Friday, October 21, 2016

The childhood roots of illness

A growing body of scientific evidence reveals the dramatic impact of early-life adversity on lifelong health.

Kelly Kelleher compares childhood health to a boulder sitting on the peak of a mountain. A slight push could send the boulder in many directions. And once it starts rolling, it’s hard to change its path. The same goes for children. What happens to them early in life can send them hurtling toward or away from a lifetime of good health.

Over the past two decades, research has confirmed this idea, showing the biological connections between childhood adversity and poor health later in life. Most people, of course, recognize the importance of childhood. However, recent research has raised the stakes, revealing how poverty, violence, parental dysfunction and other social factors can alter the architecture of the brain and lead to such health problems as heart disease, obesity, depression and substance abuse.

“The longer you’re in a high-risk class, the more health deficits you accrue,” says Dr. Kelleher, MD, the director of the Center for Innovation in Pediatric Practice at Nationwide Children’s Hospital.

At the heart of the problem is what pediatric researchers call “toxic stress,” chronic adversity that can overwhelm a child. To be sure, some stress is good. In fact, adversity can help children develop resilience and coping skills with the support of caring adults. But when the adversity is constant — and adults don’t help children feel safe and emotionally connected — then the stress can turn toxic.

“Research has demonstrated that stress is not just correlated with illness, but it actually is related to biological changes that we know affect rates of illness,” says Tom Boyce, MD, professor of pediatrics at the University of California San Francisco.

The discovery highlights the importance of childhood and prenatal programs. For these early-life interventions to succeed, however, they require a new way of thinking: a coordinated, comprehensive approach that addresses the wide variety of environmental conditions — from crime to nutrition to poor housing — that influence lifelong health.

“That’s why we talk about how being born healthy, learning healthy and living healthy all fit together now,” Dr. Kelleher says. “The education system, the neighborhood and the health care system are not separate anymore.”…

That began to change toward the end of 20th century. In the 1980s, David Barker, a British physician and epidemiologist, noticed in the United Kingdom a strong geographic correlation between neonatal and post-neonatal mortality and death from heart disease 60 to 70 years later. The discovery shaped what became known as the “Barker hypothesis” — that the environment of the fetus and infant can determine pathologies later in life.

The idea was supported by the landmark ACE Study, an ongoing collaboration between the U.S. Centers for Disease Control and Prevention in Atlanta and Kaiser Permanente’s Health Appraisal Clinic in San Diego. In the late 1990s, the study surveyed more than 17,000 patients about their adverse childhood experiences (ACEs), including abuse, neglect and family dysfunction. The findings showed that traumatic experiences pose major risk factors for the leading causes of illness and death.

Since then, scientific research has provided a deeper understanding of early-life exposures. In 2000, the Institute of Medicine and National Research Council releasedFrom Neurons to Neighborhoods: The Science of Early Childhood Development, an influential report that synthesized research on the topic. The report described the scientific evidence as “incontrovertible” on the developmental impacts of early experience. The effect could be felt even before birth. Individuals exposed to severe nutritional deficits in utero during the Dutch famine of 1944, for instance, showed a higher prevalence of heart disease 50 years later…

Environmental factors such as extreme poverty, recurrent physical or emotional abuse, chronic neglect and severe maternal depression can result in prolonged activation of the body’s stress-response systems. This phenomenon, according to research, can lead to early genetic aging, heightened immune responses and behavioral and cognitive problems, such as anxiety, aggression and memory lapses.

Elevated cortisol can cause emotional and physiologic dysregulation. “When you’re a kid who doesn’t have anybody to turn to, and you go from one stressful event to another in a dangerous place, and you don’t have a calming influence in your life, what happens is your brain has constant cortisol, and you down regulate,” Dr. Kelleher says. “You can’t learn. You can’t interact with others effectively. You appear flattened emotionally — depressed, basically.

