Advances achieved in diagnosis and improvements in treatment for breast cancer have resulted in a favourable survival rate. Therapeutic physical exercise (TPE) is presented as an intervention strategy that seeks to improve the functional capabilities of the subject. To analyse if clinical practice guidelines recommend therapeutic physical exercise to reduce the adverse effects of treatment in breast cancer survivors, and on what level of scientific evidence are these recommendations based. This systematic review was prepared by searching nine electronic databases to identify eligible studies. Thirteen met the criteria for inclusion. The Appraisal of Guidelines for Research and Evaluation (AGREE II) scale was used to analyse the quality of Clinical Practice Guideline (CPGs). The percentages obtained ranged between 30.07% and 75.70%. Specifically, the highest degree of evidence could be found in the application of TPE to offset adverse effects leading to effects such as: an increase in the quality of life, fatigue reduction, and reduction in body weight alterations. TPE is presented as an optimal intervention strategy to alleviate the negative effects that patients with breast cancer suffer as a result of the treatments received. The level of evidence that supports this claim is very strong for the majority of the side effects analysed. However, this evidence is not always included in the clinical practice guidelines. Breast cancer is a pathology whose highest annual incidence rate is found in industrialised countries . FurtherHowever, it is a pathology whose adverse effects and treatment processes mean that the quality of life of patients is altered, which leads to a series of health needs that generate certain costs in society. Hospitalisation, drug administrations, and sick leave, which the disease entails, are some examples of these costs .The increase in healthcare costs in patients who are survivors of breast cancer is usually derived, to a large extent, from compensating for the adverse effects resulting from the treatment of breast cancer . The mosTherapeutic physical exercise (TPE) is presented as an intervention strategy that seeks to improve or maintain the functional capabilities of the subject . ExercisClinical practice guidelines (CPGs) are reference documents for clinical professionals that include recommendations on the care, diagnosis, and appropriate treatment of certain diseases ,10. ClinOne of the objectives of this study was to analyse if clinical practice guidelines recommend therapeutic physical exercise to reduce the adverse effects of treatment in breast cancer survivors, and on what level of scientific evidence are these recommendations based. In addition, it also aimed to specify the adverse effects of breast cancer that can be reduced by intervention with a TPE programme.This systematic review was prepared according to the protocol registered in PROSPERO: International prospective register of systematic reviews, with reference number CRD42018103258, and has been submitted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.The following databases were used for the literature search: PubMed, ScienceDirect, Google Scholar, CINAHL, PEDro, Scopus, National Guideline Clearinghouse (NGS), and National Institute for Health and Clinical Excellence (NICE). The following keywords were used for the search: “Breast cancer”, “Physical treatment”, “Exercise”, and “Guideline”. Keywords were combined using the Boolean operators “AND” and “OR”.Initially, two independent investigators (AdRJ and MTF) analysed and selected studies that could potentially be included based on title and abstract. In the case of disagreement, a third investigator (MGS) issued a judgment. The full texts of the selected articles were evaluated in the same manner. For the selection of clinical practice guidelines the following inclusion criteria were used: clinical practice guidelines for breast cancer, published in Spanish, French, English, Italian, and/or Portuguese, published before March 2020 and, in case of successive editions, the latest version was selected. Exclusion criteria used were guidelines that did not include TPE as part of the post-intervention strategy and reports not on humans.For the evaluation of the various selected documents, the Appraisal of Guidelines for Research and Evaluation (AGREE II) was used to determine the quality of these CPGs. This scale evaluates the quality of the various guidelines and recommendations offered by the CPG, it also provides a methodological strategy for the development of various guidelines and instructs on how the information given by the CPGs should be transmitted .Independently, two authors (AdRJ and MTF) examined the full text of the clinical guidelines included in the study to analyse the risks of bias according to the AGREE II . In ordeOnce the CPGs that meet the inclusion/exclusion criteria were identified, with the intention of being able to compare the level of evidence on which the recommendations made by each CPG are based, and in order to unify the different levels of evidence shown in the selected CPGs, a scale of evidence was developed following the literature search . This scTo establish the degree of recommendation of the CPGs, a colour code system was established in order to facilitate the capture of the necessary information  Table 2Table 2. Thirteen document were selected. For more details of the search results see To summarize and be able to compare the level of evidence and the degrees of recommendations made by the different CPGs regarding the recommendation of TPE as an intervention to reduce the adverse effects derived from treatment in surviving patients with breast cancer, Several of the adverse effects caused by treatment received during breast cancer could be reduced by applying TPE as a therapeutic strategy. However, it was also observed that the different CPGs that were analysed in the present study showed disparity regarding the levels of evidence and degrees of recommendation for TPE as a strategy to diminish the adverse effects that the treatment of breast cancer entails .Mortality is one of the most important adverse effects for breast cancer survivors; however, only one CPG proposed TPE as a strategy to achieve reduced mortality from breast cancer. Despite the moderate degree of evidence that this CPG presented , the degThe reduction of recurrence of a new breast cancer when performing TPE generates some controversy in the different CPGs. Two of the CPGs contemplated TPE to reduce the likelihood of recurrence of a new breast cancer ,24, but However, a document with a high degree of evidence (grade A), demonstrated how TPE decreases certain pro-inflammatory markers and with it the risk of recurrence of a new breast cancer . A systeRegarding the increase in the quality of life of breast cancer survivors, only two CPGs mentioned the practice of TPE as a tool to achieve this increase. The degrees of evidence presented by these CPGs ,14 were Pain is a common side effect of all breast cancer treatments. Only 3 of the 13 CPGs analysed recommended using a TPE programme to reduce this adverse effect. The grades of recommendation presented by these CPG ranged from moderately recommendable ,21, to hThe physical and mental fatigue that this pathology causes in patients is an adverse effect that generated significant disparity in the different CPGs analysed. There was no clear consensus regarding the level of evidence or the degree of recommendation that they presented for the application of TPE to reduce fatigue in breast cancer survivors. The degrees of recommendation that we found ranged between neither recommending nor disapproving of ,16 to hiThe appearance of lymphedema is a frequent adverse effect in the ipsilateral upper limb after a surgical intervention . The recThe recommendations offered by a CPGs analysed in the present study  presenteThe reduction of the joint range of the shoulder ipsilateral to the surgical intervention, in breast cancer, is another of the adverse effects that can be diminished with the application of a TPE programme. Only 2 of the 13 CPGs analysed recommended applying this strategy with a moderate degree. We emphasise the CPG  that preThe changes suffered both from the disease itself and the treatments received on the body weight of breast cancer patients are adverse effects for which it is recommended to perform TPE. These recommendations are very different in the various CPGs analysed. The degrees of recommendation found in them were: neither recommended nor disapproved of ,13,21 orThe gastrointestinal alterations suffered by breast cancer survivors can be reduced by applying a TPE programme. Only two of the analysed CPGs recommended TPE to a moderate degree  or highlThe hot flashes caused by post-treatment of breast cancer is an adverse effect that only one CPG contemplated could be reduced by applying TPE. A CPG  presenteThere is a clear consensus among the different CPGs analysed on the degree of recommendation for TPE to reduce bone alterations in breast cancer survivors. All of them neither recommended nor disapproved of TPE to reduce this adverse effect. Note that, despite the low grade of recommendation, Carolyn D. Runowicz’s CPG  presentsOnly two of the CPG analysed in this study contemplated the application of TPE to reduce the neuropathies caused by the treatments received or by the disease itself. The grades of recommendation vary between moderately recommendable  and highStress, anxiety, and depression are common side effects presented by breast cancer survivors. Several CPGs contemplated in their recommendations the use of TPE to reduce such adverse effects. There was a similarity in the degrees of recommendation and evidence of the different CPGs about this therapeutic strategy. Some CPGs ,19,23 haSurvivors of breast cancer, as a consequence of the interventions and treatments to which they have been subjected, present numerous adverse effects, many of which were not contemplated by the different CPGs included in the present study to be reducible with a TPE programme. Some of them, such as cardiorespiratory alterations or inflammatory processes, could be reduced by applying a TPE programme. A systematic review with a high grade of evidence (grade A) , showed It has been observed how TPE may improve the following outcomes: 1. Recurrence risk reduction; 2. Increase quality of life; 3. Reduction of gastrointestinal disorders; 4. Neuropathy reduction; 5. Stress; 6. Depression; 7. Anxiety; 8. Pain reduction; 9. Fatigue reduction. 