Multiple Adverse Events in Kids Linked to Top Causes of Death

Tara Haelle

November 07, 2019

Hardship, violence, or other extreme childhood stress can have a substantial lifetime impact, contributing to half of the top 10 causes of death in the United States, according to new research from the Centers for Disease Control and Prevention (CDC). One in six American adults has experienced multiple adverse childhood experiences (ACEs), and prevention of these ACEs could have a far-reaching impact on public health, suggests a Vital Signs report published online November 5.

The report is the "first-ever comprehensive estimate of how much ACEs affect adults' long-term health and social situations," said Anne Schuchat, MD, the principal deputy director of the CDC, in a telebriefing November 5. "Multiple different types of ACEs together can produce toxic stress, which is a chronic activation of the stress response system that results in negative effects on brain development, behavior, and well-being," Schuchat said. Heart disease, cancer, respiratory diseases, diabetes, and suicide are five leading causes of death linked to ACEs, she added.

The new CDC analysis suggests that "preventing ACEs would have potentially resulted in up to 1.9 million avoided cases of coronary heart disease, 2.5 million avoided cases of overweight or obesity, and 21 million cases of avoided depression," she said.

Related findings published in JAMA Pediatrics November 4 provide insight into the link between ACEs and inflammation in adulthood, putting forth a new biomarker to use in screening people for inflammation associated with ACEs.

ACEs include a range of traumatic exposures, including child abuse or neglect, sexual abuse, and living in a household with stressful events, such as incarceration or drug use. Since the original study identifying ACEs, researchers have increasingly identified associations between ACEs and multiple health problems.

"Fundamental to adverse childhood experience prevention is the creation of safe, stable, nurturing relationships and environments for all children and families," write Melissa T. Merrick, PhD, and her colleagues at the CDC's National Center for Injury Prevention and Control in the Vital Signs report. "Multiple studies have documented that substantial reductions in adverse childhood experiences are possible and can have broad and sustained benefits."

Rolled out with the new report is a new CDC resource, Preventing Adverse Childhood Experiences: Leveraging the Best Available Evidence, which healthcare providers, policy makers, teachers and other stakeholders can use to implement protective measures to reduce ACEs' prevalence.

ACEs Associated With Multiple Chronic Health Conditions

The CDC researchers analyzed results from 25 states who added questions about ACEs to the Behavioral Risk Factor Surveillance System, an annual phone survey of adults in all US states and territories. The 11 questions covered eight ACEs experienced before age 18 years: physical, emotional, and sexual abuse; a parent divorce; and living in a household with substance use, interpersonal violence, an incarcerated member, or someone with a mental illness. Response rates ranged from 31% to 59% across different states (total 144,017 respondents).

Researchers grouped respondents into four categories on the basis of experiencing zero, one, two or three, or four or more ACEs. The surveys collected data on respondents' body mass index, smoking status, alcohol use, health insurance status, employment, and education. Respondents also reported diagnoses of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease (COPD), cancer (except skin cancer), kidney disease, diabetes, or depression.

One in six adults (15.6%) had experienced at least four ACEs, and 60.9% of respondents had experienced at least one. Likelihood of ACEs was also greater for women compared with men, for younger adults compared with older adults (over 65 years) and for blacks, American Indian/Alaskan Natives, and those identifying their race/ethnicity as "Other" compared with whites.

Chronic health conditions occurred more often in adults with the most ACEs exposure (4+) compared with those with no ACEs. Depression was 5.3 times more likely in those with at least four ACEs (adjusted odds ratio [aOR], 5.3), and odds more than doubled for stroke (aOR, 2.1), asthma (aOR, 2.2), and COPD (aOR, 2.8). Increased odds for obesity, diabetes, cancer, kidney disease, and coronary heart disease ranged from 1.2 to 1.8 times greater. Confidence intervals indicated significance on all these associations.

Adults with the most ACEs were also more likely to smoke (aOR, 3.1) and drink heavily (aOR, 1.8), and they were less likely to complete high school (aOR, 1.4), be employed (aOR, 1.7) or have health insurance (aOR, 1.3).

In their statistical analysis, depression emerged as the public health problem most likely to be alleviated by prevention of ACEs: 44.1% of depression diagnoses were attributed to ACEs, which also accounted for an estimated 32.9% of smoking and 23.9% of heavy drinking. About a quarter of asthma (24%) and COPD (27%) cases were attributed to ACEs. Obesity (1.7%), diabetes (5.7%), and cancer (5.9%) had the lowest percentages whereas kidney disease, coronary heart disease, and stroke ranged from 12.6 to 15.7%. Percentages of the burdens of unemployment, lower education, and no insurance could also be reduced with ACEs prevention.

The authors note that social desirability and recall bias may have underestimated ACEs prevalence and emphasize that the associations from their cross-sectional survey could not demonstrate causality. Other limitations include lack of additional information about the traumatic experiences and inability to control for confounders linked to both ACEs and the health outcomes.

