Chinese Herbal Medicines for Threatened Miscarriage

8/20/2019 Chinese Herbal Medicines for Threatened Miscarriage

http://slidepdf.com/reader/full/chinese-herbal-medicines-for-threatened-miscarriage 1/88

Chinese herbal medicines for threatened miscarriage (Review)

Li L, Dou L, Leung PC, Wang CC

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 5

http://www.thecochranelibrary.com

Chinese herbal medicines for threatened miscarriage (Review)

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

http://www.thecochranelibrary.com/

http://www.thecochranelibrary.com/



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

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

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

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

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

4OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12 AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13 ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

71DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Chinese herbal medicines versus Western medicines (primary outcome and non-specific

secondary outcome), Outcome 1 Effectiveness of intervention (primary outcome). . . . . . . . . . . 73

Analysis 1.2. Comparison 1 Chinese herbal medicines versus Western medicines (primary outcome and non-specific

secondary outcome), Outcome 2 No relief of clinical signs. . . . . . . . . . . . . . . . . . . 74

Analysis 1.12. Comparison 1 Chinese herbal medicines versus Western medicines (primary outcome and non-specificsecondary outcome), Outcome 12 Effectiveness of intervention (non-prespecified secondary outcome). . . . 75

Analysis 3.1. Comparison 3 Combined medicines versus Western medicines (primary outcome and non-specific secondary

outcome), Outcome 1 Effectiveness of intervention (primary outcome). . . . . . . . . . . . . . . 76


outcome), Outcome 2 No relief of clinical signs. . . . . . . . . . . . . . . . . . . . . . . 77


outcome), Outcome 12 Effectiveness of intervention (non-prespecified secondary outcome). . . . . . . . 78

79 ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

81 APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

84HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

85CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

85DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

85SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .85DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .

85INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iChinese herbal medicines for threatened miscarriage (Review)




[Intervention Review]

Chinese herbal medicines for threatened miscarriage

Lu Li1 , Lixia Dou2 , Ping Chung Leung 3 , Chi Chiu Wang 1

1Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong. 2 Cochrane Pregnancy and

Childbirth Group, Department of Women’s and Children’s Health, The University of Liverpool, Liverpool, UK. 3 Institute of Chinese

Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong

Contact address: Chi Chiu Wang, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales

Hospital, Shatin, New Terrorities, Hong Kong. [email protected] .

Editorial group: Cochrane Pregnancy and Childbirth Group.

Publication status and date: New, published in Issue 5, 2012.

Review content assessed as up-to-date: 2 April 2012.

Citation: Li L, Dou L, Leung PC, Wang CC. Chinese herbal medicines for threatened miscarriage. Cochrane Database of Systematic Reviews 2012, Issue 5. Art. No.: CD008510. DOI: 10.1002/14651858.CD008510.pub2.


A B S T R A C T

Background

Threatened miscarriage occurs in 10% to 15% of all pregnancies. Vaginal spotting or bleeding during early gestation is common,

with nearly half of those pregnancies resulting in pregnancy loss. To date, there is no effective preventive treatment for threatened

miscarriage. Chinese herbal medicines have been widely used in Asian countries for centuries and have become a popular alternative

to Western medicines in recent years. Many studies claim to show that they can prevent miscarriage. However, there has been nosystematic evaluation of the effectiveness of Chinese herbal medicines for threatened miscarriage.

Objectives

To review the therapeutic effects of Chinese herbal medicines for the treatment of threatened miscarriage.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 January 2012), Chinese Biomedical Database (1978 to

31 January 2012), China Journal Net (1915 to 31 January 2012), China National Knowledge Infrastructure (1915 to 31 January 2012),

WanFang Database (1980 to 31 January 2012), Chinese Clinical Trial Registry (31 January 2012), EMBASE (1980 to 31 January

2012), CINAHL (31 January 2012), PubMed (1980 to 31 January 2012), Wiley InterScience (1966 to 31 January 2012), International

Clinical Trials Registry Platform (31 January 2012) and reference lists of retrieved studies. We also contacted organisations, individual

experts working in the field, and medicinal herb manufacturers.

Selection criteria

Randomised or quasi-randomised controlled trials that compared Chinese herbal medicines (alone or combined with other pharma-

ceuticals) with placebo, no treatment (including bed rest), or other pharmaceuticals as treatments for threatened miscarriage.

Data collection and analysis

Two review authors independently assessed all the studies for inclusion in the review, assessed risk of bias and extracted the data. Data

were checked for accuracy.

1Chinese herbal medicines for threatened miscarriage (Review)


mailto:[email protected]

mailto:[email protected]



Main results

In total, we included 44 randomised clinical trials with 5100 participants in the review.

We did not identify any trials which used placebo or no treatment (including bed rest) as a control.

The rate of effectiveness (continuation of pregnancy after 28 weeks of gestation) was not significantly different between the Chinese

herbal medicines alone group compared with the group of women receiving Western medicines alone (average risk ratio (RR) 1.23;

95% confidence interval (CI) 0.96 to 1.57; one trial, 60 women).

Chinese herbal medicines combined with Western medicines were more effective than Western medicines alone to continue the

pregnancy beyond 28 weeks of gestation (average RR 1.28; 95% CI 1.18 to 1.38; five trials, 550 women).

Authors’ conclusions

There was insufficient evidence to assess the effectiveness of Chinese herbal medicines alone for treating threatened miscarriage.

A combination of Chinese herbal and Western medicines was more effective than Western medicines alone for treating threatened

miscarriage. However, the quality of the included studies was poor. More high quality studies are necessary to further evaluate the

effectiveness of Chinese herbal medicines for threatened miscarriage.

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

Chinese herbal medicines for threatened miscarriage

Miscarriage or spontaneous abortion is the loss of a pregnancy without medical or mechanical means before completion of the 20th week

of gestation. The fetus is not sufficiently developed to have been able to survive outside the mother’s womb. Threatened miscarriage

is a very common in early pregnancy. Most threatened miscarriages occur in the first 12 weeks of pregnancy and become evident as

vaginal bleeding, abdominal and low back pain that persist for days or weeks. So far, therapies have limited effectiveness in preventing

early pregnancy loss due to threatened miscarriage. Chinese herbal medicines are a part of Traditional Chinese Medicines and are made

up of products from plants and some animal and mineral substances. They have become very popular and are commonly used as an

alternative treatment for threatened miscarriage.

This review compared the therapeutic effects of Chinese herbal medicines with other pharmaceutical agents. Among the 44 includedrandomised trials involving 5100 participants, all from China, no trial used placebo or bed rest as a control intervention. Twenty

trials used a common prescription of Shou Tai Pill as a basic formula, while the other 24 trials used other formulae. The Western

medicines included tocolytic drugs such as salbutamol and magnesium sulfate, hormonal supplementation with human chorionic

gonadotrophin or progesterone and supportive supplements including vitamin E and folic acid. Five trials followed 550 women until

after 28 weeks of gestation and delivery and showed that combined Chinese herbal and Western medicines were more effective than

Western medicines alone in the treatment of threatened miscarriage. The remaining studies looked at the immediate effects of treatment.

Combined treatment was more effective than Western medicines in preventing inevitable miscarriage so that the pregnancy continued.

Many of the trials did not report on side effects during treatment or throughout continuing pregnancy and birth. Chinese medicine

practitioners slightly modify the classical prescriptions depending on the individual women’s clinical presentations. All the trials had

poor methodological quality. In conclusion, there is a lack of evidence from randomised controlled trials on the effectiveness of Chinese

herbal medicines for the treatment of threatened miscarriage and to determine if Chinese herbal medicines alone are more beneficial

than Western medicines alone for threatened miscarriage.

B A C K G R O U N D

Description of the condition





Miscarriage

Miscarriage is defined as spontaneous abortion occurring with-

out medical or mechanical means before completion of the 20th

week of gestation so that the fetus is not sufficiently developed to

survive (Cunningham 2005). It denotes pregnancy loss prior to

completion of the 20th

gestational week, or 139 days, counting from the first day of the last normal menses (DeCherney 2007).

The incidence of miscarriage is commonly stated as 10% to 15%

of all pregnancies, and is the most common complication during

pregnancy (Petrozza 2006). However, the incidence is difficult to

determine precisely, since as many as 30% may go unrecognised,

and these can occur very early during a pregnancy.

Threatened miscarriage

Threatened miscarriage presents with vaginal bleeding or any

bloody vaginal discharge during early pregnancy, and although the

bleeding is frequently slight, it may persist for days or weeks with-

out cervical dilatation and fetal loss (Cunningham 2005). Threat-ened miscarriage will become inevitable when gross rupture of

fetal membranes occurs along with severe vaginal bleeding and

cervical dilatation; imminent fetal loss is almost certain in these

cases (Cunningham 2005). Vaginal bleeding during early gesta-

tion occurs in 20% to 25% pregnancies and may last for days or

weeks; nearly half of these pregnancies will result in pregnancy loss

(Cunningham 2005). If the miscarriage is avoided, there is still a

high risk of preterm labour (Batzofin 1984), and low birthweight

(Funderburk 1980), and perinatal death ( Weiss 2004).

Major causes of miscarriage

More than 80% of miscarriages occur in the first 12 weeks of preg-nancy (Loue 2004). There are many factors that put a pregnancy

at a high risk of miscarriage.

Genetic defects

Chromosomal anomalies contribute to at least half of miscarriages

at the early stage of pregnancy, and it could depend on paternal,

maternal or fetal factors (Cunningham 2005). Chromosomal ab-

normalities from either parent can be inherited by their offspring.

Numerical abnormality, such as haploid and triploid, and struc-

tural abnormality, such as deletion and translocation, are two clas-

sical types of chromosomal anomalies for miscarriage. Fetal factors

include abnormal zygotic development and aneuploidy (numeri-cal chromosomal abnormality).

Immunological dysfunction

Miscarriage, caused by immunological dysfunction, is also related

to the parents. The paternal factor includes human leukocyte anti-

gens (HLA) (Kano 2007) and antisperm antibodies (Choudhury

2010). For the mother, a pregnancy is like an allograft, the mater-

nal body may have a rejection reaction to the fetus. Maternal fetal

incompatibility occurs because of ABO and Rhesus (Rh) blood

group antigens (Bandyopadhyay 2010) and excess antiphospho-

lipid antibodies (Suzumori 2010).

Other maternal factors

The risk of miscarriage appears to increase with parity as well as

with maternal and paternal age (Gracia 2005). A variety of ma-

ternal diseases and developmental abnormalities have been impli-

cated, including chronic infection, anatomic defects, endocrine

deficiencies, toxin exposure, immunologic disorders, and physical

or emotionaltrauma,which may leadto recurrent miscarriagesand

threatened miscarriages (DeCherney 2007). Some isolated events

such as laparotomy, chronic debilitating disease, nutrition, high

fever, tobacco, drug abuse, or alcoholism, are also considered to

be causes of threatened miscarriage (Lyttleton 2004).

Environmental factors

Over orlastingexposure tosome chemicalsand metalssuchas lead,

cadmium, and arsenic, could also cause harm to the pregnancy

and lead to pregnancy loss (Tabacova 1994).

Clinical management

In current clinical practice, surgical and non-surgical interven-

tions are used in the management of miscarriage. However, in

threatened miscarriage, non-surgical interventions, which prevent

the inevitable consequence of pregnancy loss, are rather empirical

(Tien 2007). Most cases will progress to the next stage no matter

what is done. Bed rest and avoidance of sexual intercourse, thoughcommonly advised, are without sufficient proven benefit ( Aleman

2005). Supportive care may reduce inevitable miscarriage (Tien

2007). Progesterone support hasbeen used to reducethe incidence

of miscarriage (El-Zibdeh 2009), but the conclusion is still very

limited (Haas 2008). Hence, to date, no therapy has been con-

firmed as efficacious for threatened miscarriage.

Description of the intervention

Traditional Chinese medicine (TCM) has been used for more than

3000 years in China (Ma 2006). Chinese herbal medicine, one

of the commonly therapeutic approaches of TCM, mainly refersto products made of, or from, plants, or parts of plants, and also

includes animal and mineral substances.

How the intervention might work

Unlike mainstream Westernmedicine, TCMhas a unifiedmedical

theory for clinical diagnosis and treatment which focuses on ’Qi’





and ’blood’ as the two basic elements of human physiology. ’Qi’ is

equivalent to vital energy. There is an overall or essential ’Qi’ for

each organ (such as kidney ’Qi’, liver ’Qi’, etc). ’Qi deficiency’ (or

Qi vacuity) can lead to aging and weakness, whereas ’Qi’ stagnant

can cause pain. ’Blood’ is the sustenance of the body; ’Blood defi-

ciency’ (or Blood vacuity) can lead to pallor and dizziness, whereas’Blood stasis’ can result in bleeding tendency.

TCM practitioners use ’inquiry, inspection, hearing, and palpa-

tion’ to makediagnosesand prescribe Chinese herbal medicinesac-

cordingto the’Jun, Chen,Zuo, Shi’ principle(which standsfor the

charactersas Monarch, Minister, Assistant and Guide) (Li 2005b).

As each of the herbal medicines has its own properties and poten-

tial interactivity, the application of this principle will decrease or

avoid the side effects of the other herbs, enhance the therapeutical

actions of some herbs and collaborate with all the herbs to create

a more harmonious effect on the human body resulting in a more

enhanced and direct impact on treatments. Among allthe systems,

deficiency in the ’kidney’ and ’liver’ functions are particularly im-

portant in the pathology and mechanism of miscarriage. ’Kidney’stores the essential ’Qi’ that warms up and activates all the other

systems in the body. It is responsible for growth, development,and

reproduction (Li 2005b). ’Liver’ stores the ’blood’ that regulates

the flow of ’Qi’ and maintains reproductivity (Li 2005b). The

main causes of miscarriage include ’Qi’ deficiency, ’blood’ heat,

’blood’ deficiency and ’kidney’ deficiency (Ma 2006). Amongst

all of these, ’kidney deficiency’ is the most frequent clinical type

in miscarriage (Lyttleton 2004); women with ’kidney deficiency’

tend to miscarry earlier in the pregnancy (Lyttleton 2004). Chi-

nese herbal medicines such as Radix rehmanniae (Rehmania root),

Fructus lycii (Lycium fruit) and Semen cuscutae (Cuscuta fruit), are

commonly used to correct ’kidney deficiency’ through nourishing

the “Kidney” and benefiting the fetus in preventing miscarriage(Liu 2002).

Why it is important to do this review

Chinese medicines and other herbal medicines or botanicals are

principally used in China and South East Asia, but these are in-

creasingly becoming accepted worldwide as an alternative to West-

ern medicines to promote the health of both mothers and fetuses

and to relieve medical problems during pregnancy. Based on our

preliminary literature search, miscarriage, in particular threatened

miscarriage, is one of the most common clinical indications for

Chinese herbal medicines during pregnancy (Li 2011b).

Despite the wide use of Chinese herbal medicines for preventing

pregnancy loss, the therapeuticeffects of Chinese herbalmedicines

for threatened miscarriage in early pregnancy has not been eval-

uated systematically. Similarly, medication exposures during early

pregnancy are known to result in birth defects, but currently there

is insufficient information on the risks and safetyof Chinese herbal

medicines.

O B J E C T I V E S

To review the therapeutic effects of Chinese herbal medicines for

the treatment of threatened miscarriage.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Randomised or quasi-randomised controlled trials, as well as clus-

ter-randomised trials, comparing Chinese herbal medicines (alone

or combined with other pharmaceuticals) with placebo, no treat-

ment (including bed rest), or other pharmaceuticals as treatments

for threatened miscarriage.

Trials were included regardless of publication status, with or with-out full text. We only identified studies that compared Chinese

herbal medicines with other pharmaceuticals (mainly Western

medicines). We did not identify any trials which used placebo or

bed rest as a control.

We did not apply any language restrictions, and most of the papers

were in Chinese or English, which was the mother language or

second language for all the authors, who fully understood the

papers as well as the design and intervention of the trials.

Types of participants

All pregnant women with a viable pregnancy diagnosed with

threatened miscarriage, regardless of underlying causes. No treat-ment wasgivenbefore the trial interventions. Fetal viability wasas-

sessed by ultrasound to ensure exclusion from the study of women

with inevitable, incomplete, or missed miscarriage. Women with

vaginal bleeding after the 20th week of pregnancy were also ex-

cluded. We included women regardless of whether the pregnancy

was singleton or multiple, and irrespective of thematernal age and

parity.

Types of interventions

All types of Chinese herbal medicines in either standard or com-

binedformulaefor the treatmentof threatenedmiscarriage, regard-

lessof the dose or duration of administration, were compared with

other pharmaceuticals. The pharmaceuticals were mostly Western

medicines. We planned the following comparisons.

• Chinese herbal medicines versus placebo.

• Chinese herbal medicines versus no treatment (including

bed rest).

• Chinese herbal medicines alone versus other

pharmaceuticals.





• Combined Chinese herbal medicines and other

pharmaceuticals versus other pharmaceuticals.

Types of outcome measures

Primary outcomes

(1) Effectiveness of intervention: continuation of pregnancy after

28 weeks of gestation.

Pregnancy after 28 weeks of gestation is generally considered vi-

able, and pregnancy loss before 28 weeks is considered to be non

viable due to extreme low birthweight and underdeveloped struc-

tures. In this review, only viable pregnancy at 28 weeks was con-

sidered as the primary outcome.

Secondary outcomes

Mother

During treatment

(2) No relief of clinical signs (vaginal bleeding and abdominal

pain).

(3) No improvement in laboratory investigations (urinary and

serum beta human chorionic gonadotropin (ß-HCG) titre).

After treatment

(4) Repeated threatened miscarriage before 28th week of the same

pregnancy (current miscarriage signs and symptoms remitted after

intervention but relapsed in the same pregnancy).

(5) Preterm labour.

(6) Any other adverse pregnancy outcomes reported, including

side effects, toxicity, etc.

Fetus(7) Live birth (non-prespecified outcomes).

(8) Preterm birth.

(9) Stillbirth.

(10) Neonatal death.

(11) Fetal structural malformations.

(12) Any other adverse perinatal outcomes reported, including

side effects, toxicity, etc.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Group’s Tri-als Register by contacting the Trials Search Co-ordinator (31 Jan-

uary 2012).

The Cochrane Pregnancy and Childbirth Group’s Trials Register

is maintained by the Trials Search Co-ordinator and contains trials

identified from:

1. monthly searches of the Cochrane Central Register of

Controlled Trials (CENTRAL);

2. weekly searches of MEDLINE;

3. weekly searches of EMBASE;

4. handsearches of 30 journals and the proceedings of major

conferences;

5. weekly current awareness alerts for a further 44 journals

plus monthly BioMed Central email alerts.Guidelines of the search strategiesfor CENTRAL, MEDLINEand

EMBASE, the handsearched journals and conference proceedings

and the journals reviewed via the current awareness service were

followed according to the ’Specialized Register’ section from the

Cochrane Pregnancy and Childbirth Group.

In addition, we searched:

1. EMBASE (1980 to 31 January 2012) ( Appendix 1)

2. Cumulative Index to Nursing and Allied Health Literature

(CINAHL) (31 January 2012) ( Appendix 2)

3. PubMed (1980 to 31 January 2012) ( Appendix 3)

4. China Journal Net (CJN) (1915 to 31 January 2012)

( Appendix 4)

5. China National Knowledge Infrastructure (CNKI) (1915to 31 January 2012) ( Appendix 4)

6. WanFang Database (Chinese Ministry of Science &

Technology) (1980 to 31 January 2012) ( Appendix 5)

7. Chinese Biomedical Database (CBM) (1978 to 31 January

2012) ( Appendix 6)

8. Wiley Inter Science (1966 to 31 January 2012) ( Appendix

6)

9. Chinese Clinical Trial Registry (31 January 2012)

( Appendix 7)

10. International Clinical Trials Registry Platform (ICTRP) (31

January 2012) ( Appendix 7)

Searching other resources

Handsearching

We searched 64 Chinese language journals ( Appendix 8).



http://apps.who.int/trialsearch/

http://apps.who.int/trialsearch/



References from published studies

We searched the reference lists of relevant trials and reviews iden-

tified.

