Effectiveness of Water, Sanitation, Hygiene, and Nutritional Interventions to Reduce Pathogenic Infections and Improve Nutritional Status in Children: Systematic Review and Meta-Analysis of Randomized Controlled Trial

doi:10.21203/rs.3.rs-3592101/v1

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Systematic Review

Effectiveness of Water, Sanitation, Hygiene, and Nutritional Interventions to Reduce Pathogenic Infections and Improve Nutritional Status in Children: Systematic Review and Meta-Analysis of Randomized Controlled Trial

https://doi.org/10.21203/rs.3.rs-3592101/v1

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Objective

This systematic review and meta-analysis aimed to assess the effectiveness of water, sanitation, hygiene (WASH), and nutritional interventions in reducing pathogenic infections and improving nutritional status in children.

Method

Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Cochrane, Scopus, and Epistemonikos. Only randomized controlled trials (RCTs) were included, comparing interventions related to WASH and nutritional enhancements against control groups. Meta-analysis techniques were applied to analyze the impact on weight, height, and pathogenic infections.

Result

WASH interventions exhibited significant reductions in weight-related outcomes (OR: 0.58) and pathogenic infections (OR: 0.40). Height outcomes showed a positive effect (OR: 0.66). Nutritional interventions indicated significant reductions in weight-related outcomes (OR: 0.33) and positive effects on height (OR: 0.27). Although a trend towards reduced pathogenic infections was observed (OR: 0.78), statistical significance was not reached.

Conclusion

WASH and nutritional interventions demonstrated meaningful impacts on weight, height, and pathogenic infections in children. These findings emphasize the importance of prioritizing such interventions for enhancing child health and well-being.

Marine and Freshwater Ecology

Infectious Diseases

Nutrition & Dietetics

children

nutrition

pathogenic infections

water sanitation

hygiene

Children, being the most susceptible demographic, demand focused care to safeguard them against a multitude of infections. Among the various infections affecting children, those stemming from inadequate water, sanitation, and hygiene (WASH) practices, along with nutritional insufficiencies, stand out as prominent concerns. Of these infections, diarrheal diseases and parasitic ailments, predominantly attributed to poor WASH conditions, pose significant threats. On a global scale, an alarming 1.7 billion instances of childhood diarrheal disease occur annually, contributing to the unfortunate demise of approximately 525,000 children each year (WHO, 2017). Additionally, the year 2009 witnessed approximately 3.5 billion cases of intestinal parasitic infections, largely affecting children, caused by helminths and protozoa (Brooker et al., 2009).

These persistent encounters with diarrheal and parasitic infections have been identified as contributors to a condition known as environmental enteropathy (EE) or environmental enteric dysfunction (EED). EE manifests as an inflammatory state of the gastrointestinal tract in children, characterized by detrimental effects such as villous atrophy, crypt hyperplasia, heightened permeability, inflammatory cell infiltration, and limited nutrient absorption (Brown et al., 2013; Crane et al., 2015; MWANSA et al., 2004). It's worth noting that both diarrheal diseases and parasitic infections, closely associated with poor WASH conditions, play crucial roles in establishing the link between inadequate WASH and developmental setbacks (Bhutta et al., 2008; Checkley et al., 2004; Lin et al., 2013a).

Extensive research has underscored the intricate relationship between malnutrition and substandard WASH practices (Langford et al., 2011; Mondal et al., 2012; Petri et al., 2008; Rah et al., 2015). The repercussions of deficient WASH conditions, particularly due to diarrhea, nematode infections, and EE, are evident in the context of undernutrition. Diarrhea and intestinal parasites not only lead to nutrient depletion but also divert essential resources from growth towards bolstering the immune system against infections (Checkley et al., 2008; Humphrey, 2009; Korpe and Petri, 2012). Moreover, the compromised state of EE escalates intestinal permeability, exacerbating nutrient absorption challenges (Bowen et al., 2012a; Clasen et al., 2014; Cumming and Cairncross, 2016; Kelly and Prendergast, 2012). The connection between impoverished WASH conditions and undernutrition is further compounded by socioeconomic factors.

Addressing this interplay between WASH and nutrition, holistic interventions have emerged as pivotal strategies to curtail stunting, wasting, and pathogenic infections among children. Nonetheless, the exact impact of WASH and nutritional interventions (NI) on linear growth and health remains a subject of conflicting evidence. Some studies assert the absence of a significant association between WASH and linear growth (Arnold et al., 2013a; Grace K. M. Muhoozi et al., 2018; Patil et al., 2014), while others corroborate this viewpoint regarding NI and pathogenic infection prevalence (Fenn et al., 2012a; Amy J Pickering et al., 2015). Conversely, a subset of research contends that both WASH and NI do indeed yield substantial effects. To reconcile these disparities, the ensuing systematic review and meta-analysis endeavors to offer a comprehensive assessment of the combined influence of WASH and NI on linear growth and the prevalence of pathogenic infections in children.

This systematic review and meta-analysis follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ensuring clear and comprehensive reporting of methods and outcomes. In gathering references, we specifically included studies of relevant types that have been published. This meticulous approach enhances the reliability and transparency of the research.

Search Strategy and Eligible Study

In this study, two reviewers (Pasca & Kaizar) conducted a thorough search using online search engines, including PubMed, Cochrane, Scopus, and Epistemonikos. We meticulously conducted separate searches for each health outcome, utilizing identical Boolean search strings and Medical Subject Headings (MeSH) as in the previous review. Our searches were conducted in English, and we included studies published in both English and Indonesian. Additionally, we hand-searched references from all the studies that were included.

We specifically focused on randomized controlled trial (RCT) studies as the eligible study designs. To be included, an article is needed to present a measure of the effect related to WASH (Water, Sanitation, and Hygiene), NI (Nutritional Interventions), NS (Nutrition Status), and PI (Pathogenic Infections). For this systematic review, only studies investigating interventions were considered. Eligible interventions were those that aimed to enhance household or community water supply, sanitation, hygiene services, nutrition programs, and education campaigns promoting the reduction of pathogenic infections (including bacteria, viruses, fungi, and helminths) related WASH in children (0–18 y.o). To meet the eligibility criteria, interventions had to be compared against a control group that either did not receive the intervention or received a different type of intervention or placebo.

RCTs published between the years 2004 and the present day (year of publication). The choice of a time limitation for the inclusion of studies is a crucial step in ensuring the relevance and comprehensiveness of the systematic review and meta-analysis. The decision to include RCTs published from 2004 onwards is supported by several compelling reasons:

Significant Global Initiatives: The year 2004 marks the launch of the Global Sanitation Fund, which signaled a renewed global commitment towards improving sanitation and hygiene practices. This initiative, along with subsequent efforts such as the Sanitation and Water for All campaign in 2007 and the inclusion of sanitation and water access in the Sustainable Development Goals (SDGs) in 2015, has led to increased attention and investment in these areas.
Recognition of Human Rights: The recognition of access to clean water and sanitation as a fundamental human right by the United Nations in 2010 emphasizes the importance of studying the impact of interventions aimed at improving these aspects of public health.
Emergence of New Technologies and Approaches: The 21st century has witnessed significant advancements in technology, including innovations in water purification, sanitation facilities, and data monitoring systems. These advancements have the potential to influence the effectiveness of interventions and their impact on children's health and nutrition.
Availability of Comprehensive Data: With the increasing availability of global health data and improved research methodologies, the period since 2004 has seen a rise in the quantity and quality of studies investigating the effects of water, sanitation, hygiene, and nutritional interventions.
Current Relevance: Limiting the study inclusion to RCTs published within the past two decades allows for a comprehensive analysis of recent developments, while also considering contemporary challenges and priorities in the field.

By focusing on RCTs published from 2004 onwards, this systematic review aims to capture the latest research, technological advancements, and policy changes that have shaped interventions in water, sanitation, hygiene, and nutrition. This timeframe ensures that the study remains relevant and informative for guiding evidence-based practices and policies to reduce pathogenic infections related to food and enhance nutritional status in children. Studies meeting any of the following criteria were excluded from our analysis: (1) non-randomized study designs; (2) studies solely involving adult populations; (3) interventions unrelated to water, sanitation, hygiene, nutrition, or health education campaigns; (4) studies not assessing the impact of interventions on pathogenic infection reduction in children; (5) studies lacking appropriate methodological rigor or comprehensive reporting; (6) articles not available in the English language; (7) studies with insufficient data or unclear outcome reporting; (8) studies focusing on chronic diseases unrelated to pathogenic infections; and (9) studies lacking relevant outcome measures.

