Testing and Measuring Biomarkers in Children

Can Biomarkers Help Parents Make Sense of a Child’s Symptoms or Behaviors?

When it comes to investigating the source of children’s symptoms and behaviors and finding clinical guidance for their healing journeys, lab tests that measure biomarkers can be very valuable. Biomarkers come from tissue samples such as blood, urine, stool, hair, and saliva and help us form a mental image of what is happening inside the body currently or across time. Functional-oriented practitioners (often abiding by the saying “test don’t guess”) will attain biomarkers, through either standard or specialty labs, to help parents:

• Identify imbalances or areas of dysregulation
• Establish a child’s baseline body burden or “total load”
• Investigate possible root causes of a child’s signs and symptoms
• Get a better sense of a child’s inherent strengths and vulnerabilities
• Assess functions of different bodily systems and availability of resources
• Track a child’s physiologic response to known internal or external influences
• Support the systems of elimination (emunctories) that clear toxins and waste
• Prioritize and sequence the safest, most effective, bio-individual interventions

Functional labs, as the name implies, are measured to reflect how well a body in general, or its specific systems are functioning and how their environment is helping or hindering. Such labs are chosen to help parents take actionable steps to improve and optimize their child’s health – e.g., to safely and effectively make diet and lifestyle changes that improve a child’s health and lower their body burden without causing harm. The way a sharp knife might be handled by a skilled chef to create a healthy meal, a skilled practitioner or well-informed parent can use biomarkers as a tool to safely, thoughtfully, and artfully, support a child’s resiliency and strength and help them live a healthier, happier, more balanced life.

Modern functional testing relies on bio-samples to read various biomarkers, biologic “messages,” from a child’s body (the messenger). Biomarkers reflect a child’s physiologic state as influenced by exposure, experience, or current environment. Some biomarkers are commonly associated with the health of a particular organ, a biochemical pathway, or a complex of systems (emunctories like the kidneys, the liver, and lymphatics, other organs, pancreas, bone, GI tract, the mitochondria, the immune, cardiovascular, or nervous systems). Some biomarkers measure the quality or quantity of fundamental building blocks of growth and repair. Others are risk factors for conditions like cancer, stroke, heart disease, diabetes, immune reactivity, poor detoxification, or metabolic dysregulation.

How Might Functional Testing Be Supported by a Wholistic View of the Body?

When we think of the body as just a machine (or mode of transportation), we are tempted to think of testing as just a way of discovering what is “broken” then replacing or removing components. However, a child is better served when we realize that the human body is not a mere vehicle or “bunch of separate parts,” rather a bio-regulatory miracle machine – an elegant system of complimentary and interdependent systems that work tirelessly (no pun intended) to keep its many cells, organs and tissues functioning together coherently.

Each of us living today is alive because of our body’s natural attempt to keep these systems running smoothly, even when we are unaware of past or present influences. We don’t typically have to think about our breathing, our heart beating, or our body’s reactions to discomforts or stressors – we’re essentially on autopilot. A paper cut heals without a band aid, a broken bone knits itself back together, brains adapt to new languages, a nervous system reacts to a perceived threat, a sensation or an emotion, a fever helps us clear infections.

We are internal alchemists; our bodies manufacture chemicals that correspond with fear, stress and joy, with growth, and repair (destruction when necessary). Even when bodies are compromised or can’t do everything well, they are, to the best of their ability, trying to survive and thrive in environments not always conducive to either.

An important thing to understand is how aspects of modern living take a toll on different body systems, some more than others. Even without being broken, some parts may not seem to be “cooperating” because they are overtaxed or lacking in resources for regulation and repair (e.g., nutritional building blocks, quality sleep, adequate hydration, access to natural light, a low-stress environment, or meaningful human contact). Systems can get dysregulated (unable to do all their jobs well under the circumstances) and need help re-regulating. Testing can often reveal how certain roles and responsibilities of bodily systems are compromised, challenged, or functionally delayed. This can guide further testing and interventions that target the appropriate system or support systems for healing and repair.

How Do Biomarkers Provide Clues About the Status of Important Bodily Functions?

