Early Antibiotic Exposure in Low-resource Settings Is Associated with Increased Weight in the First Two Years of Life

Journal of Pediatric Gastroenterology and Nutrition, Volume 65, No. 3, Year 2017

Interpretação

Objectives: The potential growth-promoting effects of antibiotics are not well understood among undernourished children in environments with high pathogen exposure. We aimed to assess whether early antibiotic exposure duration and class were associated with growth to 2 years of age across 8 low-resource sites in the MAL-ED birth cohort study. Methods: We followed 1954 children twice per week from birth to 2 years to record maternally reported antibiotic exposures and measure anthropometry monthly. We estimated the associations between antibiotic exposure before 6 months of age and weight-for-age and length-for-age (LAZ) z scores to 2 years. We assessed the impact of class-specific exposures and duration, and compared these results to effects of antibiotic exposures after 6 months of age. Results: Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years, whereas associations with length were less consistent across sites and antibiotic classes. Compared to unexposed children, 2 or more courses of metronidazole, macrolides, and cephalosporins were associated with adjusted increases in weight-for-age of 0.24 (95% confidence interval (CI): 0.04, 0.43), 0.23 (95% CI: 0.05, 0.42), and 0.19 (95% CI: 0.04, 0.35) from 6 months to 2 years, respectively. Conclusions: Antibiotic use in low-resource settings was most associated with the ponderal growth of children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy. Opportunities for rational and targeted antibiotic therapy in low resource settings may also promote short-term weight gain in children, although longer-term physical growth and metabolic impacts are unknown. The MAL-ED study was conducted between November 2009 and February 2014 at 8 sites in Dhaka, Bangladesh, Fortaleza, Brazil, Vellore, India, Bhaktapur, Nepal, Naushahro Feroze, Pakistan, Loreto, Peru, Venda, South Africa, and Haydom, Tanzania. Study design and methods have been previously described (23). Children were enrolled within 17 days of birth if their enrollment weight was ≥1500 g, they were not hospitalized, and they did not have severe or chronic conditions. Follow-up was conducted twice per week at home visits until 2 years of age to document illnesses, breast-feeding practices, and antibiotic use. Caregivers reported all oral or injected antibiotics given to their child. Medication packaging and prescriber documentation were used to confirm antibiotic use and class. Non-diarrheal surveillance stool samples were collected monthly and tested for 40 enteropathogens (24). Weight and length were measured monthly, and weight-for-age (WAZ) and length-for-age (LAZ) z scores were calculated using the 2006 WHO child growth standards (25). Length measurements from Pakistan were excluded due to poor data quality. Socioeconomic status was assessed biannually and summarized using the child’s average WAMI (Water, Assets, Maternal education, Income) score, which is based on monthly household income, maternal education, wealth measured by 8 assets, and access to improved water and sanitation (26). All sites received ethical approval from their respective governmental, local institutional, and collaborating institutional ethical review boards. Written, informed consent was obtained from the caregiver of each child. Assessment of antibiotic use practices in the MAL-ED cohort has been previously described (22). A new antibiotic course was defined after 2 antibiotic-free days, assuming antibiotics were not received on the 2% of days with missing surveillance information. Diarrhea was defined as maternal report of 3 or more loose stools in 24 hours or at least 1 loose stool with visible blood (27). Respiratory illness was defined as cough or shortness of breath, and was considered an acute lower respiratory infection if accompanied by fieldworker-determined rapid respiratory rate (27). Fever and vomiting were caregiver reported. We used multivariable linear regression to estimate the association between antibiotic use in the first 6 months of life and monthly WAZ and LAZ from 6 to 24 months of age. Antibiotic exposure was modeled as a continuous measure of duration in days from 0 to 5 months of age and as a categorical variable by number of courses received to assess the potential for a nonlinear dose-response. We also stratified antibiotic effects by sex and site. Generalized estimating equations with robust variance were used to account for correlation between anthropometric measurements within children across time points. Confounding variables for adjustment included baseline characteristics and indications for treatment, and were selected by causal diagram (28) based on expert opinion and a previous analysis of factors associated with antibiotic use in MAL-ED (22). All analyses were adjusted for site, child sex, enrollment WAZ, WAMI score, crowding (people/room in household), maternal height, maternal education, and characteristics of the child’s first 6 months of life: percent days exclusively breast-fed; number of diarrhea episodes; days with fever, vomiting, and respiratory illness; and presence of acute lower respiratory infection, bloody stools, and hospitalization. Length models also included enrollment LAZ. We further explored the effects of class-specific antibiotic exposure use by modeling class-specific exposure as dichotomous (exposed to a specific class on at least 1 day vs not) and as a categorical variable by number of class-specific courses received, using the models above and additionally adjusting for other antibiotic class exposures to isolate class-specific effects. We also explored effect measure modification by malnutrition (stunted and underweight) at 6 months and pathogen burden from 0 to 5 months (presence of Campylobacter, enteroaggregative Escherichia coli, and Giardia, and average number of bacterial pathogens detected (24)) by including interaction terms between the exposures and these variables and estimating subgroup-specific effects. To assess the period during which the effects of early antibiotic use (before 6 months of age) were manifested, we estimated these effects on anthropometry at different age periods, from 0 to 5, 6 to 11, 12 to 17, and 17 to 24 months, adjusting for the child’s anthropometric z scores at the beginning of the age period. To compare early life exposures with later exposures, we used linear regression to estimate the effects of exposures from 6 to 24 months on cross-sectional WAZ and LAZ at 2 years. A child’s measurement closest to 24 months, between 23 and 25 months was considered their anthropometry at 2 years. Adjustment variables included the same baseline characteristics as above, including enrollment WAZ, enrollment LAZ (for length models only), illness burden as characterized above over the whole 2 years of follow-up, and antibiotic use in the first 6 months of life. Using these models with cross-sectional outcomes of WAZ and LAZ at 2 years, we demonstrated that the early life effects were insensitive to further statistical adjustment for illnesses and antibiotic use after 6 months of age.

