Pediatrics in Review_February2011

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ArticlesThe Common Cold and Decongestant Therapy47Diane E. Pappas, J. Owen Hendley

Somatization Disorders:Diagnosis, Treatment, and Prognosis56Tomas Jose Silber

Focus on Diagnosis: Urine Electrolytes65J. Bryan Carmody

Ethics for the Pediatrician:Ethical Issues in Organ Donation69Robert Macauley

Research and Statistics:Distinguishing Statistical Significance fromClinical Importance: The Value of the P Value73Sharon R. Ghazarian

Index of SuspicionCase 1: Nonbilious Projectile Vomiting in a NeonateCase 2: Fever, Rash, Headache, Myalgia, and

Arthralgia in an 11-year-old BoyCase 3: Ecchymotic Lesions on the Backs of Asian Boys75Case 1: John D.A. Campagna, Minela Fernandez,

Lance YamashiroyaCase 2: Ronen Zipkin, Marwa Moustafa, Shira RosenbergCase 3: Ryan P. Flanagan, Neil Mullen

In BriefCataracts82Karen M. Davenport, Archana A. Patel

Balance and Vertigo in Children84Jacques Benun

Issues in Chemotherapy86Elizabeth A. Van Dyne

Internet-Only ArticlesAbstracts appear on page 81.

Complementary, Holistic,and Integrative Medicine:Therapies for Learning Disabilitiese18Elaine Z. Galicia-Connolly, Larissa Shamseer, Sunita Vohra

Global Child Healthe25Donna Denno

Cover: The artwork on the cover of thismonth’s issue is by one of the winners ofour 2009 Cover Art Contest, 8-year-oldErica G of Everett, WA. Erica’s pediatri-cian is Carolyn Sherman, MD.

contentsPediatrics inReview� Vol.32 No.2 February 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: Sydney Sutherland, Kathleen BernardEditorial 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 2010 for print and online/online only: AAP Fellow $172/$131; AAP Candidate Fellow $161/$120; Nonmember $215/$167; AlliedHealth or Resident $160/$108. Institutions call for pricing (866-843-2271). Foroverseas delivery, add $95. Current single issue price is $10 domestic, $12international. Replacement issues must be claimed within 6 months from the dateof issue and are limited to three per calendar year.Periodicals postage paid at ARLINGTON HEIGHTS, ILLINOIS and atadditional 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.

● 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.

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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.32-2-47 2011;32;47-55 Pediatr. Rev.

Diane E. Pappas and J. Owen Hendley The Common Cold and Decongestant Therapy

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The Common Cold and Decongestant TherapyDiane E. Pappas, MD, JD,*

J. Owen Hendley, MD*

Author Disclosure

Drs Pappas and

Hendley have

disclosed no financial

relationships relevant

to this article. This

commentary does

contain a discussion

of an unapproved/

investigative use of a

commercial

product/device.

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

1. Discuss the clinical presentation, diagnosis, and complications of the common cold inchildren.

2. Describe the viral causes and pathogenesis of the common cold.3. Describe transmission of the common cold.4. Explain the systemic effects of oral decongestants and antihistamines in infants and

young children.5. Recognize that over-the-counter cough and cold preparations have not been ade-

quately studied in children younger than 6 years of age and are not recommended.6. List the active ingredients and potential toxicities of over-the-counter cough and cold

medications.

IntroductionThe common cold heralds the beginning of the fall and winter seasons for pediatricians.Almost every ill patient presents with the runny nose, cough, and congestion that are thehallmarks of the common cold. Although colds are self-limited, most patients (and theirparents) are tired and uncomfortable as a result of these symptoms. No effective treatmentscan be prescribed or recommended beyond ordinary supportive care.

Clinical PresentationChildren typically present with cough, sneezing, nasal congestion, and runny nose. Nasaldischarge may be clear initially but often turns yellow-green within a few days. Fever maybe present initially in preschool-age patients, but vomiting and diarrhea are uncommon.Parents also may report sleep disturbance and increased fatigue. Symptoms persist for atleast 10 days in most children but should begin to lessen by this time. This clinical picturediffers substantially from colds in adults, which present with the typical nasal discharge,cough, and congestion but no fever and a usual duration of only 5 to 7 days. Sore throator hoarseness also may be present in children and adults. (1)

DiagnosisCommon cold is a clinical diagnosis. Subjective complaints may include nasal stuffiness,sore throat, and headache. Objective findings are few but may include fever, anteriorcervical lymphadenopathy, erythema of the nasal mucosa and oropharynx, and nasaldischarge. Laboratory tests are not helpful; commercially available rapid tests are availablefor detection of respiratory syncytial virus (RSV) and influenza. Other conditions toconsider in the diagnosis include nasal foreign body, allergic rhinitis, vasomotor rhinitis,bacterial sinusitis, rhinitis medicamentosa, and structural abnormalities of the nose orsinuses. History and physical examination should be sufficient to differentiate theseconditions from the common cold.

ComplicationsSecondary bacterial infections and wheezing may complicate the common cold. Bacterialinfections include otitis media, sinusitis, and pneumonia. About 30% of colds in preschool-age children may be complicated by otitis media, (2) and this risk is highest in children 6 to11 months of age. Sinusitis may occur in 5% to 10% of children who have colds and may be

*Department of Pediatrics, University of Virginia, Charlottesville, VA.

Article respiratory

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considered when symptoms are not improving after10 days, although diagnostic criteria and the benefit ofantimicrobial therapy are controversial. (3)(4) Other po-tential complications include peritonsillar cellulitis andabscess, conjunctivitis, mastoiditis, and meningitis.

Infants and children who have histories of reactiveairway disease or asthma are at particular risk for compli-cations, (5) most importantly for increased severity andduration of respiratory symptoms. As many as 50% ofasthma exacerbations in children are associated with viralinfections, especially rhinovirus. Children who have ele-vated immunoglobulin E concentrations and rhinovirusinfection experience more severe respiratory symptomsthan do other children. Studies in adults suggest that animpaired cellular response to rhinovirus infection resultsin increased viral replication, leading to severe and pro-longed symptoms. RSV also is associated with wheezingexacerbations.

CausesRhinoviruses cause at least 50% of the colds in childrenand adults and, thus, are the most common sources ofcold infections. Other causes of the common cold in-clude adenoviruses, influenza viruses, enteroviruses,RSV, and coronaviruses. Cold viruses are not part of thenormal human flora but are transferred from person toperson and cause the appearance of symptoms 1 to 2 daysafter inoculation.

