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![Conceptual Framework for Immune Dysfunction as a Cause and Consequence of Malnutrition. Immune dysfunction can arise before birth via developmental pathways (purple), compounded by environmental and behavioral factors (yellow), particularly those experienced during early life. Immune dysfunction (blue; as defined in a recent systematic review [23] and summarized in Box 2) can contribute both directly and indirectly to a range of causal pathways (green) that lead to clinical malnutrition (red; refer to Box 1 for the clinical features of under- and overnutrition in humans). Abbreviations: HPA, hypothalamus–pituitary–adrenal axis; IGF-1, insulin-like growth factor 1; *, refers to predisposition to metabolic syndrome in adulthood following exposure to undernutrition in infancy.](profile/Claire-Bourke/publication/303555993/figure/fig1/AS:366355367907328@1464357334348/Conceptual-Framework-for-Immune-Dysfunction-as-a-Cause-and-Consequence-of-Malnutrition.png)
Conceptual Framework for Immune Dysfunction as a Cause and Consequence of Malnutrition. Immune dysfunction can arise before birth via developmental pathways (purple), compounded by environmental and behavioral factors (yellow), particularly those experienced during early life. Immune dysfunction (blue; as defined in a recent systematic review [23] and summarized in Box 2) can contribute both directly and indirectly to a range of causal pathways (green) that lead to clinical malnutrition (red; refer to Box 1 for the clinical features of under- and overnutrition in humans). Abbreviations: HPA, hypothalamus–pituitary–adrenal axis; IGF-1, insulin-like growth factor 1; *, refers to predisposition to metabolic syndrome in adulthood following exposure to undernutrition in infancy.
Source publication
Trends
Undernourished children principally die of common infections, and immune defects are consistently demonstrated in under- and overnutrition.
Parental malnutrition leads to epigenetic modifications of infant immune and metabolic genes.
Healthy gut development relies on sensing of dietary nutrients, commensal, and pathogenic microbes via immune...
Citations
... Biological causes like exposure to diseases also increase the risks posed to health by undernutrition. Many studies have established the significant relationship between diseases, such as malaria, bacterial infections, poorer protein and micronutrient status, and immune dysfunction, and undernutrition among children (Gaiha et al., 2014;Arthur et al., 2015;Bourke et al., 2016). This implies the need for better policies and programmes related to increasing sanitisation and hygiene facilities both at a community level and public health facilities and implementation of vitamin-supplementation programmes at community level, which should be some of the priorities of the political representatives in order to uplift the status of their respective constituencies. ...
In India, undernutrition among children has been extremely critical for the last few decades. Most analyses of undernutrition among Indian children have used the administrative boundaries of a state or a district level as a unit of analysis. This paper departs from such a practice and focuses instead on the political boundaries of a parliamentary constituency (PC) as the unit of analysis. The PC is a critical geopolitical unit where political parties and party candidates make election promises and implement programmes to improve the socio-economic condition of their electorate. A focus on child undernutrition at this level has the potential for greater policy and political traction and could lead to a paradigm shift in the strategy to tackle the problem by creating a demand for political accountability. Different dimensions and new approaches are also required to evaluate the socio-economic status and generate concrete evidence to find solutions to the problem. Given the significance of advanced analytical methods and models embedded into geographic information system (GIS), the current study, for the first time, uses GIS tools and techniques at the PC level, conducting in-depth analysis of undernutrition and its predictors. Hence, this paper examines the spatial heterogeneity in undernutrition across PCs by using geospatial techniques such as univariate and bivariate local indicator of spatial association and spatial regression models. The analysis highlights the high–low burden areas in terms of local hotspots and identifies the potential spatial risk factors of undernutrition across the constituencies. Striking variations in the prevalence of undernutrition across the constituencies were observed. Most of these constituencies that performed poorly both in terms of child nutrition and socio-economic indicators were located in the northern, western, and eastern parts of India. A statistically significant association of biological, socio-economic, and environmental factors such as women’s body mass index, anaemia in children, poverty, household sanitation facilities, and institutional births was established. The results highlight the need to bring in a mechanism of political accountability that directly connects elected representatives to maternal and child health outcomes. The spatial variability and pattern of undernutrition indicators and their correlates indicate that priority setting in research may also be greatly influenced by the neighbourhood association.
