CHAPTER 3

The amazing newborn brain is composed of 100 million neurons and 10 times as many glial elements. These organize, migrate, connect, and specialize in response to dopaminergic, adrenergic, and serotonergic neurotransmitter systems. Newborns have 50 trillion synapses connecting these neurons at birth, and an explosion in synaptogenesis leads them to develop 20 times that number by their first birthday. This overproduction is followed by a period of synaptic pruning. Synapses that are used become stronger, and those neglected are pruned away. By the time a person reaches 20 years of age, that person has only half the number of synapses he or she had at 1 year of age. This process happens in a sequential way, with the number of synapses in sensory and motor areas peaking as early as 4 months, followed by stabilization in the number of synapses by preschool age. However, not every area of the brain follows this timeline. For example, in the prefrontal cortex, where executive functions are controlled, the number of synapses peaks at 1 year of age but does not stabilize until late adolescence or early adulthood. Myelination of neuronal sheaths also occurs early in motor and sensory areas and later in the prefrontal cortex.1,2

Thus synaptic pruning and myelination are 2 mechanisms by which an individual neurobiologically adapts to his or her environment. These are also mechanisms by which the environment shapes brain architecture. Often-used examples of this are the images of small and underdeveloped brains of children raised under circumstances of extreme neglect experienced in some orphanages.² Recently, more subtle neuroimaging confirms this impact of environment on brain structure. For example, maternal support observed in the preschool years has been found to be strongly predictive of hippocampal volume at school age.³

The Impact of Early Childhood Adversity and Toxic Stress on Child Development and Behavior

The field of pediatrics has continued to evolve since it emerged as a specialized entity in clinical medicine in the late 19th century. Initially, pediatricians focused on optimizing nutrition, treating infectious diseases, and preventing premature death. As advances in antibiotics, effective immunizations, and public health initiatives have diminished or, in some cases, eradicated many childhood illnesses, increased focus has been placed on child development, behavior, and family functioning. Over this time, parental substance abuse and mental illness, as well as exposure to violence, have been identified as factors that negatively impact children’s health and development. More recently, societal concerns, such as the adverse effects of watching excessive amounts of television, the influence of new technologies, epidemic increases in obesity, and the persistent economic, racial, and ethnic disparities in health status, have been brought to the forefront of pediatrics.4 In fact, a recent American Academy of Pediatrics (AAP) technical report reviewing 58 years of published studies characterized racial and ethnic disparities in children’s health to be extensive, pervasive, persistent, and, in some cases, worsening.⁵

As the practice of pediatrics has evolved, so has the understanding of the process of child development. As described in Chapter 2, (Nature, Nurture and Their Interactions in Child Development and Behavior), a child’s learning, behavior, and physical and mental health are influenced both by his or her genetic predisposition and by the environment. The relatively new field of epigenetics has allowed us to understand that environmental influences occurring prenatally and in early life can start to shape development before birth, throughout childhood, and beyond, potentially affecting subsequent generations. It is in this context that early childhood adversity and toxic stress in the lives of young children can be understood as a significant risk factor for poor outcomes in development, behavior, and learning across the life course.

Physiological responses to stress are well studied and defined.^6–8 During the stress response, the hypothalamic-pituitary-adrenocortical axis and the sympatheticadrenomedullary system are activated, resulting in increased levels of stress hormones, such as corticotrophin-releasing hormone (CRH), cortisol, norepinephrine, and adrenaline. At the same time, other mediators, such as inflammatory cytokines, are released. Meanwhile, the parasympathetic nervous system responds to provide a counterbalance and attempt to achieve homeostasis within the body. Transient increases in these hormones in response to stress are protective and essential for survival. In contrast, excessively high or prolonged elevations in stress hormones are harmful and can be considered toxic, leading to chronic changes in brain architecture and bodily function, including alterations in physiological and emotional regulation and in executive function.^6–8 The AAP describes 3 distinct types of stress in young children: positive, tolerable, and toxic stress.⁴

Toxic stress can stimulate a child’s reticular activating system and lead to sleep disturbances. Elevated circulating catecholamines can also produce anxiety, suppression of the satiety center (leading to overeating or failure to thrive), enuresis, and encopresis. Toxic stress can impact working memory and lead to slow acquisition of milestones or learning challenges. It can decrease inhibitory control, causing tantrums or fighting. Its impact on cognitive flexibility may result in difficulty with frustration tolerance, organization, concentration, and activity level.9