Unpublished literature

As some of the trials showed that there would be on-going stud-

ies, we tried to contact the authors for more details if the stud-

ies were completed and results were available. We contacted the

pharmaceutical companies for more information of the relevant

medicines/products.

Personal communications

We contacted organisations, individual experts working in the

field, and medicinal herb manufacturers in order to obtain addi-

tional references.

We did not apply any language restrictions.

Data collection and analysis

Selection of studies

To determine which clinical trials to include, we screened the

titles, abstracts, and keywords of the trials identified by the search.

Two review authors (LL and LD) independently assessed each

trial for inclusion and any disagreements were discussed. If thedisagreementscould not be resolved, we contactedthe trial authors

forclarification. We did notblindthe reviewauthors to thejournal

of origin or institution.

Data extraction and management

We designed a form to extract data, and two review authors (LL)

and (LD) extracted the data using the agreed form for study eligi-

bility. We resolved discrepancies through discussion or consulted

the third review author (CCW). We entered data into Review

Manager software (RevMan 2011), and checked for accuracy. We

assessed the abstracts in the same way as full papers, then included

them in the analyses. We excluded trials that did not meet our

eligibility criteria (or as a result of the study authors’ replies to our

queries) and noted the reasons for exclusion in the Characteristics

of excluded studies table. Studies awaiting classification are those

for which the authors of the original reports have not yet provided

information. However, we will reconsider these trials for inclusion

if the authors provide more information or once the full publica-

tions become available to confirm our queries.

Assessment of risk of bias in included studies

Two review authors (LL and LD) independently assessed the risk

of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

It includes seven parts as follows. Any disagreements were resolved

by discussion or by involving the third assessor (CCW).

(1) Random sequence generation (checking for possible

selection bias)

We describe for each included study the method used to generate

the allocation sequence in sufficient detail to allow an assessment

of whether it should produce comparable groups.

We assessed the method as:

• low risk of bias (any truly random process, e.g. random

number table; computer random number generator);

• high risk of bias (any non-random process, e.g. odd or even

date of birth; hospital or clinic record number);

• unclear risk of bias.

(2) Allocation concealment (checking for possible selection

bias)

We describe for each included study the method used to conceal

allocation to interventions prior to assignment and assess whether

intervention allocation could have been foreseen in advance of, or

during recruitment, or changed after assignment.

We assessed the methods as:

• low risk of bias (e.g. telephone or central randomisation;

consecutively numbered sealed opaque envelopes);

• high risk of bias (open random allocation; unsealed or non-

opaque envelopes, alternation; date of birth);• unclear risk of bias.

(3) Blinding (checking for possible performance bias)

We describe for each included study the methods used to blind

study participants and personnel from knowledge of which inter-

vention a participant received. We assessed blinding separately for

different outcomes or classes of outcomes. We judged studies at

low risk of bias if they were blinded. Trials with no blinding or

blinding of participants only were considered at high risk of bias

which may affect the results.


• low, high or unclear risk of bias for participants;• low, high or unclear risk of bias for personnel;

• low, high or unclear risk of bias for outcome assessors.

(4) Incomplete outcome data (checking for possible attrition

bias due to the amount, nature and handling of incomplete

outcome data)





We describe for each included study, and for each outcome or class

of outcomes, the completeness of data including attrition and ex-

clusions from the analysis. We state whether attrition and exclu-

sions were reported and the numbers included in the analysis at

each stage (compared with the total randomised participants), rea-

sons for attrition or exclusion where reported, and whether miss-ing data were balanced across groups or were related to outcomes.

Where sufficient information was reported, or was supplied by

the trial authors, we re-included the missing data in the analyses

which we undertook.

We assessed methods as:

• low risk of bias (e.g. no missing outcome data; missing

outcome data balanced across groups);

• high risk of bias (e.g. numbers or reasons for missing data

imbalanced across groups; ‘as treated’ analysis done with

substantial departure of intervention received from that assigned

at randomisation);


If data for more than 20% of participants were missing, we ex-cluded the outcome or study from the analysis.

(5) Selective reporting (checking for reporting bias)

We describe for each included study how we investigated the pos-

sibility of selective outcome reporting bias and what we found.


• low risk of bias (where it is clear that all of the study’s pre-

specified outcomes and all expected outcomes of interest to the

review have been reported);

• high risk of bias (where not all the study’s pre-specified

outcomes have been reported; one or more reported primary

outcomes were not pre-specified; outcomes of interest arereported incompletely and so cannot be used; study fails to

include results of a key outcome that would have been expected

to have been reported);


(6) Other sources of bias (compliance and baseline

similarity)

We describe for each included study any important concerns we

had about other possible sources of bias. For example, if the trial

stopped early, or if there was a baseline imbalance (e.g. severeblood

loss before intervention) or differential diagnosis (e.g. pattern/

syndrome differentiation for individualised treatment) between

the comparing groups.

We assessed whether each study was free of other problems that

could put it at risk of bias as follows.

Compliance

• Good: more than 95% participants received the treatment

exactly following the physicians’ instructions.

• Fair: 95% to 90%.

• Poor: 90% to 80%.

• Failed: less than 80%.

Baseline similarity

• Yes: all participants were inpatients or outpatients, with the

symptoms, signs, examinations or diagnosis related to threatened

miscarriage and suitable for each study, then were randomly

selected for different study groups.

• No.

• Unclear.

(7) Overall risk of bias

We made explicit judgements about whether the studies were at

high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

With reference to (1) to (6) above, we assessed the likely magnitude

and direction of the bias and whether we considered it was likely

to impact on the findings. We planned to explore the impact of

the level of bias through undertaking sensitivity analyses - see Sensitivity analysis.

Measures of treatment effect

Statistical analysis was performed using (RevMan 2011).

Continuous data

Not applicable in this review.

Dichotomous data

We presented results as summary risk ratio with 95% confidence

intervals for dichotomous data.

Unit of analysis issues

Trials with three arms (Chinese herbal medicines alone, West-

ern medicines alone, combined Chinese herbal and Western

medicines) were included and are described in the Characteristics

of included studies. We input the data separately for the respective

meta-analysis for a better understanding on the effectiveness of

each intervention.





Dealing with missing data

For included studies, we noted levels of attrition, and explored the

impact of included studies with high levels of missing data for the

overall assessment of treatment effect by using sensitivity analysis.

For all outcomes, we carried out analyses, on an intention-to-treat

basis; we attempted to include all participants randomised to eachgroup in the analyses. The denominator for each outcome in each

trial was the total number of participants randomised minus any

participants whose outcomes were known to be missing.

Assessment of heterogeneity

We assessed statistical heterogeneity in each meta-analysis using

the T², I² and Chi² statistics. We regarded heterogeneity as sub-

stantial if T² was greater than zero and either I² was greater than

30% or there was a low P value (less than 0.10) in the Chi² test

for heterogeneity.

Data synthesis

We carried out statistical analysis using RevMan 2011 and used

fixed-effect inverse variance meta-analysis for combining data

when the studies were estimating the same underlying treatment

effect and the populations and methods of the trials were judged

sufficiently similar. For clinical heterogeneity sufficient to expect

that the underlying treatment effects differed between trials, or if

substantial statistical heterogeneity was detected, we used random-

effects meta-analysis to produce an overall summary if an average

treatment effect across trials was considered clinically meaningful.

We treated the random-effects summary as the average range of

possible treatment effects and we discussed the clinical implica-

tions of treatment effects differing between trials. Where the av-erage treatment effect was not clinically meaningful, we did not

combine trials. For random-effects analyses, we presented the re-

sults as the average treatment effect with its 95% confidence in-

terval, and the estimates of T² and I².

Subgroup analysis and investigation of heterogeneity

Due to lack of data we were unable to carry out anyof theprespec-

ified subgroup analysis. In future updates of this review, if more

data become available, we will carry out the following prespecified

subgroup analyses:

1. maternal age below 35 versus 35 and above;

2. primipara versus multipara;

3. threatened miscarriage in first trimester versus second

trimester;

4. referred herbal medicines versus non-referred herbal

medicines, according to the formulary stated in the Chinese

Pharmacopeia;

5. short-term treatment (one course only) versus long-term

treatment (more than one course);

6. quasi-randomised clinical trials versus randomised clinical

trials.

In future updates of this review, we will use the following outcome

in subgroup analysis:

• continuation of pregnancy after 28 weeks of gestation.

For fixed-effect meta-analyses, we will conduct planned subgroup

analyses classifying whole trials by interaction tests as described by

Deeks 2001. For random-effects meta-analyses, we will assess dif-

ferences between subgroups by inspection of the subgroups’ con-

fidence intervals; non-overlapping confidence intervals indicating

a statistically significant difference in treatment effect between the

subgroups.

Sensitivity analysis

It was not necessary to carry out the planned sensitivity analyses

in this review. In future updates, we will carry out the following

prespecified sensitivity analyses, wherenecessary. We will carry outsensitivity analysis to explore the effect of trial quality for impor-

tant outcomes in the review. Sensitivity analyses will be performed

to examine the effect of:

1. high risk of bias in the allocation of participants to groups

associated with a particular study (Schulz 1995); or

2. high levels of missing data (Higgins 2011).

R E S U L T S

Description of studies

See: Characteristicsof included studies; Characteristicsof excluded

studies; Characteristics of studies awaiting classification.

From the169 clinical trialsof Chinese herbal medicines for threat-

ened miscarriage identified by the search, we assessed 63 poten-

tially eligible trials for inclusion in this review. We included 44

trials, excluded 17 trials, and two trials are still awaiting classifica-

tion, see Characteristics of studies awaiting classification.

Included studies

Forty-four trials (5100 women) were included for assessment and

meta-analysis in this review. All the participants were pregnant

Chinese women, and the studies were carried out in different

provinces of mainland China (middle-income country), mainly in

municipal hospitals and provincial level hospitals. For full details,

see Characteristics of included studies and Table 1 which is a qual-

ity assessment of selected randomised clinical trials.





Types of studies

All of the included studies were declared as randomised controlled

trials, although only a few of them (11 trials) did report the details

of randomisation methods.

Types of participants

All of the included trials recruited women with threatened miscar-

riages before 20 gestational weeks and who had not received any

treatment before the study commenced.

Types of interventions

Five trials compared Chinese herbal medicines with Western

medicinestreatments, while39 trials comparedcombinedChinese

herbal medicines and Western medicines with Western medicines

alone. We did not identify any trials comparing Chinese herbal

medicines with placebo or no treatment (including bed rest).

Follow-up

All the included trials followed up the participants until the end

of the treatments. Four of the included trials followed up the

participants until delivery, two of which reported the development

of the infants.

Excluded studies

Seventeen trials were excluded because the control group included

normal pregnant women; different Westernmedicines in the com-

bined medicines group and Western medicines group; Chinese

medicines versus Chinese medicines; Kampoo medicines versus Western medicines; low quality of the methodology; unqualified

gestational age. See Characteristics of excluded studies.

Risk of bias in included studies

All the included trials reported that they use randomisation meth-

ods when they recruited participants for different intervention

groups, and no missing data were reported. We double checked

each included study and found that the number of participants

were consistent with the numbers reported for outcomes and fol-

low-up. As there were no reports of drop-outs, and no evidence of

reporting biases on the number of participants, the interventions

and the outcomes in the 44 included studies, no subgroup analysis

was carried out.

Allocation

All the included clinical trials reported that the participants were

randomised, allocated and grouped. However, only 11 studies re-

ported detailed randomisation and allocation methods, including

’visiting sequence’, ’visiting date’, ’layered method’, ’randomised

number table’ and ’2:1 ratio randomisation’. See Characteristics of

included studies.

BlindingTwo studies reported that single blinding was applied but without

further details; we considered that no blinding was applied in the

other studies. Blinding was not feasible in this kind of clinical

study, especially to the participants and clinicians.

Incomplete outcome data

No incomplete data were reported in the included studies. After

double checking the total number of participants and the patients

included in each intervention group, there were no missing data

in all the studies.

Selective reporting

All the studies clearly reported the prespecified outcomes and all

expected outcomes of interest, and no incomplete outcomes were

recorded.

Other potential sources of bias

All included studies followed up the patients until the end of treat-

ment (which were prespecified in their studies), some studies con-

tinually followed up thehealthconditions of mothersafterdelivery

and the development of the newborn. Thirty-fourstudies reported

that there was no significant difference amongst the groups before

treatment, and were considered to have good baseline similarity.

Effects of interventions

We did not find any comparisons of Chinese herbal medicines

with placebo or no treatment in the 44 included studies. All in-

cluded studies compared Chinese herbal medicines with active in-

terventions (pharmaceuticals, mostly Western medicines). So only

two comparisons were included.

• Chinese herbal medicines alone versus Western medicines

alone.• Combined Chinese herbal and Western medicines versus

Western medicines alone.

Western medicines included tocolytic drugs (e.g. salbutamol and

magnesium sulfate), hormonal supplementations (e.g. HCG and

progesterone), immunotherapy (e.g. IgG immunisation and anti-

phospholipid antibodies) and supportive supplements (e.g. vita-

min E and folic acid).





Chinese herbal medicines alone versus Western

medicines alone

Primary outcomes

1. Effectiveness of the intervention: continuation of

pregnancy after 28 weeks of gestation

The rateof effectiveness (continuationof pregnancy after28 weeks

of gestation) appeared tobe higherin theChinese herbalmedicines

group (90.0%) compared with the group of women receiving

Western medicines (73.3%) but this difference was not statisti-

cally significant (risk ratio (RR) 1.23; 95% confidence interval

(CI) 0.96 to 1.57) ( Analysis 1.1). Only one trial (Zhong 2002)

was included in the analysis, with 60 participants, half of whom

were treated with Chinese herbal medicines while the other half

received with Western medicines.

2. Subgroup analysis

No data were available for subgroup analyses of maternal age be-

low 35 versus 35 and above, primipara versus multipara, threat-

ened miscarriage in first trimester versus second trimester, referred

herbal medicines versus non-referred herbal medicines, short-term

treatment (one course only) versus long-term treatment (more

than one course), or quasi-randomised clinical trials versus ran-

domised clinical trials.

Secondary outcomes

3. No relief of clinical signs (vaginal bleeding and abdominal

pain)

The incidence of no relief of clinical signs was lower in the women

in the Chinese herbal medicines group than those in the Western

medicines group, 10% versus 26.7%, respectively, however, the

difference was not statistically significant (RR 0.38; 95% CI 0.11

to 1.28) ( Analysis 1.2). Only one trial (Zhong 2002), involving

60 women, was included in this analysis.

4. Other prespecified outcomes

No data were available from the included studies for the follow-

ing prespecified outcomes: no improvement in laboratory inves-

tigations; repeated threatened miscarriage; preterm labor; adverse

pregnancy outcomes; livebirth; preterm birth; stillbirth; neonatal

death; fetal structural malformations; and other adverse perinatal

outcomes.

Non-prespecified outcomes

5. Effectiveness of intervention: continuation of pregnancy

after treatment

Fifteen studies with 1807 participants assessed the outcomes im-mediately after the course of treatment, instead of long-term ob-

servations after 28 weeks of gestation. Therefore, as a supplement

to the primary and secondary outcomes, we have included these

clinical trials and analysed the data as non-prespecified outcomes,

i.e., ’continuation of pregnancy after treatment’.

Chinese herbal medicine alone was, on average, significantly more

effective than Western medicines in preventing inevitable miscar-

riage and continuing the pregnancy, 87.7% versus 71.0%, respec-

tively (average RR 1.22; 95% CI 1.12 to 1.32) ( Analysis 1.12).

Substantial heterogeneity was observed (T² = 0.02; I² = 68%; Chi2 = 43.10, df = 14 (P less than 0.0001)), so we used a random-

effects model for this analysis.

Combined Chinese herbal medicines and Western

medicines versus Western medicines alone

Primary outcomes


after 28 weeks of gestation

A combination of Chinese herbal medicines and Western

medicines was more effective than Western medicines alone to

continue the pregnancy after 28 weeks of gestation, 94.4% ver-sus 73.6%, respectively (average RR 1.28; 95% CI 1.18 to 1.38)

( Analysis 3.1). In total, five clinical trials with 550 participants

were included (Chen 2002; Feng 1997; Lu 2011; Lv 2007; Zhong

2002).

2. Subgroup analysis

Due to a lack of detailed information, it was not possible to carry

out the planned subgroup analyses. Only the mean values and/or

ranges of maternal age in each group were reported in all the tri-

als, however, a comparison of women below 35 years and women

above 35 years old was not possible. All the clinical trials reported

the parity of the participants but did not provide details about

the parity in each group, so further comparisons of primipara and

multipara were not possible. Data on gestational age at threat-

ened miscarriage were only available in one study (Lu 2011), so a

comparison between first trimester and second trimester was not

possible. All of the Chinese herbal medicines and the supplements

were standard formulae as stated in Chinese Pharmacopeia, so no

subgroup analysis of referred and non-referred herbal medicines





was carried out. As to the treatment course, Chen’s study (Chen

2002) stopped the treatments around 12 weeks to five months of

gestation, Feng’s (Feng 1997) and Lu’s (Lu 2011) studies did not

report the termination of treatment but evaluated the effectiveness

after the relief of clinical signs. Lv’s study (Lv 2007) reported one

week as one course but did not give details on the total numberof the courses for the treatment. Zhong’s study (Zhong 2002) re-

ported that the treatment was stopped at two weeks after clinical

signs were relieved. Therefore, it is difficult to extract the data

and carry out subgroup analysis. There were no quasi-randomised

clinical trials in the included studies.

Secondary outcomes

3. No relief of clinical signs (vaginal bleeding and abdominal

pain)

The result showed that combined medicines treatment was moreeffective in the reliefof clinical signs than Westernmedicines treat-

ment, the incidence rates were 5.6% versus 26.4%, respectively,

(RR 0.21; 95% CI 0.13 to 0.36) ( Analysis 3.2). In total, five clin-

ical trials with 550 participants were included (Chen 2002; Feng

1997; Lu 2011; Lv 2007; Zhong 2002).

4. No improvement in laboratory investigations (urinary and

serum 08-HCG titre)

Only one trial (Lv 2007) measured serum ß-HCG and proges-

terone levels during the treatments. However, the author did not

report the results, so we could not include any data for further

analysis.

5. Other prespecified events

No data were available from the included studies for the following

prespecified outcomes: repeated threatened miscarriage; preterm

labour; adverse pregnancy outcomes; livebirth; preterm birth;still-

birth; neonatal death; fetal structural malformations; and other

adverse perinatal outcomes.

Non-prespecified outcomes


after treatment

Combined Chinese herbal and Western medicines was signifi-

cantly more effective than Western medicines alone for preventing

inevitable miscarriage (continuation of pregnancy), than Western

medicines alone 92.4% versus 72.8%, respectively (average RR

1.24; 95% CI 1.18 to 1.30;) ( Analysis 3.12). In total, 26 clinical

trials (involving 2809 women) were included in the analysis. Sub-

stantial heterogeneity was observed (T² = 0.00; I² = 37%; Chi²

= 39.91, df = 25 (P equal to 0.03)), so we used a random-effects

model in our analysis.

D I S C U S S I O N

Effectiveness

Chinese herbalmedicines claim to be effective, and are accepted as

an alternative treatment for threatened miscarriage in most Asian

countries. This review aimed to evaluate the therapeutic effects of

Chinese herbal medicines for threatened miscarriage. The most

valuable and important comparison to evaluate the intervention

is for Chinese herbal medicines to be compared with placebo.