Some of these viral infections may present as a com-mon cold or as a more specific syndrome. For example,RSV infection in older children and adults typically pre-sents the same as any other cold, but RSV may producebronchiolitis involving the lower respiratory tract in in-fants and toddlers and can produce a severe presentation.Similarly, infection with parainfluenza viruses maypresent as croup in younger children and as a typical coldin the older child. Adenoviral infection may present as acommon cold or as pharyngoconjunctival fever, withinjected palpebral conjunctivae, watery eye discharge,and erythema of the oropharynx in addition to the usualfever and upper respiratory tract symptoms. Enterovi-ruses may produce aseptic meningitis. Coxsackievirus A,an enterovirus, may cause herpangina, with fever andulcerated papules on the posterior oropharynx. Infectionwith influenza viruses may present as a febrile respiratoryillness involving the lower respiratory tract, fatigue, andmuscle aches.

EpidemiologyThe occurrence of the common cold is predictable interms of who is most affected and when colds usually

occur. Cold season begins in September after childrenare back in school, at which time their frequency sharplyelevates and remains at a constant level until springreturns. This epidemic results not from a single cold virusbut from a number of viruses moving through the com-munity during the fall and winter seasons. In the earlyfall, rhinovirus begins to increase; parainfluenza virusesfollow in late fall, with RSV and coronavirus infectionsincreasing during the winter months. Cold season con-cludes with a final surge of rhinovirus infections in thespring. Only a few rhinovirus and enterovirus infectionsare still present in the community in the summer.

Colds are most common in children younger than theage of 6 years, who routinely experience six to eight coldsannually. This frequency may result from susceptibilitydue to lack of previous exposure as well as from thenatural attributes of childhood, namely, curious explora-tion of the world with concomitant poor hygiene. Childcare attendance increases the number of colds experi-enced by young children as a result of repeated exposureto other children. By the teenage years, the frequencydecreases to four to five colds every year, with parents ofyoung children experiencing only three to four coldsannually. Adults who live with young children experiencemore colds than other adults living without young chil-dren in the home.

PathogenesisViral infection of the nasopharyngeal mucosa does notcause the symptoms of the common cold directly, insteadinitiating a host inflammatory response that produces thesymptoms. Cold virus is deposited on the mucosa of thenose or conjunctivae. Virus then attaches to receptors oncells in the nasopharynx and enters the cells. Only a smallnumber of cells become infected. The infected cellsrelease potent cytokines, including interleukin (IL)-8,which is a chemoattractant for polymorphonuclear cells(PMNs). PMNs accumulate in large numbers in the nasalsecretions. Vascular permeability increases and plasmaproteins, including albumin and bradykinin, leak into thenasal secretions, increasing the volume of secretions pro-duced.

Bradykinin can cause rhinitis and sore throat, whichmay contribute further to the discomfort caused by thecold. Mucociliary clearance is slowed. Histamine concen-trations do not increase during the course of the com-mon cold. The nasal mucosa is not destroyed duringrhinovirus and coronavirus infections, but adenovirusand influenza viruses do destroy the nasal mucosa. Symp-tom severity correlates with IL-8 concentration over thecourse of the infection.

respiratory common cold

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Infected cells are extruded and washed away with thesecreted inflammatory mediators, preventing spread ofthe virus to nearby cells. Viral replication declines, theinflammatory response decreases, and symptoms beginto subside. Although symptoms are improved, virus stillcan be recovered from the nasopharynx for at least2 weeks after inoculation. Finally, after 2 to 3 weeks,adequate neutralizing antibody is available to end theinfection.

As shown in healthy adults who have experimentallyinduced rhinovirus colds, bradykinins and PMNs accu-mulate in nasal secretions at the onset and for the dura-tion of cold symptoms. It is believed that the presence ofPMNs in the nasal secretions, as well as their enzymaticactivity, may be the source of the yellow-green colortypical of the nasal discharge of the common cold. Thenasal mucosa in children has more secretory capacity thanthat in adults, which may contribute to significant nasaldischarge for days.

Viral rhinosinusitis is a frequent finding during thecourse of the common cold. Imaging of the paranasalsinuses in children who have uncomplicated colds dem-onstrates abnormalities of the paranasal sinuses in abouttwo thirds of children, most commonly the maxillary andethmoidal sinuses. Significant resolution occurs within2 weeks. This finding implies that accumulation of fluidin sinus cavities may be part of the cold and is notdiagnostic of a bacterial infection. It is not known if sinusinvolvement results from actual viral infection of thesinus mucosa or from impaired mucus clearance.

Abnormal middle ear pressures also occur commonlyduring the course of illness in both adults and children.Abnormal middle ear pressures may be present in up totwo thirds of school-age children during the course of acold. This effect occurs most frequently during the firstseveral days of illness and resolves within 2 to 3 weeks.

ImmunityThe frequency of colds may be due either to their lack ofproducing lasting immunity or because there are so manyserotypes that immunity to some viral strains has no realimpact. Viruses that do not produce lasting immunityafter infection include RSV, parainfluenza viruses, andcoronaviruses, resulting in an individual possibly suffer-ing recurrent infection with these same agents. Otherviruses, such as rhinoviruses, adenoviruses, influenza vi-ruses, and enteroviruses, do produce lasting immunity,but there are so many serotypes that this immunity has noreal impact on reducing the frequency of cold infections.As a result, an effective vaccine for the common cold isunlikely.

TransmissionThere are three proposed mechanisms for transmission ofthe common cold: small particle aerosols produced fromcoughing that are inhaled by another person, large par-ticle droplets produced from saliva expelled during asneeze that land on the conjunctivae or nasal mucosa ofanother person, or self-inoculation of one’s own con-junctivae or nasal mucosa after touching a person orobject contaminated with cold virus. In the experimentalsetting, sneezing (large-particle aerosol) has been shownto be a very inefficient method of transmission of rhino-virus. (6) Small-particle aerosol transmission of rhinovi-rus has been shown to occur but also appears to beinefficient. (7)

Substantial evidence from the experimental settingsuggests that rhinovirus can be transmitted efficiently viaself-inoculation. Rhinovirus is excreted in nasal secre-tions but is only present minimally in saliva. Fingers andhands are frequently contaminated with rhinovirus, as aretelephones and other everyday objects. (8) In experimen-tal settings, hand-to-hand transfer and hand-to-surface-to-hand transfer have been shown to be feasible mecha-nisms for transfer of rhinovirus to susceptible individuals.Once the hands are contaminated with cold virus, self-inoculation readily occurs when a person touches his ownnose or eyes with the contaminated hand or fingers. (6)(9)

Self-inoculation also appears to be an effectivemethod of rhinovirus transmission in the home environ-ment because secondary transmission in the home can bereduced if self-inoculation is interrupted. In one study,mothers whose fingertips were treated with virucidal 2%aqueous iodine were much less likely to become infectedthan mothers whose fingertips were treated with placebo.(9) Similarly, the use of virucidal tissues to interrupt viraltransfer has been shown to decrease secondary transmis-sion of colds in the home modestly. (10)

Influenza viruses and coronaviruses can be transmit-ted by small-particle aerosol. RSV is not transmitted bysmall-particle aerosol but has been shown to be transmis-sible by large-particle aerosol. RSV and rhinoviruses arenot transmissible by oral inoculation.

