Protocol and registration
The protocol for this systematic review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) CRD42020221570.
Research Question Development
This research protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P 2015). The PICO strategy (P- population; I- intervention; C- comparison; O- outcomes) guided the research question (26) (Table 1).
Table 1
Research question development
PICO
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COMPONENTS
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Research question
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Are integrative and complementary practices effective in managing nausea and vomiting in pregnant women compared to placebo, routine treatment, or pharmacological interventions?
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Population
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Pregnant women with symptoms of nausea and vomiting.
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Intervention
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Integrative and complementary practices.*
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Comparison
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Placebo, routine treatment, and pharmacological interventions.
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Outcomes
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Management of nausea and vomiting, and adverse effects from the treatment.
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*Specified under the topic: Intervention Types and Comparison |
Eligibility Criteria
Types of Research
Only randomized clinical trials on the use of complementary therapies to manage nausea and vomiting in pregnant women will be included.
Types of Participants
Healthy pregnant women of any gestational age (GA), who are experiencing nausea and vomiting. Parturient and puerperal women will be excluded. Papers involving symptoms characterized as hyperemesis gravidarum will not be included, since these diverge from the population of interest in this study, which represents 1% of pregnant women who have developed the pathological form of gestational nausea and vomiting (6). There will be no age or ethnicity limitations.
Types of Intervention and Comparison
Studies that aimed to manage nausea and vomiting in pregnant women by employing aromatherapy (19), hypnotherapy (20), homeopathy (21), acupuncture (22), auricular acupuncture (23), music therapy (24), phytotherapy (21), and yoga (25) will be analyzed. The use of these ICPs is justified due to their frequent use in the obstetric setting, in addition to the previous concept of their efficacy with pregnant women from current systematic reviews, even if for other study purposes. The intervention may have been used alone or as an adjuvant to other methods.
Management interventions may include: (a) any placebo method (specific to each ICP); (b) vitamin B6 alone or in combination with doxylamine, which is considered the gold standard in managing nausea and vomiting in gestation (27); (c) other pharmacological interventions; (d) other non-pharmacological interventions.
Types of Results
The primary results to be evaluated will be nausea and vomiting in pregnant women at any gestational age. The secondary results to be evaluated will be possible adverse events arising from the use of these complementary therapies to manage nausea and vomiting in pregnant women.
It should be noted that there is currently no set COS for clinical trials in which the effects of interventions to manage nausea and vomiting in pregnant women are studied, therefore, all the instruments proposed by the included studies will be evaluated.
Information Sources
The search for studies will be carried out in the following databases: Medical Literature Analysis and Retrieval System Online (Medline) via PubMed, EMBASE (via Embase.com), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the World Health Organization's International Clinical Trials Registry Platform (ICTRP), Literatura Latino-Americana em Ciências da Saúde (LILACS), Cuban National Center for Information on Medical Sciences (CUMED), Índice Bibliográfico Español en Ciencias de la Salud (IBECS), China National Knowledge Infrastructure (CNKI).
There will be no restrictions on the publication year or language of the manuscripts. For each article selected, abstracts and full articles will be obtained. Aiming to increase the literature coverage, reference lists of included studies and systematic reviews identified during the screening process will also be examined. In addition, papers from the gray literature will be captured and ongoing studies will be identified through the World Health Organization's International Clinical Trials Registry Platform, and the Brazilian Registry of Clinical Trials (ReBEC).