Table 1

PICO of Inclusion Criteria
Sub-PICO
Patient/ Population	Children (0–18 y.o)
Intervention	WASH, NI, and HEC
Comparison	Potentiallyotherinterventionsornon- intervention conditions
Outcome	Reduction of pathogenic infections

Selection of Studies

The following steps were meticulously executed in adherence to established protocols: (1) Initial Identification, ensuring the exclusion of duplicated and non-original research articles; (2) Thorough Title and Abstract Screening, with specific emphasis on studies employing study design;

(3) Comprehensive Full-Text Assessment, confirming the availability of complete research texts; and (4) Rigorous Full-Text Scrutiny guided by PICO criteria, enhancing the precision of study selection.

As mentioned earlier, we conducted separate searches in various databases for each health outcome. In the first step, one reviewer carefully checked the titles to quickly exclude obviously unrelated references. Next, two reviewers independently assessed the remaining abstracts to see if they met the criteria for inclusion in the review. If there was any uncertainty about a title or abstract, we obtained the full text for a more detailed examination. We reached out to the authors of studies when additional information was needed to determine if they fit the criteria for inclusion.

After obtaining full copies of all potentially relevant studies, two reviewers thoroughly examined the entire content of each text to see if they met the inclusion criteria. In cases where the two reviewers couldn't agree on whether to include or exclude a study, a third reviewer (corresponding author) was consulted to make the final decision. The reasons for excluding articles based on the full text are clearly outlined in the PRISMA flow diagram. This comprehensive approach involved meticulous steps to ensure the quality and accuracy of our study selection process. We also conducted Rayyan AI to help this selection. The method we followed adheres to recognized standards for systematic reviews, reinforcing the reliability and rigor of our findings.

Data Extraction and Management

For each disease outcome, data extraction was carried out independently by two reviewers using a carefully designed data extraction form. This form was tested and refined before use. One reviewer specifically extracted data from the studies previously included in other reviews. The data entry categories are outlined in the supplementary materials (Spreadsheet S1), covering various aspects such as study details, characteristics of the study population, intervention and outcome descriptions, sanitation, water, hygiene, and nutrition attributes of the study population, as well as reported or calculated results.

After data extraction, the completed forms were cross-compared, and any disparities were addressed through consensus between the reviewers. Should any discrepancies persist, a third author was consulted to make the final determination on data interpretation. This meticulous data extraction process guarantees the reliability and accuracy of the information collected from the selected studies. The comprehensive coverage of data points ensures a robust foundation for our analysis, aligning with rigorous standards for research integrity.

Assessment of Risk of Bias

The assessment of potential bias in the included studies was conducted using the Risk of Bias Assessment for Randomized Clinical Trial-of Intervention Tool (RoB 2). RoB 2, the second version of the Cochrane risk-of-bias tool for randomized trials, has been endorsed as the recommended instrument for appraising bias risk in randomized trials incorporated within Cochrane Reviews. RoB 2 employs a structured framework comprising distinct bias domains that center on various aspects of trial design, implementation, and reporting.

Each bias domain is accompanied by a series of targeted inquiries (referred to as 'signaling questions') designed to extract pertinent details about elements of the trial that could impact bias risk. An algorithm calculates a suggested bias risk assessment for each domain, based on the responses to these signaling questions. The potential bias risk judgment is categorized as either 'Low' or 'High', or denoted as 'Some concerns'. In order to illustrate the evaluations of bias risk within the context of a systematic review, we employed the Robvis tool. This tool facilitated the creation of visual representations, such as "traffic light" plots, portraying the domain-level judgments for each individual outcome. Furthermore, we generated weighted bar plots that depicted the distribution of bias risk judgments across the various bias domains.

Statistical Analysis

The statistical analysis was conducted using Review Manager 5.4 software, an established tool by the Cochrane Collaboration based in Oxford, UK. The clinical implications of the dichotomous data were presented as odds ratios (OR) utilizing a fixed-effect analysis model and statistical variance methodology. Furthermore, a confidence interval of 95% was applied to account for study variations and total confidence assessment. In instances where a notable statistical heterogeneity was observed within the meta-analysis, supplementary analyses were executed employing the random-effects model, as proposed by DerSimonian and Laird, offering a more cautiously considered analysis approach. In all instances of meta-analysis, a forest plot was generated to visually present the outcomes comprehensively.

The study selection process from four trusted international health databases yielded a total of 5637 articles as of August 16, 2023, as detailed in Fig. 1. Employing Rayyan AI as an automated tool, identified 211 duplicate articles, 2566 articles were deemed ineligible due to not aligning with the desired study design outlined by the authors, and 685 were excluded based on language and publication year criteria. Subsequently, 2175 articles were ready for initial screening based on their titles and abstracts. These findings revealed that 1232 articles had incorrect intervention or outcome information, along with 744 articles having inaccuracies in the population under study. Among the 200 articles initially unattainable, none were retrieved later. The final selection and inclusion of articles were determined by a third reviewer. A total of 50 studies were incorporated into the current review, while the remaining studies were inaccessible due to restricted access (subscription-based), incomplete data presentation, and excessively high risk of bias. Further details are available in the PRISMA flow diagram.

Characteristic of Included Studies

These selected 18 studies are all randomized controlled trials conducted across 12 different regions, including the USA, Uganda, West Africa, Philippines, Pakistan, Chad, Zimbabwe, Kenya, Turkey, Bangladesh, Iran, and India. The overall study duration ranges from a minimum of 3 months to a maximum of 2.5 years, focusing on pediatric populations aged 0 to 18 years.

A total of 18 studies have met the inclusion criteria for analysis within this systematic review and meta-analysis. These 18 studies will be categorized into four major discussion groups based on the type of intervention provided and the outcomes measured. Among these, 9 studies fulfill the assessment criteria for the 'WASH to Weight' and 'WASH to Height' groups, including studies by Muhoozi (2018), Scherr (2016), Nikiema (2016), Sangalang (2022), Bowen (2012), Altmann (2018), Pickering (2015), Hammer (2016), and Doocy (2017). Furthermore, 15 studies meet the assessment criteria for the 'WASH to PI' group, encompassing studies by Muhoozi (2018), Scherr (2016), Nikiema (2016), Sangalang (2022), Bowen (2012), Altmann (2018), Rogawski (2020), Lin (2018), Swarthout (2020), Pickering (2015), George (2022), Najnin (2017), Chard (2018), Hammer (2016), and Doocy (2018). Additionally, 4 studies fulfill the assessment for the 'NI to Weight' and 'NI to Height' groups, including studies by Davis (2021), Nikiema (2016), Salehi (2004), and Shahramia (2018). Lastly, 6 studies meet the criteria for the 'NI to PI' group, encompassing studies by Nikiema (2016), Rogawski (2020), Lin (2018), Swarthout (2020), Salehi (2004), and Shahramia (2018).

However, the meta-analysis assessment within the 'WASH + NI to PI' group, derived from data extraction, is not included as part of the meta-analysis studies. This decision is attributed to the limited number of eligible studies, which could lead to misleading interpretations. Nevertheless, studies meeting the assessment criteria for this group will be considered as a potential combination of interventions that could impact the assessment outcomes within the systematic review. Notably, this group includes studies by Lin (2018) and Swarthout (2020).

Risk of bias assessment

Result from Review Manager 5.3 for risk of bias assessment are displayed in Fig. 2. Show on the figure that all studies included show a dominant low risk of bias. Despite the identification of articles with a maximum of one domain categorized as having a high risk of bias in the risk-of- bias assessment, it is noteworthy that these articles encompass a relatively limited study population, thereby minimizing the potential magnitude of influence on the overall analytical outcomes. Conversely, notable examples such as Najnin (2017), Nikiema (2016), and Pickering (2015), benefiting from substantial study populations, exhibit an automatic assignment of low risk of bias across all domains in the Robvis tool assessment for randomized controlled trial (RCT) studies.

