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Predicting Children’s Health: The Promise of Blood Tests

Predicting Children’s Health: The Promise of Blood Tests What if children could get a test at the doctor’s office that would tell them if stress experienced in their early lives is putting themselves at high risk of poor health and early death? And what if the results of that test could tell them exactly what treatment would help?

Childhood Adversity — and why it matters

For several decades, physicians, neuroscientists, and psychologists have been mapping the harmful impacts of high levels of stress on the body. Significant childhood adversity, such as abuse and neglect, is a form of stress that can affect brain architecture, neurochemistry, and biological processes. Childhood adversity is a particularly strong predictor for poor health across the lifespan, as shown by the famous Adverse Childhood Experiences (ACE) Study, conducted at Kaiser Permanente and the Center for Disease Control (CDC). The ACE story was born out of the frustration and curiosity of endocrinologist, Dr. Vincent Felitti. The story goes that nearly 25 years ago, Dr. Felitti was running a weight-loss clinic. He could not understand why some patients were losing weight, but then gaining it back, or prematurely dropping out of the study. He began to interview these patients and a pattern emerged: a disproportionately high percentage of these patients had histories of childhood adversity, specifically childhood abuse, neglect, and house dysfunction. With his colleague, Dr. Robert Anda, they ran a study where 17,000 US adults filled out a questionnaire about ten potential adverse childhood experiences, called ACEs, at their annual health exam. ACEs covered a range of stressful experiences from more common stressful experiences, such as divorce, to even more severe experiences, such as physical abuse.


Source: Centres for Disease Control and Prevention; Credit: Robert Wood Johnson Foundation

The findings were clear. Firstly, ACEs were incredibly common (50% of people have at least one). But ACEs were also the strongest predictor of adult disease and early death.

Importantly, ACEs predicted both physical and mental health outcomes. For individuals with four or more ACEs, the likelihood of developing physical diseases (e.g., stroke) and psychological disorders (e.g., depression) was particularly high.

ACEs had long-reaching and widespread influences on virtually all aspects of health from injury to mental health to risky behaviors to chronic diseases.


These findings entered our public stream of consciousness.

Over two decades later, renowned American pediatrician Dr. Nadine Burke Harris delivered a Ted Talk (“How Childhood Trauma Affects Health Across a Lifetime”); it would amass over 2.8 million views. You can even find out your own ACE score with a quick Internet quiz.

But, what does this score mean? What can it tell us, and what can it not tell us?

Could we just get an ACE score at the doctor? What would it mean?


Moving Beyond an ACE Score


An ACE score is a solid predictor of health outcomes in a large research study. But it may not be able to accurately predict your individual health outlook.

While ACE exposure generally predicts poor health, it is not true for all people.

In other words, some people are more resilient to adversity than others — or, better, some children are more resilient than others.

One important reason is the caregiving environment. Caregiving high in warmth, sensitivity, and responsiveness is a powerful buffer against stress.


Positive caregiving can buffer children against the negative impacts of adversity

One other important reason is children’s biological functioning. In some children, ACEs “get under the skin,” and may negatively impact a variety of biological health processes — how their cells communicate and function, the circuitry of their brain, and more.

These may be the children that, when they become adults, are at risk of poor health.

And perhaps these children can be identified, and helped, early on in their lives.

As a Clinical Psychology doctoral student at the University of Oregon, my research is rooted in these two primary goals:

1) examine the impact of childhood adversity on children’s biological systems and

2) translate this knowledge to help predict which children may be at highest risk for poor health trajectories.

Is it that simple though?

Could something like a blood test really tell us that which child is at high risk for poor health, all the way from metabolic problems (for example, diabetes or obesity) to mental health problems (for example, depression or anxiety)?


Biomarkers of Adversity and Risk


Neuroscientists believe that there are tests, or biomarkers, that can tell us if childhood adversity has “gotten under the skin.”

Such markers may help us understand if the stress is high enough to have infiltrated the body’s biological functions early on in development — which may, in turn, serve as an initial sign for future poor health, before symptoms or disorders have developed.

Unfortunately, nothing in neuroscience is that simple. Here, I discuss what stands in the way of this worthy goal, and what can be done to reach it.


Which blood tests should we use?


If your pediatrician thinks a child has diabetes, they will likely order a blood test to examine blood sugar, or the blood levels of a protein called ‘glycosylated hemoglobin’ which is basically a protein where excess sugar sticks. Those one or two biomarkers, in combination with early symptoms, are usually enough information to make a diagnosis and guide your child to the proper treatment.

But blood tests become much trickier when you are trying to predict future possible diseases, ones where symptoms may not be obvious yet.


Blood test at the pediatrician’s office may provide valuable information about children’s future health. Source: Dell Children









And that is an unanswered question when it comes to biomarkers — can they actually predict the early formation of an illness, before you can see it?

Even more tricky is that we are trying to predict diseases that span across mental and physical health domains. Is it realistic that a blood test would predict both depression and obesity?


Future Direction: A Panel of blood tests


Childhood adversity predicts a wide range of negative health outcomes, many of which do not fully manifest until adulthood. As such, careful attention must be paid to selecting which biomarkers are most likely to connect early signs of stress to a host of diseases and disorders.

One advantage is that we now know a lot more about how physical and mental health coincide.

Broadly, neuroscientists study what we call stress responsivity systems. In other words, these are the systems in our body responsible for responding to stress and helping our body regulate properly.

Chronic levels of stress and adversity can alter how these systems work in important ways. And these systems are key players in a child’s health and development.

Altered functioning in the immune, metabolic and neuroendocrine systems can influence both physical health (think, diabetes) andmental health (think, depression).