However, no such trials were identified.

We identified five randomised clinical trials comparing Chineseherbal medicines with Western medicines. Meta-analysis indicates

that a combination of Chinese herbal and Western medicines

are more effective than other pharmaceuticals (Chinese herbal

medicines or Western medicines alone) for treating threatened

miscarriage, to prevent inevitable miscarriage and to continue the

pregnancy beyond 28 weeks’ gestation. However, we have no evi-

dence to assess whether Chinese herbal medicines alone are more

effective because no controlled trials of placebo versus no treat-

ment (including bed rest) were identified. As a non-prespecified

outcome, we examined the 39 studies that assessed effectiveness

immediately after the course of treatment (rather than long-term

observations after 28 weeks of pregnancy). These studies indi-

catedthat Chinese herbal medicinesalone weremore effectivethan Western medicines alone in treating threatened miscarriage. Chi-

nese herbal medicines alone or combined with Western medicines

were more effective than Western medicines alone in relieving the

clinical signs of threatened miscarriage, including vaginal bleed-

ing, low back pain and abdominal pain.

However, it should be emphasized that the use of Western

medicines, such as human chorionic gonadotropin (HCG) which

maintains the luteotrophic effects in supporting continued secre-

tion of placental oestrogen, and progesterone and progesterone,

are also not supported by evidence proving them to be beneficial

(Devaseelan 2010; Haas 2008), yet they are considered as classical

therapies for threatened miscarriage (Devaseelan 2010; Wahabi

2011). Most cases will progress to the next stage no matter what is

done. Even bed rest has no significant effects in altering the course

and progress of miscarriage ( Aleman 2005). So any conclusion on

the effectiveness of Chinese medicines for threatened miscarriage

is very tentative.

This review favoured Chinese herbal medicines for threatened

miscarriage. Most Chinese medicine practitioners have slightly

modified the classical prescriptions depending on the individual





clinical presentations. In the 44 included clinical trials, 20 trials

used a common prescription of Shou Tai Pill as a basic formula,

while the other 24 trials used other referred formulae. Some herbal

medicines have been added to, or removed from the standard for-

mula during treatment.

Adverse effects and follow-up

Chinese herbal medicines have been commonly used to treat

threatened miscarriage in attempts to promote maternal health

and embryo-fetal development. However, confirmation of safety

claims is still pending, so it is important to study the potential

adverse effects of Chinese medicines on mothers and fetuses. Most

of the clinical trials did not report whether there were side effects

of Chinese herbal medicines during treatment or afterwards. Very

few clinical trials followed up the pregnancy until, and after birth.

So we are unable to draw any conclusions about the safety of Chi-

nese herbal medicines for mothers and fetuses. Xiao’s study ( Xiao

2008), mentioned that all the participants were followed up after

one month of delivery, but didnot report anyfurther information.

Zhang’s study (Zhang 2008b), reported that no complications oc-

curred during the deliveries andthat all the infants developed well,

both mentally and physically, in the half-year follow-up. Song’s

study (Song 2007), reported that there were no congenital mal-

formations of the newborns and that no adverse effects occurred

during the treatment, but did not provide any detailed data. Li’s

study (Li 2006), reported detailed information and data on the

percentage of follow-up, termdelivery and preterm delivery, Apgar

scores of newborns and average newborn weight. Thus, only one

in four trials was available but no further analysis could be carried

out.

Study design

With regard to the design of the clinical trials of Chinese herbal

medicines, there are still many limitations. Firstly, well-conducted

randomised controlled trials are important for meta-analysis. All

the selected trials in this review had inadequate methodological

quality, compared with foreign literature. For the five trials in-

cluded for the primary outcome analysis, the authors reported

that the women were randomised in the control and intervention

groups, but none of them reported the detailed methods used for

randomisation. For the other 39 trials, only seven trials reported

adequate sequence generation, “layered method” (Li 2004), “ran-

domised number table” (Li 2006; Wang 2011; Xiao 2008; Zhang

2008a ) and “2:1 ratio randomisation” (Hou 2010; Yang 2006);

while four trials reported inadequate sequence generation, “visit-

ing sequence” (Chen 2003) and “visiting date” (Liu 2008; Song

2007; Sun 2003). None of the 44 trials reported the method of

blinding, but from the descriptions of methods reported in each

trial, we believe that all studies were open to both the doctors and

the women. In line with other reports ( Wu 2007; Wu 2009; Zhuo

2008), it is not surprising that many problems in the study designs

and methodologies of clinical trials of Chinese herbal medicines

were identified. Trial quality would be greatly improved if the tri-

alists were adequately trained to carry out and report such clini-

cal trials according to the international standard, including suffi-cient details of randomisation method and having adequate allo-

cation concealment, double-blinded participants, researchers and

outcome assessors, participants classifications, and effects assess-

ments.

Secondly, a good clinical trial should also provide some essential

information, such as the average days or weeks of the treatments,

the changes in medicine dosage and compositions, the number

of women with a successful pregnancy until 28 weeks or after-

wards, and the mortality and follow-up of newborns, which would

be helpful to examine the effects of Chinese herbal medicines

in the treatment of this condition. Thirdly, there is a potential

risk that the interventions were delivered in a way that automat-

ically favoured the group receiving Chinese medicines. Detailedinformation on the standardisation of the treatment in the con-

trol groups is lacking, so there is no way of knowing whether the

treatment periods in the two groups were similar. This leads to

concerns about whether the two groups were treated equivalently.

Finally, the small numbers of qualified clinical trials and insuffi-

cient information in this review prevented us from carrying out

planned subgroup analysis which could inform this review on the

effectiveness and safety of Chinese herbal medicines.

In summary, comparisons made between different treatments

of threatened miscarriage suggest that combined Chinese herbal

and Western medicines were more effective than Chinese herbal

medicines alone or Western medicines alone for treatment of

threatened miscarriage.

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

No placebo controlled trials were available for comparison.

Paucity of evidence supported the effectiveness of Chinese herbal

medicines alone for the treatment of threatened miscarriage for

preventing pregnancy loss and continuing the pregnancy after 28

weeks. However, combined treatments were significantly more ef-

fective than Western medicines alone for preventing miscarriage.

Systematic information regarding the potential harm and long-term effects to the mother or child, or both, with the use of Chi-

nese herbal medicines in the treatment of threatened miscarriage

was lacking.

Implications for research

It is both interesting and important to identify the active com-

poundsin theChinese herbalmedicines that are beneficialin treat-





ingthreatenedmiscarriage.Thiswill involve studyingpharmacoki-

netics as well as the mechanismand the interactions of these active

compounds with Western medicines. In addition, lack of quali-

fied placebo controlled trials, adequate randomisation methods,

potential bias in intervention limit the conclusions of the system-

atic reviews in Chinese herbal medicines. We strongly recommendstandardisation of clinical trials on the efficacy of Chinese herbal

medicines during pregnancy.

A C K N O W L E D G E M E N T S

We appreciate the help given by the Managing Editor (Sonja Hen-

derson), and other associates (Denise Atherton, Frances J Kellie,

Jill Hampson, Lynn Hampson and Therese Dowswell) in the ed-

itorial office of the Cochrane Pregnancy and Childbirth Group.

As part of the pre-publication editorial process, this review has

been commented on by three peers (an editor and two referees

who are external to the editorial team), a member of the Pregnancy

and Childbirth Group’s international panel of consumers and the

Group’s Statistical Adviser.

The preparation of this review was partially supported by the

Health and Health Service Research Grant from Food and HealthBureau, Hong Kong Special Administration Region (HHSRF

06070511 & 09100031) to CCW and PCL.

LL received the Hop Wai Scholarship and Zi Ying Scholarship

from the Institute of Chinese Culture and Postgraduate Stu-

dent Grants for Overseas Academic Activities from the Graduate

School, The Chinese University of Hong Kongto attend Cochrane

training workshops in Oxford and Freiburg and to visit the Edi-

torial Base of the Cochrane Pregnancy and Childbirth Group at

University of Liverpool in order to receive one to one training and

support; LL received a Yu To Sang Memorial Scholarship 2008/

2009 and 2009/2010 from The Chinese University of Hong Kong

to pursue her PhD study.

R E F E R E N C E S

References to studies included in this review

Chen 2002 {published data only}

Chen JH, Wang J, Shang L. Integrated medicines for 51

cases of threatened miscarriage. Ning Xia Medicine Journal

2002;24(8):506.


Chen LZ. Combined TCM and west medicine to treating

45 cases of threatened miscarriage. Hunan Guiding Journal of TCMP 2003;9(3):29.

Cui 2002 {published data only}

Cui XP, Yang JB, Deng YC. Tai Er An decoction for

threatened miscarriage. Shan Xi Traditional Chinese

Medicine 2002;23(5):387–8.

Deng 2009 {published data only}

Deng WH. Integrated treatment for 100 cases of threatened

miscarriage during early pregnancy. Zhe Jiang Journal of

Traditional Chinese Medicine 2009;44(2):117.

Feng 1997 {published data only}

Feng ZR. Integrated medicines for 61 cases of threatened

miscarriage. Jiang Su Journal of Traditional Chinese Medicine

1997;18(9):23.Feng 2010a {published data only}

Feng YQ. The effects on ß-HCG and CA125 of Bu Shen

An Tai method for threatened miscarriage. Shan Xi Journal

of Chinese Medicine 2010;31(7):790–1.

Feng 2010b {published data only}

Feng YQ, Wang L. Clinical observational study of Bu Shen

An Tai method for threatened miscarriage. He Bei Journal of

Chinese Medicine 2010;32(1):52–3.

Fu 2006 {published data only}

Fu XX. Integrated medicines for threatened miscarriage.

Forum on Traditional Chinese Medicine 2006;21(3):40–1.

Hou 2010 {published data only}

Hou LL, Shen WW. Chinese medicines for threatened

miscarriage. Si Chuang Journal of Chinese Medicine 2010;28

(11):96–7.

Hu 2010 {published data only}Hu HJ, Xie YH. San Huang An Tai decoction for early

threatened miscarriage. Journal of Emergency Traditional


Huang 2011 {published data only}

Huang P, Zhang L, Wei YH, Ma BM. Combined Chinese

medicines and western medicines for early threatened

miscarriage. Chinese Journal of Modern Drug Application

2011;5(7):90–1.

Kuang 2007 {published data only}

Kuang LJ, Kuang JL. Integrated treatment for threatened

miscarriage during early pregnancy. Chinese Archives of

Traditional Chinese Medicine 2007;25(7):1527–8.

Li 2004 {published data only}

Li WL, Li DJ, Lu Y, Zhou J, Liu CL. Bu Shen An Tai Yin

for threatened miscarriages. Clinical Journal of Traditional



Li SX, Chen HY. Integrated medicines for threatened

miscarriage. He Bei Journal of Traditional Chinese Medicine

2005;27(3):216–7.






Li L, Zhou CX, Liu JY. Bu Shen Gu Tai Decoction with

Hermone Therapy for Threatened Miscarriage. Guang Xi


Li 2009a {published data only}

Li YM, Yang Y. Integrated medicines for threatened

miscarriages during early pregnancy. Journal of ChangchunUniversity of Traditional Chinese Medicine 2009;25(2):

255–6.

Li 2009b {published data only}

Li Z, Nong YS. Integrated medicines for 91 cases of

threatened miscarriage in early pregnancy. He Bei Journal of



Li GR, Zhang N. An Tai decoction for threatened

miscarriage. Shan Xi Journal of Chinese Medicine 2010;31

(11):1447–9.

Liu 2008 {published data only}

Liu SM. Integrated medicines for threatened miscarriages.

Family Nurse 2006;6(5c):1370.Liu 2009 {published data only}

Liu F, Meng QC, Yao J, Jiang LP. Bu Shen Jian Pi formula

for 30 cases of threatened miscarriage. Journal of New


Liu 2011a {published data only}

Liu SL. Bao Chang decoction for early threatened

miscarriage. Guang Ming Journal of Chinese Medicine 2011;

26(10):2023–4.

Liu 2011b {published data only}

Liu XM. Bao Tai decoction for threatened miscarriage.

Chinese Journal of Misdiagnosis 2011;11(13):3111.

Lu 2011 {published data only}

Lu YJ. Chinese medicines for threatened miscarriage: 104cases. Shan Dong Journal of Chinese Medicine 2011;30(3):

176.

Lv 2007 {published data only}

Lv XH, Han YP, Luo Y. Integrated medicines for 58 cases

of threatened miscarriages. Yun Nan Journal of Traditional

Chinese Medicine 2007;28(12):11.

She 2008 {published data only}

She XH, Tang JQ. Integrated medicines for threatened

miscarriages. Guang Xi Journal of Traditional Chinese

Medicine 2008;31(3):43.

Shen 2010 {published data only}

Shen YQ, Wu XH, Wei JM. Combined Chinese and

western medicines for early threatened miscarriage. Jiang Su

Journal of Chinese Medicine 2010;2:11.

Song 2005 {published data only}

Song YL, Zhao YQ, Zhang XY. Clinical observations on

126 cases of early threatened miscarriage treated by Zhi Xue

Bao Tai Yin. Journal of Traditional Chinese Medicine 2005;

46(2):116–8.

Song 2007 {published data only}

Song YL, Zhu LP. The fetus protection effects of Zhi Xue

Bao Tai decoction on women of early threatened miscarriage

with dark area surrounding pregnancy sac. Chinese Journal

of Integrated Traditional and Western Medicine 2007;27(11):

1025–8.

Sun 2003 {published data only}

Sun GY, Yin XH. Clinical efficacy on the sex hormone of

combination of Chinese medicine and west medicine for

the treatment of threatened miscarriage. Hunan Guiding Journal of TCM 2003;9(11):33–4.

Wang 2005 {published data only}

Wang XF, OuYang XB. Intergrated medicines for threatened

miscarriages. Fujian Journal of Traditional Chinese Medicine

2005;36(1):43–4.


Wang YB, Li XH. Bu Shen Gu Chong decoction for 48

cases of threatened miscarriages. Liao Ning Journal of



Wang ZM, Ji QY. Integrated medicines for early threatened

miscarriage. Traditional Chinese Medicine Research 2010;23

(9):46–7. Wang 2011 {published data only}

Wang F, Liu XH. Clinical efficacy of Gushen Antai pill for

early threatened abortion. Evaluation and Analysis of Drug-

use in Hospitals of China 2011;11(12):1121–3.

Xiao 2008 {published data only}

Xiao ZX. Integrated medicines for 30 cases of threatened

miscarriage. Cuiding Journal of Traditional Chinese Medicine

and Pharmacy 2008;14(6):59–60.

Xu 2005 {published data only}

Xu H, Hu YJ. Integrated medicines for 32 cases of

threatened miscarriages, with progesterone as control. Zhe

Jiang Journal of Traditional Chinese Medicine 2005;9:383.

Xun 2008 {published data only} Xun AH, Xia QH. Integrated medicines for threatened

miscarriages. Modern Traditional Chinese Medicine 2008;5

(16):7.

Yang 2001 {published data only}

Yang LF. Integrated medicines for threatened miscarriage

(42 cases). Jiang Xi Journal of Traditional Chinese Medicine

2001;32(2):57.

Yang 2006 {published data only}

Yang MQ. Integrated medicines for 100 cases of threatened

miscarriage in early pregnancy. Guangxi Medical Journal

2006;28(12):1984–5.

Zeng 2011 {published data only}

Zeng JT. Clinical observation of integrated medicines for

threatened miscarriage. Guide of Chinese Medicine 2011;9(17):295–6.

Zhang 2007 {published data only}

Zhang XF, Li X, Wang XR. Integrated medicines for

threatened miscarriages. Hu Bei Journal of Traditional

Chinese Medicine 2007;29(6):40.

Zhang 2008a {published data only}

Zhang XM. Integrated medicines for 50 cases of threatened

miscarriage in early pregnancy. Cuiding Journal of





Traditional Chinese Medicine and Pharmacy 2008;14(10):

38–9.

Zhang 2008b {published data only}

Zhang H. Integrated treatment to threatened miscarriage

and the effects on estrogen levels. Journal of Sichuan of


Zhong 2002 {published data only}

Zhong DM, Jiang HZ. Jian Pi Gu Shen therapy for 90 cases

of threatened miscarriage. Traditional Chinese Medicine

Research 2002;15(4):24–6.

Zhou 2010 {published data only}

Zhou BQ. An Tai decoction for threatened miscarriage.

Chinese Journal of Ethnomedicine and Ethnopharmacy 2010;

16:168.

References to studies excluded from this review

Bi 2010 {published data only}

Bi LM. Outcomes of integreated medicines for threatened

miscarriage. Chinese Community Physician 2010;17:99.

Chan 2010 {published data only}Chen M. Integrated medicines for theatened miscarriage.

Chinese journal of ethnomedicine and ethnopharmacy 2010;

15:196–8.

Gao 2011 {published data only}

Gao J, Luo SP. Clinical observation of Shoutai pills for

treatment of early threatened abortion. Journal of New


Guo 2010 {published data only}

Guo YQ, Jiao LM. Integrated medicines for early threatened

miscarriage. He Nan Journal of Traditional Chinese Medicine

2010;30(2):176–7.

Hu 2010b {published data only}

Hu YF, Zhang JM. Yun Kang decoction for threatened

miscarriage. Shan Xi Journal of Chinese Medicine 2010;41(330):49.


Li W. Integrated medicines for threatened miscarriage.

Chinese Journal of Coal Industry Medicine 2011;14(6):

885–6.

Lin 2010 {published data only}

Lin GQ. An Tai decoction for early threatened miscarriage.

Family Medicine 2010;9:665–6.

Lu 2007 {published data only}

Lu Z, Jin S, Chen H. Clinical observation on Chinese

integrative medicine in the treatment of threatened

abortion. China Medical Herald 2007;4(32):73–4.

Lu 2011b {published data only}Lu QB, Ren QL, Haung MH, Lu Y, Ni YY, Xu JY. Clinical

evaluation of An Zi mixture’s effects on treating threatened

abortion. Journal of Nan Jing Traditional Chinese Medicine

2011;27(5):414–7.

Lu 2011c {published data only}

Lu QY, Shen JH. Chinese medicines for threatened

miscarriage: 30 cases. Hu Nan Journal of Traditional Chinese

Medicine 2011;27(1):63–110.

Luo 2010 {published data only}

Luo LH, Gui P, Zhou AL. Shoutai pill combined with

western medicines for threatened miscarriage. Shen Zhen

Journal of Integrated Medicines 2010;20(1):51–2.

Qin 2010 {published data only}

Qin XR. Chinese medicines for early threatened miscarriage:

150 cases. Si Chuan Journal of Traditional Chinese Medicine

2010;28(12):88–90.

Ushiroyama 2006 {published data only}

Ushiroyama T, Araki R, Sakuma K, Nosaka S, Yamashita Y,

Kamegai H. Efficacy of the kampo medicine Xiong-Gui-

Jiao-Ai-Tang, a traditional herbal medicine, in the treatment

of threatened abortion in early pregnancy. American Journal

of Chinese Medicine 2006;34(5):731–40.

Wu 2010 {published data only}

Wu JF, Zhao HY. Integrated medicines for threatened

miscarriage. China Naturopathy 2010;8(1):44.


Zhang JF, Zhang YF, Liu GZ, Feng QJ. Clinical and

experimental study on Yun’an granule in treating threatened

abortion. Chinese Journal of Integrative Medicine. 2000;20

(4):251–4.


Zhang TT, Huang CM, Qin BF, Su LD, Dai DY. Treatment

to 140 cases of threatened miscarriage (kidney deficiency).

Shan Dong Journal of Chinese Medicine 2006;25(4):235–7.


