Children are one-third of our population and all of our future.
Select Panel for the Promotion of Child Health 1981
Kids Swallowing Pennies
Doctors at Duke University Medical Center in Durham, North Carolina, have learned that a penny saved isn't always a good thing, particularly if that penny was minted after 1982. A team of doctors found that children who swallow post-1982 pennies may develop stomach ulcers if the coins become lodged in their digestive tracts. More than 21,000 children visited the emergency room in 1997 after swallowing coins.
In a presentation at the 84th annual meeting of the Radiological Society of North America, held 29 November-4 December 1998, Sara M. O'Hara, an assistant professor of pediatric radiology at Duke, and colleagues described the case of a two-year-old boy who was brought to the emergency room complaining of stomachache. Upon taking an initial X ray of the boy's abdomen, O'Hara spotted a small, metal disc in his stomach. A follow-up X ray four days later indicated that the item appeared to be dissolving.
Once the object was removed from the boy's stomach with an endoscope, it was found to be a 1989 penny, riddled with holes. Intrigued, O'Hara and colleagues Lane F. Donnelly, William H. Briner, and George S. Bissett of the Duke radiology department and Emil M. Chuang of the Duke pediatrics department decided to investigate what had happened to the penny.
O'Hara visited the U.S. Mint Web site to find out what pennies are made of. She learned that pennies minted after 1982 are composed largely of zinc. O'Hara checked with a staff chemist, who told her that the chemical reaction between zinc and stomach acid (hydrochloric acid) is similar to that in wet cell batteries and would likely be caustic to the stomach lining. Apparently, when the penny became trapped in the boy's stomach, its zinc base reacted with stomach acid to produce hydrogen gas and zinc chloride (a major ingredient in the smoke from smoke bombs). According to O'Hara, this chemical reaction dissolved the zinc base of the coin, creating holes in the coin and ulcerations in the stomach lining. Other U.S. coins, which are made mostly of nickel, would not be expected to present this problem.
Zinc is an important nutrient that aids in maintaining a healthy immune system and promotes wound healing and reproductive health. Too much zinc can result in ulcers, anemia, and damage to the kidneys, liver, and bone marrow. But it takes much more than the recommended daily dose of 12-15 mg to cause adverse health effects. Large doses of dietary zinc (120-150 mg) can cause stomach cramps, nausea, and vomiting. Taking in high levels of zinc over several months may cause anemia, pancreatic damage, and decreased levels of high-density lipoprotein ("good") cholesterol.
While one penny is not typically enough to cause such systemic damage in a child, it can spell trouble for a pet. For children, the more likely danger would be if the penny became lodged in the stomach, where it would effectively act as a small blowtorch, eating away at the stomach lining. According to Dr. O'Hara, coins rarely cause bowel obstruction, and there are no other known problems associated with a coin lodged in the gut. The major hazard associated with children swallowing coins is that the child might choke.
Children and pets who swallow pennies should be monitored to ensure the coin passes. If it doesn't show up within two days or if the swallower starts having stomach problems, the child or animal should be taken to the doctor immediately.
The Lincoln penny was introduced in 1959 and minted until 1982, when the rising price of copper dictated a change in its makeup. The penny's composition was changed from an alloy of 95% copper and 5% tin and zinc to 97.5% zinc and 2.5% copper. Several billion new pennies are minted each year in the United States.
O'Hara's findings at the U.S. Mint prompted her and her colleagues to conduct an experiment. They exposed 18 pennies, 6 minted before 1982 and 12 minted after, to postprandial concentrations of stomach acid. The post-1982 pennies began eroding immediately; perforations had appeared by the second day. Within 7 days, the post-1982 pennies had decreased in weight by 5-8% and were lacy with holes, while the pre-1982 pennies were unchanged.
The Duke researchers' findings may be pertinent to nations besides the United States. In 1997, the Royal Canadian Mint began producing a 98.4% zinc version of its formerly bronze penny. Pierre Morin, communications advisor for the Royal Canadian Mint, says, "We are interested in reviewing this study once the results become available because our one-cent penny has changed to a copper-plated zinc coin. We want to review their methodology as well as their results."