10. Increase in range of movement of the shoulder. TPE may not improve or have controversial impacts on the following outcomes: 1. Hot flashes reduction; 2. Reduction of body weight alterations; 3. Reduction of bone alterations; 4. Lymphedema reduction. . HoweverHowever, as with healthy subjects, the predominant type of training in the TPE program could determine the magnitude of the improvement and the adverse effect on which it occurs. Below are the most important aspects when planning a predominantly resistance, strength or flexibility training that should be taken into account when planning a TPE protocol.Regarding resistance training, we highlight the duration of the session, which the recommendations of the scientific literature show to be between 30–60 min a day, with moderate to vigorous intensity ,14,38. FThe main objective of this type of training is to recover the range of motion lost in the shoulder joint post-surgery. A programme for strengthening the upper limb carried out by a physiotherapist is recommended . During This type of training presents its main benefits at the level of joints and soft tissues . The decThere is no pre-established training programme based on the treatment received or the adverse effects experienced by the patient. Some authors recommend the fusion of training styles to obtain the best benefits for survivors of breast cancer . With thThe literature proposes the combination of resistance training and the Pilates method three times a week in 50 min sessions. With this, it seems that a greater reduction in musculoskeletal alterations is achieved . In addiCPGs are the reference documents of clinicians for the use and consultation of therapeutic strategies applied to their patients ,41. ScieThe present study demonstrates how to reduce the probability of suffering a recurrence of breast cancer, increase the quality of life, and reduce fatigue, lymphedema, body weight, bone alterations, and depression; as the recommendations for all these adverse effects are outdated. Most CPGs show a very low grade recommendation for TPE to decrease the effects mentioned above. But current studies show that there is evidence that TPE reduces such effects. Therefore, it will be necessary that both clinical recommendations and scientific evidence advance in parallel, to ensure therapeutic success.On the other hand, in a paradigm where the evidence acquires increasing clinical relevance, it should be necessary that the healthcare professionals in charge of carrying out the rehabilitation process in patients who survive breast cancer acquire the necessary skills to search, identify and select studies with the most solid evidence so that they can integrate new approaches immediately to their clinical practice without having to wait for the updates of the different CPGs.Among the strengths of the present study is that it proposes a parallel vision for the scientific literature and clinical practice, thereby achieving the most effective treatments for patients. In the same way, a proposal is also made to update the evidence proposed in the different CPGs through the identification of documents with a high level of evidence .However, the present study also presents some limitations that must be taken into account when interpreting the results presented, such as, for example, the exclusion of documents written in a language other than Spanish, French, English, Italian, or Portuguese. Documents published in other languages were not selected in this study.Future research directions: considering the results observed in the present study, it would be necessary to carry out studies that would consolidate the evidence, as well as better define the effects of the different interventions whose evidence is not sufficiently consolidated or even that is contradictory.Therapeutic physical exercise is presented as an optimal intervention strategy to alleviate the negative effects that patients with breast cancer suffer as a result of the treatments received. The level of evidence that supports this claim is very strong for the vast majority of the side effects analysed. However, this evidence is not always included in the clinical practice guidelines, which have been shown to be outdated in many cases as far as TPE intervention in patients surviving breast cancer is concerned. Therefore, it is necessary to increase the frequency of updates of CPGs to avoid this type of document from diminishing in its clinical utility.


Breastfeeding has positive impacts on the health, environment, and economic wealth of families and countries. The World Health Organization (WHO) launched the Baby Friendly Hospital Initiative (BFHI) in 1991 as a global program to incentivize maternity services to implement the Ten Steps to Successful Breastfeeding (Ten Steps). These were developed to ensure that maternity services remove barriers for mothers and families to successfully initiate breastfeeding and to continue breastfeeding through referral to community support after hospital discharge. While more than three in four births in Australia take place in public hospitals, in 2020 only 26% of Australian hospitals were BFHI-accredited. So what is the social return to investing in BFHI accreditation in Australia, and does it incentivize BFHI accreditation? This study aimed to examine the social value of maintaining the BFHI accreditation in one public maternity unit in Australia using the Social Return on Investment (SROI) framework. This novel method was developed in 2000 and measures social, environmental and economic outcomes of change using monetary values.The study was non-experimental and was conducted in the maternity unit of Calvary Public Hospital, Canberra, an Australian BFHI-accredited public hospital with around 1000 births annually. This facility provided an opportunity to illustrate costs for maintaining BFHI accreditation in a relatively affluent urban population. Stakeholders considered within scope of the study were the mother-baby dyad and the maternity facility. We interviewed the hospital’s Director of Maternity Services and the Clinical Midwifery Educator, guided by a structured questionnaire, which examined the cost  and benefits of each of the Ten Steps. Analysis was informed by the Social Return on Investment (SROI) framework, which consists of mapping the stakeholders, identifying and valuing outcomes, establishing impact, calculating the ratio and conducting sensitivity analysis. This information was supplemented with micro costing studies from the literature that measure the benefits of the BFHI.The social return from the BFHI in this facility was calculated to be AU$ 1,375,050. The total investment required was AU$ 24,433 per year. Therefore, the SROI ratio was approximately AU$ 55:1 , which meant that every AU$1 invested in maintaining BFHI accreditation by this maternal and newborn care facility generated approximately AU$55 of benefit.Scaled up nationally, the BFHI could provide important benefits to the Australian health system and national economy. In this public hospital, the BFHI produced social value greater than the cost of investment, providing new evidence of its effectiveness and economic gains as a public health intervention. Our findings using a novel tool to calculate the social rate of return, indicate that the BHFI accreditation is an investment in the health and wellbeing of families, communities and the Australian economy, as well as in health equity. Breastfeeding is the natural way and biological standard of infant feeding for all mammals. It has benefits to infant and maternal health, and reduces health inequality, as well as reducing harmful impacts to the environment and decreasing health expenditure attributed to preventable illness. Socioeconomic groups with lower education and income levels are less likely to breastfeed when compared to their higher education and income group peers . ChildreHealth Initiative in order to more accurately reflect the expansion of the initiative into community health facilities [Factors associated with low breastfeeding initiation and/or duration include maternal and paternal lower education , 12, parcilities .Implementing the Ten Steps and achieving BFHI accreditation is essential to ensure quality of maternity care received by mothers and families, regardless of their social, economic, race and religious background. The benefits of implementing Ten Steps and achieving BFHI accreditation and its impact on breastfeeding has been demonstrated in research internationally –24, and This study aimed to examine the social return on