Zhang Y. Hu tai decoction combined with western

medicines for threatened miscarriage. Shan Xi Journal of


References to studies awaiting assessment


Chen SQ. Clinical observations on integrative medicines

for 480 cases of threatened miscarriage. Hu Nan Journal of

Traditional Chinese Medicine Mar. 1999;15(2):15.

Guan 2008 {published data only}

Guan HF. Combined Chinese medicines and Western

medicines for 50 cases of threatened miscarriages. Modern

Traditional Chinese Medicine Jul. 2008;28(4):26–7.

Additional references

Aleman 2005

Aleman A, Althabe F, Belizán JM, Bergel E. Bed rest during

pregnancy for preventing miscarriage. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/

14651858.CD003576.pub2]

Bandyopadhyay 2010

Bandyopadhyay AR, Chatterjee D, Chatterjee M, Ghosh

JR. Maternal fetal interaction in the ABO system: A

comparative analysis of healthy mother and couples with

spontaneous abortion in Bengalee population. American

Journal of Human Biology 2011;23(1):76–9.





Batzofin 1984

Batzofin JH, Fielding WL, Friedman EA. Effect of vaginal

bleeding in early pregnancy on outcome. Obstetrics &

Gynecology 1984;63:515.

Choudhury 2010

Choudhury SR, Knapp LA. Human reproductive failure I:

immunological factors. Human Reproduction Update 2010;

7(2):113–34.

Cunningham 2005

Cunningham G, Leveno KL, Bloom SL, Hauth JC, Gilstrap

LC III, Wenstrom KD. Williams Obstetrics . 22nd Edition.

New York: Mcgraw-Hill Professional Publishing, 2005.

DeCherney 2007

DeCherney AH, Nathan L. Current Diagnosis & Treatment

Obstetrics & Gynecology . 10th Edition. New York: McGraw-

Hill Professional Publishing, 2007.

Deeks 2001

Deeks JJ, Altman DG, Bradburn MJ. Statistical methods

for examining heterogeneity and combining results fromseveral studies in meta-analysis. In: Egger M, Davey Smith

G, Altman DG editor(s). Systematic reviews in health care:

meta-analysis in context . London: BMJ Books, 2001.

Devaseelan 2010

Devaseelan P, Fogarty PP, Regan L. Human chorionic

gonadotrophin for threatened miscarriage. Cochrane

Database of Systematic Reviews 2010, Issue 5. [DOI:

10.1002/14651858.CD007422.pub2]

El-Zibdeh 2009

El-Zibdeh MY, Yousef LT. Dydrogesterone support in

threatened miscarriage. Maturitas 2009;65 Suppl 1:

S43–S46.

Funderburk 1980Funderburk SJ, Guthrie D, Meldrum D. Outcome of

pregnancies complicated by early vaginal bleeding. British

Journal of Obstetrics and Gynaecology 1980;87:100.

Gracia 2005

Clarisa R, Gracia. Risk factors for spontaneous abortion in

early symptomatic first-trimester pregnancies. Obstetrics &

Gynecology 2005;106(5):993–9.

Haas 2008

Haas DM, Ramsey PS. Progestogen for preventing

miscarriage. Cochrane Database of Systematic Reviews 2008,

Issue 2. [DOI: 10.1002/14651858.CD003511.pub2]

Higgins 2011

Higgins JPT, Green S, editors. Cochrane Handbook forSystematic Reviews of Interventions Version 5.1.0 [updated

March 2011]. The Cochrane Collaboration, 2011.

Available from www.cochrane-handbook.org.

Kano 2007

Kano T, Mori T, Furudono M, Ishikawa H, Watanabe H,

Kikkawa E, et al.Human leukocyte antigen may predict

outcome of primary recurrent spontaneous abortion treated

with paternal lymphocyte alloimmunization therapy.

American Journal of Reproductive Immunology 2007;58(4):

383–7.

Li 2005b

Li JB. Zhong Yi Xue . 6th Edition. People’s Health

Publishing House, 2005.

Li 2011b

Li Lu. Efficacy and safety of Chinese medicines for

pregnancy. PhD thesis, The Chinese University of Hong

Kong, Hong Kong 2011.

Liu 2002

Liu RF. Clinical observation of integrated traditional and

western medicine. Chinese Journal of Integrated Traditional

and Western Medicine 2002;22:68–9.

Loue 2004

Loue S, Sajatovic M. Encyclopedia of Women’s Health.

Springer, 2004:420–1.

Lyttleton 2004

Lyttleton J. Treatment of Infertility with Chinese Medicine .

Churchill Livingstone, 2004:315.

Ma 2006

Ma B. Zhong Yi Fu Ke Xue . Vol. 8, Shanghai: Science &

Technology Press, 2006:4.

Petrozza 2006

Petrozza JC. Early pregnancy loss. http://

emedicine.medscape.com/article/260495-overview

(accessed 2009) 2006.

RevMan 2011

The Nordic Cochrane Centre, The Cochrane Collaboration.

Review Manager (RevMan). 5.1. Copenhagen: The Nordic

Cochrane Centre, The Cochrane Collaboration, 2011.

Schulz 1995

Schulz KF, Chalmers I, Hayes R, Altman D. Empirical

evidence of bias. JAMA 1995;273:408–12.Suzumori 2010

Suzumori N, Sugiura-Ogasawara M. Genetic factors as a

cause of miscarriage. Current Medicinal Chemistry 2010;17

(29):3431–7.

Tabacova 1994

Tabacova S, Little RE, Balabaeva L, Pavlova S, Petrov I.

Complications of pregnancy in relation to maternal lipid

peroxides, glutathione, and exposure to metals. Reproductive

Toxicology 1994;8(3):217–24.

Tien 2007

Tien JC, Tan TYT. Non-surgical interventions for

threatened and recurrent miscarriages. Singapore Medical

Journal 2007;48(12):1074–89.

Wahabi 2011

Wahabi HA, Abed Althagafi NF, Elawad M, Al Zeidan RA.

Progestogen for treating threatened miscarriage. Cochrane

Database of Systematic Reviews 2011, Issue 3. [DOI:

10.1002/14651858.CD005943.pub3]

Weiss 2004

Weiss JL, Malone FD, Vidaver J. Threatened abortion:

a risk factor for poor pregnancy outcome, a population-





based screening study. American Journal of Obstetrics and

Gynecology 2004;190:745.

Wu 2007

Wu TX, Liu GJ. What about the concepts, design, practice

and report of allocation concealment and blinding exactly?

. Chinese Journal of Evidence-Based Medicine 2007;7(3):

203–7.

Wu 2009

WuTX, Li YP, Bian ZX, Liu GJ, Moher D. Randomized

trials published in some Chinese journals:how many are

randomized?. Trials 2009;10:46.

Zhuo 2008

Zhuo Q, Wu TX, Yang XZ, Zeng XX, Yuan Y. Identification

and authentication of claimed RCTs for Cochrane

systematic review. 16th Cochrane Colloquium, Freiburg.

3–7 October 2008.∗ 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]

Chen 2002

Methods Randomised controlled trial of combined medicines (Chinese herbal medicines + West-

ern medicines) compared with Western medicines alone

Participants 84 inpatients or outpatients from People’s Hospital of Ning Xia were recruited. Partici-

pants were all diagnosed as threatened miscarriage due to vaginal bleeding and abdomi-

nal pains

Interventions Treatment group received Chinese herbal medicines combined with Western medicines

1) The Chinese medicine formula was Shou Tai Pill, including Chinese Dodder Seed 30

g; Himalayan Teasel Root, Chinese Taxillus Twig 20 g, and Donkey-hide Glue 15 g

2) Formula changes• Qi deficiency: Pilose Asiabell Root, Mongolian Milkcetch Root 15 g each; and

Liquorice Root 6 g were added.

• Blood deficiency: Chinese Angelica, and White Paeony Root 10 g were added.

• Blood heat: Baical Skullcap Root 10 g was added.

• Yin deficiency: Rehmannia Root 15 g, Glossy privet fruit 10 g, and Yerbadetajo

Herb 10 were added.

• Severe vomiting: tangerine peel 10 g, Villous Amomrum Fruit 10 g, and Perilla

Stem 10 g were added.

• Spleen deficiency: Largehead Atractylodes Rhizome 10 g was added.

• Severe bleeding: Hairyvein Agrimonia 15 g, Chinese Arborvitae Twig 12 g,

Dragon Bone 30 g, and Fortune Windmillpalm 10 g were added.

3) Decoction: po, BID until 12 weeks or 5 months of pregnancy

4) Western medicines were received at the same time, including HCG 2000 U, im, qd;progesterone 20~40 mg, im, bid; vitamin E 100 mg, po, qd; folic acid 5 mg, po, tid;

Salbutamol sulfate 2 pills, po, tid; 25% magnesium sulfate 60 ml ivgtt

Control group was treated with Western medicines alone.

Same as above, HCG 2000U, im, qd; progesterone 20~40 mg, im, bid; vitamin E 100

mg, po, qd; folic acid 5 mg, po, tid; Salbutamol Sulfate 2 pills, po, tid; 25% magnesium

sulfate 60 mL ivgtt

Outcomes Symptoms subsided and pregnancy maintained until del ivery were considered as effec-

tive. The effectiveness rate of combined medicines group was 96.07%, and Western

medicines group was 69.69% (P < 0.05)

Notes RCT with 2 arms.

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence generation (selection

bias)

Unclear risk “patients were randomly allocated.”





Chen 2002 (Continued)

Allocation concealment (selection bias) Unclear risk “patients were randomly allocated.”

Blinding (performance bias and detectionbias)

All outcomes

High risk Blinding of participants and clinicians wasnot feasible.

Incomplete outcome data (attrition bias)

All outcomes

Low risk No exclusion was reported. No losses were

reported. It was an ITT

Selective reporting (reporting bias) Unclear risk The protocol of the trial was not available.

Other bias Unclear risk No information was provided on the bal-

ance of baseline.

Chen 2003



Participants 83inpatientsfromAffiliatedHospitalofHengDongNurse School wererecruited(1999-

2002). Participants were all diagnosed as threatened miscarriage due to vaginal bleeding

and abdominal pains


1) The Chinese medicine formula was Tai Shan Pan Shi Yin, including Pilose Asiabell

Root 12 g, Mongolian Milkcetch Root 10 g, Largehead Atractylodes Rhizome 10 g,

Liquorice Root 5 g, Chinese Angelica 12 g, Szechuan Lovage Rhizome 3 g, White Paeony

Root 9 g, Steamed Rehmannia Root 12 g, Himalayan Teasel Root 10 g, Baical SkullcapRoot 8 g, and Villous Amomrum Fruit 3 g

2) Formula changes

• Heat excess: Villous Amomrum Fruit was removed and Baical Skullcap Root was

increased to 16 g.

3) Decoction: po, bid.

4) Western medicines were received at the same time, including HCG 1000 U, im, qd

till bleeding stopped; vitamin E 20 mg, po, tid

Control group was treated with Western medicines alone. Same as above, HCG 1000U,

im, qd till bleeding stopped; vitamin E 20 mg, po, tid

Outcomes Symptoms such as vaginal bleeding and abdominal pains subsided, and clinical exam-

inations showed pregnancy maintained were considered as effective. The effectiveness

rate of combined medicines group was 93.33%, and Western medicines group was 76.

32% (P < 0.05)


Risk of bias






Chen 2003 (Continued)


bias)

High risk “Randomised into two groups by visiting

sequence.”

Allocation concealment (selection bias) High risk “Randomised into two groups by visiting

sequence.”

Blinding (performance bias and detection

bias)

All outcomes

High risk Blinding of participants and clinicians was

not feasible.


All outcomes


reported (but the participants were allo-

cated according to attending sequence and

therewas a gap betweenthe numbers of the

2 groups). It was an ITT


Other bias Low risk The intervention groups were comparable,

“no significant difference was found be-

tween groups”

Cui 2002

Methods Randomised controlled trial of Chinese herbal medicines compared with Western

medicines

Participants 70 inpatients or outpatients from Affiliated Hospital of Shan Xi Chinese MedicineCollege were recruited (1995 March-2000 December). Participants were all diagnosed

as threatened miscarriage due to vaginal bleeding and abdominal pains

Interventions Chinese herbal medicine group:

1) Tai Er An decoction: mainly used Chinese Taxillus Twig, Chinese Dodder Seed,

Himalayan Teasel Root, 15 g each; Cattail Pollen, Trogopterus Dung 9 g each; Danshen

Root, Villous Amomrum Fruit, Perilla Stem, Donkey-hide Glue, White Paeony Root

10 g each; and Liquorice Root 6 g

2) Decoction: po, TID.

The Western medicines group used progesterone 20 mg, im, qd; 3 days as a course,

usually 5 courses

Outcomes Symptoms such as vaginal bleeding and abdominal pains subsided, and clinical exami-

nations shows pregnancy maintained were considered as effective. The effectiveness rate

of Chinese medicines group was 98%, and Western medicines group was 65% (P < 0.

05)


Risk of bias





Cui 2002 (Continued)


Random sequence generation (selectionbias)




bias)

All outcomes

Low risk Single blinding was reported in this study,

but the review authors doubt if it was a real

single-blinding, as the study author did not

report the detailed method of blinding of

participant


All outcomes






tween groups”

Deng 2009



Participants 200 participants at the Department of Obstetrcis and Gynaecology, Chinese Medicine

Hospital of Foshan (Guangzhou, China) were recruited. Participants were all diagnosed

as threatenedmiscarriageby HCGand ultrasound examination, and suffered withvaginal

bleeding and abdominal pains


1) The Chinese medicine formula: included Donkey-hide Glue, Pilose Asiabell Root,

White Paeony Root, Himalayan Teasel Root 15 g each; Prepared Rhizome of Adhesive

Rehmannia, Chinese Taxillus Twig, 20 g each; Chinese Dodder Seed 30 g; and Chinese

Mugwort leaf and Liquorice Root 10 g each

2) Formula changes

• Significant low back pain: Eucommia Bark 15 g was added, Chinese Taxillus Twig

was increased to 30 g.• Hard stool: Desertliving Cistanche 10 g was added.

• Combined with habitual miscarriage: Lotus Seed, and Ramie Root 10 g were

added.

3) Decoction: po, qd

4) Western medicines were received at the same time, including HCG 1000U, im, qd

for 10 days then decline the dosage; vitamin E 100 mg, po, tid; folic acid 0.4 mg, qd






Deng 2009 (Continued)

im, qd for 10 days then decline the dosage; vitamin E 100 mg, po, tid; folic acid 0.4 mg,

qd

Outcomes Symptoms such as vaginal bleeding and abdominal pains subsided and pregnancy main-

tained were considered as effective. The effectiveness rate of combined medicines group

was 95% while Western medicines group was 72% (P < 0.05)


Risk of bias



bias)

Unclear risk “the patients were randomized divided into

2 groups.”

Allocation concealment (selection bias) Unclear risk “the patients were randomized divided into

2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Feng 1997



Participants 108 outpatients from Second Affiliated Hospital of Hunan University of Chinese

Medicine were recruited (1995 January-1996 Novenber). Participants were all diagnosed



1) The Chinese medicine formula was Shou Tai Pill, included Chinese Dodder Seed 30

g, Himalayan Teasel Root 20 g, Chinese Taxillus Twig 20 g, Donkey-hide Glue 10 g;

Pilose Asiabell Root, White Paeony Root, Himalayan Teasel Root 15 g each; Prepared

Rhizome of Adhesive Rehmannia, Chinese Taxillus Twig 20 g each; Chinese Dodder

Seed 30 g; and Chinese mugwort leaf and Liquorice Root 10 g each

2) Formula changes





Feng 1997 (Continued)

• Qi deficiency: Pilose Asiabell Root 15 g, Mongolian Milkcetch Root 15 g, and

Liquorice Root 6 g were added.

• Blood deficiency: Chinese Angelica 10 g and White Paeony Root 10 g were added.


• Yin deficiency: Rehmannia Root 15 g, Glossy Privet Fruit 10 g, and Yerbadetajo

Herb 10 g were added.

• Increased vomiting: Tangerine Peel 10 g, Villous Amomrum Fruit 10 g, and

Perilla Stem 10 g were added.

• Spleen deficiency: Largehead Atractylodes Rhizome 10 g was added.

• Increased bleeding: Herb of Hairyvein Agrimonia 15 g, Chinese Arborvitae Twig

10 g, Dragon Bone 30 g were added.

3) Decoction: po, QOD.

4) Western medicines were received at the same time, including vitamin E, folic acid,

progesterone (regular dosage but not listed in the study)

Control group was treated with Western medicines alone. Same as above, vitamin E,

folic acid, progesterone (regular dosage but not listed in the study)

Outcomes Symptoms subsided and pregnancy maintained till delivery were considered as effective.

The effectiveness rateof combined medicinesgroup was 95.08%, and Westernmedicines

group was 70.21% (P < 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes





ance of baseline.





Feng 2010a


medicines

Participants 202 outpatients from Chinese Medicine Hospital of Shi Jia Zhuang were recruited.Participants were all diagnosed as threatened miscarriage due to vaginal bleeding and

abdominal pains


1) Bu Shen An Tai decoction: mainly used Chinese Taxillus Twig, Chinese Dodder Seed,

Himalayan Teasel Root, Milkvetch Root, Pilose Asiabell Root, Eucommia Bark, 15 g

each; Medicinal Cornel Fruit, Yerbadetajo Herb, 12 g each; Donkey-hide Glue, Glossy

Privet Fruit, 10 g each; Morinda Root 9 g

2) Decoction: po, BID.

The Western medicines group used dydrogesterone 4 pills, po, once, then 1 pill, po,

TID; till 3 days after bleeding stopped



of Chinese medicines group was 87.5%, and Western medicines group was 77% (P < 0.

01). ?-HCG significantly increased (P < 0.01) while CA-125 significantly decreased (P

< 0.01)


Risk of bias


Random sequence generation (selectionbias) Unclear risk “the patients were randomized divided into2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”





Feng 2010b


medicines

Participants 78 outpatients from Chinese Medicine Hospital of Shi Jia Zhuang were recruited. Par-ticipants were all diagnosed as threatened miscarriage due to vaginal bleeding and ab-

dominal pains


1) Bu Shen An Tai decoction: mainly used Chinese Taxillus Twig, Chinese Dodder Seed,

Himalayan Teasel Root, Milkvetch Root, Pilose Asiabell Root, Eucommia Bark, 15 g

each; Medicinal Cornel Fruit, Yerbadetajo Herb, 12 g each; Donkey-hide Glue, Glossy

Privet Fruit, 10 g each; Morinda Root 9 g


The Western medicines group used dydrogesterone 4 pills, po, once, then 1 pill, po,

TID; till 3 days after bleeding stopped



of Chinese medicines group was 87.5%, and Western medicines group was 76.3% (P <

0.01). CA-125 significantly decreased (P < 0.01)


Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”





Fu 2006



Participants 87 inpatients from First Affiliated Hospital of Zhong Shan University were recruited(2004 May-2006 May). Participants were all diagnosed as threatened miscarriage due to

vaginal bleeding and abdominal pains


1) The Chinese medicine formula was Si Wu soup, included Steamed Rehmannia Root

12 g, Chinese Angelica 9 g, White Paeony Root 9 g, Szechuan Lovage Rhizome 6 g;

Donkey-hide Glue, Pilose Asiabell Root, White Paeony Root, Himalayan Teasel Root

15 g each; Prepared Rhizome of Adhesive Rehmannia, Chinese Taxillus Twig 20 g each;

Chinese Dodder Seed 30 g; and Chinese Mugwort Leaf and Liquorice Root 10 g each

2) Formula changes

• Kidney deficiency: Chinese Dodder Seed 15 g, Chinese Taxillus Twig 15 g,

Himalayan Teasel Root 15 g, and Donkey-hide Glue 10 g were added; Szechuan

Lovage Rhizome was decreased (no information on the dosage).

