Pediatrics in Review_May2011

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Answer Key: 1. E; 2. D; 3. A; 4. C; 5. C; 6. C; 7. B; 8. C; 9. C;10. D; 11. A

Articles

Infant Formulas179J. Andres Martinez, Martha P. Ballew

Addressing Environmental Contaminants inPediatric Practice190Catherine Karr

Complementary, Holistic, and IntegrativeMedicine: Mind-Body Medicine201Hilary McClafferty

Ethics for the Pediatrician: Just Distribution ofHealth-care Resources and the Neonatal ICU204Charles C. Camosy

Correction207Index of SuspicionCase 1: Abdominal Pain and Coffee Ground Emesis

in a 9-year-old BoyCase 2: Vomiting, Headache, and Seizures

in a 7-year-old BoyCase 3: Primary Amenorrhea in a 15-year-old Girl209Case 1: Thomas C. Martin, Joshua M. CareskeyCase 2: Heather Harle, Sean Rose, Howard P. GoodkinCase 3: Rachel Dawson, Shana Hansen

Visual Diagnosis: Sore Throat and Difficulty Swallowingin a 9-year-old Boy215Nirav Shastri, Getchen Black, Milton A. Fowler, Jr

In BriefHistiocytosis218Jan E. Drutz

Online-Only ArticleAbstract appears on page 208.

The Preparticipation Sports Evaluatione53Andrew R. Peterson, David T. Bernhardt

Cover: The artwork on the cover of thismonth’s issue is by one of the winnersof our 2009 Cover Art Contest, 8-year-old Josie P of Wyckoff, NJ. Josie’spediatrician is Mondana Yazdi, MD.

contentsPediatrics inReview� Vol.32 No.5 May 2011

Editor-in-Chief: Lawrence F. Nazarian, Rochester, NYAssociate Editors: Tina L. Cheng, Baltimore, MD

Joseph A. Zenel, Sioux Falls, SDEditor, In Brief: Henry M. Adam, Bronx, NYConsulting Editor, In Brief: Janet Serwint, Baltimore, MDEditor, Index of Suspicion: Deepak M. Kamat, Detroit, MIConsulting Editor Online and Multimedia

Projects: Laura Ibsen, Portland, OREditor Emeritus and Founding Editor:

Robert J. Haggerty, Canandaigua, NYManaging Editor: Luann ZanzolaMedical Copy Editor: Deborah K. KuhlmanEditorial Assistants: Kathleen Bernard, Melissa Schroen,

Sydney SutherlandEditorial Office: Department of Pediatrics

University of RochesterSchool of Medicine & Dentistry601 Elmwood Avenue, Box 777Rochester, NY [email protected]

Editorial BoardHugh D. Allen, Columbus, OHMargie Andreae, Ann Arbor, MIRichard Antaya, New Haven, CTDenise Bratcher, Kansas City, MOGeorge R. Buchanan, Dallas, TXBrian Carter, Nashville, TNJoseph Croffie, Indianapolis, INB. Anne Eberhard, New Hyde Park, NYPhilip Fischer, Rochester, MNRani Gereige, Miami, FLLindsey Grossman, Springfield, MAPatricia Hamilton, London, United Kingdom

Jacob Hen, Bridgeport, CTHal B. Jenson, Springfield, MADonald Lewis, Norfolk, VAGregory Liptak, Syracuse, NYSusan Massengill, Charlotte, NCJennifer Miller, Gainesville, FLBlaise Nemeth, Madison, WIRenata Sanders, Baltimore, MDThomas L. Sato, Milwaukee, WISarah E. Shea, Halifax, Nova ScotiaAndrew Sirotnak, Denver, CONancy D. Spector, Philadelphia, PA

Publisher: American Academy of PediatricsMichael J. Held, Director, Division of Scholarly Journals and Professional Periodicals

Pediatrics in Review�Pediatrics in Review�(ISSN 0191-9601) is owned and controlled by the American Academy ofPediatrics. It is published monthly by the American Academy of Pediatrics, 141Northwest Point Blvd., Elk Grove Village, IL 60007-1098Statements and opinions expressed in Pediatrics in Review� are those of the authorsand not necessarily those of the American Academy of Pediatrics or its Committees.Recommendations included in this publication do not indicate an exclusive courseof treatment or serve as a standard of medical care.Subscription price for 2011 for print and online/online only: AAP Fellow $177/$135; Nonmember $222/$172; Allied Health or Resident $165/$111.Institutions call for pricing (866-843-2271). For overseas delivery, add $109.Current single issue price is $10 domestic, $12 international. Replacement issuesmust be claimed within 6 months from the date of issue and are limited to threeper calendar year. Periodicals postage paid at ARLINGTON HEIGHTS,ILLINOIS and at additional mailing offices.© AMERICAN ACADEMY OF PEDIATRICS, 2011. All rights reserved. Printedin USA. No part may be duplicated or reproduced without permission of theAmerican Academy of Pediatrics.POSTMASTER: Send address changes to PEDIATRICS IN REVIEW�, AmericanAcademy of Pediatrics Customer Service Center, 141 Northwest Point Blvd., ElkGrove Village, IL 60007-1098.Pediatrics in ReviewPrint Issue Editorial Board DisclosuresThe American Academy of Pediatrics (AAP) Policy on Disclosure of FinancialRelationships and Resolution of Conflicts of Interest for AAP CME Activities isdesigned to ensure quality, objective, balanced, and scientifically rigorous AAP CMEactivities by identifying and resolving all potential conflicts of interest before theconfirmation of service of those in a position to influence and/or control CME content.All individuals in a position to influence and/or control the content of AAP CMEactivities are required to disclose to the AAP and subsequently to learners that theindividual either has no relevant financial relationships or any financial relationships withthe manufacturer(s) of any commercial product(s) and/or provider(s) of commercialservices discussed in CME activities. Commercial interest is defined as any entityproducing, marketing, reselling or distributing health-care goods or services consumedby, or used on, patients.Each of the editorial board members, reviewers, question writers, PREP CoordinatingCommittee members and staff has disclosed, if applicable, that the CME content he/she edits/writes/reviews may include discussion/reference to generic pharmaceuticals,off-label pharmaceutical use, investigational therapies, brand names, and manufacturers.None of the editors, board members, reviewers, question writers, PREP CoordinatingCommittee members, or staff has any relevant financial relationships to disclose, unlessnoted below. The AAP has taken steps to resolve any potential conflicts of interest.Disclosures● Richard Antaya, MD, FAAP, disclosed that he participates in Astellas Pharma, US,

Inc., clinical trials, speaker bureau and advisory board; and that he participates in theNovartis speaker bureau.

● Athos Bousvaros, MD, MPH, FAAP, disclosed that he has research grants from Merckand UCB; and that he is a paid consultant and on the speaker bureau for Millennium.

● Brian Carter, MD, FAAP, disclosed that he participates in the MedImmune speakerbureau.

● David N. Cornfield, MD, FAAP, disclosed that he has National Institutes ofHealth grants.

● Donald W. Lewis, MD, FAAP, disclosed that he is a consultant for and has aresearch grant from Astra Zeneca and Merck; and that he has research grantsfrom Ortho McNeil, Lilly, Bristol-Myers Squibb, GlaxoSmithKline, andBoehringer Ingelheim Pharmaceutical.

● Blaise Nemeth, MD, MS, FAAP, has disclosed he has an unrestrictededucational grant for fellowship from Biomet.

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Pediatrics in Review� is supported, in part, through aneducational grant from Abbott Nutrition, a division ofAbbott Laboratories, Inc.

CME Statements:The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) toprovide continuing medical education for physicians.The AAP designates this journal-based CME activity for a maximum of 36 AMA PRA Category 1 CreditsTM. Physicians should claim onlythe credit commensurate with the extent of their participation in the activity.This activity is acceptable for a maximum of 36 AAP credits. These credits can be applied toward the AAP CME/CPD* Award availableto Fellows and Candidate Members of the AAP.The American Academy of Physician Assistants accepts AMA PRA Category 1 CreditsTM from organizations accredited by the ACCME.This program is approved for 36 NAPNAP CE contact hours; pharmacology (Rx) contact hours to be determined per the NationalAssociation of Pediatric Nurse Practitioners (NAPNAP) Continuing Education Guidelines.*Continuing Professional DevelopmentHow to complete this activityPediatrics in Review can be accessed and reviewed in print or online at http://pedsinreview.aappublications.org. Learners can claim creditmonthly online or submit their scannable answer sheet for credit upon completion of the 12-month activity. A CME scannable answer sheetfor recording your quiz answers can be found bound in the January 2011 issue. The deadline for submitting the 2011 answer sheet for thisactivity is December 31, 2013. Credit will be recorded in the year in which it is submitted. It is estimated that it will take approximately3 hours to complete each issue. This activity is not considered to have been completed until the learner documents participation in thatactivity to the provider via online submission of answers or submission of the answer sheet. Course evaluations will be requested online andin print.

DOI: 10.1542/pir.32-5-179 2011;32;179-189 Pediatr. Rev.

J. Andres Martinez and Martha P. Ballew Infant Formulas

http://pedsinreview.aappublications.org/cgi/content/full/32/5/179located on the World Wide Web at:

The online version of this article, along with updated information and services, is

Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347. Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy of published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1979. Pediatrics in Review is owned, Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly

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Infant FormulasJ. Andres Martinez, MD,*

Martha P. Ballew, MEd,

RD, CNSC, LDN†

Author Disclosure

Dr Martinez and Ms

Ballew have disclosed

no financial

relationships relevant

to this article. This

commentary does not

contain a discussion

of an unapproved/

investigative use of a

commercial product/

device.

Objectives After completing this article, readers should be able to:

1. Describe the macronutrient content of formulas used as substitutes for human milk forterm and preterm infants.

2. Identify appropriate clinical applications of infant formulas that have altered nutrientcontents based on the physiologic significance of specific changes in formulacomposition.

3. Discuss the physiologic role and potential health benefits associated with four compo-nents added to infant formulas in the past decade.

4. Delineate current regulatory guidelines that define standards for composition andperformance and safety criteria for commercial infant formulas.

Historical BackgroundDevelopment of infant formulas can be traced to the late 19th century. In 1867, Liebigdeveloped and marketed a product for infant feeding that contained cow milk, wheat flour,malt flour, and potassium bicarbonate. In 1915, Gerstenberger reported a 3-year experi-ence using “synthetic milk, adapted” that contained nonfat cow milk, lactose, oleo oils,and vegetable oils. This product represented early understanding that cow milk requiredalteration to improve its acceptability for human consumption and is considered theprecursor to modern infant formulas. (1)

Government regulation of infant formula composition in the United States began in1941 and underwent significant expansion with passage of the Infant Formula Act of1980, a direct and prompt response to an epidemic of a Bartterlike syndrome (hypochlo-remic, hypokalemic metabolic alkalosis). Most cases were later attributed to consumptionof a chloride-deficient soy infant formula. The Infant Formula Act of 1980 and itsamendments in 1986 defined minimum concentrations of 29 nutrients and establishedquality control standards for commercial production of infant formulas. Current standardsare summarized in the Electronic Code of Federal Regulations: Title 21:107—Infant

Formula. (2) Organic infant formulas must also meet allstandards required for United States Department ofAgriculture Organic certification.

The addition of nucleotides to infant formulas in 1999 andlong-chain polyunsaturated fatty acids (LCPUFAs) in 2002marked a new era in infant formula development. In 2004,anticipating continued competition among infant formulamanufacturers to develop products that mimic the com-plexities and performance of human milk, a special commit-tee of the Food and Nutrition Board of the Institute ofMedicine proposed enhanced regulatory and research proce-dures to assess the safety of potential new ingredients ininfant formulas. (1)

Challenges continue in ensuring the quality and safety ofcommercial infant formulas. Within the past 5 years, pow-dered infant formulas have been recognized as potentialcarriers of food-borne illness after the death of an infant due

*Assistant Professor, Director Pediatric Nutrition Support Program, Department of Pediatrics, Division of Gastroenterology,Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, TN.†Pediatric Nutrition Support Dietitian, Department of Nutrition Services, Monroe Carell Jr Children’s Hospital at Vanderbilt,Nashville, TN.

Abbreviations

AAP: American Academy of PediatricsARA: arachidonic acidCMPA: cow milk protein allergyDHA: docosahexaenoic acidEHF: extensively hydrolyzed formulaGERD: gastroesophageal reflux diseaseIg: immunoglobulinLCPUFA: long-chain polyunsaturated fatty acidMCT: medium-chain triglycerideNEC: necrotizing enterocolitisPHF: partially hydrolyzed formulaVLBW: very low birthweight

Article nutrition

Pediatrics in Review Vol.32 No.5 May 2011 179. Provided by Health Internetwork on May 2, 2011 http://pedsinreview.aappublications.orgDownloaded from


to Enterobacter sakazakii meningitis in the United Statesand a case of infantile botulism in the United Kingdom.These incidents led to stricter safety guidelines for homeand institutional preparation and handling of commercialinfant formulas. (3) The Table offers a comparison ofcurrently available formulas.

Cow Milk-based Formulas for Term InfantsOften referred to as “standard” infant formulas, these prod-ucts are the most commonly used substitutes for humanmilk. They are available as ready-to-use liquids (20 kcal/ozor 67 kcal/100 mL) and as powder or liquid concentratesthat may be mixed with specific quantities of water to yieldcaloric densities between 20 and 30 kcal/oz.

ProteinDifferences in the serum amino acid profiles of breastfedand formula-fed infants are due to variations in the specificprotein content of human and bovine milk. Human milkhas a higher whey-to-casein ratio (70:30) than bovine milk(18:82). Unlike casein, which forms large curds on expo-sure to gastric acid, whey protein is resistant to precipitationand undergoes more rapid gastric emptying. These charac-teristics are the primary reason for continued modificationof the whey:casein ratio of cow milk-based formulas. It isimportant to note that the whey proteins in human andbovine milk are vastly different from both compositionaland functional standpoints. In an effort to match the pro-tein quality of human milk, cow milk-based formulas cur-rently contain almost 50% higher total protein content (2.1to 2.2 g/100 kcal) than human milk. Most infant formulasalso contain supplemental taurine. The physiologic signifi-cance of differences in serum amino acid profiles of infantsfed cow milk-based formulas versus human milk remainsunclear. More importantly, casein-predominant (20:80),whey-predominant (60:40), and 100% whey formulas haveall been shown to support normal growth patterns in bothterm and preterm infants.

CarbohydrateLactose is the predominant carbohydrate in most cowmilk-based formulas and human milk. The lactase en-zyme in the brush border of the small intestine reachesmaximum concentrations late in fetal development, butsome unsplit lactose usually reaches the distal bowel,where its fermentation permits proliferation of acido-philic bacteria, namely, Lactobacillus. Lactose has alsobeen shown to enhance absorption of calcium in terminfants between 8 and 12 weeks of age. The significanceof this benefit in term infants is unclear because adequatecalcium absorption has been demonstrated in infantsconsuming lactose-free formulas.

FatApproximately 50% of the caloric content of human milkis contained in its lipid component, which is rich inpalmitic, oleic, linoleic, and linolenic fatty acids. Currentformulas contain specific blends of vegetable oils de-signed to mimic the ratios of saturated, monounsatu-rated, and polyunsaturated fatty acids in human milk;increase the essential fatty acid content; and reduce gas-trointestinal symptoms previously associated with infantfeeding of whole cow milk.

Docohexaenoic acid (DHA) and arachidonic acid(ARA) are LCPUFAs present in human milk (meancontent of DHA 0.32% and ARA 0.47% of total fattyacids) and have been found to accumulate rapidly in thefetal retina and brain during the last trimester of preg-nancy, continuing until 2 years of age. DHA and ARAcan be synthesized from precursor essential fatty acidsand before 2002 were not added to infant formulas.Studies have shown that breastfed infants have a highercontent of DHA in the brain cortex compared withinfants consuming nonsupplemented formulas. Fur-thermore, numerous studies have observed improvedvisual and neurodevelopmental outcomes in childrenwho had been supplemented with DHA or DHA plusARA as infants. In 2008, two Cochrane meta-analyses ofrandomized, controlled trials found that milks supple-mented with these LCPUFAs did not improve growth,visual acuity, or neurodevelopment in either preterm orterm infants, which called their standard supplementa-tion into question. (4)(5) However, recent studies thathave focused on higher doses of DHA (between 0.3%and 0.5% of total fatty acids) and at least equal amountsof ARA have consistently reported significant benefits.Preterm infants may have a higher requirement, based oncalculated accretion rates in the last trimester of preg-nancy. No negative effects have been observed withDHA and ARA supplementation, and both are presentlyadded to all formulas in a dose range of 0.15% to 0.32%DHA and 0.4% to 0.64% ARA (% total fatty acids).More studies are needed to define better the benefits andthe correct dose needed for supplementation. (6)

Vitamins and MineralsIron fortification was implemented in 1959 in responseto recognition of a high prevalence of iron deficiencyanemia among formula-fed infants. Iron from humanmilk is absorbed at a higher rate (20% to 50%) comparedwith cow milk (4% to 7%). To compensate for lowerbioavailability, all fortified formulas contain 1.8 mg/100 kcal of iron as compared with 0.45 to 0.9 mg/100 kcal in human milk. It is strongly recommended that

nutrition infant formulas

180 Pediatrics in Review Vol.32 No.5 May 2011. Provided by Health Internetwork on May 2, 2011 http://pedsinreview.aappublications.orgDownloaded from


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all formula-fed infants receive iron-fortified formulas toprevent anemia. Infant formula content of other micro-nutrients is based on a combination of data sets, includ-ing age-specific dietary reference intakes, human milkcomposition, inherent differences in the bioavailability ofspecific nutrients in human milk and formula, and regu-latory guidelines.

NucleotidesThese nitrogenous substances have been added to severalcow milk-based formulas since the late 1990s due toexpanding knowledge of their physiologic role and rec-ognition of their presence in relatively high concentra-tions in human milk. Nucleotides, which consist of oneRNA nucleoside (adenine, guanine, cytosine, or uri-dine), one 5-carbon sugar moiety, and one or morephosphate groups, have been proposed as conditionallyessential during periods of rapid growth because theypossess immunomodulating capabilities. In clinical stud-ies, nucleotide supplementation has been shown to en-hance growth in small-for-gestational age infants, en-hance immunoglobulin A (IgA) and IgM concentrationsin preterm infants, decrease the incidence of diarrhealdisease, and enhance antibody response to certain vac-cines. However, additional research is needed to definethe mechanism of action, confirm the clinical response,and monitor long-term effects of nucleotide supplemen-tation of infant formulas.

Prebiotics, Probiotics, and SynbioticsThe intestinal flora of breastfed infants differs from thatof formula-fed infants. Breastfed infant flora is predomi-nantly composed of Bifidobacterium and Lactobacillus,whereas the flora of formula-fed infants is more complex,including also Bacteroides, Enterobacteriaceae, Clostrid-ium, and Streptococcus. This difference is due, in part, tothe high concentrations of oligosaccharides present inhuman milk that selectively stimulate bifidobacteria andlactobacilli. These bacteria are believed to be importantfor nutrient absorption, protection against pathogencolonization, development of the intestinal and systemicimmune systems, and acquisition of mucosal tolerance.In an attempt to reproduce the intestinal flora of hu-man milk-fed infants, prebiotics, probiotics, and synbiot-ics have been added to formulas with promising results.

Prebiotics are nondigestible short-chain carbohydrates,commonly galacto-oligosaccharides, fructo-oligosaccharides,or lactulose, that stimulate growth and function of specificspecies of bacteria. When added to formulas, prebioticshave been shown to increase the concentration of bifido-bacteria and lactobacilli in the stools of preterm and term

infants. The fermentation of prebiotics in the colon can leadto acidic, more frequent, and looser stools, but they are safeat the currently prescribed doses. Probiotics are live micro-organisms that survive digestion and colonize the colon,leading to a more beneficial colonic microbiota. Synbioticsare a combination of prebiotics and probiotics. Both pre-biotics and probiotics allow for normal growth in infancy.

Prebiotics and probiotics have been used for the pre-vention and treatment of allergy. The intestinal flora ofatopic infants differs from that of nonatopic infants in thefirst few weeks after birth. These differences were notedbefore the development of atopy, suggesting a possiblecausative relationship. A lower number of bifidobacteriaand higher numbers of clostridia may lead to an unbal-anced, Th2-predominant immune response with in-creased IgE secretion, which is theorized to be a factorin the development of atopy. Both prebiotics and pro-biotics have been used in an attempt to achieve a morefavorable intestinal flora, thereby preventing the devel-opment of atopic diseases. Evidence for the use of pre-biotics in the prevention of atopy is inconclusive. Thisuncertainty could be due to a significant heterogeneityamong the studies, including types and doses of pre-biotics, types of milk used, and patient selection.

A Cochrane review showed that probiotic supplementa-tion to high-risk infants decreased the incidence of clinicaleczema but not of other atopic diseases. However, cautionwas raised about the heterogeneity of studies, the lowfollow-up numbers, and the fact that this effect did not holdfor eczema with proven sensitization. (7) Probiotics havebeen studied for the treatment of allergies. One studyshowed that infants suspected of having cow milk proteinallergy (CMPA) had faster recoveries when LactobacillusGG was added to an extensively hydrolyzed formula, withfaster resolution of blood per rectum and increased reduc-tion of fecal calprotectin concentrations. (8)

Perhaps the most promising effect of probiotics is inthe prevention of necrotizing enterocolitis (NEC). NECis believed to have a multifactorial cause, with contribu-tory factors including prematurity, aggressive initiationof feedings, pathogenic bacteria, and ischemia, all ofwhich ultimately lead to immunologic injury to the gut.The intestinal flora of preterm infants contains less ben-eficial bacteria, which may be due to delayed feedings,broad-spectrum antibiotic courses, and acquisition ofpathogenic environmental bacteria. Probiotics are be-lieved to reduce the intestinal inflammatory response andmay prevent NEC. In a recently updated meta-analysis,probiotics led to a reduction in cases of NEC (at least a30% reduced incidence) and all-cause mortality in verylow-birthweight (VLBW) infants (1,000 to 1,500 g).




Probiotics did not reduce the risk of sepsis or mortalitydue to NEC. (9) There are rare reports of probiotic-associated sepsis in neonates, but this complication wasnot seen in the studies reviewed for the meta-analysis.Other potential concerns about the safety of probioticshave been raised, including risks for transmission of anti-biotic resistance and negative effect on neurodevelopment.In conclusion, probiotics appear to be effective in reduc-ing the risk of NEC, but more studies are needed todetermine the most beneficial type, dose, and durationof probiotic therapy. The safety and efficacy need to beestablished for each product. Currently, data in extremelylow-birthweight (�1,000 g) infants are insufficient toreach any conclusions. The evidence for use of prebioticsin the prevention of NEC is very limited.

Studies have shown that formulas supplemented withprebiotics led to prevention of respiratory and intestinalinfections. In one study, this beneficial effect persisted at2 years of age. (10)

Preterm Infant FormulasPreterm formulas were developed to meet the unique nu-tritional needs of rapidly growing preterm or low-birthweight infants. These products have a higher caloricdensity than standard formulas (24 kcal/oz or 80 kcal/100 mL). They contain supplemental taurine and 3 to3.3 g/100 kcal of whey-predominant protein, which hasbeen demonstrated to support growth and body composi-tion changes comparable to intrauterine standards. The fatand carbohydrate compositions of these formulas are de-signed to overcome nutrient losses from low concentrationsof lipase, bile salts, and intestinal lactase. In currently avail-able products, medium-chain triglyceride (MCT) oil pro-vides between 40% and 50% of total fat, with the remainderderived from a vegetable oil blend and supplemental DHAand ARA. MCT is absorbed directly into the portal vascularsystem and does not depend on the availability of bile acidsfor micellar solubilization.

Although lactase concentrations do not reach maxi-mal values until term, carbohydrate is provided as a60:40 or 50:50 mixture of glucose polymers and lactosedue to the beneficial effects of lactose for calcium absorp-tion and as a prebiotic. Preterm formulas contain higheramounts of numerous minerals and vitamins (particularlycalcium, phosphorus, and vitamins A and D). It is impor-tant to note that intakes of some nutrients may beexcessive if preterm formulas are consumed in quantitiesthat exceed 12 oz/day (360 mL), and this risk increasesas the infant’s weight approaches 2,000 g. Preterm for-mulas should always be discontinued before hospitaldischarge.

