Clinical Assessment – Clinical Evaluation of a Child with a History of Known or Suspected Exposures

Upon completion of this section, you will be able to

• describe how to conduct an “exposure assessment” (medical and environmental evaluation) as part of the clinical evaluation of a child with exposure (known or suspected) to hazardous substances.

If an environmentally related problem seems likely, a full evaluation will be needed. What follows is a description of the complete clinical evaluation of a child with a known or suspected environmental exposure. This process includes an “exposure assessment” as part of a pediatric environmental medicine clinical assessment. This section also discusses what is feasible within the pediatric generalist’s practice and what is usually referred to a specialist in pediatric environmental medicine.

The first step in evaluating a possibly exposure-related health concern is taking an exposure history. For the child with a history of a known exposure, with or without symptoms, concerned parents may visit their child’s pediatrician with worries that their child may become sick in the future. The parents may inquire about signs and symptoms associated with exposures.

Pediatricians can use the history, physical examination, and problem-specific laboratory tests to establish a problem list and a differential diagnosis.

The evaluation may identify an environmentally related condition such as headache and fatigue related to carbon monoxide exposure, as illustrated by the case study. Common environmentally related conditions are asthma (related to second-hand smoke (SHS) exposure or indoor air pollutants from a wood stove or fireplace) and otitis media (related to SHS exposure). Eczema may possibly be related to an adolescent’s job exposure.

In other situations, the initial problem list may include only signs, symptoms, and laboratory test results. The pediatrician who has experience with environmental toxicants may quickly suspect that a disease or syndrome (such as asthma or acute lead toxicity) is associated with a hazardous environmental exposure. The problem list should still be used, however, to keep the differential diagnosis broad in the beginning. Any and all specific exposures identified by the child’s parents or caregiver(s) or suspected by the pediatrician should be listed.

Pediatricians who suspect an unusual environmental cause for an illness will often find it useful to contact an expert in pediatric environmental medicine. Pediatric Environmental Health Specialty Units (PEHSU), located in the ten Federal Regions of the United States and in Canada and Mexico, can provide information, assistance, and referral for clinical evaluation if environmental exposures are verified (see the “For More Information” section later in this CSEM for additional information regarding the PEHSU and visit http://www.aoec.org/PEHSU/.

Pediatricians should identify all the routes by which a child may be exposed to chemicals. The child may be exposed via

• the oral route (ingestion),
• the respiratory tract (inhalation), or
• through the skin (dermal exposure).

Taking a careful environmental exposure history is the key to establishing to which chemicals the child may have been exposed and the route(s) of exposure.

When considering environmental health hazards relevant to children, pediatricians should keep in mind that exposures may have occurred during the preconception period, transplacentally during the prenatal period, or via breastfeeding. These past exposures are not generally of primary relevance during an acute illness but they can contribute to chronic illnesses.

Pediatricians are advised to collect information about all possible exposures to environmental hazards, even if a parent is focused on a specific exposure. For example, in this monograph’s case study, even though the major focus was on carbon monoxide, the patient also had symptoms suggestive of allergy and/or asthma. After the acute and potentially life-threatening exposure is remedied, the pediatrician can ask additional questions about allergens or irritants at school, the playground, or the home. Given time constraints of a busy practice, asking these additional questions may be most appropriate at a follow-up visit. As with other areas in pediatrics, it is important to prioritize the issues.

The pediatrician should be alert to clusters of cases presenting to the office; these situations will prompt further investigations.

When parental occupations may result in the parents’ bringing home a toxicant on clothes or shoes (“take-home exposures”), the pediatrician may recommend that parents request copies of Material Safety Data Sheets (MSDS) from the employer. MSDS provide key information regarding substances used at work that may be hazardous.

An MSDS describes routes of exposure for specific hazardous substances. The route of exposure often determines whether an environmental contaminant will cause harm. For example, a child might bite and break a mercury thermometer and swallow its liquid contents. Fortunately, elemental mercury is relatively nontoxic when ingested because it is not well absorbed by the intestinal tract. However, because of its high absorption by the respiratory tract, elemental mercury is highly toxic when it volatilizes and is inhaled. A child will have greater exposure by playing with a tiny ball of mercury than by eating it.

