Herbal Medicines use in Pregnancy in Northern Cyprus

Objective: To identify the herbal medicinal products used in pregnancy in community pharmacies, the approach of pharmacists in Northern Cyprus and to compare the availability of the most commonly mentioned medicinal plants in accessible databases, in Northern Cyprus. Design: Questionnaire was designed and administered to 263 community pharmacists in Northern Cyprus and gathered the data on herbal medicinal products they had and recommended to pregnant women. Databases such as ScienceDirect, PubMed, OpenAcces Journals were searched through the Near East University Grand Library’s Online Resources for keywords relating to the ‘herbal medicine’, ‘pregnancy’ ‘pregnant women’, ‘herbal products’. Descriptive statistics was used with IBM® Statistical product and service solutions software platform. Location/Setting: Northern Cyprus Outcome Measures: Herbal medicinal products used and recommended in pregnancy by community pharmacists in Northern Cyprus were identified. It has also been determined which of the most used plants in the world are grown in Northern Cyprus. Results: The most recommended herbal pharmaceutical forms were herbal lozenges (n = 76, 31%), then herbal form of teas (n = 60, 24%), herbal oils (n = 57, 23%), herbal capsules (n = 36, Original Research Article Tülek et al.; JPRI, 33(43A): 487-504, 2021; Article no.JPRI.72774 488 14%), other pharmaceutical forms (n=20, 8%). Within the limitation of our literature search, totally 650 medicinal plants (single or formula) used in pregnancy were determined. Out of these 74 were mostly used worldwide, and it was discovered that 56 species out of these plants are grown or cultivated; 18 of the compiled species were imported species some of the genera have species growing naturally growing in Cyprus. Conclusion: Pregnant women in Cyprus also follow their counterparts in other countries in developing interest in herbal medicines. The number of herbal medicines in the pharmacies owned by Turkish Cypriots is small. Interestingly, the result of this study showed that the pharmacists that were mainly Turkish Cypriots were found not to be selling herbal medicinal products to pregnant women without doctor’s prescriptions. This study recommends that the herbal medicines use in pregnancy should be the ones that have undergone in-depth evidence-based scientific researches with clinically proven efficacy that are known not only to the healthcare professionals such as medical doctors, midwives but also the pharmacists and the general public.


INTRODUCTION
Taking care of pregnancy is important to pregnant women at all stages of development of the fetus. In an effort to do that, both chemotherapy and phytotherapy are commonly taken into consideration. The use of latter for example is receiving attention among pregnant women especially in the past thirty years, remarkable increase has been recorded in the last twenty. This is because of the perception that herbal medicines are of comparatively lesser side effects than the conventional medicines largely by women as opposed men [1,2]. Likelihood of such usability is higher at pregnancy especially second trimester when the signs of the pregnancy are eminent. All in the name of protecting the health of the fetus from perceived harmful effects of the conventional medicines. As evident in various part of the world, different types and forms of herbal medicinal products were used by pregnant women for different purpose.
In this study plant based medicinal products used during pregnancy were reviewed, their indications as observed in pregnant women were documented and tabulated alongside related published researches on how safe and or effective they are. This is to enable provision of starting point for future studies on the safety and efficacy of phytomedicines and their products use in treating different health related issues during pregnancy with belief that the outcome could important to both the consumers and healthcare professionals alike. Safety related issues and efficacies of the herbal medicines such as mutagenic and teragenic effects are usually not completely known however inferences are usually drawn on basis of outcomes of researches conducted in laboratories and on animal models [3]. This does not to deny the fact that the inherent pharmacologic effects of some of the active components of these herbal products used by pregnant women might affect the fetus and such potential effects are known to the pregnant women themselves.
Because of the aforementioned issues and the importance attached doing research in these regards, this work aims to search and review accessible literatures on the use of plant-based medicinal products use in pregnancy as well as conduct survey on herbal medicinal use recommendations by North Cyprus pharmacists through administering questionnaires as permitted by the Turkish Pharmacists Association. And the availability of these medicinal plants found in North Cyprus was compared to that of other countries based on the literatures reviewed.