Preterm Transitional Formulas“Transitional” or “enriched” formulas that have inter-mediate nutrient concentrations have been available forseveral years and are marketed to bridge the gap betweenpreterm and term formulas. Preterm infants are usuallytransitioned from preterm formulas to enriched formulas(22 kcal/oz or 73 kcal/100 mL) at 1,800 to 2,000 g or34 weeks gestational age and continued on these for-mulas until 6 to 9 months of age. These formulas canachieve vitamin and mineral goal requirements withoutadditional supplementation. However, the data on growthand neurodevelopment have been disappointing. In fact,a 2007 Cochrane meta-analysis found no evidence thatfeeding enriched formulas (versus standard infant for-mulas) to preterm infants after hospital discharge leadsto improvements in growth or neurodevelopment by18 months of age. (11)

Human Milk FortifiersHuman milk alone is inadequate to meet the nutritionalneeds of preterm infants, particularly VLBW infants(�1,500 g). Thus, fortification of human milk (ie, theaddition of multinutrient supplements) is recommended.Currently available commercial human milk fortifiers con-tain protein, carbohydrate, fat, and up to 23 vitamins andminerals. When mixed according to manufacturer’s direc-tions, fortified human milk matches growth and metaboliceffects of preterm infant formulas. As with preterm formu-las, ongoing use of commercial human milk fortifiers even-tually may lead to excessive intake of certain nutrients thathave known potential for toxicity. Therefore, it has becomecommon clinical practice to use specific quantities of stan-dard infant formula powder or liquid concentrate to fortifyhuman milk in preterm infants who have progressed be-yond specific age, weight, and intake volumes.

Soy FormulasCurrently available soy formulas contain a higher con-centration of protein (2.45 to 2.8 g/100 kcal) andsupplemental amino acids (L-methionine, taurine, andL-carnitine) to improve their biologic value. Glucosepolymers from corn syrup solids or maltodextrin are theprimary source of carbohydrate in soy formulas. Someproducts also contain sucrose, and all soy formulas arelactose-free. Fiber oligosaccharides, naturally occurringsoy carbohydrates, are also present in soy formulas. Thesecompounds and soy phytates have a high affinity forcalcium, phosphorus, zinc, and iron and have beenshown to interfere with their absorption. Therefore, soyformulas contain 20% higher concentrations of calciumand phosphorus and additional zinc and iron to compen-




sate for their diminished bioavailability. The fat contentof soy formulas is similar to cow milk-based formulas,containing a blend of vegetable oils and supplementalARA and DHA in all currently marketed products.

According to the 2000 United States Census, 18% ofinfants were fed soy formula in their first postnatal year.However, evidence-based indications for their use arelimited. Soy protein-based formulas have been shown tobe safe in term infants, with evidence for adequategrowth rates and bone mineralization compared withinfants fed cow milk-based formulas. However, for pre-term infants, soy formulas cannot meet the increasedrequirements for calcium and phosphorus to match intra-uterine accretion values, and this inadequacy can lead toosteopenia. Soy formulas contain increased concen-trations of aluminum, which may compete with calciumfor absorption, further affecting bone mineralization.For these reasons, soy formulas are not recommendedfor preterm infants. Concerns have been raised about thehigh concentrations of phytoestrogens/isoflavones insoy. These compounds bind to estrogen receptors andhave been reported to have various negative effects onestrogen-related functions in animal studies, althoughresults are conflicting and may be species-specific. In fact,a recent retrospective follow-up study showed no repro-ductive or estrogen-related adverse effects in adults whohad been fed soy formula exclusively as infants. (12)

Soy formulas have not been shown to be of benefitin the management of infantile colic or cow milk intol-erance, and there is no indication for their use in theprevention of atopic diseases. Infants who have nonIgEallergic enteropathy or enterocolitis due to CMPA havea 30% to 64% rate of cross-reaction to soy protein.Therefore, soy formulas are not indicated in the manage-ment of nonIgE allergies to cow milk protein. However,only 8% to 14% of infants who have IgE-mediated aller-gic reactions to cow milk proteins are sensitized to soy.

A statement by the European Society for PediatricGastroenterology, Hepatology, and Nutrition recom-mends that use of soy formulas be limited to infants olderthan 6 months of age who have signs consistent withIgE-mediated allergy after successful clinical challenge.(13) Soy formulas are free of all lactose and are indicatedwhen strict lactose avoidance is required, as in the rarecase of congenital lactase deficiency or in the manage-ment of galactosemia. It is important to note that cowmilk protein formulas said to be free of lactose, in whichother sugars are the predominant source of carbohy-drates, still can contain small amounts of lactose and arenot appropriate for infants who have galactosemia. Anyformula said to be lactose-free may be used for transient

lactase deficiency, such as a postviral enteropathy, al-though such affected infants generally tolerate continu-ation of a standard lactose-containing formula. Becausesoy formulas in this setting were only shown to decreasethe duration of the diarrhea from 6 to 4 days without asignificant change in weight at 14 days, their use for thispurpose is discouraged. (14) Finally, strict vegetarianfamilies may prefer soy formula for their infants.

Hydrolyzed and Amino Acid-based FormulasMore than 50 years ago, infant formulas containingextensively hydrolyzed protein were developed for feed-ing infants who were unable to digest or tolerate formu-las containing intact cow milk protein. Casein, which isheat-treated and enzymatically hydrolyzed, is the proteinsource for all currently marketed formulas of this typein the United States. Hydrolysis results in a combina-tion of short-chain peptides and free amino acids. Spe-cific free amino acids are supplemented to improve thebiologic value of the resulting nitrogenous content. Ithas been shown that peptides containing as few as threeamino acids can induce T-cell activity in vitro. Thus, tobe labeled as hypoallergenic, the American Academy ofPediatrics (AAP) guidelines state that “formulas mustdemonstrate that they do not provoke reactions in 90% ofinfants or children with confirmed cow milk allergy with95% confidence when given in prospective randomized,double-blind, placebo-controlled trials.” Currently, onlyextensively hydrolyzed and free amino acid-based formu-las are considered to be hypoallergenic by these criteria.

Glucose polymers from various combinations of in-gredients are the primary carbohydrate source in exten-sively hydrolyzed formulas (EHFs). One currently avail-able formula (Similac Expert Care Alimentum®, AbbottNutrition, Columbus, OH) contains a combination ofglucose polymers and sucrose. All formulas are lactose-free.

The fat content of EHFs varies considerably. Allcontain a blend of vegetable oils similar to that in stan-dard formulas and a total fat content of 48%. In two ofthree currently marketed products (Pregestimil®, MeadJohnson Nutritionals, Evansville, IN, and Similac ExpertCare Alimentum®, Abbott Nutrition, Columbus, OH),a portion of this oil blend is replaced with MCT oil,which is helpful in certain malabsorptive conditions.Because essential fatty acids are long-chain triglycerides,no formula contains 100% MCT as a fat source.

Carbohydrate and fat composition are important cri-teria for specific EHF selection because clinical applica-tion of these formulas has expanded over time to in-clude various conditions characterized by malabsorptionof nutrients. Examples include short bowel syndrome,




hepatobiliary disease, pancreatic insufficiency, autoim-mune diseases, and immunodeficiency syndromes. Theseformulas may be poorly accepted unless introduced earlyin infancy, and their high cost necessitates judicious use.

In recent years, formulas containing partially hydro-lyzed whey protein have been marketed in the UnitedStates. They contain fat blends similar to those in stan-dard formulas as well as reduced lactose content (lactosepartially or fully replaced by glucose polymers).

Three amino acid-based formulas have been approvedby the United States Food and Drug Administration:Neocate® (Nutricia North America, Gaithersburg, MD),Elecare® (Abbott Nutrition, Columbus, OH), andNutramigen AA® (Mead Johnson Nutritionals, Evansville,IN). Unlike EHFs, the protein content of amino-acid basedproducts is composed of individual free amino acids.

Glucose polymers from various dietary sources are theprimary source of carbohydrate. With regard to fat content,one product (Nutramigen AA®) contains an oil blendsimilar to that in standard formulas. The other two products(Neocate® and Elecare®) contain a combination of oilsresulting in a long-chain triglyceride-to-MCT ratio (67:33)that can be beneficial for certain malabsorptive disorders.

The increasing incidence of atopic diseases in recentdecades has prompted interest in the use of hydrolyzedformulas for the prevention of atopy, particularly ec-zema, asthma, and food allergies. Hydrolyzed proteinformulas appear to be superior to standard cow milkformulas, but not to human milk, in the prevention ofallergy. The German Infant Nutritional InterventionProgram, a longitudinal prospective study, showed thatinfants who had a high risk for developing atopic diseases(first-degree relative who had allergy) had a 33% lowerincidence of atopic dermatitis when human milk wassupplemented with hydrolyzed protein formula com-pared with supplementation with regular cow milk for-mula in the first 4 postnatal months. (15) This beneficialeffect persisted at 6 years of age. Extensively hydrolyzedcasein was more effective than partially hydrolyzed whey;extensively hydrolyzed whey showed no benefit.

In 2008, updated AAP recommendations stated thatfor infants at high risk of developing atopic disease whoare not breastfed exclusively for 4 to 6 months or areformula-fed, there is evidence that atopic dermatitis maybe delayed or prevented by the use of EHF or partiallyhydrolyzed formula (PHF) compared with cow milk-based formula. (16)

A more recent meta-analysis of 18 studies of high-riskinfants who were fed a partially hydrolyzed whey formulafound a 45% reduced risk for atopic dermatitis at 1 year ofage and 36% reduction at 3 years of age. (17) Consider-

ing the high prevalence of allergic diseases in the popu-lation, one third of all infants would be candidates for ahydrolyzed formula, but their higher cost must be takeninto consideration. Amino acid-based formulas have notbeen studied in the prevention of allergy.

Today, CMPA or hypersensitivity is reported in 2%to 3% of all infants. PHFs are not indicated for themanagement of CMPA due to the high percentage ofreactions to these formulas. Therefore, infants who haveproven CMPA and are not breastfeeding should be fedEHFs. A subgroup of patients who have CMPA, thosewho have nonIgE-mediated enterocolitis and failure tothrive, severe eczema, or symptoms during exclusivebreastfeeding, may respond better to amino acid-basedformulas than hydrolyzed formulas. (18) However,amino acid-based formulas should be reserved for thosewho do not respond to EHFs.

A percentage of infants who experience colic do re-spond to hydrolyzed formulas. Thus, a 1- to 2-week trialof a hydrolyzed formula can be recommended.

Modified Cow Milk- andSoy-based Formulas for Term InfantsIn the past several years, the infant formula market hasexpanded to include several formulas marketed as solu-tions to specific conditions such as acid reflux, diarrhea,and excessive gas or fussiness often associated with colic.These formulas vary considerably in their macronutrientprofile and typically contain one or more of the follow-ing modifications: partially hydrolyzed whey and soyproteins; reduced lactose or lactose-free carbohydrateblends; and other added ingredients such as thickeners,soy fiber, and prebiotics. With the exception of thickenedformula, evidence for and against these modifications hasbeen addressed in previous sections of this review.

Thickened infant formulas are commonly used to helpmanage gastroesophageal reflux disease (GERD). A recentmeta-analysis reviewed 14 randomized, controlled trialsthat used different thickeners, including carob-bean gum,cornstarch, rice starch, cereal, and soy fiber. (19) Thickenedmilk was associated with an increased percentage of infantswho had no regurgitation and reduced number of episodesof vomiting, regurgitation, and signs of GERD such asirritability and crying. However, the clinical significance ofthis reduction is unclear because vomiting was reduced byonly 0.9 episodes/day. pH probe indices were not signifi-cantly improved, with the exception of a shorter duration ofthe longest episode of pH lower than 4. Thickened feedingsmay reduce nonacidic episodes of reflux, which may explainthe disparity between clinical observations and standard pHprobe measurements. Prethickened formulas are not supe-




rior to formulas thickened later with corn starch or ricecereal. Concerns have been raised about the safety of thick-ened milks, including malabsorption of macro- and micro-nutrients. The only adverse effects reported in the meta-analysis were increased coughing and diarrhea. Largerstudies are needed to address these safety concerns better.

Follow-up FormulasFollow-up formulas were developed to meet the nutri-tional needs of infants and young toddlers whose solidfood intake is not fully adequate to meet age-specificnutritional requirements. As compared with standardformulas, follow-up formulas are slightly higher in thecontent of protein and selected minerals. They are avail-able as modifications of both cow and soy milk-basedproducts. According to the AAP, follow-up formulas areconsidered nutritionally adequate when used in combi-nation with solid foods but offer no clear advantage overinfant formulas designed to meet 100% of nutritionalneeds throughout the first postnatal year. These productsmay offer a small cost advantage over standard infantformulas.

References1. Committee on the Evaluation of the Addition of IngredientsNew to Infant Formula. Comparing infant formulas with humanmilk. In: Infant Formula: Evaluating the Safety of New Ingredients.Washington, DC: The National Academies Press; 2004:41–54

2. Electronic Code of Federal Regulations; Title 21:107, Infant For-mulas. Washington, DC: Government Printing Office; 20103. Robbins ST, Beker LT, Pediatric Nutrition Practice Group.Infant Feedings: Guidelines for Preparation of Formula and Breast-milk in Health Care Facilities. Chicago, IL: American DieteticAssociation; 20044. Simmer K, Patole S, Rao SC. Long-chain polyunsaturated fattyacid supplementation in infants born at term. Cochrane DatabaseSyst. Rev. 2008;1:CD0003765. Schulzke SM, Patole SK, Simmer K. Long-chain polyun-saturated fatty acid supplementation in preterm infants. CochraneDatabase of Syst. Rev. 2008;2:CD0003756. Hoffman DR, Boettcher JA, Diersen-Schade DA. Toward opti-mizing vision and cognition in term infants by dietary docosahexa-enoic and arachidonic acid supplementation: a review of random-ized controlled trials. Prostaglandins Leuko Essent Fatty Acids.2009;81:151–1587. Osborn DA, Sinn JK. Probiotics in infants for prevention ofallergic disease and food hypersensitivity. Cochrane Database SystRev. 2007;4:CD0064758. Baldassarre ME, Laforgia N, Fanelli M, Laneve A, Grosso R,Lifschitz C. Lactobacillus GG improves recovery in infants withblood in the stools and presumptive allergic colitis comparedwith extensively hydrolyzed formula alone. J Pediatr. 2010;156:397–4019. Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis inpreterm neonates. Pediatrics. 2010;125:921–93010. Arslanoglu S, Moro GE, Schmitt J, Tandoi L, Rizzardi S,Boehm G. Early dietary intervention with a mixture of prebioticoligosaccharides reduces the incidence of allergic manifestationsand infections during the first two years of life. J Nutr. 2008;138:1091–109511. Henderson G, Fahey T, McGuire W. Nutrient-enriched for-mula versus standard term formula for preterm infants followinghospital discharge. Cochrane Database Syst Rev. 2007;4:CD00469612. Strom BL, Schinnar R, Ziegler EE, et al. Exposure to soy-basedformula in infancy and endocrinological and reproductive out-comes in young adulthood. JAMA. 2001;286:807–81413. ESPGHAN Committee on Nutrition, Agostoni C, Axelsson I,Goulet O, et al. Soy protein infant formulae and follow-on formu-lae: a commentary by the ESPGHAN Committee on Nutrition.J Pediatr Gastroenterol Nutr. 2006;42:352–36114. Allen UD, McLeod K, Wang EE. Cow’s milk versus soy-basedformula in mild and moderate diarrhea: a randomized, controlledtrial. Acta Paediatr. 1994;83:183–18715. von Berg A, Filipiak-Pittroff B, Kramer U, et al. Preventiveeffect of hydrolyzed infant formulas persists until age 6 years:long-term results from the German Infant Nutritional InterventionStudy (GINI). J Allergy Clin Immunol. 2008;121:1442–144716. Greer FR, Sicherer SH, Burks AW. Effects of early nutritionalinterventions on the development of atopic disease in infants andchildren: the role of maternal dietary restriction, breastfeeding,timing of introduction of complementary foods, and hydrolyzedformulas. Pediatrics. 2008;121:183–19117. Alexander DD, Cabana MD. Partially hydrolyzed 100% wheyprotein infant formula and reduced risk of atopic dermatitis: ameta-analysis. J Pediatr Gastroenterol Nutr. 2010;50:422–43018. Hill DJ, Murch SH, Rafferty K, Wallis P, Green CJ. Theefficacy of amino acid-based formulas in relieving the symptoms of

Summary• Based on strong research evidence, formulas

supplemented with DHA (between 0.3% and 0.5%of total fatty acids) and at least equal amounts ofARA are beneficial for visual and neurologicaldevelopment.

• Based on strong research evidence, formulassupplemented with probiotics reduce the incidenceof clinical eczema in high-risk infants (parent orsibling who has atopy).

• Based on strong research evidence, formulassupplemented with probiotics reduce the incidenceof NEC and all-cause mortality in VLBW infants.

• Based on some research evidence, formulassupplemented with prebiotics or probiotics decreasethe risk of infections during infancy.

• Based on strong research evidence, partially orextensively hydrolyzed formulas are effective inpreventing or delaying development of atopicdermatitis in high-risk infants.

• Based on strong research evidence, thickenedformulas reduce the number of episodes of vomiting,regurgitation, and signs of GERD such as irritabilityand crying.




cow’s milk allergy: a systematic review. Clin Exp Allergy. 2007;37:808–82219. Horvath A, Dziechciarz P, Szajewska H. The effect of

thickened-feed interventions on gastroesophageal reflux in infants:systematic review and meta-analysis of randomized, controlledtrials. Pediatrics. 2008;122;e1268–e1277

PIR QuizQuiz also available online at: http://pedsinreview.aappublications.org.

1. Which of the following statements about infant nutrition is true?

A. Human milk contains more casein than infant formulas.B. Infants who receive increased whey protein have been shown to grow better than those who receive

primarily casein.C. Iron is absorbed better from cow milk formulas than from human milk.D. Lactose-free formulas result in decreased absorption of calcium.E. There are no apparent negative effects from the addition of DHA and ARA to formulas.

2. Which of the following statements regarding prebiotics and probiotics is true?

A. Both have been proven to decrease the incidence of atopy.B. Prebiotics are live microorganisms.C. Probiotics are carbohydrates that stimulate bacterial growth.D. The use of probiotics has been shown to reduce the incidence of necrotizing enterocolitis.E. They should be routinely prescribed to exclusively breastfed infants.

3. The characteristic that is more typical of casein than of whey is that it:

A. Forms large curds on exposure to gastric acid.B. Is only found in trace amounts in cow milk.C. Is resistant to precipitation.D. Is the predominant protein in human milk.E. Undergoes more rapid gastric emptying.

4. Which infant feeding is best for the prevention of atopic disease?

A. Cow milk-based formula.B. Extremely hydrolyzed formula.C. Human milk.D. Partially hydrolyzed formula.E. Soy formula.

5. Which of the following supplements has been added to formulas for the longest period of time?

A. Arachidonic acid.B. Docosahexaenoic acid.C. Iron.D. Nucleotides.E. Prebiotics.

6. A young mother has brought her newborn to your clinic for his first visit. She has heard that soy formulasare better than milk-based formulas. For which of the following conditions is soy formula indicated?

A. Allergic enteropathy.B. Colic.C. Galactosemia.D. Gastroesophageal reflux.E. Prematurity.





J. Andres Martinez and Martha P. Ballew Infant Formulas

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Catherine Karr Addressing Environmental Contaminants in Pediatric Practice







Addressing Environmental Contaminants inPediatric PracticeCatherine Karr, MD, MS,

PhD*

Author Disclosure

Dr Karr has disclosed

no financial



commentary does not


of an unapproved/


commercial

product/device.


1. Recognize the basis for children’s susceptibility to environmental contaminants.2. Identify common pediatric environmental health problems.3. Take an environmental history to discern risks.4. Access reliable and useful resources on pediatric environmental health topics.5. Discuss environmental exposure reduction and prevention with patients and families.

IntroductionThe past decade has been marked by a rapid expansion of scientific inquiry, media reports,and public interest in the topic of environmental contaminants and child health. There arefew pediatric environmental health specialists, and most health conditions associated withcontaminants in food, water, the home environment, and the community present initiallyto the primary care clinician. Consequently, pediatricians are increasingly called on toanswer questions about environmental health.

Although standard medical education on these topics is limited and self-reportedconfidence among pediatric clinicians is low, extensive knowledge of toxicology is notrequired to suspect environmental health problems. This article reviews core concepts ofpediatric environmental health, commonly encountered pediatric environmental hazards,and the environmental history. Understanding these areas of knowledge should allow theclinician to develop a degree of suspicion that is the foundation for discerning andpreventing the potential adverse effects of environmental contaminants in child health.

Core Concepts in Pediatric Environmental HealthChildren’s susceptibility to environmental contaminants differs from that of adults.Pediatricians are familiar with the differences inherent in children across the life stages.Therapeutic interventions such as dosing based on weight or surface area is part of everydaypractice. Injury prevention advice for a newborn is unique from that given during anadolescent visit. Similar concepts apply to the potential vulnerability of children to adverseconsequences of exposure to environmental contaminants, reinforcing the perspective that“children are not small adults.”

Disruption of Normal Developmental ProcessesMaternal exposure in pregnancy to teratogenic drugs, chem-icals, and infections may result in structural or functionalanomalies. Major organ development occurs in the embry-onic period, just 18 to 60 days postconception, and thisperiod is a high-risk window for structural anomaly develop-ment, such as the common birth defects. Organ systemdevelopment, such as nervous, pulmonary, and immunesystem function and maturation, is a continuum that persiststhrough later gestation, postnatally, and even into adoles-cence. Endocrine system changes in later childhood andpubertal periods influence ongoing reproductive system de-velopment. Chemicals that alter these processes may com-promise the function of these organ systems. Chemicals that

*Assistant Professor of Pediatrics; Director, Pediatric Environmental Health Specialty Unit, University of Washington, Seattle,WA.

Abbreviations

ADHD: attention-deficit/hyperactivity disorderBLL: blood lead levelBPA: bisphenol ACDC: Centers for Disease Control and PreventionEPA: Environmental Protection AgencyFDA: Food and Drug AdministrationHUS: hemolytic-uremic syndromeNEEF: National Environmental Education FoundationPCB: polychlorinated biphenyl

Article poisoning



are associated with carcinogenesis are also of high con-cern in children because cells that undergo carcinogenictransformation in childhood have more time to developinto tumors.

One well-described example of functional develop-mental toxicity is lead exposure. The current publichealth threshold for action is a blood lead level (BLL)of 5 �g/dL for a pregnant woman and 10 �g/dL(0.48 �mol/L) for a child, but 25 �g/dL (1.21�mol/L) is the threshold for a nonoccupationally ex-posed adult. This discrepancy reflects the knowledge thatchildren are far more vulnerable than adults to leadneurotoxicity. Accumulating evidence of neurodevelop-mental effects in children who have BLLs below 10�g/dL (0.48 �mol/L) has led to an active debate thatthe action level for children should be even lower. (1)(2)

Opportunities for Receiving Higher DosesBecause metabolic rate is largely influenced by an organ-ism’s size, children eat more food, drink more water, andbreath more air than adults on a per-kilogram bodyweight basis. Consequently, if food supplies, water, or aircontain a contaminant, exposed children receive a higherdose.

Children have unique, life-stage-specific behaviorsthat also may influence their exposure to environmentalcontaminants. For example, the diet of young infants islimited to single foods (eg, human milk or infant for-mula). This unique feeding pattern partly explains thevulnerability of Chinese infants who suffered acute renalfailure due to melamine-contaminated infant formula inChina in 2008. Despite the detection of melamine inother foods and dairy products, infants whose sole sourceof nutrition was highly contaminated formula receiveddoses hundreds of times higher than that received byolder children or adults, who consumed a variety offoods. In older children eating idiosyncratic diets oflimited variety, if one of their primary foods is contami-nated, they are at risk for accumulating relatively highexposures. The recognition that children eat much largerquantities of certain fruits and vegetables has been welldocumented and is now among considerations for devel-opment of federally regulated pesticide residue toler-ances.