AI Digest

Study Justification:

The study aimed to investigate the potential growth-promoting effects of antibiotics on undernourished children in low-resource settings with high pathogen exposure. This is important because the impact of antibiotics on growth in these specific conditions is not well understood.

Highlights:

– The study followed 1954 children from birth to 2 years of age across 8 low-resource sites.
– Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years.
– Associations with length were less consistent across sites and antibiotic classes.
– Multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy were most associated with increased weight.
– Rational and targeted antibiotic therapy in low-resource settings may promote short-term weight gain in children.

Recommendations for Lay Reader:

– The study found that giving antibiotics to children before 6 months of age in low-resource settings can lead to increased weight gain from 6 months to 2 years.
– However, the effects on length were not consistent across different sites and types of antibiotics.
– Antibiotics with broad spectrum and anaerobic activity had the strongest association with weight gain.
– This suggests that using antibiotics in a targeted and rational way in low-resource settings may help children gain weight in the short term, although the long-term effects on growth and metabolism are still unknown.

Recommendations for Policy Maker:

– Consider implementing guidelines for the rational and targeted use of antibiotics in low-resource settings to promote short-term weight gain in undernourished children.
– Provide training and education to healthcare providers in these settings to ensure appropriate antibiotic prescribing practices.
– Support research to further understand the long-term effects of early antibiotic exposure on growth and metabolism in undernourished children.
– Collaborate with international organizations and stakeholders to develop strategies for improving nutrition and reducing the need for antibiotics in low-resource settings.

Key Role Players:

– Healthcare providers in low-resource settings
– Policy makers and government officials
– International organizations and NGOs
– Researchers and scientists
– Community health workers

Cost Items for Planning Recommendations:

– Training and education programs for healthcare providers
– Development and dissemination of guidelines for antibiotic use
– Research funding for studying the long-term effects of early antibiotic exposure
– Collaboration and coordination efforts with international organizations and stakeholders
– Monitoring and evaluation of the implementation of guidelines and interventions