investment (SROI) of maintaining the BFHI accreditation in one public maternity unit in Australia and whether it incentivize maternity and newborn care facilities to gain or maintain BFHI accreditation.The study was conducted in Calvary Public Hospital, Canberra, an Australian BFHI-accredited public hospital in August 2019. We selected this hospital because three in four Australian mothers give birth in public hospital  and thisInterviews aimed to elucidate the costs of maintaining the BFHI accreditation. Underpinned by the Social Return on Investment (SROI) framework, and in collaboration with the Director of Midwifery, the Clinical Midwife Consultant, and the Clinical Midwifery Educator, AP, SB, JD and JS developed a structured questionnaire based on the 2018 Ten Steps to Successful Breastfeeding (Ten Steps) which was used for the interview. AP and SB interviewed the Director of Midwifery and the Clinical Midwife Consultant on 21st August 2019 and took one and a half hours. The interviewees were approached through JD’s network and selected purposively for their understanding of the cost of BFHI implementation, accreditation and maintenance. The interview was conducted by AP and SB. AP is an International Board-Certified Lactation Consultant (IBCLC) and a PhD candidate at the Australian National University (ANU); SB is a Health Economist with expertise in using the SROI framework.; JS is an experienced economist with focus in breastfeeding, regulations of markets in mother’s milk and gender analysis of Australia’s taxation and fiscal policies; and JD is a registered nurse and midwife with experience in qualitative research design and implementation. All authors were female.The interview was audio-recorded and then transcribed verbatim. Data was stored on password protected computer at the university and only accessible to the primary researcher.Data was analyzed in excel using the SROI framework, which uses monetary values to measure social, environmental and economic outcomes of change. The SROI is a framework for measuring and accounting for the much broader concept of value; it seeks to reduce inequality and environmental degradation, and improve wellbeing by incorporating social, environmental and economic costs and benefits . The benSROI analysis involves a 5-step process: establishing scope and involving stakeholders, mapping outcomes, evidencing and valuing outcomes, establishing impact, and calculating the SROI ratio. Each step is explained in detail below.First, we identified the stakeholders for SROI analysis. For our analysis, implementation of the Ten Steps as a framework for the BFHI involved two main stakeholders: the mother and baby dyad. The mother and baby dyad included as they were identified to derive the greatest benefits from the BFHI accreditation and sufficient evidence was available, and it was feasible to measure and include. While the maternity facility stakeholders could not be included as the evidence was insufficient to be measured.Second, we mapped the outcomes for each stakeholder. A theory of change was developed from the literature, representing how the BHFI were expected to bring about change. For mothers, the benefits included risk reduction of breast cancer, cardiovascular disease, ovarian cancer, hypertension, and for no cost related to buying formula , 57–59. Third, we searched the literature to evidence outcomes Table . The cosDeadweight, attribution, and displacement were subtracted from the outcome to reduce the risk of over-claiming benefits . To deteIn this step we estimated how long the outcomes will last and used them in the analysis. Here we knew the duration of the outcome due to earlier literature search and interviews. We assumed the benefit included the risk reduction of diarrhea, respiratory infection, acute otitis media and necrotizing enterocolitis lasted for three years; higher IQ, risk reduction of obesity, type 1 and type 2 diabetes and SIDS for 30 years; risk reduction of breast and ovarian cancer, hypertension and cardiovascular disease for 15 years; and formula supply for two years. The costs and benefits were discounted to calculate the net present value, to ensure that the costs and benefits in different time periods were comparable. The recommended rate of 4%  was usedThe average number of births in Calvary public hospital was 1000 annually, with exclusive breastfeeding rate on discharge of 97% in 2019. The value of benefits and costs is summarized in Table The social return (benefits) was calculated to be AU$ 1,375,050 and total investment required was AU$ 24,433 per year. Therefore, the SROI ratio was 55:1, which meant that every AU$ 1 invested in the BFHI generated approximately AU$55 of benefit to the Australian economy. The payback period was 0.63 month, which meant that all the investment would return in around 1 month.For our baseline estimation of the SROI we used conservative assumptions. We conducted sensitivity analysis by trying different assumptions Table . The SROAll scenarios tested demonstrated the SROI ratio in favor of the BHFI was > 1, indicating that social value of the BHFI is likely to be greater than the investment made in the program.Our results demonstrate that every investment of AU$1 drives a social return of AU$55. This evaluation also demonstrated the impact of the BHFI whose principal goals are to ensuring maternity service quality is equitable for every mother and family. Other studies have also found a positive social return for breastfeeding support programs; for example, a nutritional counselling and breastfeeding support program in Nairobi brought US$71 for every US$1 invested or AU$71.07 for every AU$1 (US41 = AU$1.35) . A breasOne strength of the SROI methodology includes deep engagement with stakeholders, enabling practice-based identification of outcomes and values. Difficulties can be encountered in valuing outcomes and what might have happened anyway. This type of research is most commonly conducted by consultants, which can be costly . There aModelling conducted for the Lancet Breastfeeding Series estimates that global economic losses related to lower cognition from not breastfeeding reached a staggering US$302 billion in 2012, equivalent to 0.49% of world gross national income. In high-income countries alone these losses amounted to US$231.4 billion, equivalent to 0.53% of gross national income . The annAs part of our SROI analysis, stakeholder engagement did not provide all the inputs to the SROI model resulting in some of the outcome values being taken from the literature. Compared to conventional Return on Investment analysis, SROI not only calculates benefits against capital invested, but also takes into account externalities (spillover effects from the intervention) . In factBreastfeeding can play an important role in narrowing health inequalities. Low breastfeeding rates are related to several factors, and exacerbated by disparities including access to services and socioeconomic and educational background of the mother , 82. PreThe perceived lack of policy commitment to BFHI in Australia might be due to low valuation of breastfeeding as a result of the invisibility of breastfeeding and breast milk’s contribution from an economic perspective . BreastfHow health care is financed and who benefits from the BHFI impacts the support for BHFI implementation and/or accreditation. Hospital management may not perceive the returns from investing in BFHI accreditation to be high enough if the hospital funding is activity based i.e. on how many cases of illness and disease are treated. Health issues avoided by breastfeeding not only benefits baby and mother, as we measured in this study, but also benefits to the health system and society by avoiding child and mother morbidity and mortality , 87. It Supporting mothers in the early days after birth in hospital through the BFHI is essential for health equity, as exclusive breastfeeding in hospital is associated with longer duration of breastfeeding , 24, 89,The results of our study align with previous research regarding the SROI of breastfeeding programs. Investment in breastfeeding support programs, including the BFHI, benefits the community. As the social benefits are greater than the investment and it provides the best start for every infant, the BFHI needs to be prioritized by the government. In principal, the Australian government supports and promotes breastfeeding, and specifically the BFHI, at the national , 91, 92 This study measured the benefits compared to the cost invested by the hospital. Nevertheless, our study did not include cost savings for healthcare providers, which were not taken into account due to large gaps in the literature relevant to the Australian health system. There is also no literature on the benefits to healthcare professionals in implementing and/or achieving the BFHI accreditation. Moreover, mothers’ time and effort to breastfeed were not included in the calculation, with only limited data on this important investment available in the current literature –100. TheThe results of our study indicate that implementation of the Ten Steps and the BFHI is worth the investment; the social return received was far greater than the investment. BFHI accreditation is a way to ensure equitable quality maternity care, but lacks incentives for individual facilities in Australia’s health financing system. This study was the first that measured the social return of BFHI accreditation and provides strong evidence to prioritize measures driving wider implementation of the BFHI at a national level.