It is common for toddlers to explore nonfood itemsorally. The crawling child is in close contact with surfacesindoors and out, increasing his or her exposure to con-taminated dust, soil, or household products as well asitems such as lead paint. This situation likely explains theobservation that peak BLLs in children typically occur at

age 18 to 24 months, when mobility expands and oralexploratory behaviors are still present.

Commonly Identified Pediatric EnvironmentalHazardsChildren may encounter environmental contaminants indrinking water, food, inside their homes, or in the com-munity. There are more than 80,000 chemicals in com-merce and hundreds of human pathogens. The pediatricclinician should be familiar with the relatively few agentsdescribed in this article, which represent the more com-monly encountered environmental contaminants thathave well-described health consequences, as well asemerging contaminants undergoing enhanced scrutiny.Sources of these contaminants and information on test-ing and health-based regulatory levels are highlighted inTable 1. In some cases, where suspicion of an environ-mental factor is raised but remains unclear or is notstraightforward, consultation or referral to specialistswho have experience in pediatric environmental health isnecessary to determine appropriate next steps (Table 2).

Drinking Water ContaminantsCommunity or public drinking water supplies in theUnited States are regularly monitored under the SafeDrinking Water Act. Several regulatory standards areestablished for multiple contaminants determined by theUnited States Environmental Protection Agency (EPA).The Act also requires suppliers to provide an annualreport explaining the source of the water, how it istreated, a list of the chemicals for which it is tested, andthe highest concentration of each chemical found in thepast year. If a serious problem is identified, public watersuppliers are required to inform consumers quickly. All ofthe contaminants discussed in this article are monitoredin public drinking water supplies.

This oversight does not apply to the approximately15% to 20% of households in the United States thatobtain their water from private wells. With few excep-tions, private well owners bear the responsibility for theirown wells, although states provide guidance on con-struction, maintenance, and testing. A recent AmericanAcademy of Pediatrics Policy Statement describes thecommon concerns for groundwater and wells and in-cludes recommendations for inspection, testing, and re-mediation (Table 2).

Asking patients about their sources of drinking water,such as whether it is from a public source or private well,is a key component of the environmental history, dis-cussed in more detail in the “Environmental History”section of this article. The range of potential contami-

poisoning environmental contaminants



Table 1. Common Environmental Contaminants of Concern for Children inthe United States: Sources and Testing Information

Contamination Source Testing and Regulatory Information

Biological AgentsCryptosporidium Pathogen shed in human and animal

feces can enter water used fordrinking water supplies.

• Routine testing is conducted in all municipal watersupplies.

• Recommend water testing if private well andsuspected illness.

Escherichia coli0157

Human and animal fecal coliform foundin contaminated water, raw milk, rawor rare ground beef, unpasteurizedapple juice or cider, uncooked fruitsand vegetables.


• Conduct water testing if private well (see Table 2).

Chemical AgentsLead Lead service lines or corrosion of

plumbing systems leach lead intowater or natural deposits erode (rare).Lead-containing paint maycontaminate house dust or soil. Take-home lead dust from the workplace.

Lead in consumer products and otheremerging sources. (3)

• Routinely tested in municipal water supplies and in asample of residential taps (point of use).

• EPA residential water regulatory level >15 �g/L(0.72 �mol/L)

• Lead may be tested in paint, dust, soil (see Table 2).• Biomarker for suspected child exposure: BLL.• CDC Public Health Action Level: BLL >10 �g/dL

(0.48 �mol/L)Arsenic Natural sources in rock/sediment leach

into water supplies, foods.Wood preservatives or arsenical

pesticides.


• Consider if private well. EPA regulatory level: >10 �g/L.• Biomarker for suspected child exposure: consult pediatric

environmental health specialist or clinical toxicologist.Nitrate/nitrite Nitrate-containing fertilizers, sewage

and septic tanks, and decaying animalwaste.

• Routine testing is conducted in all municipal watersupplies. Conduct testing if private well.

• If >10 mg/L, do not use for formula mixing or foodpreparation for children <1 year of age.

• If >3 mg/L, indicates contamination.• Biomarker of effect: methemoglobin value

Trichloroethylene,tetrachloroethylene

Improper disposal to surface waters andgroundwater by industry commerceand individual consumers. Leachingfrom hazardous waste landfills intogroundwater.


• Consider if private well. EPA regulatory level for bothchemicals: >5 �g/L

Pesticide residues Conventional agriculture results inresidues in foods and potential watercontamination in agricultural areas.Residential use of pesticides maycontaminate indoor and outdoorsurfaces or air where children spendtime.

• Food residues tolerances are enforced by theDepartment of Health and Human Services/FDA formost foods (United States Department of Agriculturefor meat, poultry, egg products). Surveys of pesticideresidues in food typically reveal that most samples arebelow tolerance. Regulatory oversight for pesticideapplication is shared by EPA and United StatesDepartment of Agriculture.

• For biomarker for suspected child exposure: consultpediatric environmental health specialist.

Fish contaminants:mercury

Industrial air pollution accumulates instreams and oceans and is convertedto methylmercury. Fish absorb themethylmercury. Larger, long-lived fishaccumulate the highestconcentrations.

• Testing of fish and seafood jointly regulated by EPAand FDA.

• See Joint Federal Fish consumption guidelines andlocal fish advisories (Table 2).

• Biomarker for suspected methylmercury exposure:whole blood mercury value. Reference dose forpossible health effects: >5.8 �g/L.

BLL�blood lead level, CDC�Centers for Disease Control and Prevention, EPA�Environmental Protection Agency, FDA�Food and Drug Administration




Table 2. Core Topics for the Environmental History and RelatedAnticipatory Guidance and Resources

Environmental HistoryTopics Anticipatory Guidance Resources

General Help parents prioritize environmental risksand discuss reduction strategies andresources.

• CDC/EPA-sponsored Pediatric Environmental HealthSpecialty Unit (PEHSU) Network. Regionally basedexpertise for consultation and information at:www.pehsu.net.

• National Environmental Education Foundation.Pediatric Environmental History Initiative at:http://www.neefusa.org/health/PEHI/index.htm

• EPA. Children’s Environmental Health: OnlineResources for Health Care Providers at: http://yosemite.epa.gov/ochp/ochpWeb.nsf/content/hcp_resources.htm

Healthy Habits, HealthyProducts

Fish consumption Discuss federal and local fish advisories toavoid fish with high concentrations ofmercury or other contaminants.Nationally, avoid consumption ofswordfish, shark, king mackerel, andtilefish.

FDA & EPA Joint Federal Advisory for Fish.Consumption Advice: Joint Federal Advisory forMercury in Fish and links to local fish advisories at:http://www.epa.gov/fishadvisories/advice/factsheet.html

Tobacco Promote no tobacco use/exposure. CDC. Smoking and Tobacco Use Resources at: http://www.cdc.gov/tobacco/quit_smoking/how_to_quit/index.htm

Occupational exposure totoxic substances

Hobbies involving toxicsubstances (solvents,lead in pottery glazes,lead solder, lead dust atfiring range)

Address take-home pathway andrecommended strategies.

Focus on specific risks identified andstrategies to reduce contamination ofchild’s environments.

Under the Hazard Communications Standard of theOccupational Health and Safety Administration(OSHA), employers must maintain a Material SafetyData Sheet for each hazardous chemical used andmake it available to workers. Information availableat: http://www.osha.gov/dsg/hazcom/index.html

Organic versusconventional foods

Recommend washing of fresh produce withwater, peeling, scrubbing with a brush,and throwing away the outer leaves ofleafy vegetables. This action maysignificantly reduce the amount ofpesticides.

Information on produce that contains more versusless pesticide residues at Environmental WorkingGroup Shoppers Guide To Pesticides™ at: http://www.foodnews.org/fulllist.php

Plastics: Bisphenol A (BPA)and phthalates(emerging concern)

Avoid plastics with recycling codes 3, 6, or7 (may contain BPA or phthalates).Decrease leaching/degradation of thesechemicals by not microwaving plastics orwashing in dishwasher. Choose BPA- andphthalate-free baby bottles, toys, andother products for children.

PEHSU Fact sheets for health care providers andpatients at: www.pehsu.net

Healthy HomeWater damage, leaks,

floods, or mold odor/growth

Leaks and water damage should be cleanedup within 24 to 48 hours to reduce moldgrowth, and relative humidity should bekept at less than 60% (ideally 30% to50%).

EPA. Mold Resources at: http://www.epa.gov/mold/moldresources.html

Active or recentrenovation orremodeling in homebuilt before 1978

Assume lead paint, unless tests showotherwise. Special containmentmethods applied by trained individualsare needed for safe repair. Repair worknot applying these methods can escalateexposure.

EPA. Lead in Paint, Dust, and Soil Resources at:http://www.epa.gov/lead/pubs/leadinfo.htm

Home built before 1978,paint chipping/peeling/cracked

See above. EPA. Lead in Paint, Dust, and Soil Resources at:http://www.epa.gov/lead/pubs/leadinfo.htm

(Continued)




Table 2. Core Topics for the Environmental History and RelatedAnticipatory Guidance and Resources—continued

Environmental HistoryTopics Anticipatory Guidance Resources

Friable ceiling material ordegraded insulationaround pipes, boilers,and furnaces.

Asbestos materials that are crumbling,damaged, or friable should be removed andcleaned up by trained and licensed workers.Asbestos-containing materials that are ingood condition do not present a risk andshould be left alone.

EPA. Asbestos in Your Home at: http://www.epa.gov/asbestos/pubs/ashome.html

Carbon monoxide detector Use a carbon monoxide detector withUnderwriters Laboratory certification.

Do not use oven or charcoal to heat homeindoors. Do not idle car in attached garage.

EPA. Protect Your Family and Yourself From CarbonMonoxide Poisoning at: http://www.epa.gov/iaq/pubs/coftsht.html

Radon testing Test home if living spaces are below third floor.Fix home if radon level is 4 pCi/L or higher.

EPA. A Citizen’s Guide to Radon at: http://www.epa.gov/radon/pubs/citguide.html

Drinking water source(private or shared wellversus public)

If private well, recommend testing.If suspect lead-containing pipes or fixtures,

test home water.

Local health department for local contaminants ofconcern

American Academy of Pediatrics Committee onEnvironmental Health. Drinking water from privatewells and risk to children. Policy statement.Pediatrics. 2009;123:1599–1605 at: http://aappolicy.aappublications.org/cgi/reprint/pediatrics;123/6/1599.pdf

Annual report of drinking water quality in publicsystems at: http://water.epa.gov/drink/local/index.cfm

EPA. Is There Lead in My Drinking Water? at: http://www.epa.gov/ogwdw000/lead/leadfactsheet.html

Wood stove or fireplaceuse

Avoid use if child has asthma or respiratoryhealth conditions. If used as source ofheat, have a qualified technician inspectfuel-burning appliances and chimneysannually to ensure appropriate venting.

EPA Fact Sheet. Reducing Air Pollution FromResidential Wood Burning at: http://www.epa.gov/oaqps001/community/guide/wood_stoves_comm_info.pdf

EPA Best Burn Practices at: http://www.epa.gov/burnwise/bestburn.html

Pesticides in home or onlawn/garden, storage

Store in locked box/cabinet outside of thehome.

Use least toxic products/integrated pestmanagement to manage pests. Do not usebroadcast sprays.

National Pesticide Information Center. Pesticides inIndoor Air of Home at: http://npic.orst.edu/factsheets/air_gen.pdf

Karr C, Solomon GM, Brock-Utne A. Health effects ofcommon home, lawn and garden pesticides. Pediatr Clin

North Am. 2007;54:63–80Healthy CommunityNear highways or highly

trafficked roadwaysAvoid housing, play areas in close proximity. EPA and CDC. Asthma and Outdoor Air Pollution at:

http://www.epa.gov/airnow/asthma-flyer.pdfNear industrial site,

hazardous waste site,landfill

Avoid play near these areas.Identify specific exposures and information

from public health and regional EPA.

Local or state health or environmental department forsite-specific information

Near pesticide-treatedagricultural fields

Advise against play on treated soil/fields. Washhands and outdoor toys frequently. Avoid petcontact with treated fields. Remove shoeswhen entering home. Close windows, stayinside during spray application.

National Pesticide Information Center. Pesticides inIndoor Air of Home at: http://npic.orst.edu/factsheets/air_gen.pdf

Knowledge of air qualityindex

Discuss patient susceptibility to poor air qualitydays, particularly for children who haveasthma. Discuss air quality alerts.

EPA. Local air quality conditions and forecasts at:http://www.airnow.gov/

EPA and CDC. Asthma and Outdoor Air Pollution at:http://www.epa.gov/airnow/asthma-flyer.pdf

Copper chromated arsenic(CCA)-treated wood onplaygrounds/decks

Avoid use of arsenic-treated wood on decks/playgrounds. If present, wash hands aftercontact and apply sealant annually. Do notburn CCA-treated wood.

Consumer Product Safety Commission. Fact Sheet onCCA-Treated Wood Used in Playground Equipmentat: http://www.cpsc.gov/phth/ccafact.html

School and child care See topics above as applicable EPA. Healthy School Environment Resources at:http://cfpub.epa.gov/schools/Index.cfm

CDC�Centers for Disease Control and Prevention, EPA�Environmental Protection Agency




nants includes chemical, microbiologic, and physical (ra-diation) hazards. Among those most commonly foundand to which children may be particularly vulnerable areCryptosporidium, Escherichia coli, lead, arsenic, nitrates/nitrites, and trichloroethylene/perchloroethylene.

In some regions, source water comes in contact withbedrock, soil, or sediment that contains naturally occur-ring arsenic. Arsenic is a known human carcinogen, andemerging evidence suggests that it may also be a neuro-developmental toxicant. Local health departments canprovide information about regional experience with ar-senic (or other important contaminants) detected inregional well water.

Lead is one of the most important pediatric environ-mental health concerns, and it has been estimated that,on average, 20% of a child’s lead exposure is attributableto water. Although rarely found in source water, leadleaches into drinking water from lead-containing plumb-ing materials, lead pipes, or lead-containing solder orfixtures. This fact underlies practical recommendationsfor running the faucet for 2 minutes or until the waterturns cold to ensure that the water in a system is“flushed.” Removing water that has had long-standingcontact with plumbing components avoids consumptionof water that contains higher concentrations of leachedlead.

The two most common microbiologic water contam-inants of concern for children are E coli and Cryptospo-ridium. Cryptosporidium is a protozoan that causes se-vere gastroenteritis and dehydration among infants orimmunocompromised individuals. Due to its small size,standard water filtration may be inadequate, and boilingfor at least 1 minute (3 minutes above 6,500 feet [2,000m] of altitude) is required for decontamination. Thepresence of E coli in water is considered a marker ofrecent sewage or animal waste that may contain disease-causing organisms. Although most strains of E coli areharmless and commensal in healthy mammals, E coli0157:H7 produces a powerful toxin and can cause severehemorrhagic enterocolitis. Children younger than 5years of age are at risk of hemolytic-uremic syndrome(HUS) as a complication.

Nitrate is a common contaminant in well water fromsewage contamination or agricultural use of fertilizer.The presence of nitrate is an indication for testing forcoliforms; lack of coliforms indicates the source is fertil-izer. Young infants are at risk for developing methemo-globinemia, which results from conversion of nitrate tonitrite in their stomachs. With age, stomach acidity in-creases, reducing the numbers of nitrite-producing bac-

teria. After age 6 months, the conversion of nitrate tonitrite in the gut is greatly reduced.

Trichloroethylene and perchloroethylene are com-monly used industrial solvents. It has been estimated thatmore than 400,000 sites in the United States contain soiland ground water contaminated by chlorinated solvents.The primary health concern for low-level chronic expo-sure is increased cancer risk, and both compounds arealso liver and kidney toxicants. Reproductive and devel-opmental effects have not been assessed adequately.

Whether used when the usual source of drinkingwater is contaminated or as a convenience, bottled wateris an important source of drinking water for many people.The United States Food and Drug Administration(FDA) regulates bottled water products that are in inter-state commerce under the Federal Food, Drug, andCosmetic Act. The FDA’s bottled water standard-of-quality regulations generally mirror the EPA’s nationalprimary drinking water regulations under the Safe Drink-ing Water Act.

Bisphenol A (BPA) is an emerging contaminant ofconcern that may leach into water or food from plasticcontainer materials that contain the compound (eg,polycarbonate bottles, linings of cans). The Centers forDisease Control and Prevention (CDC) identified BPAin 93% of Americans sampled (age 6 years and older).This finding raises concern based on animal studies thathave linked prenatal exposure to this weakly estrogeniccompound with neurotoxicity, early puberty, mammarytumors, prostate hypertrophy, and increased adiposityand body weight. (4)

Food ContaminantsFood-borne infections pose an ongoing public healthchallenge. Most are associated with acute enterocolitisthat may be mild to severe. Among the most concerningfood-borne chemical contaminants for children are pes-ticide residues and other contaminants that concentratein some fish, including mercury and chlorinated hydro-carbons such as polychlorinated biphenyls (PCBs). Thehealth concerns are related to potential chronic healthconditions, such as compromised cognitive or behavioraldevelopment and cancer. In addition to BPA, phthalatesare contaminants of emerging concern that may leachfrom plastic packaging materials into food. Concern forthe endocrine-disrupting properties of these newerchemicals is largely derived from multiple animal studiesin which human health risks are inadequately character-ized. An abbreviated review of the evidence base anddocuments for guiding health care clinicians and families




is available from the Pediatric Environmental HealthSpecialty Unit Network (Table 2). (4)

The predominant foodborne pathogens are Salmo-nella, Campylobacter jejuni/coli, Toxoplasma gondii, andNorwalk virus. Listeria monocytogenes and E coli0157:H7 are of particular concern for newborns andchildren. E coli 0157:H7 produces shiga toxin, and theinfection often is accompanied by severe abdominalcramps, diarrhea (often bloody), and vomiting. If there isfever, the temperature is usually not very high(�38.5°C). Approximately 5% to 10% of those in whomE coli 0157:H7 infection is diagnosed develop HUS,with young children at higher risk for this severe compli-cation. Listeria poses a risk to the fetus and newborn ofan infected mother because pregnant woman have anapproximately 20-fold increased risk of listeriosis. Theinfection manifests with fever, muscle aches, and some-times gastrointestinal symptoms such as nausea or diar-rhea. With spread to the central nervous system, symp-toms such as headache, stiff neck, confusion, loss ofbalance, and seizures can occur.

The EPA, under the Food Quality Protection Act,determines pesticide residue “tolerances” for food. Pes-ticide chemicals comprise a broad group that has varyingtypes and levels of toxicity. Animal and epidemiologicstudies identify some agents that cause concern for im-paired neurologic development, immune system effects,endocrine disruption, and increased cancer risk. Currentpolicy is intended to consider children’s vulnerability,which is increasingly understood from studies of expo-sure and toxicologic science. For example, emergingepidemiologic studies suggest that children who havehad higher in utero exposure to organophosphate pesti-cides in both urban and agricultural settings are at in-creased risk for abnormal neurodevelopment. (5)

In addition to exposure from indoor pest control orproximity to agricultural production, children can beexposed to these chemicals on some fruits that are com-mon dietary staples. A study in which children wereplaced on an organic diet for 5 consecutive days revealeda rapid and dramatic decrease in their urinary excretion oforganophosphate metabolites. (6) Although this resultdemonstrates the opportunity to reduce exposure, theevidence base for the specific health implications fromlow-level dietary exposures is not established.

Fish is an important source of nutrients for childrenbut may contain contaminants that outweigh this bene-fit. In 2004, the EPA and the FDA issued targeted adviceconcerning mercury in fish for women who might be-come pregnant, women who are pregnant, nursingmothers, and young children. The recommendations

outline selecting and eating fish or shellfish that maintainthe benefits of fish eating while reducing exposure to theharmful effects of mercury (Table 2). (7)

In addition, state, tribal, and local governments mon-itor regional waterways and issue local fish advisorieswhen contaminant levels are unsafe, including postingadvisories at waterways. In addition to the well-established neurodevelopmental toxicant mercury, mostadvisories involve highly lipid-soluble organochlorinessuch as PCBs, chlordane, dioxins, and DDT. In addition,brominated flame retardant chemicals such as PBDE(polybrominated diphenyl ethers) are of increasing con-cern for having similar properties. These chemicals per-sist in the environment and can bioaccumulate as theymove up the aquatic food chain. In some cases, prepara-tion and cooking techniques to reduce consumption ofthe lipid-rich fish components can reduce levels of con-taminants significantly. The affected population is oftenunaware of local advisories and identifies clinicians as themost desirable source of information on such adviso-ries. (8)

The Healthy Indoor Environment: Home,School, Child Care

Children spend most of their time in indoor settings,particularly their homes (85% of time), followed byschool or child care. Although the importance of ad-dressing tobacco smoke or pet allergen is familiar to mostclinicians, the indoor environment is a primary source forseveral other hazardous exposures. Many fact sheets andresources for patients and health professionals on“healthy home” topics have been developed (Table 2).(9)(10). These resources include some focused particu-larly on children who have asthma, given the importanceof indoor triggers for this disease. (11)(12)

More than 90% of the 2 million poisonings reportedto national poison centers each year occur in the home.Household cleaning agents, pesticides that include insectkillers and lawn and garden products, and automotiveproducts may contain acutely toxic components thatpose a poisoning risk if not stored safely. Surveys suggestthat 75% of United States households used at least onepesticide product indoors during the past year. Theseand other chemical products may represent insidiousexposures that occur as daily low-level doses that accu-mulate from exposure to contaminated indoor air, dust,or surfaces and may increase chronic health risks such asasthma or cognitive and behavioral problems.

An Institute of Medicine review found sufficientevidence that leaks and water damage that give rise toexcess mold or other microbial growth may result in




upper respiratory tract (nasal, throat) symptoms,cough, wheezing, and asthma in sensitized individuals.Evidence was suggestive but more limited for lowerrespiratory tract illness and new-onset asthma. (13)Clues to excessive mold exposure include a known waterleak or damage, mildewy odor, and visible water damageor mold growth on household surfaces such as walls orceilings.

Improper remediation and repair of surfaces that con-tain lead-based paint or disruption of asbestos insulationon pipes, boilers, or furnaces may result in concerningindoor exposures. The use of asbestos-containing build-ing materials has declined substantially since the 1970s.Lead paint was also common before being banned in1978. Deteriorating lead-containing paint is the mostcommon cause of lead poisoning in young children.Low-level lead exposure is associated with a reducedintelligence quotient and behavioral problems, includingattention-deficit/hyperactivity disorder (ADHD). Leaddust can form when lead-based paint is dry scraped, drysanded, or heated. Dust also forms when painted surfacesbump or rub together. Lead dust accumulates in win-dowsills, on floors, and in soil.

Radon is estimated to cause approximately 21,000lung cancer deaths each year. Radon comes from theradioactive decay of naturally occurring uranium in soil,rock, and water that can infiltrate into homes throughcracks and other holes in the foundation. An estimated 1in 15 United States homes has elevated levels, and be-cause it is difficult to predict specific risk for individualhomes, all homes below the third floor should be tested,according to the EPA and Surgeon General of theUnited States.

Improper or inadequate ventilation that allowsbuildup of carbon monoxide from household combus-tion sources (eg, furnace, fireplace, attached garage) maycause health consequences ranging from mild nuisancesymptoms to fatalities. Clues to such exposures includean environmental history that identifies potential sourcesof carbon monoxide, clustering of symptoms amongindividuals who spend the most time in the affectedareas, and symptom worsening and relief associated withentering and leaving specific environments. Discussion ofa functional carbon monoxide detector should be a partof routine anticipatory guidance.

Exposures encountered by household members atwork may be brought home as dust or residues onclothing and shoes. It is important to become familiarwith the occupations of patients and household membersand ask about potential toxic exposures. If there arequestions about chemicals in the workplace, employers

are required by law to provide material safety data sheets,which offer information on the chemical constituents ofproducts that are used. Hygiene practices of removingwork clothes and shoes and showering before enteringthe home can reduce the “take-home” pathway.