“So we have a whole bunch of kids whose systems have shut down. They can be angry. They can be sad. But they’re not learning. They’re not growing in development. They’re not developing social skills and resilience. And so this has physical consequences. Their bodies are more likely to get infected, more likely to have asthma, more likely to have these other problems.”…

Research also indicates that high quality childhood intervention programs can have a significant impact. In 2014, a team of scientists, including Nobel-winning economist James Heckman, published a study in Science looking at the Abecedarian preschool program, a North Carolina social experiment in the 1970s that tested whether an intellectually stimulating early childhood environment could prevent developmental delays among poor children. The 2014 study found that participants had significantly better health, such as lower risks for heart disease and diabetes, than similar individuals who weren’t in the program…

Indeed, nurturing adults can shield children from stressful environments. If you can provide or restore sensitive caregiving relationships, you can foster remarkable recoveries in children, researchers have concluded. But interventions must recognize the complex socioeconomic problems that surround the issue. If advocates don’t address housing instability, income disparity and other poverty-related factors, even the most well-meaning and stimulating preschool program will be undermined. “There is no single magic bullet,” says Dr. Braveman, the co-author of a 2014 report from the Robert Wood Johnson Foundation on early childhood experiences.

Campbell F, Conti G, Heckman JJ, Moon SH, Pinto R, Pungello E, Pan Y. Early
childhood investments substantially boost adult health. Science. 2014 Mar

High-quality early childhood programs have been shown to have substantial benefits in reducing crime, raising earnings, and promoting education. Much less is known about their benefits for adult health. We report on the long-term health effects of one of the oldest and most heavily cited early childhood interventions with long-term follow-up evaluated by the method of randomization: the Carolina Abecedarian Project (ABC). Using recently collected biomedical data, we find that disadvantaged children randomly assigned to treatment have significantly lower prevalence of risk factors for cardiovascular and metabolic diseases in their mid-30s. The evidence is especially strong for males. The mean systolic blood pressure among the control males is 143 millimeters of mercury (mm Hg), whereas it is only 126 mm Hg among the treated. One in four males in the control group is affected by metabolic syndrome, whereas none in the treatment group are affected. To reach these conclusions, we address several statistical challenges. We use exact permutation tests to account for small sample sizes and conduct a parallel bootstrap confidence interval analysis to confirm the permutation analysis. We adjust inference to account for the multiple hypotheses tested and for nonrandom attrition. Our evidence shows the potential of early life interventions for preventing disease and promoting health.

1 comment:

  1. Karlén J, Ludvigsson J, Hedmark M, Faresjö Å, Theodorsson E, Faresjö T. Early psychosocial exposures, hair cortisol levels, and disease risk. Pediatrics. 2015 Jun;135(6):e1450-7.

    Early psychosocial exposures are increasingly recognized as being crucial to health throughout life. A possible mechanism could be physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity. The objective was to investigate whether early-life adverse psychosocial circumstances influence infant cortisol levels in hair and health outcomes in children prospectively until age 10.
    A cohort study in the general community using a questionnaire covering 11 psychosocial items in the family during pregnancy and the cumulative incidence of diagnoses until age 10 years in 1876 children. Cortisol levels in hair were measured by using a radioimmunoassay in those with sufficient hair samples at age 1, yielding a subsample of n = 209.
    Children with added psychosocial exposures had higher infant cortisol levels in hair (B = 0.40, P < .0001, adjusted for gender and size for gestational age) in a cumulative manner and were significantly more often affected by 12 of the 14 most common childhood diseases, with a general pattern of increasing odds ratios.
    The findings support the model of physiologic dysregulation as a plausible mechanism by which the duration and number of early detrimental psychosocial exposures determine health outcomes. The model indicates that the multiplicity of adversities should be targeted in future interventions and could help to identify children who are at high risk of poor health. Furthermore, given the prolonged nature of exposure to a stressful social environment, the novel biomarker of cortisol in hair could be of major importance.