TreatmentAlthough much desired, effective treatments for thecommon cold remain elusive. Over-the-counter (OTC)cough and cold medications are readily available forchildren and are sold in various combinations to addresssymptoms. Antihistamines, antitussives, expectorants,decongestants, and antipyretics/analgesics are com-monly sold in combinations. Every week, more than 10%of children in the United States are treated with a cough




and cold medication, and most of these preparations aremultiple-ingredient products. Symptomatic relief is the pri-mary goal of treatment, although preventing disease spreadand reducing the likelihood of secondary bacterial infec-tions are also considerations. However, little scientific evi-dence supports their use, and there is increasing evidence ofpotential adverse effects that may result from their use.

In the past few years, the use of OTC cough and coldmedications for children and infants has been underintense scrutiny. A total of 123 deaths in childrenyounger than the age of 6 years have resulted from OTCcough and cold medications in the past 20 years. OTCmedications also are a common cause of emergencydepartment visits because of adverse effects or accidentalingestions. Poison control centers reported more than750,000 calls related to the use of OTC cough and coldmedications since 2000.

The risk for accidental overdose and adverse effects islikely the result of many factors. Dosing guidelines forchildren have not been established but are extrapolatedfrom adult data. Parents may be easily confused by prod-uct labeling. The availability of multi-ingredient prod-ucts may increase the likelihood of inadvertent overdosebecause parents may not understand what they havegiven to their child. Finally, multiple caregivers for youngchildren may increase the risk of accidental overdose andadverse reactions further.

As a result of a citizen petition filed in March 2007,the United States Food and Drug Administration (FDA)initiated a review of the safety and effectiveness of coughand cold medications for children. In October 2007,FDA advisers voted to recommend that OTC cough andcold medications not be used for treatment of childrenyounger than the age of 2 years. Since then, the numberof emergency department visits for adverse events relatedto the use of cough and cold medications in childrenyounger than 2 years of age has decreased by more thanhalf. (11) Drug manufacturers voluntarily discontinuedmarketing these products for children younger than age2 years. The FDA has since issued a public health advisoryrecommending that cough and cold medications not beused in children younger than age 2 years. FDA advisorycommittees have voted to ban OTC cough and coldmedications for use in children younger than age 6 years.FDA review of this recommendation is underway. Somemanufacturers have changed the labeling of their prod-ucts to recommend against their use in children youngerthan the age of 4 years. (12) The American Academy ofPediatrics recommends against the use of OTC coughand cold medications in children younger than the age of6 years. (13)

AntibioticsThe common cold is a viral infection, and there is no rolefor antibiotics. Antibiotics cannot treat the underlyinginfection and will not decrease the likelihood of bacterialcomplications. Antibiotics are indicated only when sec-ondary bacterial complications are diagnosed.

Antiviral AgentsExcept in the case of influenza, no antiviral drugs areavailable to treat the common cold. For influenza, anumber of antiviral agents are available and providemodest reduction in symptoms and duration, includingoseltamivir, amantadine, rimantadine, and zanamivir.These medications inhibit release of virus from infectedcells.

Antihistamines (H1 Receptor Blockers)First-generation antihistamines are common ingredientsin OTC cough and cold medications. Triprolidine, di-phenhydramine, hydroxyzine, and chlorpheniramine areall in this class of medications. These medications arewell-absorbed, with onset of action within 15 to 30 min-utes and duration of action of 3 to 6 hours or more.Because these medications are also anticholinergic, theydecrease mucus secretion. In addition, anticholinergicaction may result in dry mouth, blurred vision, andurinary retention. Gastrointestinal upset may occur. Car-diac effects have been reported, including tachycardia,prolongation of the QTc interval, heart block, and ar-rhythmias. Central nervous system (CNS) effects such assedation, paradoxic excitability, respiratory depression,and hallucinations may result, especially in cases of over-dose. Dystonic reactions have been reported.

Second-generation antihistamines (egs, terfenadine,astemizole, loratadine, and cetirizine) lack anticholin-ergic activity. These medications have fewer CNS effectsthan first-generation antihistamines. Cardiac effects, al-though rare, may occur, including prolonged QT inter-val, ventricular arrhythmia, and heart block.

In adults, several studies show that first-generationantihistamines (chlorpheniramine) provide some symp-tomatic relief of cold symptoms, specifically, decreasedsneezing and increased mucociliary clearance. Anotherstudy showed decreased nasal discharge and duration ofsymptoms when first-generation antihistamines (chlor-pheniramine) were used to treat adults who had thecommon cold.

There are few studies of antihistamine use in children.(14) In one study, children treated with an antihistamine-decongestant combination (brompheniramine maleate/phenylpropanolamine hydrochloride) showed no improve-




ment in cough over placebo other than the treated childrenbeing more likely to be asleep 2 hours after receiving med-ication. A study of clemastine treatment in children whohad colds showed no decrease in nasal discharge, althoughthe color of the nasal discharge changed from yellow towhite. In another study, diphenhydramine at bedtime wasno better than placebo or dextromethorphan in reducingcough or improving sleep. Few adverse effects are reportedfrom first-generation antihistamine use in children.

DecongestantsOral sympathomimetic decongestants are available andare common ingredients in OTC cough and cold medi-cations. A significant proportion of children (1 in20) have taken pseudoephedrine in any given week, withthe greatest use in children younger than the age of 2years (1 in 12). Oral decongestants include pseudo-ephedrine, phenylpropanolamine, and phenylephrine.These compounds are vasoconstrictors, acting on adren-ergic receptors to decrease blood flow in the mucosa.Unfortunately, not only the nasal mucosa is affected; theuse of oral decongestants also results in generalizedvasoconstriction with a resultant increase in blood pres-sure. Other adverse effects include headaches, seizures,nausea, vomiting, decreased appetite, agitation, tachy-cardia, nervousness, irritability, dystonia, and dysrhyth-mias.

Evidence in adults shows that both pseudoephedrineand phenylpropanolamine effectively reduce nasal symp-toms, including nasal congestion and sneezing. Phenyl-ephrine undergoes extensive biotransformation, result-ing in variable bioavailability, which limits its usefulness.

Increasing governmental control has greatly limitedthe availability of oral decongestants. Phenylpropanol-amine has been associated with intracranial hemorrhageand was removed from the market in 2000 after beingclassified as “unsafe” by the FDA. As a result of the 2005Combat Methamphetamine Act and potential for abuseof the agent, products containing pseudoephedrine arenow kept behind pharmacy counters with monitoringwho is purchasing such products.