Despite its well-known benefits, breastfeeding practices remain suboptimal worldwide, including in Southeast Asia. Many countries in the region have thus enacted policies, such as maternity protection and the World Health Assembly International Code of Marketing of Breast-milk Substitutes (the Code), that protect, promote, and support breastfeeding. Yet the impact of such national legislation on breastfeeding practices is not well understood.This study aims to review the content, implementation, and potential impact of policies relating to maternity protection and the Code in Myanmar, the Philippines, Thailand, and Vietnam.This mixed methods study includes a desk review, trend and secondary data analyses, and quantitative and qualitative data collection. Desk reviews will examine and compare the contents, implementation strategies, coverage, monitoring, and enforcement of national policies focusing on maternity protection and the Code in each country with global standards. Trend and secondary data analyses will examine the potential impact of these policies on relevant variables such as breast milk substitute (BMS) sales and women’s workforce participation. Quantitative data collection and analysis will be conducted to examine relevant stakeholders’ and beneficiaries’ perceptions about these policies. In each country, we will conduct up to 24 in-depth interviews (IDI) with stakeholders at national and provincial levels and 12 employers or 12 health workers. Per country, we will survey approximately 930 women who are pregnant or have a child aged 0-11 months, of whom approximately 36 will be invited for an IDI; 12 partners of the interviewed mothers or fathers of children from 0-11 months will also be interviewed.This study, funded in June 2018, was approved by the Institutional Review Boards of the relevant organizations . The dates of data collection are as follows: Vietnam: November and December 2019, May and June 2020; the Philippines: projected August 2020; Myanmar and Thailand: pending based on permissions and funding. Results are expected to be published in January 2021. As of July 2020, we had enrolled 1150 participants. We will present a comparison of key contents of the policies across countries and against international standards and recommendations and a comparison of implementation strategies, coverage, monitoring, and enforcement across countries. We will also present findings from secondary data and trend data analyses to propose the potential impact of a new or amended policy. For the surveys with women, we will present associations between exposure to maternity protection or BMS promotion on infant and young child feeding practices and their determinants. Findings from IDIs will highlight relevant stakeholders’ and beneficiaries’ perceptions.This study will increase the understanding of the effectiveness of policy interventions to improve breastfeeding, which will be used to advocate for stronger policy adoption and enforcement in study countries and beyond.DERR1-10.2196/21286 The benefits of breastfeeding for child survival, health, and development as well as maternal health and wellbeing have been well-documented in low-income, middle-income, and high-income countries . By imprDespite all that is known about the benefits of breastfeeding, breastfeeding practices remain suboptimal worldwide ,11. AlthBreastfeeding is also influenced at the structural level, such as by policies that can support, protect, or promote the practice, including maternity protection and the international code on the marketing of breast milk substitutes (BMS).Across the globe, a mother’s return to work after childbirth is one of the primary reasons for not breastfeeding or for early cessation of breastfeeding . IncreasThe International Labor Organization (ILO) Maternity Protection Convention, 2000 (No. 183)  and its Breastfeeding is also affected by the aggressive marketing and widespread availability of BMS. Such marketing can influence social norms in favor of BMS and undermine mothers’ confidence to breastfeed, resulting in suboptimal breastfeeding practices . To limiAs of April 2020, 136 of 194 (70%) WHO member states have implemented legal measures related to the Code. Of these, only 25 countries have measures “substantially aligned” with the Code based on a WHO/UNICEF/ International Baby Food Action Network checklist of provisions of the Code and relevant WHA resolutions . FurtherAlthough there is evidence of the negative impact of the provision of free BMS samples or promotion through trusted health workers ,33, therThe goal of this study is to determine the impact of breastfeeding-related policies in Myanmar, the Philippines, Thailand, and Vietnam. To do so, researchers will review the content, implementation, and potential impact of policies relating to breastfeeding promotion, protection, and support in these countries; however, depending on the local context, the study in each country will examine key policies related to maternity protection and the Code.Specific study objectives are to (1) review the content of national policies on maternity protection and the Code; (2) review the implementation, coverage, monitoring, and enforcement of these policies across countries; (3) examine the potential impact of these policies on relevant outcomes ; and (4) examine perceptions of relevant stakeholders and beneficiaries  about these policies .The study will be conducted in Myanmar, the Philippines, Thailand, and Vietnam. In recent years, each of these countries has made a significant policy change related to maternity protection or the Code.Working mothers in Myanmar are entitled to 14 weeks of paid maternity leave (18 weeks for twins) in the private sector under the Social Security Law (2012) and the Leave and Holidays Act  . MothersIn 2014, Myanmar’s Food and Drug Board of Authority issued the Order of Marketing of Formulated Food for Infant and Young Child under the National Food Law, which regulates the marketing and labeling of BMS, complementary foods, and bottles and teats intended for children under 2 years of age.In the Philippines, working mothers are entitled to 9 weeks of paid maternity leave, all of which is funded by social security . Since 2Republic Act revised the definition of BMS by law to include any type of milk marketed for feeding of infants aged up to 36 months.The Philippines was among the first countries to pass national legislation on the Code in 1986. In 2006, the Implementing Rules and Regulations of the Code were revised to align with international standards and were approved . ExecutiThailand has not yet ratified ILO Convention 183, which provides maternity protection. In 1990, Thailand approved the Social Security Act B.E 2553 entitling mothers to 90 days of maternity leave. During maternity leave, 50% of the salary is paid by the employer for 45 days, and 50% is paid by social security for 90 days. To be eligible for social security payments, the insured person must have paid contributions for at least 7 months during the 15 months prior to the date of receiving medical benefits. Currently, there is no mention of breastfeeding breaks in the Thai law.In 2017, the National Legislative Assembly passed the Marketing Control on Food for Infants and Young Children Act to restrict the marketing of food for infants and young children. Under the revised legislation, the government of Thailand prohibits all marketing of BMS for children under 12 months of age, with further regulations that apply to marketing of similar products to children under 3 years of age.The National Assembly extended paid maternity leave from 4 to 6 months, effective from 2013. Working mothers in Vietnam are also entitled to paid nursing breaks (up to 60 minutes) by law, for up to 12 months . The funIn 2012, the National Assembly voted in favor of implementing a total ban on the promotion of BMS for children up to 2 years of age. The government guiding decree on marketing and use of feeding products for young children, feeding bottles, teats, and pacifiers was approved in 2014 .This is a mixed-methods study, employing desk reviews, secondary data analysis, and primary quantitative and qualitative data collection . Our stuFor each country, we will collect and review relevant maternity protection and the Code policies. These will be collected through government websites  and other official sources. Key informants, consultants, or country staff will help to identify and collect documents not publicly available. Researchers will extract key information from the collected documents using a semiquantitative policy data extraction form . Two resWe will review the implementation, coverage, monitoring, and enforcement of relevant policies focusing on maternity protection and the Code. Key informants, consultants, or country staff will help to identify and collect documents and data related to the number and proportion of working mothers receiving maternity benefits, details of monitoring and reporting activities, as well as the number of