Allergy Receptor Pictured
For many people, the rites of spring have historically involved stocking up on plenty of antihistamines and tissue, but that may not be the case in the future. Researchers at Northwestern University in Chicago and Harvard Medical School in Boston have determined the precise shape of the receptor protein for immunoglobin E (IgE), the antibody that is responsible for the springtime sniffles and other allergic symptoms that afflict some 20% of the U.S. population. This may be the first step toward developing an allergy medication that stops the allergic response before it happens, rather than merely treating the symptoms.
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Captured! The IgE receptor, shown front and back above, is composed of protein atoms (white) and carbohydrates (blue). The IgE antibody binds to the top point of the inverted V shape.
Photo credit: Scott Garman, Northwestern University
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The study was reported in the 23 December 1998 issue of Cell. Theodore S. Jardetzky, an assistant professor in the Department of Biochemistry, Molecular Biology, and Cell Biology at Northwestern, was the principal investigator for the team. His collaborators were Jean-Pierre Kinet, a professor of pathology at Harvard Medical School who first cloned the gene for the IgE receptor in 1986, and Scott Garman, a postdoctoral fellow in the Northwestern Department of Biochemistry, Molecular Biology, and Cell Biology.
About 50 million people in the United States have some form of allergy. Many allergies, such as hay fever and eczema, are more inconvenient than life-threatening, but some allergic responses, such as anaphylaxis, can result in death. Allergies are also strongly suspected of playing a role in asthma. According to the National Institute of Allergy and Infectious Diseases, 90% of asthmatic children and 50% of asthmatic adults also have allergies. According to the Centers for Disease Control and Prevention, asthma accounts for almost 500,000 hospitalizations each year and is the foremost reason that children miss school. And the problem is growing--asthma prevalence in the United States is expected to rise by 5% each year.
Allergic responses are mediated by IgE, which is one of five classes of antibodies. As IgE circulates through the blood and the lymph, it binds to receptors found on the surface of mast cells (a type of white blood cell). There, IgE acts as an antenna, patrolling its airspace for allergens. When an antibody picks up the signal of a nearby allergen, the mast cell responds by releasing histamine and other powerful chemicals that cause an inflammatory response in surrounding tissues.
Mast cells are found throughout the body but are most highly concentrated in tissues that are exposed to the outside world, such as the skin and nasal and lung linings. So when an allergic response occurs, those tissues are most likely to be affected, resulting in the rashes, welts, runny noses, and watery eyes traditionally associated with allergies.
The IgE receptor had previously defied imaging because it has a heterogenous sugar coating that solubilizes the receptor and prevents it from crystallizing into a structure that can be examined through X-ray diffraction. To counteract this problem, the scientists expressed the human IgE receptor gene in cultured insect cells from the cabbage looper and the fall armyworm, which attach fewer sugars to the molecule. Next, they applied a technique called multiple isomorphous replacement, in which IgE receptor crystals were soaked in one of two solutions containing either gold or platinum. The large, heavy atoms of the metals were absorbed into the crystals, adding mass in the form of electrons to the receptor at key points and making it possible to calculate its image. According to Jardetzky, by comparing data that correspond to the receptor by itself to another set of data that reflects the changes effected by the binding of one of these heavy metals to the receptor, the researchers can calculate the structure of the receptor.
The researchers then used the very high intensity X rays of the Advanced Photon Source at Argonne National Laboratory in Illinois to scrutinize the IgE crystals. The Advanced Photon Source is a synchrotron, which uses magnetic fields to maintain charged particles in an orbit. The orbiting particles give off energy in the form of X rays. Special detectors measure the X rays as they bounce off the crystal being analyzed, and computers convert the data into an image of the crystal.
The researchers found that the receptor has an inverted "V" shape. At one end of the V is a spike that attaches the receptor to the cell membrane. The IgE antibody binds at the upward-pointing elbow of the V shape. Jardetzky and colleagues are currently investigating several potential inhibitors and are working on capturing an image of IgE bound to its receptor. "It may be more fruitful for drug development if we can get a picture of this 'lock and key' mechanism," says Jardetzky. "From that, it may emerge that it is better to design an inhibitor for the antibody than for the receptor."
Because allergic responses result only from IgE binding to the IgE receptor, therapeutic strategies aimed at inhibiting IgE-receptor interactions could provide a single treatment to fight multiple conditions such as asthma and sinusitis. The researchers believe that blocking the IgE receptor from binding the IgE antibody will short-circuit the allergy cycle.
