Full breastfeeding protection against common enteric bacteria and viruses: Results from the MAL-ED cohort study

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Study Justification:
– Breastfeeding is known to reduce the risk of enteropathogen infections, but the specific protection against different enteropathogens is not well understood.
– This study aimed to estimate the association between full breastfeeding and the detection of enteropathogens, focusing on 11 specific pathogens.
– The results of this study would provide valuable insights into the protective effects of full breastfeeding against enteric bacteria and viruses.
Study Highlights:
– The study included 2145 newborns from 8 sites, with breastfeeding and enteropathogen data available for 1712 infants up to 6 months of age.
– Logistic regression and survival analysis were used to estimate the risk of enteropathogen detection and the timing of first detection.
– Infants with a higher proportion of days of full breastfeeding within the preceding 30 days were less likely to have certain bacterial pathogens detected in their stool.
– Full breastfeeding was associated with delays in the first detection of certain bacterial and viral pathogens.
– These findings highlight the importance of exclusive or full breastfeeding during the first 6 months of life for optimal early health.
Recommendations for Lay Reader and Policy Maker:
– Encourage and support exclusive or full breastfeeding for the first 6 months of life to reduce the risk of enteric infections.
– Promote awareness among parents and caregivers about the benefits of breastfeeding in protecting infants against enteropathogens.
– Provide education and resources to help mothers initiate and sustain breastfeeding, including addressing barriers and challenges.
– Strengthen policies and programs that support breastfeeding, such as maternity leave policies, workplace accommodations, and community support networks.
Key Role Players:
– Healthcare professionals: Provide guidance and support to mothers regarding breastfeeding practices.
– Community health workers: Educate and raise awareness about the benefits of breastfeeding.
– Policy makers: Develop and implement policies that support breastfeeding, including maternity leave and workplace accommodations.
– Non-governmental organizations: Provide resources and support for breastfeeding promotion and education.
– Research institutions: Conduct further studies to explore the long-term effects of breastfeeding on child health and development.
Cost Items for Planning Recommendations:
– Breastfeeding education and promotion materials: Printing and distribution costs.
– Training programs for healthcare professionals and community health workers: Staff salaries, training materials, and logistics.
– Support services for breastfeeding mothers: Staff salaries, counseling services, and breastfeeding support groups.
– Policy development and implementation: Administrative costs, research and data collection, and policy advocacy efforts.
– Monitoring and evaluation: Data collection and analysis, staff salaries, and reporting.
– Research funding: Grants and resources for further studies on breastfeeding and child health.
Please note that the cost items provided are general categories and may vary depending on the specific context and implementation strategies.

The strength of evidence for this abstract is 8 out of 10.
The evidence in the abstract is strong, but there are some areas for improvement. The study design is robust, with a large sample size and a multicenter cohort study design. The statistical analysis methods used are appropriate, including logistic regression and survival analysis. The abstract provides clear results, indicating that full breastfeeding is associated with a lower likelihood of detecting certain enteric pathogens and delays in their first detection. However, to improve the evidence, it would be helpful to include more specific information about the statistical significance of the findings, such as p-values or confidence intervals. Additionally, providing more details about the study population, including demographic characteristics and potential confounding factors, would enhance the strength of the evidence.

Background: Breastfeeding is known to reduce the risk of enteropathogen infections, but protection from specific enteropathogens is not well characterized. Objective: The aim was to estimate the association between full breastfeeding (days fed breast milk exclusively or with nonnutritive liquids) and enteropathogen detection. Methods: A total of 2145 newborns were enrolled at 8 sites, of whom 1712 had breastfeeding and key enteropathogen data through 6 mo. We focused on 11 enteropathogens: adenovirus 40/41, norovirus, sapovirus, astrovirus, and rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp., and typical enteropathogenic E. coli as well as entero-aggregative E. coli, Shigella and Cryptosporidium. Logistic regression was used to estimate the risk of enteropathogen detection in stools and survival analysis was used to estimate the timing of first detection of an enteropathogen. Results: Infants with 10% more days of full breastfeeding within the preceding 30 d of a stool sample were less likely to have the 3 E. coli and Campylobacter spp. detected in their stool (mean odds: 0.92-0.99) but equally likely (0.99-1.02) to have the viral pathogens detected in their stool. A 10% longer period of full breastfeeding from birth was associated with later first detection of the 3 E. coli, Campylobacter, adenovirus, astrovirus, and rotavirus (mean HRs of 0.52-0.75). The hazards declined and point estimates were not statistically significant at 3 mo. Conclusions: In this large multicenter cohort study, full breastfeeding was associated with lower likelihood of detecting 4 important enteric pathogens in the first 6 mo of life. These results also show that full breastfeeding is related to delays in the first detection of some bacterial and viral pathogens in the stool. As several of these pathogens are risk factors for poor growth during childhood, this work underscores the importance of exclusive or full breastfeeding during the first 6 mo of life to optimize early health.