Recently, concern for exposure to phthalates in softplastic consumer products such as toys and personal careproducts for children (lotions, shampoos, diaper creams)has emerged. These antiandrogenic chemicals canaffect androgen-sensitive tissues adversely duringspecific windows of development. Both animal and hu-man studies suggest that exposure may compromise nor-mal male reproductive system development and func-tion. Preliminary data also link these chemicals to allergicdisease. (4)

The Healthy Community and Outdoor SettingsCommunity characteristics, such as proximity topesticide-treated agricultural fields, high-traffic road-ways, industrial sites, or waste sites, should be assessedfor the areas where children spend time during outsideactivities. In addition, children may encounter exposuresat a workplace (eg, teen workers or young children offarm workers brought to fields). Community ozone con-centrations typically are maximal in the late afternoon, atime when children participate in outdoor play and sportsactivities. The Air Quality Index can provide local infor-mation on daily air quality and help guide decisions onoutdoor activities. Playground or decking equipmentmade with copper chromated arsenic-treated wood mayincrease a child’s exposure to arsenic. These factors maycompromise access or participation in outside play and itshealthful benefits. Such considerations are an importanttopic of an emerging multidisciplinary subject termed“the built environment.”

Some ambient pollutants permeate readily into theindoor environment, such as traffic-derived fine partic-ulate air pollution. Traffic-related pollutant concentra-tions are much higher within 150 to 300 m of majorroadways and highways and drop off rapidly withincreasing distance. Such knowledge underlies policiesthat consider proximity to large roadways in schoolsiting decisions or instigate “anti-idling” campaigns atschools.

In studies of farm worker children, those living closerto treated fields showed higher levels of exposure topesticides, based on urinary metabolites measurements,than their peers who lived further away (�200 m). (14)Also, concentrations of pesticides in household dustexceeded concentrations in soil, demonstrating the“take-home pathway.” Pets and people can track pesti-




cide residues from treated fields or lawns indoors andcontaminate surfaces where children crawl and play.Knowledge of environmental hazards in the communitycan help in the creation of prevention messages andcommunity improvements that promote healthier resi-dences, schools, and play areas.

The Environmental HistoryOne of the most important tools in discerning the im-portance of environmental hazards for health conse-quences or to prioritize anticipatory guidance is theenvironmental history. Questions about the environ-ment are a natural component of the routine clinicalhistory. The environmental history focuses on under-standing the quality and extent of hazards in environ-ments where a child spends time and on identifyingsuspicious patterns or aspects that prompt further evalu-ation.

In routine child health supervision, taking an environ-mental history can help identify potential risks in theenvironments of children and the need for focused antic-ipatory guidance on reducing exposures. Asking aboutgenerally recognized exposures of concern (eg, tobaccosmoke, lead, pesticides, radon, occupation) as well as

more locally relevant factors (eg,toxic waste sites, wood smoke,sportfishing, contaminants in wellwater) may direct guidance on pre-vention measures or local or na-tional resources that may help inreducing the hazards identified.Table 2 summarizes the primarytopics and provides resources formore detailed information on spe-cific topics and resources.

A basic environmental history hasbeen developed by the National En-vironmental Education Foundation(NEEF) as part of their PediatricEnvironmental Health History Ini-tiative (Table 3). This brief set ofquestions, designed to be adminis-tered by the clinician in less than5 minutes, captures the most com-mon environmental exposures inchildren. The NEEF Pediatric Envi-ronmental Health Initiative pro-vides additional background infor-mation on issues included in thisbrief history as well as a more de-tailed environmental history and

recommendations that clinicians can make to families tocontrol or eliminate the hazards identified.

In the context of illness or disease, an environmentalhistory helps discern the link between environmentalfactors (activities/place/time/substances) and the na-ture, onset, worsening, and improvement of symptoms.Such information can help elevate or reduce suspicionregarding a role for particular environmental hazards andhelp determine the need for further evaluation throughspecific aspects of physical examination or laboratorytesting. Consultation with a pediatric environmentalhealth specialist may be appropriate in some situations(Table 2).

Emerging Knowledge and RiskCommunicationFortunately, frank acute poisonings from lead and pesti-cides are rare because public health and regulatory ac-tions have reduced exposures in United States children.Concern now reflects information gathered from emerg-ing basic, applied, and community-based research ef-forts. These studies link chronic, routine, low-levelexposures to environmental factors with many of themajor current chronic pediatric morbidities, such as

Table 3. Brief Screening Environmental HistoryForm Example*Where does your child live and spend most of his/her time?What are the age, condition, and location of your home?Does anyone in the family smoke? Yes No Not sureDo you have a carbon monoxide detector? Yes No Not sureDo you have any indoor furry pets? Yes No Not sureWhat type of heating/air system does your home have?

Radiator Forced air Gas stove Wood stove OtherWhat is the source of your drinking water?

Well water City water Bottled waterIs your child protected from excessive sun exposure? Yes No Not sureIs your child exposed to any toxic chemicals of which you are aware?

Yes No Not sureWhat are the occupations of all adults in the household?Have you tested your home for radon? Yes No Not sureDoes your child watch TV or use a computer or video game system more than

2 hours a day? Yes No Not sureHow many times a week does your child have unstructured, free play outside for

at least 30 minutes?Do you have any other questions or concerns about your child’s home

environment or symptoms that may be a result of his or herenvironment?

*From the National Environmental Education Foundation Pediatric Environmental History Initiative.Form available as pdf with supplementary materials at www.neefusa.org/health/PEHI/.




asthma, obesity, ADHD, learning disabilities, birth de-fects, cancer, and low birthweight or preterm birth.Public interest in children’s environmental health ishigh, and media attention raises questions and concerns.Interest and knowledge should expand with ongoingresearch commitments to topics in children’s environ-mental health, including the National Children’sStudy. This landmark project of the National Institutesof Health, CDC, and EPA plans to follow 100,000mothers and their children from birth to adulthood,exploring the role of environmental exposures in thecontext of other influences on child health, such as genes,the psychosocial context, and gene-environment interac-tions.

Pediatricians are a trusted source of reliable informa-tion. They play an important role in providing reassur-ance, allaying fears and anxiety, and avoiding misplacedresources. They are practiced in making use ofimperfect, evolving information and promoting precau-tion. Knowing the potential vulnerabilities of children,major exposures of concern, environmental history tak-ing, and evidence-based resources, pediatricians areuniquely poised to identify established and emerging

environmental health threats to children and provideimportant anticipatory guidance for reducing risks intheir patients and their communities.

References1. Gilbert SG, Weiss B. A rationale for lowering the blood leadaction level from 10 to 2 �g/dL. Neurotoxicol. 2006;27:693–7012. Binns HJ, Campbell C, Brown MJ, for the Advisory Committeeon Childhood Lead Poisoning Prevention. Interpreting and man-aging blood lead levels of less than 10 �g/dL in children andreducing childhood exposure to lead: recommendations of theCenters for Disease Control and Prevention Advisory Committeeon Childhood Lead Poisoning Prevention. Pediatrics. 2007;120:e1285–e12983. Karr CJ. Reducing childhood lead exposure: translating newunderstanding into clinic-based practice. Pediatr Ann. 2008;37:748–7564. Pediatric Environmental Health Specialty Unit. Health CareProvider Guide to Safer Plastics: Phthalates and Bisphenol A.Accessed February 2011 at: www.pehsu.net5. Rosas LG, Eskenazi B. Pesticides and child neurodevelopment.Curr Opin Pediatr. 2008;20:191–1976. Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. Organicdiets significantly lower children’s dietary exposure to organophos-phorus pesticides. Environ Health Perspect. 2006;114:260–2637. United States Environmental Protection Agency/Food andDrug Administration. Consumption Advice: Joint Federal Advisoryfor Mercury in Fish. Backgrounder for the 2004 FDA/EPA ConsumerAdvisory: What You Need To Now About Mercury in Fish andShellfish. (Advice for women who might become pregnant, womenwho are pregnant, nursing mothers, young children.) AccessedFebruary 2011 at: http://www.epa.gov/fishadvisories/advice/factsheet.html8. Kuntz SW, Hill WG, Linkenbach JW, Lande G, Larsson L.Methylmercury risk and awareness among American Indian womenof childbearing age living on an inland northwest Indian reserva-tion. Environ Res. 2009;109:753–7599. United States Environmental Protection Agency. HealthyHome. (20-page consumer booklet.) Accessed January 2011 at:http://www.epa.gov/ne/healthyhomes/pdfs/healthyhomes.pdf10. Centers for Disease Control and Prevention. Healthy Homes(Web-based consumer information on multiple topics.) AccessedFebruary 2011 at: http://www.cdc.gov/healthyhomes/11. National Environmental Education Foundation. PediatricAsthma Initiative. (Evidence-based guidelines for environmentalmanagement of asthma and environmental history form forchildren who have asthma.) Accessed February 2011 at: http://www.neefusa.org/health/asthma/index.htm12. United States Environmental Protection Agency. EPA’sAsthma Program. (Information for patients and health care profes-sionals on asthma and environmental triggers.) Accessed February2011 at: http://www.epa.gov/asthma/programs.html13. Committee on Damp Indoor Spaces and Health. Board onHealth Promotion and Disease Prevention. Institute of Medicine.Damp Indoor Spaces and Health. Washington, DC: National Acad-emies Press; 200414. Loewenherz C, Fenske RA, Simcox NJ, Bellamy G, Kalman D.Biological monitoring of organophosphorus pesticide exposureamong children of agricultural workers in central Washington State.Environ Healt Perspect. 1997;105:1344–1353

Summary• Pediatricians are a trusted, desired, and important

source of information on environmental healthtopics. (8)(15)

• It is well established that children are morevulnerable to environmental contaminants due totheir rapid and ongoing growth and developmentand potential for higher exposures based onbehavioral and physiologic differences. (16)

• Evidence and consensus highlight the importance ofthe environmental history in identifying andreducing children’s exposure to hazardouscontaminants. (11)(16)

• There is sufficient evidence that lead exposure iscommon among United States children and thatconcentrations below the current action level (BLL>10 �g/dL [ 0.48 �mol/L]) are associated withadverse effects on neurodevelopment and behavior.(1)(2)(3)

• A joint federal advisory from the FDA and the EPArecommends reducing exposure to mercury byhighlighting the importance of selecting fish thatcontain lower concentrations of methylmercury. (7)

• Multiple studies identify risks in the indoorenvironment that reflect housing quality, choice ofbuilding sites, and exposures that include lead frompaint or water, asbestos, radon, particulate matter,mold, pesticide use patterns, and carbon monoxide.(2)(3)(11)(13)(16)




15. Galvez M, Peters R, Graber N, Forman J. Effective risk com-munication in children’s environmental health: lessons learnedfrom 9/11. Pediatr Clin North Am. 2007;54:33–46

16. American Academy of Pediatrics Committee on Environmen-tal Health. Handbook on Pediatric Environmental Health. 2nd ed.Elk Grove Village, IL: American Academy of Pediatrics; 2003

PIR QuizQuiz also available online at: http://pedsinreview.aappublications.org.

7. Which of the following best describes the reason why young infants are at risk for developingmethemoglobinemia from agricultural nitrate contamination of water?

A. Increased nitrates in the gut cause severe constipation in young infants.B. In infants, lower stomach acidity results in more nitrite-producing bacteria.C. Iron in infant formula protects against nitrate toxicity.D. Significantly more absorption of nitrates occurs through the skin of young infants.E. Younger children have a higher exposure to contaminated water.

8. What major complication of E coli 0157:H7 infection occurs in approximately 5% to 10% of affectedchildren?

A. Bacterial meningitis.B. Erythema multiforme major.C. Hemolytic-uremic syndrome.D. Osteomyelitis.E. Seizures.

9. Which of the following statements about organophosphate pesticide exposure in children is true?

A. Animal and epidemiologic studies have identified only birth defects as an area of concern.B. A normal diet poses no risk for exposure to these chemicals.C. Children placed on organic diets show marked decreases in urinary excretion of organophosphate

metabolites.D. Exposure results from proximity to agricultural production but not from indoor pest control.E. In utero exposure produces no discernible effect on the developing fetus.

10. Which of the following is true about leaks and water damage in the home?

A. Strong evidence suggests that excessive mold growth can lead to pneumonia.B. This issue has not been studied by the Institute of Medicine.C. Water damage in the home has no effect on the health of children.D. Water damage that gives rise to mold can result in upper respiratory tract symptoms.E. Water stains on walls do not correlate with excessive mold growth.

11. What are the potential health risks to children from exposure to phthalates?

A. Their antiandrogenic effect may compromise development of the male reproductive system.B. They are linked to poor enamel deposition in developing teeth.C. They have a subtle adverse effect on linear growth.D. They may lead to interstitial nephritis.E. They pose no risk to children.





Catherine Karr Addressing Environmental Contaminants in Pediatric Practice




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Hilary McClafferty Complementary, Holistic, and Integrative Medicine: Mind-Body Medicine







Complementary, Holistic, and IntegrativeMedicine: Mind-Body MedicineHilary McClafferty, MD*

Author Disclosure

Dr McClafferty has

disclosed no financial



commentary does not


of an unapproved/


commercial

product/device.


1. Define mind-body medicine.2. Review evidence-based pediatric mind-body therapies and identify medical conditions

where these therapies have proven beneficial.3. Encourage pediatricians to consider integrating mind-body medicine into practice.

What is Mind-Body Medicine?Mind-body medicine might be defined as the deliberate harnessing of positive thought andemotion and using them for the purpose of enhancing health.

It has been well established that poorly managed pain and stress can activate theinflammatory cascade, depress immune function, and increase the risk of chronic depres-sion, anxiety disorders, and posttraumatic stress disorder. (1)(2)(3)(4)(5) The field ofmind-body medicine capitalizes on the inverse association that positive emotions and useof self-regulation skills can trigger beneficial physiologic reactions, including enhancedimmunity, decreased inflammation, and improved mental health. (6)

A wide variety of mind-body techniques can be used to achieve a state of calm, positivefocus. The modalities that have the best supporting evidence of efficacy in pediatricscurrently are biofeedback, hypnosis, guided imagery, mindfulness, music therapy, andyoga. (7)

Challenges in Mind-Body MedicineNew fields of medicine present unique challenges, and mind-body medicine is no excep-tion. This broad, wide-ranging topic rarely is addressed in medical education. Mastery ofnew skills is required, treatment is highly individualized, insurance reimbursement mayvary, colleagues may be skeptical, and pressure to prescribe medication rather than suggestan unfamiliar therapy may deter physicians from recommending it.

Why is Mind-Body Medicine Important?Mind-body therapies encourage children to become active participants in their care and arelow risk and cost-effective. They can be used as evidence-based alternatives to conventionaltherapies if conventional treatments have undesirable adverse effects, as adjunct supportivetherapies, or as primary treatments in cases where they offer superior efficacy. Mind-bodytherapies can provide powerful, noninvasive techniques to reduce fear, stress, and pain,while building confidence, self-control, and resiliency. Mind-body therapies have beenused successfully in the treatment of children experiencing acute or chronic pain, anxietyand stress, dysfunctional voiding, constipation and encopresis, sleep disorders, habitdisorders, attention-deficit/hyperactivity disorder (ADHD), asthma, obesity, diabetes,inflammatory bowel disease, irritable bowel syndrome, and cancer. (7)

The Importance of Language in Mind-Body MedicineWord choice can inadvertently increase fear and anxiety or convey calm, confidentencouragement. (8) Thoughtful language use is important in mind-body treatments. Infact, skillful use of language in educating parents about mind-body modalities caninfluence treatment outcomes. Studies show that parents, children, and clinicians all mayhave preexisting expectations about which mind-body modalities are most likely to be

*Assistant Director of the Fellowship, Arizona Center for Integrative Medicine, University of Arizona Health Sciences Center,Phoenix, AZ.

Article complementary medicine



effective. It is important to be able to offer more than onechoice of therapy if the first suggestion does not meetexpectations. (9)

Stress Diagnosis in ChildrenIdeally, stress diagnosis and management would be in-cluded in routine anticipatory guidance, and childrenwould learn self-regulatory skills from a very early age.Nonjudgmental questions about stressors can provide anopening to discuss the impact of stress on children’shealth as well as an opportunity to educate families aboutthe power of the mind-body connection.

In reality, however, stress is not discussed routinely inhealth supervision visits, and even experienced practitio-ners can find it challenging to diagnose pediatric stressaccurately, which often manifests as vague or confusingphysical or behavioral symptoms. Familiarity with com-mon stress symptoms by age group and an elevateddegree of suspicion can be useful in helping to avoidexcessive medical testing. (10) The possibility of stressorsis important to consider in any pediatric evaluation whensymptoms do not make sense after a thorough historyand physical examination are complete.

In some cultures, succumbing to stress implies weak-ness, making it harder to initiate a discussion on thetopic. Reluctance to discuss stressors can also be found incases of bullying, a prevalent, serious, and often hiddencause of childhood stress. Mind-body therapies havebeen shown to be helpful in certain patterns of bullyingand should be considered in the approach to this com-plex and challenging problem. (11)(12)(13)(14)(15)

Selected Mind-Body Modalities: BestEvidence in Children

BiofeedbackBiofeedback can be defined as the systematic process ofincreasing awareness and control over various physicalfunctions by using instruments that provide immediatefeedback to the individual. Biofeedback is painless, andchild-friendly tools are available that use games andappealing graphics to help children learn self-regulationskills in an enjoyable process.

A recent survey of 43 accredited academic pediatricanesthesia centers in the United States indicated thatbiofeedback was the most frequently chosen therapy forpain management in the 38 centers offering complemen-tary or integrative therapies. (16)

The types of biofeedback used most commonly inchildren are electromyography for reduction of muscletension, thermal biofeedback to promote vasodilation,heart rate monitoring in regulation of heart rate variabil-

ity, and neurofeedback using electroencephalography forregulation of slow cortical potentials.

Although biofeedback has the potential for use in arange of conditions, some of the strongest evidencesupporting this therapy is in children who have migraineheadaches, (17)(18)(19)(20) tension headaches, (21)chronic pain, (22) dysfunctional voiding, (23)(24) con-stipation, and recurrent abdominal pain. (25) Newerresearch provides evidence of benefit with impulsivity inADHD. (26)(27)

HypnosisClinical hypnosis is an especially powerful mind-bodytherapy for children and has been described by Olnessand Gardner as “an altered state of consciousness, usuallyinvolving relaxation, in which a person develops height-ened concentration on a particular idea or image for thepurpose of maximizing potential in one or more areas.”(28) An excellent hypnosis resource for the interestedpractitioner is Olness and Kohen’s definitive text Hypno-sis and Hypnotherapy with Children. (29)

A hypnosis session has six classic stages: introduction,induction, deepening, therapeutic suggestions, awaken-ing, and debriefing. Each session is unique to the indi-vidual patient. (30) Children as young as 2 to 3 years ofage have been successfully taught self-hypnosis, whichoften involves guided imagery and is facilitated by theiropenness to storytelling, imagination, and fantasy.

A wealth of research supports the use of hypnosis inpediatrics for a wide variety of conditions, includingacute and chronic pain, migraine, habit disorders, anxi-ety, asthma, nausea and vomiting associated with cancertreatment, insomnia, hypertension, and anxiety as well asin preparation for surgery and other invasive procedures,such as voiding cystourethrography and bone marrowaspiration. (31)(32)(33)(34)(35)(36)(37)(38)

A 2005 survey of 43 pediatric anesthesia fellowshipprograms in the United States indicated that 44% of the38 responding institutions offered hypnosis as a treat-ment therapy for pain. (16) Hypnosis has also been usedto reinforce health suggestions and reduce anxiety in theroutine pediatric office visit. (39) It is important to workwith fully certified hypnosis practitioners and considerconsultation with a mental health specialist for any childwho has a history of abuse or preexisting mental illness.

Music TherapyResearch exploring the science of music therapy is reveal-ing the amazingly complex nature of the positive effect ofmusic on the neurohormonal and immune systems andits links to pain perception and emotional processing.

complementary medicine mind-body medicine



(40)(41) The American Music Therapy Association de-fines music therapy as the clinical and evidence-based useof music interventions to accomplish individualized goalswithin a therapeutic relationship by a credentialed pro-fessional who has completed a music therapy programdegree.

A growing body of research in infants and childrendemonstrates the efficacy of music therapy for reductionof pain and anxiety in a variety of pediatric settings,including neonatal intensive care units, procedurerooms, emergency department waiting rooms, and in theperioperative setting. (42)(43)(44)(45)(46)(47)(48)Music therapy can be used alone or combined with othermind body therapies.

MindfulnessMindfulness is the cultivation of awareness in the presentmoment, regardless of ongoing events, and can beadapted for use in children of a variety of ages who havea wide range of conditions. Mindfulness is often linked tobreath work or body scanning exercises. Mindfulnesstraining has been shown to improve coping capacity, aidin chronic pain management, and reduce anxiety anddepression. (6)(49)(50)(51)(52)(53)(54) Training inmindfulness was offered by 21% of academic pediatricanesthesia pain management services in the United Statessurveyed for provision of complementary and alternativemedicine programs at their institutions. (16) Innovativeresearch exploring the potential of mindfulness trainingon brain plasticity and neuronal allocation is ongoing.

YogaThe word “yoga” comes from the Sanskrit root yuj,which means “to join” or “to yoke”, and the practice isbased on the concept of bringing together mind, body,and spirit. It is an ancient combination of breathingexercises and postures used to increase mindfulness, im-prove fitness and flexibility, and reduce stress. Yoga is

versatile and can be adapted to many skill levels and agegroups in both inpatient and outpatient settings. Studiesshow yoga’s beneficial effects in children who havechronic pain, (55) asthma, (56)(57) irritable bowel syn-drome, (58) and ADHD symptoms. (59)

Progressive Muscle RelaxationProgressive muscle relaxation, a systematic tensing andrelaxing of muscle groups, is easy for children to masterand is often used with other mind-body therapies. Al-though few studies have evaluated it as an isolated treat-ment, progressive muscle relaxation has been used suc-cessfully with other therapies in the treatment of chronicpain, (36) asthma, depression, (60) migraine headache,anxiety, and juvenile arthritis. (61)

Note: To view the references for this article as well asonline resources, visit http://pedsinreview.aappublications.org and click on the article title.

Summary• Mind-body therapies can add an important

dimension to pediatric care and allow practitionersto offer gentle, effective, drug-free, and cost-effective treatment options.

• Children of all ages can derive benefit from mind-body therapies, which are used in a both inpatientand outpatient settings.

• Some of the best-studied populations for mind-bodyinterventions are children who have chronicconditions, such as pain, anxiety, arthritis, migraineor tension headache, recurrent abdominal pain,dysfunctional voiding, and cancer.

• Use of mind-body skills to mitigate caregiver stressis an interesting area of emerging research that mayhave important pediatric implications in the future.

• Many educational and training programs areavailable in the field of mind-body medicine, someof which are included in the resources section.

complementary medicine mind-body medicine




Hilary McClafferty Complementary, Holistic, and Integrative Medicine: Mind-Body Medicine



Supplementary Material

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IssuesBehavioral and Mental Health ntary_holistic_integrative

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Charles C. Camosy Neonatal ICU

Ethics for the Pediatrician: Just Distribution of Health-care Resources and the







Author Disclosure

Dr Camosy has disclosed no financial

relationships relevant to this article.

This commentary does not contain a

discussion of an unapproved/

investigative use of a commercial

product/device.

Just Distribution of Health-careResources and the Neonatal ICUCharles C. Camosy, PhD*


1. Explore some implications of the finite nature of human beings (as exem-plified by sickness and mortality) and of resources, both for medicine ingeneral and the neonatal intensive care unit (NICU) in particular.

2. Explain the refusal to discriminate on the basis of disability for even thesickest members of the NICU population.

3. Show how taking cost into consideration, at both macro and clinical levels,does not violate human dignity.

4. Respond to arguments that NICU care is among the most cost-effective inmedicine.

5. Suggest future strategies for combating a culture of overtreatment in theNICU.

IntroductionThe debate over health-care reformin the United States brought discus-sions of “comprehensive health ben-efits” and “cost containment mea-sures” to the dinner tables of averageAmericans. However, the AmericanAcademy of Pediatrics (AAP) facedthis issue in 1998: (1)

“The American Academy of Pedi-atrics (AAP) advocates universal andinsured financial access to qualityhealth care for all newborns, infants,children, adolescents, young adultsthrough age 21 years, and pregnantwomen . . . Such insurance shouldprovide a comprehensive benefitpackage that should include, but notbe limited to, pregnancy related ser-vices, preventive care services recom-mended by the AAP, acute andchronic care services, and emergencycare services.”