Topical decongestants act on the adrenergic receptorsin the nasal mucosa to cause vasoconstriction, causingnasal tissues to shrink. Onset is rapid, within a fewminutes, and may last several hours. Systemic absorptionis minimal. Common topical decongestants includeoxymetazoline, xylometazoline, and phenylephrine.These topical agents can reduce nasal congestion inadults, but their usefulness is limited to only a few daysbecause of their potential for rebound congestion (rhini-

tis medicamentosa) when the medication is discontin-ued.

No information supports the effectiveness of either oralor topical decongestants in children who have colds. Inchildren ages 6 months to 5 years, one study of adecongestant/antihistamine combination (phenyl-propanolamine/brompheniramine) compared with pla-cebo found no improvement in nasal congestion, rhinor-rhea, or cough. (15) In a study of children 6 to 18 monthsof age treated with topical phenylephrine, neither nasalobstruction nor abnormal middle ear pressures improved.(16) In another study in children, xylometazoline had noeffect on eustachian tube function. (17) Because infants areobligate nose-breathers, there is much concern about thepotential dangers of these agents. Deaths in infants andyoung children treated with pseudoephedrine have beenreported.

AntitussivesAlthough cough is a protective action that clears airwaysecretions to maintain airway patency, it remains one ofthe most bothersome symptoms of the common cold.Suppressing cough effectively may actually be harmfulfor some children, especially the child who has asthmaand is unable to clear his or her airway. Nevertheless, amultitude of OTC preparations are available purportingto suppress cough in children.

One of the most common antitussive ingredients isdextromethorphan, a narcotic analog that does not haveCNS effects unless excessive doses are used. Dextro-methorphan is well tolerated at therapeutic doses, withfew adverse effects. Unfortunately, there are few studiesof antitussives in children. In one study of children 18months to 12 years of age, there was no difference incough between the placebo-, dextromethorphan-, orcodeine-treated groups. Furthermore, cough decreasedin all three groups after 3 days. (18) Another study inchildren ages 2 to 18 years who had acute cough treatedwith dextromethorphan found no improvement incough with increasing dose. (19)

Accidental overdose can cause respiratory depression,and there are reports of death in infants younger than 12months of age after dextromethorphan ingestion. In oneseries of accidental ingestions in children younger than 5years old (average age, 28 months), the children re-mained stable hemodynamically, although some experi-enced sedation. Because of the lack of efficacy and therisk of serious adverse effects, the American Academy ofPediatrics does not recommend the use of dextrometho-rphan in children. (20)

Dextromethorphan can have serious CNS effects, es-




pecially when ingested in large doses. Once ingested,absorption from the gastrointestinal tract occurs quickly.Dextromethorphan crosses the blood-brain barrier,where it blocks serotonin uptake while stimulating sero-tonin release. These effects may result in a serious adversereaction called serotonin syndrome, characterized byautonomic instability, altered mental status, and neuro-muscular abnormalities. Dextromethorphan is also anN-methyl-d-aspartate receptor antagonist and inhibitsthe neurotransmitter glutamate, which can cause a disso-ciative state and hallucinations. Dextromethorphan ismetabolized via the cytochrome P450 pathway in theliver. Some people are “slow metabolizers” and havedifficulty metabolizing dextromethorphan due to ge-netic differences. Due to cross-reactivity, rapid immuno-assay drug screens may incorrectly report excessive dex-tromethorphan ingestion as phencyclidine.

In recent years, dextromethorphan has increasinglybecome a drug of abuse for adolescents and young adultsbecause of its ability to produce intoxication, hallucina-tions, and dissociation. DXM, Dex, Skittles, Robo, andTriple-c are slang terms for dextromethorphan. A num-ber of factors make dextromethorphan an attractivechoice for abuse: it is readily available OTC at drug andgrocery stores, it is legal to purchase, it is inexpensive,and it is considered harmless. It is also available in pow-der form over the internet. With mild intoxication, dex-tromethorphan causes a mild stimulant effect that in-volves euphoria, stupor, and hyperexcitability. Othereffects may include diaphoresis, nausea, vomiting, nys-tagmus, and mydriasis. At higher doses, dextromethor-phan can cause hallucinations, delusions, an ataxic gait,and somnolence. At extreme doses, dextromethorphanmay cause a dissociative state, with paranoia, coma, anddeath. (21) The reports in the literature of death inotherwise healthy adolescents and young adults as aresult of dextromethorphan abuse is increasing.

Codeine often is used as an antitussive. Codeine is anarcotic that is believed to act centrally on the coughcenter. It is also a mild analgesic and sedative. Althoughcodeine is the “gold standard” antitussive, no studies inadults or children support the antitussive propertiesof codeine for treatment of cough associated with thecommon cold. In fact, in one study of patients ages18 months to 12 years, codeine was no more effectivethan placebo for cough suppression in children whohad nighttime cough due to a cold. (18) The AmericanAcademy of Pediatrics recommends against the use ofcodeine in children who have cough. (20)

Narcotics such as codeine may cause dose-dependentrespiratory depression, and infants seem to be particu-

larly susceptible to these effects and the subsequentdevelopment of apnea. Infants and young children maybe at risk for toxicity due to their immature hepaticenzyme systems because codeine is inactivated by conju-gation in the liver. Drug clearance is also reduced ininfants and may increase the risk of toxic effects. Infantswho have impaired lung function (such as those whohave bronchiolitis) may have increased susceptibility torespiratory depression. Death due to accidental overdosein young infants has been reported. Codeine may causeCNS depression that is reversible with naloxone. Adverseeffects in children treated with appropriate doses of co-deine include nausea, vomiting, constipation, and dizzi-ness.

First-generation antihistamines are also marketed tosuppress cough. Studies in patients who have chroniccough have reported a decrease in cough frequency whendoses causing sedation are employed. These medicationsmay cause thickening of bronchial secretions, and somebelieve that their use is contraindicated in children whohave acute wheezing or asthma. Studies in children ofantihistamine treatment alone or of decongestant/antihistamine combinations have found no improvementin cough when compared with placebo.

A recent study suggests that honey may provide somerelief from nighttime cough in children who have colds.(22) In this study, a bedtime dose of honey was betterthan no treatment in children who had cough from colds.The generalizability of the results of this single study islimited. Honey is not recommended for childrenyounger than age 12 months because of the risk ofexposure to botulinum spores.

ExpectorantsExpectorants are medications intended to increase mu-cus production. Guaifenesin is the most commonly avail-able expectorant. In young adults who have colds, treat-ment with guaifenesin failed to decrease coughfrequency, but patients did report subjective improve-ment in thickness and quantity of sputum. (23) Otherstudies in adults suggest that guaifenesin may reducecough frequency. Studies in children demonstrating ef-fectiveness do not exist.