Força da prova

N/A

Resumo

The MAL-ED study was conducted between November 2009 and February 2014 at 8 sites in Dhaka, Bangladesh, Fortaleza, Brazil, Vellore, India, Bhaktapur, Nepal, Naushahro Feroze, Pakistan, Loreto, Peru, Venda, South Africa, and Haydom, Tanzania. Study design and methods have been previously described (23). Children were enrolled within 17 days of birth if their enrollment weight was ≥1500 g, they were not hospitalized, and they did not have severe or chronic conditions. Follow-up was conducted twice per week at home visits until 2 years of age to document illnesses, breast-feeding practices, and antibiotic use. Caregivers reported all oral or injected antibiotics given to their child. Medication packaging and prescriber documentation were used to confirm antibiotic use and class. Non-diarrheal surveillance stool samples were collected monthly and tested for 40 enteropathogens (24). Weight and length were measured monthly, and weight-for-age (WAZ) and length-for-age (LAZ) z scores were calculated using the 2006 WHO child growth standards (25). Length measurements from Pakistan were excluded due to poor data quality. Socioeconomic status was assessed biannually and summarized using the child’s average WAMI (Water, Assets, Maternal education, Income) score, which is based on monthly household income, maternal education, wealth measured by 8 assets, and access to improved water and sanitation (26). All sites received ethical approval from their respective governmental, local institutional, and collaborating institutional ethical review boards. Written, informed consent was obtained from the caregiver of each child. Assessment of antibiotic use practices in the MAL-ED cohort has been previously described (22). A new antibiotic course was defined after 2 antibiotic-free days, assuming antibiotics were not received on the 2% of days with missing surveillance information. Diarrhea was defined as maternal report of 3 or more loose stools in 24 hours or at least 1 loose stool with visible blood (27). Respiratory illness was defined as cough or shortness of breath, and was considered an acute lower respiratory infection if accompanied by fieldworker-determined rapid respiratory rate (27). Fever and vomiting were caregiver reported. We used multivariable linear regression to estimate the association between antibiotic use in the first 6 months of life and monthly WAZ and LAZ from 6 to 24 months of age. Antibiotic exposure was modeled as a continuous measure of duration in days from 0 to 5 months of age and as a categorical variable by number of courses received to assess the potential for a nonlinear dose-response. We also stratified antibiotic effects by sex and site. Generalized estimating equations with robust variance were used to account for correlation between anthropometric measurements within children across time points. Confounding variables for adjustment included baseline characteristics and indications for treatment, and were selected by causal diagram (28) based on expert opinion and a previous analysis of factors associated with antibiotic use in MAL-ED (22). All analyses were adjusted for site, child sex, enrollment WAZ, WAMI score, crowding (people/room in household), maternal height, maternal education, and characteristics of the child’s first 6 months of life: percent days exclusively breast-fed; number of diarrhea episodes; days with fever, vomiting, and respiratory illness; and presence of acute lower respiratory infection, bloody stools, and hospitalization. Length models also included enrollment LAZ. We further explored the effects of class-specific antibiotic exposure use by modeling class-specific exposure as dichotomous (exposed to a specific class on at least 1 day vs not) and as a categorical variable by number of class-specific courses received, using the models above and additionally adjusting for other antibiotic class exposures to isolate class-specific effects. We also explored effect measure modification by malnutrition (stunted and underweight) at 6 months and pathogen burden from 0 to 5 months (presence of Campylobacter, enteroaggregative Escherichia coli, and Giardia, and average number of bacterial pathogens detected (24)) by including interaction terms between the exposures and these variables and estimating subgroup-specific effects. To assess the period during which the effects of early antibiotic use (before 6 months of age) were manifested, we estimated these effects on anthropometry at different age periods, from 0 to 5, 6 to 11, 12 to 17, and 17 to 24 months, adjusting for the child’s anthropometric z scores at the beginning of the age period. To compare early life exposures with later exposures, we used linear regression to estimate the effects of exposures from 6 to 24 months on cross-sectional WAZ and LAZ at 2 years. A child’s measurement closest to 24 months, between 23 and 25 months was considered their anthropometry at 2 years. Adjustment variables included the same baseline characteristics as above, including enrollment WAZ, enrollment LAZ (for length models only), illness burden as characterized above over the whole 2 years of follow-up, and antibiotic use in the first 6 months of life. Using these models with cross-sectional outcomes of WAZ and LAZ at 2 years, we demonstrated that the early life effects were insensitive to further statistical adjustment for illnesses and antibiotic use after 6 months of age.

Materiais

Inovações

Based on the provided description, the innovation recommendation to improve access to maternal health could be:

1. Implementing targeted antibiotic therapy: Based on the findings of the study, there is a potential for rational and targeted antibiotic therapy in low-resource settings to promote short-term weight gain in children. This approach could be extended to maternal health, where targeted antibiotic therapy can be used to treat specific infections or conditions that affect maternal health, thereby improving overall outcomes.

It’s important to note that this recommendation is based on the specific findings of the study mentioned and may require further research and evaluation before implementation. Additionally, it is crucial to consider the potential risks and benefits of antibiotic use in maternal health and consult with healthcare professionals for personalized recommendations.