In this same statement, the AAPacknowledged that:

“Cost containment is essential but

must not impair the quality of caredelivered. Physicians must play animportant role in establishing princi-ples of evidence-based medicine, val-idating the measurements used, andensuring quality in any cost-containment process. Responsibilityfor controlling costs should be acombined responsibility of employ-ers, families, clinicians, payers, andadministrators of health care plans.”

Two additional points could ben-efit the the approach outlined by theAAP. First, especially when discuss-ing health-care financing, the disci-pline of pediatrics should not imag-ine itself in an isolated vacuum,somehow disconnected from otherareas of medicine and concerns abouthuman flourishing more generally.Second, although some cost contain-ment measures do not hurt quality ofcare (and may even help it), we mustnevertheless face the tragic fact ofvirtually unlimited health needs (weare all going to die some day, afterall) competing with limited health-care resources. We simply cannotprovide as much of the best health

*Department of Theology, Fordham University,Bronx, NY.

ethics for the pediatrician



care we wish to every patient whoneeds it. Rationing is part of the hu-man condition. Although every as-pect of medicine should take this factmore seriously, this article briefly ex-plores the issues in the context ofneonatology (see Camosy (2) for amore detailed argument).

The Moral Status ofNeonatesFor many, rationing conjures up im-ages of “death panels” that decidewhich lives are fit to live and whichare not. This concern is not withoutreason. Some NICUs that would liketo limit care explicitly claim that notevery member of the population has alife worth living, and some, such asPrinceton’s Peter Singer, even arguethat they are nonpersons. (3) Theargument is set forth that the limitedhealth-care resources should bespent only on persons who have livesworth living. The AAP, however,could not accept this argument. Theorganization’s past refusal to supporttaking organs from anencephalic in-fants is evidence of a belief that eventhe most brain-damaged infant is aperson who has rights. Further, AAPpolicies specifically forbid discrimina-tion on the basis of disability, (4)which rules out claims that certaindisabilities constitute a life that is notworth living.

Some claim that rationing is offthe table once we admit that all pa-tients, even the very sickest NICUinfants, have full moral status. Ra-tioning would violate the dignity andright to equal care and respect that allpersons deserve. However, althoughall patients should be treated equally,I argue that it is precisely this rightthat necessitates rationing of care.For although a person’s dignity is notviolated by refusing him or her adisproportionately large share ofcommunity resources, giving some-one just such a share does violate

the right to equal treatment of thoseleft with a disproportionately smallshare.

Taking Cost intoConsiderationExplicit cost consideration is obviousin the context of federal or state gov-ernments working with fixed bud-gets to cover their Medicare/Medicaid populations. Indeed, theDepartment of Health and HumanServices decides not only what will becovered, but in issuing the Center forMedicare & Medicaid Services(CMS) rate, it decides how much willbe covered. Private insurance compa-nies also use the CMS number as abaseline to determine their own re-imbursement rates and until recently,used preexisting conditions, abilityto pay, and lifetime limits to rationcare themselves.

However, a person could acceptthis argument and still object to cli-nicians being forced to considerthese facts. Should not the clinician’sonly concern be the patient in frontof him or her? Edmund Pellegrino (5)says:

“The physician is then bound by acovenant of trust which must not becompromised by other roles of, forexample, the physician as gatekeeper,entrepreneur, guardian of social re-sources, or by the economic pres-sures to undertreat . . . The welfareof the patient, jointly determined be-tween physician and patient or pa-tient’s morally valid surrogate mustcontinue to be the end of medicine inthe clinical encounter and first in theorder of priorities for the physician’srole.”

Although this is a good rule ofthumb, an absolute prohibition playsinto the anthropologic myth that hu-mans can act in total isolation fromeach other. Is a triage medic actingagainst the “end of medicine” whenputting the care of one very seriously

ill patient ahead of another who isless seriously ill? What about a familypractice physician who refuses to pre-scribe antibiotics that would benefit apatient but might harm society atlarge by helping to create drug-resistant diseases? Insofar as cliniciansmake medical decisions that have ef-fects beyond the isolated physician-patient relationship, they should notbe prohibited absolutely from takinginto account external considerations.

Why Pick on the NICU?Even if accepting the argument tothis point, why take the approach ofthe United Kingdom’s NuffieldCouncil on Bioethics? (6)

“There is now much broader pub-lic awareness of the need for difficultchoices to be made by the providersof national healthcare. . . . Conten-tiously, this has caused questioningof whether funds spent on resuscitat-ing or prolonging the life of babieswhere the prognosis is very poor arespent appropriately.”

Should we not instead follow thelead of John Lantos and WilliamMeadow, (7) who claim that neona-tal treatment and care is cost-effective and that rationing should bedirected elsewhere? After all, if a babysurvives the NICU, then any addedyears of life are, on the average, muchgreater than those associated withthe care offered by other types ofmedicine. Further, very few bed daysare given to nonsurvivors becausemost NICU patients who die do soquickly. Thus, NICU care looks likea good investment of health-caredollars.

Although the de facto rationingsituation in which clinicians findthemselves certainly applies to otherareas of medicine, this perspectivedoes not give a reason to spend re-sources disproportionately in theNICU. In response to Lantos andMeadow, it must be pointed out that




Medicaid and other community re-sources are almost never limited towhat is spent in the NICU. As theNuffield Council says, “Economicstudies of premature birth and lowbirthweight have tended to overlookthe costs, for example, of day-careservices and respite care, as well asthose borne by the local authorities,voluntary organizations and by fam-ilies as a result of modifications oftheir everyday activities.” (6) It isnotoriously difficult to estimate thecosts of these treatments and servicesover time, but the Nuffield Councilcited an EPICure study that lookedat spending (in pounds) over 12months at age 6, comparing the costfor extremely low-birthweight chil-dren with that of a control group ofterm infants (Table). These numbersare even more striking when consid-ered in total over the entire life of thepatient. Consider the case of “BabySidney,” who was the subject of theimportant HCA v. Miller case inHouston, Texas, in 1998. Sidney’sparents decided that they would notresuscitate her after she was born, butthe hospital did so anyway. Afterwinning a lawsuit, the jury awarded“reasonable expenses of necessarymedical which, in reasonable proba-bility, SIDNEY MILLER will incurin the future” at a whopping

$28,500,000. Claims about the cost-effectiveness of NICU care mustconsider long-term follow-up care.Although extremely low-birthweightinfants are rare within the context oftotal live births, it is unclear how thisshould be considered when decidingwhether to incorporate cost into thetreatment of such patients. Whetherwe should spend $30 million of com-munity money on patients such asSidney, for example, has almostnothing to do with how frequently(or not) her medical condition oc-curs.

Some Tentative ConclusionsBoth the Nuffield Council and Lan-tos and Meadow acknowledge thatwe have a long way to go before wecould ever have a public policy thatwould take into account these long-term considerations. Acceptably ac-curate prognoses may loom as thenext frontier in neonatal medicine,but until then, caution must guideus. There remain important points totake into consideration within thecentral argument of this article.Some factors appear to lead to dis-proportionate spending in theNICU:

1. The perspective of parents who,regardless of the situation, “want ev-erything done,” often based on a

misunderstanding of the Christiantradition on withdrawal and refusalof treatment. (2)

2. Institutionalization of NICUtreatments in which “doctors act likedoctors” and “nurses act likenurses.” Health-care professionalsare often viewed simply as organicplumbers who are neither trained norencouraged to take broader goodsinto consideration. (8) Of note, re-cent moves toward family-centeredand palliative care have moved thefocus of the attention in a better di-

Table. Spending Over 12 Months for 6-year-oldChildren

Cost Category

Cost for ExtremelyLow-birthweightChild

Cost forTerm Child

Hospital Inpatient £605 £116Hospital Outpatient £255 £53Community Health £422 £104Drug Cost £10 £3Education £7,620 £3,470Additional Family Expenses £573 £120Indirect Costs £56 £17

Data from Nuffield Council on Bioethics. (6)

Summary• Human beings have virtually

unlimited health-care needsand limited health-careresources. The question is not ifwe will ration, but what kind ofrationing we will do.

• Even the most brain-damagedor sick patient is a person whodeserves to be treated the sameas any other patient. It is neveracceptable to aim at the deathof a person because his or herdisability makes life “not worthliving.”

• Taking cost into a considerationdoes not violate the rights of aperson. Indeed, the right toequal treatment may requireexplicit steps to avoid adisproportionately small shareof community health-careresources going to certainindividuals.

• The data show that NICUtreatment is among the mostexpensive in the health-caresystem, especially whenincluding the costs over apatient’s lifetime.

• The data show that althoughthe technology is not availableto make acceptably accuratelong-term prognoses inneonates, several importantapproaches can be undertakento combat disproportionatespending in the NICU.




rection, but not far enough to con-sider broader community concerns.

3. Prestige and ego. Some neona-tologists (including the acclaimed fa-ther of neonatology) admit that thisfactor is a motivation in some cases ofovertreatment. (9)

4. Indirect and direct applicationof the law. Many wrongly believe thatBaby Doe regulations demand morethan what is actually required. (10)

5. Profitability. The market andCMS rates help to contribute to aculture of disproportionate spend-ing. Many hospitals are buildingNICUs because of this profitability.Lantos and Meadow (11) make thisargument in some detail. For exam-ple, they cite a study that showed thatfrom 1980 to 1995 the number ofhospitals grew by 99%, the numberof NICU beds by 138%, and thenumber of neonatologists by 268%.By contrast, the growth in neededNICU bed days was only 84%.

If clinicians accept the central ar-gument of this article and its applica-bility to the NICU, attacking thepreviously cited problems is a goodstarting point.

References1. American Academy of Pediatrics Com-mittee on Child Health Care Financing.Principles of child health care financing.Pediatrics. 1988;102:994–9952. Camosy C. Too Expensive to Treat?—Finitude, Tragedy, and the Neonatal ICU.Grand Rapids, MI: Wm. B. Eerdmans Press;20103. Camosy C. Common ground on surgicalabortion?—Engaging Peter Singer on themoral status of potential persons. J MedPhilos. 2009;33:577–5934. American Academy of Pediatrics Com-mittee on Pediatric Workforce. Nondis-crimination in pediatric health care. Pediat-rics. 2007;120:9225. Pellegrino E. The goals and ends of med-icine: how are they to be defined? In: Han-son MJ, Callahan D, eds. The Goals of Med-icine: The Forgotten Issue in Health Care

Reform. Washington, DC: GeorgetownUniversity Press; 1999:55–686. Nuffield Council on Bioethics. CriticalCare Issues in Fetal and Neonatal Medicine:Ethical Issues. London, United Kingdom:Nuffield Council on Bioethics; 2006. Ac-cessed February 2011 at: http://www.nuffieldbioethics.org/sites/default/files/CCD%20web%20version%2022%20June%2007%20(updated).pdf7. Lantos J, Meadow W. Changes in mor-tality for extremely low birth weight infantsin the 1990s: implications for treatment de-cisions and resource use. Pediatrics. 2004;113:12268. Guillemin JH, Holmstrom LL. Thesanctity of newborn life: aggressive inter-vention. In: Mixed Blessings: Intensive Carefor Newborns. New York, NY: Oxford Uni-versity Press; 1986: 114–1159. Silverman WA. Overtreatment of neo-nates? A personal retrospective. Pediatrics.1992;90:97110. Stanley JM. The Appleton Consensus:Suggested International Guidelines for Deci-sions to Forego Medical Treatment. Vol. 15.London, United Kingdom: British MedicalAssociation; 1989:12911. Lantos J, Meadow W. Neonatal Bioeth-ics. Baltimore, MD: Johns Hopkins Univer-sity Press; 2006: 31, 131

CorrectionIn the article entitled “Sacral Dimples” in the March issue (Pediatr Rev. 2011;32:109–114), Figure 1 inadvertently contains the wrong picture. The image in this correctionshould be substituted, and the caption should read, “Solitary dimple whose locationgreater than 2.5 cm above the anus indicated the need for further evaluation, whichrevealed an occult spinal dysraphism requiring neurosurgical intervention.” Also, Figures2A and 4 of the same article are published through the courtesy of Janelle Aby, MD. Weregret the error.





Charles C. Camosy Neonatal ICU

Ethics for the Pediatrician: Just Distribution of Health-care Resources and the




rehttp://pedsinreview.aappublications.org/cgi/collection/critical_ca

Critical Care diatricianhttp://pedsinreview.aappublications.org/cgi/collection/ethics_pe

Ethics for the Primary Care Pediatrician born_infanthttp://pedsinreview.aappublications.org/cgi/collection/fetus_new

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Nirav Shastri, Gretchen Black and Milton A. Fowler, Jr Visual Diagnosis: Sore Throat and Difficulty Swallowing in a 9-year-old Boy







Sore Throat and DifficultySwallowing in a 9-year-old Boy

Author Disclosure

Drs Shastri, Black, and Fowler have disclosed no financial

relationships relevant to this article. This commentary does

not contain a discussion of an unapproved/investigative

use of a commercial product/device.

Nirav Shastri, MD, FAAP,* Gretchen Black, DO,*

Milton A. Fowler, Jr, MD, FACEP†

PresentationA 9-year-old boy presents with sore throat and difficultyswallowing of 3 days’ duration. He was seen at a clinic onthe first day of his illness, where the result of a rapidstreptococcal antigen test was negative. He was dis-charged with a diagnosis of sore throat with cough andprescribed a 5-day course of azithromycin and a 3-daycourse of prednisolone suspension. However, his sorethroat has persisted and his dysphagia has worsened. Hismother is seeking further medical attention because shehas noted the roof of his mouth to be red and swollenposteriorly. The boy describes a feeling that “somethingis stuck in my throat” but still can swallow. Dysphagiaoccurs with both solids and liquid foods.

On physical examination, his vital signs are withinnormal limits; there is no fever or respiratory distress.Examination of the pharynx reveals an erythematous,swollen uvula (Fig. 1). He has no drooling, cervicallymphadenopathy, or erythema or exudate on his pha-ryngeal wall. No other abnormality is noted. He hastaken three doses of azithromycin and two doses ofprednisolone.

The boy had croup last winter, has occasional nasalsymptoms due to seasonal allergies, and underwent ton-sillectomy with adenoidectomy 2 years ago for repeatedear infections. His immunizations are up to date. He hashad no ill contacts.

Diagnosis is made on clinical findings.Figure 1. Erythematous, swollen uvula.

*Assistant Professor of Pediatrics, University of Missouri, Kansas City, MO; Children’s Mercy South Urgent Care Center, Overland Park, KS.†University of Missouri, Kansas City, MO; Section Chief, Children’s Mercy South Urgent Care Center, Overland Park, KS.

visual diagnosis



Diagnosis: UvulitisThe diagnosis of uvulitis is based on the complaints of asore throat with dysphagia; the presence of a red, swollenuvula; and the absence of physical findings suggestive ofother causes of sore throat and dysphagia, such as retro-pharyngeal abscess or peritonsillar abscess.

DiscussionUvulitis is defined as inflammation of the uvula andtypically presents with marked uvular edema and ery-thema. (1) The condition most commonly results fromcellulitis due to infection by group A Streptococcus inchildren 5 to 15 years of age. Among unimmunizedchildren younger than 5 years of age, Haemophilus influ-enzae type b (Hib) is the next most common bacterialcause. (1)(2)(3) Other reported pathogens include Fuso-bacterium nucleatum, Prevotella, and Streptococcus pneu-moniae. (4) Uvulitis can also be caused by viral infectionsdue to coxsackievirus, herpes simplex virus, and varicella-zoster virus and by fungal infection due to Candidaalbicans. Noninfectious causes of uvulitis include traumaduring instrumentation (eg, intubation), inhalation ofchemical irritants (eg, cannabis), inhalation of steam, andvasculitis. (5)(6)

PresentationUvulitis usually presents with fever, sore throat, dyspha-gia, drooling, and respiratory distress. Significant respi-ratory distress is uncommon unless there is an associated

epiglottitis or if the uvulitis is due to a noninfectiouscause such as a chemical irritant. Diagnosis is based onclinical characteristics alone in the absence of other find-ings. However, if respiratory distress is present or if anadequate examination of the oropharynx cannot be per-formed, imaging is essential to rule out epiglottitis orretropharyngeal abscess. (2) Blood and throat culturesmay help to identify an infectious cause.

Differential DiagnosisThe most common differential diagnosis for uvulitis isstreptococcal pharyngitis, which presents with pharyn-geal edema and erythema with tonsillar exudates andpalatal petechiae. Other potential diagnoses include ret-ropharyngeal and peritonsillar abscesses and epiglottitis.Retropharyngeal abscesses present with swelling of thepharyngeal wall; peritonsillar abscesses manifest withtonsillar swelling and deviation of the uvula. Both maypresent with signs of upper airway obstruction and lim-ited ability to open the mouth adequately for examina-tion. Epiglottitis presents with fever, drooling, stridor,anxiety, and rapid progression of upper airway obstruc-tion.

ManagementTreatment should be decided on a case-by-case basis anddirected at the most likely pathogens that cause age-associated symptoms (pharyngitis or epiglottitis) andlocal antimicrobial susceptibility data. Many children canbe treated as outpatients. If group A Streptococcus isisolated or suspected on the basis of associated pharyn-gitis, oral therapy with penicillin or amoxicillin is appro-priate. The initial treatment of isolated uvulitis withoutevidence of pharyngitis or epiglottitis or uvulitis withepiglottitis consists of empiric antimicrobial treatment,such as a third-generation cephalosporin (eg, ceftriax-one) to provide coverage for typical pathogens such asHib and S pneumoniae, which may produce beta-lactamase or be resistant to penicillin, respectively. Onceblood cultures are negative, changing to an oral antibi-otic such as amoxicillin-clavulanate or an oral cephalo-sporin such as cefuroxime or cefdinir is appropriate tocontinue treatment for a possible bacterial uvulitis. Non-infectious causes of uvulitis can be treated with conser-vative supportive care. Evidence to support the role ofcorticosteroid therapy in the management of uvulitis isnot apparent in the medical literature.

Patient CourseThe patient was admitted for 1 day for observation.Testing showed a white blood cell count of 12.0�103/�L

Figure 2. Neck radiograph documenting a lack of epiglottitis.E�esophagus, U�uvula.

visual diagnosis



(12.0�109/L) with 65% neutrophils, 26% lymphocytes,and 7.8% monocytes. His hemoglobin measured12.8 g/dL (128 g/L), hematocrit was 36.5% (0.365),and platelet count was 295�103/�L (295�109/L).Neck radiographs did not show any evidence of epiglot-titis (Fig. 2). He received intravenous ampicillin-sulbactam at 200 mg/kg per day in four divided dosesand dexamethasone 0.5 mg/kg for three doses every8 hours after an otolaryngology consultation. His bloodand throat cultures were negative. He was able to eat and

drink without difficulty, and he did not have any oxygendesaturations or fever throughout his inpatient stay. Hewas discharged on the second inpatient day receiving oralamoxicillin-clavulanic acid 500 mg twice a day for10 days for presumed bacterial uvulitis.

References1. Woods CR. Clinical features and treatment of uvulitis in chil-dren and adolescents. UptoDate Online 18.3. 20102. McNamara RM. Clinical characteristics of acute uvulitis. Am JEmerg Med. 1994;12:51–523. Wynder SG, Lampe RM, Shoemaker ME. Uvulitis and Haemo-philus influenzae b bacteremia. Pediatr Emerg Care. 1986;2:23–254. Brook I. Uvulitis caused by anaerobic bacteria. Pediatr EmergCare. 1997;13:2215. Holden JP, Vaughan WC, Brock-Utne JG. Airway complicationfollowing functional endoscopic sinus surgery. J Clin Anesth. 2002;14:154–1576. Boyce SH, Quigley MA. Uvulitis and partial upper airway ob-struction following cannabis inhalation. Emerg Med. 2002;14:106–108

Summary• Uvulitis is an infrequently recognized pediatric

condition.• The diagnosis should be considered for the patient

who presents with a sore throat, dysphagia, and anerythematous, edematous uvula in the absence ofother, more serious disorders such as retropharyngealor peritonsillar abscess.

visual diagnosis




Nirav Shastri, Gretchen Black and Milton A. Fowler, Jr Visual Diagnosis: Sore Throat and Difficulty Swallowing in a 9-year-old Boy




throat_disordershttp://pedsinreview.aappublications.org/cgi/collection/ear_nose_

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DOI: 10.1542/pir.32-5-207 2011;32;207 Pediatr. Rev.

Correction







rection, but not far enough to con-sider broader community concerns.

3. Prestige and ego. Some neona-tologists (including the acclaimed fa-ther of neonatology) admit that thisfactor is a motivation in some cases ofovertreatment. (9)

4. Indirect and direct applicationof the law. Many wrongly believe thatBaby Doe regulations demand morethan what is actually required. (10)

5. Profitability. The market andCMS rates help to contribute to aculture of disproportionate spend-ing. Many hospitals are buildingNICUs because of this profitability.Lantos and Meadow (11) make thisargument in some detail. For exam-ple, they cite a study that showed thatfrom 1980 to 1995 the number ofhospitals grew by 99%, the numberof NICU beds by 138%, and thenumber of neonatologists by 268%.By contrast, the growth in neededNICU bed days was only 84%.

If clinicians accept the central ar-gument of this article and its applica-bility to the NICU, attacking thepreviously cited problems is a goodstarting point.

References1. American Academy of Pediatrics Com-mittee on Child Health Care Financing.Principles of child health care financing.Pediatrics. 1988;102:994–9952. Camosy C. Too Expensive to Treat?—Finitude, Tragedy, and the Neonatal ICU.Grand Rapids, MI: Wm. B. Eerdmans Press;20103. Camosy C. Common ground on surgicalabortion?—Engaging Peter Singer on themoral status of potential persons. J MedPhilos. 2009;33:577–5934. American Academy of Pediatrics Com-mittee on Pediatric Workforce. Nondis-crimination in pediatric health care. Pediat-rics. 2007;120:9225. Pellegrino E. The goals and ends of med-icine: how are they to be defined? In: Han-son MJ, Callahan D, eds. The Goals of Med-icine: The Forgotten Issue in Health Care

Reform. Washington, DC: GeorgetownUniversity Press; 1999:55–686. Nuffield Council on Bioethics. CriticalCare Issues in Fetal and Neonatal Medicine:Ethical Issues. London, United Kingdom:Nuffield Council on Bioethics; 2006. Ac-cessed February 2011 at: http://www.nuffieldbioethics.org/sites/default/files/CCD%20web%20version%2022%20June%2007%20(updated).pdf7. Lantos J, Meadow W. Changes in mor-tality for extremely low birth weight infantsin the 1990s: implications for treatment de-cisions and resource use. Pediatrics. 2004;113:12268. Guillemin JH, Holmstrom LL. Thesanctity of newborn life: aggressive inter-vention. In: Mixed Blessings: Intensive Carefor Newborns. New York, NY: Oxford Uni-versity Press; 1986: 114–1159. Silverman WA. Overtreatment of neo-nates? A personal retrospective. Pediatrics.1992;90:97110. Stanley JM. The Appleton Consensus:Suggested International Guidelines for Deci-sions to Forego Medical Treatment. Vol. 15.London, United Kingdom: British MedicalAssociation; 1989:12911. Lantos J, Meadow W. Neonatal Bioeth-ics. Baltimore, MD: Johns Hopkins Univer-sity Press; 2006: 31, 131

CorrectionIn the article entitled “Sacral Dimples” in the March issue (Pediatr Rev. 2011;32:109–114), Figure 1 inadvertently contains the wrong picture. The image in this correctionshould be substituted, and the caption should read, “Solitary dimple whose locationgreater than 2.5 cm above the anus indicated the need for further evaluation, whichrevealed an occult spinal dysraphism requiring neurosurgical intervention.” Also, Figures2A and 4 of the same article are published through the courtesy of Janelle Aby, MD. Weregret the error.