Just as the health of a community must rely on adequate resources and a diverse population of people with different skill sets to run smoothly, a body’s ability to operate effectively depends on its systems’ diverse resources and skill sets. The body has an elaborate (primarily subconscious) interplay between different integrated systems that run the miraculous “business” of keeping us alive and functioning. Biomarkers are used alone or in combination to get a sense of how the body’s systems are co-regulating.

Here are a few of the many examples of how systems’ functions are measured through specific biomarkers:

• Quantifying a child’s inflammatory processes:

• • Phospholipase A2 (PLA2)
  • ESR

• Investigating a child’s nutritional status:

• • Zinc
  • Copper
  • Selenium
  • Magnesium

• Documenting the presence or absence of building blocks for growth and repair:

• • Zinc
  • Magnesium
  • Vitamin D

• Measuring chemical toxins in various body parts or excretion pathways:

• • Metabolites of bacteria
  • Metabolites of mold
  • Metabolites of fungi

• Determining the availability of resources to handle toxins or oxidative stress:

• • Glutathione
  • Vitamin C

• Learning about a child’s metabolic pathways and mitochondrial power:

• • Carnitine (total and free)
  • Amino acids

• Understanding a child’s immune system activity and adequacy:

• • Immunoglobulin levels (IgG, IgA, IgM, IgE)
  • Antibodies to viruses or bacteria

• Studying the body’s “inhabitants” – the living microbiome, or the virome:

• • Genetic or other biomarkers provide clues to the type, diversity and character of organisms that may be residing in the gut or other tissues

Humans are bio-individual and dynamic creatures, and many biomarker measurements reflect a discreet point in time, which sometimes requires re-testing at intervals (e.g., during or after a particular intervention) to track progress or severity. Some tests help differentiate between acute and chronic conditions, while others, most notably the testing of the human genome, remain constant throughout life.

Genetic testing and our interpretative capacity are evolving rapidly for inherited and de novo genes (de novo genes in a child differ from their biologic parents and are becoming more prevalent). While there can be tremendous value in testing one’s genome, it is primarily the child’s environment and lifestyle that will determine epigenetically how those genes impact a child’s health.

What Determines the Type of Testing Used for the Pediatric Population in General?

Many factors determine the type of testing chosen for children, including cost and insurance coverage, a child’s size, age, a family’s beliefs, or a child’s ability to cooperate. Different labs provide different levels of interpretation. Sometimes we need an indirect test (or clinical judgment) as a surrogate for a biomarker that is difficult to capture or otherwise unattainable. Some biomarkers do not have standardized ranges for children. Some testing is only available to researchers. The type of testing and tissue source selected depends on both availability and a person’s familiarity or trust in the accuracy or usefulness of the report (e.g., some clinicians are not versed in using a given test or interpreting the results and some states such as New York and California limit access to certain tests).

“Boutique labs” are mostly utilized by skilled users in the integrative medicine space, and some of these specialized tests are less invasive, or can be done at home, or ordered direct-to-consumer. Conventional medical offices often rely on standard labs, using these blood tests to establish baseline health, or confirm inflammation, or nutrient sufficiency:

• Comprehensive Metabolic Panel (CMP) – metabolic elements of blood
• Complete Blood Count (CBC) – red and white blood cells and subtypes
• Lipid Panel (usually includes LDL, HDL, and triglycerides)
• Thyroid Panel (TSH, free T3, free T4, reverse T3, thyroid antibodies)
• Fasting glucose, insulin, HbA1c (reflecting average blood sugar over time)
• Nutrient tests: (iron panel, specific vitamins or minerals not in a CBC or CMP)

Mainstream blood tests can be valuable in and of themselves or may provide clues for deeper exploration. It is also important to keep in mind that there are many, many more measurable biomarkers. Advances in technology and the use of artificial intelligence is also rapidly changing the landscape of testing. It may dramatically improve the sensitivity and specificity of testing and in some ways, it is already replacing human interpretation. Also, as accuracy and availability improve, topical devices, or personal wearables (that discern energy patterns), may render testing of some biomarkers unnecessary or obsolete.