... An exhaustive assessment of the literature looked at malnutrition and compromised immune function [46,47]. A literature review [48] that included 3402 articles published between 1970 and 1990 and 33 articles after 2003, of which 245 met the inclusion criteria, found that malnutrition was associated with impaired gut-barrier function, decreased exocrine secretion of protective substances, low plasma complement levels along with atrophic thymus, and significant reductions in antibody levels in severely malnourished children after vaccination, as opposed to no such change. ...
Acute poverty has a severe impact on children in India, where 30% of all children living in extreme poverty worldwide are born. The truth is that 36% of the world's poorest children reside in South Asia, with India hosting 84 percent of this population. Besides, more than 45 million children in India are affected by the COVID-19 pandemic's extreme poverty, which accounts for 30% of all children worldwide. Childhood poverty, which is frequently associated with accelerated aging, may have a significant impact on immune system function, which may lead to dysregulation of inflammatory processes in response to foreign substances and a change to unfavorable proinflammatory states. The term "Metabolic Syndrome" (MetS) describes a group of disorders, such as high blood pressure, high blood sugar, insulin resistance (IR) and elevated adiposity, that frequently co-occur and increase the risk of stroke, type 2 diabetes (T2DM), and cardiovascular diseases. An extensive incidence of IR among children exhibiting MetS was found in an Indian cross-sectional investigation. Over time, the scientific community has become more cognizant of the critical role the immune system plays in maintaining systemic metabolic homeostasis. The maintenance of excellent "metabolic health" over the course of a person's life depends critically on this interaction between the immune and metabolic systems. Two major stress-signaling pathways that contribute to immunological dysregulation in children during poverty are the Autonomic Nervous System (ANS) and the Hypothalamic-Pituitary-Adrenal (HPA) axis. Prolonged HPA axis activation brought on by poverty-induced stress can directly contribute to the pathophysiology of T2DM. Early traumatic events and lifestyle modifications induced by poverty may also have an impact on how quickly telomeres shorten throughout the course of a person's lifespan. Telomere shortening brought on by immune system aging slows down T-and B-cell population renewal and clonal proliferation, aggravating MetS. Early-life nutrition results in long-lasting alterations in DNA methylation that have an effect on a person's health and aging-related disorders throughout their lifetime. In order to further validate the causal relationship between these crucial intersecting events that the article seeks to capture during poverty, additional research will be needed to collect data on the prevalence of MetS, immunological parameters, including retrospective and prospective longitudinal studies in larger Indian cohorts.
... Several biological mechanisms have been identified which could be responsible for the association between ambient air pollution and stunting. First, exposure to PM in early-life can adversely affect the development of immune function in children, contributing to recurrent illness [37]. For example, PM might impair linear growth through repeated episodes of febrile respiratory illness, which is associated with an increased risk of child stunting [38]. ...
Background
The evidence regarding the relationship between postnatal exposure of air pollution and child malnutrition indicators, as well as the corresponding urban-rural disparities, is limited, especially in low-pollution area of low- and middle-income countries (LMICs). Therefore, our aim was to contrast the effect estimates of varying ambient particulate matter (PM) on malnutrition indicators between urban and rural areas in Tibet, China.
