Effectiveness of water, sanitation, hygiene, and nutritional interventions to reduce pathogenic infections and improve nutritional status in children: a systematic review and meta-analysis of randomized controlled trial

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 (Kaminsky & Jordan 2017). 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 2024). 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 (MWANSA et al. 2004; Brown et al. 2013; Crane et al. 2015). It is 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 (Checkley et al. 2004; Lin et al. 2013; Das et al. 2019).

Behavioral interventions that target the enhancement of individual practices and habits are frequently employed at the micro-level to prevent and treat undernutrition in children. One example of effective strategy to mitigate undernutrition among children residing in resource-poor environments is the implementation of complementary dietary supplements and nutrition education (Bhutta et al. 2008; Nounkeu & Dharod 2021). Nevertheless, it is acknowledged that employing a solitary nutritional intervention (NI) yields positive outcomes alone under particular circumstances. Utilizing a combination of nutrition-specific and nutrition-sensitive interventions is often more effective in addressing and preventing undernutrition across various contexts (Nounkeu & Dharod 2021).

The World Health Organization (WHO), in partnership with the US Agency for International Development (USAID) and UNICEF, has emphasized the significance of WASH and nutrition in improving the health and nutrition of children. They have advocated for the integration of WASH and nutrition programs to maximize the positive impact on children's well-being (United Nations Children's Fund (UNICEF) 2020; Nounkeu & Dharod 2021). In particular, UNICEF outline the strategic goal is to assist national governments and partners in protecting children's right to nutrition and, throughout the following 10 years, eradicating all kinds of malnutrition (United Nations Children's Fund (UNICEF) 2020).

Extensive research has underscored the intricate relationship between malnutrition and substandard WASH practices (Petri et al. 2008; Langford et al. 2011; Mondal et al. 2012; 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 toward bolstering the immune system against infections (Checkley et al. 2004; Humphrey 2009; Korpe & Petri 2012). Moreover, the compromised state of EE escalates intestinal permeability, exacerbating nutrient absorption challenges (Bowen et al. 2012; Kelly & Prendergast 2012; Clasen et al. 2014; Cumming & Cairncross 2016). 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 (PIs) among children. Nonetheless, the exact impact of WASH and NIs 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. 2013; Patil et al. 2014; Muhoozi et al. 2018a, 2018b), while others corroborate this viewpoint regarding NI and PI prevalence (Fenn et al. 2012; Pickering et al. 2015). Conversely, a subset of research contends that both WASH and NI do indeed yield substantial effects (Esteves Mills et al. 2016). 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 PIs in children.

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

In this study, two reviewers (Pasca and 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 (Supplementary material, can access in link https://figshare.com/account/articles/25802575). Our searches were conducted in English. Additionally, we hand-searched references from all the studies included.

We specifically focused on randomized controlled trial (RCT) studies as the eligible study designs (see Table 1). To be included, an article needs to present a measure of the effect related to WASH, NIs, nutrition status (NS), and PIs. 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 PIs (including bacteria, viruses, fungi, and helminths) related WASH in children (0–18 y.o). Children as old as 18 years are included in the inclusion criteria due to the potential influence of WASH interventions on critical academic achievements (such as literacy and numeracy), which may not be discernible in children younger than 5 years. 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 were 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:

• 1. Significant global initiatives: The year 2004 marks the launch of the Global Sanitation Fund, which signaled a renewed global commitment toward 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.

• 2. 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.

• 3. 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.

• 4. 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 WASH and NIs.

• 5. 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 PIs related to food and enhance NS 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 (HECs); (4) studies not assessing the impact of interventions on PI 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 PIs; and (9) studies lacking relevant outcome measures.

Defining and measuring WASH behaviors present challenges (Halder et al. 2013). Aligning reported water and sanitation variables with established WHO and UNICEF definitions proved difficult (WHO 2023). In this study, we clarified terms: ‘treated water' signifies chemically or physically treated potable water; ‘piped water' involves water from piped infrastructure, regardless of maintenance; ‘sanitation access' denotes latrine use; ‘washing after defecation' relates to handwashing near sanitation facilities or reported behavior; and ‘soap use or availability' refers to washing practices. These definitions lack compliance criteria due to limited literature. Addressing heterogeneity, random-effect models were employed, utilizing adjusted estimates to mitigate confounding (Reeves et al. 2013). Inversion of estimates was sometimes required for meta-analysis, introducing potential bias. Effect presence does not necessarily equate to absence's inverse impact.

The NI under scrutiny in this meta-analysis pertains specifically to interventions targeted at enhancing the nutritional well-being of children. This encompasses a range of evidence-based strategies designed to address malnutrition, including dietary supplementation, nutrient-enriched foods, fortified beverages, micronutrient supplementation, and nutrition education programs. The interventions aim to optimize children's growth, development, and overall health by rectifying deficiencies and imbalances in their dietary intake. These interventions may encompass diverse approaches, such as the provision of fortified meals, the distribution of nutrient-rich supplements, or educational initiatives to promote healthier eating habits. Precise details of the interventions, including formulation, dosages, frequency, and duration, will be meticulously evaluated.