Because the IgE-receptor interaction controls only the allergy branch of the body's immune response, it could be inhibited without compromising the entire immune response, says Kinet. The IgE receptor is thought to play some as-yet undefined role in immunity to parasitic infections. Jardetzky allows that inhibition of the IgE-receptor interaction may result in susceptibility to parasitic infections, particularly in developing nations, where such diseases are endemic. However, notes Kinet, IgE is not the only natural defense the body has against parasites. The advantages offered by such an inhibitor, he says, would far outweigh the disadvantages.
Safer Drugs for Children
When prescribing drugs for children, pediatricians must often resort to guesswork in determining the appropriate dose as well as in assessing the effectiveness of most pharmaceuticals currently on the market. While drug testing on humans has been required by the Food and Drug Administration (FDA) since the 1960s, an overwhelming majority of the testing has been conducted on adults. As of 1 April 1999, however, the FDA is requiring drug manufacturers to provide sufficient data and labeling on the safe use of drugs in children.
"Pediatricians and other health care providers will now have more specific dosing information based on scientific evidence," said First Lady Hillary Rodham Clinton in an FDA press release announcing the regulation. "This will make prescribing medication for children safer and may also lessen the number of side effects."
In 1994, the FDA issued a regulation that simplified the pediatric data required to obtain pediatric labeling in order to encourage drug manufacturers to voluntarily submit such data. The effort was unsuccessful, and about 75% of drugs currently on the market still lack adequate pediatric labeling.
In 1997, Congress passed the Food and Drug Administration Modernization Act and established an incentive--six months of protected market exclusivity--for manufacturers to conduct tests on the effects of drugs frequently used in children. The act's provision for exclusivity is applicable until 2002. "That exclusivity solves some of the missing information problem," says Diane Murphy, associate director for pediatrics at the FDA, "but it doesn't apply to products that don't have a patent."
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Ensuring safety. New FDA regulations will require testing of some drugs for use by children. |
The FDA issued a regulation in November 1998 (which became effective last April) that requires manufacturers to assess the safety and effectiveness of all drugs that are therapeutically important or commonly prescribed for children. The new rule also requires that some drugs already on the market be tested if they are commonly prescribed for use in children and if the absence of adequate labeling could pose significant risks to children.
In some cases, pediatric data can be submitted to the FDA after a new drug has been approved, especially if the FDA has safety concerns about testing the drug on children. "We are not going to hold up a therapy for adults just because we don't have all the information for children," Murphy says. Deferrals for pediatric testing may be granted in such cases.
The pediatric data requirement can be waived entirely if the product does not provide a meaningful therapeutic benefit over existing treatments and is not likely to be used in more than 50,000 pediatric patients. Waivers may also be granted for products that are likely to be unsafe or ineffective in pediatric patients (the assumption being that they will not be prescribed for children), if pediatric studies are impractical, or if reasonable efforts to develop a pediatric formulation have failed.
As for concerns about testing drugs on children, Robert Ward, a professor of pediatrics at the University of Utah in Salt Lake City and chair of the American Academy of Pediatrics Committee on Drugs, says there is extensive literature on how to study drugs in children. Ward says there is a general consensus that the metabolism and safety of a drug should be demonstrated in adults before being tested in children. The main issue to remember about pediatric drug testing, he says, is that it comes down to a choice of giving a child a drug under carefully controlled study conditions, or possibly giving a child a drug that has not been thoroughly tested in children.
There is more at issue than children's health. The FDA estimates that pediatric testing will cost less than 1% of the total spent to develop a new drug, or less than $50 million a year for all pediatric testing. However, health care savings due to better drug treatments for children are estimated to be $100 million annually.
The National Pharmaceutical Alliance and the Generic Drug Industry Association filed a lawsuit in federal court on 19 February 1999 opposing the FDA's interpretation of the exclusivity extensions in the act and requesting that the FDA be stopped from enforcing the rules.
The industry is arguing that the FDA has expanded the exclusivity to all forms of a particular drug, not just the form or forms used in children. The provision was intended as an incentive, says Michael Hinckle, an attorney representing the generic industry, but the way that the FDA has interpreted it has resulted in a windfall for brand name pharmaceutical companies. "This broad interpretation will cause considerable hardship to the generic industry," Hinckle says.
