CD 000035

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

Tocolytics for suspected intrapartum fetal distress (Review)

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Tocolytics versus no treatment, Outcome 1 No improvement in fetal heart rate abnormality. 10

Analysis 1.2. Comparison 1 Tocolytics versus no treatment, Outcome 2 Apgar score < 7 at 1 minute. . . . . . . 10

Analysis 1.3. Comparison 1 Tocolytics versus no treatment, Outcome 3 Apgar score < 7 after 5 minutes. . . . . . 11

Analysis 1.4. Comparison 1 Tocolytics versus no treatment, Outcome 4 Perinatal mortality. . . . . . . . . . 11

Analysis 1.5. Comparison 1 Tocolytics versus no treatment, Outcome 5 Umbilical arterial pH. . . . . . . . . 12

Analysis 1.6. Comparison 1 Tocolytics versus no treatment, Outcome 6 Umbilical artery pH < 7.2. . . . . . . 12

Analysis 1.7. Comparison 1 Tocolytics versus no treatment, Outcome 7 Neonatal intensive care unit admission. . . 13

Analysis 2.1. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 1 No improvement in fetal heart rate

abnormality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Analysis 2.2. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 2 Failure to reduce uterine activity. . 14

Analysis 2.3. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 3 Mean uterine activity after treatment

(Montevideo units). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Analysis 2.4. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 4 Time (in minutes) to reduced uterine

activity in responders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Analysis 2.6. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 6 Umbilical arterial pH < 7.20. . . 15

15WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iTocolytics for suspected intrapartum fetal distress (Review)


[Intervention Review]

Tocolytics for suspected intrapartum fetal distress

Regina Kulier1, G Justus Hofmeyr2

1Geneva Foundation for Medical Education and Research, Geneva, Switzerland. 2Department 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, CH-

1206, Switzerland. [email protected].

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.


A B S T R A C T

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.

1Tocolytics for suspected intrapartum fetal distress (Review)


P L A I N L A N G U A G E S U M M A R Y

Tocolytics for suspected intrapartum fetal distress

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.

B A C K G R O U N D

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 uteroplacen-

tal blood flow and, therefore, fetal oxygenation, and that this ad-

vantage outweighs adverse cardiovascular effects of the treatment

on the mother. Surprisingly few well-controlled studies have ad-

dressed this question.

O B J E C T I V E S

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.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All acceptable randomized trials which address the objectives of

the review were considered.

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.

Search methods for identification of studies

Electronic searches

We searched theCochrane Pregnancy andChildbirthGroupTrials

Register by contacting the Trials SearchCo-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 considerationwere evaluated formethodological qual-

ity and appropriateness for inclusion, without consideration of

their results. Included trial data were processed as described in

Mulrow 1997.

R E S U L T S

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.Nowithdrawals after randomizationwere 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 num-

ber 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-gener-

ated 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 al-

location.

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

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 tobe 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 bo-

lus with terbutaline 0.25 mg subcutaneously in women awaiting

caesarean section for fetal distress.Meanuterine activity after, com-

pared 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 ver-

sus 255.4, SD 108). Fewer women responded to magnesium sul-

phate 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 fe-

tal 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 umbil-

ical artery pH values of

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 with-

out 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 treat-

ment 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 sul-

phate.

Implications for research

Because of the small sample sizes of the two trials comparing be-

tamimetics with no treatment, evaluated in the primary compari-

son 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.

A C K N OW L E D G E M E N T S

None.

R E F E R E N C E S

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. Asia-

Oceania 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



C H A R A C T E R I S T I C S O F S T U D I E S

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 discon-

tinuation 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




Magann 1993 (Continued)

Allocation concealment? 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 0.25mg subcutaneously comparedwith control group (no placeboused - 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


Allocation concealment? 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



D A T A A N D A N A L Y S E S

Comparison 1. Tocolytics versus no treatment

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 No improvement in fetal heart

rate abnormality

2 43 Risk Ratio (M-H, Fixed, 95% CI) 0.28 [0.14, 0.55]

2 Apgar score < 7 at 1 minute 2 55 Risk Ratio (M-H, Fixed, 95% CI) 0.46 [0.16, 1.30]

3 Apgar score < 7 after 5 minutes 1 45 Risk Ratio (M-H, Fixed, 95% CI) 0.35 [0.02, 6.93]

4 Perinatal mortality 2 57 Risk Ratio (M-H, Fixed, 95% CI) 0.23 [0.01, 4.55]

5 Umbilical arterial pH 1 20 Mean Difference (IV, Fixed, 95% CI) 0.10 [-0.12, 0.32]

6 Umbilical artery pH < 7.2 1 33 Risk Ratio (M-H, Fixed, 95% CI) 0.64 [0.30, 1.35]

7 Neonatal intensive care unit

admission


Comparison 2. Terbutaline versus Magnesium sulphate

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 No improvement in fetal heart

rate abnormality


2 Failure to reduce uterine activity 1 46 Risk Ratio (M-H, Fixed, 95% CI) 0.07 [0.00, 1.10]

3 Mean uterine activity after

treatment (Montevideo units)

1 46 Mean Difference (IV, Fixed, 95% CI) -84.7 [-112.62, -56.

