Allostasis, health, and development in Latin America

Summary

The lifespan is influenced by adverse childhood experiences that create predispositions to poor health outcomes. Here we propose an allostatic framework of childhood experiences and their impact on health across the lifespan, focusing on Latin American and Caribbean countries. This region is marked by significant social and health inequalities nested in environmental and social stressors, such as exposure to pollution, violence, and nutritional deficiencies, which critically influence current and later-life health outcomes. We review several manifestations across cognition, behavior, and the body, observed at the psychological (e.g., cognitive, socioemotional, and behavioral dysfunctions), brain (e.g., alteration of the development, structure, and function of the brain), and physiological levels (e.g., dysregulation of the body systems and damage to organs). To address the complexity of the interactions between environmental and health-related factors, we present an allostatic framework regarding the cumulative burden of environmental stressors on physiological systems (e.g., cardiovascular, metabolic, immune, and neuroendocrine) related to health across the life course. Lastly, we explore the relevance of this allostatic integrative approach in informing regional interventions and public policy recommendations. We also propose a research agenda, potentially providing detailed profiling and personalized care by assessing the social and environmental conditions. This framework could facilitate the delivery of evidence-based interventions and informed childhood-centered policy-making.

Introduction

Childhood experiences and environmental exposures significantly drive overall health across the lifespan (Bhutta et al., 2023), determining different life trajectories (Hughes et al., 2017). Adverse childhood experiences (ACEs) are potentially traumatic childhood events with lasting adverse health effects, such as poverty, undernutrition, and maltreatment. ACEs are associated with a wide variety of poor outcomes, ranging from health and human capital (Victora et al., 2022), personal and country-level economy (Bellis et al., 2019), to morbidity and mortality (Grummitt et al., 2021). Rather than simple and one-to-one effects, the relationship between ACEs and life trajectories is mediated by complex interdependent influences between individual (e.g., genetics and brain development) and environmental factors (e.g., family income and neighborhood characteristics) (Lindenberger et al., 2006; Westermann et al., 2007). In Latin American and Caribbean countries (LAC), a highly heterogeneous region marked by social and health inequalities and social adversities (Messina and Silva, 2017; Parra et al., 2018; Programme, 2021), ACEs interact with the unique sociodemographic, environmental, and cultural characteristics of the region to create a unique blending between the environment and the body. In this perspective piece, we argue that an allostatic framework provides theoretical and analytical tools to address this complex set of interactions and approach health in children from LAC.

We first provide an overall background about the multilevel impact of ACEs at the psychological, brain, and physiological levels, as well as the biological mechanistic explanations provided. Then, we describe the environmental stressors from LAC and the most common ACEs that children face, such as exposure to contaminants and harmful toxins, high rates of violence against children, and the burden of nutritional deficiencies. We highlight the need to implement adequate models at research and public health policy levels to consider the interrelated environment and body health dynamics. In the next section, we introduce the concept of allostasis, which refers to a process of predictive regulation of the body systems, commanded by the brain’s feed-forward predictions about the state of the world, which guide multisystemic changes in the body to adapt to external demands (Schulkin and Sterling, 2019a). Assessing specific situations (i.e., environmental stressors) that the body faces and how it responds to them provides a unique approach to developmental health (Sterling, 2020). Lastly, we propose a new framework for implementing allostatic load measures at a public policy level and incorporating them into targeted interventions for LAC children (Figure 1). To support these claims, we performed a scoping review searching for the existing evidence on childhood and allostatic load in LAC samples. Based on this background, we propose a set of testable hypotheses and proposals to develop this framework: the use of longitudinal designs assessing the interaction between ACEs and allostatic load across developmental stages and the mediator variables; the expansion of allostatic load measurements by including the brain level into the scoring; the development of interventions to reduce allostatic load early in life and testing its effectiveness by examining developmental and health outcomes; and the implementation of a task force with policy-makers and health care providers to gather their perception on incorporating allostatic load measurements into public health policy and primary care. Those suggestions may positively impact childhood and outcomes later in life.

Figure 1.

An allostatic framework for addressing health and development in Latin America. Latin American children from disadvantaged backgrounds face a range of adverse childhood experiences at multiple levels (left panel), including increased exposure to pollutants and limited access to green spaces due to poor urban planning, amplified rates of physical and psychological violence, and a high prevalence of undernutrition and obesity. These exposures and conditions have multilevel effects on health (right panel), such as cognitive, socioemotional, and psychosocial problems; alterations in brain development, structure, and connectivity; and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function and accelerated development indexed by epigenetic changes. Allostatic load indexes, including biomarkers of the cardiovascular, metabolic, immune, and neuroendocrine systems are well situated to provide measures of cumulative burden.

Multilevel impacts of adverse childhood experiences on health

ACEs are a relevant factor associated with health outcomes (Bhutta et al., 2023), whose morbidity and mortality are equivalent to other well-established factors, such as substance use, sedentary behavior, and obesity (Grummitt et al., 2021). ACEs are highly stressful and potentially traumatic events associated with physical and emotional abuse, neglect, dysfunction in the home, caregiver-child separation, violence exposure, and poverty, among others (Prevention, 2023; Scientific Council and Barlow, 2014). Negative health outcomes ranging from depression to diabetes (Bhutta et al., 2023) are associated with antecedents of ACEs. This effect of ACEs impacts cognition, behavior, and the functioning of multiple body systems.