• Qi deficiency: Pilose Asiabell Root 30 g, Mongolian Milkcetch Root 15 g,

Donkey-hide Glue 10 g, and Villous Amomrum Fruit 6 g were added.

• Blood deficiency: Chinese Angelica was increased to 18 g, Szechuan Lovage

Rhizome was removed, Donkey-hide Glue 15 g, Himalayan Teasel Root 15 g, and

Chinese Taxillus Twig 15 g were added.

• Blood heat: Szechuan Lovage Rhizome removed, Rehmannia Root 15 g replaced

Steamed Rehmannia Root, Dwarf Lilyturf Tuber, and Cochinchinese Asparagus Root

15 g, Donkey-hide Glue 10 g, and Ramie Root 20 g were added.

3) Decoction: po, QD.

4) Western medicines were received at the same time, including progesterone 10 mg,

im, qd; HCG 2000 U, im, qd; Allylestrenol 5 mg, Ritodrine 10 mg, po, tid; vitamin C

100 mg, po, qd; folic acid 0.4 mg, tid

Control group wastreated withWesternmedicines alone. Same as above, progesterone 10

mg, im, qd; HCG 2000U, im, qd; Allylestrenol 5mg, Ritodrine 10mg, po, tid; vitamin

C 100 mg, po, qd; folic acid 0.4 mg, tid



of combined medicines group was 97.87%, and Western medicines group was 87.50%

(P < 0.05)


Risk of bias



bias)







Fu 2006 (Continued)


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Hou 2010



Participants 75 inpatients from Women’s Hospital of Nan Jing were recruited (2008 Sep-2010 Feb)

. Participants were all diagnosed as threatened miscarriage due to vaginal bleeding and

abdominal pains


The Chinese medicine formula was Jianpi Huoxue Bushen Antai decoction, including

Milkvetch Root, Hairyvein Agrimonia Herb and Bud, 30 g each; White Paeony Root,

Ramie Root, Chinese Dodder Seed, 20 g each; Largehead Atractylodes Rhizome, Don-

key-hide Glue, Chinese Taxillus Twig, 15 g each; Himalayan Teasel Root, 10 g; Largetri-

foliolious Bugbane Rhizome, Chinese Angelica, Bitter Orange, Liquoric Root, 6 g each.?

Decoction: po, dosing was not listed in the study.

Western medicines were received at the same time, including HCG and progesterone;

vitamin K and P-aminomethyl Benzoic Acid (PAMBA) if necessary. Dosage and dosing

were not listed in the study

Control group was treated with Western medicines alone. Same as above, HCG and

progesterone; vitaminK and P-aminomethyl BenzoicAcid (PAMBA) if necessary. Dosage

and dosing were not listed in the study




5% (P < 0.01)


Risk of bias






Hou 2010 (Continued)


bias)

Low risk “2:1 ratio randomization.”

Allocation concealment (selection bias) Low risk “2:1 ratio randomization.”


bias)

All outcomes


not feasible.


All outcomes





“no significant difference was found be-tween groups”

Hu 2010



Participants 68 inpatients and outpatients from Integrated Medicines Hospital of Wen Zhou were

recruited. Participants were all diagnosed as threatened miscarriage due to vaginal bleed-

ing and abdominal pains

Interventions Treatment group received Chinese herbal medicines combined with Western medicinesThe Chinese medicine formula was San Haung An Tai Yin, including Hairyvein Agri-

monia Herb and Bud, White Paeony Root, 30 g each; Milkvetch Root, Ramie Root,

Chinese Taxillus Twig, Chinese Dodder Seed, Himalayan Teasel Root, Szechwon Tang-

shen Root, 15 g each; Honeysuckle Flower, 12 g; Largehead Atractylodes Rhizome 10

g; Dock Root, 9 g; Liquoric Root, 5 g; Figwortflower Picrorhiza Rhizome, SanChi, 3 g

each

Decoction: po, bid, 15 days as a course.

4) Western medicines were received at the same time, including HCG 40 mg, im, qd,

15 days as a course

Control group was treated with Western medicines alone. Same as above, HCG 40 mg,

im, qd. 15 days as a course




71% (P < 0.05). The dark area around gestational sac was significantly reduced (P < 0.

05)






Hu 2010 (Continued)

Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes

Low risk Blinding of participants and clinicians was

not feasible.


All outcomes

High risk No exclusion was reported. No losses were





tween groups”

Huang 2011



Participants 100 inpatients or outpatients from Integrated Medicines Hospital of Gui Zhou were

recruited (2008 Jul-2010 Dec). Participants were all diagnosed as threatened miscarriage

due to vaginal bleeding and abdominal pains (Luteal Phase Defect)


1) The Chinese medicine formula was Shou Tai Pill, including Chinese Dodder Seed 30

g; Chinese Taxillus Twig, 20 g; Himalayan Teasel Root, 15 g; Largehead Atractylodes

Rhizome, Donkey-hide Glue, 10 g each; Liquoric Root, 6 g

2) Formula changes

• Abdominal pain: White Paeony Root 20 g; Eucommia Bark 15 g; Szechwon

Tangshen Root, 30 g were added.

• Blood deficiency: Medicinal Cornel Fruit, 20 g was added.• Vaginal bleeding: Garden Burnet Root, 30 g was added.

3) Decoction: po, bid, 10 days as a course.

4) Western medicines were received at the same time, including HCG 2000 U, im, qd,

progesterone 20 mg, im, qd, vitamin E, 100 mg, po, qd, folic acid, 0.4 mg, po, qd

Control group was treated with Western medicines alone. Same as above, HCG 2000

U, im, qd, progesterone 20 mg, im, qd, vitamin E, 100 mg, po, qd, folic acid, 0.4 mg,

po, qd





Huang 2011 (Continued)

Both groups had standard care for pregnancy (prohibit sexual activity, bed rest, and

psychotherapy)



rate of combined medicines group was 96%, and Western medicines group was 80% (P

< 0.05)


Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Kuang 2007

Methods Randomised c ontrolled t rial of comparisonsa mong c ombined medicines, C hineseherbal

medicines alone, and Western medicines alone

Participants 180 inpatients or outpatients from Second Affiliated Hospital of Hunan University of

Chinese Medicine were recruited (2004 May-2006 May). Participants were all diagnosed



1) mainly used Pilose Asiabell Root 10 g, Mongolian Milkcetch Root, White Paeony

Root,IndianBueadand TuberFleeceflower Root10 g each;Prepared rhizome of Adhesive

Rehmannia, Chinese Dodder Seed, Himalayan Teasel Root and Chinese Taxillus Twig

15 g each; and Liquorice Root 5 g

2) Formula changes





Kuang 2007 (Continued)

• vaginal bleeding: Cuttlefish bone 30 g, Dark Plum Fruit 15 g and Tuber of

Hyacinth Bletilla 10 g were added, and prepared Himalayan Teasel Root before add

into the formula.

• dry mouth and hard stool: White Paeony Root was increased to 30 g, Liquorice

Root was increased to 10 g, and Chinese Thorowax Root, Baical Skullcap Root, Dwarf

Lilyturf Tuber and Root of Lobed Kudzuvine 10 g each were added.

3) 7-day as a course, and usually took 1-3 courses. (Details of administration were not

available.)

The Western medicines group used vitamin E capsules 0.1 g, po, BID; HCG 1000 U,

im, QD, then alternative injection after vaginal bleeding stopped

All 3 groups had standard care for pregnancy (prohibit sexual activity, psychotherapy,

and regulate ultrasound tests)



of Chinese medicines group was 68.3%, Western medicines group was 63.3%, and com-bined medicine group was 91.7%. Significant difference was found between combined

medicine and Chinese medicines or Western medicines alone (P < 0.05). No statistic

difference was found between Chinese herbal medicines and Western medicines groups

(P > 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes




Other bias Low risk The intervention groups were comparable,“no significant difference wasfoundamong

groups”





Li 2004



Participants 50 inpatients or outpatients from Affiliated Hospital of An Hui University of ChineseMedicine were recruited (1999 June-2003 December). Participants were all diagnosed



1) The Chinese medicine formula was Bu Shen An Tai Yin, included Chinese Dodder

Seed, Eucommia Bark, Chinese Taxillus Twig, Himalayan Teasel Root, Heterophylly

FalsestarwortRoot, Mongolian MilkcetchRoot, LargeheadAtractylodes Rhizome, Baical

Skullcap Root, White Paeony Root, Steamed Rehmannia Root and Ramie Root, each

10 g

2) Formula changes (no information on the dosage)

• Blood heat: Baical Skullcap Root was increased.

• Kidney deficiency: Chinese Dodder Seed was increased.

3) Decoction: po, bid, 10 days as a course.


im, qd; vitamin E 100 mg, po, qd; folic acid 5 mg, tid

Control group was treated with Western medicines alone. Same as above, progesterone

10 mg, im, qd; vitamin E 100 mg, po, qd; folic acid 5 mg, tid



of combined medicines group was 96%, and Western medicines group was 80% (P < 0.

05)


Risk of bias



bias)

Low risk “Layered method”, but no further informa-

tion was available.

Allocation concealment (selection bias) Low risk “Layered method”, but no further informa-

tion was available.


bias)

All outcomes


not feasible.


All outcomes








Li 2004 (Continued)



tween groups”

Li 2005



Participants 90 inpatients from First Affiliated Hospital of Guang Zhou University of Chinese

Medicine were recruited (2003 April-2004 June). Participants were all diagnosed as

threatened miscarriage due to vaginal bleeding and abdominal pains


1) The Chinese medicine formula was Shou Tai Pill, included Chinese Dodder Seed15 g, Chinese Taxillus Twig 15 g, Himalayan Teasel Root 15 g, Donkey-hide Glue 10

g, Pilose Asiabell Root 15 g, Mongolian Milkcetch Root 15 g, Largehead Atractylodes

Rhizome 10 g, White Paeony Root 15 g, and Liquorice Root 5 g

2) Formula changes

• Increased bleeding: Baical Skullcap Root, Lotus Rhizome Node and Garden

Burnet Root, each 10 g were added.

• Low back pain: Eucommia Bark and Palmleaf Raspberry Fruit, each 10 g were

added.

• Stool dehydration: Desertliving Cistanche and Mulberry Fruit, each 10 g were

added.


4) Western medicines were received at the same time, including vitamin E 50 mg, po,

bid; folic acid 0.4 mg, po, qd; HCG 2000 U, im, qd; Allylestrenol, 5 mg, po, tid, if witha history of over twice habitual miscarriage

Control group was treated with Western medicines alone. Same as above, vitamin E 50

mg, po, bid; folic acid 0.4 mg, po, qd; HCG 2000 U, im, qd; Allylestrenol, 5 mg, po,

tid, if with a history of over twice habitual miscarriage



of combined medicines group was 95%, and Western medicines group was 76.67% (P

< 0.05)


Risk of bias



bias)







Li 2005 (Continued)


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Li 2006



Participants 89 inpatients or outpatients from Affiliated Hospital of Guang Xi College of Chinese

Medicine wererecruited(2003 January-2005September). Participantswere all diagnosed



1) The Chinese medicine formula was Bu Shen Gu Tai soup, included Chinese Dodder

Seed 30 g, Barbary Wolfberry Fruit 30 g, Chinese Taxillus Twig 20 g, Himalayan Teasel

Root 20 g; Pilose Asiabell Root 30 g; Common Yam Rhizome 15 g, Eucommia Bark 20

g, White Paeony Root 20 g, and Liquorice Root 5 g

2) Formula changes• Dry mouth: Glossy privet fruit 15 g and Yerbadetajo Herb 20 g were added.

3) Decoction: po, BID, for 10 days.

4) Western medicines were received at the same time, including HCG 2000 U and

progesterone 20 mg, im, qod for 10 days

Control group was treated with Western medicines alone. Same as above, HCG 2000U

and progesterone 20 mg, im, qod for 10 days



of combined medicines group was 77.78%, and Western medicines group was 70.50%

(P < 0.05)


Risk of bias



bias)

Low risk Randomised number table.





Li 2006 (Continued)

Allocation concealment (selection bias) Low risk Randomised number table.


All outcomes



All outcomes

Low risk No exclusion was reported . No losses were

reported forthe main outcomes, butfor the

secondary outcomes of this trial the level of

losses to follow up was high and the data

for these outcomes would not be included

in the review. It was an ITT


Other bias Low risk The intervention groups were comparable,“no significant difference was found be-

tween groups”

Li 2009a



Participants 138 inpatients or outpatients from Zhao Qing People’s Hospital were recruited (2004

May-2006 May). Participants were all diagnosed as threatened miscarriage due to vaginal




g, Himalayan Teasel Root 15 g, Chinese Taxillus Twig 15 g, Pilose Asiabell Root 15 g,

Donkey-hide Glue 10 g, Largehead Atractylodes Rhizome 12 g, Steamed Rehmannia

Root 12 g, Common Macrocarpium Fruit 10 g, White Paeony Root 15 g, Eucommia

Bark 15 g, and Liquorice Root 6 g

2) Formula changes

• Bleeding: Fineleaf Schizonepeta Herb 10 g, Garden Burnet Root 10 g were added.

• Yin deficiency: Pilose Asiabell Root replaced by Heterophylly Falsestarwort Root,

Baical Skullcap Root were added.

• Qi deficiency: Pilose Asiabell Root 30 g was added.

• Vomiting: Villous Amomrum Fruit, Pinellia Tuber and Bamboo Shavings were

added.• Stool dehydration: Desertliving Cistanche and Hemp Fruit were added.

3) Decoction: po, BID, 7 days as a course.

4) Western medicines were received at the same time, including HCG 2000 U, im, qod,

progesterone 20 mg, im, qd


im, qod, progesterone 20 mg, im, qd





Li 2009a (Continued)



of combined medicines group was 93.1%, and Western medicines group was 80.3% (P< 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes






tween groups”

Li 2009b



Participants 189 inpatients from Wu Yi Chinese Medicine Hospital were recruited (2005 September-

2007September). Participants wereall diagnosedas threatened miscarriagedue to vaginal



1) The Chinese medicine formula was Shou Tai Pill, included Chinese Dodder Seed 15g, Himalayan Teasel Root 10 g, Chinese Taxillus Twig 15 g, Donkey-hide Glue10 g,

Baical Skullcap Root 6 g, Pilose Asiabell Root 15 g, Largehead Atractylodes Rhizome 12

g, White Paeony Root 15 g, and Liquorice Root 6 g

2) Formula changes

• Vomiting: Bamboo Shavings 6 g, Villous Amomrum Fruit 6 g and Perilla Stem 6

g were added.

• Bleeding: Ramie Root 15 g and Hairyvein Agrimonia 15 g were added.

• Low back pain: Eucommia Bark 10 g and Barbary Wolfberry Fruit 15 g were





Li 2009b (Continued)

added.

• Stool dehydration: Hemp Fruit 15 g and Desertliving Cistanche 10 g were added.

3) Decoction: details not provided.

4) Western medicines were received at the same time, including vitamin E 50 mg, po,

bid; folic acid, 0.4 mg, po, qd; HCG 2000 IU, im, qd

Control group was treated with Western medicines alone. Same as above, vitamin E 50

mg, po, bid; folic acid, 0.4 mg, po, qd; HCG 2000 IU,im, qd



of combined medicines group was 91.75%, and Western medicines group was 75% (P

< 0.05)


Risk of bias



bias)


(In its English abstract, it reported with

“randomly divided”. But in Chinese ver-

sion no information regarding this was pro-

vided.)


(In its English abstract, it reported with

“randomly divided”. But in Chinese ver-

sion no information regarding this was pro-vided.)


bias)

All outcomes


not feasible.


All outcomes










Li 2010



Participants 268 inpatients and outpatients from Chinese Medicines Hospital of An Yang were re-cruited. Participants were all diagnosed as threatened miscarriage due to vaginal bleeding

and abdominal pains


1) The Chinese medicine formula included Chinese Dodder Seed, Chinese Taxillus

Twig, 15 g each; Himalayan Teasel Root, Largehead Atractylodes Rhizome, Donkey-

hide Glue, Szechwon Tangshen Root, Villous Amomum Fruit, 10 g each

2) Formula changes

• Abdominal pain: White Paeony Root 15~30 g; Liquoric Root 6 g were added.

• Low back pain: Eucommia Bark 10 g was added.

• Dry mouth: Baical Skullcap Root 15 g, Cape Jasmine Fruit 10 g were added.

3) Decoction: po, bid for 2 weeks.

4) Western medicines were received at the same time, including HCG 2000 U, im, qod,

progesterone, 20 mg, im, qod for 2 weeks

Control group was treated with Western medicines alone. Same as above, HCG 2000

U, im, qod, progesterone, 20 mg, im, qod for 2 weeks

Both groups had standard care for pregnancy (prohibit sexual activity and bed rest)




66% (P < 0.05)


Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes








Li 2010 (Continued)



tween groups”

Liu 2008


medicines

Participants 90 outpatients from Shan Xi Service Centre for Pregnancy were recruited (2006 June-

2007 October). Participants were all diagnosed as threatened miscarriage due to vaginal


Interventions Treatment group received Chinese herbal medicines.

1) The Chinese medicine formula was given according to different subtype of diagnosisof threatened miscarriage

i. Kidney deficiency subtype: used Shou Tai Pill, included Chinese Dodder Seed 12 g,

Chinese Taxillus Twig 12 g, Himalayan Teasel Root 12 g, Donkey-hide Glue 9 g, Pilose

Asiabell Root 9 g, and Mongolian Milkcetch Root 9 g

ii. Qi deficiencysubtype: usedTaiYuan Yin,includedPilose Asiabell Root9 g, Mongolian

Milkcetch Root 9 g, Largehead Atractylodes Rhizome 9 g, Chinese Angelica 6 g, White

Paeony Root 12 g, Chinese Taxillus Twig 12 g, and Villous Amomrum Fruit 6 g

iii. Trauma subtype: used Sheng Yu Soup, included Chinese Angelica 6 g, Szechuan

Lovage Rhizome 3 g, White Paeony Root 12 g, Rehmannia Root 9 g, Pilose Asiabell

Root 9 g, and Mongolian Milkcetch Root 9 g

iv. Blood heat: used Bao Yin Jian, included Rehmannia Root 9 g, Mongolian Milkcetch

Root 12 g, Bark of Chinese Corktree 9 g, and White Paeony Root 9 g

2) Decoction: po, QD.3) Western medicines were received at the same time, including progesterone 20 mg,

im, and vitamin E 100 mg, po, tid


20 mg, im, and vitamin E 100 mg, po, tid


nations shows pregnancy maintained at 12 weeks were considered as effective. The ef-

fectiveness rate of combined medicines group was 91.4%, and Western medicines group

was 75.5% (P < 0.05)


Risk of bias



bias)

High risk “Randomization according to visiting date.

”





Liu 2008 (Continued)

Allocation concealment (selection bias) High risk “Randomization according to visiting date.

”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Liu 2009


medicines

Participants 45 outpatients from Shen Zhen Women’s Hospital were recruited (2006 August-2007

September). Participants were all diagnosed as threatened miscarriage due to vaginal



1) mainly used Chinese Dodder Seed, Chinese Taxillus Twig, Pilose Asiabell Root each

20 g; Himalayan Teasel Root, Donkey-hide Glue, Largehead Atractylodes Rhizome,Herb of Hairyvein Agrimonia each 15 g; Villous Amomrum Fruit, Rhizome of East

Asian Tree Fern each 10 g, and Liquorice Root 5 g

2) Decoction: po, BID for 2 weeks.

