Will Dong Quai Hurt Baby if Miscarriage Fails?

Evid Based Complement Alternat Med. 2014; 2014: 753856.

Systematic Review of Chinese Medicine for Miscarriage during Early on Pregnancy

Lu Li

^aneDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

Detect articles by Lu Li

Ping Chung Leung

²Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

Tony Kwok Hung Chung

¹Department of Obstetrics and Gynaecology, The Chinese Academy of Hong Kong, Shatin, New Territories, Hong Kong

Chi Chiu Wang

¹Section of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

Received 2013 Apr 22; Revised 2013 Nov 30; Accepted 2013 Dec ane.

Supplementary Materials

The information of Chinese medicines commonly practical as treatments for threatened miscarriage has been list in the Supplementary Table ane, including the Chinese, English language and Biological names, the frequency of usage, the recorded dose in "Chinese Pharmacopeia" and the daily dose in all published literatures of each Chinese medicine.

GUID: 87B3E80D-73F1-4504-8B86-DFA65A711DFC

Abstract

Background. Miscarriage is a very mutual complexity during early on pregnancy. So far, clinical therapies accept limitation in preventing the early pregnancy loss. Chinese Medicine, regarded equally gentle, constructive, and condom, has go popular and common as a complementary and alternative handling for miscarriages. However, the evidence to back up its therapeutic efficacy and safety is still very express. Objectives and Methods. To summarize the clinical application of Chinese Medicine for pregnancy and provide scientific evidence on the efficacy and safety of Chinese medicines for miscarriage, we located all the relevant pieces of literature on the clinical applications of Chinese Medicine for miscarriage and worked out this systematic review. Results. 339,792 pieces of literature were identified, but no placebo was included and but few studies were selected for systematic review and conducted for meta-assay. A combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety problem was reported, simply potential adverse events by certain medicines were identified. Conclusions. Studies vary considerably in blueprint, interventions, and outcome measures; therefore conclusive results remain elusive. Large scales of randomized controlled trials and more than scientific evidences are yet necessary to confirm the efficacy and safety of Chinese medicines during early on pregnancy.

1. Introduction

Miscarriage is defined as spontaneous abortion without medical or mechanical means to stop a pregnancy earlier the fetus is sufficiently adult to survive [1]. Information technology denotes early pregnancy loss prior to completion of the 20th gestational week, or 139 days, counting from the offset 24-hour interval of the last normal menses [ii]. The incidence of miscarriage is commonly stated every bit 10%–15% of all pregnancies, and information technology is the most common complexity during pregnancy [3]. However, the incidence is difficult to decide precisely, since as many every bit 30% may become unrecognized, and these can occur very early during a pregnancy. The etiology of miscarriage is largely unknown and the underlying cause of well-nigh cases cannot be identified.

Miscarriage can be classified as threatened, inevitable, incomplete, missed, or recurrent. Threatened miscarriage presents as vaginal bleeding/spotting with or without cervical dilatation [ane]. It will become inevitable when gross rupture of fetal membranes occurs along with severe vaginal bleeding and cervical dilatation; imminent fetal loss is virtually certain in these cases [one]. Incomplete miscarriage refers to the internal cervical bone remaining open up and allows for passage of blood, simply the products of conception could remain entirely or partially in utero extrude [one]. Missed miscarriage is used to describe dead fetus and placenta that remained for days or weeks in the uterus with a closed cervical os and/or without any symptoms of abortion [4]. Recurrent miscarriage is mostly defined every bit spontaneous abortions repeated consecutively over iii or more times [i].

Current treatment for miscarriage is rather empirical. Bed remainder does not change the course and progress of miscarriage significantly [five]. Acetaminophen-based analgesia may take some effects on relieving the pains simply [6]. Most usually used Western medicines were progesterone and human chorionic gonadotropin (HCG). HCG maintains the luteotrophic furnishings after luteinizing hormone secretion decreases in gild to support continued secretion of estrogen and progesterone. Progesterone maintains the endometrial proliferation and prevents pregnancy loss [7, 8]. All the same, their beneficial result still cannot be verified [vii, 9].

The mission of the National Middle for Complementary and Alternative Medicine (NCCAM) defines complementary and alternative medicine equally a grouping of various medical and health care systems, practices, and products, which are not mostly considered part of the conventional medicine [10]. In that location are unlike types of CAM [11], including natural products (a variety of herbal medicines, vitamins, minerals, etc.), heed and trunk medicine (deep-breathing exercises, guided imagery, etc.), and manipulative and body-based practices (spinal manipulation, meditation, and yoga). CAM also encompasses movement therapies (a broad range of Eastern and Western move-based approaches used to promote physical, mental, emotional, and spiritual well-being) such as Feldenkrais method, Alexander technique, and Pilates.

Chinese medicine is well accepted as the mainstream of medical care throughout East Asia with a history of 5,000 years; information technology has been spread aboard since the sixth century BC [12]. It has been widely used to promote health and care for illnesses since then [thirteen] and accepted as a major arroyo of complementary and alternative medicine in Western world at present [14]. Chinese medicine includes several different treatments which are applied quite differently, but they are all based on the aforementioned understandings of assumptions and insights in the nature of the human body [fifteen]. Main therapeutic approaches [16] include acupuncture (past stimulating certain acu-points with or without acupuncture needles to treat disorders or improve the health status), Chinese medicines (applying traditional medicines, mainly from herbs, animals, and minerals, to cure illness and maintain adept wellness,), nutrient therapy (dietary recommendations on certain foods and herbs to residue inner torso), Qi Gong (promoting health by special breathing and meditation exercise), Tai Chi (benefiting unlike systems past the movements of muscles and the activities of related joints), Tui Na (applying massage on the surface of the body to clear the meridians and meliorate the blood flow), Cupping (relieving blood stasis and hurting by creating vacuum on trunk), Die Da (commonly applied in the injuries of limbs past directly stimulation on the torso surface), and Gua Sha (scaling the skin to stimulate specific acu-points until mild to moderate subcutaneous hemorrhage) [12, 13, 17].

In Chinese Medicine [18, 19], miscarriage is defined every bit "fetal irritability" or "fetal restlessness," while recurrent miscarriage is called "stirring fetus". Miscarriage shares the same clinical signs and symptoms every bit in Western Medicine. The presentations of miscarriage are similar, mainly with abdominal pains and vaginal bleeding. But unlike mainstream Western Medicine, Chinese Medicine has a unique medical theory to understand miscarriage. To make the diagnosis and guide the handling, "Qi" and "Blood" are the two bones elements involved. The major causes of threatened miscarriage include "Kidney Deficiency," "Qi Deficiency," "Blood Deficiency," "Blood Oestrus," "External Injury," and "Wei Jia" (refers to ectopic pregnancy, which is considered as a cause of threatened miscarriage in Chinese Medicine). The diagnosis and treatment are based on different causes and varied a lot in unlike patients.