the Code violations and penalties enforced.Secondary data will be drawn from national maternal, infant, and young child nutrition and health surveys, such as Multiple Indicator Cluster Surveys (MICS), Demographic and Health Surveys (DHS), or labor force surveys. Because the availability of secondary data sets and trends may vary across countries, we will identify all relevant data  and secure access via locally contracted research firms. Univariate, bivariate, and multivariate data analysis will be used to analyze individual-level data.We will analyze data using an interrupted time-series approach to quantify the change in the slope or level of selected outcomes before and after the implementation of a policy . For matWe will conduct in-depth interviews (IDIs) with stakeholders, including policy makers or authorities at national and subnational levels; staff of the United Nations, nongovernmental organizations (NGOs), research organizations, and media; and employers and health workers . ParticiWe will also collect primary data from pregnant women and mothers with children aged 0-11 months using IDI guides and structured questionnaires; we will collect data from these women’s partners using IDI guides . These pThe sample size for IDIs is based on information saturation. If saturation is achieved sooner, fewer IDIs will be conducted, while if saturation is not achieved, the sample will be expanded .P of 50% (largest sample size), confidence level of 95%, absolute precision of 7%, and design effect of 1.5. In each country, the minimum sample size is 310 women for each of the 3 following groups: pregnant women, mothers of children aged 0-5 months, and mothers of children aged 6-11 months. Thus, in each country, we will interview 930 women divided equally across the selected provinces.The sample size for the quantitative survey of women was determined by using the simple sampling equation with some adjustment for the design effect . We chosPrimary data collection will be conducted at the national, provincial, and community levels . For theThe identification of key informants at the national level will start with member lists of working groups and committees related to food, nutrition, consumer protection, and labor. Key informants for the study of the Code will include representatives from the Ministry of Health, Ministry of Trade, UNICEF, and WHO, among others. Key informants for the study of maternity protection policies include those from the Ministry of Labor, Social Insurance, ILO, UNICEF, and WHO, among others. The key informants will help to identify other potential participants from NGOs, research institutions, and media at the national level.At the provincial level, research firms will identify a potential list of provinces in which to conduct the study with the support from national key informants and the Alive & Thrive team. The selection of provinces will largely be based on feasibility considerations. The primary criteria are urban provinces or provinces with industrial zones with female workers and research firms that have good connections and working relationships in these provinces. Provinces will be excluded if they are deemed not feasible or inefficient for study conduct, such as remote provinces with low population density or those that are not safe for the research teams. Provinces that generate income mainly from the agricultural or self-employed sectors will not be included because of the lower chance of obtaining a sufficient sample size of formally employed women. In each country, from the list of eligible provinces, the research firm will purposively select 3-4 provinces to improve capture variation by region. We acknowledge that with this sampling strategy, generalizability of the findings will be limited to the selected provinces.The research firm will contact potential participants by phone to explain the purpose, requirements, and logistics of the survey, and the firm will follow-up with an official letter. The next step entails a kickoff meeting at the provincial level to develop a detailed list of potential participants. The provincial key informants will introduce the research firm and help to schedule an appropriate time and place for the interview. Informed consent will be obtained by interviewers before the IDI. If the appointment is missed, researchers will be allowed to reschedule up to 2 times.At the community level, for each country, researchers will choose which policy(ies) to evaluate and if the study will include both maternity protection and the Code. This decision will be based on each country’s situation and need, availability of funding, and the capacity of the research firm. The community-level sampling strategy relies on this decision . SpecifiFor sampling strategy 1 (with a survey of women), from each of the selected provinces, we will employ a multiple-stage cluster sampling design in each province. Stage 1 is the selection of districts. We will select 3-4 districts in each province using a simple random selection technique. Stage 2 is the selection of clusters and primary sampling units (PSUs). We will define a sample frame of clusters and use the probability-proportional-to-the-size cluster sampling technique to select 30 clusters in the selected districts. A cluster will be a next lower level of subdistricts, which could be communities, villages, or population groups depending on the country context. The proposed minimum number of mothers of children in each PSU is about 1.5 to 2 times the sample size needed in each PSU to ensure we have a sufficient number of participants. Stage 3 is the selection of participants. We will select pregnant women and mothers of children aged 0-5 and 6-11 months in each cluster using systematic random sampling. In selected clusters, 3 lists of potential participants will be created: (1) pregnant women, (2) mothers of children aged 0-5 months, and (3) mothers of children aged 6-11 months. Based on the list and required sample size in each cluster, a list of potential participants will be selected using systematic random sampling.Based on the list of potential participants, the community representative will call the potential participants to invite them to participate in the study. If they agree to participate, the community representative will introduce participants to the study representative in person and leave the interviewer with the participant. During the interview, the interviewer will introduce himself or herself as well as the purpose of the study, obtain informed consent, and conduct the interview. The interview will be conducted in a quiet, private location that is neither a health facility nor workplace to minimize the participants’ risk of exposure or discomfort. Three attempts to visit the household will be made to complete the interviews with selected and eligible participants. If the interviewers could not meet the participants after 3 attempts, the participants will be replaced with one in the pre-identified list.A subset of women surveyed will be invited for an IDI. Also, a subset of partners of mothers with children 0-11 months old will be invited to participate in an IDI. After completing the interview using the structured questionnaire, the interviewers will propose women or partners for an IDI, and the team leader will make the final decision of whom to invite for an IDI. The selection of women or their partners for an IDI will be based on the potential for increasing our understanding of how policies impact breastfeeding practices and collecting case studies. For example, IDIs with women will be conducted among those who (1) went back to work before completing maternity leave or completed maternity leave entitlement before returning to work, (2) weaned her child before or upon return to work or continued breastfeeding after returning to work, (3) experienced discrimination at work due to her pregnancy or birth or did not experience discrimination, or (4) knew the benefit of breastfeeding but stopped breastfeeding early and used infant formula or continued breastfeeding and did not use infant formula.Sampling strategy 2 is for an IDI-only evaluation study (no survey of women). In each country, we will conduct IDIs with 12 pregnant women, 24 mothers of children aged 0-11 months, and 12 fathers of children aged 0-11 months . In eachRegarding the qualitative components, IDI domains are summarized in IDIs with key informants will explore implementation, monitoring, and enforcement of the policies; bottlenecks for implementation; and proposed solutions. IDIs with employers will explore their perceptions about the benefits and disadvantages of the policies for businesses and employees.The purpose of the IDIs with pregnant women and mothers of children aged 0-11 months is to gain deeper insight into respondents’ understanding and perceptions of policies related to maternity protection and the Code including perceived benefits and challenges as they relate to study outcomes  such as challenges of continuing breastfeeding when