**1. Introduction**

#### **1.1. Chinese medicines for pregnancy**

#### *1.1.1. Application in China*

Chinese medicines have become very popular and are widely applied to different kinds of medical conditions during pregnancy [1]. It promotes both mothers' and fetuses' health,

relieves and cures common disorders in women [1]. It has been used as a main stream medicine in China with a longer history than Western medicines.

The first record of Chinese medicines treatment related to reproductive was first explained in A Chinese Bestiary 3000 years ago during Xia, Shang and Zhou era [2, 3]. Since then, Gu Rong was commonly used for contraception [2, 3]. In the following centuries, considerable progress was achieved in both clinical theory and practice while lots of milestones have been developed in Obstetrics and Gynecology. Due to historical factors of the late Qing Dynasty, and the influence of Western Medicine under the Renaissance, development of Chinese Medicine was less prominent [4]. After the establishment of People's Republic of China, with the great efforts of lots of Chinese Medicine practitioners and researchers, 6th edition of the textbook "Traditional Chinese Medicine in Obstetrics and Gynecology" [4] and lots of reference books and monographs have been published and used for daily teaching, training and self-learning. Apart from medical educations in Chinese Medicine, researches in collaborations with Chinese medicines and Western medicines have been raised to a new level and lots of meaningful conclusions have been drawn. For example, it was reported that combined Chinese medicines and Western medicines for ectopic pregnancy were more effective than conventional treatment [5, 6], and the method of combined medicines has been well studied and applied widely since then.

#### *1.1.2. Development in foreign countries*

Chinese Medicine in China has a long history, but its development for pregnant women in other countries is just within recent centuries. In foreign nations, the most common treatments are Acupuncture and Chinese herbal medicines (CHMs). Other therapies of Chinese Medicine, which could be used during pregnancy, began to spread to the world in very late twentieth century, such as Tui Na Massage and Die Da [4].

Chinese herbal medicines (CHMs) spread to the world earlier than acupuncture but only widely applied lately, due to the early advancement and modernization of Western medicines in foreign countries [7]. For instance, the "European Pharmacopoeia" had been locally well-developed, and Chinese herbs as medicines were not attractive to the practitioners and patients. With the advantages of Chinese medicines, including less side effects and greater effectiveness in some chronic diseases (such as infertility and irregular menstruation) than Western medicines, it was gradually accepted by foreigners and now has been spread to over 160 countries [3]. More and more foreign researchers and clinical doctors seriously have interests in it and come to China for further study.

#### *1.1.3. Effectiveness and efficacy*

With a long history of application of Chinese medicines to treat pregnant disorders, large amounts of case reports and clinical trials have been reported [8]. However, until now, limited data are available to overview Chinese medicines for pregnancy. Our team has reported in a systematic review [9] about the general applications, including common formulae, common individual CHMs, dosage and dosing, frequency, therapeutic efficacy, clinical indications and so on.

Chinese medicines are prescribed in formulae, and the Chinese medicine practitioners decide the formula according to the clinical presentation. Based on medical knowledge and personal experience, some use original or traditional formula, the others have individual prescription as personalized medicine. The prescribed formulae vary a lot, some formulae even lack unified theory and scientific evidence. Therefore, under a long-term collaboration with Cochrane Review Pregnancy and Childbirth Group, our team has conducted two systematic reviews with meta-analyses to study the claimed efficacy of Chinese herbal medicines for pregnancyrelated disorders [10, 11]. The results showed that combined Chinese herbal medicines and other pharmaceuticals are more beneficial than other pharmaceuticals alone for threatened miscarriage [10] and unexplained recurrent miscarriage [11], but the evidence on the effectiveness and safety of Chinese herbal medicines alone as treatment is still insufficient, due to the poor qualities of the included clinical trials.

#### *1.1.4. Safety*

relieves and cures common disorders in women [1]. It has been used as a main stream

The first record of Chinese medicines treatment related to reproductive was first explained in A Chinese Bestiary 3000 years ago during Xia, Shang and Zhou era [2, 3]. Since then, Gu Rong was commonly used for contraception [2, 3]. In the following centuries, considerable progress was achieved in both clinical theory and practice while lots of milestones have been developed in Obstetrics and Gynecology. Due to historical factors of the late Qing Dynasty, and the influence of Western Medicine under the Renaissance, development of Chinese Medicine was less prominent [4]. After the establishment of People's Republic of China, with the great efforts of lots of Chinese Medicine practitioners and researchers, 6th edition of the textbook "Traditional Chinese Medicine in Obstetrics and Gynecology" [4] and lots of reference books and monographs have been published and used for daily teaching, training and self-learning. Apart from medical educations in Chinese Medicine, researches in collaborations with Chinese medicines and Western medicines have been raised to a new level and lots of meaningful conclusions have been drawn. For example, it was reported that combined Chinese medicines and Western medicines for ectopic pregnancy were more effective than conventional treatment [5, 6], and the method of combined medicines has been well studied and