Toxic stresses are the kinds of risk factors studied in the Adverse Childhood Experiences (ACE) Study¹⁰ of more than 17,000 adults for more than 20 years. This work has shown a strong and graded association between the number of these childhood stressors and a higher risk of poor outcomes in health and educational achievement in adulthood. A recent AAP technical report summarizes the growing evidence that links childhood toxic stress with the subsequent development of unhealthy lifestyles, persistent socioeconomic inequality, and poor health.⁴

In addition to short-term changes in observable behavior in young children, toxic stress can lead to outwardly visible and permanent changes in brain structure and function.^7,8 Both human and animal studies demonstrate that persistently elevated levels of stress hormones can disrupt the brain’s developing architecture.^7,8 Therefore, this altered brain architecture in response to toxic stress in early childhood can explain, at least in part, the strong association between early adverse experiences and subsequent deficits in educational and health outcomes.

Toxic stress early in life plays a critical role in changing the course of development by disrupting brain circuitry and other important regulatory systems in ways that continue to influence physiology, behavior, and health decades later.4 Some degree of childhood adversity is inevitable, and learning to manage mild to moderate levels of stress is important for healthy development. As the central element of toxic stress is the absence of buffers needed to return the physiological stress response to baseline, pediatric health care professionals play an important role in recognizing risk factors, supporting families through anticipatory guidance, strengthening families’ social support systems, and encouraging a family’s adoption of positive parenting techniques. These actions can facilitate a child’s emerging social, emotional, and language skills. In addition to the AAP currently recommended developmental screenings at 9, 18, 24, and 30 months of age, pediatric practices should consider implementing standardized measures to identify other family- or community-level factors that place children at risk for toxic stress (eg, maternal depression, parental substance abuse, domestic or community violence, food scarcity, poor social connectedness).^11,12 See also Figure 3.1.

Figure 3.1. The Adverse Childhood Experiences (ACE) Pyramid.¹³

From Centers for Disease Control and Prevention. Adverse Childhood Experiences Web site. https://www.cdc.gov/violenceprevention/acestudy/about.html. Accessed January 22, 2018.

Important Examples of Environmental Factors That Affect Child Development and Behavior

One in 5 children grows up poor in the United States, and 42% of children are poor or near poor.14 Children are the poorest age group in our society. In comparison, only 9% of older Americans over 65 are poor. Young children are especially impacted by the effects of poverty, often leading to life-long disadvantage. Poverty’s impacts on young children are mediated by parenting. Family income affects parenting directly and through material hardship, including food insecurity, residential instability, inadequacy of medical care, serious financial difficulties, and the inability to pay monthly bills. The negative effects of low family income and increased material hardship are associated with increased parenting stress (including increased maternal depression and marital discord), decreased investment in children, and decreased positive parenting. Investment in children includes educational toys, books, high-quality early childhood care and education, as well as parent activities with the child outside the home and provision of extracurricular activities. In turn, these negative effects on parenting and provision of resources for the child lead to decreased cognitive skills (eg, reading and math) and decreased social-emotional competence (including problems with self-regulation, executive function, and increased externalizing behaviors) in the child.^15,16

The differences in developmental outcomes for poor children and nonpoor children start early. Differences in language development can be observed almost as soon as expressive language begins, and by 2 or 3 years of age, these differences are marked.¹⁷ These differences are directly related to the quantity and quality of the language that children are exposed to, primarily from their parents. By the time poor children start school, on average, their reading and math skills trail those who are at higher income, and many are never able to catch up.^18,19 Overall, poor children have higher rates of learning disabilities, serious emotional and behavioral difficulties, grade repetitions, and receipt of early intervention and special education services; their high school dropout rates are 1.5 to 2.5 the rates of nonpoor children.²⁰ There is growing evidence from studies of the Earned Income Tax Credit, Canada’s National Child Benefit, welfare reform experiments, and natural experiments (eg, comparing Native American and non–Native American families when Native American families received distributions from casino profits) that increasing family income and decreasing poverty meaningfully improve developmental and academic outcomes in poor children.^16,20 In addition, exposure to concentrated neighborhood poverty further worsens the developmental, behavioral, and academic outcomes of poor children, and it may also lead to worse outcomes as children move through adolescence into adulthood.²⁰