At the psychological level, ACEs are associated with lower executive performance in children exposed (Lund et al., 2020), in addition to socioemotional and behavioral difficulties such as depression, anxiety symptoms, and internalizing and externalizing problems in children (McLaughlin, 2016; Xiao et al., 2023a; Xiao et al., 2023b; Xu et al., 2022). In adolescents, ACEs can negatively affect socioemotional processes, predispose to mental health problems (Ceccarelli et al., 2022; Derin et al., 2022; Kovacs-Toth et al., 2021; Stinson et al., 2021), and may be associated with health risk behaviors and behavioral problems (Anderson et al., 2022; Chen, 2022; Jackson et al., 2023; Maurya and Maurya, 2023; Myat Zaw et al., 2022; Wang et al., 2023; Xu et al., 2023). These manifestations are linked to multilevel dysregulations across the body throughout development.

At the brain level, children exposed to ACEs are associated with atypical brain development of the prefrontal cortex, amygdala, hippocampus, and white matter tracts linking the prefrontal and parietal cortex (Kraaijenvanger et al., 2020; Mothersill and Donohoe, 2016; Riem et al., 2015; Sheridan et al., 2022). Such impact may not be ontogenetically uniform but depends on the age, type of adversity, and brain region. For instance, recent meta-analytical evidence (Vannucci et al., 2023) shows that interpersonal early adversity is initially associated with larger volumes in frontolimbic regions, which are maintained until more or less 10 years of age, after which the volume shrinks considerably. In the case of exposure to childhood socioeconomic disadvantage, temporal-limbic regions have smaller volumes in childhood, and this attenuates with age (Vannucci et al., 2023). ACEs in adolescence may induce alterations in the development of limbic and striatal regions critical for emotional regulation and psychosocial functioning, such as the hippocampus, subgenual cingulate, amygdala, caudate, and insula (Laricchiuta et al., 2023; Luby et al., 2019). The impact of ACEs on brain regions critical for cognitive and socioemotional functioning is connected to other body systems, which are also dysregulated by exposure to ACEs.

At the physiological level, ACEs are related to stress responses and hypothalamic-pituitary-adrenal (HPA) axis dysregulation (Hakamata et al., 2022). Maltreatment blunts cortisol response to social stress, wake-up cortisol levels, and morning-to-evening slope/change, suggesting a dysregulation of the arousal threshold of the HPA axis (Bernard et al., 2017; Bunea et al., 2017). Regarding inflammatory biomarkers, children and adolescents with antecedents of ACEs have elevated levels of the C-reactive protein, indicative of chronic inflammation (Kuhlman et al., 2020). Childhood abuse is linked with the epigenetic regulation of the glucocorticoid receptor in the brain associated with altered stress responses, which may have implications for mental health outcomes later in life (McGowan et al., 2009). Also, children and adolescents exposed to stressful life events show an accelerated pace of development measured by epigenetic clocks, also linked with depressive symptoms (Sumner et al., 2023). In adolescents, ACEs have been observed to increase the adiposity and incidence of obesity with poorer health outcomes (Davis et al., 2019; Deng and Lacey, 2022; Gardner et al., 2019; Isohookana et al., 2016; Rofey et al., 2018; Soares et al., 2018), sleep disturbances (Lin et al., 2022; Mlouki et al., 2023; Park et al., 2021; Rojo-Wissar et al., 2021), and increased incidence of cardiovascular disease and cardiometabolic dysregulation (Andrade et al., 2021; Kellum et al., 2023; Klassen et al., 2016; Kliewer and Robins, 2022). Thus, multiple body systems of children and adolescents are dysregulated by the stress generated by ACEs, which evidences its multilevel impact on health. Such impact is not only associated with short-term negative health outcomes but also with lifelong burden (Panel 1).

Panel 1. The lifelong impact of ACEs on health.

Adults exposed to ACEs are associated with subjective (Baiden et al., 2022; Terry et al., 2023) and objective cognitive imparimet (Kobayashi et al., 2020; Lin et al., 2022; Zhang et al., 2023), as well as behavioral problems such as higher incidence of problematic substance consumption (Broekhof et al., 2023; Rogers et al., 2022). At brain level, ACEs may alter the prefrontal cortex, globus pallidus, thalamus, amygdala, and insula, which could be carried over from adolescence and may be linked to the development of mental disorders in adulthood (Hakamata et al., 2022). Most of these regions are involved in brain networks critical for context processing and behavioral adjustment (i.e., the social context brain network (Baez et al., 2017)), and regulatory processes in response to environmental demands (i.e., the allostatic-interoceptive network (Kleckner et al., 2017b)). At the physiological level, ACEs are associated with a higher incidence of obesity (Chu and Chu, 2021; Wang et al., 2022; Wiss and Brewerton, 2020), sleep disturbances (Albers et al., 2022; Geng et al., 2021; Guan and Cui, 2023; Vadukapuram et al., 2022; Yu et al., 2022), accelerated epigenetic aging (McCrory et al., 2022) and increased incidence of cardiovascular disease and cardiometabolic dysregulation (Deschenes et al., 2021; Flores-Torres et al., 2020; Liu et al., 2022; Moliner et al., 2022). The persistent, multilevel effects of ACEs on health are transmitted from childhood to adulthood, ranging from cognitive deficits and maladaptive behaviors, altered neurodevelopment, and dysregulated responses to stress, to adult cognitive impairment and substance abuse, alteration of brain structures critical for social functioning and self-regulation, and poor health outcomes.

