This is a brief narrative review that focuses on the use of CAM in pediatric patients with oncological, neurological, and liver conditions. Article selection was performed using established methods as described elsewhere [8]. In this article the authors summarize key information on the use of CAM in pediatrics obtained from scientific articles published during the past 20 years, including original studies, systematic review and meta-analysis. Articles search was performed using top academic search engines [8], including the classic academic databases Web of Science, Science.gov, Core, Scopus and PubMed, the search engine of the United States National Library of Medicine. Inclusion criteria involved all peer-reviewed articles published in English language, limited to child studies and published since 2003 (20 years). There was no geographical limitation for the articles considered for the review.

Overview on complementary and alternative medicineTherapeutic use of CAM

Many CAM practices have already been used for years, and their beneficial effects on the mind and body have been known since ancient times. In recent years, evidence has increased that these practices can play an important role in the treatment of some specific diseases, including cancer, neurological and liver diseases [1, 9].

One element shared by most complementary therapies is the multifactorial, multilevel view of human disease. According to complementary disciplines, the disease is no longer seen as a single pathological process but as a collection of physical, mental, social, and spiritual disorders. They also emphasize the human body's ability to recover faster in comfortable situations and under appropriate conditions.

Based on this holistic approach, complementary therapies aim to heal individuals by restoring their physical and inner balance. The goal is to stimulate and facilitate the body's positive responses in association with, not as an alternative to, "conventional" therapies, rather than targeting individual disease processes and troublesome symptoms [6].

Efficacy of CAM

Numerous controlled clinical trials have demonstrated the usefulness of complementary therapies in treating various diseases with significant public health impact. The importance of CAM is further emphasized by the U.S. National Institutes of Health (NIH), which established the Office of Alternative Medicine, later named the National Center for Complementary and Integrative Health (NCCIH), to study the efficacy and safety of alternative therapies [7].

A wealth of information on the effectiveness of complementary and alternative medicine is available in the literature, including peer-reviewed publications, evidence-based reviews, expert group papers, and authoritative textbooks. However, no consensus has been reached on its effectiveness. Many CAM procedures have been studied and found to be effective in combination with conventional treatments, while other studies have found CAM to be ineffective or have reported contradictory and inconsistent results [9].

Standardization of data in CAM studies is difficult, which may explain the difficulty in reaching a consensus on their use in combination with the treatment of many conditions. In fact, complementary therapies cannot be standardized for individual conditions because, in most cases, their use is based on the patient's characteristics or experiences rather than on a clinically diagnosed disease in the traditional way. Outcomes are also difficult to standardize because they are often specific to individuals rather than based on objective, uniform measures such as blood pressure, blood glucose and inflammation indices. In addition, many studies lack a placebo control, which precludes any reliable conclusions. However, despite the lack of consensus on the efficacy of CAM, many studies have provided substantial data in favor of their use as integrated treatments in various serious disease conditions [9, 10].

Safety of CAM

Unlike conventional medical treatments, which are thoroughly tested and regulated, most complementary therapies have not yet been sufficiently tested for their safety. Some studies have examined suspected CAM-related adverse reactions in the pediatric population and have warned of the risks and dangers of CAM in children, especially in "fragile" patients, such as those with cancer or neurology and liver diseases [11]. Studies have also provided insights into factors that might increase the risk of serious adverse reactions associated with the use of CAM in children. Indeed, their common description as natural remedies may suggest the assumption of safety, whereas the potential effects of CAM may instead represent an increased iatrogenic risk. In particular, the use of products containing more than two components and administered concurrently with conventional medications may pose a potential risk in younger patients [11], because responses to standard treatments in this population are often unpredictable and individual-based, and complementary treatments are usually not standardized [5, 7]. Adverse effects have also been reported in the use of herbal dietary supplements (HDS), as they can affect different physiological systems [12]. Studies on the adverse effects of CAM are significantly advancing knowledge in this area. However, health care providers should familiarize themselves with CAM practices and carefully balance the associated benefits and risks to best care for their patients.

Use of complementary therapies in oncological diseases

Complementary therapies are used effectively in children with slow-moving forms of cancer to help cure or alleviate symptoms. Preferably, integrative pediatric oncology should be provided in pediatric hospitals or medical centers that participate in clinical trials or belong to pediatric oncology networks [13]. Complementary therapies, which in general are usually used in cancer patients, are summarized in Table 2.