We have not yet “arrived” at the best test, and while we anticipate better testing to come, we must remember that one-size-testing, like one-size-medicine, will not necessarily fit all sizes of people. Furthermore, a basic understanding of the what, how, and why of biomarker tests really can help parents and caretakers to make the right choices for their children now. This review is intended to improve understanding; to help with non-urgent decisions about biomarker testing to support a child’s personal health and well-being.

What Functional Tests Are Used to Help Children Overcome Health Challenges Today?

In addition to the foundational blood chemistry noted above, the following functional tests, categorized by body systems, highlight the value of relevant biomarkers to guide care.

Gut and Microbiome Tests

These tests are used to identify dysbiosis, malabsorption, infection, inflammation, and microbiota imbalances – all major drivers of neurological and immune symptoms. Functional tests commonly used in integrative medical practices include:

• Food sensitivity testing via blood samples (with IgA and/or IgG panels)
• Comprehensive Stool Analysis with biomarkers for inflammation (such as, calprotectin, lactoferrin, secretory IgA), biomarkers of digestive function (pancreatic elastase, beta-glucuronidase, short-chain fatty acids), indicators of microbial balance (overgrowth or deficit of Lactobacillus, Bifidobacterium, yeast or pathogenic bacteria), and indicators of leaky gut (e.g., zonulin, alpha-1 antitrypsin)
• Organic Acids Test (OAT) – This urine test which measures microbial metabolites, is represented here in chart form to illustrate biomarker categories, what they measure, or teach us, and why it may matter to your child’s health condition.

How a Gut’s Health, Function, and Microbiome May Affect a Child’s Health

Gut imbalances can affect digestion, immunity, mood, sleep, and behavior

Metabolic and Detoxification Tests

These tests are used to help us understand how the body processes energy, removes waste products, and handles environmental toxins. Functional tests include urine metabolic profiles (like the OAT), heavy metal and mineral testing (such as provoked urine challenge or hair analysis), porphyrin profile (to assess toxin exposure effects). Key metabolism and detoxification biomarkers help us learn more about:

• Detox Pathways – measuring glutathione levels, sulfate, cysteine, taurine
• Toxin Burden – checking hair or urine for mercury, lead, aluminum, arsenic, etc.
• Oxidative Stress – quantified or measured through 8-OHdG and lipid peroxides
• Energy Production – through Krebs cycle intermediates & mitochondria metabolites

Genetic and Epigenetic/Genomic Tests

These tests identify underlying SNPs (single nucleotide polymorphisms) that affect many functions and systems in the body, including nutrient utilization, detox capacity, methylation, neurotransmitter balance, and inflammation. Comprehensive tests are generally run from a simple cheek swab or blood tests. SNPs are constant throughout life, but the clinical usefulness of a particular report may vary. Some relevant SNPs (genetic biomarkers) in childhood health conditions are listed below:

• Methylation – MTHFR, MTR, MTRR, COMT
• Detoxification – GSTM1, GSTT1, SOD2, CYP450 family
• Neurotransmitter Balance – MAOA, GAD1, TPH2
• Inflammation and Immune Modulation – TNF, IL6, HLA shank 3

Immune, Allergy, and Environmental Sensitivity Tests

These tests help us understand immune triggers, autoimmunity, and environmental stressors contributing to inflammation and behavioral or neurological symptoms. These functional tests include biomarkers such as:

• The antinuclear antibody (ANA) screen – a non-specific immune test commonly ordered when autoimmune tendencies are suspected
• IgG/IgA/IgE and allergen panels – typically measured in the blood and used to measure adverse reactions to specific foods or to help diagnose a condition like celiac disease (e.g., tTG-IgA) or rheumatoid arthritis (e.g., RF or anti-CCP).
• Specific antibodies and titers may also identify the presence of an organism or virus (past or present) or reveal immune reactivity against organs or tissues – two examples that readily come to mind for children are folate receptor antibodies, often referred to as the FRAT test or thyroid antibodies (e.g., TPO, Anti-TG)
• Environmental toxin panels can measure mycotoxins – various molds and their metabolites – or other harmful substances like pesticides and VOCs
• Immune activation markers can be used by specialists to help confirm a diagnosis or further quantify harm from certain exposures (e.g., HLA-DR/DQ Haplotypes, C4a, TGF-beta1, MSH, VIP, ADH, MMP-9 VEGF, ACTH, IGF-1, DHEA, procalcitonin)