The primary goal of the MAL-ED study was to describe relations among enteric infections, diet, gut function, and the growth and development of infants, and a detailed description (24) and primary results are described elsewhere (25–27). Briefly, infants were enrolled at 8 sites in low- and middle-income settings and followed to 24 mo of age. Inclusion criteria were enrollment within 17 d of birth (median: 7 d; IQR: 4–12 d), born from a singleton pregnancy to a mother at least 16 y of age, birth weight or enrollment weight >1500 g and no major morbidities, and with a family planning to stay in the community for at least 6 mo. Each site chose a target for enrollment with the aim to have data on approximately 200 children per site at 24 mo. Enrollment was staggered over 2 y. The analyses presented here were restricted to the period from birth to 6 mo, covering the recommended period of exclusive breastfeeding. Households were visited twice weekly to inquire about illness symptoms since the prior visit (28). Stools were collected when mothers reported diarrhea and also collected monthly when children were considered free of diarrhea (separated from symptoms by at least 2 d) (28). The original study protocol utilized standard techniques to identify enteropathogens in stools, but then quantitative PCR using custom-designed TaqMan Array Cards (ThermoFisher) was used to re-analyze the stool samples for the presence of 29 enteropathogens (29–31). Here, we focus on the pathogens that accounted for the majority of attributable diarrhea in the first year of life (29): adenovirus 40/41, norovirus, sapovirus, astrovirus, rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp. (pan-genus), typical enteropathogenic E. coli (tEPEC), Shigella, and Cryptosporidium. We additionally considered entero-aggregative E. coli (EAEC) as it was both frequently detected and associated with growth deficits (26). Three countries (Brazil, Peru, and South Africa) had national rotavirus vaccinations at the time of data collection and were excluded from models of rotavirus because vaccination (at ∼2 and 4 mo of age) alters the likelihood of infection and/or detection and thereby any association with breastfeeding. Following Rogawski McQuade et al. (32), pathogen presence was defined as a qPCR cycle threshold of <35. Coinfections were also identified when more than 1 pathogen was detected in a stool sample. An interview at enrollment asked for specific details about the timing of breastfeeding initiation, whether or not colostrum was given, and prelacteal feeding (33). During the twice-weekly surveillance visits, mothers were asked if they had breastfed the child on the previous day and whether or not other liquids or foods had been given and what foods or liquids they were. Infants who were fully breastfed were identified based on these reports. For analysis, we considered the proportion of visits that a child was fully breastfed in 2 ways. First, to determine whether full breastfeeding was associated with a lower likelihood of pathogen detection in stool, we focused on the 30-d period prior to each stool sample collection. We also continued to disaggregate time from the stool collection back to the child's enrollment in 30-d periods to evaluate period-specific associations with full breastfeeding. Second, to determine whether full breastfeeding was associated with delays in the detection of pathogens, we considered time since birth that a child was fully breastfed (exclusive of prelacteal feeding). Full breastfeeding as an exposure variable was described either as the proportion of visits between birth and when a given stool was collected or the proportion of time from birth to the age when a pathogen was first detected. In both cases, the proportion of time was multiplied by 10 to give a per 10%-time interpretation to coefficients. At enrollment, and then monthly, anthropometric assessments (weight, length) were performed by trained workers using standardized protocols (34). Building on risk factors associated with specific pathogens (35–39), we controlled for child sex and weight-for-age z score (WAZ) at enrollment, the latter evaluated here as a continuous z score following the WHO growth standards (40). Some pathogen detections were also associated with aspects of lower household socioeconomic status (SES) (35, 37, 41), which was evaluated by questionnaire twice yearly. The SES metric is described in detail elsewhere (42), but briefly was defined using an index (with a range of 0, low SES, to 1, high SES) that included access to improved water and sanitation, maternal education, average monthly household income, and a range of assets or household attributes (e.g., household crowding). For the purposes of these analyses, the mean SES index across all sampling points was multiplied by 10 to examine a per 10% change in SES. In sensitivity analyses, the raw components of the metric were also examined to determine whether they had greater explanatory power than the combined construct. The study was conducted in accordance with the Declaration of Helsinki. Field workers explained the study protocol and obtained written informed consent from a parent or guardian for the children enrolled in the original study. The study was approved by the following institutional review boards that correspond to each site and to collaborating institutions: Institutional Review Board for Health Sciences Research, University of Virginia, Charlottesville, VA, USA; the Committee for Ethics in Research, Universidade Federal do Ceara; National Ethical Research Committee, Health Ministry, Council of National Health in Brasília and Fortaleza—Brazil (Brazil site; BRF); Institutional Review Board, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; PRISMA Ethics Committee; Health Ministry, in Loreto, Peru (Peru site; PEL); Health, Safety, and Research Ethics Committee, University of Venda; Department of Health and Social Development, Limpopo Provincial Government, in Venda, South Africa (South Africa site; SAV); Medical Research Coordinating Committee, National Institute for Medical Research; Chief Medical Officer, Ministry of Health and Social Welfare in Haydom, Tanzania (Tanzania site; TZH); Ethical Review Committee, Aga Khan University (Pakistan site in Naushahro Feroze; PKN); Ethical Review Committee, icddr,b in Dhaka—Bangladesh (Bangladesh site; BGD); Institutional Review Board, Christian Medical College, in Vellore, India, and the Health Ministry Screening Committee, Indian Council of Medical Research (India site; INV); Institutional Review Board, Institute of Medicine, Tribhuvan University; Ethical Review Board, Nepal Health Research Council; and Institutional Review Board, Walter Reed Army Institute of Research in Bhaktapur, Nepal (Nepal site; NEB). Site-specific descriptive characteristics of the study sample at enrollment were calculated, as well as site- and pathogen-specific distributions of child age at first detection. The proportion of visits at which full breastfeeding was reported was also calculated by site. Separate modeling approaches were used to address the following 2 questions. First, we hypothesized that full breastfeeding would be associated with a lower likelihood of pathogen detection in stool samples. To test this, a Bayesian multivariable logistic regression model was constructed for each pathogen, with the presence or absence of the pathogen in stool as the outcome. The proportion of visits with a report of full breastfeeding during the current month was the primary exposure variable. Also included were variables for the proportion of full breastfeeding during multiple prior 30-d periods (up to 120 d). Characterized in this way, we capture influences of current full breastfeeding and a history of earlier full breastfeeding. Covariates included infant sex, WAZ at enrollment, household SES, and the count of other pathogens detected in the same stool. Infant age (months) at stool collection was included in the model. Models were further adjusted for site and individual using random effects to account for repeated measurements (an error term to account for the correlation between measurements from the same individual). Second, we conducted a survival analysis to test the hypothesis that full breastfeeding would be associated with a delay in the time to first detection of a given pathogen. In this model, the proportion of time fully breastfed (proportion of visits from enrollment to any given stool sample) was treated as a time-varying variable (assuming a log-transformation of age) to account for potential changes with infant age in the association of full breastfeeding with first detection. Site was included as a frailty term, equivalent to a random effect in a linear regression to account for clustering in the repeated observations of each site, and covariates included sex, enrollment WAZ, SES, and the number of coincident enteropathogens. All analyses were conducted in R 4.1.0 (R Foundation for Statistical Computing).