returning to work, benefits of maternity protection policies on continued breastfeeding, and changes in breastfeeding practices due to exposure to BMS products.The purpose of the IDIs with partners of the interviewed pregnant women and mothers of children aged 0-11 months is to learn about respondents’ understanding and perceptions of policies related to maternity protection and the Code as well as paternity leave and the role of partners in taking care of children and in domestic tasks.For the quantitative survey, we adapted questionnaires from other studies such as NetCode , ILO MatWe developed separate questionnaires for pregnant women  and womeWe pretested the data collection tools. IDI guides and survey questionnaires were initially developed in English and will be translated into each country’s official language. Another translator will back-translate questionnaires into English to ensure that the content and spirit of the original questions are maintained. Data collection tools will be pretested in face-to-face interviews with at least 2 pregnant women, 2 mothers with children aged 0-11 months (using survey questionnaire and IDI guides), and 2 fathers of children aged 0-11 months (using IDI guides). IDI guides for other participants will be reviewed by an external experienced researcher. Necessary modifications will be made based on feedback from pretestingData collection teams formed by local research firms will be responsible for data collection. Each team will include one field supervisor and interviewers. Research firms will identify potential interviewers from a pool of candidates and select interviewers by screening curriculum vitae and conducting interviews.Before data collection, the principal investigator (PI) of the research firms and the FHI 360 PI will train all interviewers and field supervisors for 4 days on the purpose of the study, terminology, concepts, data collection methods, tool pretesting, and reflection. The training will cover skills, including interview techniques, confidentiality, and privacy, as well as afford the study team the opportunity to practice administering the questionnaires and IDI guides. The training will ensure all interviewers and field supervisors understand the procedures and follow the standardized guidelines to guarantee data quality.A trained interviewer will explain the research study in detail, including the study objective and potential risks and benefits of participation, and obtain oral informed consent from the participants before any study procedures are performed . The conAfter the informed consent process, participants will be assigned a personal identification number (PIN), which will be used to link all data collected from an individual in each of the research steps. The PIN is not linked with any information that would identify an individual participant. At the household level, the PIN will be first assigned to the woman participating in the survey. If she is selected for an IDI, her PIN will be unchanged. If her partner participates in an IDI, his PIN will be P (for partner) plus the PIN of the woman. This approach will help to link information of the survey questionnaire with the IDI with the women as well as to link information of a surveyed woman with her partner.Trained interviewers will conduct the IDIs. We will audio record the interviews (with participant consent). For participants who do not consent to audio recording, the interviewers will take detailed notes during the interview.For the quantitative survey of women, a computerized-assisted survey instrument will be used. The questionnaire will be set up in a web-based application and run on an Android tablet. The interviewer must ensure the completeness and logical flow of the questionnaire before leaving the household.At the end of the quantitative interview, if the interviewer finds the woman suitable for an IDI (using criteria shared during the data collector training), he or she will ask if the woman is willing to participate in an IDI. If the woman agrees, the interviewer will ask for a contact telephone number as well as set a tentative date, time, and location for the IDI. After receiving confirmation from the coordinator at the central level, the qualitative interviewer will schedule the IDI. To facilitate quality assurance , at the end of the quantitative interview, the interviewer will ask for the telephone number of the participant. Before asking for the telephone number, the interviewer will confirm that the telephone number will only be used to contact the woman in a rare case when the research team needs to clarify certain information provided or to ask about her interview experience. The interviewer will emphasize that providing the telephone number is optional.The name of audio files collected during IDIs will be linked with the respondent’s PIN. After each day, the audio files will be uploaded to password-protected computers and a secure cloud account. Research assistants from the research firm will transcribe the tapes in the local language. The analytical memos for IDIs will be translated to English to support the report writing. At a later stage, the transcriptions and notes will be translated into English for further analysis. The completed text files will be input to Microsoft Word files and uploaded to NVivo for further analysis.Qualitative data will be collected and managed using a digital approach. The questionnaire will be converted to a digital data collection form . A data management system will be developed in each country by the local research firm and validated by the FHI 360 staff to ensure that data are fit for analysis purposes.During data collection, interviewers will enter the information directly into a password-protected tablet. When connected to the internet, data will be synchronized to a secure server of the platform provider . Synchronization will be done at least once per day. After uploading, the data will be deleted from the tablets. Two back-up tablets will be provided to each data collection team.In very rare cases when data collection could not be done using tablets, a paper questionnaire will be used. The interviewer will review the questionnaire for completeness before ending the interview. The supervisor will then review and approve the questionnaire. Completed questionnaires will be entered into the tablet within 24 hours in the field, with a note about why the tablet was not used during the interview. The completed paper questionnaires (if any), consent forms, and other study documents will be stored in a locked box in the vehicle during transportation and in the hotel room at night.Supervisors at the central level will access data from the cloud, perform data checks and cleaning, and provide feedback about data quality to data collection teams within a day. This will identify and address any issues relating to the questionnaire and data collection in a timely manner.Raw data will be submitted to Alive & Thrive immediately following the end of data collection. An assigned researcher or research assistant will perform required data management  prior to data analysis. Any changes in the dataset will be done through program syntaxes to allow for cross-checking and to ensure that findings are reproducible. Corresponding justifications and individuals who approve each change will be documented.For maternity protection, we will analyze associations between exposure to maternity protection  and infant and young child feeding practices. For the Code, we will analyze associations between exposure to BMS  and infant and young child feeding practices as well as women’s intentions, knowledge, beliefs, social norms, and self-efficacy.Some data will complement the IDI with women related to perceptions of the maternity protection legislation and the Code. Each estimate will be accompanied by 95% CIs, and the cluster design effect  will be accounted for by using complex survey data analysis methods or with the robust option. Sampling weights as appropriate for each stratum  will be calculated and used when combining data from different strata, for example for the overall country-level analysis. For overall and country-specific data analyses, we will use Stata version 15 .IDI content will be transcribed and analyzed. Transcripts will be produced using notes taken and recorded audio files. The full transcripts, written in the local language, will be analyzed by in-country research teams. Depending on the availability of a data platform, the analysis will be done in NVivo (or a similar program) or by color-coding the text. The transcripts will then be translated into English for further analysis by FHI 360 or Alive & Thrive staff or consultants to facilitate comparison across countries using NVivo.The main steps will comprise codebook development, double-coding of a sample of transcripts with intercoder agreement checks, finalization of the codebook to reflect this step, and single coding of primary themes of the discussion, coding for subthemes, exploring any