The principle [14] of treatments is to supplement and regulate the balance of maternal "Qi," "Blood," and the system concerned and raise the survivals of fetuses, so as to relieve clinical signs, promote pregnancy, and prevent inevitable miscarriage. Besides its application as expectant management for threatened and recurrent miscarriages, Chinese Medicine is also used every bit agile managements for missed, incomplete, and consummate miscarriages [20], which mainly accelerate the claret circulation then as to stimulate uterine contractions and empty the uterus.

Still, there is only limited information about the awarding of Chinese medicines for miscarriage in a few systematic reviews recently [21]. Besides, the efficacy and safety claims of Chinese medicines still accept no scientific proof. The aim of this study was to access and review the bachelor literature on the clinical applications of Chinese medicine for miscarriage during early pregnancy, in order to provide scientific evidences and valuable references to clinical workers and researchers for practices and studies. The specific objectives were

1. to identify the most common therapeutic arroyo and clinical application of Chinese Medicine for miscarriage;

2. to evaluate the nigh normally used formulae and individual Chinese medicines for miscarriage and compared the clinical dose and dosing with the recommendations in Chinese Pharmacopeia;

3. to clarify the effectiveness and agin outcomes of Chinese medicines as treatment for miscarriage.

two. Materials and Methods

ii.ane. Search Method

We used bailiwick heading, keyword, and abstract including Chinese Medicine, pregnancy, and miscarriage/abortion and searched all published clinical trials of Chinese Medicine for miscarriage. The following databases were searched: Cochrane Central Register of Controlled Trials, mainly Cochrane Database of Systematic Reviews and Cochrane Database of Abstracts of Reviews of Effects (from 1996 to April 2013); EMBASE (from 1980 to April 2013); Cumulative Index to Nursing and Allied Wellness Literature (CINAHL) (from 1982 to Apr 2013); Chinese Biomedical Database (CBM) (from 1978 to April 2013); Medline (and PreMedline) (from 1950 to April 2013); China Journal Net (CJN) (from 1915 to April 2013); Mainland china National Knowledge Infrastructure (CNKI) (from 1915 to April 2013); Wiley Inter Science (from 1966 to April 2013); and Wan Fang Database (Chinese Ministry of Science and Technology) (from 1980 to Apr 2013).

We also screened bibliographies of the selected articles and searched by hand for any net inaccessible articles. We also explored the searches in the reference parts which were listed in these clinical trials and reports identified.

two.2. Systematic Review

2.2.1. Inclusion Criteria

1. Types of Studies. All clinical studies reporting the applications of Chinese Medicine to any miscarriage during early pregnancy were included. All the titles and abstracts were further reviewed.

2. Participants. All women, regardless of the age, gestational historic period, parity, and nationality of the participants, receiving Chinese Medicine for miscarriage are included.

3. Diagnosis. All the studies included for meta-analysis applied the same inclusion criteria—the standard diagnosis and exclusion criteria for threatened miscarriage according to the textbook "Obstetrics & Gynaecology" [eighteen]. Near of the patients received treatment in early pregnancy, around tertiary month of gestation. And there is no pregnant departure in the baseline of studies. However, equally the treatment was individually applied based on the presentation of patients and the experience of Chinese Medicine practitioners, the durations of treatments varied a lot in the included clinical trials, and it is difficult to make a comparison or comport out a baseline assay on this issue.

4. Interventions. Chinese Medicine was administered equally interventions in the clinical trials. Just Chinese medicines recorded by the Chinese Pharmacopeia with well-characterized principles of pharmacological and medicinal applications were included. Other pharmanutrients from various herbal agents and products were excluded. Since Chinese medicines are crude drugs of found, animate being, and mineral origins, non only those Chinese medicines originated from plants or herbs but also those from animals and minerals were included. All types of Chinese medicines in either standard or combined formulas are used in the treatment of threatened miscarriage regardless of the dose or duration of administration.

5. Outcome Measures. The therapeutic approach and clinical application of Chinese Medicine for miscarriage; the commonly used formulae and individual Chinese medicines and the clinical dose and dosing; the effectiveness and efficacy of the intervention like live birth rate, premature birth rate, miscarriage rate, and the rubber of the intervention like side furnishings and adverse events were studied.

6. Publications. No restriction on the languages was applied. Publications without full text just with abstracts only were also included.

2.2.2. Exclusion Criteria

1. Other Participants. Nonpregnancy related and other gynaecology illness, and complications were excluded.

2. Combined Therapies. If the intervention combined Chinese medicines with other therapies, the clinical trial was included but analyzed seperately.

3. Other Type of Studies. Case reports, commentary studies, and review manufactures were excluded.

two.2.iii. Data Extraction and Quantitative Assay

We designed extraction forms to extract data from the selected publications quantitatively. The numbers of the publication in different databases inside each decade were counted. The full numbers of included studies were summarized. The total numbers of excluded papers and the exclusion criteria were presented in menstruum charts. To identify the common clinical applications of Chinese medicines during pregnancy, the clinical indication of each clinical study was recorded and compared. To place the commonly used Chinese medicine formulae and individual Chinese medicines, the frequency of each formula or private medicine used in the clinical studies was calculated. The clinical daily dose and dosing of the formula and individual Chinese medicines and their effective rate were recorded and analyzed.

2.3. Meta-Analysis

2.three.1. Effectiveness Study

Study Inclusion

1. Types of Studies. Merely randomized controlled clinical trials evaluating the effectiveness of Chinese medicines for the handling of threatened miscarriage were included. Quasirandomized controlled clinical trials (quasirandom method of allocating participants were used) and cluster-randomized trials (participants are recruited in randomized groups) were also studied.

2. Types of Participants. All women in the clinical trials had a feasible pregnancy complicated with threatened miscarriage, regardless of its underlying causes. No treatment was given before interventions. Fetal viability was assessed by ultrasound to exclude the inevitable, incomplete, or missed miscarriage. Vaginal bleeding after the 20th week of pregnancy and recurrent miscarriage were excluded. We included women regardless of whether the pregnancy was singleton or multiple and irrespective of the maternal age and parity.

3. Types of Interventions. All types of Chinese medicines in either standard or new formulae for the treatment of threatened miscarriage regardless of the dose or duration of assistants were compared with other interventions, including no treatment, bed residual, placebo, and other pharmaceuticals.

