The lifelong effects of early childhood adversity and toxic stress

Advances in fields of inquiry as diverse as neuroscience, molecular biology, genomics, developmental psychology, epidemiology, sociology, and economics are catalyzing an important paradigm shift in our understanding of health and disease across the lifespan. This converging, multidisciplinary science of human development has profound implications for our ability to enhance the life prospects of children and to strengthen the social and economic fabric of society. Drawing on these multiple streams of investigation, this report presents an ecobiodevelopmental framework that illustrates how early experiences and environmental influences can leave a lasting signature on the genetic predispositions that affect emerging brain architecture and long-term health. The report also examines extensive evidence of the disruptive impacts of toxic stress, offering intriguing insights into causal mechanisms that link early adversity to later impairments in learning, behavior, and both physical and mental well-being. The implications of this framework for the practice of medicine, in general, and pediatrics, specifically, are potentially transformational. They suggest that many adult diseases should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. An ecobiodevelopmental framework also underscores the need for new thinking about the focus and boundaries of pediatric practice. It calls for pediatricians to serve as both front-line guardians of healthy child development and strategically positioned, community leaders to inform new science-based strategies that build strong foundations for educational achievement, economic productivity, responsible citizenship, and lifelong health.     

Health information technology and the medical home

The American Academy of Pediatrics (AAP) supports development and universal implementation of a comprehensive electronic infrastructure to support pediatric information functions of the medical home. These functions include (1) timely and continuous management and tracking of health data and services over a patient's lifetime for all providers, patients, families, and guardians, (2) comprehensive organization and secure transfer of health data during patient-care transitions between providers, institutions, and practices, (3) establishment and maintenance of central coordination of a patient's health information among multiple repositories (including personal health records and information exchanges), (4) translation of evidence into actionable clinical decision support, and (5) reuse of archived clinical data for continuous quality improvement. The AAP supports universal, secure, and vendor-neutral portability of health information for all patients contained within the medical home across all care settings (ambulatory practices, inpatient settings, emergency departments, pharmacies, consultants, support service providers, and therapists) for multiple purposes including direct care, personal health records, public health, and registries. The AAP also supports financial incentives that promote the development of information tools that meet the needs of pediatric workflows and that appropriately recognize the added value of medical homes to pediatric care.     

Measuring in support of early childhood development

A child’s early experiences and environments have a significant, measurable effect on later life trajectories of health and well-being. Each child’s own world, especially parents and other caregivers, literally sculpts the brain and impacts stress pathways. Effective early childhood interventions exist that can improve adult and societal outcomes. In this statement, the Canadian Paediatric Society calls on federal and provincial/territorial governments to measure and monitor the developmental progress of children in Canada, which can vary widely among communities and demographic groups. The statement explores the objectives for collecting quality information about early child development, its determinants and long-term outcomes. It also examines four approaches to collecting population-based, person-specific and longitudinal data, both in young children and later in life. A key outcome of monitoring development is timely intervention. Linking individual data to the home and community levels is a critical step, so that communities and governments can monitor and take actions that support early child development.     

A pediatric twin study of brain morphometry

BACKGROUND: Longitudinal pediatric neuroimaging studies have demonstrated increasing volumes of white matter and regionally-specific inverted U shaped developmental trajectories of gray matter volumes during childhood and adolescence. Studies of monozygotic and dyzygotic twins during this developmental period allow exploration of genetic and non-genetic influences on these developmental trajectories. METHOD: Magnetic resonance imaging brain scans were acquired on a pediatric sample of 90 monozygotic twin pairs, 38 same-sex dyzygotic twin pairs, and 158 unrelated typically developing singletons. Structural equation modeling was used to estimate the additive genetic, common environment, and unique environment effects, as well as age by heritability interactions, on measures of brain volumes from these images. RESULTS: Consistent with previous adult studies, additive genetic effects accounted for a substantial portion of variability in nearly all brain regions with the notable exception of the cerebellum. Significant age by heritability interactions were observed with gray matter volumes showing a reduction in heritability with increasing age, while white matter volume heritability increased with greater age. CONCLUSION: Understanding the relative contributions of genetic and nongenetic factors on developmental brain trajectories may have implications for better understanding brain-based disorders and typical cognitive development.     

Transitioning the patient with Turner's syndrome from pediatric to adult care

The level of medical and neuropsychological complexity throughout the life span of a patient with Turner's syndrome (TS) provides the rationale for a more structured transition from pediatric to adult health care. During late adolescence, the focus of care shifts from maximizing final adult height to completing feminization with estrogen therapy, detecting early antecedents of associated adult conditions, implementing needed therapeutic lifestyle changes, and assessing psychobehavioral risk. An increased prevalence of the dysmetabolic syndrome and osteoporosis is observed in TS. The prevention of obesity and assurance of adequate calcium intake and weight-bearing activities combined with early detection and treatment of specific abnormalities can ameliorate these associated adult morbidities. During the final phase of transition, the pediatric endocrinologist should engage the patient with TS in developing a comprehensive adult care roadmap or 'transition passport', which serves as a powerful educational tool. The aim of refining the transition process is to improve adult outcomes and quality of life for patients with TS.     