Table 2 Complementary therapies frequently used in cancer patients

The inclusion under the term CAM of several and various types of complementary practicesused for pediatric cancer patients may explain the wide range of prevalence, depending on the country (6%-91%), reported in a recent systematic review [13]. In particular, large differences have been reported between North America and Europe, which may also have been influenced by the time period over the past 30 years when CAM alone or CAM has been introduced in different countries, either in support of or as an alternative to cancer therapy [14, 15].

The increased use of CAM to relieve symptoms in oncology patients

Parents of pediatric oncology patients are inclined to introduce unconventional treatments to reduce harming symptoms and alleviate complications of therapy[14]. The most common symptoms during cancer therapy are nausea and vomiting, whose multifactorial origin is typically related to chemotherapy [14, 16]. According to a 2022 review, CAM practices have helped to alleviate nausea, vomiting, mucositis, weight loss, anxiety, pain, and, most importantly, to improve children's quality of life [13].

The routine use of CAM, in addition to standard cancer therapies, has significantly increased during the past recent years by families and caregivers of cancer patients. Currently, these therapies are often an integral part of supportive care, especially used to control the side effects of cancer therapies. However, the use of CAM in cancer therapy is still debated, and there is no final consensus regarding its effectiveness and safety [17].

Different types of complementary therapies are used during cancer treatment. The National Center for Complementary and Alternative Medicine (NCCAM), popular categories of CAM are natural products, including plants/herbs, a practice also known as "herbalism," vitamins and other dietary supplements, mind–body practices (prayer, meditation, yoga, acupuncture, guided imagery, hypnotherapy, tai chi) manipulative practices (e.g., massage, chiropractic), new "biological field therapies" (e.g., Reiki, healing touch, qi gong), traditional healers, and other medical practices such as Ayurvedic medicine or traditional Chinese medicine, when used as a support to conventional medicine [18]. Homeopathy, dietary treatments and nutritional supplements seem very popular in Germany [7], while herbal extracts are mostly used in Mexico and water therapy and Spirulina in Malaysia[17]. Although often used during cancer treatments, chiropractic care needs further studies to demonstrate its effectiveness in pediatric oncology[19]. A recent review reports that several studies first observed the effects of CAM modalities on symptoms related to cancer therapy, and that hypnosis, imagery/visualization and music therapy were found to be most useful in relieving procedure-related pain [19].

This section briefly discusses some of the most commonly used CAM procedures in pediatric oncology.

Massage

One of the most used CAM interventions for children with cancer is massage. An extensive review of massage practice in pediatric patients, which reports 24 randomized controlled trials between 1992 and 2006, found that massage was strongly effective on anxiety in children, especially after multiple sessions of this intervention [20]. In addition, evidence has been reported of other side symptoms relieved by massage, including nausea, pain, depression, stress, anger, and fatigue [21,22,23]. A study on a limited cohort of pediatric oncology patients of different ages and mixed diagnosesreported positive results in reducing heart rate and anxiety and very positive evaluations of the massage experience by the participants [24].

Studies on massage in children undergoing bone marrow transplantation (BMT) are scarce. In one study, fifty young cancer patients undergoing BMT received professional massage, parental massage, or constituted the control group. There was a significant difference in incision days after BMT in the combined group that received massage (parental and professional). A significant reduction in anxiety and immediate discomfort was seen in the group that received professional massage [21]. Another follow-up study conducted by the same team found no differences in depression, quality of life, or posttraumatic stress between a child intervention group (humor and massage), a parent intervention group (massage and relaxation), and a control group receiving only standard care, although an improvement and adjustment of symptoms were observed in all groups [25]. In a smaller pilot study, the combination of tri-weekly massage and acupressure versus standard care demonstrated benefits in terms of nausea, fatigue, pain, and reduction of mucositis and benefits were reported by caregivers using this practice [24].

Yoga

There is evidence that yoga improves physical strength and flexibility as well as mental health through toning, stretching, and relaxation exercises. It has also been shown to beneficially influence the autonomic nervous system [26] by decreasing salivary cortisol levels, plasma renin levels, and urinary norepinephrine and epinephrine levels, as well as reducing blood pressure and heart rate [27]. In two studies yoga has been shown to be safe and feasible in pediatric cancer patients undergoing chemotherapy [28, 29]. However, further research is needed to demonstrate its efficacy in effectively controlling the symptom.

A recent study reports that a significant improvement in pain was achieved in patients using yoga regardless of their age. In addition, this study also reports the benefits of yoga in parents caring for their children. It was shown that one yoga experience was important enough for parents to control emotions and contain anxiety. In summary, this study emphasized that it was feasible for children and adolescents with hematologic or oncologic disease and their parents to participate in the yoga intervention [30]. Similarly, a different study suggested that patients' guardians experienced a significant decrease in anxiety after using relaxation practices [31]. Finally, yoga has been shown to be significantly effective in reducing fatigue symptoms in pediatric brain tumor patients and in improving their sleep.