In older adults, there is evidence that ACEs are associated with deficits in cognitive (Gold et al., 2021; Halpin et al., 2022; Kobayashi et al., 2020; O’Shea et al., 2021) and functional abilites (Li et al., 2022; Peele, 2019), and substance abuse (Kim et al., 2021; Larkin et al., 2017). At the brain level, they are linked to altered structure of the rostral middle frontal, lateral orbitofrontal, superior parietal, precuneus, putamen, and thalamus (Ancelin et al., 2021), and a higher incidence of dementia (Schickedanz et al., 2022), including Alzheimer’s disease (Corney et al., 2022). At the physiological level, epigenetic age acceleration (Beach et al., 2022; Joshi et al., 2023; McCrory et al., 2022; Mian et al., 2022), frailty (Mian et al., 2022; Yan et al., 2022), immune system inflammation (Iob et al., 2023), and multimorbidity (Atkinson et al., 2023) has been observed. In summary, ACEs display a far-reaching impact on health at multiple scales, across the life course, ranging from childhood to older age.

Biological mechanistic explanations of the association between ACEs and health have been provided, being the alteration of the stress response of the HPA axis is one of the most extensively studied (Bhutta et al., 2023; Jensen et al., 2017). Although the functioning of the HPA axis is an adaptive response to cope with stressors, its persistent activity due to the presence of chronic stressors damages health at several scales. HPA axis dysfunction is associated with lower cognitive performance (Braren et al., 2020) and higher emotional reactivity (Di Iorio et al., 2017). Also, it shows long-lasting impairments in neuroendocrine stress responses (e.g., cortisol secretion), which potentially contribute to various aspects of neural circuit malfunction and future psychopathology (Malave et al., 2022). This imbalance is also associated with inflammatory and metabolic dysfunctions, as the exacerbated stress response produces immunosuppression by energy balancing effect and impairs nutrient absorption and immune defenses (Jensen et al., 2017). As the stressors generated by ACEs persist and the dysregulated HPA axis response is maintained over time, damage accumulates in the body and poor health outcomes occur (Hakamata et al., 2022).

In brief, the psychological, brain, and physiological levels are markedly affected by ACEs. Given the systemic-relational context in which ACEs occur, involving environmental and social elements, their impact on health should be approximated by considering sociodemographic, environmental, and cultural elements. To accomplish this approach, in the next section, we introduce the LAC context and highlight the most burdensome adversities children face, especially those from disadvantaged backgrounds.

Childhood adversities in the Latin American and Caribbean context

LAC is a highly heterogeneous region, characterized by marked inequalities and social adversities (Messina and Silva, 2017; Parra et al., 2018; Programme, 2021), that impacts developmental outcomes (De Barros, 2009; Piai and Olympio, 2023; Zafra-Tanaka et al., 2023). This is the region with the largest proportion of the population living in urban areas, a transition that occurred much more rapidly than in any other region leading to urban growth with little to no planning in many cases (Anza-Ramirez et al., 2022; Miranda et al., 2019). This has led to the unequal distribution of green spaces benefiting affluent groups, precluding their positive effects on health (e.g., protection against obesity and high body-mass index) to people from underserved backgrounds (Anza-Ramirez et al., 2022), and being associated with poor outcomes (e.g., higher prevalence of type two diabetes) (Moran et al., 2021). Indeed, people from underserved backgrounds from LAC tend to be more exposed to environments contaminated by harmful toxins, such as lead (an elemental heavy metal found in the environment) which have critical impacts on health outcomes (Piai and Olympio, 2023), brain development, and cognition (Ramirez Ortega et al., 2021). In addition, people in underserved conditions in LAC commonly live in unsafe neighborhoods, inadequate housing, and poor educational and healthcare facilities (Busso and Messina, 2020), generating cumulative and co-occurrent exposure to multi-environmental influences throughout the lifespan, which can be approached through the SDH perspective (Organization, 2022). Children are exposed to exposome stressors associated with nurturing, such as negative caregiver responses, violence, and nutritional deficiencies (FAO et al., 2023; UNICEF, 2022).

Violence against children in LAC is alarmingly high, usually accompanied by poor school performance, poor mental health, suicidal thoughts, and social exclusion (UNICEF, 2022). Two out of three children between the ages of one and 14 years are subjected to violence at home, such as physical punishment, which is prohibited in only 11 countries from a total of 33 (UNICEF, 2022). Violence against children can be exacerbated by parental burnout, defined as a chronic stress syndrome in the context of parenting that results from an imbalance between stressors and parental resources (Mikolajczak et al., 2021). Parental burnout increases the frequency of neglectful and violent behaviors toward children (Mikolajczak et al., 2018). This is particularly relevant in LAC, as the arrival of the COVID-19 pandemic exacerbated the prevalence of mental health disturbances among caregivers, including parental burnout. Some of the most affected countries include Chile (Ben Brik et al., 2022; Giraldo et al., 2022), Colombia, and Peru (Van Bakel et al., 2022). Thus, violence against children and adolescents in LAC seems to be a distinctive characteristic of parenting in the region.