emerging themes, calculating the frequency of subthemes by using the matrix method, and drawing out quotes from the coded phrases . The surStudy monitoring will be conducted by staff of FHI 360 and the research firms. At FHI 360, the study will be led by the study manager who is responsible for overall study administration, ensuring the availability of study resources (funding and staff) and for providing feedback and final decisions related to execution of the study. PIs will oversee technical aspects of the study, conduct overall monitoring of data collection, and ensure quality as well as review and sign off on key deliverables and coordinate activities at the regional level to ensure consistency across study sites. The PI or co-PI will also be responsible for identifying, documenting, and reporting protocol violations and social harm. Country research staff of Alive & Thrive will manage all aspects of the study in the assigned country and serve as the linkage between FHI 360 and the research firms.In the national research firm, the study manager is responsible for technical and financial oversight as well as overall study management in accordance with the signed contract. During data collection, field supervisors will be responsible for ensuring that proper informed consent is provided to each participant and that data collection processes are followed in compliance with the protocol. Field supervisors will remain with the data collection team at all times. Field supervisors will carefully check that the consent process is being performed as approved. The PI will check with field supervisors every week. Field supervisors will travel with selected data collection teams to monitor their field work and to answer any questions during data collection, providing feedback to these teams, as needed.The research study will be conducted in full compliance with the protocol, which will not be amended without prior approval by the PI or co-PI. Protocol violations will be documented on protocol violation reporting forms, and all will be reported to and addressed by the research teams as soon as possible following discovery. They are also responsible to ensure continuous safety monitoring of all research study participants and for alerting the protocol team if unexpected concerns arise. Compliance will also be checked during site visits by the PI or co-PI.From study design to the dissemination of findings, we will follow the ethical guidelines of the Helsinki Declaration . The proThis study was funded in June 2018 and approved by the relevant IRBs . Data collection will occur on the following date(s): Vietnam: November and December 2019, May and June 2020; the Philippines: projected August 2020; Myanmar and Thailand: pending based on permissions and funding. Expected results are to be published in January 2021. As of July 2020, we had enrolled 1150 participants in Vietnam.We will analyze the data using a study conceptual model . We willKey results from the study will then be contextualized within the conceptual model  for furtThe results will be disseminated through meetings with relevant ministries, institutions, and local and international NGOs in the study countries as well as within FHI 360. Study results are intended to be used by ministries and local stakeholders to advocate for relevant policy changes to improve maternity protection and strengthen the Code in the study countries and the Southeast Asia region. Findings will also be disseminated as presentations in scientific forums and in peer-reviewed publications to contribute to the global discourse of nutrition policy making.The unique strengths of this study are that it examines multiple countries, uses mixed methods, and considers 2 main policies relating to maternal, infant, and young child nutrition: the Code and maternity protection. We will collect and analyze various components from perinatal care, breastfeeding practices, behavioral determinants , and exposure to various types of interventions. We adapted standardized questionnaires, including those from the WHO NetCode Assessment Module and ILO Maternity Protection Assessment Toolkit to facilitate the comparison with other studies. We structured the research protocol and data collection tools into sections, which will allow their adaptation to other contexts and study purposes. In addition to tools relating to the data collection -6, we alYet, the study has limitations, which we recognize. Because the selection of provinces and districts will not be random, our results may only apply to study sites. Further, the cross-sectional design of the survey cannot be used to conclude causal relationships. However, we have increased the plausibility of causality by selecting age ranges for which exposure or covariate variables occurred before or at about the same time as the studied practices. In addition, if available, secondary data of repeated surveys or trend data analysis will be used to strengthen the causality by ensuring temporal criteria .This study will increase understanding of the effectiveness of policy interventions to address the structural determinants of breastfeeding, namely national policies on maternity protection and the Code. By assessing the potential impact of these policies and bottlenecks for successful implementation through the perspective of various stakeholders, including policymakers, implementors, and beneficiaries, this study will build an evidence base that can be used to advocate for stronger policy adoption and enforcement in study countries and beyond.


Pharmacoepidemiological research about antibiotics is supported by the World Health Organization (WHO), but data regarding antibiotic prevalence based on actual prescriptions and dosing patterns are insufficient. The aims were: (i) To estimate the prevalence and prescribed daily dose (PDD) of antibiotics in outpatients from Mexico City and (ii) to compare the PDD against the defined daily dose (DDD), as established by the WHO. The study included 685 prescriptions of antibiotics selected randomly from five geographical zones of Mexico City. Drug, dose, frequency, and duration of treatment were obtained from each prescription. PDD values of each antibiotic drug were calculated as the average of the daily doses. Sub-use and overuse were determined by the ratio PDD/DDD for each prescription. The most prescribed antibiotics to outpatients from Mexico City included six pharmacological groups: quinolones (28%), penicillins (23%), cephalosporins (17%), macrolides (10%), lincosamides (9%), and sulfonamides (4%). Both overuse and sub-use were high . In conclusion, most of the antibiotics with a high prevalence of prescription also had a high rate of either sub-use or overuse, with prescribed doses that significantly differ with their corresponding DDD. The dosing variation has important clinical implications since it denotes low prescription control. Antibiotic therapy has marked a threshold in modern medicine and the way infectious diseases are treated, but these drugs have represented a challenging issue since the beginning of their use in big populations, and therefore, global policies have taken place to reduce the actions that lead to an incorrect use ,2. As anIt seems that the best way to enclose antibiotic-related problems is to have a strict drug control ,6,13, anHowever, there is not a registry of any control in prescription, so there is still a long way to go until we could achieve good practices related to antibiotic use. In fact, there is poor evidence of antibiotic utilization in Mexico , and mosAntibiotic prescription is widespread in Mexico City and includes the utilization of 12 pharmacological groups . The mosThe PDD divided by the DDD was calculated to determine the discrepancy of dose utilization from a statistical point of view . We consp < 0.05). Some antibiotics had large discrepancies , including cefuroxime, clarithromycin, amoxicillin plus clavulanic acid, azithromycin, and lincomycin, while other antibiotics had small discrepancies , including levofloxacin, cefalexin, clindamycin, gentamicin, and fosfomycin.Prescription discrepancies related to doses are also described by their normalized values of PDD with respect to DDD . The norThere are only very few studies that assess the antibiotic prescription in Mexico ,20. For In this study, quinolones represented the pharmacological antibiotic group with the greatest prescription prevalence in Mexico City. This fact differs from other countries where penicillins are the most prescribed pharmacological group, as it is the case in Egypt , althougThe use of quinolones as the most prescribed drugs gives an interesting and overt pattern to future studies to relate the diagnosis with the pharmacoepidemiological results of prevalence in the outpatient setting, since it is necessary to further analyze the consequences of prescribing a given antibiotic for a determined infection. Pharmacoepidemiology establishes a specific methodology for this kind of study called prescription–indication ,28,29, wThe variability of prescription among the different pharmacological groups in this study was shown to be relatively low, as 7 out of 10 prescribed antibiotics in Mexico City belong to either a quinolone or beta-lactams , which is certainly a highlight when comparing our results to other regions around the world where diversity in prescription is wider . HoweverThe assessment of antibiotic utilization and the presence of problems related to them are difficult aspects to quantify. Nevertheless, the research in this subject should consider factors that involve both the prescriber and the patient and, in this sense, the differences that may be observed in antibiotic dosing after the statistical comparison of the PDD and the theoretical DDD might explain the point of view of the factors mentioned herein. For example, among general practitioners, several factors are associated with the antibiotic prescribing volume, including appointment duration, training practice, as well as the prescriber’s age and sex . On the Indeed, drug utilization has become a crucial matter regarding the assessment of antibiotics, especially when doses are considered into the evaluation, since it allows us to take adequate strategies into account to encourage health promotion to decrease and avoid antibiotic-related problems. Particularly, bacterial resistance has been identified as a globally recognized problem in public health related to the incorrect use of antibiotics ,26,32. BThe prescriptions did not include the diagnosis since it is not a requirement in the Mexican regulation and because of that, it was not possible to identify further reasons about the discrepancies between PDD and DDD, for example, if an antibiotic was prescribed for an indication different to the main one or if the patient was being treated concomitantly with other medications or was in a medical condition that oriented the physician to reduce the antibiotic daily dose .Antibiotic use, including prescription and administration, must reach adequacy as a key factor to avoid bacterial resistance. However, the correct utilization represents itself as a complex problem that involves the right antibiotic selection, proper posology, therapeutic adherence, and patient compliance. There is an urgent need in Mexico to continue researching about antibiotics to create a solid reference regarding the pharmacoepidemiology of antibiotics that aid future health decision-making processes . Thus, sThis study is part of the initial efforts in giving an overview and solution to antibiotic utilization in Mexico, focused on the outpatient population through the application of a formal pharmacoepidemiological methodology to get robust outcomes about drug utilization patterns and foresee better prescription practices that decrease adverse effects, inefficacy, and strongly avoid bacterial resistance. Nonetheless, considering the massive consumption of antibiotics, future studies are highly needed, especially those that explore the prevalence of antibiotics based on prescriptions in a multicentric fashion, since this ensures that the medication was actually dispensed to the patient, not in retailing sales, but also to encourage the research that explores the relationship between the antibiotic spectrum with the prescription  , the preThis study was retrospective, cross-sectional, descriptive, and observational, with a sample based on prescriptions from outpatients, and all data were retrieved from community pharmacies. There are not available databases in Mexico. Therefore, for creating the first database, we applied a sampling technique creating clusters to be able to sample data from a huge geographic zone, such as Mexico City with more than 8 million inhabitants, this technique is also useful to avoid bias since all data are randomly obtained with the same probability to be chosen and considers the population density at the moment of data collection, so representativity is guaranteed. For this study, Mexico City was divided into five geographical zones , then, 25 community pharmacies along the city were selected from a predetermined list of pharmacies using a table of random numbers . We proceeded to data collection once the pharmacies were selected, prescriptions being our unit of analysis, it is important to mention that there is not an electronic record of prescriptions in Mexico so the pharmacy must store the prescription in a hard copy (printed on paper). Previously, we calculated a sample size according to the proportions formula and considering a 20% loss in case of illegibility of prescriptions, those with incomplete posology data or prescriptions different from antibiotics or pediatric patients. Thus, the calculus was a total of 685 prescriptions which were divided equally in the 25 community pharmacies (77 prescriptions per pharmacy).Regarding the inclusion criteria, they were prescriptions delivered by physicians or odontologists, from adult patients (older than 18 years old) and with at least one antibiotic. All prescriptions were selected using random numbers generated by a computer. In this way, we could ensure that all obtained data were from outpatients from Mexico City.The protocol of the present study complies with the national and international ethical aspects as well as applicable confidentiality laws in Mexico. The Committee of Ethics for Research of the Medical Research Center CEBECI Farmacología Clínica, Sociedad Civil approved the study (protocol number ICE-1506-NIF).We extracted the whole posology from the prescription, considering the drug, the quantity of drug per dosage form, frequency of administration, and duration of treatment as independent variables. Afterward, the drugs were classified according to the anatomical, therapeutical, and chemical (ATC) coding, as indicated by the WHO, and each code has been linked with its corresponding value of DDD published on the WHO website in 2018 .All DDD values were present in the WHO database except for the combination of sulphamethoxazole and trimethoprim, for which the value used as DDD was the one of maximum daily dose, as published in the information to prescribe (ITP), this is in the technical document from the main pharmaceutical laboratory that manufactures the medication containing this drug combination . PDD was calculated as the product of the antibiotic dose per dosage form by the number of dosage forms indicated in each administration by the frequency in a day. This calculus was made for each one of the prescriptions of the same drug, and then the corresponding PDD mean was obtained and considered for the general statistical analysis.The antibiotic prevalence was calculated through the division of the number of prescriptions by the total number of prescriptions. The same analysis was made for the diverse pharmacological groups, and the results are presented as prevalence values and 95% confidence interval. According to Kolmogorov–Smirnov tests, most data did not have a normal distribution, and the results are presented as the median (percentile 25–percentile 75).The pharmacoepidemiological assessment of prescribed doses of antibiotics was done by comparing the values of medians of PDD for each ATC class against its corresponding DDD using the Wilcoxon signed-rank test. The ratio between PDD and DDD was also calculated for each prescription, to determine sub-use (defined as PDD/DDD < 1.0) or overuse (defined as PDD/DDD > 1.0) for all prescribed antibiotics. p < 0.05 was considered as significant.The doses were also normalized taking the PDD minus the DDD as the numerator and the DDD being the formula (PDD-DDD)/DDD and considering that there is no discrepancy between PDD and DDD if the value is zero as the denominator. The Wilcoxon signed-rank test was also performed comparing a value of zero against the median of the normalized value for each ATC class. The statistical analysis was performed using SPSS version 21.0 and a value of The analyzed prescription in this pioneering study in Mexico shows that most of the antibiotics with a high prevalence of prescription also had an elevated rate of either sub-use or overuse. The statistical value of the DDD reported by WHO when comparing to PDD does not necessarily reflect the quality of prescription, since the dose may vary according to the diagnosis and particular characteristics from the patient ,38, but The present study shows the utilization of antibiotics in an outpatient setting by the analysis of doses. Mexico does not have any record about this type of data, which is useful to prescribers for whom the knowledge in pharmacoepidemiological utilization tendencies may be a coadjutant daily clinical decision-making process related to prescription. This study and some others of the same class might justify to the Mexican health authorities the application of public strategies towards both health providers and patients to increase the rational use of antibiotics, and in this way, to contribute to the efforts that are globally taking place in other regions.