The Western medicines group used progesterone 20 mg, im, qd; HCG 2000 U, im, qod

for 2 weeks

Both groups had standard care for pregnancy (prohibit sexual activity, psychotherapy,




of combined medicines group was 90%, and Western medicines group was 66.7% (P <

0.05)


Risk of bias






Liu 2009 (Continued)


bias)




bias)

All outcomes


not feasible.


All outcomes





ance of baseline.

Liu 2011a


medicines

Participants 155 outpatients from Chinese Medicine Institute of Shan Xi were recruited (2008 Jun-

2010 Dec). Participants were all diagnosed as threatened miscarriage due to vaginal



1) Bao Tai decoction: mainly used Szechwon Tangshen Root, Milkvetch Root, 15 g;Chinese Dodder Seed,Chinese Taxillus Twig, WhitePaeony Root, 12 g each; Himalayan

Teasel Root, Donkey-hide Glue, Largehead Atractylodes Rhizome, India Mustard Seed,

10 g each

2) Decoction: po, BID for 2 weeks.

The Western medicines group used progesterone 100 mg, po, qd for 2 weeks




0.05)


Risk of bias



bias)


2 groups.”





Liu 2011a (Continued)


2 groups.”


bias)

All outcomes


not feasible.


All outcomes





ance of baseline.

Liu 2011b


medicines

Participants 100 inpatients and outpatients from People’s Hospital of Xing Tai were recruited (2009

Jan-2012 Jan). Participants were all diagnosed as threatened miscarriage due to vaginal



1) Bao Tai decoction: mainly used Milkvetch Root, Ramie Root, 30 g; Hairyvein Agri-

monia Herb and Bud, Chinese Taxillus Twig, 24 g; Glossy Privet Fruit, 18 g; Himalayan

Teasel Root, Chinese Dodder Seed, Eucommia Bark, Giant St.John’swort Herb, Medici-nal Cornel Fruit, Fortune Windmillpalm Petiole, Gordon Euryale Seed, 15 g; Largehead

Atractylodes Rhizome, Largetrifoliolious Bugbane Rhizome , 10 g each

2) Decoction: po, BID, 7 days as a course till symptoms subsided

The Western medicines group used progesterone 20 mg, im, qd; vitamin E, 100 mg, po,

TID, 7 days as a course till symptoms subsided



of Chinese medicines group was 80%, and Western medicines group was 72% (P < 0.

05)


Risk of bias



bias)


2 groups.”





Liu 2011b (Continued)


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Lu 2011



Participants 200 inpatients from Chinese MedicinesHospital of Ning Bo were recruited. Participants

were all diagnosed as threatened miscarriage due to vaginal bleeding and abdominal pains


1) The Chinese medicine formula included Chinese Dodder Seed, Eucommia Bark,

Glossy Privet Fruit, Chinese Taxillus Twig, 100 g each; Medicinal Cornel Fruit, 50 g

2) Decoction: external use at Yong Quan acu-point, qd.3) Western medicines (hormone treatment) were received at the same time, details were

not listed in this study

Control group was treated with Western medicines alone. Same as above, hormone

treatment but details were not listed in this study


The effectiveness rate of combined medicines group was 95.2%, and Western medicines

group was 78.2% (P < 0.01)


Risk of bias



bias)


2 groups.”





Lu 2011 (Continued)


2 groups.”


bias)

All outcomes

Low risk Single blinding was reported in this study,

but the review authors doubt if it was a real

single-blinding, as the study author did not

report the detailed method of blinding of

participant


All outcomes






tween groups”

Lv 2007

Methods Randomised controlledtrials of combined medicines(Chinese herbal medicines + West-


Participants 98 inpatients from Tian Jin Chinese Medicine University were recruited (2004 May-

2006 May). Participants were all diagnosed as threatened miscarriage due to vaginal



1) The Chinese medicine formula: included Chinese Dodder Seed 20 g, Himalayan

TeaselRoot, Chinese Taxillus Twig,PiloseAsiabell Root, Common Yam Rhizome each15

g, Largehead Atractylodes Rhizome 12 g, Common Macrocarpium Fruit 10 g, Steamed

Rehmannia Root 10 g, and Liquorice Root 6 g

2) Formula changes

• Bleeding: Donkey-hide Glue, Baical Skullcap Root and Ramie Root were added.

• Abdomen pain: White Paeony Root was added.

• Blood Hhat: Baical Skullcap Root was added.

• Insomnia: Spina Date Seed was added.

• Low back pain: Eucommia Bark was added.

• Vomiting: Villous Amomrum Fruit was added.

3) Decoction: po, QD.4) Western medicines were received at the same time, including progesterone 20 mg,

im, qd; vitamin E 100 mg, po, tid


20 mg, im, qd; vitamin E 100 mg, po, tid


The effectiveness rateof combined medicinesgroup was 91.38%, and Westernmedicines

group was 70% (P < 0.05)





Lv 2007 (Continued)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes






tween groups”

She 2008

Methods Randomised controlled trial of combined medicines (Chinese herbal medicines + West-ern medicines) compared with Western medicines alone

Participants 100 inpatients oroutpatients from ChineseMedicine Hospital of Gui Lin wererecruited.

Participants were all diagnosed as threatened miscarriage due to vaginal bleeding and

abdominal pains



g, Chinese Taxillus Twig 10 g, Himalayan Teasel Root 10 g, Donkey-hide Glue 10 g,

Pilose Asiabell Root 20 g, and Largehead Atractylodes Rhizome 15 g

2) Formula changes

• Qi and blood deficiency: Mongolian Milkcetch Root 15 g, Steamed Rehmannia

Root 10 g and White Paeony Root 10 g were added.

• Blood heat: Rehmannia Root 15 g, Baical Skullcap Root 12 g and Bark of

Chinese Corktree 6 g were added.

3) Decoction: po, BID, 10 days as a course.


im, qd; HCG 2000 U, im, qod; vitamin E 100 mg, po, qd; folic acid 0.4 mg, qd


20 mg, im, qd; HCG 2000U, im, qod; vitamin E 100 mg, po, qd; folic acid 0.4 mg, qd





She 2008 (Continued)



rate of combined medicines group was 93.3%, and Western medicines group was 70%(P < 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes






tween groups”

Shen 2010



Participants 120 inpatients or outpatients from Chinese Medicines Hospital of Dong Tai were re-

cruited. Participants were all diagnosed as threatened miscarriage due to vaginal bleeding

and abdominal pains


1) The Chinese medicine formula was Shou Tai Pill and Bu Shen Jian Pi Gu Chong decoction, including Chinese Dodder Seed, 20 g; ?Chinese Taxillus Twig, Himalayan

Teasel Root, 15 g each; Largehead Atractylodes Rhizome, Szechwon Tangshen Root,

Donkey-hide Glue, Wingde Yan Rhizome, 10 g each; Liquorice Root 6 g

2) Formula changes

• Bleeding: Ramie Root 15 g, Garden Burnet Root 10 g were added.

• Low back pain: Eucommia Bark, Palmleaf Raspberry Fruit, 10 g each were added.

3) Decoction: po, bid.

4) Western medicines were received at the same time, including HCG 10 mg, im, qd;





Shen 2010 (Continued)

vitamin E 100 mg, po, qd; 7 days as a course

Control group was treated with Western medicines alone. Same as above, HCG 10 mg,

im, qd; vitamin E 100 mg, po, qd; 7 days as a course

Both groups had standard care for pregnancy (bed rest and regulate ?-HCG and ultra-

sound tests)




< 0.01)


Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Song 2005


medicines

Participants 243 outpatients fromNing Xia Women’s Hospital were recruited(2001 May-2003 May)


abdominal pains


1) Zhi Xue An Tai Yin: mainly used Himalayan Teasel Root, Chinese Dodder Seed,

Chinese Taxillus Twig, Perilla Stem, Villous Amomrum Fruit, White Paeony Root,





Song 2005 (Continued)

Largehead Atractylodes Rhizome, Common Macrocarpium Fruit, Sharpleaf Galangal

Fruit, Mongolian Milkcetch Root, Heterophylly Falsestarwort Root, Chinese Arborvitae

Twig, Garden Burnet Root, India Madder Root, and Donkey-hide Glue 10 g each

2) Formula changes

• Heat sign: Baical Skullcap Root was added.

• Cold sign: Chinese Mugwort Leaf and Ginger each 6 g were added.

• Vomiting: Pinellia Tuber, Clove, Persimmon Calyx and Receptacle each 10 g, and

Ginger 6 g were added.

3) po, TID, for 7 days.

The Western medicines group used progesterone 20mg, im, qd; vitamin E 100 mg, po,

tid; vitamin K 8 mg, tid; An Luo Xue, 5 mg, po, tid


inations showed pregnancy maintained (HCG normal and LH > 200 mLU/ml) were

considered as effective. The effectiveness rate of combined medicines group was76.98%,

and Western medicines group was 43.59% (P < 0.05)


Risk of bias



bias)




All outcomes



All outcomes






tween groups”

Song 2007








Participants 105 outpatients from Ning Xia Women’s Hospital were recruited (2005 October-2006

August). Participants were all diagnosed as threatened miscarriagedue to vaginal bleeding

and abdominal pains


1) The Chinese medicine formula was Zhi Xue Bao Tai Yin, included Himalayan Teasel

Root, Chinese Dodder Seed, Chinese Taxillus Twig, Perilla Stem, Villous Amomrum

Fruit, White Paeony Root, Largehead Atractylodes Rhizome, Common Macrocarpium

Fruit, Sharpleaf Galangal Fruit, Mongolian Milkcetch Root, Heterophylly Falsestarwort

Root, Chinese Arborvitae Twig, Garden Burnet Root, India Madder Root, and Donkey-

hide Glue, 10 g each

2) Formula changes

• Heat sign: Baical Skullcap Root was added.

• Cold sign: Chinese Mugwort Leaf and Ginger each 6 g were added.

• Vomiting: Pinellia Tuber, Clove, Persimmon Calyx and Receptacle 10 g each, and

ginger 6 g were added.3) Decoction: po, TID, for 7 days.


im, qd; vitamin E 100 mg, po, tid; vitamin K 8 mg, tid; An Luo Xue, 5 mg, po, tid


20 mg, im, qd; vitamin E 100 mg, po, tid; vitamin K 8 mg, tid; An Luo Xue, 5 mg, po,

tid


nations showed pregnancy maintained (HCG normal and LH increased) were consid-

ered as effective. The effectiveness rate of combined medicines group was 81.5%, and

Western medicines group was 43.1% (P < 0.05)


Risk of bias



bias)

High risk “Randomization according to first visit

date.”

Allocation concealment (selection bias) High risk “Randomization according to first visit

date.”


bias)

All outcomes


not feasible.


All outcomes











tween groups”

Sun 2003



Participants 105 inpatients or outpatients from Xiang Tan Chinese Medicine Hospital were recruited

(2004 May-2006 May). Participants were all diagnosed as threatened miscarriage due to



1) mainly used Heterophylly Falsestarwort Root 15 g, Mongolian Milkcetch Root 12g, Largehead Atractylodes Rhizome 10 g, White Paeony Root 15 g, Barbary Wolfberry

Fruit 15 g, Chinese Taxillus Twig 15 g, Himalayan Teasel Root 15 g, Chinese Dodder

Seed 15 g, Common Yam Rhizome 15 g, and Liquorice Root 6 g

2) Formula changes

• Severe bleeding: Garden Burnet Root 10 g and Yerbadetajo Herb 10 g were added.

• Blood heat: Mongolian Milkcetch Root removed, Baical Skullcap Root 6 g were

added.

• Abdomen pain: White Paeony Root 20-30 g and Largetrifoliolious Bugbane

Rhizmome 10 g were added.

• Vomiting: Perilla Stem 10 g, Bamboo Shavings 10 g and Tangerine Pee 16 g were

added.

3) po, BID, 5-day as a course, and usually 1-3 courses.

The Western medicines group used vitamin E 100 mg, po, tid; folic acid 0.4 mg, po,qd; HCG 1000 U, im, qd

Outcomes Symptoms such as vaginal bleeding and abdominal pains subsided, and clinical examina-

tionsshowed pregnancy maintained wereconsidered as effective.The effectiveness rate of

Chinese medicines group was 94%, Western medicines group was 71%, and combined

medicine group was 98%. Significant difference was found between combined medicine

or Chinese medicines and Western medicines alone (P < 0.05). No statistic difference

was found between Chinese herbal medicines and combined medicines groups (P > 0.

05)


Risk of bias



bias)

High risk “Randomization according to visit date.”

Allocation concealment (selection bias) High risk “Randomization according to visit date.”





Sun 2003 (Continued)


bias)

All outcomes


not feasible.


All outcomes




Other bias High risk No information was provided on the bal-

ance of baseline.

Wang 2005


Participants 140 outpatients fromHui An Chinese Medicine Hospital were recruited(2002 October-

2004September). Participants wereall diagnosedas threatened miscarriagedue to vaginal



1) The Chinese medicine formula was Zhu Ma An Tai soup, included Ramie Root 30

g, Chinese Taxillus Twig 20 g, Himalayan Teasel Root 20 g, Chinese Dodder Seed 20 g,

Largehead Atractylodes Rhizome 10 g, Baical Skullcap Root 10 g, White Paeony Root

12 g, Rehmannia Root 15 g, Yerbadetajo Herb 30 g, and Liquorice Root 3 g

2) Formula changes

• Severe bleeding: Chinese Arborvitae Twig and root of Common Euscaphis wereadded.

• Severe vomiting: Bamboo Shavings and Villous Amomrum Fruit were added.

• Stool dehydration: Desertliving Cistanche and Platycladi Seed were added.



im, qd; HCG 2000 U, im, qod; vitamin E 100 mg, po, qd; folic acid 0.4 mg, qd, (add

Zhi Xue Min if bleeding hardly)


20 mg, im, qd; HCG 2000U, im, qod; vitamin E 100 mg, po, qd; folic acid 0.4 mg, qd,

(add Zhi Xue Min if bleeding hardly)




< 0.05)


Risk of bias





Wang 2005 (Continued)






bias)

All outcomes


not feasible.


All outcomes






tween groups”

Wang 2007


medicines

Participants 96 inpatients or outpatients from Nan Yang Chinese Medicine College were recruited

(2003 March-2006 March). Participants were all diagnosed as threatened miscarriage

due to vaginal bleeding and abdominal pains


1) Bu Shen Gu Chong soup: mainly used Chinese Dodder Seed 30 g, Himalayan Teasel

Root 15 g, Chinese Taxillus Twig 30 g, Largehead Atractylodes Rhizome 18 g, Donkey-

hide Glue 10 g, Eucommia Bark 15 g, White Paeony Root 15 g, Pilose Asiabell Root 30

g, Fineleaf Schizonepeta Herb 9 g, and Liquorice Root 6 g

2) Formula changes

• QI deficiency: Pilose Asiabell Root removed, Heterophylly Falsestarwort Root

and Mongolian Milkcetch Root, each 30 g were added.

• Severe bleeding: Herb of Hairyvein Agrimonia 30 g, Male Fern Rhizome 15 g and

Garden Burnet Root 30 g were added.

• Vomiting: Villous Amomrum Fruit 8 g and Perilla Stem 9 g were added.

• Heat sign: Baical Skullcap Root 9 g and Ramie Root 30 g were added.

• Abdomen pain: White Paeony Root 30 g was added.

3) po, BID, 7-day as a course.

The Western medicines group used HCG 1000U, im, qd, 7 day as a course









5% (P < 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes





ance of baseline.

Wang 2010


Participants 110 outpatients from He Nan Population Institute were recruited (2007 Jan-2009 Dec)


abdominal pains


1) Yi Shen An Tai decoction: mainly used Chinese Dodder Seed, Chinese Taxillus Twig,

15 g each; Largehead Atractylodes Rhizome, Himalayan Teasel Root, Baical Skullcap

Root, Donkey-hide Glue, Szechwon Tangshen Root, 10 g each; Liquoric Root, 6 g

2) Formula changes

• Bleeding: Garden Burnet Root 12 g, Argy Wormwood Leaf 6 g were added.

• Abdominal pain: White Paeony Root 15g was added.• Vomiting: Bamboo Shavings 10 g, Pinellia Tuber 6 g, Villous Amomum Fruit 6 g

were added.

• Low back pain: Eucommia Bark 12 g was added.

• Vexation: Lancelesf Lily Bulb 15 g was added.

3) Decoction: po, BID till the 12th week of gestation.

The Western medicines group used HCG 2000 U, im, qod, progesterone 20 mg, im,

qd, vitamin E, 100 mg, po, bid, folic acid, 0.4 mg, po, qd; till the 12th week of gestation.








of Chinese medicines group was 81.82%, and Western medicines group was 58.18% (P< 0.05)


Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






Wang 2011


medicines

Participants 225 outpatients from Xi Dian Company Hospital of Shan Xi were recruited (2010 Jan-

Dec). Participants were all diagnosed as threatened miscarriage due to vaginal bleeding

and abdominal pains

Interventions Treatment group received Chinese herbal medicines combined with Western medicines1) TheChinese medicine formula was Gu Shen An Tai Pill, includingLargehead Atracty-

lodes Rhizome, Chinese Dodder Seed, Chinese Taxillus Twig, White Paeony Root,

Rehmannia Root, Himalayan Teasel Root, Tuber Fleeceflower Root, Baical Skullcap

Root, Gambir Plant, Desertliving Cistanche. Details of dosage were not listed in this

study

2) Decoction: po, tid, 2 weeks as a course.

3) Western medicines were received at the same time, including progesterone, 100mg,

po,qd; vitamin E 200 mg, po, tid; 2 weeks as a course






Control group was treated with Western medicines alone. Same as above, progesterone,

100mg, po,qd; vitamin E 200 mg, po, tid; 2 weeks as a course

Both groups had standard care for pregnancy (prohibit sexual activity, psychotherapy,





18% (P < 0.05)


Risk of bias



bias)

Low risk “Randomized number method”

Allocation concealment (selection bias) Low risk “Randomized number method”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Xiao 2008



Participants 60 inpatients from Xin Shao People’s Hospital were recruited (2005 October-2007 Oc-

tober). Participants were all diagnosed as threatened miscarriage due to vaginal bleeding and abdominal pains


1) The Chinese medicine formula was Yan Xue Yi Shen soup, included Chinese Dodder

Seed 10 g, Chinese Taxillus Twig 15 g, Himalayan Teasel Root 10 g, Eucommia Bark

15 g, Mongolian Milkcetch Root 20 g, Ginseng 10 g, Common Yam Rhizome 15 g,

White Paeony Root 15 g, Donkey-hide Glue 15 g, Steamed Rehmannia Root 10 g and





Xiao 2008 (Continued)

Tangerine Peel l5 g

2) Decoction: po, BID


im, qd; HCG 2000 U, im, qd for 10 days then decline the dosage; vitamin E 50 mg,

Ritodrine 10 mg, po, tid; folic acid 0.4 mg, QD, An Luo Xue, vitamin K, vitamin C if

bleeding hardly (no detailed administration)


20 mg, im, qd; HCG 2000U, im, qd for 10 days then decline the dosage; vitamin E 50

mg, Ritodrine 10 mg, po, tid; folic acid 0.4 mg, QD, An Luo Xue, vitamin K, vitamin

C if bleeding hardly (no detailed administration)



rate of combined medicines group was 90%, and Western medicines group was 66.7%

(P < 0.05)


Risk of bias



bias)

Low risk “Randomized number method.”

Allocation concealment (selection bias) Low risk “Randomized number method.”


bias) All outcomes


not feasible.