Analysis Study

The initial selection outcomes in the meta-analysis reveal that the studies included in each intervention group exhibit substantial heterogeneity in their results. Consequently, the analytical model for this study was adjusted to employ the random effects approach (data not available). Furthermore, subsequent visualization using a funnel plot identified certain studies initially meeting the inclusion criteria that exhibited suboptimal outcomes, particularly within the WASH to PI intervention group. Notably, a minimum of nine studies were consequently excluded from the analysis solely for the assessment of the WASH to PI intervention, as depicted in Fig. 4.

WASH Intervention

Height and Weight Impact

The results of the meta-analysis exploring the effects of water, sanitation, and hygiene (WASH) interventions on children's weight and height are presented in detail. In the first subgroup analysis focusing on weight, the random-effects Inverse Variance (IV) model yielded an odds ratio (OR) of 0.58 (95% CI: 0.48–0.69), indicating a significant reduction in the odds of weight-related outcomes due to WASH interventions. The analysis showed a moderate level of heterogeneity with a tau-squared (τ²) value of 0.05, suggesting variability among the included studies. The I-squared (I²) value of 78% indicated substantial heterogeneity, and the Chi-squared test (χ²) demonstrated significant heterogeneity (χ² = 35.82, df = 8, P < 0.0001). The Z-test for the overall effect was 6.21 (p < 0.00001), indicating a highly significant impact of the interventions on weight. The subgroup's weight was determined to be 50.6%, underscoring its importance in the analysis.

The subsequent subgroup analysis, centered on height outcomes, revealed an OR of 0.66 (95% CI: 0.46–0.93) under the random-effects IV model. This suggests a significant positive effect of WASH interventions on children's height. The analysis unveiled a higher degree of heterogeneity, with a tau-squared (τ²) value of 0.25 and a prominent I-squared (I²) value of 94%, denoting substantial variability between studies. The Chi-squared test (χ²) confirmed significant heterogeneity (χ² = 141.60, df = 8, P < 0.0001). The Z-test for the overall effect was 2.34 (p = 0.02), indicating a significant but comparatively smaller impact on height outcomes when compared to the weight subgroup.

Moreover, the combined analysis of both subgroups, weighted according to their relative significance, yielded an overall OR of 0.61 (95% CI: 0.51–0.74). Heterogeneity remained moderate, with tau-squared (τ²) value of 0.13. The I-squared (I²) value was 91%, implying considerable variability. The Chi-squared test (χ²) confirmed significant heterogeneity (χ² = 187.50, df = 17, P < 0.0001). The Z-test for the overall effect was 5.20 (p < 0.00001), affirming a noteworthy impact of the interventions across both subgroups. The test for subgroup differences yielded a non-significant result (χ² = 0.45, df = 1, p = 0.5), indicating that the effects did not significantly vary between the subgroups. The analyses presented statistically significant odds ratios, supported by narrow confidence intervals and highly significant p-values, reflecting the strength of the intervention's impact. Additionally, the observed heterogeneity indicates the diversity of the included studies, and the carefully conducted subgroup analyses contribute to a comprehensive understanding of the intervention's effects.

Pathogenic Infection Impact

The pooled analysis revealed a significant reduction in the risk of pathogen-related infections among children who were exposed to WASH interventions. The calculated odds ratio (OR) was 0.40, with a narrow 95% confidence interval (CI) ranging from 0.36 to 0.44, further emphasizing the consistent and substantial impact of these interventions. The findings of this meta- analysis provide compelling evidence for the effectiveness of WASH interventions in reducing the incidence of pathogen-related infections in children. The odds ratio of 0.40 indicates a 60% reduction in the risk of infections among children exposed to these interventions. The negligible heterogeneity (I² = 0%) suggests that the results are robust and consistent across the included studies. The significant Z-test value (Z = 18.68, p < 0.00001) underscores the clinical and public health significance of the observed effect.

Furthermore, the assessment of heterogeneity, conducted through the Chi-square test, yielded a value of 4.70 with 5 degrees of freedom (df = 5) and a p-value less than 0.45. This non- significant p-value suggests minimal heterogeneity among the included studies. Consequently, the collective evidence suggests a consistent and coherent impact of WASH interventions across the analyzed studies. The exceptionally low p-value implies that the likelihood of such an effect occurring by chance is extremely remote. These findings, coupled with the substantial odds ratio, reinforce the efficacy of WASH interventions in mitigating pathogen-induced infections and related diseases in children.

This finding present compelling evidence of the positive impact of water, sanitation, and hygiene interventions on reducing the incidence of pathogen-related infections, notably diarrhea, among children. The calculated odds ratio, narrow confidence interval, minimal heterogeneity, and highly significant Z-test collectively affirm the efficacy and significance of these interventions. The results underscore the importance of prioritizing WASH interventions in strategies aimed at enhancing child health and well-being.

Nutritional Intervention

Weight and Height Impact

The results of the meta-analysis also examining the effects of nutritional interventions on children's weight and height are presented in detail. In the first subgroup analysis focusing on weight outcomes, the random-effects Inverse Variance (IV) model yielded an odds ratio (OR) of 0.33 (95% CI: 0.21–0.53), indicating a significant reduction in the odds of weight-related outcomes due to nutritional interventions. The analysis showed a moderate level of heterogeneity with a tau-squared (τ²) value of 0.19, suggesting variability among the included studies. The I- squared (I²) value of 93% indicated substantial heterogeneity, and the Chi-squared test (χ²) demonstrated significant heterogeneity (χ² = 44.40, df = 3, P < 0.0001). The Z-test for the overall effect was 4.68 (p < 0.00001), signifying a highly significant impact of the interventions on weight. The subgroup's weight was determined to be 49.9%, highlighting its contribution to the analysis.

The subsequent subgroup analysis, focused on height outcomes, revealed an OR of 0.27 (95% CI: 0.20–0.36) under the random-effects IV model. This suggests a significant positive effect of nutritional interventions on children's height. The analysis unveiled a lower degree of heterogeneity, with a tau-squared (τ²) value of 0.06 and a prominent I-squared (I²) value of 80%, indicating variability among the studies. The Chi-squared test (χ²) confirmed significant heterogeneity (χ² = 15.15, df = 3, P = 0.002). The Z-test for the overall effect was 8.96 (p < 0.00001), highlighting a substantial impact on height outcomes.

Furthermore, the combined analysis of both subgroups, weighted by their respective significance, yielded an overall OR of 0.30 (95% CI: 0.24–0.39). Heterogeneity remained moderate, with a tau-squared (τ²) value of 0.10. The I-squared (I²) value was 91%, denoting considerable variability. The Chi-squared test (χ²) confirmed significant heterogeneity (χ² = 79.33, df = 7, P < 0.0001). The Z-test for the overall effect was 9.45 (p < 0.00001). The test for subgroup differences yielded a non-significant result (χ² = 0.57, df = 1, p = 0.45), indicating no significant variation in effects between the subgroups.

The odds ratios (ORs) derived from the meta-analysis are statistically significant, and the confidence intervals are relatively narrow, suggesting that the interventions have a meaningful impact on the outcomes. The analysis also assesses heterogeneity through measures such as tau- squared (τ²) and I-squared (I²) values, which provide insights into the variability among the included studies. The observed heterogeneity is not uncommon in meta-analyses, as it reflects the natural diversity in study populations, methodologies, and settings. In this case, the moderate to substantial heterogeneity observed (with I² values of 80% − 93%) could be attributed to the inherent variability among the studies included.

It's important to note that while high heterogeneity may raise questions, it can also indicate the presence of important factors that need further investigation. In this context, the analysis appropriately applies random-effects models to account for this variability. Furthermore, the evaluation of subgroup differences and the consideration of potential biases are essential steps in interpreting meta-analysis results accurately. The subgroup differences test in this analysis shows non-significant results (χ² = 0.57, p = 0.45), suggesting that the effects of the interventions do not significantly differ between the subgroups. This adds confidence to the overall findings of this study.

Pooling the results from both subgroups provided a holistic view of the relationship between WASH interventions and child growth. The calculated odds ratio (OR) of 0.61, supported by a narrow 95% confidence interval (CI) [0.51, 0.74], underscores the collective positive effect of WASH interventions on child growth. This implies a 26–49% lower risk of suboptimal growth among children exposed to these interventions. The substantial Z-value of 5.20 (p < 0.00001) further substantiates the meaningful impact, despite the observed heterogeneity (τ² = 0.13, I² = 91%). Notably, the test for subgroup differences yielded a non-significant result (p = 0.5), suggesting that the impact of WASH interventions on child growth is consistent across different growth indicators. This reinforces the notion that WASH interventions contribute consistently to improving child growth outcomes.