Acupuncture and acupressure

Acupuncture includes a group of techniques in which small needles, heat or electrical stimulation are placed at specific anatomical points. Acupuncture points are located on meridians along which qi (a "life energy") flows, while acupressure uses pressure applied with hands or other devices on the same acupuncture points [32]. Children have been shown to tolerate acupuncture well [33] and to have no bleeding problems. In addition, acupuncture has been reported to be effective in reducing chemotherapy-induced nausea and vomiting during or at the end of chemotherapy treatment [34]. In a meta-analysis that evaluated the effects of acupuncture on postoperative nausea and vomiting, acupuncture was shown to reduce vomiting and nausea [34].

Acupressure is similar to acupuncture but uses pressure instead of needles. This practice can be helpful for children who suffer from agophobia or when an acupuncture expert is not accessible. The most popular type of acupressure is the use of wrist bands that apply pressure to the ventral surface of the wrist. A cross-over pilot study of pediatric cancer patients showed that acupressure is risk-free, feasible and well-accepted [32].

Mind–body therapies

Many mind–body therapies, such as cognitive distraction, meditation, imagination, creative arts therapy, and hypnosis, are reported to be useful for treating procedure-related anxiety, pain, and distress in pediatric cancer patients. In a small retrospective study, meditation was found to significantly reduce the use of analgesic therapies in children with neuroblastoma on monoclonal antibody therapy [35]. In particular, non-pharmacologic interventions for procedure-associated pain, such as hypnosis, seem beneficial in cancer therapy [36]. A study showed this practice to be particularly useful for pediatric patients (age range 7–14 years) who seem to be more sensitive to hypnosis when used in conjunction with pharmacological therapies [37]. Hypnotherapy refers to many different practices, including relaxation, imagination, and aromatherapy, which are the most used in pediatric cancer patients. Hypnotherapy is the most used mind–body therapy to control nausea and vomiting, the main symptoms associated with sympathetic stimulation, in children with cancer. Through a state of deep relaxation, hypnotherapy helps people easily overcome automatic thoughts such as anticipated nausea and vomiting derived from cancer treatment [37]. A review of all CAM studies for procedure-related distress in pediatric oncology showed that hypnosis is also effective in painful procedures (e.g., lumbar puncture, bone marrow) and for reducing anticipatory anxiety [35].

Energy therapies

Reiki, therapeutic touch, and healing touch are part of energy therapies. They have not been extensively studied in adults with cancer. Energy healing therapists, also known as biofield therapy practitioners, channel healing energy through the hands into the patient's body to rehabilitate normal energy balance and health. In a review of biofield therapies, it was reported that adults with cancer showed commonly positive effects on reducing pain and psychological distress characterized by anxiety, depression and stress, and improved quality of life [19]. Data on pediatric cancer patients are limited. A small study of healing touch versus a "read/play" control showed a reduction in pain, stress, and fatigue for patients, parents, and caregivers [36]. Energy therapies are well accepted by children and adult cancer patients, as they show no adverse effects. However, conclusive data in favor of their use are lacking [19].

Selected herbs and biological therapies

Many cancer patients use many herbs and biological therapies [38]. Traditional Chinese Medicine (TCM) is a health management that includes herbal medicines and various mind and body practices to prevent and treat diseases. Usually, TCM practitioners integrate many herbal medicines, and each herbal therapy is planned for each patient. The use of Chinese herbs in the adult and pediatric oncology population is controversial because several reports indicate contamination of the herbs used in therapy with drugs, toxins, or heavy metals. Therefore, their use is currently under monitoring and their content is under evaluation to acquire conclusive data about their safety [37].

Probiotics are biological CAM frequently used in children and adolescents [39]. Probiotics could have a positive effect on allogeneic stem cell transplantation (SCT). Experimentally, significant survival and reduction of acute graft-versus-host disease (aGVHD) before and after transplantation was reported using L. rhamnosus GG in a mouse model of aGVHD [38]. In a small study of chemotherapy-treated children, the use of Bifidobacterium breve strain Yakult reduced fever episodes and improved the presence of anaerobes in the gut microbiota [39]. Glutamine is an essential amino acid that has been used for the prevention of peripheral neuropathy and mucositis. Although the ideal dose and route of administration have not yet been defined, it represents a future option in CAM therapy for adult and pediatric cancer patients. In children undergoing stem cell transplantation, glutamine has helped reduce the duration of fever, and the use of total parental nutrition (TPN) and narcotics has been related to the standard of care protocol [40].