The American Academy of Pediatrics filed to intervene in the lawsuit and argue on behalf of children, but the motion was denied. "In 1968, the lack of studies on children was first pointed out," says Ward; this lack of data remains today. "There is finally some movement," he says, "and the generics are potentially going to stop that process."
The controversy about the safety of children's toys continues to play out in the scientific community and the media. Not only are there concerns about pesticides accumulating on toys, there is also fear that some of the chemicals used to manufacture toys may be posing risks to children's health. Phthalates, chemicals that are added to polyvinyl chloride (PVC) polymers to create flexible plastics, are receiving most of the attention. Phthalates are used in products such as shower curtains, raincoats, balls, squeeze toys, and medical devices such as tubing and IV bags.
Studies in the 1960s detected phthalates in biological samples, indicating that the chemicals leach out of PVC plastics. The NIEHS and the National Toxicology Program (NTP) began studying phthalates following a 1970s discovery that blood stored in PVC plastic bags that was used for transfusions contained measurable concentrations of phthalates, and that the chemicals were found in the organs of humans who had received transfusions.
Initially, the most widely studied phthalate was the commonly used di(2-ethylhexyl) phthalate (DEHP). In 1982, NTP studies showed that DEHP induced a strong liver tumor response in rats and mice. Since the 1980s, the NIEHS and the NTP have conducted carcinogenicity studies on four other phthalates, which were not found to cause cancer. They have also conducted reproductive and developmental toxicity testing on 12 phthalates and found that toxicity varies widely among the class.
In response to the finding of DEHP's carcinogenicity and to additional findings suggesting that DEHP may be toxic to the reproductive system, U.S. toy makers agreed in 1986 to limit the concentration of the chemical in teethers, pacifiers, and squeeze toys to 3%. Many toy makers began substituting diisononyl phthalate (DINP) for DEHP in these products. However, the environmental advocacy group Greenpeace released a study in December 1998 claiming that tests it had conducted found DEHP levels of 6-44% by weight in a variety of other children's products that are likely to be placed in the child's mouth, such as plastic bibs. In the controversy that continues to rage about the risks posed to children by phthalates in toys, a major point of contention is the amount of phthalates that leaches out of toys and into children's mouths.
In the first study to examine the amount of a phthalate that migrates out of children's products, the U.S. Consumer Product Safety Commission examined 31 different products containing DINP. At high doses in industry-sponsored studies, DINP has been linked with liver tumors and has been shown to cause damage to the liver, kidney, and other organs in mice and rats. The results, published in December 1998, also indicate that the amount of DINP ingested by children is well below harmful levels. The commission concluded that few, if any, children are at risk for toy-related DINP exposures and therefore did not recommend a ban on products containing the chemical. However, at the commission's request, 90% of manufacturers agreed to remove phthalates from soft rattles and teethers by early 1999. According to Greenpeace, Austria, Denmark, Finland, Greece, Norway, and Sweden have also banned or taken steps to ban phthalates in toys for children under the age of three years due to fears about infant exposure.
The Clinton administration has asked the NIEHS and the NTP to continue studying phthalates. The new NTP Center for the Evaluation of Risks to Human Reproduction announced in April that its first review will look at reproductive risks to plastics workers and consumers from seven phthalates, including DEHP and DINP, that are widely used in consumer products.
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During the first half of this century, the lead content of paint was seen as an indicator of its quality--more lead meant better paint. As a result, by the time lead was banned from house paint in 1978, the toxic metal was present in most U.S. homes. As old lead-based paint in homes ages and deteriorates, children, who are more susceptible to lead poisoning than adults, can easily ingest the resulting dust. The Centers for Disease Control and Prevention (CDC) estimate that 4.4% of U.S. children ages one to five have too much lead in their bodies, mostly as a result of the lead-based paint in their homes.