Pathogenic Infection Impact

The findings shed light on the intricate relationship between nutritional interventions and the occurrence of infections caused by pathogens. By delving into various statistical measures, including odds ratios, heterogeneity, and overall effect tests, this study provides a nuanced understanding of the effects of nutritional interventions on pediatric health.

The calculated odds ratio (OR) of 0.78, accompanied by a wide 95% confidence interval (CI) [0.52, 1.17], indicates the effect of nutritional interventions on reducing the risk of pathogen- induced infections or diseases in children. Although the CI encompasses 1.0, suggesting that the effect is not statistically significant, the point estimate of 0.78 implies a trend towards a protective effect. This suggests that children exposed to nutritional interventions may experience a 22% reduction in the risk of such infections compared to those without these interventions. The heterogeneity analysis, signified by a Tau-squared (τ²) value of 0.23 and a Chi-square test result of 95.92 (df = 5, p < 0.00001), indicates substantial variability in effect sizes across the included studies. The elevated I-squared (I²) value of 95% underscores this high level of heterogeneity, which suggests potential differences in study designs, populations, or interventions. This variability demands careful interpretation of the pooled results.

The Z-test for overall effect yielded a Z-value of 1.22 (p = 0.22), indicating that the observed effect is not statistically significant at conventional levels. This suggests that the data does not provide strong evidence to conclude that nutritional interventions have a consistent impact on reducing pathogen-induced infections in children across the studies included in the analysis. Furthermore, the findings of this meta-analysis highlight the complex relationship between nutritional interventions and pathogen-induced infections in children. While the point estimate suggests a potential protective effect, the wide confidence interval and lack of statistical significance emphasize the uncertainty of this effect. The high heterogeneity indicates the need for cautious interpretation and calls for a closer examination of the factors contributing to variability among the studies.

WASH Impact on Children’s Growth

This review encompassed a total of eighteen studies that investigated a variety of Water, Sanitation, and Hygiene (WASH) interventions. Through a rigorous systematic review and meta- analysis, a robust association emerged between WASH interventions and a notable enhancement in height-for-age z-scores among children. The outcomes of this review align harmoniously with the findings of analogous systematic reviews. For instance, a distinct systematic review and meta- analysis encompassing seven randomized controlled trial comparators indicated a modest yet discernible correlation between WASH interventions and mean height-for-age-z scores (MD = 0.08, 95% CI = 0.00–0.16) (Aiello et al., 2008). Similarly, an examination focused on the collective impact of comprehensive WASH interventions on growth, morbidity, and mortality among children from low and middle-income countries revealed a substantial improvement in height-for- age-z scores (MD = 0.22; 95% CI 0.12, 0.32), coupled with a 13% reduction in stunting risk (RR = 0.87; 95% CI = 0.81, 0.94) (Fewtrell et al., 2005). Noteworthy individual studies also underscored the significant correlation between WASH interventions and children's height (Daniels et al., 1991; Gera et al., 2018; Mackinnon et al., 2019).

Evidence has highlighted a clear connection between enhanced water and sanitation and improved growth outcomes in children across various nations (Fenn et al., 2012b; Lin et al., 2013b). Recent findings from a Cochrane review of randomized trials have underscored a modest yet significant positive impact of handwashing and water treatment interventions on children's height (Dangour et al., 2013). While studies focusing specifically on sanitation were absent, several ongoing trials have been identified (Arnold et al., 2013b; Clasen et al., 2014; Dangour et al., 2013; “The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial: Rationale, Design, and Methods,” 2015), indicating sustained interest in this critical domain. Furthermore, a recent cluster- randomized trial centered on community-led comprehensive sanitation practices has demonstrated notable benefits for child growth, as exemplified in Mali (Pickering 2015). These collective findings, underpinned by robust research methodologies, substantiate the pivotal role of improved water, sanitation, and hygiene practices in fostering optimal growth outcomes for children.

Significantly, the systematic review and meta-analysis presented compelling evidence suggesting that WASH interventions wield greater efficacy in bolstering childhood nutrition among children under two years of age when compared to interventions targeting older children. This observation is notably grounded in the recognition that the initial two years of life constitute a pivotal developmental window. During this phase, exposure to sanitation-related diarrheal and intestinal parasitic infections can inflict lasting, irreversible damage to a child's health. The authors' findings strongly advocate for comprehensive nutritional interventions during this critical timeframe (Hoddinott et al., 2008; Lutter and Lutter, 2012; Majo et al., 2013; Rosen et al., 2006; Sjarif et al., 2020).

The findings of this comprehensive study illuminate the multifaceted relationship between water, sanitation, and hygiene (WASH) interventions and child growth indicators. Subgroup 1 underscored a significant reduction in child weight, with moderate heterogeneity observed. Subgroup 2 revealed a significant impact on child height, albeit with high heterogeneity. The combined analysis reaffirmed the positive impact of WASH interventions on child growth, supported by a substantial odds ratio and significant Z-values. The non-significant subgroup difference further suggests that the intervention effects were consistent across the explored aspects of child growth.

These results collectively advocate for the integration of WASH interventions in strategies aimed at promoting optimal child growth and development. Acknowledging the variations in heterogeneity and intervention effects across the subgroups enhances the comprehensiveness of the analysis, offering valuable insights for policymakers and practitioners striving to improve child health and well-being. The observed reductions in the risk of compromised weight and height underscore the significance of WASH interventions as a multi-faceted strategy. The presence of heterogeneity across studies underscores the importance of tailoring interventions to specific contexts and needs, while the overall robust effect reinforces the role of WASH interventions in safeguarding child growth. Future research should delve into potential mediators and moderators of the observed effects, exploring factors such as cultural, socioeconomic, and geographic variables. Additionally, refining and standardizing data collection methodologies can enhance the comparability of findings across studies.

WASH Potentially Reduce Pathogenic Infection Case

The underlying mechanism linking WASH improvements and elevated mean height-for- age-z scores can be attributed to the mitigation of diarrhea and parasitic infections, which are known culprits behind compromised nutrient absorption, reduced appetite, and diversion of energy away from growth towards the immune system's defense against infections ((Behrman et al., 2009; Ezeamama et al., 2005; FREEMAN et al., 2014; Freeman et al., 2014). Furthermore, the improvement of WASH conditions prevents enteric infections, subsequently reducing the permeability of the small intestine and enhancing nutrient absorption (Cumming et al., 2014; Quick et al., 2010).

An insightful discovery was the enhanced effectiveness of combined WASH interventions in improving child nutritional status, surpassing the impact of single interventions. This phenomenon can be logically attributed to the intricate pathways through which faecal-oral pathogens spread via drinking water, sanitation, or hygiene. Isolated practices such as handwashing, drinking water treatment, food safety measures, or sanitation alone are insufficient to comprehensively counteract the occurrence of faecal-oral diseases. The integration of these interventions, as underscored, is instrumental in not only curbing infections but also in proactively promoting nutrition (Cusick and Georgieff, 2012; Danaei et al., 2016; Doyle et al., 2009).

These findings further resonate with previous research emphasizing the critical importance of clean water, improved sanitation, and proper hygiene practices in preventing the transmission of pathogens. The significant reduction in the risk of infection highlights the potential to alleviate strain on healthcare systems and improve the quality of life for children and their families. The substantiates the profound impact of water, sanitation, and hygiene interventions in curbing pathogen-induced infections and resultant diseases among children. The robust odds ratio, minimal heterogeneity, and significant Z-test underscore the significance of prioritizing WASH interventions as an essential strategy to enhance child health outcomes and reduce the burden of pathogenic infections. These findings contribute to the growing body of evidence supporting the integration of WASH interventions into comprehensive public health initiatives, ultimately leading to improved child well-being.

NI Boost Children’s Growth

In our systematic review and meta-analysis encompassing interventions involving nutritional supplements (NS) for children experiencing undernutrition or at nutritional risk, our investigation has revealed significant positive outcomes in terms of weight gain and height growth due to the provision of NS. Analysis employing the most extended follow-up duration underscored those interventions incorporating NS led to marked increases in energy intake, coupled with notable enhancements in both weight and height gains among undernourished or vulnerable children, as compared to those subjected to placebo controls or standard diets (Zhang et al., 2021). The meta- analysis highlights a significant rise in energy intake within the NS intervention group, closely associated with substantial gains in weight and height when compared to controls who received nutritional counseling (NC), placebo, or the usual diet.