Neurophysiologic and Stress Regulation Tests

These tests help parents and practitioners evaluate autonomic nervous system balance – between the sympathetic and parasympathetic branches (tendency toward fight-flight-freeze-fawn or rest-and-digest states) – to measure stress response, or understand a child’s brain-body communication, all of which are key in emotional regulation and developmental progression. Useful biomarker measures could include a waking cortisol response or serial cortisol measures at certain times of the day/night (from saliva, dried urine or blood). Stress biomarkers (from tissue) are often combined with functional assessments (in-office or through wearable tech) which may include heart rate variability (HRV) analysis, resting heart rate, respiratory rate, vagal tone and autonomic balance testing, neurofeedback baseline mapping (qEEG), or specialty evaluations and interventions like neuro-optometry, reflex integration or chiropractic.

What Strategies Help Parents and Health Care Providers Pick the Best Tests?

Throughout their lives, children may present with multiple symptoms, involving multiple systems. If a child sees multiple specialists over time, too, their medical records and timelines can get confusing – it can be hard to keep their stories and sequence of events or interventions straight.

When it comes to choosing between tests and being a child’s best advocate, an accurate history and access to chronologic record keeping is key. Each child is different, as this well-known saying attempts to capture, “If you’ve met one child with autism, you’ve met one child with autism.” Children may share symptoms, diagnoses or other behaviors in common but still have very different underlying root causes.

Biomarkers should be interpreted and utilized in context, based on the history and presentation of the child being tested and an understanding or awareness of what is possible – of what areas might be improved upon or optimized, while honoring a parent or child’s hopes and goals.

Ideally, parents, caretakers, and other health care providers will be well equipped:

1. With access to a child’s detailed and chronologic health history (lack of access may make this difficult like in the case of adoption or very high stress living situations)
2. To identify symptoms or challenges (with or without a physical exam) and discern patterns across multiple bodily systems – including areas such as sleep, digestion, brain and nervous system regulation, learning, development, communication, motor control etc.
3. To be able to clarify short or long-term goals in collaboration with parents and/or their child – such as comfort, better sleep, a sense of calm and safety, more social connection, developmental gains, better means of communication, overcoming picky eating etc.
4. To understand that lab interpretations can be quite nuanced and should not necessarily be taken at face value. For example, when a child appears to be “highly reactive” to many foods (via immune biomarkers), he or she likely has a leaky gut. In this case, restoring gut health might take precedence over eliminating “sensitive” foods. Meanwhile a low metal toxicity hair analysis might be inappropriate – suggesting a child is not effectively detoxing.

Knowing where to start can be intimidating in this age of information overload. When some parents realize how many different types of tests can shed light on the root causes of a child’s health struggles, they may feel compelled to “test everything.”

On the other hand, biomarkers may not be the most important place to start. Perhaps the child would benefit by first looking into retained primitive reflexes, postural asymmetry, cranial or fascial restrictions, or movement inefficiencies that affect nervous system regulation. This might call for starting with a structural assessment and support, e.g., pediatric physical therapy or an occupational therapy evaluation, a reflex integration assessment (Moro, ATNR, STNR, TLR, etc.), or chiropractic or osteopathic care, or vision and vestibular function testing.

Parents can help mitigate this overwhelm by slowing down and turning inward, tapping into their own gut feelings. Parent intuition is a valuable tool; experts need it, too. They don’t know a child the way a parent does and may underestimate his or her potential.

What Might a Parent or Provider Look for When Reviewing or Discussing Test Results?