Anyone who has recently bought or rented an older home knows, however, that steps are being taken to prevent U.S. children from being further exposed to the lead in old paint. Since 1996, the federal government has required property owners to provide an educational pamphlet on lead-based paint to new occupants of homes built before 1978, and to disclose any known lead-related hazards in the home. The requirement was included in the Residential Lead-Based Paint Poisoning Prevention Act, known as Title X, which was signed into law on 28 October 1992. The passage of Title X signaled renewed federal interest in the effects of lead on children, showing that the efforts of advocacy groups such as the Alliance to End Childhood Lead Poisoning were bearing fruit.
Since its inception in 1990, the alliance has worked to put childhood lead exposure back on the national agenda after interest waned following bans on lead in gasoline and paint in the 1970s. Besides being part of the driving force behind Title X, the alliance educates the public on the dangers of lead to children, publishes reports and policy analyses, convenes international workshops, and helps to secure funding for lead poisoning research from public and private sources. Information on the group's work, including an in-depth explanation of Title X and other recent government actions, is available on the alliance's Web site, located at http://www.aeclp.org.
For the most part, Title X deals with the problem of lead-based paint in publicly subsidized housing. Since this housing is often old and poorly maintained, it is likely to contain deteriorating lead-based paint. According to the alliance, children from poor families are eight times as likely to have high blood lead levels as children from wealthier families. Correcting this disparity was a major objective of Title X.
The act also established certification and licensing programs for contractors who remove lead-based paint and for laboratories that analyze paint for lead content. It established a grant program, administered by the U.S. Department of Housing and Urban Development (HUD), and a federal hotline for disseminating information on lead poisoning (1-800-LEAD-FYI). Title X's major effect on private housing is the requirement that property owners provide information on lead to people who will inhabit older homes.
More information on Title X, including a section-by-section analysis, is available on the alliance's Web site under the Lead Poisoning Policy link on the home page. Also available is information on pending Environmental Protection Agency standards for lead-contaminated soil and dust, CDC recommendations for screening children for lead poisoning, and information on state and private screening programs.
Eventually, the alliance would like to see more legislation aimed at reducing exposure to lead in private homes, and improved screening of children for lead poisoning by both the federal government and private health care providers. (Despite the Health Care Finance Administration's requirement that all children covered by Medicaid be screened for lead poisoning, it is estimated that 81% are not.) Information about what the alliance is doing to effect these changes is accessible through the Projects and Activities link on the homepage. Also located under this link is a description of the alliance's efforts to foster cooperation among groups with similar interests, including an extensive database of advocacy and community groups that are working with the alliance. There is also information here about the alliance's work to reduce childhood lead poisoning outside the United States, particularly in countries where leaded gasoline is still in use.
These international efforts are described in more detail under the What's New link on the home page. There is a description available here of a February 1999 workshop held by the alliance in Bangkok that focused on reducing lead usage in Asia, and of a similar workshop held in May 1999 in Havana that focused on the Caribbean region. Also under the What's New link is the latest information about grants being made available by HUD and other federal agencies to study ways of reducing the lead hazard in homes. Over $350 million in federal grant money has been distributed since 1992 for controlling lead hazards in low-income housing, and in 1996, Congress voted to continue this funding at the rate of $60 million per year. Updates on recent congressional actions are also available in this section of the Web site.
Brief articles on all of the latest developments related to childhood lead poisoning are provided by the alliance in its Alliance Alert newsletter, available via the What's New link. Besides giving updates on research funding, government actions, and the alliance's international activities, the newsletter summarizes recent relevant research, such as a study published in the March 1999 issue of Pediatrics that showed that education and specialized cleaning may result in a 17% decrease in blood lead levels in children.
Another announcement recently made in the Alliance Alert is that the alliance's sister organization, the National Center for Lead-Safe Housing, recently established its own Web site, located at http://www.leadsafehousing.org. The center was established in 1992 with a grant from the Fannie Mae Foundation that was given at the request of the alliance. The $5.5 million grant, the largest ever given by that organization, helps the center develop, evaluate, and promote cost-effective strategies to reduce childhood lead poisoning. The center assesses the strategies that HUD and local governments are employing to reduce lead exposure, and provides technical assistance and training to health and housing departments, nonprofit organizations, insurance companies, and real estate developers.
Information on the center's recent studies and analyses is available through the Scientific Research link on the home page. Other resources on the center's Web site include information on maintaining a lead-safe home and information on lead safety for painters, contractors, developers, and others who might encounter lead-based paint in their work
Last Updated: May 19, 1999