Children from LAC who grow up in family environments exposed to high levels of stress and violence are at increased risk of developing food insecurity (FAO et al., 2023). Those typically present a distinctive triple burden of nutritional deficiencies among children and adolescents: overweight/obesity, undernutrition, and micronutrient deficiency (UNICEF, 2021). Nutrition is critical to support metabolic processes in the brain and body (Jensen et al., 2017), affecting motor, cognitive, and socioemotional functions through its role in neurotransmitter synthesis and regulation (Batis et al., 2020; McCarthy et al., 2022; Melo et al., 2023a). Lack of nutrients impairs neurodevelopment, affecting brain structure and function, including axonal and dendritic growth, myelination, cell differentiation and proliferation, and programmed cell death, leading to neurocognitive deficits (Jensen et al., 2017). Malnutrition can also degrade skin and intestinal barriers, increasing the risk of infections and chronic inflammation (Rytter et al., 2014), and disrupt immune function by altering cytokine signaling in various immune pathways (de Heredia et al., 2012). It is estimated that the prevalence of being overweight among children under 5 years of age is 7·5%, while the world average is 5·6%. In short, three out of ten children from LAC are overweight (UNICEF, 2021), placing malnutrition as one of the most complex and burdensome LAC public health challenges (Melo et al., 2023a), constituting a significant risk factor for premature development of cardiovascular and metabolic diseases (ECLAC/UNICEF, 2018), and a leading cause of death across LAC countries (OECD and Bank, 2023). The causes of malnutrition in the region are associated with unhealthy urban lifestyles (e.g., sedentary behaviors, hyperconsumption of fast food) and obesogenic food environments (e.g., greater ease of consuming ultra-processed foods than healthy foods) (Miranda et al., 2019; UNICEF, 2021). Thus, the environmental stressors that children are exposed to get embedded in the body as nutritional deficiencies, being associated with poor health outcomes (Miranda et al., 2019).

In summary, living conditions, exposure to contaminants, violence, parental burnout, and nutritional deficiencies impact development and health. In this complex scenario of interactions between the body and environment, we will argue that a suitable model to integrate environmental exposures of the region and their impact on the body in children from LAC is through the allostatic framework.

Tackling the complexity: the allostatic framework

The allostatic framework understands health as a dynamic factor, incorporating how the body (mastered by the brain) predicts environmental stress and generates anticipatory changes (e.g., increasing the frequency of the heartbeats) to prepare against those demands (Sterling, 2020). When the anticipatory changes in the body are in line with those required to face the environmental demand (e.g., the increase in the muscular tone is adequate to lift a heavy object but the arm does not become completely rigid), the body regains its baseline functioning and the momentary overconsumption of energy (i.e., adenosine triphosphate and the molecular processes for its synthetization) dissipates and the body regains equilibrium by a homeostatic response (Schulkin and Sterling, 2019b). When environmental demands involve a significant burden on the body, the anticipatory changes must match the state of the body predicted to be adequate to cope with such demands (Schulkin and Sterling, 2019b; Sterling, 2020). Critically, when this heightened anticipatory response is repeated over time due to the presence of chronic stressors, the body is forced to constantly function over its normal capacity to match the state predicted to cope with stressors, thus damage accumulates (Sterling, 2020). When the body reaches (dys)equilibrium under this condition, allostatic load ensues and health worsens (McEwen, 2012; McEwen et al., 2015).

Under conditions of allostatic load, there is a discordance between the energy anticipated to cope with environmental demands and the actual energy required. This causes hypo or over-expression of the mediators of allostasis, such as the production of cortisol and adrenaline in response to environmental demands (McEwen, 2012; McEwen et al., 2015) In consequence, energy needs exceed the energy stores (type one allostatic load (McEwen and Wingfield, 2003)), causing the brain to divert energy from metabolically tolerant organs and tissues (e.g., kidney and skin), toward relevant muscles or organs (e.g., to the legs muscles in need to run from a potential danger) (Schulkin and Sterling, 2019b). On the other hand, energy needs cannot be considered sufficient based on brain predictions (type two allostatic load (McEwen and Wingfield, 2003)), which may induce an exacerbated amount of energy input (e.g., food consumption) in relation to the actual energy required. Importantly, considering that allostatic load impacts physiopathology (Finlay et al., 2022b; Guidi et al., 2021), its measurements may be relevant for use in clinical settings. This has been reflected in the development of allostatic load indexes as multisystemic markers for quantifying physiological dysregulation (Beese et al., 2022; Carbone et al., 2022; McCrory et al., 2023).