REMEMBER: No matter how toxic, no chemical will cause harm unless there is exposure (biologic uptake) and subsequent target organ contact that causes biologic changes that may result in disease. Preventing exposure is the key to stopping further harm. If you suspect that an exposure is occurring, you should move quickly to stop further exposure. Experts from Poison Control Centers and/or the PEHSU can give advice on how to stop further exposure from occurring.

The exposure assessment as part of the clinical assessment of a patient exposed or potentially exposed to hazardous substances generally relies on three tools:

1. the exposure history,
2. diagnostic testing of blood, urine, or other body fluids or tissues from the exposed person, and
3. environmental testing.

After compiling a list of chemicals to which the child may have been exposed, you may find it necessary to perform testing. Diagnostic medical laboratory testing for exposure and/or effect along with environmental testing of environmental contamination levels can help determine the presence, estimate dose, and assess the effects of harmful contaminants.

Principles of diagnostic medical laboratory testing.

Dose-response refers to the extent of a biologic effect in relation to the received dose of an agent.

• Generally, the higher the dose, the greater the effect (although variations exist).
• One exception, as discussed in the Principles of Pediatric Environmental Medicine, is that low doses of some substances at critical periods of organ development (such as in utero or early in life) may have a greater effect than higher doses at other times.
  • An example of the greater effect of a substance early in life is lead toxicity. Compared to the adult brain, the developing brain of the fetus and the young child is especially sensitive to the effects of lead.

An exposure assessment as part of the clinical assessment of a patient exposed or potentially exposed to an environmental toxicant seeks to estimate as closely as possible the absorbed dose. The estimation is usually done in consultation with specialists, including industrial hygienists, environmental public health assessors, or pediatric environmental medicine specialists. Exposure intensity, duration, and frequency all contribute to the received dose. Testing for health effect can provide valuable information for the clinician, especially when testing for exposure is not available.

There are published national biologic levels of many environmental contaminants. The levels are derived by testing a sample of the population as part of the National Exposure Report from CDC’s National Health and Nutrition Examination Survey (NHANES). These levels can be accessed at: https://www.cdc.gov/exposurereport/ .

As described in the case study, it is important to choose a laboratory test of exposure that is based on principles of biological monitoring, in such a way that the measure

• accurately reflects exposure,
• can be collected before the substance is excreted from the body,
• correlates the dose with the health effect, and
• is the least painful and inconvenient.

Laboratory testing that may be used in the clinical assessment of an exposed patient includes determining biomarkers of exposure that measure the substance in the body directly and biomarkers of effect that assess the effects of the substance on the body’s organs and systems.

Biomarkers of exposure: Many environmental contaminants do not have specific tests for their levels in the body after exposure. For others, there is often the need to

• have specialized and well-timed collection procedures (24 hour urines, or collection procedures to avoid contaminants),
• use specialized laboratories, and
• consult with a specialist to determine the type of measure needed and how to interpret results [Hoffman et al. 2007].

Biomarkers of effect: In order to correctly interpret these results, pediatricians must understand how the substance acts in the body (its toxicology) and the limitations of the tests ordered.

Information about a substance’s toxicokinetics (its metabolism and excretion) can help to predict the type of biologic monitoring that may be useful to measure exposure and effect. Information about half-life can help a pediatrician interpret results of biologic testing. Information about animal and human toxicities helps to focus laboratory testing on organs known to be affected.

Table 6. Examples of Laboratory Tests of Exposure

* The current level of concern; however, this level is under investigation and may be revised downwards.

**Testing for mercury and/or arsenic is not generally done in the context of a general pediatrician’s practice. Consultation with experts in pediatric environmental medicine is recommended if excessive exposure to mercury and/or arsenic is suspected.

NOTE: Several tests, e.g., fat levels of dioxins, are not readily interpretable on a clinical level. These tests are conducted in research settings and should not be ordered for clinical reasons. Similarly, testing hair and nail samples for exposures to such substances as heavy metals should not be done because the results can be inaccurate and hard to interpret.