4. Types of Issue Measures. Effectiveness of intervention was defined as either continuation of pregnancy after 28 weeks of gestation or continuation of pregnancy immediately after treatment.

Study Exclusion

1. Types of Studies. Clinical trials without randomization were excluded from this review, just if the randomization method was not clearly stated or was doubted, we contact the author for confirmation.

2. Types of Interventions. Other therapeutic approaches of Chinese Medicine were excluded. The intervention combined Chinese medicines and other therapies were also excluded from our study.

3. Types of Effect Measures. If the trials ended that Chinese medicines were constructive but no data was shown, we also exclude the studies.

2.iii.2. Rubber Report

Boosted Literature Search. Since we assumed that the adverse events of Chinese Medicine are very rare, in addition to the above search strategy, we performed additional literature search. To collect the extrainformation on safety of Chinese medicines, several online national and public resources on World Broad Web were as well referred, including Center for Nutrient Prophylactic and Applied Diet (CFSAN) from U.Due south. Nutrient and Drug Assistants (FDA, http://world wide web.fda.gov/), National Center for Complementary and Alternative Medicine (NCCAM) from U.S. National Establish of Wellness (NIH, http://nccam.nih.gov/), Agricultural Enquiry Service (ARS) from U.S. Department of Agriculture (USDA, http://www.ars-grin.gov/duke/), Medical Dictionary for Regulatory Activities (MedDRA) from International Federation of Pharmaceutical Manufacturers and Associations (IFPMA, http://world wide web.ifpma.org/), National Council Confronting Health Fraud (NCAHF) from a individual health bureau (http://world wide web.ncahf.org/), Quackwatch from an American nonprofit arrangement (http://www.quackwatch.com/), HerbMed from Culling Medicine Foundation (http://www.herbmed.org/), and ConsumerLab from an independent laboratory (http://www.consumerlab.com/), accessibility verified until 15 April 2013 [22].

Inclusion and Exclusion of Written report

1. Types of Studies. All published clinical studies that evaluated the condom of Chinese medicines for threatened miscarriage were considered. Studies of Chinese medicines in beast, chemical, and bones researches were excluded. Case reports, commentary articles, and nonsystematic reviews were also excluded. Clinical studies with incomplete records or no evaluation of agin pregnancy outcome were farther excluded. Only example controlled studies with or without randomization were included for meta-analysis. Randomized studies, blinded randomized, quasirandomized, and cluster-randomized, were included. Clinical studies without example controlled, including observational and prospective cohorts, were also included for pooled analysis if in that location are no or too few case controlled studies for invalid meta-assay.

2. Types of Upshot Measures. Adverse pregnancy outcomes in both mothers and fetuses/infants will be recorded. Maternal outcomes included toxicity, side effects, pregnancy loss, and pregnancy complications. Fetal outcomes included perinatal bloodshed, toxicity, congenital malformations, and other neonatal complications.

2.3.3. Assessment of Chance of Bias in Included Studies

We assessed the run a risk of bias, including the sequence generation to check for possible selection bias, the allocation darkening to check for possible selection bias, the blinding to check for possible performance bias, the incomplete outcome data to check for possible attrition bias through withdrawals, dropouts, protocol deviations, the selective reporting bias, and other sources of bias from compliance and baseline similarity.

2.3.iv. Measures of Treatment Effect

Statistical assay was performed by using Review Manager Version 5.ane (RevMan five). We presented results equally summary chance ratio with 95% confidence intervals for dichotomous data.

2.3.five. Unit of measurement of Analysis Issues

Trials with up to three arms (Chinese medicines alone, and Western medicines alone, combined Chinese and Western medicines) were analyzed. We input the data separately for meta-assay.

2.3.6. Dealing with Missing Data

For included studies, nosotros noted levels of attrition and explored the touch of included studies with high levels of missing data for the overall assessment of treatment effect by using sensitivity analysis. For all outcomes nosotros carried out analyses on an intention-to-treat basis; we attempted to include all participants randomized to each group in the analyses. The denominator for each outcome in each trial was the total number of participants randomized minus any participants whose outcomes were known to exist missing.

2.three.7. Assessment of Heterogeneity

Nosotros assessed statistical heterogeneity in each meta-analysis using the T ², I ², and χ ⁱⁱ statistics. We regarded heterogeneity every bit substantial if T ² was greater than zero and either I ⁱⁱ was greater than 30% or in that location was a low P value (<0.01) in the χ ² test for heterogeneity.

2.3.8. Data Synthesis

We carried out statistical assay using RevMan5 and used fixed-effect inverse variance meta-analysis for combining data when the studies were estimating the same underlying treatment consequence and the populations and methods of the trials were judged sufficiently similar. For clinical heterogeneity sufficient to expect that the underlying treatment furnishings differ betwixt trials, or if substantial statistical heterogeneity was detected, nosotros used random-effects meta-assay to produce an overall summary if an average treatment consequence 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 implications of treatment furnishings differing between trials. For the average treatment effect which is not clinically meaningful, nosotros did not combine trials. For random-effects analyses, we presented the results every bit the average treatment upshot with its 95% confidence interval and the estimates of T ^two and I ².

For dichotomous safety outcomes, we counted the number of agin events and the involved participants in each study. For continuous safety outcomes, we calculated the mean and standard deviation of the measures if appropriate. Dichotomous information were expressed as relative ratio (RR) with 95% confidence intervals (CI), while continuous data were expressed as weighted mean differences (WMD) by the meta-analysis.

2.3.9. Subgroup Assay and Investigation of Heterogeneity

To place the potential factors of the efficiency outcomes, nosotros likewise carried out subgroup analyses on maternal historic period, parity, different trimesters, standard and nonstandard herbal medicines, treatment duration, and quality of included trials. For fixed-outcome meta-analyses, we conducted planned subgroup analyses classifying whole trials past interaction tests as described [23]. For random-effects meta-analyses we assessed differences between subgroups by inspection of the subgroups' confidence intervals; not-overlapping confidence intervals indicated a statistically meaning difference in treatment issue between the subgroups.