Methods
Six malnutrition indicators were evaluated in this study, namely, Z-scores of height for age (HFA), Z-scores of weight for age (WFA), Z-scores of weight for height (WFH), stunting, underweight, and wasting. Exposure to particles with an aerodynamic diameter ≤2.5 micron (μm) (PM2.5), particles with an aerodynamic diameter ≤10 μm (PM10) and particles with an aerodynamic diameter between 2.5 and 10 μm (PMc) was estimated using satellite-based random forest models. Linear regression and logistic regression models were used to assess the associations between PM and the above malnutrition indicators. Furthermore, the effect estimates of different PM were contrasted between urban and rural areas.
Results
A total of 2511 children under five years old were included in this study. We found long-term exposure to PM2.5, PMc, and PM10 was associated with an increased risk of stunting and a decreased risk of underweight. Of these air pollutants, PMc had the strongest association for Z-scores of HFA and stunting, while PM2.5 had the strongest association for underweight. The results showed that the odds ratio (OR) for stunting were 1.36 (95% confidence interval (CI) = 1.06 to 1.75) per interquartile range (IQR) microgrammes per cubic metre (μg/m³) increase in PM2.5, 1.80 (95% CI = 1.30 to 2.50) per IQR μg/m³ increase in PMc and 1.55 (95% CI = 1.17 to 2.05) per IQR μg/m³ increase in PM10. The concentrations of PM were higher in urban areas, and the effects of PM on malnutrition indicators among urban children were higher than those of rural children.
Conclusions
Our results suggested that PM exposure might be an important trigger of child malnutrition. Further prospective researches are needed to provide important scientific literature for understanding child malnutrition risk concerning postnatal exposure of air pollutants and formulating synthetically social and environmental policies for malnutrition prevention.
... Maternal malnutrition leads to epigenetic effects. Epigenetic modifications especially through methyl group addition can influence immune system development after conception 28 . Recently the impact of paternal malnutrition has been studied in infants. ...
Eradication of hunger is one of the sustainable development goals listed by the United Nations. By 2050 the expected world population would be 10 billion and to provide food for all, we need to prioritize food security. A robust food security ecosystem will help to ensure that hygienic, nutritious food is available to the general population of a country. A decrease in the production of nutritious and safe food or limited purchasing power of consumers leads to food insecurity. Individuals facing financial constraints are affected the most because of food insecurity and hence are at a high risk of hunger and malnutrition. A deficiency, excess or imbalance of certain nutrients in the diet leads to malnutrition. Malnutrition is often used synonymously with undernutrition, which can be because of a deficiency of protein and/or micronutrients in the diet. Among the micronutrients, iron, zinc, and folic acid deficiency is very prevalent and the leading cause of undernutrition. Protein-energy malnutrition leads to conditions like Marasmus and Kwashiorkor. The common infectious diseases associated with undernutrition are pneumonia, diarrhoea, malaria, measles, and AIDS. Thus, food insecurity poses challenges not only to addressing public health but also affects the overall economic growth and socio-political stability of any nation. Hence at the global level, several programmes have been envisioned by the World Health Organization and United Nations Standing Committee on Nutrition. In context to the Indian population, the Government of India has started implementing various initiatives to establish food security. However, issues such as climate change, drought, floods, demographic changes, wars, increasing global population and pandemics need to be constantly addressed to achieve sustainable developmental goals. In this review, we have discussed what food security is and how in its absence, malnutrition predominates in a sizable population, especially children. The consequences of nutrient deficiency and their relationship with immunity and infection are highlighted and finally, the efforts that are being taken to tackle food security at a global level and in context to Indian issues are discussed.
... Malnutrition, in particular protein-energy undernutrition, is the primary cause of immunodeficiency worldwide [1]. Infection in turn may lead to weight loss and (macro/micro-) nutrient deficiencies that further perturb immune response in a self-enhancing vicious cycle [1,2]. ...
Background:
Nutritional status is a critical factor throughout COVID-19 disease course. Malnutrition is associated with poor outcomes in hospitalized COVID-19 patients.
Aim:
To assess the prevalence of malnutrition and identify its associated factors in COVID-19 survivors.