Developing pre-school surveillance tools for adaptive functioning: Lessons for neuro-oncology

Advances in neuro-oncology have resulted in dramatic increases in the survival of children with pediatric brain tumors, including those with medulloblastoma, the most common early childhood central nervous system (CNS) malignancy. Because of this increased survival, there is heightened awareness and recognition that an understanding of the impact of treatments and interventions on children’s development, learning, and adaptive behaviors is essential for optimization of long-term outcomes. One of the major reasons for studying these outcomes is that the developing nervous system has its unique vulnerabilities with respect to the primary tumor, its complications (hydrocephalus, increased intracranial pressure, hazards of tumor resection), and the late effects of treatments on children’s developmental, learning, and adaptive status. In addition, very young children are especially vulnerable to the toxic effects of radiation and other therapies, highlighting the importance of measuring emerging communication, coordination, and social adaptive skills. Lastly, there is increased concern about the long-term consequences of chemotherapy on specific neural populations and neural connectivity that affect memory, learning, and executive function.The purpose of this article is to review ways of conceptualizing CNS adaptive functioning in children diagnosed with brain tumors in early childhood. The international classification of functioning (ICF) model will be used to describe the spectrum of health and developmental outcomes of child neurodisability. An integrated strategy of surveillance for motor, communicative, and adaptive skills that can be linked to neuropsychological assessments will also be highlighted. This health, development, and functional surveillance framework will help us better evaluate how our management impacts on child and family well-being and how our interventions lessen severe multiple motor, communicative, and neurobehavioral morbidities.     

Effects of early life stress on neuroendocrine and neurobehavior: mechanisms and implications

Evidence continues to mount that adverse experiences early in life have an impact on brain functions. Early life stress can program the development of the hypothalamic-pituitary-adrenal axis and cause alterations of neurochemistry and signaling pathways involved in regulating neuroplasticity, with resultant neurobehavioral changes. Early life experiences and genetic factors appear to interact in determining the individual vulnerability to mental health disorders. We reviewed the effects of early life stress on neuroendocrine regulation and the relevance to neurobehavioral development.     

Annual Research Review: The promise of stem cell research for neuropsychiatric disorders

The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders, attention deficit hyperactivity disorder, obsessive compulsive disorder and many other neurodevelopmental conditions. However, precisely how genes may function in human brain development and how they interact with each other leading to psychiatric disorders is unknown. Because of an increasing understanding of neural stem cells and how the nervous system subsequently develops from these cells, we have now the ability to study disorders of the nervous system in a new way - by rewinding and reviewing the development of human neural cells. Induced pluripotent stem cells (iPSCs), developed from mature somatic cells, have allowed the development of specific cells in patients to be observed in real time. Moreover, they have allowed some neuronal-specific abnormalities to be corrected with pharmacological intervention in tissue culture. These exciting advances based on the use of iPSCs hold great promise for understanding, diagnosing and, possibly, treating psychiatric disorders. Specifically, examination of iPSCs from typically developing individuals will reveal how basic cellular processes and genetic differences contribute to individually unique nervous systems. Moreover, by comparing iPSCs from typically developing individuals and patients, differences at stem cell stages, through neural differentiation, and into the development of functional neurons may be identified that will reveal opportunities for intervention. The application of such techniques to early onset neuropsychiatric disorders is still on the horizon but has become a reality of current research efforts as a consequence of the revelations of many years of basic developmental neurobiological science.     

Report on the 2nd World Congress on Fetal Origins of Adult Disease, Brighton, U.K., June 7-10, 2003

In 1989, reports suggested that the fetal environment, as reflected in birth size, was related to the risk of noncommunicable diseases in adult life. This association was first described for coronary heart disease but rapidly extended to include type 2 diabetes, osteoporosis, and metabolic and endocrine homeostasis. This led to the development of the fetal origins of adult disease paradigm, which resulted in a refocusing of research effort over the next 10 y to consider the lifelong consequences of perinatal influences on chronic diseases. Previously, perinatal influences had largely been seen in terms of teratogenic effects or acute birth injury rather than whether trajectories and responses made during early development had lifelong consequences. Indeed, in developmental biology, it is widely recognized that adaptive plastic responses during early development often have consequences for function in later adulthood. Although the relative importance of this newly recognized set of phenomena to the burden of human disease has been controversial, the research precipitated by those early observations has confirmed their robustness and started to provide a mechanistic basis to this biology. Two world congresses have been held to review progress in this research. Both have been characterized by a unique multidisciplinary attendance ranging from molecular, experimental, and developmental biologists to epidemiologists and health economists.     