My own work has focused primarily on immune and metabolic functions, trying to understand if and how childhood adversity influences these systems. From there, we can make stronger predictions about how immune and metabolic function then impacts health.

There are many examples of types of immune and metabolic markers, but two I discuss here inflammation and oxidative stress.

Inflammation is a hot topic, often featured in news articles about everything from diet and exercise to depression to cardiovascular health. Inflammation is a key part of your body’s immune system and is critical to healing.




Inflammation has received a lot of attention in the news because it is implicated in many physical and mental health diseases. There are many biomarkers of inflammation, including C-reactive protein, Interleukin-6, and white blood cell count. Source: needpix.com



Inflammation has received a lot of attention in the news because it is implicated in many physical and mental health diseases. There are many biomarkers of inflammation, including C-reactive protein, Interleukin-6, and white blood cell count. Source: needpix.com

What is important is that both physical stress, like a cold, and psychological stress, like chronic childhood adversity, can set off inflammation. Crucially, inflammation is important to healing in the short-term but can be problematic when it becomes chronic.

Higher inflammation has been observed in adults with a history of childhood adversity. But we need more research on this in children.

We also see high levels of inflammation in both depression and cancer as well as cardiovascular disease.


Depression is one example of mental health disorder where we see high levels of inflammation. Schizophrenia, post-traumatic stress disorder (PTSD), and Obsessive Compulsive Disorder (OCD) are other examples. Source: pixabay.com





Depression is one example of mental health disorder where we see high levels of inflammation. Schizophrenia, posttraumatic stress disorder (PTSD), and Obsessive Compulsive Disorder (OCD) are other examples. Source: pixabay.com

Oxidative stress is another critical factor in many diseases, such as cancer and obesity.

Oxidative stress occurs when there is an imbalance between the body’s production of free radicals and antioxidants.

Free radicals are highly-reactive molecules that are missing an electron in their outer shell. Electrons prefer to be in pairs, so these free radicals will doanything to seek out other electrons to become a pair, including “stealing” from other cells.

Left unchecked, this cellular thievery can lead to damage in the cell’s membranes and eventually start to harm important components of the cell, like the DNA, lipids, or proteins.

Thankfully, our bodies have antioxidants that act as neutralizers by donating an electron to these free radicals, and thus protecting cell health.





Antioxidants neutralize free radicals (sometimes called Reactive Oxygen Species) by donating an electron. Source: Medical News Today





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Unfortunately, stress can lead to an excess of free radicals, which can then overwhelm those antioxidant defenses, leading to poor metabolic health and cell damage.

In my work, we demonstrated that a biomarker of oxidative stress was detectable in the urine of teens exposed to childhood adversity.


That marker was also associated with emerging symptoms of mental health problems, like depression. This work is very new, but it provides some initial evidence that childhood adversity may affect metabolic health in teens and is linked with initial warning signs of mental health problems.

These are just two examples, but a panel of blood tests will be the most helpful in predicting risk, rather than one single marker.


A panel of biomarkers could enhance pediatrician’s ability to predict which children are at highest risk for poor health outcomes, especially when results from a blood panel are paired with other risk markers, like early behavioral problems or developmental delays. Source: Wikipedia



A panel of biomarkers could enhance pediatrician’s ability to predict which children are at highest risk for poor health outcomes, especially when results from a blood panel are paired with other risk markers, like early behavioral problems or developmental delays. Source: commons.wikimedia.org

Even more helpful will be to pair these biomarkers with psychological risk markers, such as early behavior problems and developmental delays.

However, for these blood tests to be clinically useful, we need to know what the results of a blood test would mean for the child’s health.

The issue is that we do not necessarily know yet how reliable these biomarkers are or how to interpret them.

Simply put, more research is needed that connects these biomarkers to both childhood adversity and poor health. This requires longitudinal studies, or studies that start by measuring these biomarkers at early ages and then follow the children as they age to start tracking their health.

Of course, these studies are costly and time-consuming. But they will be instrumental to helping us understand which biomarkers are the most reliable and how we can interpret them effectively.


Integrating into Clinical Services


In the United States, the average pediatric primary care visit lasts 16.4 minutes.

In 16.4 minutes, the following is done: a child’s history, measurements (e.g., height/weight), sensory screening, behavioral health screening (e.g., developmental milestones), a physical examination, bloodwork, and immunizations.



Doctor’s visits are very short — often under 20 minutes! And there is a lot to cover in that visit. It is important that new screening tools are implemented in a way that minimizes disruption to the patients and medical staff. Source: health.mil





Doctor’s visits are very short — often under 20 minutes! And there is a lot to cover in that visit. It is important that new screening tools are implemented in a way that minimizes disruption to the patients and medical staff. Source: health.mil

The constraints of quick visits will make it harder to add biomarkers into screening.


Collaboration is thus essential.


This will take on-site efforts in pediatrician offices to test out the feasibility of adding in new biomarker testing and conversations. Important considerations, such as the ethics of biological screening, cost and complexity of assays, and invasiveness to the patients, must be considered.

This will take collaborative efforts with pediatricians, nurses, and medical assistants and patients.

Cultural differences — such as how health access, payment and insurance work in different countries, varying cultural norms — must also be considered when we think about this on a global scale.

Conclusion

We can all recognize that a blood test alone will never tell us everything we need to know.

But it could be an important tool in identifying high-risk children and families. From there, the next step is key: we bridge to the fields of clinical and intervention sciences.

Once we know a child is at high-risk, we can arm parents with more knowledge about how to help their child, including connecting families to parenting services or programs.

It could mean adding in more frequent preventative testing for certain diseases or disorders.

The possibilities have yet to be fully explored, but the promise is bright.




 

Header image source: The Honest Company

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