Methods:
Study cohort included 1230 COVID-19 survivors aged 18-86 attending a post-COVID-19 outpatient service. Data on clinical parameters, anthropometry, acute COVID-19 symptoms, lifestyle habits were collected through a comprehensive medical assessment. Malnutrition was assessed according to Global Leadership Initiative on Malnutrition (GLIM) criteria.
Results:
Prevalence of malnutrition was 22% at 4-5 months after acute disease. Participants who were not hospitalized during acute COVID-19 showed a higher frequency of malnutrition compared to those who needed hospitalization (26% versus 19%, p < 0.01). Malnutrition was found in 25% COVID-19 survivors over 65 years of age compared to 21% younger participants (p < 0.01). After multivariable adjustment, the likelihood of being malnourished increased progressively and independently with advancing age (Odds ratio [OR] 1.02; 95% CI 1.01-1.03) and in male participants (OR 5.56; 95% CI 3.53-8.74). Malnutrition was associated with loss of appetite (OR 2.50; 95% CI 1.73-3.62), and dysgeusia (OR 4.05; 95% CI 2.30-7.21) during acute COVID-19.
Discussion:
In the present investigation we showed that malnutrition was highly prevalent in a large cohort of COVID-19 survivors at 4-5 months from acute illness.
Conclusions:
Our findings highlight the need to implement comprehensive nutritional assessment and therapy as an integral part of care for COVID-19 patients.
... Frequent infections combined with decreased cardiac output increase the risk of heart failure exacerbation and reduce the survival rate of patients. 36 As a chronic state, multiple forms of malnutrition may occur and may overlap in different ways, and the co occurrence of undernutrition with overweight and obesity can create a double burden of malnutrition. The most likely pathogenesis of metabolic syndrome is overnutrition, leading to the accumulation of excessive lipids in organs or tissues. ...
Purpose:
There is a lack of research on nutritional status and poor prognosis in patients with metabolic syndrome and heart failure. This study evaluated the relationship between nutritional status as defined by the PNI and adverse outcomes in patients with metabolic syndrome and heart failure.
Methods:
A total of 1048 heart failure patients with metabolic syndrome admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2019 were consecutively. PNI was used to assess their nutritional status.
Results:
A total of 51.0% of the patients were in the nonmalnutrition group (PNI≥45), 27.9% were in the mild malnutrition group (40≤PNI<45), and 21.1% of patients were in the malnutrition group (PNI<40). At 36 months of follow-up, after adjusting for other confounding factors, malnutrition (PNI<40) was independently associated with all-cause death (HR: 1.787, 95% CI: 1.451-2.201, P<0.001) and cardiovascular death (HR: 1.837, 95% CI: 1.467-2.301, P<0.001). PNI showed additional prognostic predictive value when included in the established risk factor model, both for all-cause death (AUC: 0.620, 95% CI: 0.579-0.661, P<0.001) and cardiovascular death (AUC: 0.596, 95% CI: 0.555-0.636, P<0.001).
Conclusion:
In patients with metabolic syndrome and heart failure, malnutrition assessed by PNI is an independent predictor for all-cause death and cardiovascular death, and PNI is negatively correlated with the occurrence of adverse outcomes.
... [28][29][30] Emerging evidence shows that undernutrition impairs innate and adaptive immune function in children. 31 Deficiencies in micronutrients, including vitamin A and zinc, also increase the risk of infectious illness. 32 In Bangladesh, improvements in child nutrition, as marked by reductions in stunting, are estimated to be one of the most important factors for reducing diarrhearelated mortality. ...