An allostatic load index can be obtained from the quantification of multisystemic biomarkers reflecting the ‘wear and tear’ caused in the body due to exposure to environmental demands (McCrory et al., 2023). Typically biomarkers of the cardiovascular (e.g., systolic and diastolic blood pressure), metabolic (e.g., high-density lipoprotein, hemoglobin A1c), immune (C-reactive protein, interleukin-6), and neuroendocrine systems (e.g., cortisol, epinephrine) are employed (Beese et al., 2022). Level quantification and cutoff values are based on specific sample distribution or a clinically determined value (Carbone et al., 2022). These markers also can be decomposed into specific body systems (Carbone et al., 2022). The allostatic load indexes provide a measure of the functioning of the body systems employed in a variety of diseases (cancer, diabetes, cardiovascular diseases, and mental and psychiatric health (Finlay et al., 2022b; Guidi et al., 2021)) useful as targets for interventions (Rosemberg et al., 2020). More importantly, ACEs have been associated with elevated allostatic load and poor health outcomes (Finlay et al., 2022a) (Figure 2). The allostatic load indexes can provide an informative assessment of health at the interface between the body and environment to address the current challenges in LAC.

Figure 2.

Relationships between ACEs, allostatic load, and health and cognitive outcomes. The figure shows the studies included in the systematic review performed by Finlay et al. (Finlay et al., 2022a) considering measures of ACEs, their influence on biomarkers of allostatic load, and health and cognitive outcomes. Rogosch et al.(Rogosch et al., 2011) and O’Shields & Gibbs(O’Shields and Gibbs, 2021) (red lines) showed that childhood maltreatment increases the allostatic load, including biomarkers of the neuroendocrine (dehydroepiandrosterone [DHEA], cortisol, and norepinephrine; brown rectangles), immune (interleukin-6 [IL-6] and C-reactive protein [CRP]; black rectangles), metabolic (waist circumference, hemoglobin A1C [HbA1c], high-density lipoprotein cholesterol [HDL], and body mass index [BMI]; gray rectangles), and cardiovascular systems (systolic blood pressure and heart rate; purple rectangles). Increased allostatic load, in turn, was associated with the intensity of depressive symptoms, somatic complaints, attention problems, and thought problems. Scheuer et al.(Scheuer et al., 2018) (yellow lines) showed that the effect of childhood trauma and abuse (physical and emotional) on depressive symptoms was mediated by allostatic load, taking into account neuroendocrine (cortisol), immune (CRP), metabolic (waist circumference, HbA1c, HDL, and BMI), and cardiovascular systems (systolic blood pressure) biomarkers. Atkinson et al.(Atkinson et al., 2023) (red lines) reported that allostatic load biomarkers of the metabolic (waist circumference, HbA1c, HDL, and BMI) and cardiovascular systems (systolic blood pressure and heart rate) mediated the impact of childhood physical, emotional and sexual abuse, and neglect on multimorbidity. Lastly, Evans & Fuller-Rowell(Evans and Fuller-Rowell, 2013) (blue lines) showed that childhood poverty was associated with elevated allostatic load, as indexed by biomarkers of the neuroendocrine (cortisol and norepinephrine), metabolic (BMI), and cardiovascular systems (systolic blood pressure and heart rate), which in turn were associated with poorer working memory performance. Asterisks indicate a significant mediation effect of allostatic load biomarkers on health outcomes.

Allostasis and ACEs in LAC

We propose to incorporate the theoretical and analytical tools provided by the allostatic framework to approach the interaction between ACEs and the sociodemographic, environmental, and cultural characteristics of LAC to inform the health status of children from LAC. Specifically, we propose to rethink the approach to health, from the mere state of the body to the interface between the brain, body, and environment (i.e., predictive regulation). In concrete, this could be materialized at a public health policy level by the inclusion of the allostatic load index, allowing important benefits such as the identification of children at risk of poor health outcomes. Also, the allostatic load index decomposition into body systems could inform pre-clinical screening and tailored interventions.

This framework advances the current research on allostatic loading in LAC. To identify the usefulness and novelty of our proposal, we performed a scoping review following PRISMA guidelines (Tricco et al., 2018) searching for articles measuring allostatic load in children from LAC or associating allostatic load retrospectively with ACEs (see Panel 2 for the keywords used, Figure 3 for the PRISMA flow diagram, and Table 1 for the summary of the articles selected). This evidence, yet incipient and not without contradictory results (Arevalo et al., 2014; Cedillo et al., 2019), shows associations between ACEs such as socioeconomic adversity (Gallo et al., 2019) and migration with allostatic load (Arevalo et al., 2014). Also, higher allostatic load in children from LAC compared to other regions (Cedillo et al., 2019). In summary, the evidence addressing the relationship between allostatic load and ACEs in the LAC population shows promising initial results but is limited and presents contradictory findings. For instance, while Hispanic American children tend to exhibit higher allostatic load than their African American and European American counterparts (Cedillo et al., 2019), there is a consistent line of research documenting health advantages among Hispanic individuals living in the United States (i.e., the “Hispanic paradox”) (Montoya-Williams et al., 2021). These antecedents highlight the need to develop a common integrated framework that can account for the granularity of the phenomenon through a detailed analysis of the different levels involved in the interaction between the body and the environment.

Panel 2. Keywords used in the PRISMA scoping review.