Search Strategy
Table 2 - Descriptors for the search strategy
A. Search strategy to search for "Integrative and Complementary Therapies":
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1. Terapias complementares
2. Medicina Complementar
3. Medicina Integrativa e Complementar
4. Práticas Integrativas e Complementares
5. Aromaterapia
6. Hipnoterapia
7. Homeopatia
8. Acupuntura
9. Acupuntura Auricular
10. Musicoterapia
11. Fitoterapia
12. Ioga
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1. Complementary Therapies
2. Alternative Therapies
3. Complementary Medicine
4. Medicine, Alternative
5. Aromatherapy
6. Hypnosis
7. Homeopathy
8. Acupuncture
9. Acupuncture, Ear
10. Music Therapy
11. Phytotherapy
12. Medicine, Herbal
13. Yoga
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B. Search strategy to search for "Nausea and Vomiting":
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1. Náusea
2. Ânsia de Vômito
3. Enjoo
4. Náuseas
5. Vômito
6. Êmese
7. Êmese Gravídica
8. Enjoo do Começo da Gravidez
9. Náuseas e Vômitos Matinais da Gravidez
10. Náuseas e Vômitos da Gravidez
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1. Nausea
2. Vomiting
3. Emesis
4. Morning Sickness
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C. Search strategy to search for "Pregnant":
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1. Gravidez
2. Gestação
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1. Pregnancy
2. Gestation
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Chart 1 - Search strategies
Database
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Descriptor system
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Search Strategy
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LILACS CUMED
IBECS
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DeCS
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(Terapias Complementares) OR (Medicina Complementar) OR (Medicina Integrativa e Complementar) OR (Práticas Integrativas e Complementares) AND (Náusea) OR (Ânsia de Vômito) OR (Enjoo) OR (Náuseas) AND (Gravidez) OR (Gestação)
(Terapias Complementares) OR (Medicina Complementar) OR (Medicina Integrativa e Complementar) OR (Práticas Integrativas e Complementares) AND (Vômito) OR (Êmese) AND (Gravidez) OR (Gestação)
(Terapias Complementares) OR (Medicina Complementar) OR (Medicina Integrativa e Complementar) OR (Práticas Integrativas e Complementares) AND (Êmese Gravídica) OR (Enjoo do Começo da Gravidez) OR (Náuseas e Vômitos Matinais da Gravidez) OR (Náuseas e Vômitos da Gravidez)
(Terapias Complementares) OR (Medicina Complementar) OR (Medicina Integrativa e Complementar) OR (Práticas Integrativas e Complementares) AND (Aromaterapia) OR (Hipnose) OR (Homeopatia) OR (Acupuntura) OR (Acupuntura Auricular) OR (Musicoterapia) OR (Fitoterapia) OR (Ioga) AND (Gravidez) OR (Gestação)
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Medline
Web of Science Scopus
ICTRP CENTRAL CNKI
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MeSH
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(Complementary Therapies) OR (Alternative Therapies) OR (Complementary Medicine) OR (Medicine, Alternative) AND (Nausea) AND (Pregnancy) OR (Gestation)
(Complementary Therapies) OR (Alternative Therapies) OR (Complementary Medicine) OR (Medicine, Alternative) AND (Vomiting) OR (Emesis) AND (Pregnancy) OR (Gestation)
(Complementary Therapies) OR (Alternative Therapies) OR (Complementary Medicine) OR (Medicine, Alternative) AND (Morning Sickness)
(Complementary Therapies) OR (Alternative Therapies) OR (Complementary Medicine) OR (Medicine, Alternative) AND (Aromatherapy) OR (Hypnosis) (Homeopathy) OR (Acupuncture) OR (Acupuncture, Ear) OR (Music Therapy) OR (Phytotherapy) OR (Yoga) AND (Pregnancy) OR (Gestation)
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CINAHL
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Termo CINAHL
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(Alternative Therapies) AND (Nausea) AND (Pregnancy)
(Alternative Therapies) AND (Vomiting) AND (Pregnancy)
(Alternative Therapies) AND (Aromatherapy) OR (Hypnosis) OR (Homeopathy) OR (Acupuncture) OR (Acupuncture, Ear) OR (Music Therapy) OR (Medicine, Herbal) OR (Yoga) AND (Pregnancy)
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EMBASE
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Emtree Tesouros
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(Alternative Therapies) AND (Nausea) AND (Pregnancy)
(Alternative Therapies) AND (Vomiting) AND (Pregnancy)
(Alternative Therapies) AND (Aromatherapy) OR (Hypnosis) OR (Homeopathy) OR (Acupuncture) OR (Auricular Acupuncture) OR (Music Therapy) OR (Naturopathy) OR (Phytotherapy) OR (Yoga) AND (Pregnancy)
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Data Management
The search will be carried out in the aforementioned databases and then loaded into the EndNote® reference manager, which allows the organization of references identified in different electronic databases. All results will be entered into this manager and duplicate studies will be identified and removed. Then, this database will be exported to the Rayyan® software, where the selection process of the studies will take place since this tool allows the articles to be mined by independent reviewers with the option of blinding amongst them.