Diarrhea and respiratory illness are leading causes of mortality and morbidity among young children. We assessed the impact of a homestead food production intervention on diarrhea and acute respiratory infection (ARI) in children in Bangladesh, secondary outcomes of the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) cluster-randomized trial. The trial enrolled 2,705 married women and their children 3 years or younger in 96 rural settlements (geographic clusters) in Sylhet Division, Bangladesh. The intervention promoted home gardening and poultry rearing alongside child nutrition and health counseling over 3 years (2015–2018). An 8-month food hygiene behavior change component using emotional drivers was delivered beginning in mid-2017. Caregiver-reported diarrhea and symptoms of ARI in the week preceding the survey were recorded every 2 months. We analyzed 32,460 observations of 3,276 children over 4 years and found that 3.9% of children had diarrhea and 3.4% had an ARI in the prior 7 days. There was no overall effect of the intervention on 7-day diarrhea period prevalence (odds ratio [OR], 0.92; 95% CI, 0.71–1.19), diarrhea point prevalence (OR, 1.03; 95% CI, 0.78–1.36), or 7-day ARI period prevalence (OR, 1.18; 95% CI, 0.88–1.60). There was no impact on diarrhea severity or differences in health-seeking behaviors. Our findings suggest that this homestead food production program was insufficient to reduce morbidity symptoms among children in a rural setting. More comprehensive water, sanitation, and hygiene measures, and behavioral recommendations may be needed to achieve impacts on child health.
... Without treatment, stunting leads to a significant risk of mortality in children under the age of five and is associated with severe lifelong heath and socioeconomic problems. Common issues associated with stunting include immune system dysfunction [3,4], cognitive impairment [5,6], poverty, and paradoxically excessive weight gain later in life often resulting in obesity and with it diseases such as type 2 diabetes and cardiovascular diseases [7,8]. While nutrient limitation plays a significant role in the development of stunting, it is not the sole driver. ...
Background
Stunting is a global health problem affecting hundreds of millions of children worldwide and contributing to 45% of deaths in children under the age of five. Current therapeutic interventions have limited efficacy. Understanding the epigenetic changes underlying stunting will elucidate molecular mechanisms and likely lead to new therapies.
Results
We profiled the repressive mark histone H3 lysine 9 trimethylation (H3K9me3) genome-wide in peripheral blood mononuclear cells (PBMCs) from 18-week-old infants (n = 15) and mothers (n = 14) enrolled in the PROVIDE study established in an urban slum in Bangladesh. We associated H3K9me3 levels within individual loci as well as genome-wide with anthropometric measurements and other biomarkers of stunting and performed functional annotation of differentially affected regions. Despite the relatively small number of samples from this vulnerable population, we observed globally elevated H3K9me3 levels were associated with poor linear growth between birth and one year of age. A large proportion of the differentially methylated genes code for proteins targeting viral mRNA and highly significant regions were enriched in transposon elements with potential regulatory roles in immune system activation and cytokine production. Maternal data show a similar trend with child’s anthropometry; however, these trends lack statistical significance to infer an intergenerational relationship.
Conclusions
We speculate that high H3K9me3 levels may result in poor linear growth by repressing genes involved in immune system activation. Importantly, changes to H3K9me3 were detectable before the overt manifestation of stunting and therefore may be valuable as new biomarkers of stunting.
... This presents a significant health challenge given that undernutrition in children raises their risk of infection and causes poor or delayed cognitive development [4]. Additionally, undernourished children are more likely to die of diseases such as respiratory infections and malaria as they have decreased biological capacity to fight infections [5]. These issues suggest the need for urgent strategies toward decreasing undernutrition in children. ...
Background
Benin ranks as one of the countries in the world with an alarmingly high prevalence of stunt- ing, wasting, and underweight in children under five years. However, limited studies have examined the factors associated with the prevalence of these undernutrition indicators among children under five years in the country. This study aimed to fill this research gap by examining the prevalence rates and factors associated with stunting, wasting, and under- weight among this specific population of interest.
Methods
This quantitative study utilised data from the most recent Benin Demographic and Health Survey (BDHS) conducted in 2017–18. The survey employed a nationally representative cross-sectional design and utilised a two-stage stratified cluster sampling technique to select participants. The study included a sample of 13,589 children under the age of five years. The main analytical approach employed was binary logistic regression, which was used to explore the associations between undernutrition (the combined outcome variable representing stunting, wasting, and underweight) and various socio-demographic factors.