Scopus: (TITLE-ABS-KEY (aruba OR bahamas OR barbados OR “cayman islands” OR cuba OR dominica OR “dominican republic” OR grenada OR guadeloupe OR haiti OR jamaica OR martinique OR “puerto rico” OR “saint barthélemy” OR “virgin islands” OR belize OR “costa rica” OR “el salvador” OR guatemala OR honduras OR mexico OR nicaragua OR panama OR argentina OR bolivia OR brazil OR chile OR colombia OR ecuador OR “french guiana” OR guyana OR paraguay OR peru OR suriname OR uruguay OR venezuela OR “South America” OR “Latin America” OR “Central America” OR “Hispanic Americans”) AND TITLE-ABS-KEY (allostasis OR allostatic))

PubMed: (“Aruba”[Mesh] OR “Bahamas”[Mesh] OR “Barbados”[Mesh] OR “West Indies”[Mesh] OR “Cuba”[Mesh] OR “Dominican Republic”[Mesh] OR “Grenada”[Mesh] OR “Guadeloupe”[Mesh] OR “Haiti”[Mesh] OR “Jamaica”[Mesh] OR “Martinique”[Mesh] OR “Puerto Rico”[Mesh] OR “Belize”[Mesh] OR “Costa Rica”[Mesh] OR “Guatemala”[Mesh] OR “Honduras”[Mesh] OR “Mexico”[Mesh] OR “Nicaragua”[Mesh] OR “Panama”[Mesh] OR “Argentina”[Mesh] OR “Bolivia”[Mesh] OR “Brazil”[Mesh] OR “Chile”[Mesh] OR “Ecuador”[Mesh] OR “French Guiana”[Mesh] OR “Guyana”[Mesh] OR “Paraguay”[Mesh] OR “Peru”[Mesh] OR “Suriname”[Mesh] OR “Uruguay”[Mesh] OR “Venezuela”[Mesh] OR “South America”[Mesh] OR “Latin America”[Mesh] OR “Central America”[Mesh]) AND (“Allostasis”[Mesh]))

Web Of Science: (aruba OR bahamas OR barbados OR “cayman islands” OR cuba OR dominica OR “dominican republic” OR grenada OR guadeloupe OR haiti OR jamaica OR martinique OR “puerto rico” OR “saint barthélemy” OR “virgin islands” OR belize OR “costa rica” OR “el salvador” OR guatemala OR honduras OR mexico OR nicaragua OR panama OR argentina OR bolivia OR brazil OR chile OR colombia OR ecuador OR “french guiana” OR guyana OR paraguay OR peru OR suriname OR uruguay OR venezuela OR “South America” OR “Latin America” OR “Central America” OR “Hispanic Americans” (Title)) AND (Allostasis OR allostatic (All Fields))

Scielo: (*aruba OR bahamas OR barbados OR “islas cayman” OR cuba OR dominica OR “república dominicana” OR grenada OR guadalupe OR haití OR jamaica OR martinica OR “puerto rico” OR “saint barthélemy” OR “islas vírgenes” OR belice OR “costa rica” OR “el salvador” OR guatemala OR honduras OR méxico OR nicaragua OR panamá OR argentina OR bolivia OR brasil OR chile OR colombia OR ecuador OR “guayana francesa” OR guyana OR paraguay OR perú OR surinam OR uruguay OR venezuela OR “américa del sur” OR “américa latina” OR “centroamérica” OR “hispanoamericanos” (All Fields)) AND (Alostasis OR “carga alostatica” OR alostatic* (All Fields))

Lilacs: (aruba OR bahamas OR barbados OR “islas cayman” OR cuba OR dominica OR “república dominicana” OR grenada OR guadalupe OR haití OR jamaica OR martinica OR “puerto rico” OR “saint barthélemy” OR “islas vírgenes” OR belice OR “costa rica” OR “el salvador” OR guatemala OR honduras OR méxico OR nicaragua OR panamá OR argentina OR bolivia OR brasil OR chile OR colombia OR ecuador OR “guayana francesa” OR guyana OR paraguay OR perú OR surinam OR uruguay OR venezuela OR “américa del sur” OR “américa latina” OR “centroamérica” OR “hispanoamericanos” (All Fields)) AND (“Alostasis” OR “carga alostatica” OR “alostatic* (All Fields)).

Figure 3.

PRISMA flow diagram.

Table 1.

Selected articles from the PRISMA scoping review.