Chinese Medicine in China has a long history, but its development for pregnant women in other countries is just within recent centuries. In foreign nations, the most common treatments are Acupuncture and Chinese herbal medicines (CHMs). Other therapies of Chinese Medicine, which could be used during pregnancy, began to spread to the world in very late

Chinese herbal medicines (CHMs) spread to the world earlier than acupuncture but only widely applied lately, due to the early advancement and modernization of Western medicines in foreign countries [7]. For instance, the "European Pharmacopoeia" had been locally well-developed, and Chinese herbs as medicines were not attractive to the practitioners and patients. With the advantages of Chinese medicines, including less side effects and greater effectiveness in some chronic diseases (such as infertility and irregular menstruation) than Western medicines, it was gradually accepted by foreigners and now has been spread to over 160 countries [3]. More and more foreign researchers and clinical doctors seriously have inter-

With a long history of application of Chinese medicines to treat pregnant disorders, large amounts of case reports and clinical trials have been reported [8]. However, until now, limited data are available to overview Chinese medicines for pregnancy. Our team has reported in a systematic review [9] about the general applications, including common formulae, common individual CHMs, dosage and dosing, frequency, therapeutic efficacy, clinical indications and

medicine in China with a longer history than Western medicines.

28 Chinese Medical Therapies for Diabetes, Infertility, Silicosis and the Theoretical Basis

applied widely since then.

*1.1.2. Development in foreign countries*

twentieth century, such as Tui Na Massage and Die Da [4].

ests in it and come to China for further study.

*1.1.3. Effectiveness and efficacy*

so on.

Safety is always the biggest issue in daily medical practice, and the issue is also a major concern to pregnant women. Chinese herbal medicines have been used to treat diseases and complications during pregnancy, and it is apparently well accepted as with fewer side effects.

There are 31 Chinese herbal medicines that were classified as toxic and contraindicated during pregnancy, which have been listed in many textbooks. The website of Chinese Medicine Council of Hong Kong (CMCHK) recently released another five CHMs, which contain aristolochic acid, which could induce abortion, kidney damage and cancer. Further studies of these Chinese herbal medicines have been carried out in the last 20 years and have demonstrated their adverse effects on both/either mothers and/or newborns. For example, Kansui Root (Radix Kansui, Gan Sui) is prohibited in pregnancy because it can poison the fetus and stimulate uterine contraction [12].

On the other hand, numbers of clinical trials have also been carried out to assess the safety of some Chinese herbal medicines in pregnancy and associated conditions, or to compare the adverse effects of Chinese herbal medicines with other medicines. Among the commonly used Chinese medicines, there are not too many studies of their potential harmful effects however. Our team has carried out a systematic review [13, 14] with meta-analyses to record the potential adverse effects and safety issues of CHMs as treatment for threatened miscarriage, but conclusive results remain elusive, as studies varied considerably in design, interventions and outcome measures. In the absence of placebo-controlled trials, the safety of Chinese medicines for the treatment of threatened miscarriage is unknown. Rigorous scientific and clinical studies to assess the possible risks of Chinese medicines are needed.

In conclusion, it is not clear how safe the Chinese medicines are being used during pregnancy and if there is any adverse effects to embryo-fetal development and prenatal and postnatal growth.

#### **1.2. Chinese pharmacopeia**

Unlike those pharmaceutical drugs not recommend for use during pregnancy because of known or suspected adverse or teratogenic effects evident by animal studies and/or clinical trials, most of the Chinese medicines were utilized for long history in culture which, however, has very limited scientific data regarding the adverse pregnant outcomes.

"Chinese Pharmacopeia", acknowledged by World Health Organization (WHO) as the official pharmacopeia for Chinese medicines, records 1146 different Chinese medicines [15]. It provides information on the herbs with their characteristics, identity, impurity, contents, extractum, analysis, property and channel, therapeutic action, pharmacological data, dose and dosing, precautious, storage, authentication methods and so on.

Among all this valuable information, we will obtain the most specific safety information for pregnancy from the Chinese Pharmacopeia and provide to the doctors, scholars and patients as scientific evidence on the safe application of Chinese medicines during pregnancy.