Fetal Programming and the Risk of Noncommunicable Disease

The “developmental origins of health and disease” (DOHaD) hypothesis proposes that environmental conditions during fetal and early post-natal development influence lifelong health and capacity through permanent effects on growth, structure and metabolism. This has been called ‘programming’. The hypothesis is supported by epidemiological evidence in humans linking newborn size, and infant growth and nutrition, to adult health outcomes, and by experiments in animals showing that maternal under- and over-nutrition and other interventions (e.g., glucocorticoid exposure) during pregnancy lead to abnormal metabolism and body composition in the adult offspring. Early life programming is now thought to be important in the etiology of obesity, type 2 diabetes, and cardiovascular disease, opening up the possibility that these common diseases could be prevented by achieving optimal fetal and infant development. This is likely to have additional benefits for infant survival and human capital (e.g., improved cognitive performance and physical work capacity). Fetal nutrition is influenced by the mother’s diet and body size and composition, but hard evidence that the nutrition of the human mother programmes chronic disease risk in her offspring is currently limited. Recent findings from follow-up of children born after randomised nutritional interventions in pregnancy are mixed, but show some evidence of beneficial effects on vascular function, lipid concentrations, glucose tolerance and insulin resistance. Work in experimental animals suggests that epigenetic phenomena, whereby gene expression is modified by DNA methylation, and which are sensitive to the nutritional environment in early life, may be one mechanism underlying programming.     

High fat programming of beta cell compensation,exhaustion, death and dysfunction

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co‐presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease.     

Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development

The gut microbiota is a vast, complex, and fascinating ecosystem of microorganisms that resides in the human gastrointestinal tract. As an integral part of the microbiota–gut–brain axis, it is now being recognized that the microbiota is a modulator of brain and behavior, across species. Intriguingly, periods of change in the microbiota coincide with the development of other body systems and particularly the brain. We hypothesize that these times of parallel development are biologically relevant, corresponding to ‘sensitive periods’ or ‘critical windows’ in the development of the microbiota–gut–brain axis. Specifically, signals from the microbiota during these periods are hypothesized to be crucial for establishing appropriate communication along the axis throughout the life span. In other words, the microbiota is hypothesized to act like an expected input to calibrate the development of the microbiota–gut–brain axis. The absence or disruption of the microbiota during specific developmental windows would therefore be expected to have a disproportionate effect on specific functions or potentially for regulation of the system as a whole. Evidence for microbial modulation of neurocognitive development and neurodevelopmental risk is discussed in light of this hypothesis, finishing with a focus on the challenges that lay ahead for the future study of the microbiota–gut–brain axis during development.     

儿童发育监测和筛查在儿童保健中的应用

早期识别儿童发育迟缓、障碍或行为异常是儿童保健的重要任务之一,有利于儿童发育障碍及相关疾病的早期发现和早期干预、治疗,促进儿童早期发展并减少残疾率。发育监测和发育筛查是早期识别儿童发育迟缓或障碍的有效途径。发育监测是发现、鉴认具有发育迟缓风险儿童的过程;发育筛查是采用简单、标准化筛查工具帮助识别可能有发育迟缓、障碍或需要进行复杂、综合评估的儿童。定期的标准化发育筛查可提高儿童发育迟缓、障碍的早期识别率。重视基层儿童保健医生发育监测和筛查技能的培训,将发育监测和筛查纳入儿童保健常规工作,推动其在实践中的应用,对儿童发育迟缓或障碍的早干预、早治疗有重要意义。     

Developmental intervention during neonatal hospitalization. Critiquing the state of the science

Recent investigations, such as those discussed, focus attention on the need for additional studies that explore the emerging neuroregulatory mechanisms in premature infants. Data from these investigations may augment current high standards of neonatal medical care that now focus on treating the heart, lungs, and digestive systems. The various studies of early developmental processes encourage clinicians to recognize and treat premature infants as individuals, a principle acknowledged long ago about full-term infants and parents. Through understanding the critical role of parents in guiding the continued health and development of infants after hospital discharge, hospital staff are exploring methods for helping parents feel involved, respected, and supported as primary caregivers. Similarly, staff are reacting to the growing realization that optimal developmental outcome requires close coordination between hospital and community services for infants and families. Continued attention to the developmental needs of hospitalized infants and their parents, along with further integration of medical, developmental, and emotional care, will surely succeed in bringing early hope to the fragile beginning of life after high-risk birth.     