DOI: 10.1542/pir.32-5-207 2011;32;207 Pediatr. Rev.

Correction












Goodkin, Rachel Dawson and Shana Hansen Thomas C. Martin, Joshua M. Careskey, Heather Harle, Sean Rose, Howard P.

Case 3: Primary Amenorrhea in a 15-year-old Girl9-year-old Boy • Case 2: Vomiting, Headache, and Seizures in a 7-year-old Boy •

Index of Suspicion • Case 1: Abdominal Pain and Coffee Ground Emesis in a







The reader is encouraged to writepossible diagnoses for each case beforeturning to the discussion.

The editors and staff of Pediatrics in

Review find themselves in the

fortunate position of having too

many submissions for the Index of

Suspicion column. Our publication

slots for Index of Suspicion are filled

through 2013. Because we do not

think it is fair to delay publication

longer than that, we have decided

not to accept new cases for the

present. We will make an

announcement in Pediatrics in

Review when we resume accepting

new cases. We apologize for having

to take this step, but we wish to be

fair to all authors. We are grateful

for your interest in the journal.

Author Disclosure

Drs Martin, Careskey, Harle, Rose,

Goodkin, Dawson, and Hansen have

disclosed no financial relationships

relevant to these cases. This

commentary does not contain a



product/device.

Case 1: Abdominal Pain and Coffee Ground Emesisin a 9-year-old BoyCase 2: Vomiting, Headache, and Seizuresin a 7-year-old BoyCase 3: Primary Amenorrhea in a 15-year-old GirlCase 1 PresentationA 9-year-old boy presents to the EDwith severe abdominal pain and vom-iting. He has no history of diarrhea,fever, chills, rash, trauma, arthralgia,or headache. He has no prior historyof gastrointestinal complaints orother chronic illnesses. He cannottolerate clear liquids and is admittedfor observation. He vomits coffeeground material and then blood.

On physical examination, his tem-perature is 38.5°C, heart rate is140 beats/min, blood pressure is123/83 mm Hg, and respiratory rateis 24 breaths/min. He is uncomfort-able and diaphoretic. He has tachy-cardia, but his cardiopulmonary ex-amination results are normalotherwise. He has generalized ab-dominal tenderness, with guardingand rebound tenderness most pro-nounced in the periumbilical regionand extending to the right lowerquadrant. Hip abduction elicits pain.

CBC documents a normal Hgbvalue and platelet and leukocytecounts, with a left shift and 78% neu-trophils. Urinalysis shows moderateblood and trace proteinuria, with 2RBCs per high-power field. Thechest radiograph appears normal.The abdominal radiograph shows afew mildly distended small bowelloops but no radiographic evidenceof obstruction. CT scan of the abdo-men leads to exploratory laparoscopyand the correct diagnosis.

Case 2 PresentationA 7-year-old developmentally appro-priate boy presents to the ED with a

3-day history of forceful vomiting,headache, and reduced oral intake.Several times after vomiting, he hadcomplained of numbness in his handsand feet that lasted several seconds.Two hours after receiving a dose ofpromethazine prescribed by his pedi-atrician, he could not be aroused byhis parents.

On arrival at the ED by ambu-lance, he is initially sleepy and con-fused. He is afebrile. His blood pres-sure is 99/74 mm Hg, heart rate is89 beats/min, and oxygen saturationis 98% in room air. He has no dys-morphic features and no skin find-ings. His funduscopic findings andextraocular movements are normal.There is a left homonymous hemi-anopsia. He has difficulty moving hisleft upper extremity that is more pro-nounced distally. He has decreasedsensation to light touch and pin prickin the left upper extremity. His re-flexes are symmetric, but the left toeis upgoing.

Laboratory evaluation, includingCBC, serum electrolytes, ESR,C-reactive protein, antinuclear anti-bodies, liver function tests, and CSFanalysis, yields normal results. Re-sults of a noncontrast cranial CT scanare within normal limits.

The following day, the boy hasmultiple brief seizures characterizedby left gaze version, behavioral ar-rest, and clonic movements of the lefthand. Benzodiazepines, fospheny-toin loading, and rapid titration ofoxcarbazepine are necessary to ob-tain control of these events. EEGshows generalized slowing of thebackground and focal slowing over

index of suspicion



the right hemisphere. Additional im-aging studies reveal the diagnosis.

Case 3 PresentationWhen a 15-year-old girl presents forevaluation of pectus excavatum, shereports that she has never had a men-strual period. Pubarche and the-larche occurred at ages 13 and 14years, respectively. She denies anysexual activity, medication use, orsubstance abuse and has had no re-cent weight changes, heat or coldintolerance, constipation, skin or hairproblems, vision difficulties, or head-aches. She does report infrequentlower abdominal cramping. Pastmedical history includes a urinarytract infection as an infant and subse-quent diagnosis of a single kidneyand pectus excavatum. Her father haspectus excavatum, and her motherwas found to have a brain aneurysmat 42 years of age.

On physical examination, thegirl’s height is at the 40th percentile,weight is at the 33rd percentile, body

mass index is at the 30th percentile,blood pressure is 107/65 mm Hg,and heart rate is 81 beats/min. Herskin is normal and without any ab-normal hair pattern or hirsutism. Herpalate is high-arched, with mandibu-lar dental crowding. She has pectusexcavatum. Her breasts are at SexualMaturity Rating 3 and appear nor-mal. External genitalia appear nor-mal, with moist, pink mucosa. A littlefinger can be passed 3 cm into thevagina. She reports discomfort withmanual examination, and further ex-amination is deferred.

On laboratory evaluation, serumelectrolytes, BUN, creatinine, glu-cose, follicle-stimulating hormone,luteinizing hormone, prolactin, freethyroxine, thyroid-stimulating hor-mone, and estradiol results are withinnormal limits for age. Imaging stud-ies identify the cause of her amenor-rhea.

Case 1 DiscussionCT scan without contrast revealed adilated loop of small bowel with wallthickening and surrounding edema

located anteriorly in the midline (Fig.1). There was excess free fluid in theabdomen. The differential diagnosisof acute abdominal pain with theseabnormal CT findings includes ap-pendicitis, volvulus, enteric duplica-tion cyst, intussusception, inflamma-tory bowel disease, and abscess.

Following blood and urine cul-tures, the boy was placed on nothingby mouth and started on intravenous(IV) fluids at 11⁄2 times maintenance.IV lansoprazole, metronidazole, andcefotaxime also were initiated, andhis pain was controlled by morphineas needed. Following evaluation by apediatric surgeon, exploratory lapa-roscopy was recommended. The lap-aroscopy showed dilated loops ofischemic small bowel (Fig. 2). Theprocedure was converted to a lapa-rotomy, which revealed a Meckel di-verticulum connected by a fibrousadhesive band to the mesentery. Aninternal hernia was present, and ap-proximately 2 ft of bowel hadherniated through this space, result-ing in ischemia. The adhesive bandwas divided. Approximately 23 in(58 cm) of small bowel between the

Figure 1. Axial image from CT scan showing a dilated loop of small bowel withincreased wall thickness and surrounding soft-tissue edema.

Frequently Used Abbreviations

ALT: alanine aminotransferaseAST: aspartate aminotransferaseBUN: blood urea nitrogenCBC: complete blood countCNS: central nervous systemCSF: cerebrospinal fluidCT: computed tomographyECG: electrocardiographyED: emergency departmentEEG: electroencephalographyESR: erythrocyte sedimentation

rateGI: gastrointestinalGU: genitourinaryHct: hematocritHgb: hemoglobinMRI: magnetic resonance imagingWBC: white blood cell

index of suspicion



Meckel diverticulum and the termi-nal ileum was resected, and anend-to-end ileoileostomy was per-formed. The boy had an uneventfulrecovery.

Differential DiagnosisVomiting and abdominal pain arecommon symptoms in childhood.The causes may range from func-tional abdominal pain or viral gastro-enteritis to abdominal abscess orischemic bowel. The initial approachis to consider common, self-limitedcauses and provide symptomatic re-lief and oral rehydration therapy. Theuse of IV fluids may be considered iforal rehydration therapy is not toler-ated. Antiemetic, opioid analgesic,and sedative medications are notneeded for the self-limited causes ofabdominal pain and vomiting.

If abdominal pain and vomitingfail to improve with symptomatictreatment, additional assessment isindicated. A chemistry panel may beuseful in documenting hydration sta-tus and electrolyte abnormalities.A CBC may provide useful informa-tion regarding infection or other sys-temic diseases. A urinalysis can helpassess hydration status and rule out aurinary tract infection. Finally, bil-ious emesis in a neonate, infant, orchild is never normal and should beevaluated promptly for potential me-chanical bowel obstruction, such asintestinal malrotation with midgutvolvulus.

Imaging studies have assumed anincreasing role in the assessment ofabdominal complaints in children.An abdominal radiograph may behelpful in assessing for the presenceof bowel obstruction or perforation.Abdominal ultrasonography is usefulfor diagnosing some age-specificcauses of vomiting, such as pyloricstenosis or appendicitis, but accuracyis largely operator-dependent. In theabsence of a clear clinical diagnosis,CT scans are used widely as an ad-junctive diagnostic tool for evaluat-ing severe or persistent abdominalpain with vomiting. The use of con-trast makes the CT scan sensitive andspecific for diseases such as appendi-citis and abdominal abscess. MRI hassome advantages in terms of soft-tissue imaging compared with CTscan, but the lack of availability, needfor sedation, and added time for im-aging make MRI less attractive thanCT scan.

The ConditionMeckel diverticulum is a vestigialremnant of the omphalomesentericduct located on the antimesentericborder in the terminal ileum that oc-curs in about 2% of the general pop-ulation. The diverticulum is about2 in long, is present in twice as manyboys as girls, and is located within 2 ftof the ileocecal valve. Most Meckeldiverticula are asymptomatic.

The most common clinical mani-festation is painless acute lower gas-trointestinal bleeding (eg, hemato-chezia) caused by ectopic gastricmucosa in the diverticulum. Sixtypercent of patients present before theage of 2 years. A Meckel scan (99mtechnetium pertechnetate, which hasaffinity for gastric mucosa) may helpmake the diagnosis in the 50% ofdiverticula that contain gastric tissue.A Meckel diverticulum in older chil-dren may present with diverticulitis,perforation, bowel obstruction, vol-

vulus, or intussusception. Symptom-atic Meckel diverticula should be re-sected. Whether an asymptomaticMeckel diverticulum discovered inolder children or adults should beresected remains controversial.

In this case, the bowel was dam-aged by the ischemia that resultedfrom trapping of small intestine in aspace created by a band of tissue thatwas attached to the diverticulum.

Lessons for the Clinician● Meckel diverticulum is an uncom-

mon pediatric condition most of-ten presenting with painless hema-tochezia.

● Meckel diverticulum may be asso-ciated with a variety of acute pedi-atric surgical problems, includingintussusception and small bowelobstruction due to volvulus.

(Thomas C. Martin, MD, JoshuaM. Careskey, MD, Eastern MaineMedical Center Bangor, ME)

Case 2 DiscussionThis boy’s original presentation ofacute-onset left homonymous hemi-anopsia, left upper extremity weak-ness, and sensory change as well as aleft upgoing toe was concerning for aright posterior quadrant cerebralprocess. The history of forceful vom-iting was concerning for an arterialdissection. Therefore, the initial dif-ferential diagnosis considered at thetime of his presentation includedstroke, postictal state, complicatedmigraine, and, less likely, an expand-ing mass, encephalitis, or a demyeli-nating lesion.

Brain MRI/angiography was per-formed. Both MRI and EEG con-firmed an abnormality of the rightcerebral hemisphere. Imaging of theintracranial vessels and vessels in theneck was negative for evidence of adissection. The postcontrast MRI

Figure 2. A photograph from the initialexploratory laparoscopic procedureshowing dusky, dilated loops of bowel.

index of suspicion



(Fig. 3) showed enhancement of thepial blood vessels and swelling of theunderlying gyri. This finding can beseen in Sturge-Weber syndrome(SWS) as well as hemiplegic migraineand meningoencephalitis. Results ofstudies of the CSF were within nor-mal limits, reducing the possibilitythat this presentation was the resultof an infectious process. The com-mencement of seizures during hishospital stay made SWS without fa-cial nevus the likely diagnosis.

The ConditionSWS is a neurocutaneous disordercharacterized by angiomas of the lep-tomeninges and skin of the face, of-ten with eye abnormalities. The facialangiomas or port wine stains are, at aminimum, in the distribution of theophthalmic (V1) division of the tri-geminal nerve and may extend intothe maxillary (V2) division. Initiallypink, this congenital lesion candarken with age to a dark red orpurple. However, in darkly pig-mented individuals, the facial angi-oma may be difficult to see. The lep-tomeningeal angioma (LA) isbelieved to be an embryonic remnantof the venous plexus that fails to re-gress. The LA is most frequently uni-lateral, overlying the parietal and oc-cipital lobes, and ipsilateral to thefacial nevus.

Not all patients born with portwine stain have LA. Port wine stainsare present in 3 to 5 in 1,000 livebirths. They can occur anywhere onthe body but are located most fre-quently on the face. The frequency ofSWS is more difficult to quantify, butexperts estimate that the conditionoccurs in approximately 1 in 20 to50,000 live births. Furthermore, notall patients born with SWS have afacial nevus; to date, approximately25 such cases have been reported.Some have suggested that between10% and 13% of people who haveSWS do not have a facial nevus. Toaccount for these individuals, Roach(1) proposed the following classifica-tion system:

● Type I: The presence of both afacial nevus and LA with possibleglaucoma (classic SWS)

● Type II: Facial nevus, may haveglaucoma, in the absence of LA

● Type III: Isolated LA with lowlikelihood of glaucoma

Classically, SWS was diagnosedwhen linear calcifications resulting inthe “tram-track sign” were seen onskull radiographs. More recently,cranial CT scan has confirmed thepresence of calcifications in the men-ingeal arteries as well as cortical andsubcortical veins in the region of theLA.

Several mechanisms can contrib-ute to the development of the calci-fications. Altered venous drainageand impaired perfusion results in per-sistent hypoxia in the brain underly-ing the LA. The hypoxia, exacer-bated by ischemia as the result ofthrombosis within the LA or pro-longed or frequent seizures, poten-tially may lead to neuronal deathwith resultant laminar necrosis, glio-sis, and calcifications. In addition, ithas been proposed that the increasedpermeability of the abnormally thin-walled vessels of the LA may lead todeposition of calcium and phospho-rus outside the blood vessels.

Today, the diagnosis of SWS isconfirmed by the presence of LA oncerebral MRI with contrast. OtherMRI findings can include cortical at-rophy, accelerated myelination, en-largement of the choroid plexus, andenlargement of the deep drainingveins.

SWS often is complicated byheadache, strokelike episodes, sei-zures, hemianopsia, glaucoma, andintellectual disability. Seizures usu-ally begin before 5 years of age, withonset before 2 years potentially her-alding a greater probability of medi-cally refractory epilepsy and intellec-tual disability. Type III SWS tends topresent later and have a less severecourse. Glaucoma or other eye ab-normalities typically are absent in thisgroup.

TreatmentAspirin at a dose of 2 mg/kg hasbeen recommended at the onset ofseizures or neurologic deficit or evenas soon as the diagnosis is confirmedon imaging. The antiplatelet effectsof aspirin are believed to prevent theprogressive neurologic deteriorationthat accompanies SWS by reducingthe risk of thrombosis due to venousstasis within the LA.

Therapy for focal seizures with an

Figure 3. MRI with contrast (A, B) demonstrates prominent pial vascular enhance-ment over the right posterior, frontal, temporal, and parietal cortex. FLAIRsequence (C) demonstrates hyperintensity and swelling, with partial effacement ofthe sulci over the same area.

index of suspicion



appropriate antiepileptic agent is ad-vised after the first seizure. Emergentevaluation and potentially hospital-ization are necessary to control pro-longed or frequent seizures asquickly as possible to prevent neuro-nal death from impaired blood flow.Seizures may be medically refractory,and hemispherectomy may be re-quired.

Ophthalmologic surveillance forbuphthalmos and glaucoma is re-quired. If they are present, treatmentshould be undertaken to decrease in-traocular pressure and prevent visualloss.

Finally, laser therapy can be con-sidered for those who have port winestains.

Six months after discharge, thispatient has had no additional sei-zures, and his neurologic deficitshave resolved.

Lessons for the Clinician● SWS may be diagnosed with appro-

priate MRI imaging of an LA, evenwhen a facial nevus is not present.

● Those patients who do not haveport wine stains may present laterand have less severe courses.

● Treatment of SWS attempts to pre-vent progressive problems causedby neuronal death and gliosis thatoccurs as a consequence of the LA.

(Heather Harle, MD, Sean Rose,MD, Howard P. Goodkin, MD, PhD,The University of Virginia School ofMedicine, University of VirginiaHealth Systems, Charlottesville, VA)

Reference1. Roach ES. Neurocutaneous syndromes.Pediatr Clin North Am. 1992;39:591–620

Case 3 DiscussionPelvic ultrasonography showed auterine anomaly. The differential di-agnosis for this anomaly included bi-

cornuate uterus with cervical sep-tum, bicornuate bicollis uterus(uterus with two horns and two cer-vical openings), and uterine didel-phys (double uterus with two cervi-ces). Asymmetric enlargement of theright ovary, which otherwise ap-peared normal, also was noted. MRIof the pelvis favored uterus didelphysand indicated a lower likelihood ofbicornuate bicollis uterus, displayingcomplete duplication of widely diver-gent uterine corneae and cervices inclose approximation (Figs. 4 and 5).The possibility of myometrial tissuebetween the two cervical canals wasbelieved to be unlikely.

The development of the femalegenital tract begins at 3 weeks ofgestation and continues into the sec-ond trimester of pregnancy. It is acomplex process involving cellulardifferentiation, migration, fusion,and canalization. Disrupted develop-ment of mullerian ducts, such asagenesis, failure of lateral fusion, orfailure of canalization, results in var-ious congenital anomalies.

Evaluation and DifferentialDiagnosis

Primary amenorrhea can be orga-nized into four categories:

● Primary amenorrhea without sec-ondary sexual characteristics butwith normal genitalia (uterus andvagina)

● Primary amenorrhea with normalbreast development but absent orabnormal uterus

● Primary amenorrhea with no breastdevelopment and no uterus

● Primary amenorrhea and second-ary amenorrhea with normal sec-ondary sexual characteristics andnormal genitalia

In this case, the adolescent pre-sented with normal growth and puber-

Figure 5. MRI showing two cervical ca-nals.

Figure 4. MRI of pelvis shows widely divergent uterine corneae with cervices in closeapproximation.

index of suspicion



tal development, including breast de-velopment, but abnormal menstrualonset due to a structural abnormalityof the female reproductive organ.

Congenital structural abnormali-ties of the female reproductive or-gans account for approximately 20%of cases of primary amenorrhea.Congenital abnormalities of the fe-male reproductive tract are common,occurring in 1% to 3% of women.These abnormalities are caused bygenetic errors or teratologic eventsduring embryonic development.Anomalies of the mullerian systemclinically present at varying times, in-cluding during pubertal develop-ment, and major abnormalities maylead to serious impairment of men-strual and reproductive functions.

Menses cannot occur without anintact uterus, endometrium, cervix,cervical os, and vaginal conduit. Inwomen who have an imperforate hy-men, the menstrual cycle is normal,but the menstrual products cannotbe expelled. This condition occurs inapproximately 1 in 1,000 live-bornfemales, and the diagnosis often ismade after puberty. Primary amenor-rhea and cyclic abdominal crampingare the most common symptoms.However, many patients aresymptom-free. A bluish, bulgingmembrane at the introitus (hemato-colpos) is a characteristic finding.

Transverse vaginal septum occursin 1 in 75,000 females. The patientmay complain of cyclic cramping andprimary amenorrhea. On physical ex-amination, the vagina appears short,and a mass is palpable above the ex-amining finger. At puberty, if thetransverse septum is complete, pa-tients present with hematocolposand hematometrium. If the septum isincomplete, some bleeding does oc-cur, but over time, it leads to thedevelopment of hematocolpos andhematometrium.

Uterine fusion anomalies usually

do not result in complete disruptionof menstrual flow. Instead, they typ-ically manifest as heavy menstrualflow, increased pain at menses, pelvicmasses, ectopic pregnancy, or mis-carriage.

Other congenital causes of absentuterus or outflow problems includecomplete androgen insensitivity andvaginal agenesis. Vaginal agenesis isthe congenital absence of the vaginawith variable mullerian duct abnor-malities. This condition usually is as-sociated with cervical and uterineagenesis, but 7% to 10% of affectedfemales may have a normal but ob-structed uterus. Androgen insensitivitysyndrome is categorized by normalbreast development but sparse or ab-sent pubic and axillary hair. The vaginais short, and the uterus and cervix areabsent. The karyotype is 46 XY, withgonads that are usually intra-abdominal and a serum testosteronevalue in the pubertal male range.

The ConditionUterus didelphys represents a uterinemalformation in which the uterus ispresent as a paired organ due to failedfusion of the mullerian ducts. Amongmullerian duct anomalies, didelphicuteri account for approximately 11%of anomalies. In the United States,uterus didelphys is reported to occurin 0.1% to 0.5% of the population.The abnormality is characterized by adouble uterus with two separate cer-vices and, in approximately 75% ofcases, a longitudinal vaginal septumthat presents as a double vagina Thiswas not the case in this patient. Eachuterus has a single horn linked to theipsilateral fallopian tube that faces itsovary. Unilateral hematometrocol-pos can occur even without a hori-zontal vaginal septum.

The constellation of a single kid-ney, uterine anomaly, joint hypermo-bility, high-arched palate with dentalcrowding, hypertelorism, and pectus

is very common with the 22q11 de-letion syndrome. However, this di-agnosis could not be established inthis patient because the family re-fused fluorescence in situ hybridiza-tion testing.

ManagementTreatment of primary amenorrhea ina patient born with uterine didelphysis directed toward correcting the un-derlying pathologic anatomy, maxi-mizing fertility potential, and pre-venting complications of the diseaseprocess. Treatments include weightmanagement, hormone therapy, sur-gery, and psychological support.

Imaging studies did not show he-matocolpos in this patient. There-fore, the decision was made to deferany further examinations until sheturned 16 years of age, with the planto follow up sooner if she experi-enced marked cyclic pain withoutmenses efflux.

Lessons for the Clinician● When evaluating a patient who has

primary amenorrhea, it is importantto consider structural anomalies.

● MRI may be necessary to delineateabnormalities found on ultra-sonography.

● All females who have primaryamenorrhea should be counseledregarding the cause, treatment,and their reproductive potential.Psychological counseling is impor-tant in many patients, particularlythose with who have absent mulle-rian structures or a Y chromosome.

(Rachel Dawson, DO, Fort SamHouston Primary Care Clinic, FortSam Houston, TX; Shana Hansen,MD, Naval Medical Center Ports-mouth, Portsmouth, VA)

To view Suggested Reading lists forthe cases, visit pedsinreview.aappublications.org and click onIndex of Suspicion.

index of suspicion




Goodkin, Rachel Dawson and Shana Hansen Thomas C. Martin, Joshua M. Careskey, Heather Harle, Sean Rose, Howard P.

Case 3: Primary Amenorrhea in a 15-year-old Girl9-year-old Boy • Case 2: Vomiting, Headache, and Seizures in a 7-year-old Boy •

Index of Suspicion • Case 1: Abdominal Pain and Coffee Ground Emesis in a



Supplementary Material

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Jan E. Drutz Histiocytosis







In BriefHistiocytosisJan E. Drutz, MDTexas Children’s Hospital and

Baylor College of MedicineHouston, TX

Author Disclosure

Dr Drutz has disclosed no financial

relationships relevant to this article.

This commentary does not contain a



product/device.