2.3.10. Sensitivity Analysis

We also carried out sensitivity analysis to explore the outcome of trial quality for important outcomes in the review. Sensitivity analyses on results were performed on wait at the possible contribution of loftier hazard of bias in the resource allotment of participants to groups associated with a detail report [24] or loftier levels of missing data [21].

iii. Results and Discussion

3.1. Chinese Medicine for Pregnancy

Upward to 15 April 2013, 339,792 literature reported studies of Chinese Medicine for all applications were identified (Figure 1). Amidst all the studies, only 12,912 (3.8%) literature studied Chinese Medicine for pregnancy or pregnancy related applications (Tabular array 1). Chinese medicines for other disorders for nonpregnancy applications (91.9%) were excluded (Figure two). Most of the pieces of literature were mainly plant in CNKI and CJN Full-Text Database and WanFang Database but much less in PubMed, Cochrane Library, EMBASE, MEDLINE, and WILEY Interscience (Effigy 3). Well-nigh of the pieces of literatures (78.6%) were published in Chinese, whilst few of the pieces of literature (21.4%) were published in English and other languages.

The pieces of literature of Chinese Medicine for all medical fields published in decades. Numbers on the top: total numbers of literature in each decade.

Study inclusions and exclusions for systematic review (Chinese medicines for pregnancy).

The pieces of literatures of Chinese Medicine for pregnancy published in various databases.

Table 1

Number of literature studies on clinical application of Chinese Medicine.

Chinese Medicine approaches	Clinical application in all medical fields	Clinical application for pregnancy	Clinical awarding for miscarriage
Chinese medicines	241,237 (80.0%)	3,338 (90.5%)	one,444 (91.1%)
Acupuncture	28,754 (9.five%)	208 (half-dozen.2%)	96 (six.two%)
Food Therapy	13,382 (iv.five%)	96 (two.nine%)	32 (2.0%)
Qi Gong	xi,671 (3.9%)	7 (0.two%)	two (0.i%)
Tui Na	3,061 (ane.0%)	xvi (0.5%)	2 (0.1%)
Tai Chi	1,646 (0.five%)	7 (0.two%)	ii (0.1%)
Cupping	864 (0.3%)	8 (0.two%)	two (0.1%)
Dice Da	529 (0.2%)	eight (0.ii%)	2 (0.one%)
Gua Sha	403 (0.1%)	1 (<0.ane%)	3 (0.2%)
Total	301,547 (100%)	iii,689 (100%)	1,585 (100%)

In Cathay, it is considered not just every bit a primary medicine for treatment but also every bit a supplementary therapy to promote health in general population. Chinese medicines (56.2%) were the well-nigh common therapeutic approach of Chinese Medicine for pregnancy, while acupuncture (forty.8%) was the second. Amongst all the pieces of literature studied Chinese medicines for pregnancy, man studies (46.3%) were included, while animal studies (31.ix%), chemic studies (12.vii%), genetic studies (5.9%), and microbiology studies (3.3%) were excluded. Most Chinese medicines are derived from nature, including plants, animals, and minerals. Herbal medicines from plants are much more unremarkably applied than the others. two,858 (85.0%) studies used herbal medicines for intervention were included. Other studies used medicines originated from animals (ix.5%) and minerals (4.8%) were too included. Other medicines not included past the Chinese Pharmacopeia (0.3%) and included the pharmanutrients from various herbal biological agents and products (0.three%) were farther excluded. In total, 3,338 pieces of literature were included for systematic review (Figure iii).

3.2. Chinese Medicines for Miscarriage

Amongst all pieces of literature of Chinese medicines for pregnancy, miscarriage (43.3%) was the nigh common clinical indication of the Chinese medicines for pregnancy [25] (Table 2). Less mutual clinical indications included infertility (27.9%), therapeutic ballgame (11.vii%), immunological disorders (6.2%), hypertensive disorders (3.8%), infection (2.six%), fetal growth restriction (ii.2%), preterm labor (ane.5%), postdate (0.3%), gestational diabetes mellitus (0.vi%), puerperium (0.i%), and other obstetric complications. Amid different types of miscarriage, threatened miscarriage was the most common 1 for Chinese medicines (Effigy 4).

Clinical application of Chinese medicines for different types of miscarriage.

Table ii

Clinical applications of Chinese medicines during pregnancy.

Pregnancy disorders	Frequency* (%)	Therapeutic applications
Spontaneous abortion	one,444 (43.3)	Improve maternal health Promote embryo-fetal development Reduce irregular vaginal haemorrhage
Infertility	930 (27.9)	Improve women'due south health Elevate the female person fertility
Induced ballgame	392 (xi.7)	Enhance lethal effect on embryos Decrease incomplete abortion rate Improve vaginal irregular bleeding
Immunological disorders	206 (6.2)	Inhibit the release of inflammatory molecules
Hypertensive disorders	126 (3.8)	Promote vasodilatation Increase claret flow Decrease platelet aggregation
Infection	87 (2.6)	Decrease intrauterine transmission
Fetal growth brake	73 (2.2)	Improve uteroplacental circulation Promote fetal growth
Preterm labour	49 (1.five)	Inhibit uterine contractility
Postdate or term	9 (0.three)	Accelerate labor process
Gestational diabetes mellitus	20 (0.six)	Better insulin levels Enhance glucose metabolism
Puerperium	2 (0.i)	Better hormone levels Promote lactation and uterine wrinkle Heal perineum injuries
Total	iii,338 (100)

three.iii. Chinese Medicines for Threatened Miscarriage

In that location were 418 clinical studies of Chinese medicines for threatened miscarriages. However, 97 (24.one%) were case reports, 67 (16.0%) were commentary articles, and 43 (10.three%) were review articles. Since case reports are only involved with very small number of participants, by and large with just one instance and all less than 5 individuals, which could hardly represent the general application of Chinese medicines. Commentary articles focused on the theory and hypothesis without details and data for further study. Other review articles contributed to summary and conclusion on clinical topics, other than systematically review the clinical trials. Nosotros further excluded the example reports, commentary manufactures, and the review articles. In total, 211 clinical trials 2 duplicated papers excluded, were selected for meta-analysis and quantitative analysis (Figure 5).

Study inclusions and exclusions for systematic review (east.g., clinical trials of Chinese medicines for threatened miscarriage).

iii.iii.1. Common Formulae

Among all the formulae studied for threatened miscarriage (Table 3), "Shou Tai Pill" was the most often used formula (72.0%). Its main role is to enhance the function of "Kidney" and regulate the "Qi" in the human body, so to amend the health condition of mothers and benefit the fetus. Its basic formula includes four individual Chinese medicines, Chinese Dodder Seed (Semen Cuscuta), Chinese Taxillus Twig (Floralia Taxillus), Himalayan Teasel Root (Radix Dipsaci), and Donkey-hide Mucilage (Colla Corii Asini). The onetime three medicines improve the "Qi" in the body, while Donkey-hide Glue regulates the "Blood" circulation. Therefore, the therapeutic effects of "Shou Tai Pill" are mainly for the pregnant women to improve body condition of mothers and the fetuses. Supplementary of Largehead Atractylodes Rhizome (Rhizoma Atractylodis Macrocephalae) and Pilose Asiabell Root (Radix Codonopsis) in the formula can enhance the therapeutic furnishings by farther improving the "Qi" of pregnant women [26].