Analgesics/AntipyreticsAnalgesics/antipyretics such as acetaminophen, aspirin,and ibuprofen may be useful for the fever and generaldiscomfort of the common cold. However, both aspirinand acetaminophen suppress the neutralizing antibodyresponse, which results in increased nasal symptoms and




prolonged viral shedding. The use of aspirin is not rec-ommended in children because of its association withReye syndrome.

EchinaceaEchinacea is a common herbal therapy recommended fortreatment of the common cold, but few well-controlledstudies have evaluated its safety and effectiveness. Themost complete and well-controlled study to date dem-onstrated no effect of echinacea on severity of symptomsor rate of infection in adults. (24)

MentholMenthol is a common ingredient in vapor therapies.Objective evaluation of nasal resistance in adults beforeand after menthol inhalation showed no effect, althoughpatients did report a sense of improved air flow. In arecent study in school-age children, inhalation of men-thol did not decrease cough or increase nasal patency,but patient perception of improved nasal patency wasreported. (25) In a recent study, bedtime applicationof a vapor rub (camphor, menthol, and eucalyptus oils)to the chest and neck of children ages 2 to 11 yearsresulted in symptomatic relief of nighttime cough, con-gestion, and sleep difficulty when compared with petro-latum or no treatment. (26) Chemical irritation of thenasal mucosa may result from topical treatment withmenthol preparations. Gastrointestinal and CNS effectsmay result from accidental ingestion.

Ipratropium BromideIpratropium bromide is a nasal spray that decreases nasaldischarge of the common cold via its anticholinergicactivity. Unfortunately, its usefulness is limited to chil-dren older than age 5 years, and adverse effects includenosebleeds, nasal dryness, and headache.

ZincZinc often is proposed as a treatment for cold symptomsbecause in vitro studies have demonstrated that zincinhibits rhinovirus replication. Adverse effects includenausea, bad taste, diarrhea, and mouth or throat irrita-tion. Some studies in adults suggest that early treatmentwith zinc gluconate can reduce the duration of coldsymptoms. Usefulness may be limited by the need forfrequent administration (5 to 6 times/day) and commonadverse effects, including bad taste and gastrointestinalupset. In schoolchildren (first through twelfth grade),treatment with zinc lozenges did not decrease the dura-tion of cold symptoms. (27)

VaporizersEfforts to establish steam inhalation as an effective treat-ment for nasal congestion due to the common cold havefailed to demonstrate benefit. Some studies in adults haveeven shown that the duration and severity of symptomsmay increase after treatment with humidified air. Inhala-tion of steam has not been shown to increase nasalpatency, although many people report subjective im-provement in nasal obstruction following inhalation. Be-cause rhinoviruses replicate best at 33 to 34°C, inhala-tion of steam was hypothesized to reduce rhinovirusreplication, but steam did not reduce viral titers in nasalsecretions during rhinovirus infection.

Saline Nose Drops/Bulb SuctionSaline drops with bulb suction are often used to moistenthe nasal mucosa and loosen secretions for removal frominfants and children. Adults may use saline nose sprays forsimilar purposes. A recent study in school-age childrensuggests that nasal symptoms and sore throat improvemore quickly with daily saline washes. (28)

PreventionThe best treatment of a cold is prevention. Annual influ-enza vaccination is recommended and is the only vaccineavailable to prevent a respiratory viral infection. Hand-washing effectively removes cold viruses from the hands.Virucidal tissues have been shown to reduce secondarytransmission modestly in the home. Virucidal hand gelsare also available, but there are no published studiesevaluating their usefulness. Alcohol-based hand sanitiz-ers have not been shown to reduce secondary transmis-sion of colds in the home or school environment, likelybecause rhinovirus is not affected by these products.Limiting contact with one’s own nasal and conjunctivalmucosa can reduce self-inoculation.

References1. Pappas DE, Hendley JO, Hayden FG, Winther B. Symptomprofile of common colds in school-aged children. Pediatr Infect DisJ. 2008;27:8–112. Revai K, Dobbs LA, Nair S, Patel JA, Grady JJ, Chonmaitree T.Incidence of acute otitis media and sinusitis complicating upperrespiratory tract infection: the effect of age. Pediatrics. 2007;119:e1408–e14233. Wald ER, Nash D, Eickhoff J. Effectiveness of amoxicillin/clavulanate potassium in the treatment of acute bacterial sinusitis inchildren. Pediatrics. 2009;124:9–154. Garbutt JM, Goldstein M, Gellman E, Shannon W, LittenbergB. A randomized, placebo-controlled trial of antimicrobial treat-ment for children with clinically diagnosed acute sinusitis. Pediat-rics. 2001;107:619–625




5. Rakes GP, Arruda E, Ingram JM, et al. Rhinovirus and respira-tory syncytial virus in wheezing children requiring emergency care:IgE and eosinophil analyses. Am J Respir Crit Care Med. 1999;159:785–7906. Hendley JO, Wenzel RP, Gwaltney JM Jr. Transmission ofrhinovirus colds by self-inoculation. N Engl J Med. 1973;288:1361–13647. Dick EC, Jennings LC, Mink KA, et al. Aerosol transmission ofrhinovirus colds. J Infect Dis. 1987;156:442–4488. Winther B, McCue K, Ashe K, Rubino JR, Hendley JO. Envi-ronmental contamination with rhinovirus and transfer to fingers ofhealthy individuals by daily life activity. J Med Virol. 2007;79:1606–16109. Gwaltney JM Jr, Hendley JO. Mechanisms of transmission ofrhinovirus infections. Epidemiol Rev. 1988;10:242–25810. Farr BM, Hendley JO, Kaiser DL, Gwaltney JM. Two random-ized, controlled trials of virucidal nasal tissues in the prevention ofnatural upper respiratory infections. Am J Epidemiol. 1988;128:1162–1172