While the control group, receiving only NC, reported marginal gains in weight or height, the effects were significantly less pronounced than those observed in the intervention group. It is noteworthy that NC continues to serve as the primary approach for fostering catch-up growth in children at nutritional risk. However, studies contrasting the impact of interventions combining NC with NS against interventions without NC yielded diverse outcomes, ranging from minimal to noteworthy successes. Factors contributing to this variation encompass the intensity of dietary counseling, the specific behaviors targeted, time constraints faced by caregivers, and the challenges associated with ensuring dietary diversity to meet nutritional demands (Michaelsen et al., 2009). Given these intricacies, nutritional supplementation and food fortification emerge as recommended strategies to attain the desired nutrient density and adequacy for promoting growth in undernourished children.

In a parallel vein, the study conducted by Roberts et al. (Roberts and Stein, 2017) embarked on a systematic review and meta-analysis concentrating on specific dietary components and linear growth in children over the age of 2, who faced undernutrition or vulnerability. Their findings resonate with ours, indicating that interventions providing elements such as zinc, vitamin A, multiple micronutrients, or protein have favorable effects on height, while those involving iron, calcium, iodine, or food supply did not significantly impact linear growth. It is pertinent to note that interventions focusing solely on single or multiple micronutrient supplementation, without additional macronutrients and calories, did not consistently promote catch-up weight. In contrast, NS supplementation, offering a comprehensive blend of both macronutrients and micronutrients, has consistently demonstrated efficacy in promoting catch-up weight among children facing nutritional risk. As undernutrition-induced growth faltering often results from deficiencies in multiple nutrients, particularly in developing nations, the integrated approach of NS holds promise as an effective nutritional intervention for addressing both weight and height challenges in at-risk or undernourished children.

Furthermore, a recent Cochrane review by Das et al. (Das et al., 2019) corroborates our findings. Their study emphasizes the value of lipid-based nutritional supplements (LNS) when administered alongside complementary feeding as a preemptive measure among vulnerable populations. The positive impact of LNS, which contains a combination of macronutrients and micronutrients, is consistent with our conclusions, reinforcing the utility of nutritional supplements in meeting the diverse nutritional requirements and enhancing the overall nutritional status of children at risk of undernutrition.

NI is Not Potential to Reduce Pathogenic Infection in Children

Exploring the lack of statistical significance requires a consideration of potential underlying mechanisms. Nutritional interventions may indeed impact the immune system and reduce susceptibility to infections. However, variations in intervention strategies, duration, dosages, and the specific nutritional components targeted could contribute to the observed heterogeneity. Examining immune markers, micronutrient status, and potential confounding factors could provide insights into these mechanisms.

The non-significant Z-test result prompts further exploration into the factors that may influence the effectiveness of nutritional interventions in mitigating pathogen-related infections. Potential reasons for the lack of significance could include variations in intervention strategies, study populations, or disease etiologist. The results of this meta-analysis underscore the intricate nature of the relationship between nutritional interventions and pathogen-induced infections in children. While there appears to be a trend towards a protective effect, the high heterogeneity and lack of statistical significance warrant further investigation and a nuanced interpretation of the findings. Future research should focus on identifying specific conditions under which nutritional interventions may yield more pronounced effects and contribute to improved pediatric health outcomes.

Study Strengths and Limitations

The study demonstrates several notable strengths. Firstly, it conducts a comprehensive systematic review and meta-analysis that encompasses a broad spectrum of studies, ensuring a thorough examination of the impacts of interventions involving water, sanitation, hygiene, and nutrition on children's growth and the prevalence of pathogenic infections. The study's objectives are clearly delineated, focusing on comprehending the collective effects of these interventions on growth indicators and pathogen-related infections. This precision enhances the study's relevance and concentration. Employing robust methodologies, such as random-effects Inverse Variance (IV) models and subgroup analyses, the study adeptly accommodates heterogeneity among studies and provides nuanced insights, bolstering the dependability and applicability of the results to various contexts. Additionally, the study's emphasis on vital public health concerns, such as the intricate links between inadequate water, sanitation, hygiene, undernutrition, and child well-being, underscores its significance in guiding evidence-based interventions.

The study, however, does recognize several limitations that warrant consideration. Notably, there is substantial heterogeneity observed in certain analyses due to variations in interventions. While the utilization of random-effects models helps address this variability to some degree, the diverse nature of the included studies might constrain the generalizability of the findings. Additionally, the variability in study quality might influence the reliability of the results. Conducting sensitivity analyses or subgroup analyses based on study quality could provide a more nuanced perspective on the findings' robustness.

The study acknowledges that the effectiveness of interventions could be influenced by contextual factors, such as geographic, cultural, and socioeconomic differences, which are not extensively explored. Delving into these contextual variations could provide insights into how interventions might be tailored to specific settings. Furthermore, while the study comprehensively examines the impacts of interventions, it does not deeply delve into the mechanistic pathways through which these interventions influence growth indicators and infection rates. Further research focusing on these mechanistic insights could offer a more comprehensive understanding of the observed effects. Finally, the duration of follow-up in the included studies might impact the study's findings. Longer-term follow-up could provide insights into the sustainability of the observed intervention effects over time.

In conclusion, the systematic review and comprehensive meta-analysis presented herein provide a robust examination of the effects of water, sanitation, hygiene, and nutritional interventions on children's growth indicators and pathogenic infection rates. The study's meticulous analysis reveals significant insights into the multifaceted relationships between these interventions and child health outcomes.

In summary, this comprehensive study contributes valuable evidence to inform public health interventions aimed at improving child health and well-being. The results emphasize the importance of integrated approaches, such as combined WASH interventions and nutritional supplementation, in addressing the intricate interplay between growth indicators and pathogenic infection rates. Nonetheless, the study also underscores the need for continued research to delve into contextual factors, mechanistic pathways, and the optimization of intervention strategies to maximize their impact on child health outcomes. Ultimately, this systematic review and meta- analysis serve as a vital resource for policymakers, practitioners, and researchers dedicated to advancing child health through evidence-based interventions.

Financial interests: The authors declare they have no financial interests.

Data availability statement: All data supporting the findings of this study are available within the paper.