Table three

Chinese medicine formulae studied for threatened miscarriage.

Order	Name	Frequency*	Main composition	Therapeutic actions			Other applicationsb
				Dosea (g)	Dosinga	System/organ
1	Shou Tai Pill	301 (72.0%)	Colla Corii Asini Herba Taxilli Radix Dipsaci Semen Cuscutae	five–15 9–15 nine–xv 6–12	QD/BID	Reproductive organization and Spleen and Kidney	Belly distension, lower belly pain, dizziness, frequent urination, urinary incontinence, tinnitus, lower-limb weakness.
2	Si Junzi Decoction	52 (12.5%)	Ginseng, Poria Radix Glycyrrhizae Rhizoma Atractylodis Macrocephalae	9–30 iii–nine six–12	QD/BID	Immune organisation and Kidney and Spleen	Chronic gastritis, gastric ulcer, duodenal ulcer, antitumor
iii	An Tai Decoction	28 (6.seven%)	Cortex Eucommiae Folium Artemisiae argyi Giseng, Radix Dipsaci Poria cocos Radix Angelicae sinensis Radix Astragali Radix Paeoniae Alba Radix Rehmanniae Praeparata, Cyperi Radix Scutellariae Rhizoma Atractylodis Macrocephalae Rhizoma	six–15 iii–9 9–thirty 9–15 6–12 ix–30 6–15 9–fifteen 6–9 ix–xxx 6–12	QD/BID	Reproductive arrangement and Kidney and Spleen	Vitiligo
four	Wu Zi Decoction	16 (3.eight%)	Caulis Perillae Colla Corii Asini Cortex Eucommiae Fructus Lycii, Fructus Rubi Fructus Schisandrae chinensis, Herba Taxilli Radix Dipsaci Radix Scutellariae Southwardemen Cuscutae	5–9 v–15 6–15 half-dozen–12 3–ten 3–6 9–15 nine–15 9–30 6–12	QD/BID	Kidney	Uterine hypoplasia, male infertility
5	An dian Er tian Decoction	10 (2.iv%)	Eucommia ulmoides Oliver Fructus Corni, Preparata Fructus Lycii, Giseng Radix Glycyrrhizae Radix Rehmanniae Rhizoma Atractylodis Macrocephalae Rhizoma Dioscoreae	half dozen–fifteen 6–12 6–12 ix–30 3–nine 9–15 6–12 6–12 15–30	QD/BID	Spleen Kidney	Postmenopausal bleeding
6	Jiao Ai Decoction	6 (1.iv%)	Colla Corii Asini Folium Artemisiae Argyi P. Lactiflora Curtain Radix Angelicae Sinensis Radix Glycyrrhizae Radix Rehmanniae Praeparata	v–15 3–9 6–15 6–12 three–9 9–15	QD/BID	Liver Spleen Kidney	Thrombocytopenic purpura, abdominal pain
7	Others	5 (1.two%)	Nonstandard Formulae	3–thirty	QD/TID	Spleen

Other pop formulae (Table 3) include "Si Jun Zi Decoction," "An Tai Yin," "Wu Zi Decoction," "An Dian Er Tian Decoction," and "Jiao Ai Decoction". The therapeutic furnishings of "Si Jun Zi Decoction" in the treatment of miscarriage ameliorate the functions of "Spleen" and "Tummy" and regulate "Qi" [27]. "An Tai Yin" improves the office of "Kidney" and then regulates "Qi" and "Blood" [28]. "Wu Zi Decoction" promotes the luteal office by supplementing the "Qi" and "Blood" [29]. "An Dian Er Tian Decoction" relieves the clinical signs such as vaginal bleeding and is mainly applied for recurrent miscarriage [30]. "Jiao Ai Decoction" enhances "Kidney" and regulates "Blood" to improve the health status of mothers and also to relieve vaginal bleeding [31]. Most of these regimes comprise Largehead Atractylodes Rhizome (Rhizoma Atractylodis Macrocephalae), Ginseng (Panax Giaseng), and Baical Skullcap Root (Scutellaria Baicalensis), which are generally used to nourish and regulate the "Qi". It has been reported that the combination of Largehead Atractylodes Rhizome and Baical Skullcap Root is highly recommended for their effects to do good and survive the fetus [17].

In the literature, in that location were lots of modified formulae, which were not recorded in either Chinese Pharmacopeia or the textbooks. They were prescribed co-ordinate to the experience of physicians and clinical presentations of the patients. For instance, Rehmannia root (Radix Rehmanniae), Lycium fruit (Fructus Lycii), and Cuscuta fruit (Semen Cuscutae) are added into the basic formula of Shou Tai pill and prescribed equally a new formula, which was used to correct "Kidney" deficiency in treatment of miscarriage [32].

three.3.2. Individual Chinese Medicines

According to Chinese Pharmacopeia, the official Pharmacopeia for Chinese medicines, acknowledged by World Health Arrangement (WHO), simply 130 out of i,150 individual Chinese medicines had been used in the clinical trials [29] (see total list in Supplementary Table 1 available online at http://dx.doi.org/10.1155/2014/753856, acme x list in Table 4).

Table 4

Top ten of most commonly studied individual Chinese medicines for threatened miscarriage.

Order	English name	Biological name	Frequency*	Hateful daily dosea	Therapeutic actionsb	Other applicationsc
1	Largehead Atractylodes Rhizome	Rhizoma Atractylodis Macrocephalae	59 (41%)	12.7 g	Prevent miscarriage	—
2	Chinese Dodder Seed	Semen Cuscutae	55 (38%)	21.8 grand	Prevent miscarriage and prelabor	Cataract, diarrhea, sperm abnormality, chronic prostatitis.
3	Himalayan Teasel Root	Radix Dipsaci	55 (38%)	15.iii g	Stop vaginal bleeding Prevent miscarriage	Fractures and injuries, Lower dorsum pain.
four	Donkey-hide Glue	Colla Corii Asini	49 (35%)	6.3 g	Increment platelet count Stop vaginal spotting	Chronic bleeding, anemia, tuberculosis, uterine fibroids, endometriosis.
v	Chinese Taxillus Twig	Herba Taxilli	48 (34%)	17.nine thou	Prevent miscarriage Lower high claret force per unit area	Lower back pain, tendons atrophy.
half-dozen	Milkvetch Root	Radix Astragali	48 (34%)	22.9 g	—	Chronic nephritis, diabetes mellitus, diuresis.
7	White Peony Root	Radix Paeoniae Alba	44 (31%)	15.five one thousand	Regulate menstruation	Belly and limb pain, bank check sweating.
8	Chinese Angelica	Radix Angelicae Sinensis	42 (29%)	x.ane thou	Improve claret circulation Regulate menstruum	General pain, bowels overactivity.
nine	Liquorice Root	Radix Et Rhizoma Glycyrrhizae	40 (28%)	6.2 g	—	Detoxification, dispel phlegm, cough, spasmodic pain.
10	Baical Skullcap root	Radix Scutellariae	35 (24%)	10.1 grand	Cease vaginal bleeding Forestall miscarriage	Detoxification.