Authors	Year	Type of study	Country of origin of the sample	Age	Group size	Allostatic load measurement	Hypotheses tested	Findings
Gallo, L. C., Roesch, S. C., Bravin, J. I., Savin, K. L., Perreira, K. M., Carnethon, M. R., Delamater, A. M., Salazar, C. R., Lopez-Gurrola, M., & Isasi, C. R.	2020	Cross-sectional	Central or South America Cuba Dominican Republic Mexico Puerto Rico	8–16	1343	BMI DBP e-Selectin Fasting glucose HbA1c HDL cholesterol HOMA-IR CRP LDL cholesterol PAI-1 Pulse rate SBP Triglycerides Waist circumference	Socioeconomic adversity and allostatic load will be associated. Protective social resources will attenuate the association between socioeconomic adversity and allostatic load Social resources and allostatic load will be associated.	Higher socioeconomic adversity was associated with higher allostatic load. The association between socioeconomic adversity and allostatic load was not affected by protective social resources. Higher social resources were not associated with lower allostatic load.
Cedillo, Y. E., Murillo, A. L., & Fernandez, J. R.	2019	Cross-sectional	African American European American Hispanic American	9.5	80 Hispanic Americans 120 European Americans 107 African Americans.	CRP DBP HDL cholesterol HOMA-IR LDL cholesterol SBP Total cholesterol Triglycerides	Allostatic load will differ by race/ethnicity. Allostatic load will be associated with obesity-related measures.	Hispanic American children exhibited higher allostatic load than African American and European American counterparts. Higher allostatic load was associated with higher BMI, total body fat mass, body percent fat, and waist circumference.
Arevalo, S., Tucker, K., Falcon, M.	2014	Retrospective	Puerto Rico	56.9	984	Cortisol CRP DBP DHEA-S Epinephrine HbA1c Norepinephrine SBP Total cholesterol HDL cholesterol Waist circumference	Stressful life events will be associated with allostatic load. Language acculturation will be associated with allostatic load and mediated by stressful life events. Migrating during middle childhood and adolescence will be associated with allostatic load, increasing by experiencing stressful live events.	Trajectories of low stress were associated with higher allostatic load. Language acculturation was associated with allostatic load. Migration during middle childhood and adolescence was associated with higher allostatic load, which increased when experiencing stressful live events.
Gersten, O., Dow, W. H., & Rosero-Bixby, L.	2010	Retrospective	Costa Rica	70.5	2827	Cortisol DHEA-S Epinephrine Norepinephrine	Early childhood conditions will be associated with allostatic load.	Allostatic load was independent of early childhood conditions.

BMI: body mass index; CRP: C-reactive protein; DBP: diastolic blood pressure; DHEA-S: dehydroepiandrosterone sulfate; HbA1c: hemoglobin A1C; HDL: high-density lipoprotein; HOMA-IR: homeostatic model assessment for insulin resistance; LDL: low-density lipoprotein; PAI-1: plasminogen activator inhibitor-1; SBP: systolic blood pressure.

The framework shifts the focus from the state of the body to the dynamic interface between the body and environment, specifically how the brain perceives the environmental demands to generate anticipatory changes. The equilibrium between the energy required to generate the anticipatory changes and the energy left to the rest of the systems is what defines health (Sterling, 2020). Thus, by targeting the predictions that lead to anticipatory changes, a new landscape of opportunities for characterization, intervention, and promotion of health emerges. For example, therapeutic efforts to treat child obesity, one of the most burdensome public health challenges in LAC (Melo et al., 2023b), could be complemented by assessing hypothalamic-pituitary-thyroid axis dysregulations and its association with obesity from an allostatic perspective (Tropeano et al., 2023). The excess in fat mass induces a regulatory response from the hypothalamic-pituitary-thyroid axis to reach equilibrium, this causes the oversecretion of leptin and excessive adipogenesis.

Thus, a cycle of disequilibrium emerges, wherein the body’s energy demands are not met, leading to continuous excessive energy storage (Tropeano et al., 2023). By promoting adaptive coping strategies in obese persons and reinforcing the mechanisms to face environmental demands, the allostatic load could be reduced by lowering the predictions about energy needs to non-obesogenic levels (Brindal and Wittert, 2016).

The allostatic framework could also facilitate the articulation with current public health policies. The indexes can provide metrics of the overall health of the body. These can be estimated from biomarkers obtained in current national health surveys from LAC (e.g., Peru: Young Lives; México: Encuesta Nacional de Salud y Nutrición; Chile: Encuesta Nacional de Salud Infantil y Adolescencia Temprana; Brazil: Pesquisa Nacional de Saúde). By quantifying the allostatic load index from these datasets, the specific groups of children presenting elevated allostatic load could be identified. This might help to improve diagnosis, access to primary healthcare, and early interventions.

The framework may be also useful to guide targeted interventions and personalized healthcare. An individual inspection of the most affected body systems could be performed to identify those driving the elevated allostatic load index. These systems could then be targeted to detect pre-clinical manifestations and intervene to reduce the allostatic load (for a review, see Rosemberg et al. (2020)). This can potentially be achieved, for instance, by promoting positive childhood experiences (Panel 3). Thus, the detailed physiological profiling given by the allostatic load index can also be useful in providing comprehensive assessment and personalized healthcare (see Panel 4 for an example of how the framework could be articulated at the public policy level.).

Panel 3. Positive childhood experiences as a potential therapeutic target.

Positive childhood experiences (PCEs) are independent of ACEs (Bunting et al., 2023; Craig et al., 2022; Geng et al., 2021; Gunay-Oge et al., 2020; Zhu et al., 2023), with some studies suggesting that PCEs may have a greater predictive importance for later-life outcomes compared to ACEs (Craig et al., 2022). This has drawn attention to PCEs as a potential target for interventions and public health and policy efforts (Bethell et al., 2019; Merrick and Narayan, 2020). PCEs have significant positive impacts across levels. At the psychological level, PCEs may have significant positive benefits on cognitive, socioemotional, and behavioral domains. For instance, there is evidence that PCEs are associated with better later-life cognitive functioning (Lee and Schafer, 2021), promote wellbeing via mental toughness (Shaw et al., 2022), may buffer the effect of child maltreatment on affective lability (Almeida et al., 2023), and can be protective against adulthood tobacco consumption and high-risk alcohol use behaviors (Graupensperger et al., 2023). At the brain level, PCEs support brain development (Shonkoff et al., 2012). At the physiological level, PCEs may mitigate overweight when children have been exposed to ACEs (Crouch et al., 2022), and are associated with better health in adulthood (Crandall et al., 2019; Novilla et al., 2022). In summary, PCEs seem to protect health across levels, even in the presence of ACEs. One relevant mechanism through which PCEs may promote health is resilience, which may help to manage stress and adapt to dynamic environments (Merrick and Narayan, 2020). Thus, to a similar or equal degree as ACEs, PCEs have an impact on health.