Aiello, A.E., Coulborn, R.M., Perez, V., Larson, E.L., 2008. Effect of Hand Hygiene on Infectious Disease Risk in the Community Setting: A Meta-Analysis. Am J Public Health 98, 1372–1381. https://doi.org/10.2105/AJPH.2007.124610
Altmann, M., Altare, C., Van Der Spek, N., Barbiche, J.C., Dodos, J., Bechir, M., Aissa, M.A., Kolsteren, P., 2018. Effectiveness of a household water, sanitation and hygiene package on an outpatient program for severe acute malnutrition: A pragmatic cluster-randomized controlled trial in Chad. American Journal of Tropical Medicine and Hygiene 98, 1005–1012. https://doi.org/10.4269/ajtmh.17-0699
Arnold, B.F., Null, C., Luby, S.P., Unicomb, L., Stewart, C.P., Dewey, K.G., Ahmed, T., Ashraf, S., Christensen, G., Clasen, T., Dentz, H.N., Fernald, L.C.H., Haque, R., Hubbard, A.E., Kariger, P., Leontsini, E., Lin, A., Njenga, S.M., Pickering, A.J., Ram, P.K., Tofail, F., Winch, P.J., Colford, J.M., 2013a. Cluster-randomized controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: the WASH Benefits study design and rationale. BMJ Open 3, e003476. https://doi.org/10.1136/bmjopen-2013-003476
Arnold, B.F., Null, C., Luby, S.P., Unicomb, L., Stewart, C.P., Dewey, K.G., Ahmed, T., Ashraf, S., Christensen, G., Clasen, T., Dentz, H.N., Fernald, L.C.H., Haque, R., Hubbard, A.E., Kariger, P., Leontsini, E., Lin, A., Njenga, S.M., Pickering, A.J., Ram, P.K., Tofail, F., Winch, P.J., Colford, J.M., 2013b. Cluster-randomized controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: the WASH Benefits study design and rationale. BMJ Open 3, e003476. https://doi.org/10.1136/bmjopen-2013-003476
Behrman, J.R., Calderon, M.C., Preston, S.H., Hoddinott, J., Martorell, R., Stein, A.D., 2009. Nutritional supplementation in girls influences the growth of their children: prospective study in Guatemala. Am J Clin Nutr 90, 1372–1379. https://doi.org/10.3945/ajcn.2009.27524
Bhutta, Z.A., Ahmed, T., Black, R.E., Cousens, S., Dewey, K., Giugliani, E., Haider, B.A., Kirkwood, B., Morris, S.S., Sachdev, H., Shekar, M., 2008. What works? Interventions for maternal and child undernutrition and survival. The Lancet 371, 417–440. https://doi.org/10.1016/S0140-6736(07)61693-6
Bowen, A., Agboatwalla, M., Luby, S., Tobery, T., Ayers, T., Hoekstra, R.M., 2012a. Association Between Intensive Handwashing Promotion and Child Development in Karachi, Pakistan. Arch Pediatr Adolesc Med 166, 1037. https://doi.org/10.1001/archpediatrics.2012.1181
Bowen, A., Agboatwalla, M., Luby, S., Tobery, T., Ayers, T., Hoekstra, R.M., 2012b. Association between intensive handwashing promotion and child development in Karachi, Pakistan: A cluster randomized controlled trial. Arch Pediatr Adolesc Med 166, 1037–1044. https://doi.org/10.1001/archpediatrics.2012.1181
Brooker, S., Kabatereine, N.B., Smith, J.L., Mupfasoni, D., Mwanje, M.T., Ndayishimiye, O., Lwambo, N.J., Mbotha, D., Karanja, P., Mwandawiro, C., Muchiri, E., Clements, A.C., Bundy, D.A., Snow, R.W., 2009. An updated atlas of human helminth infections: the example of East Africa. Int J Health Geogr 8, 42. https://doi.org/10.1186/1476-072X-8-42
Brown, J., Cairncross, S., Ensink, J.H.J., 2013. Water, sanitation, hygiene and enteric infections in children. Arch Dis Child 98, 629–634. https://doi.org/10.1136/archdischild-2011-301528
Chard, A.N., Trinies, V., Moss, D.M., Chang, H.H., Doumbia, S., Lammie, P.J., Freeman, M.C., 2018. The impact of school water, sanitation, and hygiene improvements on infectious disease using serum antibody detection. PLoS Negl Trop Dis 12. https://doi.org/10.1371/journal.pntd.0006418
Checkley, W., Buckley, G., Gilman, R.H., Assis, A.M., Guerrant, R.L., Morris, S.S., Mølbak, K., Valentiner- Branth, P., Lanata, C.F., Black, R.E., 2008. Multi-country analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol 37, 816–830. https://doi.org/10.1093/ije/dyn099
Checkley, W., Gilman, R.H., Black, R.E., Epstein, L.D., Cabrera, L., Sterling, C.R., Moulton, L.H., 2004. Effect of water and sanitation on childhood health in a poor Peruvian peri-urban community. The Lancet 363, 112– 118. https://doi.org/10.1016/S0140-6736(03)15261-0
Clasen, T., Boisson, S., Routray, P., Torondel, B., Bell, M., Cumming, O., Ensink, J., Freeman, M., Jenkins, M., Odagiri, M., Ray, S., Sinha, A., Suar, M., Schmidt, W.-P., 2014. Effectiveness of a rural sanitation programme on diarrhoea, soil-transmitted helminth infection, and child malnutrition in Odisha, India: a cluster-randomised trial. Lancet Glob Health 2, e645–e653. https://doi.org/10.1016/S2214-109X(14)70307- 9
Crane, R.J., Jones, K.D.J., Berkley, J.A., 2015. Environmental Enteric Dysfunction: An Overview. Food Nutr Bull 36, S76–S87. https://doi.org/10.1177/15648265150361S113
Cumming, O., Cairncross, S., 2016. Can water, sanitation and hygiene help eliminate stunting? Current evidence and policy implications. Matern Child Nutr 12, 91–105. https://doi.org/10.1111/mcn.12258
Cumming, O., Elliott, M., Overbo, A., Bartram, J., 2014. Does Global Progress on Sanitation Really Lag behind Water? An Analysis of Global Progress on Community- and Household-Level Access to Safe Water and Sanitation. PLoS One 9, e114699. https://doi.org/10.1371/journal.pone.0114699
Cusick, S.E., Georgieff, M.K., 2012. Nutrient supplementation and neurodevelopment: timing is the key. Arch Pediatr Adolesc Med 166, 481–2. https://doi.org/10.1001/archpediatrics.2012.199
Danaei, G., Andrews, K.G., Sudfeld, C.R., Fink, G., McCoy, D.C., Peet, E., Sania, A., Smith Fawzi, M.C., Ezzati, M., Fawzi, W.W., 2016. Risk Factors for Childhood Stunting in 137 Developing Countries: A Comparative Risk Assessment Analysis at Global, Regional, and Country Levels. PLoS Med 13, e1002164. https://doi.org/10.1371/journal.pmed.1002164
Dangour, A.D., Watson, L., Cumming, O., Boisson, S., Che, Y., Velleman, Y., Cavill, S., Allen, E., Uauy, R., 2013. Interventions to improve water quality and supply, sanitation and hygiene practices, and their effects on the nutritional status of children. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD009382.pub2
Daniels, D.L., Cousens, S.N., Makoae, L.N., Feachem, R.G., 1991. A study of the association between improved sanitation facilities and children’s height in Lesotho. Eur J Clin Nutr 45, 23–32.
Das, J.K., Salam, R.A., Hadi, Y.B., Sadiq Sheikh, S., Bhutta, A.Z., Weise Prinzo, Z., Bhutta, Z.A., 2019. Preventive lipid-based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes. Cochrane Database of Systematic Reviews 2019. https://doi.org/10.1002/14651858.CD012611.pub3
Davis, J.N., Pérez, A., Asigbee, F.M., Landry, M.J., Vandyousefi, S., Ghaddar, R., Hoover, A., Jeans, M., Nikah, K., Fischer, B., Pont, S.J., Richards, D., Hoelscher, D.M., Van Den Berg, A.E., 2021. School-based gardening, cooking and nutrition intervention increased vegetable intake but did not reduce BMI: Texas sprouts - a cluster randomized controlled trial. International Journal of Behavioral Nutrition and Physical Activity 18. https://doi.org/10.1186/s12966-021-01087-x
Doocy, S., Tappis, H., Villeminot, N., Suk, A., Kumar, D., Fazal, S., Grant, A., Pietzsch, S., 2018. Point-of-use water treatment improves recovery rates among children with severe acute malnutrition in Pakistan: results from a site-randomized trial. Public Health Nutr 21, 3080–3090. https://doi.org/10.1017/S1368980018001647
Doyle, O., Harmon, C.P., Heckman, J.J., Tremblay, R.E., 2009. Investing in early human development: Timing and economic efficiency. Econ Hum Biol 7, 1–6. https://doi.org/10.1016/j.ehb.2009.01.002