Results
The combined prevalence of stunting, wasting, and underweight among children under five years in Benin during the 2017–18 survey period was 14.95%. Several factors were signifi- cantly associated with these indicators of undernutrition, including female gender (AOR = 0.71, 95% CI = 0.59–0.85), birth weight of 4.1 kg and over (AOR = 0.26, 95% CI = 0.14– 0.48), multiple births (AOR = 3.22, 95% CI = 2.11–4.91), and a child’s experience of diar- rhoea (AOR = 1.76, 95% CI = 1.40–2.20). Furthermore, the prevalence of these undernutrition indicators was higher among children whose mothers had lower levels of edu- cation (AOR = 0.82, 95% CI = 0.01–0.42) and were unmarried (AOR = 0.67, 95% CI = 0.49– 0.93).
Conclusions
This present study confirms that undernutrition rates are elevated in Benin and are closely linked to perinatal factors such as birth weights and multiple births, postnatal health condi- tions including diarrheal episodes, and socio-demographic determinants such as a child’s gender, maternal education level, and marital status. Therefore, there is the need to con- sider specific modifiable factors, such as low birth weight, episodes of child diarrhoea, and maternal education as priority targets for child nutrition interventions in Benin.
... Almost half of deaths among children under the age of five are due to undernutrition [1], making this a crucial global public health issue. Undernutrition at an early age affects brain development [2] and immune function [3] resulting in lower educational attainment, later cognitive impairment [4] and increased risks of infection and chronic diseases. Altogether, impacts of undernutrition can lead to higher morbidity and mortality [5], result in substantial losses in disability-adjusted life years, inhibit productive work [6], and reduction in economic productivity [7]. ...
Background
Several studies have been conducted to understand the impact of socioeconomic and maternal factors on child undernutrition. However, the past literature has not directly examined the joint impacts of fuel use and ambient pollution and have primarily focused on PM2.5.
Objective
This study explored the individual and community-level associations of both indoor (cooking fuel type) and ambient air pollution (PM2.5, NO2 and SO2) during maternal gestation on child undernutrition.
Methods
This study analysed stunting, being underweight, and anaemia of children aged 0–59 months (n = 259,627) using the National Family Health Survey. In-utero exposures to ambient PM2.5, NO2, and SO2 were measured using satellite data and self-reported fuel type was a marker of indoor pollution exposure. The study used univariate and bivariate Moran’s I, spatial lag model and multivariable logistic regression models after adjusting for other covariates to understand the effect of pollution on in-utero exposure and child health status at the individual and community-levels.
Results
Higher concentration of indoor and ambient air pollution was found in the Northern and parts of Central regions of India. Estimates of spatial modelling show that each 1 μg/m–3 increase in maternal exposure to ambient PM2.5 across the clusters of India was associated with a 0.11, 9 and 19 percentage points increase in the prevalence of stunting, underweight and anaemia, respectively. The results of multi-pollutant model show that a higher ambient PM2.5 exposure during pregnancy was linked to higher odds of stunting (AOR:1.38; 95% CI:1.32–1.44), underweight (AOR:1.59; 95% CI:1.51–1.67) and anaemia (AOR:1.61; 95% CI:1.52–1.69) in children. Weaker but similar associations were observed for NO2, but not with SO2. Indoor pollution exposure during in-utero periods was also significantly associated with childhood undernutrition and this association was modified by ambient PM2.5 levels, where exposure to both indoor and ambient air pollution had even greater odds of being undernourished.
Impact statement
Our research on multi-pollutant models has revealed the initial proof of the individual impacts of indoor and outdoor pollution (PM2.5, NO2, and SO2) exposure during fetal development on children’s nutrition.
