Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

Early Childhood Adversity, Toxic Stress, and the Impacts of Racism on the Foundations of Health.

Inequalities in health outcomes impose substantial human and economic costs on all societies-and the relation between early adversity and lifelong well-being presents a rich scientific framework for fresh thinking about health promotion and disease prevention broadly, augmented by a deeper focus on how racism influences disparities more specifically. This review begins with an overview of advances in the biology of adversity and resilience through an early childhood lens, followed by an overview of the unique effects of racism on health and a selective review of findings from related intervention research. This article presents a framework for addressing multiple dimensions of the public health challenge-including institutional/structural racism, cultural racism, and interpersonal discrimination-and concludes with the compelling need to protect the developing brain and other biological systems from the physiological disruptions of toxic stress that can undermine the building blocks of optimal health and development in the early childhood period.

From Innovation to Impact at Scale: Lessons Learned From a Cluster of Research-Community Partnerships.

This article presents a description of how an interdisciplinary network of academic researchers, community-based programs, parents, and state agencies have joined together to design, test, and scale a suite of innovative intervention strategies rooted in new knowledge about the biology of adversity. Through a process of cocreation, collective pilot testing, and the support of a measurement and evaluation hub, the Washington Innovation Cluster is using rapid cycle iterative learning to elucidate differential impacts of interventions designed to build child and caregiver capacities and address the developmental consequences of socioeconomic disadvantage. Key characteristics of the Innovation Cluster model are described and an example is presented of a video-coaching intervention that has been implemented, adapted, and evaluated through this distinctive collaborative process.

Leveraging the biology of adversity to address the roots of disparities in health and development.

Extensive evidence that personal experiences and environmental exposures are embedded biologically (for better or for worse) and the cumulative knowledge of more than four decades of intervention research provide a promising opportunity to mobilize evolving scientific insights to catalyze a new era of more effective early childhood policy and practice. Drawing on emerging hypotheses about causal mechanisms that link early adversity with lifelong impairments in learning, behavior, and health, this paper proposes an enhanced theory of change to promote better outcomes for vulnerable, young children by strengthening caregiver and community capacities to reduce or mitigate the impacts of toxic stress, rather than simply providing developmental enrichment for the children and parenting education for their mothers.

Rethinking evidence-based practice and two-generation programs to create the future of early childhood policy.

Half a century of research and program evaluation has fueled a diverse landscape of early childhood policies and practices that produce a range of positive effects on the life prospects of children who face the burdens of significant adversity. Drawing on advances in neurobiology, developmental psychology, developmental psychopathology, and prevention science, this paper presents a framework for elucidating underlying causal mechanisms that explain differences in outcomes, formulating enhanced theories of change about how to shift developmental trajectories, designing creative interventions and rethinking the concept of a two-generation strategy to produce breakthrough impacts, and launching a new era of investment in young children and their families that will achieve greater reductions in intergenerational disparities in learning, behavior, and health than those produced by current best practices. Particular attention is focused on the hypothesis that substantially better outcomes for vulnerable, young children could be achieved by greater attention to strengthening the resources and capabilities of the adults who care for them rather than by continuing to focus primarily on the provision of child-focused enrichment, parenting education, and informal support. Central to achieving this goal is the need to establish an innovation-friendly environment that embraces fast-cycle sharing, supports risk taking, and celebrates learning from failure.

State-Level Anti-Immigrant Sentiment and Policies and Health Risks in US Latino Children.

BACKGROUND: Although systemic inequities, broadly defined, are associated with health disparities in adults, there is a dearth of research linking contextual measures of exclusionary policies or prejudicial attitudes to health impairments in children, particularly among Latino populations. In this study, we examined a composite measure of systemic inequities in relation to the cooccurrence of multiple health problems in Latino children in the United States. METHODS: Participants included 17 855 Latino children aged 3 to 17 years from the National Survey of Children's Health (2016-2020). We measured state-level systemic inequities using a factor score that combined an index of exclusionary state policies toward immigrants and aggregated survey data on prejudicial attitudes toward immigrants and Latino individuals. Caregivers reported on 3 categories of child health problems: common health difficulties in the past year, current chronic physical health conditions, and current mental health conditions. For each category, we constructed a variable reflecting 0, 1, or 2 or more conditions. RESULTS: In models adjusted for sociodemographic covariates, interpersonal discrimination, and state-level income inequality, systemic inequities were associated with 1.13 times the odds of a chronic physical health condition (95% confidence interval: 1.02-1.25) and 1.24 times the odds of 2 or more mental health conditions (95% confidence interval: 1.06-1.45). CONCLUSIONS: Latino children residing in states with higher levels of systemic inequity are more likely to experience mental health or chronic physical health conditions relative to those in states with lower levels of systemic inequity.