Use of CAM to relieve pain and anxiety

Pain is a common symptom frequently related to cancer diagnosis procedures and treatment, and it can also result from disease progression, due to obstruction of nerves, tissues, or organs by tumors at any stage of the cancer process [41]. Many studies emphasize the importance of complementary modalities in helping children undergoing cancer treatment in general and especially in painful procedures, including lumbar puncture, bone marrow aspiration, access to implanted ports, and venipuncture [42, 43].

In several studies investigating various painful procedures, mind–body techniques and hypnosis have shown positive results in reducing pain and anxiety. These two noninvasive techniques are reported to help mitigate or control the effects of painful procedures in children during cancer treatment [43, 44].

The importance of communication in the use of CAM

The most important motivations for the use of CAM have been the goal to improve the patient's overall condition, strengthen the immune system, and reduce the adverse effects of conventional therapy. Parents often do not choose CAM because they lack information about it, are convinced that it is ineffective, and want their children to be stress-free [14].

A recent study emphasizes a lack of communication between pediatric oncologists and their patients [9]. According to this report, 7% of pediatric oncologists never ask their patients an open question about CAM use, while 43% sometimes ask their patients a general question about their use. Pediatric oncologists' questions to their patients about specific CAM therapies depend greatly on the type of therapy. For example, more than one-third of pediatric oncologists routinely ask their patients about the use of dietary supplements, phytotherapy, special diets and vitamins. However, the use of aromatherapy, enzymes, acupuncture, homeopathy, magnets, prayer, chiropractic, guided imagery, martial arts, meditation and yoga is never asked to pediatric patients by their oncology team. The use of vitamins, special diets, nutritional supplements, herbal medicine, and antioxidants is often requested by cancer patients from their physicians. However, they are often discouraged. The reasons why pediatric oncologists do not ask their patients about CAM therapies are lack of time in 49% of cases and lack of knowledge in 47% of cases [9].

In conclusion, the main reasons for cancer patients to use CAM are improvements in physical and psychosocial well-being and increasing hope[45], but also despair, disappointment with some features of standard healthcare, lack of physician–patient relationship, availability, and perceived efficiency [46].

Complementary therapies in neurological diseases

Use of CAM in neurological diseases has increased in recent years, mainly because they are usually chronic conditions and often associated with various comorbidities. A survey reported that children affected by neurological diseases used CAM more frequently than healthy children (24% vs. 12.6%, respectively) [47].

In Canada, 44% to 76% of children with common neurological conditions reported the use of integrative medicines [48, 49].

CAM therapies mainly used in neurological diseases range from nutritional supplements such as herbs and vitamins to massage and osteopathic manipulation, acupuncture, mind–body therapies and relaxation techniques (Table 3) [47].

Table 3 CAM therapies mainly used in neurological diseases

Here in, we analyzed the most common neurological diseases where CAM is used (Fig. 1).

Fig. 1

Summary of neurological diseases where CAM therapies are more commonly used

Cerebral palsy

Cerebral palsy (CP) is a group of disorders characterized by a spectrum of motor and posture impairment caused by non-progressive damage that may happen during prenatal, perinatal, or postnatal stages of the development of the nervous system [50].

The prevalence of CP is estimated to range between 2 and 3 per 1000 live births, representing the leading cause of pediatric disability [51].

Children affected by CP present various neuromotor limitations in their physical activities, leading to a psychological, social and functional impairment [50].

Although neurological injury may happen during each stage of neurological development, perinatal injury accounts for about 90% of all cases and it must be kept in mind in order to prevent and early recognize CP. The principal manifestations of CP are posture, reflexes and muscular impairment, usually associated with sensory problems, coordination imbalance and learning, speech, and cognitive disabilities [52]. Moreover, CP is frequently associated with other neurodevelopmental disorders, particularly attention-deficit hyperactivity disorder (ADHD) represents the most frequently associated comorbidity [53].

Signs and symptoms of CP may be various and range from mild to severe clinical presentations and they may be evaluated according to Gross Motor Function Classification System (GMFCS) [54].

Until now, there is no curative therapy for CP, and the available treatments depend on the specificity of the symptoms. Usually, a multidisciplinary approach is fundamental to reduce the symptoms and improve the quality of life [55].

Many types of therapies are used. The most used conventional treatments include occupational therapies to improve movement and balance impairment, selective dorsal rhizotomy, systemic muscle relaxants, intramuscular on botulinum toxin A to reduce spasticity, and pharmacological therapies to improve neuropsychiatric comorbidities [