3.iii.3. Clinical Dose and Dosing

A big range of clinical doses of the Chinese medicines was recorded in the reported clinical trials (Supplementary Matrial Tabular array 1). The hateful and median daily dose for each medicine ranged from vi 1000/24-hour interval to 23 g/day. About 90.9% of Chinese medicines, 10 to twenty g/day, was recommended, while 9.one% less than 5 m/day or more than than 25 g/day was recommended. For example, Fructus Amomi has been prescribed as small as 2 g/solar day only, while Rehmannia Root has been used more than than thirty g/solar day. In 95% of cases, the Chinese formulae were taken once a solar day, while 4% twice a day and merely 1% three times a day. The summit 10 about unremarkably used single Chinese medicines included Largehead Atractylodes Rhizome, Chinese Clump Seed, Himalayan Teasel Root, Donkey-hide Glue, Chinese Taxillus Twig, Mongolian Milkcetch Root, White Paeony Root, Chinese Angelica, Liquorice Root, and Baical Skullcap Root in descending order (Table 4).

iii.4. Efficacy and Effectiveness

3.four.1. Efficacy

Constructive rate of Chinese medicines for threatened miscarriages in each clinical trial was recorded [29], and the charge per unit ranged from 75% to 100%. Among all the records, over 84.6% of the studies exceeded 90%, while 24.3% exceeded 95%. 2 studies reported 100% [33, 34]. However, no significant correlation was found between frequency of use and effective rate of the studied Chinese Medicine (r = 0.1086, P = 0.335). The superlative x Chinese medicines merely had effective rates from 91.three% to 93.ii% (Figure 6). Information technology suggests that normally used Chinese medicines might non upshot in a better efficacy.

Efficacy of private Chinese medicines.

To evaluate the human relationship betwixt dosage and efficacy of Chinese Medicines in the handling of threatened miscarriage, the daily dose of the studied Chinese medicine was correlated with the effective charge per unit of the intervention. Chinese medicines with 95% or higher efficacy were less usually used, 0.72%–7.91%. The Chinese medicines in 20 yard or higher mean daily dose, the efficacy ranged from 83.33% to 95.83%. However, in that location was still no significant correlation between hateful daily dose and efficacy (r = 0.2324, P = 0.513) (Figure seven). It suggests that increased dose might not result in a better efficacy.

There were also different dosing records in different clinical studies. The constructive charge per unit of dosing once per day has everyman effective rate, while dosing twice per day has highest effective rate, simply dosing iii times per day did not further increase the constructive charge per unit. At that place was no significant difference between effective rate and the daily dosing times (Figure 8). It suggests that increasing dosing could non increase the efficacy.

3.4.2. Effectiveness

With a long history of application of Chinese medicines to care for significant disorders, big amounts of case reports and clinical trials have been reported [35]. However, until now, no data are available to overview the effectiveness of Chinese medicines for pregnancy.

In our previous review [36], no placebocontrolled trial was establish. The effectiveness of Chinese medicine treatments can be compared simply through the comparisons amongst Chinese medicines, Western medicines, and combined medicines. Nonetheless, virtually Western medicines included tocolytic drugs (due east.g., salbutamol and magnesium sulfate), hormonal supplementations (eastward.grand., human chorionic gonadotrophin and progesterone), immunotherapy (e.g., IgG immunization and antiphospholipid antibodies) and supportive supplements (east.yard., vitamin E and folic acid), which have no proved benefits. The meta-analysis in express randomized clinical trials did not support that Chinese medicines alone were more effective than Western medicines. Simply information technology showed that combined Chinese and Western medicines were more than effective than Western medicines alone to prevent inevitable miscarriage and go along pregnancy after 28 weeks of gestation. Meta-analysis in other clinical trials indicated that Chinese medicines alone or Chinese medicines combined with Western medicines were more effective than Western medicines alone to treat threatened miscarriage in relieving the clinical signs, including vaginal bleeding, low back pain, and intestinal pains. The result confirmed the therapeutic effects of Chinese medicines solitary and combined with other pharmaceuticals for threatened miscarriage. In current update study, only one new randomized clinical trial was included [37] for meta-analysis; the new analysis resulted in same decision (Figure nine).

Efficacy of Chinese medicines versus pharmaceuticals.

Due to insufficiency of data, analysis for all designed subgroups was not employed. Mean maternal historic period and/or range in each group were not reported. Comparing between the participants of below 35 years old and above 35 years one-time cannot be performed. All the clinical trials reported the overall parity of all participants but did not provide details nigh the parity in each groups, so farther comparisons were not possible. Gestational historic period at threatened miscarriage was non available either. Comparing betwixt get-go trimester and 2nd trimester could not be carried out due to insufficient data. All of the Chinese medicines and the supplements were standard formulae equally stated in the Chinese Phamacopeia, so no subgroup assay between standard formula and nonrecorded formula was carried out. Equally to the treatment course, only one report [38] reported the termination of intervention (with unknown reason), while the other three studies [39–41] did not written report the details on the total amount of the courses for the treatment. Therefore, it is difficult to extract the information and deport out assay on the elapsing of intervention for the effectiveness. No trials had whatsoever loftier run a risk of bias in the allocation of participants to groups or significanty of missing data was identified, then the sensitivity analysis was not carried out. If a sufficient number of trials are found in the future update, we volition further specify sensitivity analyses.