11. Shehab N, Schaefer MK, Kegler SR, Budnitz DS. Adverseevents from cough and cold medications after a market withdrawalof products labeled for infants. Pediatrics. 2010;126:1100–110712. Kuehn BM. Debate continues over the safety of cold andcough medicines for children. JAMA. 2008;300:2354–235613. American Academy of Pediatrics Urges Caution in Use ofOver-The-counter Cough and Cold Medicines [press release].2008. Accessed November 2010 at: http://www.aap.org/advocacy/releases/jan08coughandcold.htm14. Smith SM, Schroeder K, Fahey T. Over-the-counter medica-tions for acute cough in children and adults in ambulatory settings.Cochrane Database Syst Rev. 2008;1:CD00183115. Clemens CJ, Taylor JA, Almquist JR, Quinn HC, et al. Is anantihistamine-decongestant combination effective in temporarilyrelieving symptoms of the common cold in preschool children?J Pediatr. 1997;464–46616. Turner RB, Darden PM. Effect of topical adrenergic decon-gestants on middle ear pressure in infants with common colds.Pediatr Infect Dis J. 1996;15:621–62417. van Heerbeek N, Ingels JAO, Zielhuis GA. No effect of a nasaldecongestant on eustachian tube function in children with ventila-tion tubes. Laryngoscope. 2002;112:1115–111818. Taylor JA, Novack AH, Almquist JR, Rogers JE. Efficacy ofcough suppressants in children. J Pediatr. 1993;122:799–80219. Paul IM, Shaffer ML, Yoder KE, Sturgis SA, et al. Dose-response relationship with increasing doses of dextromethorphanfor children with cough. Clin Ther. 2004;26:1508–151420. American Academy of Pediatrics Committee on Drugs. Use ofcodeine- and dextromethorphan-containing cough remedies inchildren. Pediatrics. 1997;99:918–92021. Logan BK, Goldfogel G, Hamilton R, Kuhlman J. Five deathsresulting from abuse of dextromethorphan sold over the internet. JAnalyt Toxicol. 2009;33:99–10322. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, BerlinCM Jr. Effect of honey, dextromethorphan, and no treatment onnocturnal cough and sleep quality for coughing children and theirparents. Arch Pediatr Adolesc Med. 2007;161:1140–114623. Kuhn JJ, Hendley JO, Adams KF, Clark JW, Gwaltney JM Jr.Antitussive effect of guaifenesin in young adults with natural colds:objective and subjective assessment. Chest. 1982;82:713–71824. Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. Anevaluation of Echinacea angustifolia in experimental rhinovirusinfections. N Engl J Med. 2005;353:341–34825. Kenia P, Houghton T, Beardsmore C. Does inhaling mentholaffect nasal patency or cough? Pediatr Pulmonol. 2008;43:532–53726. Paul IM, Beiler JS, King TS, Clap ER, et al. Vapor rub,petrolatum, and no treatment for children with nocturnal coughand cold symptoms. Pediatrics. 2010;126:1092–109927. Macknin ML, Piedmonte M, Calendine C, Janosky J, Wald E.Zinc gluconate lozenges for treating the common cold in children:a randomized controlled trial. JAMA. 1998;279:1962–196728. Slapak I, Skoupa J, Strnad P, Hornik P. Efficacy of isotonicnasal wash (seawater) in the treatment and prevention of rhinitis inchildren. Arch Otolarngol Head Neck Surg. 2008;134:67–74

Summary• Although colds are self-limited viral infections that

generally resolve in 10 to 14 days, they are acommon cause of discomfort and distress forchildren and their parents.

• Complications can occur, including secondarybacterial infections and wheezing exacerbations.

• Given the lack of proven benefit and the risk ofsignificant adverse effects, no prescription or OTCtreatments are recommended for children; supportivecare remains the only recommended treatment.

• Education of parents should include the currentrecommendations against the use of cough and coldmedications in children younger than the age of 6years as well as the potential risks of such OTCtreatments in children of all ages.

• Although colds may be spread through large-particleaerosols, small-particle aerosols, and self-inoculation, increasing evidence suggests that self-inoculation is a common method of transmission inthe home. (6)(9)

• Based on consensus, OTC cough and coldmedications are not recommended for use inchildren younger than 6 years of age. (12)

• Based on moderate evidence, colds are a commontrigger for asthma exacerbations in children. (5)

• Consensus evidence suggests that because of themany different serotypes of some cold viruses andother cold viruses not producing lasting immunity, itis unlikely that effective vaccines for the commoncold will be developed.




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

1. A 5-year-old boy is brought to your office because of clear nasal discharge, nasal congestion, sore throat,and temperature of 38.2°C for 2 days. He appears well on physical examination, although his nasal mucosaand pharynx are erythematous and he has yellowish nasal discharge. Which of the following is the mostlikely etiologic agent causing his symptoms?

A. Adenovirus.B. Haemophilus influenzae.C. Respiratory syncytial virus.D. Rhinovirus.E. Streptococcus pneumoniae.

2. You are evaluating a 2-year-old girl who has a 3-day history of nasal congestion and clear rhinorrhea.Findings on physical examination reveal erythema of the nasal mucosa and no other abnormalities. Youdiagnose a simple viral upper respiratory tract infection. Which of the following is the most likelycomplication of this condition?

A. Conjunctivitis.B. Mastoiditis.C. Meningitis.D. Otitis media.E. Reactive airway disease.

3. A mother brings in her 18-month-old daughter because of a runny nose and congestion for the sixth timesince she started child care 12 months ago. She is worried about the number of “colds” that her daughterhas had and is concerned that something else is wrong. The girl has grown well, and findings on physicalexamination are normal except for mild nasal congestion and clear rhinorrhea. Which of the following isthe most likely reason for her recurrent symptoms?

A. Anatomic abnormality of the sinuses.B. Bacterial colonization of her nasopharynx.C. Immunoglobulin subclass deficiency.D. Repetitive exposure to infected children who are coughing or sneezing.E. Transmission of illness from child care staff.

4. A 3-year-old girl who has the acute onset of nasal congestion, sore throat, and cough presents to theemergency department in the middle of the night because the cough is keeping her awake. Her parents areupset because both they and the girl are losing sleep, and they request something to “get rid of the cough.”Which of the following is the most appropriate recommendation at this time?

A. Oral codeine.B. Oral dextromethorphan.C. Oral diphenhydramine.D. Topical (nasal) phenylephrine.E. Topical (nasal) saline drops.





Diane E. Pappas and J. Owen Hendley The Common Cold and Decongestant Therapy

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Tomas Jose Silber Somatization Disorders: Diagnosis, Treatment, and Prognosis







Somatization Disorders:Diagnosis, Treatment, and PrognosisTomas Jose Silber, MD*

Author Disclosure

Dr Silber has




commentary does not


of an unapproved/


commercial

product/device.


1. Identify the various manifestations of somatization disorders in children andadolescents.

2. Understand the association of psychosomatic disorders with personality traits andstressors such as physical and sexual abuse, bullying, parental anxiety, and pressure fora child to perform.

3. Recognize secondary gains of somatization disorders.4. Explain why it is necessary to focus on school attendance and the management of

school avoidance.5. Develop a partnership with patients and their parents to address the symptoms of a

somatization disorder.6. Plan the treatment and management of somatization disorders

IntroductionChildren and adolescents suspected of having somatization disorders present a challengeto pediatricians. Clinicians are often concerned about “missing something,” while alsoworrying about alienating both the patient and the family when explaining the condition.Many clinicians are baffled by the onslaught of symptoms, feel frustrated by the never-ending recurrent complaints, or become annoyed by the time consumed in caring forpatients who might be perceived as “not really being sick.”