All outcomes






tween groups”

Xu 2005



Participants 62 inpatients or outpatients from Affiliated Hospital of Zhe Jiang University were re-

cruited. Participants were all diagnosed as threatened miscarriage due to vaginal bleeding

and abdominal pains





Xu 2005 (Continued)


1) The Chinese medicine formula was Yun Kang decoction. (Further information of

herbs and dosages were not available.)2) Decoction: 20 ml, po, BID, for 14 days.


im, qd; vitamin E 1 pill, po, qd


40 mg, im, qd; vitamin E 1 pill, po, qd




6% (P < 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes





ance of baseline.

Xun 2008



Participants 75 inpatients or outpatients from Jiang Su East West Medicine Hospital were recruited







Xun 2008 (Continued)


1) The Chinese medicine formula, included Pilose Asiabell Root 10 g, Mongolian

Milkcetch Root 10 g, Largehead Atractylodes Rhizome 10 g, White Paeony Root 10 g,Steamed Rehmannia Root 10 g, Chinese Taxillus Twig 12 g, Donkey-hide Glue 10 g,

and Tangerine Peel 10 g



im, qd; HCG 2000 U, im, qd, qod if vaginal bleeding stopped


20 mg, im, qd; HCG 2000U, im, qd, qod if vaginal bleeding stopped



rate of combined medicines group was 93.3%, and Western medicines group was 80%

(P < 0.05)


Risk of bias



bias)




All outcomes



All outcomes





ance of baseline.

Yang 2001



Participants 55 inpatients or outpatients from Jiang Xi Ning Dou Chinese Medicine Hospital were

recruited. Participants were all diagnosed as threatened miscarriage due to vaginal bleed-

ing and abdominal pains





Yang 2001 (Continued)


1) TheChinese medicine formula wasShou Tai Pill, included Chinese Dodder Seed 30 g,

Chinese Taxillus Twig 12 g, Himalayan Teasel Root 12 g, Donkey-hide Glue 15 g, Pilose Asiabell Root 30 g, Largehead Atractylodes Rhizome 10 g, Common Yam Rhizome 15

g, and Liquorice Root 6 g



im, qd; vitamin K 3 4 mg, po, bid.


20 mg, im, qd; vitamin K 3 4 mg, po, bid.




5% (P < 0.05)


Risk of bias



bias)




All outcomes



All outcomes





ance of baseline.

Yang 2006



Participants 150 inpatients or outpatients from Guang Zhou Qin Zhou Chinese Medicine Hospital

were recruited (2004 January-2006 May). Participants were all diagnosed as threatened

miscarriage due to vaginal bleeding and abdominal pains





Yang 2006 (Continued)


1) The Chinese medicine formula was Jiao Ai soup, included Donkey-hide Glue 15 g,

Chinese Mugwort Leaf 12 g, Steamed Rehmannia Root 20 g, Szechuan Lovage Rhizome5 g, White Paeony Root 10 g, Chinese Angelica 10 g, and Liquorice Root 6 g

2) Formula changes

• Qi and blood deficiency: Mongolian Milkcetch Root 30 g and Pilose Asiabell

Root 20 g were added.

• Kidney deficiency: Chinese Taxillus Twig 15 g, Eucommia Bark 15 g, Himalayan

Teasel Root 15 g and Chinese Dodder Seed 15 g were added.


• Adominal distension: Villous Amomrum Fruit 3 g and Tangerine Peel 6 g were

added.


4) Western medicines were received at the same time, including HCG 1000 U, im, qd

for 10 days then decline the dosage; vitamin E 100 mg, po, tid; folic acid 0.4 mg, qd

Control group was treated with Western medicines alone. Same as above, HCG 1000U,im, qd for 10 days then decline the dosage; vitamin E 100 mg, po, tid; folic acid 0.4 mg,

qd




< 0.05)


Risk of bias



bias)

Low risk “2:1 ratio randomization.”

Allocation concealment (selection bias) Low risk “2:1 ratio randomization.”


bias)

All outcomes


not feasible.


All outcomes





ance of baseline.





Zeng 2011



Participants 118 inpatients and outpatients from Dong Keng Hospital of Dong Wan were recruited

(2009 Jun-2011 Feb). Participants were all diagnosed as threatened miscarriage due to



1) The Chinese medicine formula was Bu Shen Yang Xue Gu Qi decoction, including

Chinese Taxillus Twig, Eucommia Bark, White Paeony Root, Wingde Yan Rhizome,

Donkey-hide Glue, 15 g each; Chinese Dodder Seed, Steamed Rehmannia Root, Hi-

malayan Teasel Root, 10 g each; Milkcetch Root 20 g; Tangerine Peel, 5 g

2) Decoction: po, bid till 7 days after symptoms subsided.

3) Western medicines were received at the same time, including progesterone, 2 pills,

po, bid till 7 days after symptoms subsided

Control group was treated with Western medicines alone. Same as above, progesterone,2 pills, po, bid till 7 days after symptoms subsided




0% (P < 0.05)


Risk of bias



bias)


2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”





Zhang 2007


medicines

Participants 102 inpatients from Shan Dong Ji Nan Hospital were recruited (2004 May-2006 May). Participants were all diagnosed as threatened miscarriage due to vaginal bleeding and

abdominal pains


1) Shou Tai Pill: mainly used Chinese Dodder Seed 10 g, Himalayan Teasel Root 15

g, Chinese Taxillus Twig 15 g, Donkey-hide Glue 10 g, Deer Horn 10 g, and Morinda

Root 10 g

2) Formula changes

• Low back pain: Eucommia Bark was added.

• Abdominal distension: Mongolian Milkcetch Root and Largetrifoliolious

Bugbane Rhizmome were added.

• Bleeding: Herb of Hairyvein Agrimonia, Garden Burnet Root and Lotus Seed Pot

were added.

3) Decoction: po, qd.

The Western medicines group used vitamin E 0.1g, po, qd; progesterone 20~40 mg, im,

qd; folic acid 5 mg, po, qd; HCG, 2000 IU, im, qod




85% (P < 0.05)


Risk of bias



bias)




bias)

All outcomes


not feasible.

Incomplete outcome data (attrition bias) All outcomes

Low risk No exclusion was reported. No losses werereported. It was an ITT




tween groups”





Zhang 2008a



Participants 96 inpatients or outpatients from Liu Yang Central Hospital were recruited (2006 Oc-

tober-2008 January). Participants were all diagnosed as threatened miscarriage due to



1) The Chinese medicine formula was Shou Tai Pill, included Chinese Dodder Seed

20 g, Chinese Taxillus Twig 25 g, Donkey-hide Glue, Himalayan Teasel Root, Steamed

Rehmannia Root, Pilose Asiabell Root and Largehead Atractylodes Rhizome, each 15 g;

and Liquorice Root 10 g

2) Formula changes

• Qi deficiency: Mongolian Milkcetch Root 30 g was added.

• Severe bleeding: Herb of Hairyvein Agrimonia 30 g, Male Fern Rhizome 15 g,

Garden Burnet Root 30 g were added.• Vomiting: Villous Amomrum Fruit 8 g and Perilla Stem 9 g were added.

• Heat sign: Baical Skullcap Root 9 g and Ramie Root 30 g were added.

• Abdomen pain: White Paeony Root 30 g was added.

• Insomnia: Spina Date Seed 8 g was added.

3) Decoction: po, BID, 7-day as a course.

4) Western medicines were received at the same time, including HCG 2000 U, im, qod;

vitamin E 100 mg, po, qd; folic acid 2.5 mg, po, qd


im, qod; vitamin E 100 mg, po, qd; folic acid 2.5 mg, po, qd



rate of combined medicines group was 90.0%, and Western medicines group was 87.1% (P < 0.05)


Risk of bias



bias)

Low risk “Randomized number table.”

Allocation concealment (selection bias) Low risk “Randomized number table.”


bias)

All outcomes


not feasible.


All outcomes







Zhang 2008a (Continued)


Other bias Low risk The intervention groups were comparable,“no significant difference was found be-

tween groups”

Zhang 2008b



Participants 100 inpatients or outpatients from Second Affiliated Hospital of Hunan University of

Chinese Medicine were recruited (2004 January-2006 December). Participants were all

diagnosed as threatened miscarriage due to vaginal bleeding and abdominal pains


1) The Chinese medicine formula was Bao Tai Yin, included Steamed Rehmannia Root

20 g, Common Macrocarpium Fruit 15 g, Donkey-hide Glue 15 g, Himalayan Teasel

Root 15 g, White Paeony Root 10 g, Chinese Dodder Seed 15 g, Chinese Taxillus Twig

15 g, Eucommia Bark15 g, Largehead Atractylodes Rhizome 15 g, Mongolian Milkcetch

Root 20 g, Pilose Asiabell Root 10 g, and Liquorice Root 6 g

2) Formula changes

• Blood heat: Bamboo Shavings, Mulberry Leaf and Towel Gourd Vegetable Sponge

each 10 g were added.

• Abdominal distension: Villous Amomrum Fruit 3 g and Tangerine Pee 16 g were

added.

3) Decoction: po, tid, 1 or 2 weeks.

4) Western medicines were received at the same time, including progesterone, 20 mg,

qd; vitamin E 100 mg, po, tid

Control group was treated with Western medicines alone. Same as above, progesterone,

20 mg, qd; vitamin E 100 mg, po, tid




< 0.05)


Risk of bias



bias)







Zhang 2008b (Continued)


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Zhong 2002



Participants 90 inpatients or outpatients from Guang Zhou Second People’s Hospital were recruited




1) mainly used Pilose Asiabell Root, Largehead Atractylodes Rhizome, Common Yam

Rhizome, Chinese Taxillus Twig, Chinese Dodder Seed, Himalayan Teasel Root and

Baical Skullcap Root (no information on the dosage)

2) Formula changes (no information on the dosage)

• Blood deficiency: Donkey-hide Glue was added.• Cold sign: Chinese Mugwort Leaf was added.

• Blood heat: Garden Burnet Root was added.

• Abdomen pain: White Paeony Root, Nutgrass Galingale Rhizome and Perilla

Stem were added.

• Vomiting: Bamboo Shavings, Villous Amomrum Fruit and Tangerine Peel were

added.

• Dry mouth: Rehmannia Root, Glossy Privet Fruit and Yerbadetajo Herb were

added.


The Western medicines group used HCG 2000 U, im, qod, then decline the dosage

after 12 weeks of pregnancy


The effectiveness rate of Chinese medicines group was 90%, Western medicines group

was 73.3%, and combined medicine group was 93.3%. Significant difference was found

between Chinese herbal medicines and Western medicines alone (P < 0.05). No statistic

difference was found between Chinese herbal medicines and combined medicines (P >

0.05)






Zhong 2002 (Continued)

Risk of bias



bias)




bias)

All outcomes


not feasible.


All outcomes






tween groups”

Zhou 2010


medicines

Participants 87 outpatients from Central Hospital of Jia Ling were recruited (2005 May-2010 May). Participants were all diagnosed as threatened miscarriage due to vaginal bleeding and

abdominal pains


1) An Tai Yin: mainly used White Paeony Root 30 g; Chinese Dodder Seed, Eucommia

Bark, Steamed Rehmannia Root, 25 g each; Chinese Taxillus Twig, Szechwon Tang-

shen Root, Largehead Atractylodes Rhizome, Donkey-hide Glue, Chinese Angelica, Hi-

malayan Teasel Root, Liquorice Root, 15 g each

2) Decoction: po, TID till 7 days after vaginal bleeding stopped

The Western medicines group used progesterone 20 mg, im, qd; vitamin E, 100 mg, po,

qd; folic acid, 5 mg, po, tid; till 7 days after vaginal bleeding stopped




0.05)


Risk of bias





Zhou 2010 (Continued)



Unclear risk “the patients were randomized divided into2 groups.”


2 groups.”


bias)

All outcomes


not feasible.


All outcomes






tween groups”

Po (per os): by mouth; Im: (intramuscular); iv: (intravascular); ivgtt: (intravenously guttae, or IVdrop ) referred to different adminis-

tration methods; QOD: (every other day); QD: (once per day); BID: (twice per day); TID: (3 times per day); PIN: (taken when

necessary) referredto different dosing; HCG: human chorionic gonadotropin; ITT (intention-to-treat); RCT: randomised controlled

trial.

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Bi 2010 Comparisons were made between patients with threatened miscarriage and normal pregnant women. No out-

comes were reported on the effectiveness of treatments. So the review authors decided to exclude this trial

Chan 2010 This study included some participants with longer than 20 weeks of gestation, which did not meet our inclusion

criteria. So the review authors decided to exclude this paper

Gao 2011 This study did not mention the randomisation methods. Also, the number of participants in each group couldindicate randomisation was not applied to the allocation and intervention. So the review authors decided to

exclude this paper

Guo 2010 Comparison was between combined medicine and Westernmedicines. However, the women in2 groups received

different Western medicines. So the review authors considered that these 2 groups were not comparable and

doubt if the trial author could reach his conclusion that combined medicine was better than Western medicines.

We decided to exclude this paper





(Continued)

Hu 2010b Comparison was between combined medicine and Westernmedicines. However, the women in2 groups received


doubt if the trial author could reach his conclusion that combined medicine was better than Western medicines. We decided to exclude this paper

Li 2011 Comparison was between combined medicine and Westernmedicines. However, the women in2 groups received




Lin 2010 This study did not mention the randomisation methods. And the number of participants in each group could

indicate randomisation was not applied to the allocation and intervention. So the review authors decided to

exclude this paper

Lu 2007 Comparison was between combined medicine and Westernmedicines. However, the women in2 groups received




Lu 2011b This study did not mention the randomisation methods. And the number of participants in each group could

indicate randomisation was not applied to the allocation and intervention. So the review authors decided to

exclude this paper

Lu 2011c Both treatment group and control group received a second Chinese medicine intervention, so the review authors

considered that these 2 groups were not comparable and doubt if the trial author could reach his conclusion that

the test Chinese medicine was effective. We decided to exclude this paper

Luo 2010 Comparison was between combined medicine and Westernmedicines. However, the women in2 groups receiveddifferent Western medicines. So the review authors considered that these 2 groups were not comparable and



Qin 2010 Comparison was between one Chinese medicine and another Chinese medicine. The review authors considered

that the trial author could not reach his conclusion on the benefits of Chinese medicines as treatments. So this

paper was excluded

Ushiroyama 2006 Comparisons were made between a Kampo medicine and Western medicines. Kampo medicine is Japanese

traditional medicine, which may originate from China. To avoid the confusion of readers on the topic of our

review, which is about Chinese herbal medicines, we decided to exclude this trial

Wu 2010 This study did not mention the randomisation methods. And the number of participants in each group couldindicate randomisation was not applied to the allocation and intervention. So the review authors decided to

exclude this paper

Zhang 2000 This study included some participants with longer than 20 weeks of gestation, which did not meet our inclusion

criteria. Furthermore, the amount of participants in each group differed greatly. There were 580 participants in 1

Chinese medicine group, but 50 participants in another Chinese medicine group and 50 participants in Western

medicines group. Therefore, the review authors considered the participants were not randomly allocated, and





(Continued)

decision was made to exclude this paper

Zhang 2006 Data were collected from 1995 to 2005, using 10 years. So the review authors doubt if this is a real RCT.

Also, the number of participants in each group differed. There were 140 participants in the combined medicine

group, but 128 participants in Western medicines group, and the author did not give further information on

the randomisation method. Thus, we decided to exclude this paper

Zhang 2011 Comparison wasbetween combined medicine and Westernmedicines. However, the women in 2 groupsreceived




RCT: randomised controlled trial

Characteristics of studies awaiting assessment [ordered by study ID]

Chen 1999

Methods RCT of Chinese herbal medicines combined with Western medicines compared with Western medicines alone

Participants 720 participants diagnosed with threatened miscarriage were 2:1 divided into 2 groups. (480 for combined medicine

group, and 240 for Western medicines group)

Interventions Comparison between combined medicines and Western medicines was made

Outcomes The effectiveness of combined medicine is higher than Western medicines. Chinese herbal medicine could help andimprove the treatment of Western medicines alone

Notes Dates of data collection started from 1991, and the result was published in 1999, without mentioning the duration

that the 720 patients were involved in the treatments. So the review authors doubt if this was a real RCT, and have

been awaiting response from authors for further information

Guan 2008

Methods RCT of Chinese herbal medicines combined with Western medicines compared with Western medicines alone

Participants 100 participants diagnosed with threatened miscarriage were divided into 2 groups

Interventions Comparison between combined medicines and Western medicines was made

Outcomes The effectiveness of combined medicines is higher than Western medicines. Chinese herbal medicines could help

and improve the treatment of Western medicines alone





Guan 2008 (Continued)

Notes Dates of data collection were from March 1999 to March 2006, using 7 years. So the review authors doubt if this

was a real RCT, and have been awaiting response from authors for further information

RCT: randomised controlled trial





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

Comparison 1. Chinese herbal medicines versus Western medicines (primary outcome and non-specific secondary

outcome)

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Effectiveness of intervention

(primary outcome)

1 60 Risk Ratio (M-H, Random, 95% CI) 1.23 [0.96, 1.57]

2 No relief of clinical signs 1 60 Risk Ratio (M-H, Random, 95% CI) 0.38 [0.11, 1.28]

3 No improvement of laboratory

investigations

0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

4 Repeated threatened miscarriage 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

5 Preterm labour 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

6 Adverse pregnancy outcomes 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

7 Preterm birth 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]8 Stillbirth 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

9 Neonatal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

10 Fetal structural malformations 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

11 Adverse neonatal outcomes 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(non-prespecified secondary

outcome)


Comparison 2. Chinese herbal medicines versus Western medicines (subgroup analysis)


studies

No. of



(maternal age)


1.1 Maternal age below 35 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

1.2 35 and above 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(parity)


2.1 Primipara 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

2.2 Multipara 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

3 Effectiveness of intervention(gestational stage) 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

3.1 First trimester 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

3.2 Second trimester 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(reference)


4.1 Referred herbal medicines 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

4.2 Non-referred herbal

medicines







(treatment course)


5.1 Short-term treatment 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

5.2 Long-term treatment 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(randomisation)


6.1 Quasi-RCTs 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

6.2 RCTs 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

Comparison 3. Combined medicines versus Western medicines (primary outcome and non-specific secondary

outcome)


studies

No. of



(primary outcome)


2 No relief of clinical signs 5 550 Risk Ratio (M-H, Random, 95% CI) 0.21 [0.13, 0.36]

3 No improvement of laboratory

investigations


4 Repeated threatened miscarriage 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

5 Preterm labour 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

6 Adverse pregnancy outcomes 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

7 Preterm birth 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

8 Stillbirth 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

9 Neonatal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

10 Fetal structural malformations 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

11 Adverse neonatal outcomes 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

12 Effectiveness of intervention(non-prespecified secondary

outcome)


Comparison 4. Combined medicines versus Western medicines (subgroup analysis)


studies

No. of



(maternal age)


1.1 Maternal age below 35 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

1.2 Versus 35 and above 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(parity)


2.1 Primipara 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

2.2 Multipara 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(gestational stage)






3.1 First trimester 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

3.2 Second trimester 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(reference)


4.1 Referred herbal medicines 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

4.2 Non-referred herbalmedicines



(treatment course)


5.1 Short-term treatment 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

5.2 Long-term treatment 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]


(randomisation)


6.1 Quasi-RCTs 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

6.2 RCTs 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

Analysis 1.1. Comparison 1 Chinese herbal medicines versus Western medicines (primary outcome and

non-specific secondary outcome), Outcome 1 Effectiveness of intervention (primary outcome).

Review: Chinese herbal medicines for threatened miscarriage

Comparison: 1 Chinese herbal medicines versus Western medicines (primary outcome and non-specific secondary outcome)

Outcome: 1 Effectiveness of intervention (primary outcome)

Study or subgroup

Chineseherbal

medicines Western medicines Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Zhong 2002 27/30 22/30 100.0 % 1.23 [ 0.96, 1.57 ]

Total (95% CI) 30 30 100.0 % 1.23 [ 0.96, 1.57 ]

Total events: 27 (Chinese herbal medicines), 22 (Western medicines)

Heterogeneity: not applicable

Test for overall effect: Z = 1.63 (P = 0.10)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours Western medicines Favours Chinese herbal






non-specific secondary outcome), Outcome 2 No relief of clinical signs.



