal of Perinatal Medicine 1997;25:97100.
Magann 1993 {published data only}
Magann EF, Cleveland RF, Dockery JR, Chauhan SP,
Norman PH, Martin JN, et al.Acute tocolysis for fetal
distress: terbutaline versus magnesium sulphate. 41st
Annual Clinical meeting, American College of Obstetricians
and Gynecologists; 1993 May 3-6; USA. 1993:13.
Magann EF, Cleveland RS, Dockery JR, Chauhan SP,
Martin JN, Morrison JC. Acute tocolysis for fetal distress:
terbutaline versus magnesium sulphate. Australian and New
Zealand Journal of Obstetrics and Gynaecology 1993;4:3626.
Magann EF, Norman PF, Bass JD, Chauhan SP, Matin JN,
Morrison JC. Acute tocolysis for suspected intrapartum
fetal distress: maternal effects of terbutaline vs magnesium
sulfate. International Journal of Obstetric Anesthesia 1995;4:
1404.
Patriarco 1987 {published data only}
Patriarco MS, Viechnicki BM, Hutchinson TA, Klasko SK,
Yeh SY. A study on intrauterine fetal resuscitation with
terbutaline. American Journal of Obstetrics and Gynecology
1987;157:3847.
References to studies excluded from this review

Burke 1989 {published data only}
Burke SM, Porreco RP, Day D, Watson JD, Haverkamp
AD, Orleans M, et al.Intrauterine resuscitation with
tocolysis. An alternate month clinical trial. Journal of
Perinatology 1989;9:296300.
Eckblad 1988 {published data only}

Eckblad U, Erkkola R, Uotila P, Kanto J, Palo P. Ritodrine
infusion at term: effects on maternal and fetal prostacyclin,
thromboxane and prostaglandin precursor fatty acids.
Gynecologic and Obstetric Investigation 1988;25:10612.
Gerris 1980 {published data only}
Gerris J, Thiery M, Bogaert M, De Schaepdryver A.
Randomized trial of two beta-mimetic drugs (Ritodrine and
Fenoterol) in acute intrapartum tocolysis. European Journal
of Clinical Pharmacology 1980;18:4438.
Hidaka 1987 {published data only}
Hidaka A, Komatini M, Ikeda H, Kitanaka T, Okada
K, Sugawa T. A comparative study of intrauterine fetal
resuscitation by beta-stimulant and O2 inhalation. AsiaOceania Journal of Obstetrics and Gynaecology 1987;13:
195200.
Visser 1979 {published data only}
Visser AA, Prinoloo OT, Sicatoira MVK. Suppression of
uterine activity with salbutamol before caesarean section.
South African Medical Journal 1979;56:10938.
References to studies awaiting assessment

Afschar {published data only}
Afschar P, Scholl W, Bader A, Bauer M, Winter R.
A prospective randomised trial of atosiban versus
hexoprenaline for acute tocolysis and intrauterine
resuscitation. BJOG: an international journal of obstetrics
and gynaecology 2004;111(4):3168.
Additional references
Mulrow 1997
Mulrow CD, Oxman AD. Cochrane Collaboration
Handbook (updated 1 March 1997). In: The Cochrane
Library (database on disk and CDROM). The Cochrane
Collaboration. Oxford: Update Software; 1996-. Updated
quarterly..

References to other published versions of this review

Hofmeyr 1998
Hofmeyr GJ. Betamimetics for suspected intrapartum
fetal distress. In: Neilson JP, Crowther CA, Hodnett
ED, Hofmeyr GJ (eds.) Pregnancy and Childbirth
Module of The Cochrane Database of Systematic Reviews,
[updated 02 December 1997]. Available in The Cochrane
Library [database on disk and CDROM]. The Cochrane
Collaboration; Issue 1. Oxford: Update Software; 1998.
Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Kulier 1997
Methods
Randomization by computer-generated random numbers in groups of 10, allocation by numbered, sealed,

