The Unique Sensitivity of Children
The manner in which a child's body handles foreign substances, whether by prescribed dose or accidental exposure, and the resulting response may vary substantially from the average adult. Absorption, distribution, metabolism, and excretion rates change as we age and are major determining factors for the actual dose received by the targeted organ in the body. The response elicited by chemical exposure can vary greatly between different age groups. This is due to variation among the stages of development within the body. In some cases the actual response may be opposite the expected response.
The development of drugs and instructions for dosages for most medications are based on the average young adult. Adjustment of dose based on body weight alone may put an infant or child at risk of injury or be insufficient to produce the desired effect.
For example, using caffeine as a model, from term to one year of age, clearance (elimination from the body) changes dramatically from only a fraction of what is seen in adults to above adult levels (1). At puberty there is readjustment down to adult levels. These patterns may change for various substances. Factors contributing to the differences between adults and children are:
From embryonic development in the womb through adolescence children are forming organs to last a lifetime. Exposure to chemicals that target developing organ systems can cause organ malformations (birth defects), disruption of organ function, and premature death. The nervous system and the lungs have little ability to repair themselves if harmed during development. The nervous system developes throughout childhood, making it especially vulnerable. The immune and endocrine (hormonal) system may also be important targets of environmental toxicants.
Immature organ systems may not be capable of metabolizing or neutralizing certain foreign materials quite as effectively for purposes of excretion, to rid the body of waste. Also, an immature immune system will not respond as quickly to remove or neutralize foreign materials harmful to the body.
Some exposure pathways are significant for children due to their habits. Children spend more time playing outdoors than adults. Also, they play in soil and standing water found in fields, empty lots, and near canals which may contain pesticides or industrial waste. Furthermore, children are unaware as to how to protect themselves from exposure to harmful chemicals or to the risks involved from not washing after playing and their typical hand-to-mouth behavior.
Per pound of body weight a child ingests more food, drinks more water, and inhales more air than an adult. So exposure to dangerous substances translates into higher doses for children under the same exposure scenario as adults.
Drugs and Examples of their Effects on Children
Some drugs elicit an odd response in children when compared to the average adult.
A common example of an adverse paradoxical (opposite) response to drugs in children is their response to antihistamines and barbiturates. Typically these drugs sedate adults, in many children they have been known to cause hyperactivity.
Other disturbing effects of common drugs include significant effects on learning and behavior after the chronic intake of Phenobarbital.
Permanent staining of teeth caused by tetracycline deposits.
Stunting of growth by corticosteroid therapy.
And, compared to adults, high risk of liver toxicity from valproic acid.
The accumulation of drugs in the infant due to lack of clearance mechanisms are known to occur. Two examples are the inadequate metabolism of chloramphenicol, resulting in accumulation of the drug and gray baby syndrome, and sulfonamide induction of kernicterus; which displaces bilirubin from plasma proteins resulting in acidosis and decreased blood-brain barrier (1).
Drug preparation and in particular, drug administration to children is now considered a specialty in itself.
Environmental Toxicants, Exposure, and their Effects on Children
Even though lead based paint and leaded gas have been taken off of the market there is still a concern about lead poisoning among children according to the Centers for Disease Control and Prevention. More than 80% of homes built before 1973 still contain lead based paint (2), the primary source of exposure. Children have been known to ingest chipping and peeling paint. They are also exposed to dust containing excessive amounts of lead. In 1990 930,000 children in the U.S. had whole blood lead levels over 10 ug/dL, putting their intellectual development at risk (3). Lead exposure in children is linked to aggressive behavior problems, IQ deficiencies, learning and reading disabilities, impaired hearing, reduced attention span, and hyperactivity (2). Other sources of exposure to lead include old food cans, industrial waste emissions, and the clothes of industrial workers. See lead in food.
Nitrites and nitrates, used as fertilizers and occuring primarily from crop runoff, are the most pervasive contaminants found in drinking water. Infants are at special risk for methemoglobinemia or 'Blue Baby Syndrome' from the ingestion of nitrates. Coupled with the large amounts of fluid ingested by infants is the fact that nitrates are converted to nitrites in the infant's immature digestive system. Nitrites can bind to hemoglobin in the blood, effectively blocking the binding sites for oxygen. The term 'Blue Baby Syndrome' comes from the resulting blue color of the skin under oxygen deprived conditions. Other clinical signs are shortness of breath, increased sensitivity to illness, heart attacks, and possibly death by asphyxiation. Public drinking water supplies are monitored for nitrates and nitrites, and advisories are sent out if concentrations rise above set standards. Private water supplies are not monitored regularly by local agencies, and it may be advisable to use bottled drinking water for infants, especially in agricultural areas. See Nitrites and Nitrates in drinking water.
PCBs are found in electrical equipment such as transformers. Although banned in 1976 they are persistent in the environment and can accumulate in animal tissues. Consumption of fish from fresh water sources near industrial areas by pregnant and nursing women can result in delayed development and learning disabilities in children. PCBs and DDT; which is also banned but very persistent, are associated with disruption of the endocrine (hormones) system. Even very low levels are thought to affect prenatal development and play a role in reproductive cancers (4). See PCBs in food.
The conversion of elemental mercury to methyl mercury in the environment allows for the absorption and accumulation of mercury in animal tissues, including fish. Ingestion of contaminated fish by pregnant women can lead to neural damage in the infant such as cerebral palsy, severe mental retardation, neurodevelopmental delays and seizures (3). Fish advisories or limits are regularly posted in areas where mercury concentrations pose a health threat. Pregnant women are advised not to ingest fish from these sources. See mercury in food.
Many of the most common air pollutants, such as tobacco smoke, ozone, and small particulates cause respiratory illness and are a contributing factor to asthma incidence. Asthma is the leading cause of hospital admissions for U.S. children. The death rate from asthma in children has doubled since 1980 (3). Twenty-five percent of our children live in areas that do not meet national air quality standards; which are based on healthfulness (2). Also, children spend a good deal of their time outdoors. Cockroaches, house-dust mites, pollens, and molds will also trigger respiratory illness. See indoor air pollutants.
Environmental Protection Agency standards are currently under scrutiny to assure that the potentially heightened risk faced by children are considered when setting standards for protecting the public at large. Efforts are also being made to identify child-specific susceptibility to various substances found in our environment. Adults can do a lot to protect children by educating themselves about the environment in which they live and taking necessary precautions with regards to exposure among children.
Agency for Toxic Substances and Disease Registry's Child Health Home Page
1. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Ninth Ed. Edit. by Molinoff and Ruddon. McGraw-Hill, New York.
2. Report on Environmental Health Threats to Children. September 1996. EPA 175-F-96-001.U.S. Environmental Protection Agency. Washington DC.
3. Healthy Children-Toxic Environments. Report of the Child Health Workgroup Board of Scientific Counselors. April 1997. U.S. Dept. of Health and Human Services, Agency for Toxic Substances and Disease Registry. Atlanta, Georgia.
4. Principals and Methods of Toxicology. Second Edit. edited by A. Wallace Hayes. Raven Press, New York.
This page was prepared by Theresa L. Pedersen, UCD EXTOXNET FAQ Team. August 1997.