Langerhans Cell Histiocytosis: A Reviewof the Current Recommendations ofthe Histiocyte Society. Satter EK,High WA. Pediatr Dermatol. 2008;25:291–295

LCH in Children. Histiocytosis Associa-tion of America. Accessed March2011 at: http://www.histio.org/site/c.kiKTL4PQLvF/b.1764433/k.8BCD/LCH_in_Children.htm

Langerhans Cell Histiocytosis, JuvenileXanthogranuloma, and Erdheim-Chester Disease. McClain KL.UpToDate Online 18.3. 2010. Ac-cessed for subscription March 2011at: http://www.uptodate.com/contents/langerhans-cell-histiocytosis-juvenile-xanthogranuloma-and-erdheim-chester-disease?source�search_result&selectedTitle�1%7E86

Case 16-2010: A 48-year-old ManWith a Cough and Pain in the LeftShoulder. Medoff BD, Abbott GF,Louisaint A, Jr. N Engl J Med. 2010;362:2013–2022

The term “histiocyte” refers to a num-ber of different cell types (monocytes/macrophages, dermal/interstitial den-dritic cells, and Langerhans cells [LCs]),all believed to arise from a common bone

marrow progenitor cell (CD�34�). Forpurposes of this review, discussion ofhistiocytosis is confined to Langerhanscell histiocytosis (LCH). First describedat the beginning of the 20th century,LCH is considered a rare proliferativedisorder that primarily affects children.LCs have the potential to accumulate ina number of different sites and organs,including the bone, lungs, liver, spleen,and lymph nodes, ultimately leading toa disease process.

To simplify confusing terminologypreviously used to describe LCH (eosino-philic granuloma, Letterer-Siwe disease,Hand-Schuller-Christian disease, histio-cytosis X), it is preferable to definehistiocytosis with regard to involve-ment of a single system (ie, skin, bone,lymph node), multiple systems, a singleorgan, or multiple organs. This perspec-tive is extremely important in helpingto determine treatment and prognosiswhen organs such as the liver, spleen,bone marrow, and lungs are involved.

LCs generally are localized to epi-thelial surfaces, particularly skin. Theirprimary function is to transport foreignantigens to T cells within the lymphaticsystem, contributing to an overall im-mune response.

Although the cause of LCH remainsunknown, this disorder possibly is anautoimmune phenomenon. LCH is nei-ther a cancer nor believed to be attrib-utable to an infectious process. Of note,several studies have been unsuccessfulin establishing a linkage between hu-man herpesvirus 6 and LCH.

Every year, LCH affects nearly200,000 individuals, particularly chil-dren 1 to 15 years of age. Among thoseyounger than 4 years of age, 50% to70% present with multiorgan involve-ment. Symptoms in children vary and

may include abdominal pain, bone pain,or other complaints; those younger than5 years generally present with bonepain only. Of the bone sites in chil-dren, the most frequent finding is alytic scalp lesion. Such a lesion may beaccompanied by a mass impinging onthe dura. The most common endocrineabnormality associated with LCH isdiabetes insipidus.

Diagnosis of LCH requires the iden-tification of specific clinical features aswell as characteristic histopathologicand immunohistochemical findings. Inmore than 50% of affected patients,skin findings are evident. A diffuse,vesicular (herpes simplex virus-like) orexcoriated exanthem may be present atbirth. In older infants, LCH may presentwith scaling of the scalp, suggestiveof seborrhea. In addition to the skinfindings and bone pain, other clinicalfeatures can include abdominal pain,pulmonary infiltrates, gingival hyper-trophy and ulcerations, exophthalmos,destructive damage to the mandible,and marked developmental delay.

Definitive diagnosis is dependentupon specific characteristics of cellstaining and the identification by elec-tron microscopy of Birbeck granules.The number of LCs containing thesegranules varies, depending on the organfrom which the tissue specimen is ob-tained. Whether the patient has single-site or multiorgan involvement, evalu-ation should include a skeletal survey,skull radiographic series, bone scan,chest radiograph, computed tomogra-phy (CT) head scan (if there is orbital ormastoid involvement), and CT scan ofthe spine or pelvis if there is neurologicdysfunction. In neonates, a CT scan ofthe lungs should be performed.

in brief



Treatment consists primarily of corti-costeroids or immunosuppressive agents,such as 6-mercaptopurine, vinblastine,or methotrexate. Individual treatmentprotocols should be tailored to specificrisk factors. Those patients who haveonly single-system involvement shouldbe subcategorized according to thenumber of sites involved within thatsystem. For those who have multiorgandisease, treatment should be deter-mined in relation to whether organdysfunction is present.

In general, no therapy is requiredfor individuals whose involvement islimited to the skin. Treatment is some-what controversial for those who havemultiorgan disease. Some experts advo-cate high-dose prednisone as first-linetherapy; others advocate single-agentchemotherapy. A review of a large num-ber of cooperative studies revealed thatmultiagent chemotherapy, administered

over a long period of time, resulted in agreater response with fewer recurrences.

The prognosis for patients who haveLCH depends on the number of organsystems involved and the degree oforgan dysfunction. To a less significantdegree, the patient’s age may be afactor. Mortality is greater for the youngchild who has multiorgan involvementand organ failure. Involvement of thespleen, lung, liver, or hematopoietic sys-tem portends a poor prognosis. Newbornswho have isolated cutaneous lesions doexceptionally well. The best indicator fora favorable prognosis is the patient’sresponse to chemotherapy during thefirst 6 weeks of the induction phase.Those who respond to initial chemother-apy have an 88% to 91% survival rate;those who do not exhibit an early re-sponse have only a 17% to 34% survival.

Comment: LCH is a fascinating dis-ease. I have been involved with two

cases: a neonate who had an enlargedinguinal lymph node without a perinealrash, thus having no readily apparentreason for the adenopathy, and a2-year-old child initially believed tohave periorbital cellulitis who subse-quently developed proptosis and wasfound to have an orbital bone lesion.These diagnoses were challenging tomake because the patients presentedwith more common initial symptomsthat became atypical over time. Be-cause of the multiple sites and organsin the body that can be involved, pedi-atricians need to have knowledge ofthis disease and consider it when whatinitially appear to be common symp-toms recur or do not resolve in theexpected time frame.

Janet R. Serwint, MDConsulting Editor, In Brief

in brief




Jan E. Drutz Histiocytosis




of_blood_neoplasmshttp://pedsinreview.aappublications.org/cgi/collection/disorders_

Disorders of Blood/Neoplasms dershttp://pedsinreview.aappublications.org/cgi/collection/skin_disor

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DOI: 10.1542/pir.32-5-e53 2011;32;e53-e65 Pediatr. Rev.

Andrew R. Peterson and David T. Bernhardt The Preparticipation Sports Evaluation

http://pedsinreview.aappublications.org/cgi/content/full/32/5/e53located on the World Wide Web at:




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The Preparticipation Sports EvaluationAndrew R. Peterson, MD,

MSPH,* David T.

Bernhardt, MD†

Author Disclosure

Drs Peterson and

Bernhardt have

disclosed no financial



commentary does not


of an unapproved/


commercial

product/device.


1. Perform a preparticipation history and physical examination and identify children andadolescents who may be at increased risk of morbidity or mortality from sportsparticipation.

2. Recognize that many adolescents make infrequent contact with the medical systemand that the mandatory preparticipation evaluation serves as an opportunity to addressmedical issues not necessarily associated with sports participation.

3. Know the conditions that should be evaluated by a cardiologist before sportsparticipation.

4. Discuss the importance of assessing and documenting neurocognitive function in apreparticipation sports examination.

5. Understand that disqualification from one sport does not imply disqualification fromall sports.

IntroductionSports participation among people of all ages has increased steadily over the past 4 decades.This trend generally has been considered to be a positive development, with conventionalwisdom asserting that sports participation teaches leadership and cooperative skills thathave a lifelong impact. In addition, as the obesity pandemic worsens, organized sportsparticipation and unstructured play or physical exercise can be a source of needed physicalactivity for children and adolescents. The pediatrician often is asked to evaluate a child’s oradolescent’s suitability for sports participation. The purpose of this evaluation has re-mained constant since it was first described in 1978. (1)(2) The goals are to fulfill theinstitution’s legal and liability requirements, provide some assurance to coaches thatathletes will start the season at an acceptable level of health and fitness, provide anopportunity to discover treatable conditions, and aid in predicting and preventing futureinjuries. The evaluation should be practical and applicable to all sports. The specificobjectives of the evaluation can vary, depending on viewpoint, which can create a situationin which parents, athletes, clinicians, and sponsoring institutions or organizations havediscordant expectations. Parents may want to ensure the health and safety of their child.Clinicians may seek to provide preventive care and anticipatory guidance. Institutions and

organizations may want to limit or transfer their liability for injuriesor illnesses caused or worsened by sports participation. Finally, theathletes may just want to have their paperwork signed so they cango play with their friends. The clinician should coordinate andaddress the goals of parents, athletes, and organizations whilepromoting safe participation in physical activity.

The utility of the sports preparticipation evaluation (PPE) hasbeen questioned in recent years. Very few athletes are disqualifiedfrom sports on the basis of findings from the PPE. In the largestevaluation of the PPE, only 1.9% of 2,729 high school athleteswere disqualified from sports participation and only 11.9% requiredany type of follow-up evaluation. (3) A recent systematic review ofthe literature identified 310 studies of the PPE and concluded that

*Department of Pediatrics, University of Iowa, Iowa City, IA.†Departments of Pediatrics and Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI.

Abbreviations

ADHD: attention-deficit/hyperactivity disorderAHA: American Heart AssociationDM1: type 1 diabetes mellitusEIB: exercise-induced bronchospasmNCT: neurocognitive testingPPE: preparticipation evaluationTUE: therapeutic use exemptionVCD: vocal cord dysfunction

Article sports medicine

Pediatrics in Review Vol.32 No.5 May 2011 e53. Provided by Health Internetwork on May 2, 2011 http://pedsinreview.aappublications.orgDownloaded from


the evaluation likely does little to prevent morbidity andmortality in screened athletes and is ineffective for iden-tifying athletes at risk for sudden cardiac death or ortho-pedic injuries and at detecting exercise-induced bron-chospasm (EIB). (4) However, use of the PPE isendorsed by the American Academy of Pediatrics, Amer-ican Academy of Family Physicians, and American Col-lege of Sports Medicine because it allows for establish-ment of a medical home, updating of immunizations,identification and management of chronic health condi-tions, and provision of anticipatory guidance related tosports and other lifestyle risk factors.

Structure of the EvaluationThe PPE is required before practice and play by mostsporting organizations. The requirement is typically inplace to shield the organization from liability and toensure that the athlete can participate safely in sports.The evaluation is required by law in many states andsome countries. Nearly all high-school and middle-school athletes are required to obtain signed documen-tation of a completed examination every 1 to 2 academicyears. Athletes engaged in club- or federation-level sportsare also often required to have documentation of anevaluation, but this practice varies regionally and bysport. Rarely, sports competitions not affiliated withinstitutions or federations (eg, open races or tourna-ments) require documentation of the athlete’s suitabilityfor competition. Generally, open or free play (such as onan open playground) does not require such documenta-tion. However, the 2010 PPE Monograph emphasizesthat clinicians should perform a PPE-type evaluation onall patients when promoting physical activity. (5)

Most institutions and organizations that require anevaluation strictly prevent participation until proper doc-umentation has been obtained. This practice seems to bedue to a sense that protection from liability is not presentuntil there is “proof” that the athlete is safe to participate.(6)(7) Although this concept has not been legally tested,a 1990 New York State Appellate Court decision (Mur-phy v. Blum) suggests that the issue of transfer of liabilitydepends on the specifics of the relationship between theorganization and the physician as well as between thephysician and the athlete. (8)

The athlete should be encouraged to schedule thePPE well in advance of the season, ideally at least 6 weeksbefore the start of practice. This timing allows sufficienttime for full evaluation of issues that may arise during theinitial visit. It also allows implementation of injury pre-vention programs or rehabilitation of injuries before thestart of the season. The clinician should not be pressured

into premature clearance of an athlete before appropriateevaluation is completed.

The PPE can be completed in any of several formats,each of which has advantages and shortcomings. Themost common and ideal format is the office-based PPE inwhich an athlete visits his or her primary care clinician inthe office. The advantages of this strategy include im-proved continuity of care, access to medical records, timefor anticipatory guidance, and ease of arrangingfollow-up diagnostic tests and treatment. The primarydisadvantages are the time burden and cost of an officevisit in addition to the possible limited availability ofappointments before the start of sports seasons.

To alleviate the time and cost burden of the PPE, theother strategy commonly employed is the station-basedPPE. With this approach, the athlete cycles through aseries of stations at which a single aspect of the evaluationis performed. Separate stations may address vital signs,visual acuity screening, medical history and physical ex-amination, orthopedic history and physical examination,updating immunizations, and finally meeting with a cli-nician to review all of the accumulated data and make adecision regarding clearance. This approach is very effi-cient, can be inexpensive, and allows specialty care ateach of the stations, limiting the need for a specialist.Entire teams or schools can be evaluated in a singlesession, reducing the administrative burden of schedul-ing each athlete privately.

However, there are significant disadvantages to thestation-based approach. Continuity of care is severelylimited, including access to previous medical records.Coordination of care may be difficult for issues requiringfollow-up. There is less privacy and time for anticipatoryguidance, and the athlete may be less likely to discusssensitive issues. Finally, athletes who previously havebeen disqualified from sports participation may attemptto take advantage of unfamiliar clinicians and use thestation-based format as a second chance to get cleared.

Obtaining the Medical HistoryThe history portion of the PPE is similar to the history ina typical health supervision visit for a child or adolescentof the same age. Although several efficient screeningtools that have been designed specifically for the PPE areendorsed by multiple professional societies, they shouldnot replace more extensive history collection when it iswarranted. The history form from the 2010 PPE Mono-graph is shown in Figure 1.

It is important to explore the past medical, surgical,family, social, and developmental histories, much as itwould be done for a nonsports-related evaluation. It is

sports medicine preparticipation sports evaluation

e54 Pediatrics in Review Vol.32 No.5 May 2011. Provided by Health Internetwork on May 2, 2011 http://pedsinreview.aappublications.orgDownloaded from


Figure 1. History form for preparticipation evaluation.




also important to interview a parent or guardian, ifavailable, because athlete and parent histories are ofteninconsistent. (9)(10)

Some aspects of the history require additional atten-tion. Although the following list is not comprehensive, itrepresents some of the most common challenges to theclinician during the PPE.

CardiovascularThe component of the PPE that receives the most atten-tion from parents, coaches, administrators, the medicalliterature, and the popular press is the cardiovascularevaluation. Although a comprehensive discussion of thecontroversy surrounding preparticipation cardiovascularscreening is beyond the scope of this article, Pediatrics inReview has published a summary of the topic, (11)(12)and clear guidelines from the American Heart Associa-tion (AHA) discuss the controversy surrounding theevaluation and the role of preparticipation electrocardi-ography and echocardiography. (13) The AHA-recommended components of the preparticipation car-diovascular evaluation are listed in the Table.

Several red flags that may appear in the past medicaland family history should prompt further investigation.Known congenital heart disease, cardiac channelopathies(such as long QT or Brugada syndrome), any history ofmyocarditis, and coronary anomalies such as thosecaused by Kawasaki disease should be evaluated by acardiologist before sports participation. A personal his-tory of syncope, near-syncope, chest pain, palpitations,or excessive shortness of breath or fatigue with exertionshould prompt a more thorough evaluation, either by theprimary clinician or a cardiologist. Postexertional syn-cope is a common occurrence that is frequently elicited inthe PPE history. This benign condition should be differ-entiated from exercise-associated collapse, which occursduring exertion and is an ominous sign of hemodynam-ically significant cardiovascular disease or ventriculartachyarrhythmias. All patients who experience syncopeshould undergo electrocardiography, with further test-ing on a case-by-case basis.

A family history of early sudden cardiac death, Marfansyndrome, cardiomyopathy, and arrhythmias (especiallylong QT syndrome) should prompt further cardiovascu-lar evaluation. Particular attention should be paid to anyfamily history of unexplained or poorly characterizeddeaths, such as from drowning, unexplained motor vehi-cle crashes, or seizures. These events may represent un-recognized sudden cardiac death.

MusculoskeletalThe musculoskeletal history is a remarkably sensitivemethod for identifying abnormalities and injuries. Go-mez and associates (14) found the sensitivity of a basicmusculoskeletal history to be 92%, which compares fa-vorably with the estimated 75% sensitivity of a generalmedical history. Inquiring about current injuries and ahistory of injuries requiring evaluation, casting, bracing,surgery, or missed practice or play captures nearly allmusculoskeletal abnormalities that require evaluation ortreatment before sports participation. A sports medicinespecialist may ask about specific orthopedic injuries thatare unique or common to the athlete’s sport, but thisinquiry generally is not necessary for a primary carescreening evaluation.

MedicationsA review of the athlete’s list of current and past medica-tions may provide clues to chronic or recurring medicalconditions that may affect sports participation. In addi-tion, the athlete’s institution or governing sports feder-ation may ban some medications and substances. A com-prehensive review of banned substances is beyond thescope of this article. In general, the athlete is responsiblefor knowing what medications may be banned in his orher sport. The clinician may assist athletes by directingthem to their governing body’s website and bannedsubstance list. Physicians who frequently care forcollege-, national-, and international-level athletesshould be aware of the substances that are banned by theNational Collegiate Athletic Association (15) and theWorld Anti-Doping Agency. (16) Comprehensive lists ofbanned substances can be found at: http://www.ncaa.org/wps/wcm/connect/public/ncaa/student-athlete�experience/ncaa�banned�drugs�list andhttp://www.wada-ama.org/en/World-Anti-Doping-Program/.

Some medications can be taken if the athlete has atherapeutic use exemption (TUE) on file. In some cases,special testing may need to be obtained to meet therequirements of the TUE. TUEs should be filed wellbefore the start of the season to avoid the possibility ofmiscommunication or a gap in treatment of chronicmedical conditions. Often, a permitted medication canbe substituted for a banned substance.

Use of alcohol, tobacco, and other recreational drugsis common among teenagers, including athletes. It isuseful to discuss these substances when discussing med-ications, vitamins, and supplements that the athlete maybe taking.




DermatologicAthletes in certain sports are at addi-tional risk for dermatologic conditionsassociated with their environment orcontact with other athletes. Openwounds should be cleaned and cov-ered for practice and play to reduce therisk of blood-borne pathogen trans-mission. Methicillin-resistant Staphylo-coccus aureus infections have receivedconsiderable attention because theycan result in necrotizing fasciitis, sep-sis, and even amputation. Skin infec-tions such as impetigo, molluscumcontagiosum, tinea, and herpes sim-plex infection are common in sportsthat involve close skin-to-skin contact,such as wrestling and rugby. Each ofthese conditions requires treatment tominimize the risk of transmission.

Many sport federations have spe-cific regulations for how skin infec-tions should be treated and how longathletes should be asymptomatic orunder treatment before returning topractice and competition. Some ath-letes and teams use prophylactic dosesof antiviral medications, such as acy-clovir, for prevention of herpes out-breaks during the season. This practice has not beensystematically evaluated but anecdotally does seem effec-tive for decreasing herpes gladiatorum transmissionamong wrestlers.

Athletes who practice and compete in the sun shoulduse a sun block lotion to minimize their risk of sundamage and skin cancer. Controversy surrounds the ap-propriate sun protection factor for outdoor athletes. Ingeneral, any over-the-counter sun block applied liberallyand frequently provides sufficient protection. Athleteswho have already had significant sun exposure require acareful examination of the sun-exposed skin to monitorfor skin cancer and precancerous lesions.

NeurologicAlthough sports-related concussions are most commonin contact and collision sports, all athletes should beasked about a personal history of concussion or otherhead injury. Often, directed questions about head inju-ries are required to elicit a history of concussion becausemany athletes do not consider an injury in which therewas no loss of consciousness to be a concussion. Specif-

ically, the clinician should ask about any type of headinjury, feeling “dazed” or “foggy,” memory loss, head-aches following a hit to the head, difficulty playing orpracticing following a hit to the head, and any type ofinjury that resulted in a loss of consciousness. The clini-cian should be attuned to the fact that the presentingsigns and symptoms of concussion can be subtle.

If the athlete does provide a history of concussion,more detailed questioning is required to determine thepresence or absence of frequent concussions, prolongedpostconcussion symptoms, and concussions that oc-curred with seemingly trivial trauma. Athletes who havehad rare, mild concussions that resolved spontaneouslydo not need additional evaluation. For athletes who havehad frequent concussions, are more easily concussed, orhave had prolonged postconcussive symptoms, carefuldiscussion with the athlete and family is necessary tounderstand the risks of repeated concussions. A symp-tomatic athlete should never be allowed to return to play,and a graduated, stepwise approach should be used forreturning to physical activity. (17)

Obtaining baseline computer-based neurocognitive

Table. The 12-element American HeartAssociation Recommendations forPreparticipation Cardiovascular Screeningof Competitive AthletesMedical History

• Personal history–Exertional chest pain/discomfort–Unexplained syncope/near-syncope–Excessive exertional and unexplained dyspnea/fatigue associated withexercise

–Prior recognition of a heart murmur–Elevated systemic blood pressure

• Family history–Premature death (sudden and unexpected, or otherwise) before age 50years due to heart disease in first-degree relative

–Disability from heart disease in a close relative younger than 50 years ofage

–Specific knowledge of certain cardiac conditions in family members:hypertrophic or dilated cardiomyopathy, long QT syndrome and other ionchannelopathies, Marfan syndrome, and clinically important arrhythmias

Physical Examination

• Heart murmur• Femoral pulses to exclude aortic coarctation• Physical stigmata of Marfan syndrome• Brachial artery blood pressure (sitting position)

Data from American Heart Association, Inc.




testing (NCT) before the start of the season is contro-versial. Although clinical assessment should be the main-stay of concussion evaluation, NCT increases the sensi-tivity for detecting residual concussion symptoms. (18)Specifically, if baseline NCT is available when a con-cussed athlete clinically appears ready to return to play,repeat NCT can provide an objective measurement of hisor her recovery. However, NCT has poor specificity forconcussion, and the utility of postinjury NCT in anathlete who does not have a baseline study is controver-sial.

“Stingers,” also called “burners,” are injuries to thebrachial plexus caused either by direct trauma or a trac-tion injury. Symptoms are typically brief. Athletes whohave had stingers with persistent symptoms of arm pain,paresthesia, or weakness may have more significant inju-ries to the brachial plexus or cervical nerve root injury.No athlete should be permitted to return to practice orplay who has persistent symptoms.

Cervical cord neurapraxia, also called transient quad-riplegia, is a frightening condition characterized by tem-porary loss of motor control, with or without loss ofsensation or paresthesia, caused by transient compressionof the cervical spinal cord due to forced hyperextension,hyperflexion, or axial loading. The condition is morecommon in athletes who have cervical spinal stenosis.(19) Episodes are transient and typically last less than15 minutes. It is very rare for symptoms to last longerthan 48 hours. There is no increased risk of permanentspinal cord injury following a single episode, (19)(20)but athletes who have multiple episodes or persistentsymptoms require additional evaluation. Those who arefound to have instability, fractures, or degenerativechanges in the cervical spine should not be allowed toreturn to contact or collision sports. Although athleteswho have cervical spinal stenosis are at increased risk ofcervical cord neurapraxia, it is unknown if they are atincreased risk for permanent spinal cord injury. Whetherathletes who have spinal stenosis should be allowed toplay contact sports is controversial and should be evalu-ated on a case-by-case basis by a qualified physician.

Heat IllnessHeat illness kills more than 1,000 people in the UnitedStates every year. (21) Athletes who have had a history ofheat illness are at risk for future heat illness, includingheat stroke. Once identified, the athlete can take mea-sures to assure proper hydration and acclimatization tominimize their risk. In addition, stimulants and antihis-tamines increase the risk of heat illness and should be

avoided, if possible, during training and competition inwarmer weather.

OphthalmologicAthletes who require corrective lenses for sports partici-pation may need to work with an optometrist or ophthal-mologist to ensure that they have appropriate lenses forsport. Some sports, such as wrestling, boxing, and rugby,do not allow eyewear, so athletes in need of correctivelenses must use contact lenses. Athletes whose best-corrected vision is worse than 20/40 in one eye (alsoreferred to as “functionally one-eyed”) must wear Amer-ican Society for Testing and Materials-approved protec-tive eyewear. (22)

Athletes who practice and compete in the sun or onthe snow should wear ultraviolet-blocking eyewear toprevent acute photoretinitis and possibly decrease thechance of developing cataracts. In addition, any baselineocular abnormality or normal variant should be docu-mented. Being aware of baseline anisocoria or abnor-mally shaped pupils can help to prevent an unnecessaryevaluation if the athlete presents later with a head or eyeinjury.