Recent studies have documented structural changes in the brain related to poverty. Children in poor families have been shown to have reduced volumes in the frontal and temporal cortices as well as the hippocampus. These are key areas of the brain necessary for school readiness and academic achievement and are associated with the development of executive function, language, and memory. It has been shown that brain volumes in the frontal and temporal cortices explain 15% to 20% of the difference in academic achievement test scores between poor and nonpoor children.21 Parental income and education have also been shown to be related to the surface areas of the frontal, temporal, and parietal cortices of children, and these findings are strongest in those living below the federal poverty level.²² Early childhood adversity and toxic stress is also more likely to be experienced by children growing up in poverty, and therefore, the disruption of brain architecture associated with toxic stress is another feature of poor children’s development.²³ Other studies have documented increased cortisol levels in children living in poverty, with higher levels related to the duration of the poverty. A 2016 AAP technical report on the adverse effects of child poverty delineates these and other mediators of the negative effects of poverty on child development, behavior, mental health, and academic performance.²⁴

In summary, children living in poverty receive fewer resources and less environmental stimulation for the normal progression of the child’s cognitive, language, and social-emotional development, as well as school readiness/academic achievement. Children living in poverty also experience a high level of stress that is toxic to their brain’s development and behavior. To a large degree, especially for young children, these impacts are mediated by parenting. Parenting may be less nurturing and positive in many poor households due to increased parenting stress related to low income and material hardship. For older children and adolescents, exposure to neighborhoods with concentrated poverty and inferior schools further worsens their outcomes.

Interventions to ameliorate the impact of poverty on children, as well as to decrease the number of children in poverty, as outlined in the AAP policy statement on poverty and child health,²⁵ include both advocacy for maintaining and strengthening government supports for poor families (eg, the Earned Income Tax Credit, the Supplemental Nutrition Assistance Program, and maternal-child home visiting programs), and screening and referral in the pediatric medical home for child developmental, behavioral, and mental health problems as well as for maternal depression. Importantly, the AAP also recommends screening and referral for risk factors for material hardship (often referred to as the social determinants of health) and supports early literacy and positive parenting programs integrated into the pediatric medical home.²⁵

Parental Depression/Substance Abuse/Mental Health Issues and Family Systems

Behavioral health challenges are common in American families. According to the National Institute of Mental Health, 6.7% of American adults experienced at least 1 major depressive episode of 2 weeks or longer in 2015.²⁶ This figure is even higher in new mothers. According to the Centers for Disease Control and Prevention (CDC), in 2012, 11.5% of US mothers giving birth reported having postpartum depression (PPD) symptoms. Factors associated with the highest rates of PPD symptoms were: (1) being a teenage mother; (2) being of Native American or Asian Pacific Islander race/ethnicity; (3) having ≤12 years of education; (4) being unmarried; (5) being a smoker; (6) having experienced ≥3 life stresses in the year before birth; (7) giving birth to a low birth weight term infant or to multiple births (eg, twins, triplets); and (8) having an infant who required neonatal intensive care.27

Many studies have documented a higher prevalence of psychiatric disorders in children of depressed than in those of nondepressed parents. The risk for psychiatric disorders may be particularly high in children of low-income depressed mothers.²⁸ Exposure to both intimate partner violence and depression before age 3 years is associated with preschool-aged onset of attention-deficit/hyperactivity disorder (ADHD), and early exposure to parental depression is associated with preschoolers being prescribed psychotropic medication.²⁹ A 30-year study of 2 generations of individuals at high versus low risk for depression found that the biological offspring with 2 previous generations affected with major depression were at highest risk for major depression.³⁰

Prospective research has shown that lower income and lower maternal education are associated with more behavioral concerns in children. Adjustment for maternal smoking, depressive symptoms, and alcohol use have been shown to attenuate the associations between socioeconomic status and child behavior problems by 25% to 50%.³¹ This effect may be mediated through family functioning, maternal sensitivity and differential sensitivity to social adversities within populations of children, and it may be guided by epigenetic mechanisms.^32,33 This work also demonstrates that social disparities in women’s health conditions may help shape the likelihood of behavior problems in subsequent generations. Improved public health services for disadvantaged women across the life course may address their own health needs and thereby reduce social disparities in the well-being and health of their children.