Selection Process
All articles will be selected by two different reviewers in a blinded approach, and at the end, any disagreements will be settled by a third researcher after mutual discussion. The article selection process will be carried out in three stages. The first is the title reading, in an attempt to find the keywords that indicate the use of some type of ICPs in pregnant women. The second stage involves reading the abstracts, attempting to filter out whether the studies focused on nausea and vomiting management. Finally, in the third stage, the pre-selected articles will be read in their entirety and checked against the pre-defined eligibility criteria. The entire process of searching, screening, and selecting studies will be presented using the PRISMA flow chart.
Data Extraction
Data collection will be carried out after the study selection process, using a data extraction form, which will be adapted for this review, based on the data extraction and evaluation model proposed by the Cochrane Handbook for Systematic Reviews of Interventions (26). Training on how to fill out the form will be proposed. In addition, the forms will be reviewed and discussed by the authors, based on the extraction of data by everyone, individually from a study, which will be compared in order to unify the understanding of each topic and minimize inconsistencies.
Two authors will be involved in the data extraction process of each one of the selected studies, for the aforementioned form, individually. Another reviewer will be responsible for cross-referencing this information. In case of contradiction between the data, the two authors who carried out the extraction will discuss it; if there is no common agreement, a third author will analyze it and provide the final opinion.
If the data presentation is incomplete, the corresponding authors of the research will be contacted by e-mail (maximum of three attempts) to complement the information.
The data extraction form will be based on the identification, design, and methods of the study and information will be collected regarding the participants, intervention, outcome measures used, and results (28) ( Chart 2).
Chart 2 - Data extraction form items
Identification
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First author, title, year of publication, journal, country.
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Eligibility
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Confirm eligibility for review
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Introduction
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Study objectives and included hypotheses
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Method - design and group allocation
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Study design, allocation and concealment technique, randomization, blinding and masking.
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Method - Participants
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Age, race, Gestational Age, eligibility criteria.
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Method - Interventions
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Duration, ICP used, treatment protocol, comparison group, control group.
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Method - Statistical Analysis
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Statistical analyses used.
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Results
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Sociodemographic data, number of participants randomized/allocated per group/analyzed, sample losses, summary data for each group at each time point, intervention compliance, frequency and duration of nausea and vomiting, adverse effects, quality of life, what tools were used for assessment, and other pertinent variables.
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Discussion
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Interpretation of results and main conclusions.
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Risk of Bias
It is believed that the quality of a study is inversely proportional to its risk of bias. The eligible articles will be assessed for their methodological quality by using the Cochrane Risk of Bias Tool ROB2 (29). With this tool, it is possible to assess each study's risk of bias in six different domains. These domains are as follows: randomization process, intervention attribution, incomplete data on outcomes, measurement of results, selective reporting of outcomes, and general risk of bias.
For each of these domains, the risk of bias will be classified as follows: high, uncertain, or low, therefore enabling the visibility of the reliability of the results of the analyzed studies. This evaluation will be carried out by two independent authors and a third author will be consulted to solve possible divergences.
Data Synthesis and Analysis
If meta-analysis can be carried out, the statistical software Stata SE/12.0 will be used for data analysis. The absolute difference between means, with 95% confidence intervals, will be selected to describe the mean differences between the treated and control groups at the evaluation performed immediately after the treatment completion. A p-value of < 0.05 will be considered statistically significant.
The potential heterogeneity among studies will be examined using Cochran's Q statistics (30) and Higgins' method (I2 statistics), (31). Values of 25%, 50%, and 75% for I2 represent low, medium, and high heterogeneity, respectively (31). The result will be presented using a forest plot. If necessary, subgroup analysis will be performed, which will be based on possible factors that may lead to heterogeneity, such as intervention, control, age, treatment duration, and the quality of the study.
If the data are considered inadequate to be analyzed quantitatively, a systematic narrative synthesis will be performed to present the studies included in the review.
Quality of certainty of evidence
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification will be used to assess the certainty of the evidence (32). This assessment classifies the evidence into four levels: very low, low, moderate, or high and will be performed individually by two reviewers, while a third reviewer will be invited should there be any divergence.