opaque envelopes
Participants
37 women with fetal heart rate changes consistent with fetal distress in active labour. The trial was
conducted in 2 university hospitals in Johannesburg/South Africa
Interventions
Hexoprenaline 10 mg intravenous administered over 5 minutes vs no treatment
Outcomes
No improvement in fetal heart rate pattern, Apgar score < 7 after 1 minute and 5 minutes, umbilical
artery pH < 7.2 and base excess < -10, perinatal mortality
Notes
Fetal heart rate tracings were analysed blinded with regard to treatment allocation
Risk of bias
Item
Authors judgement
Description
Allocation concealment?
Unclear
B - Unclear
Magann 1993
Methods
Random allocation by random number table using sealed opaque envelopes
Participants
Inclusion criteria: fetal distress diagnosed in labour by (1) decreased variability and variable decelerations
of less than 50 beats per minute lasting longer than 60 seconds with a slow return to baseline; (2) acute,
persistent bradycardia of less than 120 beats per minute for longer than 10 minutes; (3) persistent late
fetal heart rate decelerations with little or no variability; (4) failed maternal manipulations such as discontinuation of oxytocin, fluid bolus, position change, oxygen, amnioinfusion. Exclusion criteria: potential
compromised haemodynamic stability, eg abruptio placentae, maternal haemorrhage, pre-eclampsia
Interventions
Comparison of terbutaline 0.25 mg by subcutaneous injection versus 4 g intravenous bolus of magnesium

sulphate, when decision taken to perform caesarean section
Outcomes
Reduced uterine activity; uterine activity after treatment; response time in those with reduced activity;
persistent fetal heart rate abnormality; umbilical arterial pH < 7.20
Notes
Risk of bias
Item
Authors judgement

Description
Magann 1993
(Continued)
Unclear
D - Not used
Patriarco 1987
Methods
Allocation by randomly generated numbers.
Participants
Inclusion criteria: ominous fetal heart rate changes and fetal scalp blood Ph < 7.25
Interventions
Terbutaline sulphate 0.25 mg subcutaneously compared with control group (no placebo used - not blinded)
Outcomes
No improvement in fetal heart rate pattern; Apgar score < 7 at 1 minute; umbilical arterial pH; perinatal
death
Notes
Blinding by placebo injections was not employed. No withdrawals after randomization were recorded.
The assessment of fetal heart rate response may have been biased as evaluation of the tracings was not
noted to have been blinded
Risk of bias
Item
Authors judgement
Description
Unclear
D - Not used
mg: microgram
vs: versus
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Burke 1989
This study was excluded because an alternate month study/control allocation policy at three hospitals resulted in
a large imbalance in group sizes (31 vs 19). Selection bias could not therefore be excluded with confidence. The
experimental policy included intravenous terbutaline 0.25 mg prior to caesarean section for fetal distress. The control
group included two women with twin pregnancies. Outcomes were apparently improved in terms of one-minute
Apgar scores below seven (13/31 vs 15/21). Five-minute Apgar scores below seven were not significantly reduced (2/
31 vs 5/21)
Eckblad 1988
This study was excluded because data are not available in an appropriate form for inclusion. Two hours before elective
caesarean section at term, eight women were treated with ritodrine 300 micrograms per minute for 30 minutes,
then 150 micrograms per minute, and seven received normal saline at similar infusion rates. During the infusion of
ritodrine, maternal plasma levels of thromboxane were reduced, and 6-keto PGF1alpha (a metabolite of PGI2) were
unchanged. In the control group, thromboxane levels were unchanged, and 6-keto PGF1alpha levels were increased.
Cord blood prostaglandin levels were similar between the two groups

(Continued)
Gerris 1980
This trial was excluded because two betamimetic agents were compared without a control group. Nulliparous women
in normal established labour were allocated at random to receive a 30 minute infusion of fenoterol, one, two or
four micrograms per minute, or ritodrine 100, 200 or 400 micrograms per minute (four cases per sub-group). The
short-term tocolytic effect and maternal and fetal side-effects were similar for the two drugs. After termination of
the infusion, uterine activity resumed much more quickly after fenoterol than ritodrine, presumably an advantage
when short-term tocolysis only is required, as in fetal resuscitation
Hidaka 1987
This trial was excluded because allocation was not random. The obstetricians were divided into two groups, one of
which used betamimetics, and one of which used oxygen inhalation for late fetal heart rate decelerations occurring
three or more times (Hidaka, personal communication). Late fetal heart rate decelerations persisted less frequently
in women who received 5 mg isoxuprine intravenously than in the group who received oxygen therapy (3/57 to 36/
44, p < 0.01). The numbers of women in the first and second stage of labour were unequally distributed between
the groups
Visser 1979
This study was excluded because exclusion of 13/60 enrolled women may have impaired the comparability of the
groups. The 30 women who received salbutamol 250 micrograms had slightly better cord blood pO2 and base deficit
values (relative to previous scalp blood samples) than did the 15 controls
vs: versus

DATA AND ANALYSES
Comparison 1. Tocolytics versus no treatment
Outcome or subgroup title