Outcome: 2 No relief of clinical signs

Study or subgroup

Chineseherbal


n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Zhong 2002 3/30 8/30 100.0 % 0.38 [ 0.11, 1.28 ]

Total (95% CI) 30 30 100.0 % 0.38 [ 0.11, 1.28 ]


Heterogeneity: not applicable

Test for overall effect: Z = 1.57 (P = 0.12)


0.01 0.1 1 10 100

Favours experimental Favours control






non-specific secondary outcome), Outcome 12 Effectiveness of intervention (non-prespecified secondary

outcome).



Outcome: 12 Effectiveness of intervention (non-prespecified secondary outcome)

Study or subgroup

Chineseherbal


n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Cui 2002 49/50 13/20 4.1 % 1.51 [ 1.09, 2.08 ]

Feng 2010a 89/102 77/100 8.8 % 1.13 [ 0.99, 1.29 ]

Feng 2010b 35/40 29/38 6.4 % 1.15 [ 0.93, 1.42 ]

Kuang 2007 41/60 38/60 5.3 % 1.08 [ 0.83, 1.40 ]

Liu 2008 53/58 37/49 7.3 % 1.21 [ 1.01, 1.45 ]

Liu 2009 27/30 10/15 3.3 % 1.35 [ 0.93, 1.97 ]

Liu 2011a 72/77 65/78 9.2 % 1.12 [ 1.00, 1.26 ]

Liu 2011b 40/50 36/50 6.2 % 1.11 [ 0.89, 1.39 ]

Song 2005 97/126 51/117 6.0 % 1.77 [ 1.41, 2.22 ]

Song 2007 44/54 22/51 3.8 % 1.89 [ 1.34, 2.65 ]

Sun 2003 34/36 25/36 5.9 % 1.36 [ 1.08, 1.71 ]

Wang 2007 46/48 43/48 9.3 % 1.07 [ 0.96, 1.20 ]

Wang 2011 107/115 97/110 10.1 % 1.06 [ 0.97, 1.15 ]

Zhang 2007 67/69 27/33 7.7 % 1.19 [ 1.01, 1.40 ]

Zhou 2010 41/45 31/42 6.7 % 1.23 [ 1.01, 1.51 ]

Total (95% CI) 960 847 100.0 % 1.22 [ 1.12, 1.32 ]


Heterogeneity: Tau?? = 0.02; Chi?? = 43.10, df = 14 (P = 0.00008); I?? =68%

Test for overall effect: Z = 4.74 (P < 0.00001)


0.02 0.1 1 10 50






Analysis 3.1. Comparison 3 Combined medicines versus Western medicines (primary outcome and non-

specific secondary outcome), Outcome 1 Effectiveness of intervention (primary outcome).


Comparison: 3 Combined medicines versus Western medicines (primary outcome and non-specific secondary outcome)

Outcome: 1 Effectiveness of intervention (primary outcome)

Study or subgroup

CombinedChi-

nese/Western Western medicines Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Chen 2002 49/51 23/33 11.6 % 1.38 [ 1.09, 1.74 ]

Feng 1997 58/61 33/47 16.4 % 1.35 [ 1.11, 1.65 ]

Lu 2011 99/104 75/96 47.7 % 1.22 [ 1.09, 1.37 ]

Lv 2007 53/58 28/40 13.1 % 1.31 [ 1.05, 1.62 ]

Zhong 2002 28/30 22/30 11.2 % 1.27 [ 1.01, 1.61 ]

Total (95% CI) 304 246 100.0 % 1.28 [ 1.18, 1.38 ]

Total events: 287 (Combined Chinese/Western), 181 (Western medicines)

Heterogeneity: Tau?? = 0.0; Chi?? = 1.51, df = 4 (P = 0.83); I?? =0.0%



0.01 0.1 1 10 100

Favours Western medicines Favours Combined






specific secondary outcome), Outcome 2 No relief of clinical signs.



Outcome: 2 No relief of clinical signs

Study or subgroup Combined medicines Western medicines Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Chen 2002 2/51 10/33 12.2 % 0.13 [ 0.03, 0.55 ]

Feng 1997 3/61 14/47 18.3 % 0.17 [ 0.05, 0.54 ]

Lu 2011 5/104 21/96 29.5 % 0.22 [ 0.09, 0.56 ]

Lv 2007 5/58 12/40 27.9 % 0.29 [ 0.11, 0.75 ]

Zhong 2002 2/30 8/30 12.0 % 0.25 [ 0.06, 1.08 ]

Total (95% CI) 304 246 100.0 % 0.21 [ 0.13, 0.36 ]

Total events: 17 (Combined medicines), 65 (Western medicines)

Heterogeneity: Tau?? = 0.0; Chi?? = 1.06, df = 4 (P = 0.90); I?? =0.0%



0.01 0.1 1 10 100

Favours Combined Favours Western






specific secondary outcome), Outcome 12 Effectiveness of intervention (non-prespecified secondary

outcome).



Outcome: 12 Effectiveness of intervention (non-prespecified secondary outcome)

Study or subgroup Combined medicines Western medicines Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Chen 2003 39/45 24/38 2.3 % 1.37 [ 1.05, 1.79 ]

Deng 2009 95/100 72/100 5.8 % 1.32 [ 1.16, 1.50 ]

Fu 2006 46/47 35/40 6.1 % 1.12 [ 0.99, 1.27 ]

Hou 2010 48/51 15/24 1.7 % 1.51 [ 1.10, 2.07 ]

Hu 2010 30/34 22/34 2.2 % 1.36 [ 1.03, 1.80 ]

Huang 2011 48/50 40/50 5.0 % 1.20 [ 1.03, 1.39 ]

Kuang 2007 55/60 38/60 3.4 % 1.45 [ 1.18, 1.78 ]

Li 2004 24/25 20/25 3.3 % 1.20 [ 0.97, 1.48 ]

Li 2005 57/60 23/30 3.4 % 1.24 [ 1.01, 1.52 ]

Li 2006 35/45 31/44 2.6 % 1.10 [ 0.86, 1.41 ]

Li 2009a 67/72 53/66 5.6 % 1.16 [ 1.01, 1.33 ]

Li 2009b 91/97 69/92 5.9 % 1.25 [ 1.10, 1.42 ]

Li 2010 129/140 93/128 6.4 % 1.27 [ 1.13, 1.43 ]

She 2008 56/60 29/40 3.5 % 1.29 [ 1.05, 1.58 ]

Shen 2010 53/58 45/56 5.0 % 1.14 [ 0.98, 1.32 ]

Sun 2003 35/36 25/36 3.0 % 1.40 [ 1.12, 1.75 ]

Wang 2005 76/80 30/60 2.4 % 1.90 [ 1.47, 2.46 ]

Wang 2010 45/55 32/55 2.5 % 1.41 [ 1.09, 1.82 ]

Xiao 2008 27/30 20/30 2.1 % 1.35 [ 1.02, 1.79 ]

Xu 2005 29/32 26/30 4.1 % 1.05 [ 0.87, 1.25 ]

Xun 2008 42/45 24/30 3.7 % 1.17 [ 0.96, 1.42 ]

Yang 2001 38/42 8/13 1.0 % 1.47 [ 0.95, 2.28 ]

Yang 2006 95/100 36/50 4.1 % 1.32 [ 1.10, 1.58 ]

Zeng 2011 65/68 41/50 5.4 % 1.17 [ 1.01, 1.34 ]

0.01 0.1 1 10 100


(Continued . . . )





12. 1 AND 10 AND 11

Appendix 2. Search strategy for CINAHL

1. exp PREGNANCY/

2. (spontaneous adj2 abortion*).af 3. (threat* adj3 (pregnancy ADJ loss)).af

4. (abortion* adj3 threat*).af

5. (spontaneous adj3 (pregnancy ADJ loss)).af

6. miscarriage*.af

7. (chin* adj6 herb*).af

8. ((china OR chinese) AND (tradition* adj4 medicine*)).af

9. DRUGS, CHINESE HERBAL/

10. 2 OR 3 OR 4 OR 5 OR 6

11. 7 OR 8 OR 9

12. 1 AND 10 AND 11

Appendix 3. Search strategy for PUBMED

1. ((“Chin Med”[Journal] OR (“chinese”[All Fields] AND “medicine”[All Fields]) OR “chinese medicine”[All Fields]) OR (“medicine,

traditional”[MeSH Terms] OR (“medicine”[All Fields] AND “traditional”[All Fields]) OR “traditional medicine”[All Fields] OR

(“traditional”[All Fields] AND “medicine”[All Fields]))) OR (“Trends Cardiovasc Med”[Journal] OR “Case Manager”[Journal] OR

“tcm”[All Fields])

2. (((“therapy”[Subheading] OR “therapy”[All Fields] OR “treatment”[All Fields] OR “therapeutics”[MeSH Terms] OR “therapeu-

tics”[All Fields])OR (“therapy”[Subheading] OR “therapy”[All Fields] OR “therapeutics”[MeSH Terms] OR “therapeutics”[All Fields]))

OR clinical[All Fields]) OR application[All Fields]

3. 1 AND 2

4. (“abortion, spontaneous”[MeSH Terms]OR (“abortion”[AllFields]AND “spontaneous”[AllFields]) OR “spontaneous abortion”[All

Fields] OR “miscarriage”[All Fields]) OR (“abortion, induced”[MeSH Terms] OR (“abortion”[All Fields] AND “induced”[All Fields])

OR “induced abortion”[All Fields] OR “abortion”[All Fields])

5. threatened/abrupt[All Fields] OR threatened/actual[All Fields] OR threatened/actually[All Fields] OR threatened/endangered[AllFields] OR threatened/exposed[All Fields] OR threatened/forced[All Fields] OR threatened/injured[All Fields] OR threatened/in-

volved[All Fields] OR threatened’[All Fields]

6. (“therapeutics”[MeSH Terms] OR “therapeutics”[All Fields] OR “therapeutic”[All Fields]) OR (“recurrence”[MeSH Terms] OR

“recurrence”[All Fields] OR “recurrent”[All Fields]) OR complete[All Fields] OR incomplete[All Fields] OR missed[All Fields] OR

inevitable[All Fields]

7. 4 AND 5 NOT 6

8. 3 AND 7

Appendix 4. Search strategy for CNKI and CJN (Chinese)

1. (subject =miscarriage) OR (subject =abortion)

2. (subject= threatened)

3. (subject =therapeutic) OR (subject = recurrent) OR (subject = recurrent) OR (subject = complete) OR (subject= incomplete) OR (subject= inevitable) OR (subject = missed)

4. 1 AND 2 NOT 3

5. (subject= Chinese medicine*(therapy application+ clinical use)) OR (subject= traditional medicine) OR (subject=TCM)

6. 4 AND 5





Appendix 5. Search strategy for WanFang Database (Chinese)

1. TCM OR (traditional medicine) OR (Chinese medicine)

2. application OR (clinical use) OR therapy

3. 1 AND 2

4. miscarriage OR abortion

5. (threatened abortion) OR (threatened miscarriage)6. 4 AND 5

7. 3 AND 6

Appendix 6. Search Strategies for CBM and Wiley InterScience

Searched by subject heading/keyword/abstract with:

• Traditional Chinese Medicines

• threatened miscarriage treatment

• western medicines

• comparisons studies

• randomized controlled trials

•

meta-analysis• Or could be included or replaced by similar words:

• herbal medicines

• pharmaceuticals

• miscarriage

• spontaneous abortion

• therapy

Medical Subject Headings (MeSH)Miscarriage, Abortion, Threatened [*drug therapy]; Traditional Chinese Medicines, Herbal medicines, [*therapeutic use]; Randomised

Controlled Trials [*methods/topic]; Meta analysis [*method/topic]

Appendix 7. Search Strategy for ICTRP and Chinese Clinical Trials RegistryKeywords of “Threatened”, “Threatened miscarriage”, “Threatened abortion”, “abortion”, “Chinese medicine”, “herbal medicine” were

searched in the title list of registered clinical trials in the databases.

Appendix 8. List of handsearched journals

The following journals were specifically searched for this review.

1. Acta Chinese Medicine and Pharmacology (1980 to Jan 2012)

2. Beijing Journal of Traditional Chinese Medicine (1980 to Jan 2012)

3. Central Plains Medical Journal (1980 to Jan 2012)

4. China Medical Herald (1980 to Jan 2012)

5. China’s Naturopathy (1980 to Jan 2012)

6. Chinese Archives of Traditional Chinese Medicine (1980 to Jan 2012)7. Chinese Journal of Information On Tcm (1980 to Jan 2012)

8. Chinese Journal of Medicine (1980 to Jan 2012)

9. Chinese Journal of Obstetrics and Gynecology (1953 to Jan 2012)

10. Chinese Journal of Perinatal Medicine (1999 to Jan 2012)

11. Chinese Journal of Practical Gynecology and Obstetrics (1986 to Jan 2012)

12. Chinese Medicine and Materia Medica (1980 to Jan 2012)

13. Clinical Journal of Anhui Traditional Chinese Medicine (1980 to Jan 2012)

14. Clinical Journal of Traditional Chinese Medicine (1980 to Jan 2012)





15. Forum On Traditional Chinese Medicine (1980 to Jan 2012)

16. Gansu Journal of Traditional Chinese Medicine (1980 to Jan 2012)

17. Guizhou Medical Journal (1980 to Jan 2012)

18. Hebei Journal of Traditional Chinese Medicine (1980 to Jan 2012)

19. Heilongjiang Medicine and Pharmacy (1980 to Jan 2012)

20. Henan Medical Information (1980 to Jan 2012)21. Henan Traditional Chinese Medicine (1980 to Jan 2012)

22. Hubei Journal of Traditional Chinese Medicine (1980 to Jan 2012)

23. Hunan Guiding Journal of Traditional Chinese Medicine and Pharmacology (1980 to Jan 2012)

24. Hunan Journal of Traditional Chinese Medicine (1980 to Jan 2012)

25. Jiangsu Journal of Traditional Chinese Medicine (1980 to Jan 2012)

26. Jiangxi Journal of Traditional Chinese Medicine (1980 to Jan 2012)

27. Jounal of Hubei College of Traditional Chinese Medicine (1980 to Jan 2012)

28. Jouranl of Guangzhou University of Traditional Chinese Medicine (1980 to Jan 2012)

29. Journal of Anhui Traditional Chinese Medical College (1980 to Jan 2012)

30. Journal of Changzhi Medical College (1980 to Jan 2012)

31. Journal of Chinese Medicinal Materials (1980 to Jan 2012)

32. Journal of Chinese Rural Physician (1980 to Jan 2012)

33. Journal of Guangzhou University of Traditional Chinese Medicine (1980 to Jan 2012)34. Journal of Guiyang College of Traditional Chinese Medicine (1980 to Jan 2012)

35. Journal of Handan Medical College (1980 to Jan 2012)

36. Journal of Jinzhou Medical College (1980 to Jan 2012)

37. Journal of Nanjing University of Traditional Chinese Medicine (1980 to Jan 2012)

38. Journal of New Chinese Medicine (1980 to Jan 2012)

39. Journals of Practical Obstetrics and Gynecology (1986 to Jan 2012)

40. Journal of Practical Traditional Chinese Medicine (1980 to Jan 2012)

41. Journal of Tianjin College of Traditional Chinese Medicine (1980 to Jan 2012)

42. Journal of Traditional Chinese Medicine (1980 to Jan 2012)

43. Journal of Traditional Chinese Medicine and Chinese Materia Medica of Jilin (1980 to Jan 2012)

44. Journal of Youjiang Medical College For Nationalities (1980 to Jan 2012)

45. Liaoning Journal of Traditional Chinese Medicine (1980 to Jan 2012)

46. Maternal and Child Health Care of China (1980 to Jan 2012)47. Modern Journal of Integrated Traditional Chinese and Western medicine (1980 to Jan 2012)

48. Modern Traditional Chinese Medicine (1980 to Jan 2012)

49. Nei Mongol Journal of Traditional Chinese Medicine (1980 to Jan 2012)

50. New Journal of Traditional Chinese medicine (1971 to Jan 2012)

51. Ningxia Medical Journal (1980 to Jan 2012)

52. Practical Clinical Medicine (1980 to Jan 2012)

53. Primary Journal of Chinese Materia Medica (1980 to Jan 2012)

54. Progress in Obstetrics and Gynecology (1994 to Jan 2012)

55. Qinghai Medical Journal (1980 to Jan 2012)

56. Shaanxi Journal of Traditional Chinese Medicine (1980 to Jan 2012)

57. Shanghai Journal of Traditional Chinese Medicine (1980 to Jan 2012)

58. Shanxi Journal of Traditional Chinese Medicine (1980 to Jan 2012)

59. Sichuan Journal of Traditional Chinese Medicine (1980 to Jan 2012)60. Sponsored By Gubei College of Traditional Chinese Medicine (1980 to Jan 2012)

61. The Practical Journal of Integrating Chinese With Modern Medicine (1980 to Jan 2012)

62. Tianjin Journal of Traditional Chinese Medicine (1980 to Jan 2012)

63. Traditional Chinese Medicinal Research (1980 to Jan 2012)

64. Zhejiang Journal of Traditional Chinese Medicine (1964 to Jan 2012)





H I S T O R Y

Protocol first published: Issue 5, 2010

Review first published: Issue 5, 2012

C O N T R I B U T I O N S O F A U T H O R S

Dr Li Lu and Prof Wang Chi Chiu both wrote the initial and final versions of the review. Dr Dou Li Xia and Prof Leung Ping Chung

commented on the final version of the review.

D E C L A R A T I O N S O F I N T E R E S T

None known.

S O U R C E S O F S U P P O R T

Internal sources

• Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong.

• Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong.

• Hop Wai Scholarship 2009. Institute of Chinese Culture,The Chinese University of Hong Kong, Hong Kong.

to support attending Cochrane training and workshops in United Kingdom (27 July-23 August 2009)

• Zi Ying Scholarship 2010. Institute of Chinese Culture,The Chinese University of Hong Kong, Hong Kong.

to support attending Cochrane workshop in Germany (18-20 Mar 2010)

• CUHK Postgraduate Student Grants for Oversea Academic Activities. The Chinese University of Hong Kong, Hong Kong.

to support the study trips in United Kingdom and Germany.

External sources

• Health and Health Services Research Fund (HHSRF) from Food and Health Bureau, Hong Kong Special Administration

Region, Hong Kong.

D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W

In the protocol, we planned to include studies with only abstracts available. After working on the review, we found that there are two

papers with abstract only and related to our topic, however, no detailed information is provided for our further inclusion for meta-

analysis study. Therefore, we excluded these trials and all the included papers had full texts. Additionally, we included 44 trials at first

and after having carefully read all the included studies and input data to the extraction forms, we found that 39 of the studies concluded

the outcomes immediately after the courses of treatment, instead of long-term observations until term delivery. Therefore, we still listed

the characteristics of these trials but reported the related data as non-prespecified secondary outcome (continuation of pregnancy after

treatment) to supplement the primary outcome. We have added ’livebirth’ as a secondary outcome.





I N D E X T E R M S

Medical Subject Headings (MeSH)

Abortion, Threatened [∗drug therapy]; Drugs, Chinese Herbal [∗therapeutic use]; Phytotherapy [∗methods]; Randomized Controlled

Trials as Topic

MeSH check words

Female; Humans; Pregnancy

Chinese Herbal Medicines for Threatened Miscarriage

Documents

Transcript of Chinese Herbal Medicines for Threatened Miscarriage