Ezeamama, A.E., Friedman, J.F., Acosta, L.P., Bellinger, D.C., Langdon, G.C., Manalo, D.L., Olveda, R.M., Kurtis, J.D., McGarvey, S.T., 2005. Helminth infection and cognitive impairment among Filipino children. Am J Trop Med Hyg 72, 540–548.
Fenn, B., Bulti, A.T., Nduna, T., Duffield, A., Watson, F., 2012a. An evaluation of an operations research project to reduce childhood stunting in a food-insecure area in Ethiopia. Public Health Nutr 15, 1746–1754. https://doi.org/10.1017/S1368980012001115
Fenn, B., Bulti, A.T., Nduna, T., Duffield, A., Watson, F., 2012b. An evaluation of an operations research project to reduce childhood stunting in a food-insecure area in Ethiopia. Public Health Nutr 15, 1746–1754. https://doi.org/10.1017/S1368980012001115
Fewtrell, L., Kaufmann, R.B., Kay, D., Enanoria, W., Haller, L., Colford, J.M., 2005. Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta- analysis. Lancet Infect Dis 5, 42–52. https://doi.org/10.1016/S1473-3099(04)01253-8
Freeman, M.C., Clasen, T., Dreibelbis, R., Saboori, S., Greene, L.E., Brumback, B., Muga, R., Rheingans, R., 2014. The impact of a school-based water supply and treatment, hygiene, and sanitation programme on pupil diarrhoea: a cluster-randomized trial. Epidemiol Infect 142, 340–351. https://doi.org/10.1017/S0950268813001118
Freeman, M.C., Stocks, M.E., Cumming, O., Jeandron, A., Higgins, J.P.T., Wolf, J., Prüss-Ustün, A., Bonjour, S., Hunter, P.R., Fewtrell, L., Curtis, V., 2014. Systematic review: Hygiene and health: systematic review of handwashing practices worldwide and update of health effects. Tropical Medicine & International Health 19, 906–916. https://doi.org/10.1111/tmi.12339
George, C.M., Perin, J., Parvin, T., Bhuyian, S., Thomas, E.D., Monira, S., Zohura, F., Hasan, T., Sack, D., Alam, M., 2022. Effects of a Water, Sanitation and Hygiene Mobile Health Program on Respiratory Illness in Bangladesh: A Cluster-Randomized Controlled Trial of the CHoBI7 Mobile Health Program. Am J Trop Med Hyg 106, 979–984. https://doi.org/10.4269/ajtmh.21-0679
Gera, T., Shah, D., Sachdev, H.S., 2018. Impact of Water, Sanitation and Hygiene Interventions on Growth, Non- diarrheal Morbidity and Mortality in Children Residing in Low- and Middle-income Countries: A Systematic Review. Indian Pediatr 55, 381–393.
Halder, A.K., Molyneaux, J.W., Luby, S.P., Ram, P.K., 2013. Impact of duration of structured observations on measurement of handwashing behavior at critical times. BMC Public Health 13, 705. https://doi.org/10.1186/1471-2458-13-705
Hammer, J., Spears, D., 2016. Village sanitation and child health: Effects and external validity in a randomized field experiment in rural India. J Health Econ 48, 135–148. https://doi.org/10.1016/j.jhealeco.2016.03.003
Hoddinott, J., Maluccio, J.A., Behrman, J.R., Flores, R., Martorell, R., 2008. Effect of a nutrition intervention during early childhood on economic productivity in Guatemalan adults. The Lancet 371, 411–416. https://doi.org/10.1016/S0140-6736(08)60205-6
Humphrey, J.H., 2009. Child undernutrition, tropical enteropathy, toilets, and handwashing. The Lancet 374, 1032–1035. https://doi.org/10.1016/S0140-6736(09)60950-8
Kelly, P., Prendergast, A., 2012. Enteropathies in the Developing World: Neglected Effects on Global Health. Am J Trop Med Hyg 86, 756–763. https://doi.org/10.4269/ajtmh.2012.11-0743
Korpe, P.S., Petri, W.A., 2012. Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol Med 18, 328–336. https://doi.org/10.1016/j.molmed.2012.04.007
Langford, R., Lunn, P., Brick, C.P.-, 2011. Hand-washing, subclinical infections, and growth: A longitudinal evaluation of an intervention in Nepali slums. American Journal of Human Biology 23, 621–629. https://doi.org/10.1002/ajhb.21189
Lin, A., Arnold, B.F., Afreen, S., Goto, R., Huda, T.M.N., Haque, R., Raqib, R., Unicomb, L., Ahmed, T., Colford, J.M., Luby, S.P., 2013a. Household Environmental Conditions Are Associated with Enteropathy and Impaired Growth in Rural Bangladesh. Am J Trop Med Hyg 89, 130–137. https://doi.org/10.4269/ajtmh.12- 0629
Lin, A., Arnold, B.F., Afreen, S., Goto, R., Huda, T.M.N., Haque, R., Raqib, R., Unicomb, L., Ahmed, T., Colford, J.M., Luby, S.P., 2013b. Household Environmental Conditions Are Associated with Enteropathy and Impaired Growth in Rural Bangladesh. Am J Trop Med Hyg 89, 130–137. https://doi.org/10.4269/ajtmh.12- 0629
Lin, A., Ercumen, A., Benjamin-Chung, J., Arnold, B.F., Das, S., Haque, R., Ashraf, S., Parvez, S.M., Unicomb, L., Rahman, M., Hubbard, A.E., Stewart, C.P., Colford, J.M., Luby, S.P., 2018. Effects of water, sanitation, handwashing, and nutritional interventions on child enteric protozoan infections in rural Bangladesh: A cluster-randomized controlled trial. Clinical Infectious Diseases 67, 1515–1522. https://doi.org/10.1093/cid/ciy320
Lutter, C.K., Lutter, R., 2012. Fetal and Early Childhood Undernutrition, Mortality, and Lifelong Health. Science (1979) 337, 1495–1499. https://doi.org/10.1126/science.1224616
Mackinnon, E., Ayah, R., Taylor, R., Owor, M., Ssempebwa, J., Olago, l D., Kubalako, R., Dia, A.T., Gaye, C., C. Campos, L., Fottrell, E., 2019. 21st century research in urban WASH and health in sub-Saharan Africa: methods and outcomes in transition. Int J Environ Health Res 29, 457–478. https://doi.org/10.1080/09603123.2018.1550193
Majo, F., Mbuya, M.N.N., Humphrey, J.H., Govha, M., Chasekwa, B., Mutasa, K., Boor, K.J., Mazarura, E., Curtis, V., Prendergast, A.J., Ngure, F.M., Stoltzfus, R.J., 2013. Formative Research on Hygiene Behaviors and Geophagy among Infants and Young Children and Implications of Exposure to Fecal Bacteria. Am J Trop Med Hyg 89, 709–716. https://doi.org/10.4269/ajtmh.12-0568
McQuade, E.T.R., Platts-Mills, J.A., Gratz, J., Zhang, J., Moulton, L.H., Mutasa, K., Majo, F.D., Tavengwa, N., Ntozini, R., Prendergast, A.J., Humphrey, J.H., Liu, J., Houpt, E.R., 2020. Impact of water quality, sanitation, handwashing, and nutritional interventions on enteric infections in rural zimbabwe: The sanitation hygiene infant nutrition efficacy (SHINE) trial. Journal of Infectious Diseases 221, 1379–1386. https://doi.org/10.1093/infdis/jiz179
Michaelsen, K.F., Hoppe, C., Roos, N., Kaestel, P., Stougaard, M., Lauritzen, L., Mølgaard, C., Girma, T., Friis, H., 2009. Choice of Foods and Ingredients for Moderately Malnourished Children 6 Months to 5 Years of Age. Food Nutr Bull 30, S343–S404. https://doi.org/10.1177/15648265090303S303
Mondal, D., Minak, J., Alam, M., Liu, Y., Dai, J., Korpe, P., Liu, L., Haque, R., Petri, W.A., 2012. Contribution of Enteric Infection, Altered Intestinal Barrier Function, and Maternal Malnutrition to Infant Malnutrition in Bangladesh. Clinical Infectious Diseases 54, 185–192. https://doi.org/10.1093/cid/cir807
Muhoozi, Grace K. M., Atukunda, P., Diep, L.M., Mwadime, R., Kaaya, A.N., Skaare, A.B., Willumsen, T., Westerberg, A.C., Iversen, P.O., 2018. Nutrition, hygiene, and stimulation education to improve growth, cognitive, language, and motor development among infants in Uganda: A cluster‐randomized trial. Matern Child Nutr 14. https://doi.org/10.1111/mcn.12527
Muhoozi, Grace K.M., Atukunda, P., Skaare, A.B., Willumsen, T., Diep, L.M., Westerberg, A.C., Iversen, P.O., 2018. Effects of nutrition and hygiene education on oral health and growth among toddlers in rural Uganda: follow-up of a cluster-randomised controlled trial. Tropical Medicine and International Health 23, 391–404. https://doi.org/10.1111/tmi.13036
