Introduction

Childhood is a time of rapid growth and development. It is accompanied by

• changes in organ system functioning,
• metabolic capabilities,
• physical size, and
• behavior

Given the same amount of exposure to a toxicant, persons will vary in how susceptible they are to disease induced by the exposure. Among the factors affecting susceptibility are

• genes,
• sex,
• age,
• nutritional status,
• state of health (i.e., presence of other diseases), and
• biochemical differences such as chemical metabolism, speed of DNA repair, and regulation of net cell growth [Pitot and Dragan 1996].

Research has not yet fully answered how a child's characteristics can affect the harm caused by toxic substances. The federal environmental agencies and the scientific community are both working to focus on the unique vulnerabilities of children when compared with adults [Thompson 2004; Landrigan et al. 2004b]. For some selected agents, children are no more susceptible - and are sometimes less susceptible - than adults to an adverse outcome. For most agents, however, theory and empirical observations point to increased susceptibility to environmental hazards. This susceptibility begins in the preconception period and continues throughout

• fetal life,
• birth,
• infancy, and
• childhood.

Thus the U.S. Environmental Protection Agency (EPA) has suggested additional safety factors (e.g., 10-fold uncertainty factor, a 3.16-fold factor each for toxicokinetic and toxicodynamic variability) in regulating in utero and postnatal exposures to many environmental chemicals [Cresteil 1998; Renwick 1998; Dourson et al. 2002].

"Toxicant" is used to refer to a chemical agent; "toxin" is often used for a biological agent.

Overview of Childhood Susceptibility

Environmental factors play a large role in children's health. According to the World Health Organization (WHO), more than 30% of the global burden of disease in children is due to environmental factors [WHO 2006]. Many are the traditionally considered factors such as

• infectious disease,
• malnutrition, and
• physical hazards in the environment.

Others, however, are related to chemicals and other hazardous substances such as radiation.

Children's growth and development are dynamic processes; they can be viewed at the molecular, cellular, organ, and whole-child levels. What determines the nature and severity of environmental factors' health effects is exposure occurrence within the different developmental stages [WHO 2006].

Age-specific periods of susceptibility are termed:

• "critical windows of exposure,"
• "critical windows of development," or
• "windows of vulnerability."

These are times when children are exquisitely sensitive to any adverse effects of chemicals. Even within a given developmental stage, shorter exposure intervals may determine susceptibility for particular outcomes. Different organ systems develop at different rates. Broad windows of susceptibility and more specific periods of susceptibility (e.g., radiation effects on central nervous system development during the critical 8 to 15 weeks in utero) occur at each developmental stage [Faustman et al. 2000; ORISE 2010]. In most cases, however, the exact time is unknown when organ systems are susceptible to the actions of toxic chemicals. Limited data are available on susceptibility during the adolescent period, but with the current greater interest in the effects of hormonally active agents, more information is becoming available [WHO 2006]. What determines the nature and severity of health effects of environmental factors is the occurrence of exposures within the different developmental stages [WHO 2006].

The Importance of a Life-stage Approach

The differing susceptibility of children to harm from environmental exposures results from their development—a dynamic process with many physiologic, metabolic, and behavioral aspects. Children are at increased risk because of their increased exposures and increased vulnerability. Examples of increased exposures include children's physiologic needs for more

• food,
• water, and
• air per kilogram of body weight compared with adults.

These needs result in a greater exposure per kilogram to toxicants. Increased exposures also arise from children's normal development, such as the hand-mouth and hand-object behavior exhibited by toddlers. Increased vulnerability results from children's rapidly growing and developing organ systems, such as the central nervous system and lung which, compared with adults are especially susceptible to toxic insults.

Exposure to the same chemical may cause different health outcomes in children compared with adults. A well-known example is the effect of lead on young children's developing nervous systems. Lead does have effects on the nervous systems of adult workers, which result in peripheral neuropathies. For children, however, intellectual development is exquisitely sensitive to even small amounts of lead; this sensitivity is not seen in adults.

Many of the effects on children's health from environmental exposures are unique to their life stage.

• Preconception and fetal exposures may result in
  • miscarriages,
  • stillbirths,
  • low birth weight,
  • certain birth defects, and
  • other childhood deficits.
• Exposures to infants and young children can result in adverse neurobehavioral outcomes, triggering asthma and immune impairment.
• Exposure to chemicals that mimic reproductive hormones, especially in diet, might result in precocious puberty [Wang et al. 2005; Partsch and Sippell 2001; Aksglaede et al. 2006].
• Certain exposures in childhood (such as intrauterine exposure to diethylstilbestrol (DES)) may result in the development of cancers in adolescence and adulthood [WHO 2006].

Methods used in adults to assess exposure and risk to environmental chemicals do not predict risks to children accurately. Predicting effects from toxic exposures to children are exceedingly complex and difficult processes; new methods of assessing children's exposures and their risks are needed [WHO 2006; Thompson 2004].

What Is Pediatric Environmental Medicine?

Environmental health is the field of science that concerns how the environment influences human health.

Pediatric environmental health—also known as pediatric environmental medicine—concerns the prevention, diagnosis, and treatment of illnesses due to preconception, prenatal, perinatal, and childhood exposures to environmental hazards [CEHN 1999]. Pediatric environmental medicine includes the effects on children of environmental chemicals and other hazardous substances in the global environment.

Challenges Facing Pediatric Environmental Medicine

Because pediatric environmental medicine is a young and still-developing subspecialty; many unanswered questions remain concerning the effects of environmental chemicals on children's health. Some questions concern the magnitude of the disease burden on children from environmental exposures. Other questions concern how exposures during different developmental stages affect children's current and future adult health. The exact burden of disease in the world's children caused by exposure to environmental chemicals remains largely undefined.

Needed information can fill gaps in our scientific understanding. Data needs include

• prospective studies of pregnant women and young children (such as the National Children's Study) to assess the disease burden of environmental chemicals on child health [WHO 2006; Thompson 2004],
• research on the effects of environmental exposures at different developmental stages,
• biomarkers of exposure, susceptibility, and effects in children,
• a better characterization of the "windows of susceptibility" of various human organ systems to environmental toxicants,
• understanding of the effect of breastfeeding on newborn exposures,
• research about effects of soil ingestion in children's exposure to soil-borne contaminants, and
• research on how children's changing behavior during growth changes their opportunities for exposure.

Progress Check