The study “Full breastfeeding protection against common enteric bacteria and viruses: Results from the MAL-ED cohort study” provides important insights into the association between full breastfeeding and enteropathogen detection in infants. Here are some potential innovations that can be used to improve access to maternal health based on the study findings:

1. Breastfeeding Support Programs: Implement comprehensive breastfeeding support programs that provide education, counseling, and practical assistance to mothers. These programs can help mothers overcome challenges and ensure successful initiation and continuation of exclusive breastfeeding.

2. Community Health Workers: Train and deploy community health workers who can provide personalized support and guidance to mothers in their communities. These workers can offer breastfeeding education, address concerns, and provide ongoing support to promote exclusive breastfeeding.

3. Telehealth Services: Develop telehealth services that connect lactation consultants or breastfeeding specialists with mothers remotely. This allows mothers to receive expert guidance and support from the comfort of their homes, especially in areas with limited access to healthcare facilities.

4. Workplace Support: Advocate for workplace policies that support breastfeeding mothers, such as providing dedicated lactation rooms, flexible work schedules, and paid maternity leave. These measures can enable mothers to continue breastfeeding after returning to work.

5. Peer Support Groups: Establish peer support groups where breastfeeding mothers can connect, share experiences, and receive support from other mothers who have successfully breastfed their infants. These groups can provide a sense of community and encouragement, which can enhance breastfeeding practices.

6. Maternity Care Practices: Promote evidence-based maternity care practices that support breastfeeding, such as immediate skin-to-skin contact, rooming-in, and avoiding unnecessary supplementation with formula. These practices can facilitate early initiation and establishment of breastfeeding.

7. Health Education Campaigns: Conduct targeted health education campaigns to raise awareness about the benefits of exclusive breastfeeding and address common misconceptions or cultural barriers. These campaigns can help change societal attitudes and promote breastfeeding as the norm.

8. Integration of Services: Integrate breastfeeding support services within existing maternal and child health programs, such as antenatal care, postnatal care, and immunization clinics. This ensures that breastfeeding support is readily available and accessible to all mothers.

9. Mobile Applications: Develop user-friendly mobile applications that provide evidence-based information, practical tips, and personalized support for breastfeeding mothers. These apps can serve as a convenient resource for mothers seeking guidance and information.