Environmental Monitoring

Environmental monitoring is often an important component of assessing or estimating exposure dose. Sometimes it is the major component when biological monitoring is not possible or adequate. Such environmental monitoring might include air monitoring (as in the case of CO) and monitoring of such other media as water and soil. Reference ranges are available for acceptable levels of contaminants in drinking water [EPA 2003], ambient (outdoor) air (http://www.epa.gov/ttn/naaqs/), and indoor air (http://www.epa.gov/iaq/co.html).

It is not expected that a pediatrician in a busy practice perform or interpret environmental monitoring data. However, awareness that this information is often used, if available, to estimate exposure dose is relevant. Consultation with pediatricians with expertise in environmental medicine regarding interpretation of this type of data for use within a clinical context is recommended.

After identification of the relevant environmental contaminant by history and testing, its properties must be researched. If the pediatrician is not familiar with the contaminant or if the case is complex or unusual, consultation with a specialist is indicated. Relevant specialists include experts in pediatric environmental medicine, the poison control center, and/or a toxicologist. See the “For More Information” section later in this CSEM for additional resources.

Physical and chemical properties of a contaminant help to determine the likelihood of exposure and subsequent absorption, metabolism, and excretion. For example, knowing that CO is well absorbed through the respiratory tract and that it binds tightly to hemoglobin implies excellent respiratory absorption of carbon monoxide. Air monitoring can contribute to understanding the extent of the exposure to CO.

After reviewing the results of laboratory tests and environmental monitoring, the pediatrician needs to evaluate whether sufficient exposure has occurred and whether the exposure could have resulted in the child’s illness. Several questions may clarify the possible relationship between an environmental exposure and a disease.

• Has the chemical been associated with the patient’s health effects in other people? If so, how strong is the association?
• How does the child’s estimated absorbed dose compare with what is known about dose-response relationships? Is there published information on human exposure and disease for this chemical? NOTE: if only occupational exposure standards exist, be aware that adult occupational standards are not usually considered to be protective of child health.
• Does the child have any factors that could increase or decrease susceptibility to illness from exposure to this chemical?
• Are there other exposures occurring to shift the risk of disease in this child?
• How does the environmental contribution to this illness compare with other possible causes?

For John, the child described in the case study, CO exposure has been strongly associated with health effects, including death. John’s symptoms correlate with the measured level of carboxyhemoglobin in his blood. As with many environmental toxicants, infants and children are more susceptible to the effects of CO. A child’s rapid metabolism makes children more susceptible to CO effects; fetuses are especially vulnerable. There are other possible causes for his symptoms, but CO exposure is the most likely. It is life-threatening and must be swiftly remedied.

In other environmental exposures, no certain conclusions can be drawn about the role of the chemical in causing a symptom or an illness. In these cases, the probability that the chemical is playing a role in the child’s illness must be considered. The pediatrician’s task in such cases is to

• find out as much as possible about the chemical,
• explain the possible risks to the best of the physician’s ability, and
• determine whether abatement steps are possible and/or necessary.

NOTE: More detailed information regarding the environmental exposure history, biologic monitoring, environmental monitoring, communicating about risk, and assessing a child’s risk goes beyond what most general pediatricians will realistically know and do in a busy practice. Resources are provided later in the case study to help expand pediatricians’ knowledge about the role of environmental health professionals and to enable communication with others. Resources include staff at state or local health departments, Poison Control Centers, the Agency for Toxic Substances and Disease Registry, the Association of Occupational and Environmental Clinics, and PEHSUs.

• An exposure assessment is performed to confirm an environmental exposure and/or to estimate absorbed dose.
• The clinical assessment for exposed or potentially exposed patients is a logical, stepwise approach that includes an exposure assessment in exploring the likelihood of environmentally related illness.
• The exposure assessment relies on three main tools:
  • the exposure history,
  • biological testing of blood, urine, or other body fluids or tissues from an exposed child, and
  • environmental monitoring performed on environmental samples.