The research on somatization disorders is neither easily available nor conclusive.Moreover, paradoxically, although somatoform disorders in children have been defined aspsychiatric disorders, psychiatrists seldom see these patients. By default, most children andadolescents who have symptoms are seen by primary care physicians. (1)(2)(3)(4)

This review focuses on understanding, assessing, and developing strategies for manag-ing somatization disorders.

DefinitionSomatization is “the tendency to experience and communicate somatic distress andsymptoms unaccounted by pathological findings.” (5) However, it must be stressed thatsomatization can coincide with another illness. Somatization is deemed to exist inconjunction with a physical illness whenever the physical complaints resulting in impair-ment are grossly in excess of what would be expected from the known illness or findings.Thus, the central feature of somatoform disorders is that they present with symptomssuggestive of an underlying medical condition, yet such a condition either is not found ordoes not fully account for the level of impairment the child is exhibiting. (6)(7)(8)

ClassificationThe diagnostic criteria for somatoform disorders originally were established for adults. (6)(7)A diagnostic classification of child and adolescent mental conditions in primary care has beendeveloped that takes into account developmentally appropriate considerations. (8) The manualcontaining the classification develops an approach to somatization disorders in children thatpediatricians may consider more user friendly (Table 1).

*Professor, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences; Director,Adolescent Medicine Fellowship Program, Children’s National Medical Center, Washington, DC.

Article psychosocial



EpidemiologyThe prevalence of symptoms associated with somatiza-tion in the pediatric population is high: recurrent ab-dominal pain accounts for 5% of pediatric office visits,and headaches have been reported to affect 20% to 55%of all children, with 10% of teenagers reporting frequentheadaches, chest pain, nausea, and fatigue. A sex disparityin the prevalence of somatic symptoms during adoles-cence (11% of girls and 4% of boys) persists into adult-hood. The rate of somatization is highest among lowersocioeconomic groups. (4)(9)(10)(11)(12)

PathogenesisThere is a genetic predisposition to somatization, prob-ably related to traits such as alexithymia (difficulty inreading one’s own emotions), trait anxiety (a continualtendency to react with anxiety), and anxiety sensitivity(a fear of anxiety symptoms and misinterpretation oftheir meaning). Genetic studies have shown somatoformdisorders to be concordant in identical twins. Theseconditions also cluster above what would be expected bychance in families in which there is attention-deficitdisorder and alcoholism. (13)(14)(15)

Somatization, nevertheless, is a learned behavior. Itbegins with experiences of having a somatic complaintmore easily noticed or more acceptable in a householdthan the expression of strong feelings, such as anxiety,fear, jealousy, and anger. In such an environment, a childmay repeatedly garner no attention for emotional dis-tress, instead obtaining more attention for the physicalsymptoms that often accompany the disturbed emotionalstate, such as abdominal pain (“Are you hurting, dar-

ling?”). As this “psychosomatic pathway” is reinforced, itmanifests throughout a spectrum of somatization disor-ders, ranging from the mild “somatic complaint varia-tion” (transient complaints that do not interfere withnormal functioning) to the more severe “somatoformdisorder” (associated with significant social and academicproblems).

The importance of psychosocial factors in the child’sfamily is highlighted by the finding that if a familymember has a chronic physical illness, more somaticsymptoms occur among the children. Somatizing chil-dren often live with family members who complain ofstrikingly similar physical symptoms. Theoretical contri-butions stemming from systemic family therapy alsopoint toward the importance of the family’s circum-stances. For example, it has been proposed that thesymptoms displayed by the child are a way of protectinga distressed parent who, galvanized into caring for thesuffering child, is then distracted from his or her ownpersonal concerns. (1)(2)(3)(4)

Stress has been implicated as a triggering factor, andsuch stress often is bound to parental anxiety. The mostcommon form of stress consists of pressure on the child toperform. More serious problems, such as physical or sexualabuse or being bullied, also may lead to somatic complaintsthat often develop into a somatization disorder. (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)

Clinical AspectsChildren and adolescents readily report pain and somaticcomplaints in their sick visits. These complaints oftenresult from a disease such as gastroenteritis or urinarytract infection. However, children can voice similar com-plaints in the absence of physical disease, and thesereports must be approached as possible somatization.(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) Somato-form disorders follow a developmental sequence as chil-dren experience affective distress in the form of somaticsensations. In early childhood, these symptoms are recur-rent abdominal pain and, somewhat later, headaches. Asage increases, neurologic symptoms, insomnia, and fa-tigue tend to emerge.

Somatization disorders form a continuum that rangesfrom everyday aches and pains to disabling symptoms.These symptoms are spontaneous and not feigned(which distinguishes them from malingering and facti-tious disorder) and are not explained better by anothermental illness (such as depression or an anxiety disorder).

Table 1. Current Classification ofSomatization Disorders inChildren and Adolescents• Somatic complaint variation (v 65.49)• Somatic complaint problem (v 40.3)• Somatization disorder (300.82)• Somatoform disorder (undifferentiated) (300.82)• Somatoform disorder, not otherwise specified

(300.82)• Pain disorder (307.8)• Conversion disorders (300.6)

Data from Wolraich ML, Felice ME, Drotar D. The classification ofchild and adolescent mental diagnosis in primary care. In: Diagnosticand Statistical Manual for Primary Care (DSM-PC) Child and Adoles-cent Versions. Elk Grove Village, IL: American Academy of Pediatrics;1996.

psychosocial somatization disorders



Somatic Complaint VariationThis variation involves discomfort and complaints thatdo not interfere with everyday functioning. It is a univer-sal experience. In early infancy, the complaints probablymanifest as transient gastrointestinal distress. In child-hood, classic recurrent abdominal pain, headaches, and“growing pains” make their appearance. Adolescentsmay experience more headaches, chest pain, and othertransient aches and pains, but these characteristically donot impair their ability to function. Females report moresomatic complaints after puberty.

Somatic Complaint ProblemThis condition consists of one or more physical com-plaints that cause sufficient distress and impairment(physical, social, or school) to be considered a problem.In infancy, this situation might occur when gastrointes-tinal symptoms seriously interfere with feeding and sleep.In childhood, such a condition might entail avoiding orrefusing to undertake expected activities (eg, increasedschool absences). As adolescence approaches, in additionto the somatic complaints, more emotional distress, so-cial withdrawal, and academic difficulties begin to ap-pear. More severe complaints may result in refusal toattend school and recurrent pain syndromes.