AI Innovations Description

The study titled “Early Antibiotic Exposure in Low-resource Settings Is Associated with Increased Weight in the First Two Years of Life” conducted by the MAL-ED birth cohort study aimed to assess the association between early antibiotic exposure and growth in undernourished children in low-resource settings. The study followed 1954 children from birth to 2 years of age across 8 sites in different countries.

The findings of the study suggest that antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years of age. Specifically, children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy showed the most significant increase in weight. The associations with length were less consistent across sites and antibiotic classes.

Based on these findings, a recommendation to improve access to maternal health and promote better growth outcomes in children could be to focus on rational and targeted antibiotic therapy in low-resource settings. This means ensuring that antibiotics are prescribed and administered appropriately, taking into consideration the specific needs and conditions of each child. By promoting responsible antibiotic use, healthcare providers can potentially enhance short-term weight gain in children, although the longer-term physical growth and metabolic impacts still need further research.

It is important to note that this recommendation should be implemented within the context of comprehensive maternal health programs that address other factors influencing maternal and child health, such as nutrition, hygiene, and access to healthcare services.

AI Innovations Methodology

Based on the provided information, the study titled “Early Antibiotic Exposure in Low-resource Settings Is Associated with Increased Weight in the First Two Years of Life” explores the potential growth-promoting effects of antibiotics on undernourished children in environments with high pathogen exposure. The study followed 1954 children from birth to 2 years across 8 low-resource sites in the MAL-ED birth cohort study. The objective was to assess the association between early antibiotic exposure duration and class with growth outcomes.

To improve access to maternal health, the following innovations could be considered:

1. Mobile Health (mHealth) Applications: Develop mobile applications that provide pregnant women with access to information, resources, and reminders related to maternal health. These apps can offer guidance on prenatal care, nutrition, and postnatal care, as well as reminders for appointments and medication adherence.

2. Telemedicine Services: Implement telemedicine services that allow pregnant women in remote or underserved areas to consult with healthcare professionals through video calls or phone consultations. This can help overcome geographical barriers and provide timely advice and support.

3. Community Health Workers: Train and deploy community health workers who can provide maternal health education, conduct regular check-ups, and facilitate referrals to healthcare facilities. These workers can bridge the gap between communities and healthcare systems, particularly in areas with limited access to healthcare facilities.

4. Maternal Health Vouchers: Introduce voucher programs that provide pregnant women with financial assistance to access maternal health services. These vouchers can cover costs related to prenatal care, delivery, and postnatal care, ensuring that women can afford essential healthcare services.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could include the following steps:

1. Define the target population: Identify the specific population that will benefit from the innovations, such as pregnant women in low-resource settings or underserved communities.

2. Collect baseline data: Gather data on the current state of maternal health access in the target population, including metrics such as the percentage of women receiving prenatal care, the distance to the nearest healthcare facility, and the availability of healthcare professionals.

3. Model the impact of innovations: Use modeling techniques, such as mathematical modeling or simulation models, to estimate the potential impact of the recommended innovations on improving access to maternal health. This can involve simulating scenarios with and without the innovations and comparing the outcomes.

4. Consider key variables: Take into account variables that may influence the impact of the innovations, such as population size, geographical factors, cultural beliefs, and existing healthcare infrastructure. Adjust the model accordingly to reflect these variables.

5. Analyze the results: Evaluate the simulated impact of the innovations on access to maternal health by comparing key indicators, such as the increase in the percentage of women receiving prenatal care or the reduction in travel distance to healthcare facilities.

6. Refine and iterate: Based on the results, refine the innovations and the simulation model if necessary. Iterate the process to further optimize the impact and identify any potential challenges or limitations.

By following this methodology, stakeholders can gain insights into the potential benefits and challenges of implementing the recommended innovations to improve access to maternal health.

Autor

Dima Health

Statistics:

Citations: 20

Identifiers:

DOI: 10.1097/MPG.0000000000001640

ISSN: 02772116

Research Areas:

Environmental, Food Security, Health System and Policy, Infectious Diseases, Maternal Access, Maternal and Child Health, Noncommunicable Diseases, Quality of Care, Social Determinants

Study Countries:

Multi-Countries, South Africa, Tanzania

Study Design:

Cohort Study, Cross Sectional Study

Study Approach:

Quantitative

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