PulmonaryAthletes who have baseline lung disease may requireadditional evaluation or a change in their treatmentregimen before the season. Athletes who have knownEIB should have an active prescription for a bronchodi-lator such as albuterol. Such athletes may benefit fromhaving multiple inhalers to keep in multiple settings,such as at home, at school, and with their coach orathletic trainer. In general, athletes who have isolatedEIB do not benefit from inhaled corticosteroids. How-ever, there is significant overlap between asthma andEIB. In general, if an athlete has symptoms in othersettings and the EIB is poorly controlled with broncho-dilator monotherapy, adding a controller medication,such as an inhaled corticosteroid, may be beneficial. (23)

Some athletes compete in sports or under federationrules that require them to obtain a TUE before usingbronchodilators. As mentioned, it is important to obtainappropriate pulmonary function tests and to completethe TUE paperwork well in advance of the season.

Vocal cord dysfunction (VCD) is another commonrespiratory complaint among athletes. Triggers or asso-ciated risk factors for VCD include allergic rhinitis, gas-troesophageal reflux disease, anxiety, and poorly con-trolled asthma. The diagnosis can be made with a historyof isolated inspiratory stridor (typically worse in compe-tition situations) or with laryngoscopy. Most athletes can




control their symptoms with special breathing tech-niques that require intensive teaching and are best taughtby speech therapists or other professionals who are famil-iar with VCD. Like other chronic medical conditions,gaining control of VCD symptoms before the start of thesports season is important for increasing the likelihood ofsuccess.

A history of other chronic pulmonary diseases, such ascystic fibrosis or chronic lung disease due to bronchopul-monary dysplasia, should not automatically disqualify achild or adolescent from sports participation. Carefulpartnership and close follow-up with a pulmonologist orother clinician who is familiar with the specific disorder isessential. It may be reasonable to dissuade children andadolescents who have severe lung disease from participat-ing in sports that impose a high cardiovascular demandand steer them toward sports in which they are morelikely to find success.

GastrointestinalAlthough gastrointestinal complaints are commonamong children and adolescents, very few require dis-qualification or modified sports participation. Diarrheamay put the athlete at increased risk of dehydration, butdehydration usually can be prevented with increased fluidintake. Gastroesophageal reflux disease can worsen withincreased physical activity but usually can be controlledwith diet modification. Gastric acid-suppressing medica-tions (histamine-2 receptor blockers and proton pumpinhibitors) may be necessary in some patients. Becauseinflammatory bowel disease can cause a profound anemiathat can make physical activity more difficult and impairperformance, close follow-up with a gastroenterologistto help ensure good control of symptoms is essential.

Infectious DiseaseMononucleosis and mononucleosis-like infection causedby viral infections (typically Ebstein-Barr virus, but occa-sionally cytomegalovirus) can cause splenomegaly andput the athlete at increased risk for splenic rupture. Anyathlete who has mononucleosis should be disqualifiedfrom practice and competition in any sport in whichthere is a risk of abdominal trauma. Most athletes are safeto return to sport by 3 to 4 weeks after the start ofsymptoms. (24)

Blood-borne pathogens, including human immuno-deficiency virus and infectious hepatitis, should notprompt disqualification from sports. (25) The athletemay participate in any sport that his or her health allows.Universal precautions should be used for all athletes, and

skin lesions should always be covered properly, regardlessof any known or suspected infectious disease.

GenitourinaryFew components of the genitourinary history shoulddisqualify an athlete or require modified participation.Athletes who have a solitary or horseshoe kidney requireindividual assessment for contact and collision sports.(26) Protective equipment may be necessary to protectthe remaining kidney, and the risks of injury should beweighed carefully against the benefits of contact or col-lision sport participation. Inguinal hernias may worsenwith increased physical exertion, especially in sports suchas weightlifting that impose a high static demand (in-creased muscle tension with relatively no change in mus-cle length or joint mobility). Females who experienceamenorrhea or oligomenorrhea should be assessed foreating disorders and impaired bone health. Female ado-lescents who exercise intensively or play sports (especiallythose sports that emphasize leanness) are at risk fordeveloping the “female athlete triad” of disordered eat-ing, amenorrhea, and osteoporosis that is associated withsignificant health problems later in life.

PsychologicalEating disorders are common among athletes in weight-restricted and esthetic sports. Many athletes do not meetdiagnostic criteria for anorexia nervosa or bulimia ner-vosa but clearly have disordered eating patterns. Theycan be diagnosed as having eating disorder not otherwisespecified, which has been included in the most recentversion of the Diagnostic and Statistical Manual of Men-tal Disorders. (27) Screening for disordered eatingshould be performed as part of every PPE. Several vali-dated screening instruments are available, but the mostcommonly used is the 26-item Eating Attitudes Test.(28) Screening tools for disordered eating generally as-sess the patient’s body image and screen for abnormaleating behaviors, such as irrational avoidance of certainfoods, ritualistic approaches to meals (eg, very slow eat-ing, cutting food into very small pieces, extraordinarycalorie counting), vomiting, or engaging in excessiveexercise after meals.

Disordered eating is one of the three elements of thefemale athlete triad, along with amenorrhea and de-creased bone mineral density. The presence of any one ofthese conditions should prompt the clinician to evaluatefor the other two. The female athlete triad puts theathlete at risk for stress fractures. Although not an abso-lute contraindication to sports participation, complica-tions of an eating disorder (including electrolyte abnor-




malities and cardiac rhythm disturbances) need to bemonitored. A multidisciplinary team, including physi-cians, dietitians, and mental health professionals, is essen-tial for the necessary care of an athlete who has an eatingdisorder.

Depression and anxiety are common mental healthproblems that can appear in athletes. Unless severe, theseconditions should not disqualify the athlete from sportsparticipation. Mental health professionals may help theathlete to cope better with his or her psychologicalsymptoms. Often, athletes can be persuaded to use men-tal health services by discussing the possible performanceimprovements that might come from controlling theirdepression or anxiety.

The prevalence of attention-deficit/hyperactivity dis-order (ADHD) among athletes is similar to the preva-lence among other children and adolescents of the sameage. Stimulant medications are a common treatment butmay require a TUE or documentation of ADHD testingbefore the start of the sports season.

ImmunizationThe PPE provides an opportunity to review the immu-nization history and provide catch-up immunizations.Although missing immunizations should not be criteriafor sports disqualification, athletes and clinicians shouldbe aware that some immunizations are required byschools and colleges for enrollment. In addition, athleteswho are competing internationally may need documen-tation of specific immunizations to gain entry into certaincountries.

The Physical ExaminationThe PPE physical examination varies little from the stan-dard health supervision evaluation, although a few com-ponents require additional attention in the athlete.

Vital SignsThe vital signs of an athlete may be different from what aclinician is used to seeing in nonathletes. A child oradolescent who has a high degree of cardiovascular fit-ness may have bradycardia and a wide pulse pressure.Respiratory rate may be lower than expected when rest-ing but may be elevated for several hours after exercise.Body mass index may be an inaccurate method of screen-ing for overweight and obesity in some athletes who arevery muscular. The blood pressure should be normal.Elevated blood pressure in children and adolescents,regardless of sports participation, requires evaluation andtreatment. For idiopathic or “essential” hypertension,one of the first-line treatments is exercise. Athletes who

have mild-to-moderate hypertension (�95th percentilefor age, sex, and height) require evaluation but should beencouraged, rather than prohibited, from participating insports. Athletes who have severe hypertension (charac-terized as �5 mm Hg over the 99th percentile for age,sex, and height) should be disqualified from sports char-acterized by a high static demand and avoid heavy weighttraining and powerlifting. (29)(30)

Head and NeckCorrected visual acuity should be better than 20/40 inboth eyes. If not, protective lenses are required for con-tact sports participation. (22) Auricular cartilage damageshould prompt the clinician to remind the athlete to useear protection for sports such as wrestling and rugby.Nasal septum damage should prompt referral to an oto-laryngologist. Dental carries may indicate overuse ofsports drinks or eating disorders such as bulimia.

CardiovascularThe AHA-recommended elements of the cardiovascularevaluation are listed in the Table. In general, any cardiacabnormality that is not clearly benign should be fullyevaluated before sports participation. A pediatric cardiol-ogist who is familiar with the demands of sport partici-pation should perform the follow-up evaluation. It is bestto avoid ordering echocardiography and other advancedcardiac testing from facilities that are unfamiliar withcongenital heart disease and sport participation in chil-dren.

GenitourinaryThe female genitourinary examination is not a standardpart of the PPE. However, any concerns raised by find-ings on the patient’s history should be evaluated appro-priately. Males should have two descended testicles. Anymale who has an undescended or absent testicle shouldbe evaluated by a urologist. Athletes who have only onefunctional testicle may participate in all sports but shouldbe encouraged to use a protective cup to decrease the riskof injury in contact or collision sports. The PPE allowsthe clinician an opportunity to discuss testicular self-examination with the older adolescent. Males who have ahistory of groin pain should be evaluated for an inguinalhernia with a digital examination of the inguinal ring.Asymptomatic athletes do not need to be screened forhernias. (5)

DermatologicAny infectious skin condition should be treated beforethe athlete’s return to sport. Any skin lesions that are




suspicious for malignancy should be removed and evalu-ated by a pathologist.

NeurologicAny history of neurologic injury, including concussionsand stingers, should prompt a detailed neurologic eval-uation. The assessment should include cognitive func-tion, cranial nerves, sensation, strength, tone, reflexes,and cerebellar function. Any abnormality should be eval-uated thoroughly before sports participation.

MusculoskeletalClinicians often feel compelled to perform a detailedmusculoskeletal examination on athletes who present fora PPE. However, as discussed, the physical examinationadds little diagnostic value to the orthopedic history.(14) A cursory evaluation of strength and range of mo-tion is sufficient for athletes who have no musculoskeletalcomplaints. Focused, detailed examinations of specificjoints can be reserved for evaluating previous injuries orcurrent complaints.

The Laboratory EvaluationNo screening laboratory or imaging tests are required aspart of a routine PPE. Significant controversy surroundsthe use of screening echocardiography and electrocardi-ography to detect occult congenital heart disease. (13) Inaddition, the utility of testing for hemoglobinopathies,anemia, bleeding disorders, infectious diseases, cardio-vascular risk factors (such as hypercholesterolemia), andother chronic diseases that may affect athletic perfor-mance or general health is unclear.

Special SituationsFewer than 2% of PPEs result in disqualification of theathlete from sport. However, many medical conditionsrequire adaptation or close monitoring for complicationsrelated to sports participation. In addition, sporting ac-tivities are heterogeneous in their physical and cardiovas-cular demands as well as in their level of contact. Certainmedical conditions may be incompatible with particularstatic or dynamic (changes in muscle length or jointmobility with relatively small change in muscle tension)demands or with the risks associated with contact orcollision sports. A comprehensive review of the medicalconditions affecting sports participation is beyond thescope of this article, but several conditions that fre-quently come to clinical attention during the PPE arediscussed. This list is far from exhaustive, and the readerwho is interested in learning more about the specificdemands of sports participation and how many common

and uncommon medical conditions affect sports partici-pation should see the American Academy of PediatricsCouncil on Sports Medicine and Fitness’s report on“Medical Conditions Affecting Sports Participation.”(26)

SeizuresThe child or adolescent who has a well-controlled seizuredisorder should not be disqualified from sports participa-tion. (26) In these athletes, the risk of having a seizureduring practice or competition is very low, partially dueto their already low seizure frequency but also due to theantiepileptic effects of exercise. It is sometimes surprisingto officials and policy makers that athletes who haveknown seizure histories can be allowed to participate incontact and collision sports and in sports where theywould seem to be at increased risk of injury should theyhave a seizure. The clinician may need to advocate for theathlete in such situations. A useful point of reference isthe individual state’s legal seizure-free interval beforeindividuals who have epilepsy are allowed to return todriving. In most states, it is 3 to 6 months.

Children and adolescents who have poorly controlledepilepsy also benefit from physical exercise, but more caremust be taken to ensure the safety of these athletes andthose around them. An individual assessment should bemade to determine the athlete’s suitability for contactand collision sports. The following sports should beavoided:

● Archery● Power lifting● Riflery● Swimming● Weight lifting● Weight training● Sports involving heights (eg, parachuting, hang-

gliding)

Down SyndromeDown syndrome, also known as trisomy 21, is a geneticsyndrome involving multiple congenital anomalies. Chil-dren born with Down syndrome often require interdis-ciplinary care to maximize their health outcomes andquality of life, regardless of sports participation. Of note,instability of the cervical spine (primarily atlantoaxialinstability, but also occipitoatlantal instability) has beenreported in up to 30% of patients who have Downsyndrome. (31) The Special Olympics® organizationrequires radiographic evaluation of the cervical spinebefore sports participation. It is common for patients




who have had normal cervical spine radiographs to ac-quire cervical instability. For this reason, patients whohave Down syndrome should be prohibited from partic-ipating in collision sports regardless of the radiographicappearance of their spines. However, no other limita-tions need be imposed for patients who have normalcervical spine radiographs. Patients who have radio-graphic evidence of cervical instability but no neurologicsigns or symptoms should be disqualified from “neck-stressing” sports. Special Olympics considers diving,gymnastics, butterfly stroke, high jumping, soccer, andpentathlon to be “neck-stressing.” Athletes who haveDown syndrome and cervical instability may use a cervi-cal collar, but this practice does not change their sportrestriction.

Down syndrome is associated with other abnormali-ties that may influence sports participation, such as car-diac abnormalities (septum defects in particular), cata-racts, diabetes, thyroid disease, hip and patellarinstability, and foot abnormalities. Each of these condi-tions, if present, requires evaluation before sports partic-ipation. However, no other special precautions need tobe taken for these children.

Acute Febrile IllnessAthletes who have a fever should be prohibited frompractice and competition. (26) Fever puts the athlete atrisk for acute heat illness (due to increased heat storage),reduced maximal exercise capacity, and hypotension(due to decreased peripheral vascular tone and possiblydehydration).

Type 1 Diabetes MellitusAthletes who have type 1 diabetes mellitus (DM1) arepermitted to participate in any sport without restriction.(26) However, DM1 monitoring and treatment oftenbecomes more complex with the varying demands oforganized sports. Careful evaluation and monitoring ofblood glucose, diet, insulin types and doses, and hydra-tion status are essential. Blood glucose should bechecked more frequently than usual. At a minimum,athletes who have DM1 should measure their bloodglucose every 30 minutes during continuous exercise,15 minutes after completion of exercise, and at bedtime.For optimum control and performance, many athleteswho have DM1 find that they need to measure theirblood glucose and modulate their insulin and carbohy-drate intake frequently. Insulin pumps and rapid-actinginsulins have allowed athletes to fine-tune their glycemiccontrol much more effectively than in the past. It is notuncommon for athletes who have DM1 to develop com-

plex treatment plans involving both pump and injectableinsulin therapy.

The Disabled AthleteDisabled athletes may face special challenges, but theclinician should encourage exercise and sports participa-tion for the same reasons they are encouraged in able-bodied athletes. (5) Good communication among ath-letes, coaches, parents, and clinicians is essential forensuring safe and successful sports participation. Thesupplemental history form from the 2010 PPE mono-graph (Fig. 2) can help to facilitate this communication.

When to Disqualify an Athlete From SportsParticipationAlthough most complaints and abnormalities identifiedduring the PPE are not absolute contraindications tosports participation, several conditions should promptdisqualification from sport. Most of these are cardiovas-cular conditions and have been outlined in the 36thBethesda Conference guidelines: (32)

● Pulmonary vascular disease with cyanosis or a hemody-namically significant right-to-left shunt

● Severe pulmonary stenosis (untreated)● Severe aortic stenosis or regurgitation (untreated)● Severe mitral stenosis or regurgitation (untreated)● Any cardiomyopathy● Vascular Ehlers-Danlos syndrome● Coronary anomalies (especially anomalous coronary

origins)● Catecholaminergic polymorphic ventricular tachycar-

dia● Acute pericarditis● Acute myocarditis● Acute Kawasaki disease

Although the guidelines from the 36th Bethesda con-ference only comment on disqualification for thesespecific conditions, any cardiovascular disease shouldbe thoroughly evaluated and treated by a pediatriccardiologist to ensure the athlete’s safe participation insports.

In addition to cardiac abnormalities, any conditionthat cannot be well controlled and puts the athlete at riskof significant injury or death or endangers the health ofteammates or competitors requires further evaluation ordisqualification from sport. For example, a musculoskel-etal injury that impairs the athlete’s ability to protecthim- or herself during practice and competition shouldprompt disqualification until the athlete is safely able toreturn to play. For a discussion of the evaluation and




Figure 2. Supplemental history form for athletes who have special needs.




management of specific sports-related injuries, please seethe recent Pediatrics in Review article, “Managing SportsInjuries in the Pediatric Office.” (33)

In performing the PPE, the clinician’s first responsi-bility is to ensure the health and safety of the patient.However, the physical and psychological benefits of ex-ercise and sport participation should weigh heavily ondecisions to disqualify an athlete from sport.

References1. Garrick JG. Preparticipation orthopedic screening evaluation.Clin J Sport Med. 2004;14:123–1262. Garrick JG, Requa RK. Injuries in high school sports. Pediatrics.1978;61:465–4693. Smith J, Laskowski ER. The preparticipation physical examina-tion: Mayo Clinic experience with 2,739 examinations. Mayo ClinProc. 1998;73:419–4294. Hulkower S, Fagan B, Watts J, Ketterman E, Fox BA. Clinicalinquiries: do preparticipation clinical exams reduce morbidity andmortality for athletes? J Fam Pract. 2005;54:628–6325. Bernhardt DT, Roberts WO, American Academy of FamilyPhysicians, American Academy of Pediatrics. PPE: PreparticipationPhysical Evaluation. 4th ed. Elk Grove Village, IL: American Acad-emy of Pediatrics; 2010

6. Herbert DL. Legal Aspects of Sports Medicine. 2nd ed. Canton,OH: PRC Publishers; 19957. Gallup EM. Law and the Team Physician. Champaign, IL:Human Kinetics Publishers; 19958. Murphy v Blum, 160 AD 2d 914: NY, Apellate Div, (1990)9. Risser WL, Hoffman HM, Bellah GG Jr. Frequency of prepar-ticipation sports examinations in secondary school athletes: are theUniversity Interscholastic League guidelines appropriate? Tex Med.1985;81:35–3910. Carek PJ, Futrell M, Hueston WJ. The preparticipation phys-ical examination history: who has the correct answers? Clin J SportMed. 1999;9:124–12811. Singh A, Silberbach M. Consultation with the specialist: car-diovascular preparticipation sports screening. Pediatr Rev.2006;27:418–42412. Vitiello R. Commentary: the value of the ECG in the prepar-ticipation sports physical examination: the Italian experience. Pedi-atr Rev. 2006;27:e75–e7613. Maron BJ, Thompson PD, Ackerman MJ, et al. Recommen-dations and considerations related to preparticipation screening forcardiovascular abnormalities in competitive athletes: 2007 update: ascientific statement from the American Heart Association Councilon Nutrition, Physical Activity, and Metabolism: endorsed by theAmerican College of Cardiology Foundation. Circulation. 2007;115:1643–145514. Gomez JE, Landry GL, Bernhardt DT. Critical evaluation ofthe 2-minute orthopedic screening examination. Am J Dis Child.1993;147:1109–111315. NCAA Drug Testing Program. Accessed February 2011 at:http://www.ncaa.org/wps/wcm/connect/public/ncaa/student-athlete�experience/ncaa�banned�drugs�list16. World Anti-Doping Agency. Accessed February 2011 at:http://www.wada-ama.org/17. McCrory P, Meeuwisse W, Johnston K, et al. Consensusstatement on concussion in sport: the 3rd International Conferenceon Concussion in Sport held in Zurich, November 2008. Br J SportsMed. 2009;43(suppl 1):i76–i9018. Van Kampen DA, Lovell MR, Pardini JE, Collins MW, Fu FH.The “value added” of neurocognitive testing after sports-relatedconcussion. Am J Sports Med. 2006;34:1630–163519. Pavlov H, Torg JS, Robie B, Jahre C. Cervical spinal stenosis:determination with vertebral body ratio method. Radiology. 1987;164:771–77520. Torg JS, Pavlov H, Genuario SE, et al. Neurapraxia of thecervical spinal cord with transient quadriplegia. J Bone Joint SurgAm. 1986;68:1354–137021. Centers for Disease Control and Prevention. Heat-relatedDeaths — United States, 1999–2003. MMWR Morb Mortal WklyRep. 2006;55:796–79822. Protective eyewear for young athletes. Pediatrics. 2004;113:619–62223. Expert Panel Report 3 (EPR-3): guidelines for the diagnosisand management of asthma-summary report 2007. J Allergy ClinImmunol. 2007;120(5 suppl):S94–S13824. Putukian M, O’Connor FG, Stricker P, et al. Mononucleosisand athletic participation: an evidence-based subject review. ClinJ Sport Med. 2008;18:309–31525. Committee on Sports Medicine and Fitness. American Acad-emy of Pediatrics. Human immunodeficiency virus and otherblood-borne viral pathogens in the athletic setting. Pediatrics.1999;104:1400–1403

Summary• In general, the evidence base for the PPE is limited.

(5)• The clinician should coordinate and address the

goals of parents, athletes, and organizations whilepromoting safe participation in physical activity.

• Based on at least fair evidence, the PPE does little toprevent morbidity and mortality in athletes. (4)

• Based on expert opinion, the PPE is best performedwell in advance of the competitive season. (5)

• Based on expert opinion, the office-based PPE ispreferable to the station-based approach. (5)

• Based on at least fair evidence, clinicians shouldfocus on the medical and musculoskeletal historybecause most conditions that affect participation areelicited from that history. (5)(13)(14)

• Based on expert opinion, athletes who have suffereda concussion should not be allowed to return to playwhile symptomatic and should follow a stepwiseprogression of graduated return to full activity. (17)

• Based on expert opinion, screening echocardiographyand electrocardiography should not be routine partsof the PPE. (13)

• Based on expert opinion, athletes who have lost apaired organ may compete in any sport with properprotective equipment. (22)(26)

• Based on expert opinion, most athletes who havechronic medical conditions can compete safely inmost sports. (26)




26. Rice SG. Medical conditions affecting sports participation.Pediatrics. 2008;121:841–84827. American Psychiatric Association Task Force on DSM-IV. Diag-nostic and Statistical Manual of Mental Disorders. DSM-IV-TR. 4thed. Washington, DC: American Psychiatric Association; 200028. Garner DM, Olmsted MP, Bohr Y, Garfinkel PE. The EatingAttitudes Test: psychometric features and clinical correlates. PsycholMed. 1982;12:871–87829. McCambridge TM, Benjamin HJ, Brenner JS, et al. Athleticparticipation by children and adolescents who have systemic hyper-tension. Pediatrics. 2010;125:1287–129430. The fourth report on the diagnosis, evaluation, and treatment

of high blood pressure in children and adolescents. Pediatrics.2004;114(2 suppl):555–57631. Winell J, Burke SW. Sports participation of children withDown syndrome. Orthop Clin North Am. 2003;34:439–44332. Pelliccia A, Zipes DP, Maron BJ. Bethesda Conference#36 and the European Society of Cardiology consensus recom-mendations revisited: a comparison of U.S. and European crite-ria for eligibility and disqualification of competitive athletes withcardiovascular abnormalities. J Am Coll Cardiol. 2008;52:1990–199633. Metzl JD. Managing sports injuries in the pediatric office.Pediatr Rev. 2008;29:75–84

HealthyChildren.org Parent Resources from AAPThe reader is likely to find material to share with parents that is relevant to this article bygoing to this link: http://www.healthychildren.org/English/healthy-living/sports/Pages/default.aspx




DOI: 10.1542/pir.32-5-e53 2011;32;e53-e65 Pediatr. Rev.

Andrew R. Peterson and David T. Bernhardt The Preparticipation Sports Evaluation


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