Panel 4. A case scenario of allostatic framework and public policies.

As a concrete example of how the allostatic framework could be used to approach health and development in children from Latin America and the Caribbean, consider the hypothetical case of Marta: She is a Chilean girl enrolled in a national health program (i.e., the Encuesta Nacional de Salud Infantil y Adolescencia Temprana), which includes several health measurements relevant to the allostatic load index (e.g., arterial pressure, blood sample, anthropometric measurements). After an assessment wave, the specialized team of the Chilean Ministry of Health calculates the allostatic load index of the children included in the program, determining the cut-off scores for each biomarker based on standardized population parameters. Marta’s School students, located in a low-income rural area of Santiago, are also targeted as having a high allostatic load index, which brings the school’s students to the attention of the local authorities. A team delegated by the Ministry of Health then conducts an assessment at the school level to focus on the social determinants of health that most affect the children attending the school. This provides a deeper characterization of the student’s health status calling for primary health care actions. In this step, Marta is identified as one of the students at risk of poor health outcomes based on her elevated allostatic load index and high burden. Next, a detailed examination of her allostatic load index reveals that her neuroendocrine system is altered, characterized by abnormally high levels of cortisol, epinephrine, and norepinephrine. Based on these antecedents, the delegated team cites Marta’s parents and asks about the situations at home that could be driving her altered health status, who report difficulties in raising Marta and report hitting her as a form of punishment. This information is forwarded to the local health center (i.e., Posta de Salud Rural), and Marta and her family are referred to a parenting skills program, which includes parenting tools practices that will improve Marta’s health, such as positive childhood activities (Panel 3). Thus, the allostatic framework can be useful in guiding health assessment and intervention from the public health level to the detailed examination of an individual case.

The know-how provided by the allostatic framework to approach health in children from LAC can bring a novelty beyond current evidence (Table 1), integrating the epidemiological characteristics of the region with the theoretical and analytical tools developed in research, and incorporating advances of the interactions between the brain, body, and environment. This leads to outstanding questions (Panel 6) and testable hypotheses. For instance, longitudinal designs could be employed in children from LAC to test the interaction between ACEs and allostatic load across developmental stages and the mediator variables. Also, the allostatic measurements could be expanded with brain measures such as the allostatic-interoceptive network (Kleckner et al., 2017a) and the heartbeat-evoked potential (Coll et al., 2021). Both have been linked to ACEs and body dysregulation in children (Banihashemi et al., 2022; Immanuel et al., 2014). In terms of interventions, the effectiveness of reducing allostatic load early in life could be tested by enrolling children in high physiological risk, as determined by the allostatic load index, and providing tailored interventions (for a review of interventions targeting allostatic load, see Rosemberg et al. (2020)). Then, the effectiveness of these interventions could be tested by examining developmental outcomes and disease incidence. The proposed framework can also impact public health and primary care, where a transdisciplinary task force could be conducted to gather perceptions on the allostatic load index as a tool for approaching health in children. In summary, in the long term, this multilevel framework could inspire public health policy development and multicomponent interventions guided by an integrative approach to health rather than focusing on systems in isolation.

Panel 6. Outstanding questions.

• Can the proposed framework bring a more integrative and multidimensional approach to studying lifespan trajectories in LAC?

• Which is the best combination of allostasis biomarkers in children or adolescents? What levels and metrics need to be included?

• Which analytical tools are needed to assess the high complexity of lifespan trajectories?

• How can the proposed framework be implemented in later developmental periods, such as adults and older adults?

• How to derive success metrics of the proposed approach to improve health?

• How to manage the current challenges for research and evidence-based policy-making in LAC into opportunities for improvement?

Conclusions

An allostatic framework of developmental dynamics in the LAC region can improve the understanding of the impact of childhood experiences on health across the lifespan. New agendas could help to push future developments (Panel 5) and respond to outstanding questions (Panel 6). Linking these childhood experiences with composite measures of allostatic load could help to improve health and intervention, and to develop evidence-based policy recommendations.

Panel 5. New research agendas.

Here we propose to develop a four-step framework. The first step is to map research centers and leaderships across LAC to create a large multinational working group identifying ways to develop and address the challenges. The second step envisages the compilation and harmonization of distinct population datasets from LAC that include measures of SDH, ACEs, PCEs, and biomarkers, to test the impact of ACEs and PCEs on allostatic load. Comparisons with similar databases from Europe/EEU may help to characterize the specific regional burden on life trajectories. Thirdly, a characterization of the unique characteristics of LAC should be identified, including the most prevalent SDH, lifestyle habits, and resilience-promoting factors (e.g., social bonding), among others, and their impact on health. This information will guide the development of targeted interventions aimed at mitigating the impact of environmental stressors on health dynamics.