The Use of Herbal Products during Breastfeeding: A Study from a Public Italian Hospital

Results: Two hundred forty-four breastfeeding women completed the questionnaire. The majority of them were non-smokers and non-drinkers, whereas they were regular consumers of herbal products during breastfeeding (97%). Medicinal plants most commonly used were sweet almond oil (68%) and fennel (37%). Herbal products were often associated with other prescription drugs (89%). Five percent of women have experienced dermatological and gastrointestinal adverse reactions, potentially due to herbal products.


Introduction
Natural products, particularly plant-derived ones, are generally used to improve the sense of well-being as well as to treat minor illnesses, and their use is steadily increasing worldwide [1,2]. In particular, women of 25-34 years of age seem to be the major users of plant-derived products, also and especially during pregnancy and breastfeeding [3,4], because these products are perceived as risk-free and helpful for various physiopathological conditions [1]. Even if in the recent years the scientific interest for herbal products during pregnancy is increasing all over the world, the information available on their use by breastfeeding women is still lacking and almost missing. This lack of scientific data goes along with a lack of knowledge of pharmacokinetic data on most plant-derived products, so that the amount of them that diffuses into mother's milk is unforeseeable. In this perspective, various parameters (absorption, distribution, metabolism and excretion) should be cautiously evaluated. For example, the metabolic and excretory capacities of the babies increase in a directly manner with their age [5], whereas the absorption and distribution of a xenobiotic into the breast milk depends on its chemical and physical characteristics (acid or basic nature, lipophilicity, etc.), and on many other factors (e.g., milk composition, proteins binding) [5,6]. Therefore, the exposure to herbal products should be probably avoided, in absence of correct information. Hence, the aim of the present study is to evaluate the prevalence of use and the knowledge of the safety and efficacy of herbal products by breastfeeding women.
A structured questionnaire, that included descriptive (age, country of birth, level of study, work experience, etc.) and analytical (e.g., product used and reason of use, participant's knowledge and primary source of information on herbal products, use of other therapies, perspective of safety and efficacy) questions on herbal products, was utilized. The survey was planned and validated according to other language questionnaire [8,9]. The validation procedure was carried out by a panel of experts as reported by Lapi et al. [9]. The survey was administered in Italian language; a detailed sample of its translation is reported in Table 1.
What we intended for "herbal products", as previously stated, was explained to the interviewees before the administration of the questionnaire. All data were anonymously collected in a specific database, using Office Excel software. Skilled health personnel carried out each interview.
Statistical analysis included simple descriptive statistics such as mean and standard error for normally distributed data, and medians and ranges for non-normally distributed data.
Among women surveyed, 79.8% (n=190) had taken herbal products during their life and 97.3% (n=214) started to take these products also during pregnancy and breastfeeding. Only 20.2% (n=48) of women have never used herbal products in their life, and they did not use natural products neither during pregnancy, nor during breastfeeding (2.7%, n=6).
The products most commonly used, their frequency of consumption and the duration of treatment are reported in Table 3. Breastfeeding women that used only multivitamin supplements were 1.4% (n=3).
Ninety-six percent (n=235) of nursing women responded to the next part of the questionnaire, among them was also included one puerpera who could not breastfeed, but was taking various plantderived products (i.e., fennel and sweet almond oil).
The opinion of breastfeeding women on the safety and efficacy of herbal remedies versus pharmaceutical products is reported in Figures  1A and 1B, respectively.