Studies that provide comprehensive documentation of the NIs, their delivery, and measurable outcomes, particularly in relation to indicators of underweight, wasting, and stunting, will be considered for inclusion in the meta-analysis. The assessment of these NIs will contribute significantly to a comprehensive understanding of their effectiveness in improving the PI and NS of children, ultimately informing evidence-based interventions to combat childhood malnutrition.

Furthermore, it is important to acknowledge that these interventions may also have an impact on the prevalence of pathogen-related infections, particularly those transmitted through contaminated food. The improvement of NS and immune function in children through these interventions could potentially lead to a reduction in the susceptibility to infections caused by foodborne pathogens. By enhancing the body's defenses and overall health, these interventions may indirectly contribute to lowering the incidence of infections linked to pathogens present in food sources.

The assessment of PIs in children constitutes a pivotal aspect of this meta-analysis, particularly in the context of sanitation, water, hygiene, and NIs. This assessment encompasses a meticulous examination of various infections caused by pathogenic agents, including bacteria, viruses, fungi, and helminths, that commonly affect children. Infections of interest include but are not limited to gastrointestinal infections, respiratory infections, and parasitic infestations, but also diarrhea, parasitic infections, and EED.

Eligible studies will encompass those that thoroughly investigate the occurrence and prevalence of PIs in children, either as primary or secondary outcomes. The assessment methods may involve clinical diagnoses, laboratory tests, microbiological analyses, and relevant symptomatology evaluation. Comprehensive reporting of infection types, severity, and duration will be crucial.

The evaluation of NS encompassed indicators such as underweight, wasting, and stunting. These metrics were assessed using anthropometric measurements, specifically weight, age, and height, in accordance with the WHO child growth standards. While all study settings and populations were considered eligible, the evaluation of anthropometric outcomes was confined to children in line with the established protocol outlined in the NS review by Dangour et al. (2013).

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 could not 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.

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 Table 2, 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.

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: https://www.riskofbias.info/welcome/rob-2–0-tool). 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.

The statistical analysis was conducted using Review Manager 5.4 software (revman.cochrane.org/myReviews), an established tool by the Cochrane Collaboration based in Oxford, UK. The clinical implications of the dichotomous data were presented as odds ratios (ORs) utilizing a fixed-effect analysis model and statistical variance methodology, both for subgroup studies and the overall effect. Furthermore, a confidence interval (CI) 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 Der Simonian and Laird, offering a more cautiously considered analysis approach. In all instances of meta-analysis, a forest plot and a funnel plot were generated to visually present the outcomes comprehensively.

These selected 18 studies are all RCTs 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 0–18 years (see Table 2).

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, nine studies fulfill the assessment criteria for the ‘WASH to Weight' and ‘WASH to Height' groups, including studies by Muhoozi et al. (2018a, 2018b), Scherr et al. (2017), Nikièma et al. (2017), Sangalang et al. (2022), Bowen et al. (2012), Altmann et al. (2018), Pickering et al. (2015), Hammer & Spears (2016), and Doocy et al. (2018). Furthermore, 15 studies meet the assessment criteria for the ‘WASH to PI' group, encompassing studies by Muhoozi et al. (2018a, 2018b), Scherr et al. (2017), Nikièma et al. (2017), Sangalang et al. (2022), Bowen et al. (2012), Rogawski McQuade et al. (2020), Altmann et al. (2018), Lin et al. (2018), Swarthout et al. (2020), Pickering et al. (2015), George et al. (2022), Najnin et al. (2017), Chard et al. (2018), Hammer & Spears (2016), and Doocy et al. (2018). Additionally, four studies fulfill the assessment for the ‘NI to Weight' and ‘NI to Height' groups, including studies by Davis et al. (2021), Nikièma et al. (2017), Salehi et al. (2004), and Shahramian et al. (2018). Lastly, six studies meet the criteria for the ‘NI to PI' group, encompassing studies by Nikièma et al. (2017), Rogawski McQuade et al. (2020), Lin et al. (2018), Swarthout et al. (2020), Salehi et al. (2004), and Shahramian et al. (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 et al. (2018) and Swarthout et al. (2020).

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 τ² value of 0.25 and a prominent I² value of 94%, denoting substantial variability between studies. The χ² test 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 with 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 τ² value of 0.13. The I² value was 91%, implying considerable variability. The χ² test 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 ORs, supported by narrow CIs 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.

Furthermore, the assessment of heterogeneity, conducted through the χ² 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 OR, reinforce the efficacy of WASH interventions in mitigating pathogen-induced infections and related diseases in children.

These findings present compelling evidence of the positive impact of WASH interventions on reducing the incidence of pathogen-related infections, notably diarrhea, among children. The calculated OR, narrow CI, 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.