Separate Study Links ACEs to Inflammation

The day before the Vital Signs report, Line Jee Hartmann Rasmussen, PhD, of Duke University, and colleagues published findings in JAMA Pediatrics that linked ACEs to increased chronic inflammation using the biomarker soluble urokinase plasminogen activator receptor (suPAR). Previous research has already linked ACEs to inflammation based on C-reactive protein (CRP) and interleukin 6 (IL-6) measurements.

The researchers tested plasma samples from 1391 twins in the Environmental Risk Longitudinal Twin Study in the United Kingdom who had been born in 1994 to 1995 and tracked until age 18 years.

After adjustments for sex, body mass index, and smoking, each additional ACE a person had was associated with a 0.03 ng/mL increase in suPAR levels. A greater increase of 0.09 ng/mL occurred for each additional severe stressful or violent childhood experience, and a 0.04 ng/mL increase for each severe experience of stress or violence during adolescence.

The association was additive for experiences throughout youth: compared with those who experienced no severe stress or violence, those with multiple types of violence in their childhood and adolescent history had 0.26 ng/mL higher suPAR levels.

The suPAR levels remained higher even when CRP or IL-6 levels were not elevated. And when the researchers controlled for CRP and IL-6 levels, they still found elevated suPAR levels for each additional ACE (0.05 ng/mL), severe childhood ACE (0.14 ng/mL), and severe adolescent ACE (0.10 ng/mL).

"The findings suggest that stress-related inflammation begins at a relatively young age" and that including suPAR measurements can improve assessment of the associated inflammatory burden, the authors conclude.

"We observed the strongest associations between stress exposure and inflammation when combining biomarkers, and we also found that adverse experiences were prominent in the group of participants with low CRP or low IL-6 level, who would have inadvertently been assigned to the low inflammation group if suPAR levels had not been assayed," they write.

Given the magnitude of issues that can cause trauma or stress in youth, such as climate change and increasing socioeconomic disparities, the discovery of suPAR's utility in identifying at-risk children represent "a promising step forward," write Nicole R. Bush, PhD, and Kirstin Aschbacher, PhD, of the University of California San Francisco, in an accompanying editorial. Its "stronger and more exposure-specific association," compared with other biomarkers like CRP, can advance diagnosis, treatment, and precision medicine strategies.

But they caution the need to "go deeper, elucidating for whom, under what circumstances, and by what mechanisms trauma promotes inflammation" since association vary between trauma and different biomarkers. They also noted the need to understand "positive factors to ascertain what environmental or individual difference conditions promote resilience to adversity."

Effective Interventions For Preventing Trauma

Strong, healthy relationships are a key way to reduce the impact of ACEs, explained James A. Mercy, PhD, director of the Division of Violence Prevention in the CDC's Injury Center, during the telebriefing.

"One of the really important issues is that when these ACEs occur in the absence of adult support, their impact can be even greater," Mercy said. "That really gets to the issue of prevention and the need to promote safe, stable, nurturing relationships for all children and environments for all children."

Merrick and colleagues outline in their report several evidence-based strategies for prevention of ACEs, ranging from policy initiatives to individual interventions.

"While it might not be possible to avoid every ACE, there are many opportunities to prevent ACEs from happening in the first place and to help those who have experienced ACEs," Schuchat said in the telebriefing. "Children's positive experiences, relationships, or other protective factors and interventions can strengthen resilience and reduce behavioral and health consequences even after ACEs have occurred."

Schuchat listed the six main strategies for prevention discussed in the Vital Signs report and included in the new CDC resource:

  • "intervening to lessen harms of ACEs with treatment, services, and support;

  • connecting youth to caring adults and activities through mentoring and after-school programs;

  • improving youth and parent skills, like communication and problem-solving, to manage stress and everyday challenges;

  • providing high-quality, affordable childcare and early education to ensure a strong start;

  • promoting social norms that protect against violence and adversity; and

  • strengthening families' economic stability to reduce family stress and conflict."

The Vital Signs report was funded by the CDC, and the authors have disclosed no relevant financial relationships. The JAMA Pediatrics research was supported by the Medical Research Council, National Institutes of Health, Jacobs Foundation, Lundbeck Foundation, British Academy Mid-Career Fellowship, MQ Mental Health Charity, and the UK Economic and Social Research Council. Rasmussen reported grants from ViroGates, and Eugen-Olsen disclosed fees from ViroGates, is a ViroGates shareholder, and holds a patent related to treating patients with low-grade inflammation. The editorial was supported by the Lisa and John Pritzker Family Foundation and the Lazlo N. Tauber Family Foundation. Coauthor Bush serves on the JPB Network on Toxic Stress.

MMWR. Published online November 5, 2019. Report

JAMA Pediatrics. Published online November 4, 2019. Full text, Editorial

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