Discussion
To the best of our knowledge and according to a search on PubMed website-terms that were searched on January 2014, without any Cosmetics 3.
Other food supplements (e.g. vitamins, minerals) If possible, please, specify the name of the product/s that has been used? Both ___________________________________________ What is/was the frequency and the duration of your herbal treatment/s? Please, specify: _____________________________________________ Table 1: Sample of questionnaire, administered to breastfeeding women by health professionals limit of language, were the following: "botanicals and breastfeeding" "herbal products and breastfeeding"-this is one of the few studies that examined personal use, knowledge of safety and efficacy of herbal products among breastfeeding women.
Limitation of the study is that this a mono-centric study that involved breastfeeding women from one geographic location (Rome, Italy), however data were obtained from the Umberto I-Policlinico of Rome, which is the biggest public hospital in Italy, and even one of the largest in Europe [13].
The analyzed population, despite their medium sociocultural level, appeared to be conscious to use drugs only when necessary and aware of the importance of a proper diet, during breastfeeding. This fact is important, because of the recent evidence indicating that breastfed infants, as exposed to a variety of flavors by mother's milk, have a greater acceptability of new food during their weaning period, and are less inclined to develop chronic diseases [14]. Of note is that nursing women were regular users of a variety of plant-derived products; even those who had never used herbal products during their life, began to take them (almost every day) during pregnancy and continued throughout breastfeeding. Moreover, breastfeeding women often associated herbal remedies between them, and/or with drugs. This should be avoided, considering the possibility of pharmacological interactions between different therapies that makes the final effect of the association totally unforeseeable [15,16].
Breastfeeding women considered plant-derived supplements as useful, without taking into account the possibility of adverse outcome for them and/or their baby, and considered herbal products as less dangerous than drugs, so having a poor knowledge of the risk/ benefit profile of botanicals. These beliefs have also been reported in other studies carried out in pregnant and breastfeeding women [3,17,18]. Paradoxically, interviewed women used herbal products, even if considered them less efficacious than pharmaceutical products. Compared to what happens in other countries, where family and friends are the most cited source of information about botanicals [19], in our study, participant's primary source of advice was gynecologists. However, while herbalists and pharmacists receive academic training courses on botanicals, other health practitioners (including    gynecologists) usually do not receive any professional education on herbal remedies, at least in Italy. The comforting aspect, despite the e-trade of botanicals is widespread, is that the nursing Italian women appeared to prefer pharmacies, as their favorite source of purchasing.
In our study, most of women reported no side effects, with the exception of dermatological and gastrointestinal reactions associated with cosmetics and herbal supplements. The first category is considered as safe, even if few adverse reactions due to their herbal composition are reported [3,15,20]. Some concerns raised from the daily application of almond oil to the abdomen of pregnant women, because it was associated with preterm birth [3]. The authors have hypothesized that the association between almond oil and shortening of gestation could be due to a premature contractions by a chronic mechanical stimulation of myometrium and/or to an uterotonic effect of some almond oil compounds (e.g., fatty acids), which could target the myometrium [3]. This event, although unusual and not related with lactation, should be kept in mind because if almond oil can reach the myometrium, may also be delivered to the infant through breast milk.
The use of other herbal-based cosmetics has been reported, including those containing calendula and aloe. Even if both plants appear as safe in the common practice, eczema and ocular irritations are reported [15,21], as well as contact dermatitis and oral mucositis after the topical application of aloe [22]. Consequently, they should be contraindicated in hypersensitive patients [16].
Regarding herbal supplements, safety data were not discussed in the clinical studies identified for lactation [23]. However, several reactions have been recently reported, making some medicinal plants unsuitable for their use during lactation and other specific conditions [19,23,24]. In our survey, breastfeeding women reported the use of milk thistle and fenugreek (usually in association), as galactogogues, although their effects and the dose necessary to obtain an increase of breast milk production should be further evaluated [23,25]. Both herbs have been suspected to increase the risk of bleeding, and it is suggested that they should be discontinued at least two weeks before any surgical procedure [26]. Then, their use shortly before the childbirth is not safe. In addition, fenugreek could induce hypoglycemia and gastrointestinal upsets and should be used cautiously in patients taking medications that may interfere at the same pharmacological levels [21,27].
In our study, additional concerns arise from other medicinal plants used by nursing women (e.g. fennel, licorice, aloe). Foeniculum vulgare and Glycirrizza glabra have been used as herbal dietary supplements, whereas Aloe vera has been taken as non-prescription medicine. For these plant-derived products, several adverse reactions have been reported. In particular, fennel may cause contact dermatitis, and an increase of estrogen levels [16]. Its long term use has been associated with the onset of premature thelarche in one female infant and three female children, where an increase of 15-20 fold of serum estradiol levels, and a case of vaginal discharge were found [28]. This estrogenic effect (ascribed to the anethole content) could also induce a suppression of lactation in breastfeeding mothers [28]. Noteworthy is that, in our survey, one of the fennel consumers could not breastfeed; however a definitive conclusion cannot be drawn from this case. As regards licorice, some evidences suggest that its regular intake is associated with adverse manifestation, including cardiovascular reactions [20], abortion and preterm labour [3]. In some cases, however, other drugs (e.g., antinflammatory, antihypertensives) taken in association with licorice could be involved in the adverse outcome [20]. Moreover, of concern are association of licorice and fennel with other medicinal plants, that have been reported to induce lethargy, hypotonia, and emesis in two neonates of breastfeeding women consuming a large volumes of this herbal tea mixture [29]. With regard to the use of aloe as a laxative medicine, it should be kept in mind that its use is not recommended in children under 12 years of age and, according to European Medicine Agency, during breastfeeding, "as there are insufficient data on the excretion of metabolites in breast milk", but it is hypotized that some its metabolites pass in small amounts [30]. Finally, the constipation reported in an infant of 10 weeks, whose mother had been taking a mixture of medicinal plants is not scientifically explainable, because of the complexity of the product [20]. Moreover, as it is unknown if plant ingredients are excreted in human breast milk, their use during lactation is not recommended [31][32][33]. Noteworthy is that for all of the mentioned products in our study, no information is available on their quality and this it should be taken in mind before drawing definitive conclusions on the safety of "natural" products.
In this study, taking into consideration the widespread use of botanical agents, in relation to the relatively small number of adverse reactions due to them, it seems that the incidence of adverse effects is low. However, it is clear that the implementation of the Phytovigilance system can further improve our knowledge on the safety of botanicals. In accordance to the Motherisk Program, to achieve a conclusion on this topic there is a need for future research [34]. Till then, these products should be probably contraindicated because, even if we do not know if they are dangerous, we are not sure of their safety [35].

Conclusions
This study highlights the need to provide comprehensive information on the use of plant-derived products to nursing women. In order to give them a qualified advice, the health care staff (e.g., general practitioners, gynecologists, pharmacists, nurses, pediatricians, and herbalists) should know how to access unbiased and reliable information sources, and should always update their knowledge on herbal products. This study could be of a wide audience interest and could contribute to the international knowledge, as the existing international research base on plant-derived products used during breastfeeding is still lacking.