10. Policy Advocacy: Advocate for policies at the national and international levels that prioritize and support breastfeeding as a key component of maternal and child health. This includes policies that protect and promote breastfeeding rights, regulate the marketing of breast milk substitutes, and allocate resources for breastfeeding support programs.

Implementing these innovations can help improve access to maternal health by promoting and supporting exclusive breastfeeding, which has been shown to have significant benefits for both infants and mothers.
AI Innovations Description
The recommendation based on the study “Full breastfeeding protection against common enteric bacteria and viruses: Results from the MAL-ED cohort study” is to promote and support exclusive or full breastfeeding during the first 6 months of life to improve access to maternal health.

The study found that infants who had a higher proportion of days of full breastfeeding within the preceding 30 days were less likely to have certain bacterial pathogens (enterotoxigenic Escherichia coli, Campylobacter spp.) detected in their stool. Additionally, a longer period of full breastfeeding from birth was associated with a later first detection of several bacterial and viral pathogens (E. coli, Campylobacter, adenovirus, astrovirus, rotavirus).

These findings highlight the importance of exclusive or full breastfeeding in reducing the risk of enteropathogen infections in infants. By promoting and supporting breastfeeding, particularly during the first 6 months of life, access to maternal health can be improved, leading to better health outcomes for both mothers and infants.

To implement this recommendation, healthcare providers and policymakers can:

1. Provide education and counseling to pregnant women and new mothers about the benefits of exclusive or full breastfeeding for maternal and infant health.
2. Offer lactation support and assistance to mothers to establish and maintain breastfeeding.
3. Create supportive environments in healthcare facilities, workplaces, and communities that enable mothers to breastfeed comfortably and without barriers.
4. Implement policies and programs that protect and support breastfeeding, such as maternity leave policies, workplace accommodations, and breastfeeding-friendly public spaces.
5. Collaborate with community organizations and stakeholders to raise awareness about the importance of breastfeeding and provide resources and support to mothers.

By implementing these recommendations, access to maternal health can be improved, leading to better health outcomes for both mothers and infants.
AI Innovations Methodology
The study you provided focuses on the association between full breastfeeding and the detection of enteropathogens in infants. To improve access to maternal health, here are some potential recommendations based on the findings of the study:

1. Promote and support exclusive breastfeeding: Encourage mothers to exclusively breastfeed their infants for the recommended period of 6 months. Provide education and resources to help mothers understand the benefits of exclusive breastfeeding in reducing the risk of enteropathogen infections.

2. Enhance breastfeeding support systems: Establish breastfeeding support groups and programs that provide guidance, counseling, and practical assistance to mothers. These support systems can help address challenges and provide encouragement to mothers who may face difficulties in breastfeeding.

3. Implement workplace policies: Advocate for workplace policies that support breastfeeding mothers, such as providing designated breastfeeding areas, flexible work schedules, and paid maternity leave. This will enable mothers to continue breastfeeding even after returning to work.

4. Community awareness campaigns: Conduct community-wide awareness campaigns to educate families, healthcare providers, and community leaders about the importance of breastfeeding and its role in improving maternal and infant health. These campaigns can help dispel myths and misconceptions surrounding breastfeeding and promote its benefits.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could be developed as follows:

1. Define the target population: Identify the specific population or community that will be the focus of the simulation. This could be a specific region, country, or a particular group of individuals.

2. Collect baseline data: Gather relevant data on the current status of maternal health and breastfeeding practices in the target population. This could include information on breastfeeding rates, prevalence of enteropathogen infections, healthcare infrastructure, and access to support services.

3. Develop a simulation model: Create a mathematical or computational model that simulates the impact of the recommendations on breastfeeding rates, enteropathogen infections, and overall maternal health. The model should take into account factors such as population size, demographic characteristics, healthcare resources, and the effectiveness of the recommendations.

4. Input data and parameters: Input the baseline data and parameters into the simulation model. This includes information on the current breastfeeding rates, prevalence of enteropathogen infections, and the expected impact of the recommendations on these factors.

5. Run simulations: Run multiple simulations using different scenarios and assumptions to assess the potential impact of the recommendations. This could involve varying factors such as the coverage and effectiveness of the breastfeeding support programs, the level of community engagement, and the availability of healthcare resources.

6. Analyze results: Analyze the simulation results to determine the projected impact of the recommendations on improving access to maternal health. This could include assessing changes in breastfeeding rates, reduction in enteropathogen infections, and improvements in overall maternal health indicators.

7. Validate and refine the model: Validate the simulation model by comparing the projected results with real-world data and observations. Refine the model based on feedback and additional data to improve its accuracy and reliability.

By following this methodology, policymakers and healthcare professionals can gain insights into the potential impact of implementing the recommendations on improving access to maternal health and make informed decisions on resource allocation and program implementation.

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