Scope of practice issues in the delivery of pediatric health care

In recent years, there has been an increase in the number of nonphysician pediatric clinicians and an expansion in their respective scopes of practice. This raises critical public policy and child health advocacy concerns. The American Academy of Pediatrics (AAP) believes that optimal pediatric health care depends on a team-based approach with coordination by a physician leader, preferably a pediatrician. The pediatrician is uniquely suited to manage, coordinate, and supervise the entire spectrum of pediatric care, from diagnosis through all stages of treatment, in all practice settings. The AAP recognizes the valuable contributions of nonphysician clinicians, including nurse practitioners and physician assistants, in delivering optimal pediatric care. The AAP also believes that nonphysician clinicians who provide health care services in underserved areas should be supported by consulting pediatricians and other physicians using technologies including telemedicine. Pediatricians should serve as advocates for optimal pediatric care in state legislatures, public policy forums, and the media and should pursue opportunities to resolve scope of practice conflicts outside state legislatures. The AAP affirms that as nonphysician clinicians seek to expand their scopes of practice as providers of pediatric care, standards of education, training, examination, regulation, and patient care are needed to ensure patient safety and quality health care for all infants, children, adolescents, and young adults.     

Early programming of adult diseases in resource poor countries.

Considerable evidence now exists to suggest that early exposure to nutritional deprivation can have long term consequences to health, with low birth weight now considered a risk factor for later health outcomes such as coronary heart disease, stroke, type 2 diabetes, and the metabolic syndrome. Of importance, such effects are most exaggerated when faced with over-nutrition in later life, forming the basis for the "thrifty phenotype" hypothesis. The evidence in support of these associations comes largely from retrospective cohort studies in which adult outcomes were correlated with birth weight records. Relatively little data is available from developing countries, where long term record keeping of birth weight data has not been a high priority. Arguably however, such countries are at the greatest risk from the mismatch of early nutritional deprivation and later nutritional affluence. This paper explores the importance of the "developmental origins of health and disease" hypothesis in resource poor countries.     

Early programming of adult diseases in resource poor countries

Considerable evidence now exists to suggest that early exposure to nutritional deprivation can have long term consequences to health, with low birth weight now considered a risk factor for later health outcomes such as coronary heart disease, stroke, type 2 diabetes, and the metabolic syndrome. Of importance, such effects are most exaggerated when faced with over-nutrition in later life, forming the basis for the "thrifty phenotype" hypothesis. The evidence in support of these associations comes largely from retrospective cohort studies in which adult outcomes were correlated with birth weight records. Relatively little data is available from developing countries, where long term record keeping of birth weight data has not been a high priority. Arguably however, such countries are at the greatest risk from the mismatch of early nutritional deprivation and later nutritional affluence. This paper explores the importance of the "developmental origins of health and disease" hypothesis in resource poor countries.     

CT utilization--trends and developments beyond the United States' borders

There has been an exponential rise in the use of CT during the last 25 years, with similar trending of data from regions across the world. However, variability in levels of utilization and patterns of practice in both adult and pediatric populations can be identified. Multiple technical, health care, regulatory and cultural factors are shaping our use of this modality. Surveys of pediatric CT dose are now available from several countries with the development of proposed diagnostic reference levels. Challenges of this process will be discussed. This short presentation is not intended as a comprehensive review of the infrastructure and numerous advances in pediatric CT radiation protection occurring around the world but aims to highlight a few aspects.     

Importance of education and the role of the patient and family in the care of anorectal malformations

During this early part of the 21st century online technology has prompted many major advances in medical care. In this section we argue that this is particularly evident in the treatment and care of patients born with Anorectal Malformation (ARM) and Hirschsprung's Disease (HD). Our stories show that anyone born with these complex colorectal conditions in the 20th century was destined to a life of isolation and stigma. Here we explore the lack of understanding and recognition of the psychological effects on children and families which has characterised this period. We show that advances in clinical practice has been supported by developing social media platforms.There has been a rapid creation of online support groups for patients and families which has enabled survivors’ greater access to patient and parent organizations across the globe and thereby stimulated a sense of belonging and solidarity. Online technology and social media platforms have also opened up the opportunity for pediatric medical professionals to provide a greater level of patient education.There is no doubt families have become much more aware of the complexities of ARM & HD and achieved greater comfort and understanding of their needs. We have generated “lightbulb moments” for pediatric providers with adult ARM & HD patients, enabling them to share their lived experiences in a therapeutic exchange. In the past survivors felt they were abandoned by the adult healthcare system. We are seeing evidence-based research of major psychosocial issues experienced by adult patients and, as a result, improved understanding of how to treat ARM & HD survivors across their whole of life journey.The winds of change continue to direct our cohorts to a mature approach based on improving levels of interactive communication and education. We argue that this maturity has mostly been facilitated by the use of online technology and the ensuing collaboration between providers and patient and parent organizations.