Though the issue favored Chinese medicines for threatened miscarriage, it must exist mentioned that different Chinese medicines were used in different studies. About Chinese Medicine practitioners slightly modify the standard prescriptions depending on the presentations of each patient. In the clinical trials, most of the trials used a common prescription of "Shou Tai Pill" as basic formula, while the others used dissimilar prescriptions. However, some Chinese medicines accept been supplemented into or removed from the standard formula during the treatment. Therefore, the effectiveness of the studies could but stand for the general effects of Chinese medicines but not the effects of the Chinese formula or individual Chinese medicines. Besides, the success rate for many of the clinical trials was higher than that in the general population (ofttimes over 90%). This indicated that many of the patients included were probable relatively far forth in the pregnancy (when loss rates are lower).

As in most cases, doctors would suggest the patients to accept bed rest first, although it as well has no significant furnishings in altering the form and progress of miscarriage [5]. All the same, no study compared Chinese medicines handling to bed remainder in this review. Western medicines were not considered as classical therapies for threatened miscarriage [7, 8]. Then the conclusion of the effectiveness of Chinese medicines is limited. Therefore, more placebocontrolled trials are necessary to evaluate the effectiveness of Chinese medicines.

3.four.iii. Limitations and Difficulties

In the early on years of Chinese Medicine studies, the pieces of literature could exist only obtained from Chinese databases. With the development of Chinese Medicine and its spread to foreign countries, more and more western scientists and clinical workers accept interests in Chinese Medicine, and various studies have been carried out and could exist identified in English databases since the late 70s. An increasing tendency is that Chinese Medicine was studied past foreign researchers in the following decades. From 2000 onwards, more than English database recorded Chinese Medicine in different areas and topics, covering clinical trials for various applications, animal studies for toxicity tests, laboratory research on chemic components, and commentary articles for theories of Chinese Medicine. Due to the differences in linguistic communication and theory, most pieces of literature of Chinese Medicine studies are yet identified in Chinese database, however. There are some major limitations in identifying the publications from various databases. As at that place are some discrepancies in the translation of Chinese Medicine from Chinese to English language, and lots of medical terms of Chinese Medicine are hard to interpret, literature searches are always inefficient when searched by an English subject headings and keywords in Chinese database. On the other hand, lxxx% of the pieces literature were overlapped in 2 famous Chinese databases, China National Knowledge Infrastructure (CNKI) and WanFang, and it is time consuming to double check because of limited resources and tools. As the mainstream medicine is in China, over 86% of the publications were establish in Chinese databases only. This largely limits the researchers and scientists in western countries to obtain the information and knowledge. Although some of the publications were with English abstracts, in most cases English full texts are not available. Information technology is very hard for foreigners to understand the Chinese Medicine.

Regarding the design of the clinical studies in Chinese medicines for threatened miscarriage, there are withal some limitations. Firstly, well-conducted randomized controlled trials are of import for meta-assay. Most of the selected trials accept inadequate methodology quality. Furthermore, the quality of each clinical trial was plainly not at the same level. Therefore, information technology would exist profoundly helpful to improve the quality of analysis if the authors were fairly trained to carry out and report such clinical trials according to the international standard, including sufficient randomization method and adequate allocation concealment, double-blinded participants and researchers or outcome assessors, participants' classifications, and effects assessments. Secondly, a better clinical trial should also provide some essential information, such as the average days or weeks of the treatments, the changes in the medicines dosage and compositions, the corporeality of participants with a successful pregnancy till 28 weeks or afterward, and the mortality and follow-ups of newborns, which would exist helpful to examine the effects of Chinese medicines in the handling. Thirdly, all the comparisons in these clinical trials were made between Chinese medicines and other medicines, which were non the recommended and the almost constructive treatment for threatened miscarriage. So it is hard to draw a conclusion on the therapeutic effects of Chinese medicines, and we advise more placebocontrolled trials to be involved in the time to come clinical trials. Concluding but not least, small numbers of qualified clinical trials and insufficient information in this review did limit us to comport farther subgroup analysis; more details and information of the clinical trials are essential to further understand the effects of Chinese medicines in the analysis.

three.5. Safety and Adverse Outcomes

3.five.one. Safety

Then far, Chinese medicines are claimed to be prophylactic if applied properly, and in the last 3000 years of practices, almost of the medicines have been applied in the same way as their showtime records. In fact, all Chinese Medicine practitioners concur that Chinese medicines are with their potential side effects, which could be reduced or eliminated by prescribing in formula, shortening the class of treatment and correctly adjusting the dose and constitutes of Chinese medicines. However, the scientific evidence of its condom is yet lacking.

Despite case reports of adverse furnishings accused by Chinese medicines, evidences of adverse events in the utilize of Chinese medicines for threatened miscarriage are limited. In most clinical trials, adverse effects and toxicity of the Chinese medicines were not studied. Just very few studies reported no adverse consequence and toxicity after maternal exposure [42–44] and some gastrointestinal furnishings, including nausea, dry mouth, anorexia, and constipation were reported [43]. Clinical outcomes of threatened miscarriage were not followed in about 2%–xx% cases, if Chinese medicines intervention failed. Even if the intervention was successful and pregnancies were maintained, adverse pregnancy and/or perinatal outcomes were not studied in well-nigh studies. Preterm deliveries were reported in some studies with incidence rate 0.7%–half-dozen.four% [45–48], while premature rupture of membranes and stillbirth were identified in a separate study [46]. Neonatal expiry due to prematurity, asphyxia, or infection was identified in some studies [45–47, 49], while an unspecified malformation was recorded in a study [35] and epilepsy and mental retardation in a study [47]. However, all the clinical studies did non further written report and explain the possible causes for these agin effects, and there was limited evidence for the states to observe a direct relation betwixt the adverse outcomes with Chinese medicines.

3.v.ii. Adverse Outcomes

In our previous review [21], thirty-2 relevant manufactures included ix randomized controlled trials, 1 quasirandomized controlled trial, and ii controlled trials comparing Chinese medicines alone or combined medicines with pharmaceuticals and 20 case series with no controls were studied and analyzed. All the same, sample sizes of each study were more often than not minor. There was variation in Chinese medicine formulation, dosage, and elapsing of treatment. In the pooled randomized controlled trials, dry oral cavity, constipation and insomnia (ii–x%), intervention failure (3.1–22.3%), diabetic complications (three%), preterm delivery (5%), and neurodevelopmental morbidity (1.8%) were recorded. Meta-analysis demonstrated that intervention failure was significantly lower in the combined Chinese medicines groups than in the Western medicines controls (relative hazard = 0.46; 95% conviction interval: 0.30–0.lxx, I² = 0%). No meaning differences were found between these groups for adverse effects and toxicity or for agin pregnancy and perinatal outcomes (Effigy 10). In current update study, no new randomized clinical trial was included for meta-analysis.

Adverse event of Chinese medicines versus pharmaceuticals.