Skilled providers (with access to accurate reports), often observe patterns in biomarkers, beyond noting just the normal range. For example, providers often notice whole categories that are relatively “low” or “high” or comparing things that should be in balance with one another (like the different amino acids, or ratios of omega fatty acids 3, 6 and 9 or relative amounts of minerals like zinc and copper). When a parent is reviewing their child’s labs or preparing to discuss them with a skilled practitioner, here are some opportunities for more clarity:

• Look at labs in comparison to prior testing, when possible, to note any trends/patterns
• Use testing to identify concrete actionable steps (even small steps, slow and gentle if possible) that a parent could take to help modify or reverse a child’s risk factors
• Interpret results within the context of the whole body – body systems should work like a well-conducted orchestra. Balancing one system of the body, through medicines or dietary changes, should help others too – for instance a well thought out plan should improve nutritional status, support microbiome diversity, and improve symptoms
• If a test result will lead to a specific therapy, ask whether it would address the root cause or just treat the symptoms (sometimes relieving symptoms does come first)
• Consider testing the ripple effect of an intervention, implications beyond a targeted area of the body (to maximize benefits and minimize side effects or complications)
• Prioritize labs to optimize care for a child with a unique history and presentation (not just to “normalize” labs). Beware of diagnosis overshadowing – overlooking or dismissing treatable symptoms as “just a normal part of having a particular diagnosis”
• In Goldilocks fashion, try to clarify whether a biomarker or system is overactive, underactive, or just right – consider ways to continue to optimize levels and function
• Note the areas that are out of range and consider what body systems along with diet and lifestyle choices might be involved in better regulation of those biomarkers
• Note the timing and context of a given test (past or present):
  • Was the sample collected at the right time of day, according to the package inserts instructions (with or without)? food or drink)?
  • Was the collection procedure smooth or stressful?
  • Was the child ill at the time?

Keep in mind that a test may be erroneous (a false negative or false positive) and need to be retested at another time. For instance, a difficult blood draw could result in a high potassium (released from injured red blood cells) and not indicate an emergency.

In Summary: Testing Can Be Helpful, Especially If We Understand What, Why and How

Children’s bodies are amazing miracles to behold, and they have “plasticity” – they will adapt and change to exposures, experiences and changing circumstances. How the body and mind “behave” and how a test reads make more sense if we consider the uniqueness of the one being tested (their personal history, diet, activities, likes and dislikes, strengths and weaknesses, sensitivities, and stressors, and their developmental stages).

When someone becomes blind, the function of the brain changes – more “real estate” is available for other senses, like feeling, smelling and hearing. This re-distribution of resources looks odd or inappropriate on a functional brain scan, unless we know more about the person being tested. A body does the best it can with the resources it has, adjusting, adapting or accommodating to what modern living brings to it.

If we test and treat based on thinking that an individual is “broken” or has “bad parts” – physical, mental, emotional, or familial – we miss the opportunity to understand and address the root cause of the issue at hand, or reverse reversible symptoms (while avoiding the sad reality of diagnosis overshadowing).

If we only aim to “fix a behavior” or suppress a symptom, we miss the opportunity to serve the work of a body’s systems already in process and help different parts regulate or repair and work better together. Parents are beginning to realize the transient value of things like fevers or inflammation, a cough or loose stool – as the body’s brilliant way of addressing and resolving a particular injury or insult.

One mother recently shared that she literally cried the first time her child was strong enough to fight an infection by mounting a fever. Another mother shared that after six years of testing her child for heavy metals, his biomarkers suddenly surged (from zero). His body after years of targeted dietary changes, lifestyle supports and toxin avoidance was finally able to release stored metals.

We may not find answers to any or all our questions (even with the most well-meaning guidance of experts or fancier tests), but we usually have a better chance if we understand the how and why we test. Understanding a child’s story, their symptoms, behaviors, and biomarkers can help us help them heal and craft a better ending to their story. The way a body is acting, reacting, and regulating, should give us clues to its needs – just as a crying baby who is otherwise healthy and well-cared for might need a diaper to be changed or more milk. Our child’s bodies behave differently when they are imbalanced or stuck by an experience, exposure, or limited belief. Our current Western model of medicine often leans in this direction of blocking, suppressing, punishing or overriding symptoms or “bad behaviors” rather than understanding their messages. Biomarkers can help the messenger

About Heather Tallman Ruhm MD

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