Neighborhood Opportunity and Mortality Among Children and Adults in Their Households.

BACKGROUND AND OBJECTIVES: Research has linked neighborhood opportunity to health outcomes in children and adults; however, few studies have examined neighborhood opportunity and mortality risk among children and their caregivers. The objective of this study was to assess associations of neighborhood opportunity and mortality risk in children and their caregivers over 11 years. METHODS: Participants included 1 025 000 children drawn from the Mortality Disparities in American Communities study, a cohort developed by linking the 2008 American Community Survey to the National Death Index and followed for 11 years. Neighborhood opportunity was measured using the Child Opportunity Index, a measure designed to capture compounding inequities in access to opportunities for health. RESULTS: Using hazard models, we observed inverse associations between Child Opportunity Index quintile and deaths among child and caregivers. Children in very low opportunity neighborhoods at baseline had 1.30 times the risk of dying over follow-up relative to those in very high opportunity neighborhoods (95% confidence interval [CI], 1.15-1.45), and this excess risk attenuated after adjustment for household characteristics (hazard ratio, 1.15; 95% CI, 0.98-1.34). Similarly, children in very low opportunity neighborhoods had 1.57 times the risk of experiencing the death of a caregiver relative to those in very high opportunity neighborhoods (95% CI, 1.50-1.64), which remained after adjustment (hazard ratio, 1.30; 95% CI, 1.23-1.38). CONCLUSIONS: Our analyses advance understanding of the adverse consequences of inequitable neighborhood contexts for child well-being and underscore the potential importance of place-based policies for reducing disparities in child and caregiver mortality.

Translating the Biology of Adversity and Resilience Into New Measures for Pediatric Practice.

As the science of adversity and resilience advances, and public awareness of the health consequences of stress grows, primary care providers are being increasingly asked to address the effects of adverse experiences on child wellbeing. Given limited tools for assessing these effects early in life, the authors explore how enhanced capacity to measure stress activation directly in young children could transform the role and scope of pediatric practice. When employed within a trusted relationship between caregivers and clinicians, selective use of biological measures of stress responses would help address the documented limitations of rating scales of adverse childhood experiences as a primary indicator of individual risk and strengthen the ability to focus on variation in intervention needs, assess their effectiveness, and guide ongoing management. The authors provide an overview of the potential benefits and risks of such expanded measurement capacity, as well as an introduction to candidate indicators that might be employed in an office setting. The ultimate value of such measures for both pediatricians and parents will require vigilant attention to the ethical responsibilities of assuring their correct interpretation and minimizing the harm of inappropriate labeling, especially for children and families experiencing the hardships and threats of racism, poverty, and other structural inequities. Whereas much work remains to be done to advance measurement development and ensure its equitable use, the potential of validated markers of stress activation and resilience to strengthen the impact of primary health care on the lives of young children facing significant adversity demands increased attention.

Science does not speak for itself: translating child development research for the public and its policymakers.

Science has an important role to play in advising policymakers on crafting effective responses to social problems that affect the development of children. This article describes lessons learned from a multiyear, working collaboration among neuroscientists, developmental psychologists, pediatricians, economists, and communications researchers who are engaged in the iterative construction of a core story of development, using simplifying models (i.e., metaphors) such as "brain architecture,""toxic stress," and "serve and return" to explain complex scientific concepts to nonscientists. The aim of this article is to stimulate more systematic, empirical approaches to the task of knowledge transfer and to underscore the need to view the translation of science into policy and practice as an important academic endeavor in its own right.

Leveraging the Biology of Adversity and Resilience to Transform Pediatric Practice.