Chinese medicines are non gratuitous of hazard; similar to Western pharmaceutical medicines, they have the potential to cause adverse furnishings. The active ingredients of Chinese medicines are likewise chemicals that are similar to prescription pharmaceuticals. Thus, Chinese medicines in Chinese Medicine may not but result in maternal manifestations that indirectly touch fetal health, just they may also damage the fetus directly. Despite variations in clinical practice and therapeutic prescription, Chinese medication in Chinese Medicine should comply with the same mod pharmacological principles every bit Western Medicine. Chinese medicines not only may be beneficial just may also adversely affect both mothers and fetuses in utero.

iii.v.3. Limitations and Difficulty

Over xc% of the clinical trials did not include agin issue as 1 of study outcome measures. It may due to the incidence of adverse events be indeed besides rare or the awareness on the adverse furnishings was actually likewise low. The low rate of adverse events after maternal exposure to Chinese medicines for threatened miscarriage was recorded, however. The incidences were not besides low to be hands missed. Hence lack of sensation on the safety issue of Chinese medicines in general could be the chief reason for limited safe studies available.

Apart from limited records in agin outcomes, report designs were also restricted. In that location were no placebocontrolled trial and but 1 controlled trial was with acceptable randomization method. Whilst all other cohorts had no controls for comparison, allocation methods were not described and their quality was relatively low. Nevertheless, the report results were questionable. Though the drop-out rates were not loftier, sample sizes of the selected studies were yet very small. Some of import demographic data and study exclusion criteria were non provided. Different studies used different Chinese medicine formulae to treat threatened miscarriage and as well at that place were big variations in the dose, dosing, and elapsing of the intervention among the studies. Most studies followed up the pregnancy until commitment, but the issue parameters in the pregnancy and perinatal complications were rather inconsistent. Few studies monitored adverse effects and toxicity of Chinese medicines, and complicated miscarriage was unknown. Attributable to the express number of randomized controlled trials and the clinical heterogeneity between studies, additional meta-analysis to evaluate the adverse effects of Chinese medicine for threatened miscarriage was non available.

Unlike Western herbalism, Chinese medicines include many brute materials and fifty-fifty mineraloid remedies equally well as medicinal herbs [50]. Most of the formulae are processed by decoction in humid water for hours and are orally administered every bit a "soup" [51], though information technology tin can be supplied as powders, soluble granules, and tablets nowadays. As each Chinese medicine has its ain holding and potential interaction, the awarding of formulated and individualized medication enhances the therapeutic deportment of some herbs and collaborates all the herbs to balance disharmony of each individual for treatment. Withal, the agin furnishings and toxicity of Chinese medicines may vary in different combinations, preparations, and individuals. It is hard to identify which Chinese medicine attributes to the specific adverse effects.

4. Conclusions

Chinese medicines, as the most mutual therapeutic approach of Chinese Medicine, take become pop for therapeutic and complementary utilise in healing diseases and maintaining health, not only in Prc just also effectually the world. In this study, nosotros focused on the Chinese medicines for pregnancy providing background information for overall agreement on the clinical applications of Chinese Medicine during pregnancy, and scientific evidences on their efficacy and safe for pregnancy apply.

The results showed that (1) 339,792 pieces of literature were identified, mostly from Chinese databases, and just few clinical studies were selected for systematic review; (2) Chinese medicine is the most mutual therapeutic approach for miscarriage, and the well-nigh common clinical indication was threatened miscarriage; (3) the most usually prescribed formula to prevent miscarriage and promote the pregnancy was Shou Tai Pill, and the most oft used private Chinese medicine was Largehead Atractylodes Rhizome; (4) the Chinese medicines for threatened miscarriage were mostly single dose per day, just the range of the dose was quite big; (5) the overall effectiveness charge per unit of Chinese medicines for threatened miscarriage was over 90%; however, there is no direct correlation between efficacy and usage frequency, and between efficacy and dose and dosing; (6) no placebo was included in either efficacy or safe study, and only few studies with high quality were conducted for meta-assay; (seven) based on limited clinical trials, a combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety trouble was reported, but potential agin and toxic effects by certain medicines were identified.

It is suggested that Chinese medicines combined with Western medicines may be effective to treat miscarriage and salvage the clinical signs, while Chinese medicines alone may not be constructive. However, large scales of randomized controlled trials and more scientific evidences, especially placebocontrolled trials, are still necessary to ostend the effectiveness of Chinese medicines. In nearly of the pieces of literatures, Chinese medicines are ninety% effective, and our meta-analysis too supports the therapeutic awarding of Chinese medicines. Notwithstanding, most of the studies are so flawed that meaningful conclusions cannot be made; there is a drastic demand for better clinical studies on Chinese medicines. Potential adverse effects of Chinese medicines on mothers and fetuses during pregnancies are defective, and the evidences of adverse events in the use of Chinese medicines for threatened miscarriage are limited. Studies vary considerably in pattern, interventions, and result measures; therefore conclusive results remain elusive. Rigorous scientific and clinical studies are necessary to confirm the adventure of Chinese medicines.

Supplementary Material

The data of Chinese medicines unremarkably applied equally treatments for threatened miscarriage has been list in the Supplementary Table 1, including the Chinese, English and Biological names, the frequency of usage, the recorded dose in "Chinese Pharmacopeia" and the daily dose in all published literatures of each Chinese medicine.

Acknowledgments

Lu Li received the Hop Wai Scholarship and the Zi Ying Scholarship from the Institute of Chinese Culture and Postgraduate Student Grants for Overseas Academic Activities from the Graduate Schoolhouse, The Chinese University of Hong Kong, to attend Cochrane training workshops in Oxford and Freiburg and to written report in the Cochrane Pregnancy and Childbirth Group at University of Liverpool and the Yu To Sang Memorial Scholarship 2008/2009 and 2009/2010 from the Chinese University of Hong Kong during her Ph.D. study. Lu Li has received fellowships from Deutscher Akademischer Austausch Dienst (DAAD) and Enquiry Fellowship Scheme (RFS) for her inquiry projection in Deutschland and Hong Kong, respectively.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of the paper.

Authors' Contribution

Lu Li is responsible for study identification, screening, eligibility and inclusion, data acquisition, and statistical analysis. Chi Chiu Wang is responsible for study eligibility and inclusion, conception of the project, design of the study, and research funding. Lu Li and Chi Chiu Wang both wrote the initial and terminal versions of the review. Ping Chung Leung and Tony Kwok Hung Chung were responsible for commenting and approving the final newspaper.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933529/

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