Drug Prescription and Pregnancy
Treatment of pregnant women are done by grouping them on the basis of their conditions before the pregnancy, coincidental sickness and conditions that are directly related to pregnancy [4]. This is done with the ultimate aim of achieve best pregnancy within shortest period by taking the effective and least toxic dose that would keep the pregnant women in a controlled situation [4]. It is pertinent that pregnant woman takes into cognizance of balancing of not treating medical conditions and avoidance of treating those conditions with drugs [4].
Taking some medicines during pregnancy comes with different degree of risks of harming the fetus -i.e. teratogenic effect, of medically historical importance is the thalidomide tragedy that occurred at the thereabouts of 1960 which prompted the increase in public awareness on risk of use of some drugs during pregnancy [5]. Since most of the drugs taken by pregnant women are delivered to the developing baby by passing across the placenta which may affect the fetus either positively or negatively. If wellresearched conventional medicines are reported to have negative effects to pregnant women, then there is no doubt that the herbal medicinal use in pregnancy need to be compiled and investigated as well.

Herbal Medicines in Pregnancy
Herbal medicinal treatment of pregnancy conditions are often rendered as a complementary and alternative medicine (CAM) which is defined by the National Centre for Alternative and Complementary Medicines as a "Group of health care approaches developed outside of conventional medicines for specific conditions or overall wellbeing' [6].
While the Herbal Medicinal Product (HMP) is defined by the European regulations as: "any medicinal product, exclusively containing as active ingredients one or more herbal or one or more herbal preparations, or more such substances in combination with one or more such herbal preparations" [7]. Similarly World Health Organization (WHO) defines HMP as "any medicinal product base on herbs, herbal preparations and finished herbal products that contain as active ingredient parts of plants, or other plant materials, or combinations thereof" [8].

Safety Issues of Use of Herbal Medicines in Pregnancy
The ultimate aim of the treating pregnancy using drugs is to achieve best pregnancy within shortest period by taking the effective and least toxic dose that would keep the pregnant women in a controlled situation [4].
The use of over-the-counter medicines and especially herbal medicines during pregnancy this is owing to the perceived believe that natural medicinal products are comparatively safer than the allopathic medicines and protects the fetus from negative effects of the latter. However, it is important to note that herbal medicines, despite their widely perceived safety, they were historically shown to have potent pharmacological actions that thus calls for questioning the perceived safety in comparison to their conventional counterparts [8]. And thus the clinical research outcomes on herbal medicines are medical less informative as must of the inferred safety and efficacy are animal studies, in vitro studies and laboratory researches thus making it difficult to determine their teratogenic and mutagenic effects [3, 4] so mainly their effects are largely unknown.

Prevalent Use of Herbal Products
The prevalence of use of HMPs differ from one country or region to the other for example in the European Union with lowest range of 5.9% and up to 48.3% higher than the USA with 17 Accordingly WHO report showed that about 80% of population of use their traditional medicines to take care of their health comparatively higher than of China where the prevalence of herbal medicinal use ranged from 30 to 50% [19]. However, another study has shown more than fifty percent (50%) of pregnant women in Europe as well as North America and those from regions that industrialized used CAM approximately once [19].
Health professionals do sometime recommend HMPs to pregnant women inorder to control pregnancy conditions. It was reported in a survey to determine the percentage recommendation of herbal medicine by midwives which showed that midwives endose HMPs to pregnant women in a ranges between 65% to 100% during which 78% to 96% of those midwives who participated in the survey had referred the clients to CAM practitioner similarly a study conducted in Turkey reported that 58.9% of the participated midwives have suggested the use of CAM to their patience [20]. However, despite the endorsement of CAM by the healthcare professionals, there were tendency of taking contraindicated herbal medicines in pregnancy [18], this calls for the need for urgent awareness creation [8, 20,21]. The increased use of phytomedicinal products is likely to be based upon the perception that the allopathic medicines are of lesser safety and effectiveness as compared to phytotherapeutic medications [1,2,11,22].
It is important to reiterate that herbal medicines, despite their widely perceived safety, they were historically shown to have potent pharmacological actions that thus calls for questioning the perceived safety in comparison to their conventional counterparts [8]. In view of the aforementioned information this study surveyed herbal medicinal products recommended by community pharmacists in Northern Cyprus and compared the results obtained to that of data obtained in the literatures reviewed worldwide.

RESULTS
The results from the literature searched and reviewed showed that there about six hundred and fifty, 650 medicinal plants used in pregnancy, fifty eight (58) of which are grown or cultivated in Cyprus and seventeen (17) were found to imported species but some species of same genus were recorded in Cyprus complied from the literature reviewed and obtained using the Near East Grand Library Electronic Resources of the Near East library scholarly accessible databases 650 (Table 2, Fig. 1). Note

Plants used in Pregnancy and their Comparative Availability in Northern Cyprus
Within the limit of this study there were no studies conducted previously on medicinal plants used in pregnancy in Cyprus. We believe that this may be a good starting point for future researchers including the clinical trials for Cyprus. Table 3 showed the list of medicinal plants that were used in treating pregnancy condition and indicated whether those medicinal plants are available in Cyprus or not. As indicated in the aforementioned table, 56 medicinal plant species naturally growing or traditional cultivated in the Cyprus. Eighteen of these species of these species were found not be naturally growing in the country but were imported ones or have another species of the same genus growing in the country.