The prevalence of behavioral or emotional disorders in American children is 11% to 20%.³⁴ Developmental and behavioral disorders are now the top 5 chronic conditions causing functional impairment in children.³⁵ However, the ability of pediatric health care professionals to identify developmental-behavioral problems in primary care, on the basis of clinical judgment alone without the aid of a standardized measure, has low sensitivity (14% to 54%).³⁶

Primary pediatric health care professionals play a key role in performing ongoing surveillance of families with these known sociodemographic risk factors and in referring for early intervention and resources to mitigate long-term sequelae. The AAP has clinical reports on incorporating postpartum depression screening into pediatric practice and on promoting optimal development through implementation of behavioral and emotional screening in practice.^12,34 These reports outline how pediatric practices, as medical homes, can establish systems and overcome barriers so that they can implement behavioral, emotional, and postpartum depression screening. They also help practices identify community resources for the treatment of depressed mothers, support parent-child relationships, and address the social-emotional needs of children.^12,34 The Centers for Medicare & Medicaid Services have recently recognized the importance of this type of screening by allowing state Medicaid agencies to cover maternal depression screening as part of well-child visits. States must also cover any medically necessary treatment for the child as part of their Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) benefit. In addition to covering this screening for Medicaid-eligible mothers, states may cover maternal depression screening for non-Medicaid-eligible mothers during well-child visits. States may also cover treatment for the mother when both the child and the mother are present, when treatment focuses on the effects of the mother’s condition on the child, and when services are provided for the direct benefit of the child.37

Foster Care and Adoption

The research on ACEs demonstrates that child abuse and neglect can have a profound impact on the development of a child. When children are removed from their homes due to abuse or neglect, it is important to realize that this placement can potentially be another negative stressor for the child. Children are often separated from family, friends, neighborhoods, and schools. Half of foster children experience more than 1 foster care placement. Plans for reunification or adoption are often uncertain with no clear timeline in place. These stresses can all affect a child’s behavior and development.³⁸

Children in foster care have higher rates of mental health issues, developmental delays, and learning problems compared to peers. Up to 25% of young children in foster care have a developmental delay, up to 25% of teenagers in foster care have posttraumatic stress disorder, and 80% of adolescents aging out of the foster care system have a mental health diagnosis.⁹ Over 40% of foster children receive special education services, and their rates of acute and chronic illness are also increased.³⁸

Central to a child’s social and emotional development is his or her ability to form a secure attachment to a stable, caring, responsive adult. The presence of a stable adult who provides unconditional love and acceptance is critical to helping a child overcome past abuse and neglect. The age and developmental level of a child at foster placement, as well as the quality of care he or she receives, will contribute to the emotional consequences of abuse and placement. Multiple foster care placements can further disrupt a child’s ability to form secure attachments.³⁹

The primary pediatric health care professional should keep in mind the effects that foster care placement have on a child and provide supports to both the child and the child’s foster parents. By educating foster and adoptive parents about the effects of toxic stress on a child’s learning, behavior, and health, the professional can encourage understanding of maladaptive and frustrating behaviors. A child may benefit from referral to trauma- informed counseling services, such as Parent-Child Interaction Therapy or Trauma Focused Cognitive Behavioral Therapy.⁹

Cultural and Community Factors

Cultural diversity in children and families is reflected in their traditions, languages, customs, beliefs, health practices, and social interactions.^40,41 This diversity exists within our communities, though communities may differ in other ways as well. For example, they can also vary in socioeconomic status, health status, academic attainment, and ethnic diversity. These differences have the potential to lead to a multitude of advantages or disadvantages and can result in disparities in child health and well-being. Communities with strong cultural bonds can also exhibit strong social capital, providing individuals with connections to their neighbors, supportive social networks, and a sense of trust and safety.41 Strong communities may also provide a child with protective opportunities and resources, including libraries and parks, social networks, religious establishments, quality schools, and quality child care. However, for families that must frequently relocate due to economic strife, this sense of community and the social support it provides is relatively nonexistent.

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