1 No improvement in fetal heart
rate abnormality
2 Apgar score < 7 at 1 minute
3 Apgar score < 7 after 5 minutes
4 Perinatal mortality
5 Umbilical arterial pH
6 Umbilical artery pH < 7.2
7 Neonatal intensive care unit
admission
No. of
studies
No. of
participants
43
Risk Ratio (M-H, Fixed, 95% CI)
0.28 [0.14, 0.55]
2
1
2
1
1
1
55
45
57
20
33
37

Mean Difference (IV, Fixed, 95% CI)
0.46 [0.16, 1.30]

0.35 [0.02, 6.93]
0.23 [0.01, 4.55]
0.10 [-0.12, 0.32]
0.64 [0.30, 1.35]
3.5 [0.15, 80.71]
Statistical method
Effect size
Comparison 2. Terbutaline versus Magnesium sulphate
Outcome or subgroup title

1 No improvement in fetal heart
rate abnormality
2 Failure to reduce uterine activity
3 Mean uterine activity after
treatment (Montevideo units)
4 Time (in minutes) to reduced
uterine activity in responders
6 Umbilical arterial pH < 7.20
No. of
studies
No. of
participants
46
0.29 [0.07, 1.23]
1
1
46
46

39
0.07 [0.00, 1.10]

-84.7 [-112.62, -56.
78]
-5.7 [-6.77, -4.63]
46
0.29 [0.07, 1.23]
Statistical method

Effect size
Analysis 1.1. Comparison 1 Tocolytics versus no treatment, Outcome 1 No improvement in fetal heart rate
abnormality.
Review:
Comparison: 1 Tocolytics versus no treatment

Outcome: 1 No improvement in fetal heart rate abnormality
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Kulier 1997
5/13
9/10
49.5 %
0.43 [ 0.21, 0.88 ]
Patriarco 1987
1/11
9/9
50.5 %
0.13 [ 0.03, 0.59 ]
Total (95% CI)
24
19
100.0 %
0.28 [ 0.14, 0.55 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
Total events: 6 (Treatment), 18 (Control)

Heterogeneity: Chi2 = 2.33, df = 1 (P = 0.13); I2 =57%
Test for overall effect: Z = 3.67 (P = 0.00024)
0.1 0.2
0.5
10
Analysis 1.2. Comparison 1 Tocolytics versus no treatment, Outcome 2 Apgar score < 7 at 1 minute.
Review:

Outcome: 2 Apgar score < 7 at 1 minute
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Kulier 1997
3/16
5/19
51.0 %
0.71 [ 0.20, 2.53 ]
Patriarco 1987
1/11
4/9
49.0 %
0.20 [ 0.03, 1.52 ]
Total (95% CI)
27
28
100.0 %
0.46 [ 0.16, 1.30 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

Heterogeneity: Chi2 = 1.08, df = 1 (P = 0.30); I2 =7%
0.1 0.2
0.5

10
10
Analysis 1.3. Comparison 1 Tocolytics versus no treatment, Outcome 3 Apgar score < 7 after 5 minutes.
Review:

Outcome: 3 Apgar score < 7 after 5 minutes
Study or subgroup
Treatment
Control
n/N
n/N
0/16
2/29
100.0 %
0.35 [ 0.02, 6.93 ]
16
29
100.0 %
0.35 [ 0.02, 6.93 ]
Kulier 1997
Total (95% CI)
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

Heterogeneity: not applicable
0.1 0.2
0.5
10
Analysis 1.4. Comparison 1 Tocolytics versus no treatment, Outcome 4 Perinatal mortality.

Review:

Outcome: 4 Perinatal mortality
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Risk Ratio
Kulier 1997
0/17
2/20
0.23 [ 0.01, 4.55 ]
Patriarco 1987
0/11
0/9
0.0 [ 0.0, 0.0 ]
Total (95% CI)
28
29
0.23 [ 0.01, 4.55 ]
M-H,Fixed,95% CI
M-H,Fixed,95% CI

Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
0.1 0.2

0.5
10
11
Analysis 1.5. Comparison 1 Tocolytics versus no treatment, Outcome 5 Umbilical arterial pH.
Review:

Outcome: 5 Umbilical arterial pH
Study or subgroup
Treatment
Mean
Difference
Control
Mean(SD)
Mean(SD)
Patriarco 1987
11
7.3 (0.3)
7.2 (0.2)
Total (95% CI)
11
Weight
IV,Fixed,95% CI
Mean
Difference
IV,Fixed,95% CI
100.0 %
0.10 [ -0.12, 0.32 ]
100.0 %
0.10 [ -0.12, 0.32 ]

Test for subgroup differences: Not applicable
-10
-5
10
Analysis 1.6. Comparison 1 Tocolytics versus no treatment, Outcome 6 Umbilical artery pH < 7.2.
Review:

Outcome: 6 Umbilical artery pH < 7.2
Study or subgroup
Kulier 1997
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
6/16
10/17
100.0 %
0.64 [ 0.30, 1.35 ]
16
17
100.0 %
0.64 [ 0.30, 1.35 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5

10
12
Analysis 1.7. Comparison 1 Tocolytics versus no treatment, Outcome 7 Neonatal intensive care unit
admission.
Review:

Outcome: 7 Neonatal intensive care unit admission
Study or subgroup
Kulier 1997
Total (95% CI)
Treatment
Control
n/N
n/N
Risk Ratio
Weight
1/17
0/20
100.0 %
3.50 [ 0.15, 80.71 ]
17
20
100.0 %
3.50 [ 0.15, 80.71 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
10
Analysis 2.1. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 1 No improvement in fetal
heart rate abnormality.
Review:
Comparison: 2 Terbutaline versus Magnesium sulphate

Outcome: 1 No improvement in fetal heart rate abnormality
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Magann 1993
2/23
7/23
100.0 %
0.29 [ 0.07, 1.23 ]
Total (95% CI)
23
23
100.0 %
0.29 [ 0.07, 1.23 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5

10
13
Analysis 2.2. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 2 Failure to reduce uterine
activity.
Review:

Outcome: 2 Failure to reduce uterine activity
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Magann 1993
0/23
7/23
100.0 %
0.07 [ 0.00, 1.10 ]
Total (95% CI)
23
23
100.0 %
0.07 [ 0.00, 1.10 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5
10
Analysis 2.3. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 3 Mean uterine activity after
treatment (Montevideo units).
Review:

Outcome: 3 Mean uterine activity after treatment (Montevideo units)
Study or subgroup
Treatment
Mean
Difference
Control
Mean(SD)
Mean(SD)
Magann 1993
23
115.8 (57.5)
23
200.5 (36.9)
Total (95% CI)
23
Weight
IV,Fixed,95% CI
Mean
Difference
IV,Fixed,95% CI
23
100.0 %
-84.70 [ -112.62, -56.78 ]
100.0 %
-84.70 [ -112.62, -56.78 ]

Test for overall effect: Z = 5.95 (P < 0.00001)
-10
-5

10
14
Analysis 2.4. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 4 Time (in minutes) to
reduced uterine activity in responders.
Review:

Outcome: 4 Time (in minutes) to reduced uterine activity in responders
Study or subgroup
Treatment
Mean
Difference
Control
Mean(SD)
Mean(SD)
Magann 1993
23
1.8 (0.7)
16
7.5 (2.1)
Total (95% CI)
23
Weight
Mean
Difference
100.0 %
-5.70 [ -6.77, -4.63 ]
100.0 %
-5.70 [ -6.77, -4.63 ]
IV,Fixed,95% CI
IV,Fixed,95% CI
16

Test for overall effect: Z = 10.46 (P < 0.00001)
-10
-5
10
Analysis 2.6. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 6 Umbilical arterial pH <
7.20.
Review:

Outcome: 6 Umbilical arterial pH < 7.20
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
Magann 1993
2/23
7/23
100.0 %
0.29 [ 0.07, 1.23 ]
Total (95% CI)
23
23
100.0 %
0.29 [ 0.07, 1.23 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

0.1 0.2
0.5

10
15
WHATS NEW
Last assessed as up-to-date: 11 May 2006.
Date
Event
Description
20 September 2008
Amended
Converted to new review format.
HISTORY
Protocol first published: Issue 2, 1995
Review first published: Issue 2, 1995
Date
Event
Description
12 May 2006
New search has been performed
Plain language summary added. Search updated and one new trial identified - see
Studies awaiting assessment
CONTRIBUTIONS OF AUTHORS
R Kulier and GJ Hofmeyr prepared the review. R Kulier is the guarantor of the review.
DECLARATIONS OF INTEREST
One of the authors of the review is also the principal investigator of one of the included trials.
SOURCES OF SUPPORT
Internal sources
University of the Witwatersrand, South Africa.
The Nuffield Trust, UK.

16
External sources
South African Medical Research Council, South Africa.
INDEX TERMS
Medical Subject Headings (MeSH)
Fetal Distress [ drug therapy]; Hexoprenaline [therapeutic use]; Magnesium Sulfate [therapeutic use]; Obstetric Labor Complications
[ drug therapy]; Terbutaline [therapeutic use]; Tocolytic Agents [ therapeutic use]
MeSH check words

Female; Humans; Pregnancy

17

Tocolytics For Suspected Intrapartum Fetal Distress (Review)

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Tocolytics for suspected intrapartum fetal distress (Review)