Recommended Forms of HMPs in the North Cyprus Community Pharmacies
The result from the questionnaire survey showed that 116 community pharmacist responded to questionnaires distributed to the 263 community pharmacies across the four districts covered in this study these includes the North Lefkoşa (Nicosia), Girne (Kyrenia), Güzelyurt (Morphou) and Mağusa (Famagusta). One hundred and sixteen (116) community pharmacists participated in the survey, one hundred and one (101) of answered to have HMPs in their respective pharmacies. Eleven (11) of them were found not dispensing any herbal medicinal products. Four (4) also answered not having any HMPs but stated to have almond oil their pharmacies. The years of the participants in community pharmacy ranged from two (2) years (these were mostly new graduates) to thirty seven years (37). Note that some of the medicines recorded were conventional medicines as stated to be recommended to pregnant women Turkish Cyprus pharmacies.
Most herbal medicinal products recommended were in the form of lozenges which were 76 in number, 60 different types of herbal teas, 57 oils from different herbal medicinal materials, 36 were capsulated HMPs while other forms recorded were 20 in number which includes 9 hair coloring kits, 1 soap, 4 deodorants, 2 shampoos, 2 cosmetics and 2 perfumes as shown in Fig. 2   herbal oils from eucalyptus were recorded are illustrated in Fig. 3.

Tablets
Recommended tablet forms were of the brands Pregnacare ® , Hair complex, the one from Soja hispida, Folic acid, Natracalm ® and Panadol ® constitution n=23, n=14, n=1, n=1, n=1, n=2 and n=14 ; though a conventional medicine, was stated to be recommended to pregnant women in Cypriot pharmacies, this is shown in Fig. 6.

Spray
Recommended herbal medicinal throat sprays were those containing propolis and the ones from Immumax ® and Vicks ® one (n=1) product of each as shown in Fig. 9.

DISCUSSION
There is no doubt that there is increase in the use of herbal medicinal products and the complementary and alternative medicine (CAM) in pregnancy worldwide mostly because they are considered more natural and safe. In fact some pregnant women go for safe medication using the HMPs without the consent of their healthcare professional indicating the need for educating them as well as the healthcare professionals on the pros and cons of using HMPs. The importance safe use of any medication at pregnancy cannot be over emphasized thus HMP use should be strictly on basis of scientifically and clinically proven safety and efficacy through recommendation of healthcare

CONCLUSION
Despite the wide use of herbal medicinal products use in general and in pregnancy in particular there is need for increase in awareness on their safe use. Pregnant women here in Cyprus were shown to take herbal medicines only on recommendation from their healthcare professionals. However this needs to be studied in-depth to include traditional herbal use in pregnancy and their effects to the health of the consumer. For example the use of linden elder flower tea traditionally is common among the Cypriots to treat upper respiratory tract infections need to be ascertained through evidence based research.
This study also showed that the HMPs in Turkish Cypriot community pharmacies are small in number and their recommendations to pregnant women are on the basis of doctor's prescription. The HMPs recommended to most of the pregnant women were in the form of lozenges and of the brand Otacı ® and oils for stretch mark together with almond oil making up 33% respectively. And the mostly recommended herbal teas were namely antiflatulence and nursing teas.
Professional recommendation for evidencebased scientifically researched HMPs is always sought for when taking medications especially herbal medicines use in pregnancy and it is important that all the stakeholders are aware of such HMPs as well. Turkish community pharmacists' reluctances in not recommending HMPs to pregnant women without doctor's prescription is commendable. On the other hand Turkish traditional herbal medicine sellers (locally known as 'aktar') are always eager to recommend herbal medicines to the general public including pregnant women this pose a threat to public health thus needing serious regulatory action by the governments.

LIMITATIONS
This study is limited to the availability and accessibility of literatures. Although the search of the literatures covered worldwide, questionnaire administration is restricted to only registered Turkish Cypriot pharmacists.

CONSENT
As per international standard or university standard, respondents' written consent has been collected and preserved by the author(s).

ETHICAL APPROVAL
It is not applicable.

DECLARATION
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Near Eat University, Nicosia. All co-authors have reviewed and approved of the manuscript prior to submission

FUNDING STATEMENT
All authors were employed by the Near East University except Eda Tülek who was master student in Phytotherapy Program. No additional funding was provided specifically for this study.