78]

4 Time (in minutes) to reduced

uterine activity in responders

1 39 Mean Difference (IV, Fixed, 95% CI) -5.7 [-6.77, -4.63]

6 Umbilical arterial pH < 7.20 1 46 Risk Ratio (M-H, Fixed, 95% CI) 0.29 [0.07, 1.23]



Analysis 1.1. Comparison 1 Tocolytics versus no treatment, Outcome 1 No improvement in fetal heart rate

abnormality.

Review: Tocolytics for suspected intrapartum fetal distress

Comparison: 1 Tocolytics versus no treatment

Outcome: 1 No improvement in fetal heart rate abnormality

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

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 ]

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 1 2 5 10

Analysis 1.2. Comparison 1 Tocolytics versus no treatment, Outcome 2 Apgar score < 7 at 1 minute.



Outcome: 2 Apgar score < 7 at 1 minute



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 ]


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


0.1 0.2 0.5 1 2 5 10



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



Outcome: 3 Apgar score < 7 after 5 minutes



Kulier 1997 0/16 2/29 100.0 % 0.35 [ 0.02, 6.93 ]

Total (95% CI) 16 29 100.0 % 0.35 [ 0.02, 6.93 ]


Heterogeneity: not applicable


0.1 0.2 0.5 1 2 5 10

Analysis 1.4. Comparison 1 Tocolytics versus no treatment, Outcome 4 Perinatal mortality.



Outcome: 4 Perinatal mortality

Study or subgroup Treatment Control 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 ]


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


0.1 0.2 0.5 1 2 5 10



Analysis 1.5. Comparison 1 Tocolytics versus no treatment, Outcome 5 Umbilical arterial pH.



Outcome: 5 Umbilical arterial pH

Study or subgroup Treatment ControlMean

Difference WeightMean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Patriarco 1987 11 7.3 (0.3) 9 7.2 (0.2) 100.0 % 0.10 [ -0.12, 0.32 ]

Total (95% CI) 11 9 100.0 % 0.10 [ -0.12, 0.32 ]



Test for subgroup differences: Not applicable

-10 -5 0 5 10

Analysis 1.6. Comparison 1 Tocolytics versus no treatment, Outcome 6 Umbilical artery pH < 7.2.



Outcome: 6 Umbilical artery pH < 7.2



Kulier 1997 6/16 10/17 100.0 % 0.64 [ 0.30, 1.35 ]

Total (95% CI) 16 17 100.0 % 0.64 [ 0.30, 1.35 ]




0.1 0.2 0.5 1 2 5 10



Analysis 1.7. Comparison 1 Tocolytics versus no treatment, Outcome 7 Neonatal intensive care unit

admission.



Outcome: 7 Neonatal intensive care unit admission



Kulier 1997 1/17 0/20 100.0 % 3.50 [ 0.15, 80.71 ]

Total (95% CI) 17 20 100.0 % 3.50 [ 0.15, 80.71 ]




0.1 0.2 0.5 1 2 5 10

Analysis 2.1. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 1 No improvement in fetal

heart rate abnormality.


Comparison: 2 Terbutaline versus Magnesium sulphate

Outcome: 1 No improvement in fetal heart rate abnormality



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 ]




0.1 0.2 0.5 1 2 5 10



Analysis 2.2. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 2 Failure to reduce uterine

activity.



Outcome: 2 Failure to reduce uterine activity



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 ]




0.1 0.2 0.5 1 2 5 10

Analysis 2.3. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 3 Mean uterine activity after

treatment (Montevideo units).



Outcome: 3 Mean uterine activity after treatment (Montevideo units)



Difference


Magann 1993 23 115.8 (57.5) 23 200.5 (36.9) 100.0 % -84.70 [ -112.62, -56.78 ]

Total (95% CI) 23 23 100.0 % -84.70 [ -112.62, -56.78 ]


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


-10 -5 0 5 10



Analysis 2.4. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 4 Time (in minutes) to

reduced uterine activity in responders.



Outcome: 4 Time (in minutes) to reduced uterine activity in responders



Difference


Magann 1993 23 1.8 (0.7) 16 7.5 (2.1) 100.0 % -5.70 [ -6.77, -4.63 ]

Total (95% CI) 23 16 100.0 % -5.70 [ -6.77, -4.63 ]


Test for overall effect: Z = 10.46 (P < 0.00001)


-10 -5 0 5 10

Analysis 2.6. Comparison 2 Terbutaline versus Magnesium sulphate, Outcome 6 Umbilical arterial pH

CD 000035

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