Advances in science are fundamentally changing the way we understand how inextricable interactions among genetic predispositions, physical and social environments, and developmental timing influence early childhood development and the foundations of health and how significant early adversity can lead to a lifetime of chronic health impairments. This article and companion article illustrate the extent to which differential outcomes are shaped by ongoing interactive adaptations to context that begin at or even before conception and continue throughout life, with increasing evidence pointing to the importance of the prenatal period and early infancy for the developing brain, the immune system, and metabolic regulation. Although new discoveries in the basic sciences are transforming tertiary medical care and producing breakthrough outcomes in treating disease, this knowledge is not being leveraged effectively to inform new approaches to promoting whole-child development and preventing illness. The opportunity for pediatrics to serve as the leading edge of science-based innovation across the early childhood ecosystem has never been more compelling. In this article, we present a framework for leveraging the frontiers of scientific discovery to inform new strategies in pediatric practice and advocacy to protect all developing biological systems from the disruptive effects of excessive early adversity beyond providing information on child development for parents and enriched learning experiences for young children.

Genes, Environments, and Time: The Biology of Adversity and Resilience.

Exposures to adverse environments, both psychosocial and physicochemical, are prevalent and consequential across a broad range of childhood populations. Such adversity, especially early in life, conveys measurable risk to learning and behavior and to the foundations of both mental and physical health. Using an interactive gene-environment-time (GET) framework, we survey the independent and interactive roles of genetic variation, environmental context, and developmental timing in light of advances in the biology of adversity and resilience, as well as new discoveries in biomedical research. Drawing on this rich evidence base, we identify 4 core concepts that provide a powerful catalyst for fresh thinking about primary health care for young children: (1) all biological systems are inextricably integrated, continuously "reading" and adapting to the environment and "talking back" to the brain and each other through highly regulated channels of cross-system communication; (2) adverse environmental exposures induce alterations in developmental trajectories that can lead to persistent disruptions of organ function and structure; (3) children vary in their sensitivity to context, and this variation is influenced by interactions among genetic factors, family and community environments, and developmental timing; and (4) critical or sensitive periods provide unmatched windows of opportunity for both positive and negative influences on multiple biological systems. These rapidly moving frontiers of investigation provide a powerful framework for new, science-informed thinking about health promotion and disease prevention in the early childhood period.

Building a new biodevelopmental framework to guide the future of early childhood policy.

Four decades of early childhood policy and program development indicate that evidence-based interventions can improve life outcomes, and dramatic advances in the biological and behavioral sciences now provide an opportunity to augment those impacts. The challenge of reducing the gap between what we know and what we do to promote the healthy development of young children is to view current best practices as a starting point and to leverage scientific concepts to inspire fresh thinking. This article offers an integrated, biodevelopmental framework to promote greater understanding of the antecedents and causal pathways that lead to disparities in health, learning, and behavior in order to inform the development of enhanced theories of change to drive innovation in policies and programs.

Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention.

A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in 2 ways--either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods. In both cases, there can be a lag of many years, even decades, before early adverse experiences are expressed in the form of disease. From both basic research and policy perspectives, confronting the origins of disparities in physical and mental health early in life may produce greater effects than attempting to modify health-related behaviors or improve access to health care in adulthood.

Impacts of Early Childhood Education on Medium- and Long-Term Educational Outcomes.

Despite calls to expand early childhood education (ECE) in the United States, questions remain regarding its medium- and long-term impacts on educational outcomes. We use meta-analysis of 22 high-quality experimental and quasi-experimental studies conducted between 1960 and 2016 to find that on average, participation in ECE leads to statistically significant reductions in special education placement (d = 0.33 SD, 8.1 percentage points) and grade retention (d = 0.26 SD, 8.3 percentage points) and increases in high school graduation rates (d = 0.24 SD, 11.4 percentage points). These results support ECE's utility for reducing education-related expenditures and promoting child well-being.

Capitalizing on Advances in Science to Reduce the Health Consequences of Early Childhood Adversity.