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 NIs on children's height. The analysis unveiled a lower degree of heterogeneity, with a τ² value of 0.06 and a prominent I² value of 80%, indicating variability among the studies. The χ² test 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 τ² value of 0.10. The I² value was 91%, denoting considerable variability. The χ² test 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 ORs derived from the meta-analysis are statistically significant, and the CIs are relatively narrow, suggesting that the interventions have a meaningful impact on the outcomes. The analysis also assesses heterogeneity through measures such as τ² and 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 is 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 OR of 0.61, supported by a narrow 95% 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.

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

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 NIs 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 NIs and pathogen-induced infections in children. While the point estimate suggests a potential protective effect, the wide CI 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.

This review encompassed a total of 18 studies that investigated a variety of 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 RCT 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. 2012; Lin et al. 2013). 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. 2013; Dangour et al. 2013; Clasen et al. 2014; Anon 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 et al. 2015). These collective findings, underpinned by robust research methodologies, substantiate the pivotal role of improved WASH 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 2 years of age when compared with interventions targeting older children. This observation is notably grounded in the recognition that the initial 2 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 NIs during this critical timeframe (Rosen et al. 2006; Hoddinott et al. 2008; Lutter & Lutter 2012; Majo et al. 2013; Sjarif et al. 2020).

The findings of this comprehensive study illuminate the multifaceted relationship between 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 OR 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 multifaceted 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.

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 toward the immune system's defense against infections (Ezeamama et al. 2005; Behrman et al. 2009; 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 (Quick et al. 2010; Cumming & Cairncross 2016).

An insightful discovery was the enhanced effectiveness of combined WASH interventions in improving child NS, surpassing the impact of single interventions. This phenomenon can be logically attributed to the intricate pathways through which fecal-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 fecal-oral diseases. The integration of these interventions, as underscored, is instrumental in not only curbing infections but also in proactively promoting nutrition (Doyle et al. 2009; Cusick & Georgieff 2012; Danaei et al. 2016).

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. This substantiates the profound impact of WASH interventions in curbing pathogen-induced infections and resultant diseases among children. The robust OR, 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 PIs. 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.

In our systematic review and meta-analysis encompassing interventions involving nutritional supplements (NSs) 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 with 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 with 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 & 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 under nutrition 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 NI for addressing both weight and height challenges in at-risk or undernourished children.

Furthermore, a recent Cochrane review by 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 NSs in meeting the diverse nutritional requirements and enhancing the overall NS of children at risk of undernutrition.

Exploring the lack of statistical significance requires a consideration of potential underlying mechanisms. NIs 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 NIs 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 NIs and pathogen-induced infections in children. While there appears to be a trend toward 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 NIs may yield more pronounced effects and contribute to improved pediatric health outcomes.

The study demonstrates several notable strengths. First, 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 PIs. 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 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.

There are various limitations to the study's review processes that need to be taken into account. First off, there's a chance that the search technique will be constrained by publishing bias and language constraints. The review may introduce bias by overlooking pertinent studies published in other languages or unpublished data, as a result of concentrating only on published studies and those written in English. Furthermore, it is possible that the inclusion criteria were overly stringent, leaving out studies that could have offered insightful information.

Furthermore, because various reviewers may interpret the criteria differently, the evaluation of study quality and bias risk may be subjective. This subjectivity has the potential to skew the review procedure. Furthermore, there may be a lack of openness in the decision-making process for data extraction and synthesis, which raises questions regarding the repeatability of the study's conclusions.

The systematic review and comprehensive meta-analysis presented herein provide a robust examination of the effects of WASH and NIs on children's growth indicators and PI rates. The study's meticulous analysis reveals significant insights into the multifaceted relationships between these interventions and child health outcomes.

Regarding WASH interventions, the results underscore their crucial role in improving children's growth and reducing the risk of pathogen-related infections. The meta-analysis showcases the positive impact of WASH interventions on both weight and height outcomes, supported by statistically significant ORs and narrowed CIs. The observed heterogeneity is appropriately addressed through random-effects models and subgroup analyses, which contribute to a comprehensive understanding of the interventions' effects. The substantial reduction in PI risk due to WASH interventions reflects their potential to safeguard child health. However, the study acknowledges the presence of variability among the included studies, suggesting the need for tailored approaches and further investigation into contextual factors.

The findings related to NIs further enhance our understanding of strategies to address undernutrition and promote child growth. Notably, nutritional supplementation proves effective in promoting weight and height gains among undernourished children, with significant ORs and CIs supporting its impact. However, while there is a trend toward a protective effect against PIs, the lack of statistical significance highlights the complexity of this relationship. Variations in intervention strategies and study populations contribute to the observed heterogeneity, calling for nuanced interpretation and further exploration of underlying mechanisms.

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 PI 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.

The authors acknowledge the assistance for this project from the Faculty of Military Pharmacy at the Republic of Indonesia Defense University, Sentul Campus, Indonesia.

All relevant data are included in the paper or its Supplementary Information.

The authors declare there is no conflict.