Mwansa, J., Menzies, I., Mudenda, V., Nickols, C., Feakins, R., Greenwald, S., Farthing, M., Katubulushi, M., Crane, R., Zulu, I., Kelly, P., 2004. Responses Of Small Intestinal Architecture and Function Over Time to Environmental Factors in A Tropical Population. Am J Trop Med Hyg 70, 412–419. https://doi.org/10.4269/ajtmh.2004.70.412
Najnin, N., Leder, K., Qadri, F., Forbes, A., Unicomb, L., Winch, P.J., Ram, P.K., Leontsini, E., Nizame, F.A., Arman, S., Begum, F., Biswas, S.K., Clemens, J.D., Ali, M., Cravioto, A., Luby, S.P., 2017. Impact of adding hand-washing and water disinfection promotion to oral cholera vaccination on diarrhoea-associated hospitalization in Dhaka, Bangladesh: Evidence from a cluster randomized control trial. Int J Epidemiol 46, 2056–2066. https://doi.org/10.1093/ije/dyx187
Nikièma, L., Huybregts, L., Martin-Prevel, Y., Donnen, P., Lanou, H., Grosemans, J., Offoh, P., Dramaix-Wilmet, M., Sondo, B., Roberfroid, D., Kolsteren, P., 2017. Effectiveness of facility-based personalized maternal nutrition counseling in improving child growth and morbidity up to 18 months: A cluster-randomized controlled trial in rural Burkina Faso. PLoS One 12. https://doi.org/10.1371/journal.pone.0177839
Patil, S.R., Arnold, B.F., Salvatore, A.L., Briceno, B., Ganguly, S., Colford, J.M., Gertler, P.J., 2014. The Effect of India’s Total Sanitation Campaign on Defecation Behaviors and Child Health in Rural Madhya Pradesh: A Cluster Randomized Controlled Trial. PLoS Med 11, e1001709. https://doi.org/10.1371/journal.pmed.1001709
Petri, W.A., Miller, M., Binder, H.J., Levine, M.M., Dillingham, R., Guerrant, R.L., 2008. Enteric infections, diarrhea, and their impact on function and development. Journal of Clinical Investigation 118, 1277–1290. https://doi.org/10.1172/JCI34005
Pickering, Amy J, Djebbari, H., Lopez, C., Coulibaly, M., Alzua, M.L., 2015. Effect of a community-led sanitation intervention on child diarrhoea and child growth in rural Mali: a cluster-randomised controlled trial. Lancet Glob Health 3, e701–e711. https://doi.org/10.1016/S2214-109X(15)00144-8
Pickering, Amy J., Djebbari, H., Lopez, C., Coulibaly, M., Alzua, M.L., 2015. Effect of a community-led sanitation intervention on child diarrhoea and child growth in rural Mali: A cluster-randomised controlled trial. Lancet Glob Health 3, e701–e711. https://doi.org/10.1016/S2214-109X(15)00144-8
Quick, R., Blanton, E., Mwaki, A., Ombeki, S., Wannemuehler, K., Oluoch, G.O., 2010. Evaluation of the Role of School Children in the Promotion of Point-of-Use Water Treatment and Handwashing in Schools and Households—Nyanza Province, Western Kenya, 2007. Am J Trop Med Hyg 82, 664–671. https://doi.org/10.4269/ajtmh.2010.09-0422
Rah, J.H., Cronin, A.A., Badgaiyan, B., Aguayo, V.M., Coates, S., Ahmed, S., 2015. Household sanitation and personal hygiene practices are associated with child stunting in rural India: a cross-sectional analysis of surveys. BMJ Open 5, e005180–e005180. https://doi.org/10.1136/bmjopen-2014-005180
Reeves, B.C., Higgins, J.P.T., Ramsay, C., Shea, B., Tugwell, P., Wells, G.A., 2013. An introduction to methodological issues when including non-randomised studies in systematic reviews on the effects of interventions. Res Synth Methods 4, 1–11. https://doi.org/10.1002/jrsm.1068
Roberts, J.L., Stein, A.D., 2017. The Impact of Nutritional Interventions beyond the First 2 Years of Life on Linear Growth: A Systematic Review and Meta-Analysis. Advances in Nutrition 8, 323–336. https://doi.org/10.3945/an.116.013938
Rosen, L., Manor, O., Engelhard, D., Brody, D., Rosen, B., Peleg, H., Meir, M., Zucker, D., 2006. Can a handwashing intervention make a difference? Results from a randomized controlled trial in Jerusalem preschools. Prev Med (Baltim) 42, 27–32. https://doi.org/10.1016/j.ypmed.2005.09.012
Salehi, M., Kimiagar, S.M., Shahbazi, M., Mehrabi, Y., Kolahi, A.A., 2004. Assessing the impact of nutrition education on growth indices of Iranian nomadic children: an application of a modified beliefs, attitudes, subjective-norms and enabling-factors model. British Journal of Nutrition 91, 779–787. https://doi.org/10.1079/bjn20041099
Sangalang, S.O., Lemence, A.L.G., Ottong, Z.J., Valencia, J.C., Olaguera, M., Canja, R.J.F., Mariano, S.M.F., Prado, N.O., Ocaña, R.M.Z., Singson, P.A.A., Cumagun, M.L., Liao, J., Anglo, M.V.J.C., Borgemeister, C., Kistemann, T., 2022. School water, sanitation, and hygiene (WaSH) intervention to improve malnutrition, dehydration, health literacy, and handwashing: a cluster-randomised controlled trial in Metro Manila, Philippines. BMC Public Health 22. https://doi.org/10.1186/s12889-022-14398-w
Scherr, R.E., Linnell, J.D., Dharmar, M., Beccarelli, L.M., Bergman, J.J., Briggs, M., Brian, K.M., Feenstra, G., Hillhouse, J.C., Keen, C.L., Ontai, L.L., Schaefer, S.E., Smith, M.H., Spezzano, T., Steinberg, F.M., Sutter, C., Young, H.M., Zidenberg-Cherr, S., 2017. A Multicomponent, School-Based Intervention, the Shaping Healthy Choices Program, Improves Nutrition-Related Outcomes. J Nutr Educ Behav 49, 368-379.e1. https://doi.org/10.1016/j.jneb.2016.12.007
Shahramian, I., Kalvandi, G., Javaherizadeh, H., Khalili, M., Noori, N.M., Delaramnasab, M., Bazi, A., 2018. The effects of prebiotic supplementation on weight gain, diarrhoea, constipation, fever and respiratory tract infections in the first year of life. J Paediatr Child Health 54, 875–880. https://doi.org/10.1111/jpc.13906
Sjarif, D.R., Yuliarti, K., Iskandar, W.J., 2020. Consumption of growing up milk and stunting among Indonesian toddlers: authors’ reply. Medical Journal of Indonesia 29, 111–2. https://doi.org/10.13181/mji.cor.204630
Swarthout, J., Ram, P.K., Arnold, C.D., Dentz, H.N., Arnold, B.F., Kalungu, S., Lin, A., Njenga, S.M., Stewart, C.P., Colford, J.M., Null, C., Pickering, A.J., 2020. Effects of individual and combined water, sanitation, handwashing, and nutritional interventions on child respiratory infections in Rural Kenya: A cluster- randomized controlled trial. American Journal of Tropical Medicine and Hygiene 102, 1286–1295. https://doi.org/10.4269/ajtmh.19-0779
The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial: Rationale, Design, and Methods, 2015. . Clinical Infectious Diseases 61, S685–S702. https://doi.org/10.1093/cid/civ844
Zhang, Z., Li, F., Hannon, B.A., Hustead, D.S., Aw, M.M., Liu, Z., Chuah, K.A., Low, Y.L., Huynh, D.T.T., 2021. Effect of oral nutritional supplementation on growth in children with undernutrition: A systematic review and meta‐analysis. Nutrients. https://doi.org/10.3390/nu13093036

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Effectiveness of Water, Sanitation, Hygiene, and Nutritional Interventions to Reduce Pathogenic Infections and Improve Nutritional Status in Children: Systematic Review and Meta-Analysis of Randomized Controlled Trial

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Abstract

Objective

Method

Result

Conclusion

Figures

INTRODUCTION

METHODS

Search Strategy and Eligible Study

Selection of Studies

Data Extraction and Management

Assessment of Risk of Bias

Statistical Analysis

RESULT

Characteristic of Included Studies

Risk of bias assessment

Analysis Study

WASH Intervention

Height and Weight Impact

Pathogenic Infection Impact

Nutritional Intervention

Weight and Height Impact

Pathogenic Infection Impact

DISCUSSION

WASH Impact on Children’s Growth

WASH Potentially Reduce Pathogenic Infection Case

NI Boost Children’s Growth

NI is Not Potential to Reduce Pathogenic Infection in Children

Study Strengths and Limitations

CONCLUSION

DECLARATIONS

REFERENCES

Table

Supplementary Materials

Supplementary Files

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