Advances in biology are providing deeper insights into how early experiences are built into the body with lasting effects on learning, behavior, and health. Numerous evaluations of interventions for young children facing adversity have demonstrated multiple, positive effects but they have been highly variable and difficult to sustain or scale. New research on plasticity and critical periods in development, increasing understanding of how gene-environment interaction affects variation in stress susceptibility and resilience, and the emerging availability of measures of toxic stress effects that are sensitive to intervention provide much-needed fuel for science-informed innovation in the early childhood arena. This growing knowledge base suggests 4 shifts in thinking about policy and practice: (1) early experiences affect lifelong health, not just learning; (2) healthy brain development requires protection from toxic stress, not just enrichment; (3) achieving breakthrough outcomes for young children facing adversity requires supporting the adults who care for them to transform their own lives; and (4) more effective interventions are needed in the prenatal period and first 3 years after birth for the most disadvantaged children and families. The time has come to leverage 21st-century science to catalyze the design, testing, and scaling of more powerful approaches for reducing lifelong disease by mitigating the effects of early adversity.

Racial Disparities in Child Adversity in the U.S.: Interactions With Family Immigration History and Income.

INTRODUCTION: Childhood adversity is an under-addressed dimension of primary prevention of disease in children and adults. Evidence shows racial/ethnic and socioeconomic patterning of childhood adversity in the U.S., yet data on the interaction of race/ethnicity and SES for exposure risk is limited, particularly with consideration of immigration history. This study examined racial/ethnic differences in nine adversities among children (from birth to age 17 years) in the National Survey of Child Health (2011-2012) and determined how differences vary by immigration history and income (N=84,837). METHODS: We estimated cumulative adversity and individual adversity prevalences among white, black, and Hispanic children of U.S.-born and immigrant parents. We examined whether family income mediated the relationship between race/ethnicity and exposure to adversities, and tested interactions (analyses conducted in 2014-2015). RESULTS: Across all groups, black and Hispanic children were exposed to more adversities compared with white children, and income disparities in exposure were larger than racial/ethnic disparities. For children of U.S.-born parents, these patterns of racial/ethnic and income differences were present for most individual adversities. Among children of immigrant parents, there were few racial/ethnic differences for individual adversities and income gradients were inconsistent. Among children of U.S.-born parents, the Hispanic-white disparity in exposure to adversities persisted after adjustment for income, and racial/ethnic disparities in adversity were largest among children from high-income families. CONCLUSIONS: Simultaneous consideration of multiple social statuses offers promising frameworks for fresh thinking about the distribution of disease and the design of targeted interventions to reduce preventable health disparities.

Maximizing the potential of early childhood education to prevent externalizing behavior problems: A meta-analysis.

Early childhood education (ECE) programs offer a promising mechanism for preventing early externalizing behavior problems and later antisocial behavior; yet, questions remain about how to best maximize ECE's potential. Using a meta-analytic database of 31 studies, we examined the overall effect of ECE on externalizing behavior problems and the differential effects of 3 levels of practice, each with increasing specificity and intensity aimed at children's social and emotional development. In short, we found that each successive level of programs did a better job than the prior level at reducing externalizing behavior problems. Level 1 programs, or those without a clear focus on social and emotional development, had no significant effects on externalizing behavior problems relative to control groups (ES=.13 SD, p<.10). On the other hand, level 2 programs, or those with a clear but broad focus on social and emotional development, were significantly associated with modest decreases in externalizing behavior problems relative to control groups (ES=-.10 SD, p<.05). Hence, level 2 programs were significantly better at reducing externalizing behavior problems than level 1 programs (ES=-.23 SD, p<.01). Level 3 programs, or those that more intensively targeted children's social and emotional development, were associated with additional significant reductions in externalizing behavior problems relative to level 2 programs (ES=-.26 SD, p<.05). The most promising effects came from level 3 child social skills training programs, which reduced externalizing behavior problems half of a standard deviation more than level 2 programs (ES=-.50 SD, p<.05).

From neurons to neighborhoods: old and new challenges for developmental and behavioral pediatrics.

Rapidly advancing research in neurobiology and the behavioral and social sciences, coupled with dramatic changes in the social and economic circumstances under which families are raising young children, has created a highly dynamic context for early childhood policy, service delivery, and child rearing in the United States. A recent report from the National Research Council and the Institute of Medicine, presents a critical analysis of that complex knowledge base and a set of recommendations designed to close the gap between what we know and what we do to promote the healthy development of young children. This article examines the report through the lens of developmental and behavioral pediatrics and highlights both exciting opportunities and sobering challenges.