Undifferentiated Somatoform DisorderThis condition emerges during adolescence, causing sig-nificant impairment. Multiple severe symptoms of at least6 months’ duration are required to make the diagnosis.Complaints include, but are not limited to, pain syn-dromes, gastrointestinal or urogenital complaints, fa-tigue, loss of appetite, and pseudoneurologic symptoms.To qualify for this diagnosis, the symptoms should not beexplained better by another mental disorder, such as amood or anxiety disorder, and should not be feigned orintentionally produced. A more severe form, the classicsomatization disorder, is an adult condition.

Somatoform Disorder, Not Otherwise SpecifiedThis classification encompasses adolescents who haveunexplained physical complaints (fewer than 6 months’duration) as well as those who manifest somatoformsymptoms that do not meet the criteria for any specificsomatoform disorder, such as pseudocyesis, in which thefalse belief of being pregnant can be accompanied byendocrine changes.

Pain DisorderThere are three types of pain disorder: pain associatedexclusively with psychological factors, pain associated

with both a psychological and a general medical condi-tion, and pain associated with a general medical condi-tion. The onset of pain may be related to psychologicalstressors. Often, a secondary gain is achieved by beingexcused from stressful situations or academic pressures.These symptoms may be associated with frequent visitsto the pediatrician and parental pressure for unnecessarytesting and interventions.

Conversion DisorderIn conversion disorders, one or more symptoms or defi-cits affect a sensory or voluntary motor function (eg,blindness, paresis), suggesting a medical or neurologiccondition, yet the findings are not consistent with anyknown neuroanatomic/pathophysiologic explanation.(40)(41)(42) The symptoms tend to have a “symbolicmeaning,” dealing with an unsolved and unconsciousconflict (often relating to themes of repressed aggressionor sexuality). The symptoms appear to be a symbolicattempt to resolve the conflict (primary gain), althoughthey also often result in increased attention for the pa-tient (secondary gain).

This form of somatization disorder frequently, butnot always, is accompanied by “la belle indifference,” anattitude of disinterest by the patient despite the serioussymptoms experienced. Although the symptoms usuallyare self-limited, often resolving within 3 months, theymay persist and ultimately be associated with chronicsequelae, such as contractures. Frequently, there is amodel for the symptoms, such as a grandparent who hascardiac symptoms, but sometimes the patient may beserving as his or her own model, as when pseudoseizuresoccur in patients who have epilepsy.

Additional Somatoform DisordersHypochondriasis (preoccupation with the idea of havinga serious disease) and body dysmorphic disorder (over-preoccupation with an imagined or exaggerated defect inphysical appearance) are uncommon and seen primarilyduring late adolescence and young adulthood.

Differential Diagnosis (Table 2)Organic illnesses must be considered in the differentialdiagnosis. Over time, up to one third of patients in whomconversion disorder is diagnosed eventually receive aneurologic diagnosis. Endometriosis is often a very latediagnosis following years of “functional pelvic pain,” andpersistent epigastralgia may represent a Helicobacter py-lori infection. Psychiatric disorders, such as depressionand anxiety disorder, often present initially with physicalcomplaints such as poor concentration; fatigue; weight




loss; and an increase in headaches, stomachaches, andchest pains. It is important to look for specific psychiatricdisorders. Epidemiologic studies show that 14% to 20%of American children have one or more moderate-to-severe psychiatric disorders, with the overall prevalencerising, and the treatment is somewhat different from thatof somatization. Factitious disorders, which sometimesare included in the somatization spectrum, can be ex-cluded from this category because the signs and symp-toms presented have been staged deliberately and havenot really been experienced by the patient as somatiza-tion symptoms.

EvaluationInitially, it is usually unclear whether a particular com-plaint eventually will declare itself to be caused by anunderlying disease. Establishing the diagnosis of a so-matoform illness is accomplished over time along threesimultaneous tracks: 1) ruling out an organic disease asthe cause of the symptoms, 2) identifying psychosocialdysfunction, and 3) recognizing and alleviating stressors.A concomitant biopsychosocial assessment is therapeuticand often followed by improvement and sometimes evenresolution of symptoms.

However, the differential diagnosis and evaluation arenot based solely on a process of exclusion. It involvesidentification of a set of positive psychosocial findings.During the initial evaluation, it is important to discussexplicitly the stressors detected and a possible psychoso-matic cause as one among many considerations. This willmake for an easier future “disclosure.”

Findings that are highly suggestive of a somatizationdisorder include a history of multiple somatic com-plaints, multiple physician visits, and many specialty con-sultations as well as the presence of a family member whohas chronic and recurrent symptoms and dysfunction inthe primary areas of life (family, peers, and school).Additional questions might include, “Does the parenthave any concern about the child’s behavior or emotional

well-being?” and “Is there a family history of psychiatricdisorder?” A detailed school history that reviews thenumbers of days missed is essential.

In the process of evaluating somatic complaints, theclinician should avoid the temptation to perform unnec-essary, repetitive, or extensive testing in an attempt todemonstrate to the family that the presenting complaintis of psychosomatic origin. A cost-effective method ofdetermining the appropriate extent of laboratory andradiographic evaluation is to base the diagnostic plan onthe presence of “red flags.” Such complaints and findingssuggest an organic cause, such as syncope on exercise,asymmetric location of pain, anemia, or weight loss.When the history and physical examination findings aresuggestive of somatization, a basic laboratory screeningconsisting of a complete blood count, an erythrocytesedimentation rate or a C-reactive protein, a urine dip-stick evaluation, and sometimes a blood chemistry andoccult blood stool test is sufficient. More extensive as-sessments should be reserved for the “red flags.”

Management and TreatmentEventually, the clinician must “bite the bullet.” The bestmethod of persuasion is to precede any disclosure with aclear demonstration that one has taken the complaintvery seriously, which is accomplished best when pre-ceded by careful history taking and a detailed physicalexamination. The aim is to convey a sense of specialnessto the child and family. This communication may serve asa buffer to the emotional injury stemming from having torecognize that “something is wrong” in the child’s life.Correct identification of somatization disorders may notbe sufficient to provide help to patients and families, whooften are reluctant to accept the explanation. (43) There-fore, successful communication about the condition andthe needed treatment is a crucial but sometimes elusivegoal (Table 3).

In preparation for disclosure of concerns about apossible somatization disorder, it is very important to askthe child and family about their fear or “fantasy ofdisease.” This query may elicit surprising answers, such asfear that the child may have cancer or heart disease.Conversely, the reply may convey an already harboredsuspicion or understanding of the problem such as “Itmay be stress or nerves.” Patients are more willing tolisten to the pediatrician only if he or she first listens tothem. A clear, supportive, matter-of-fact explanation alsoshould assure families that the pediatrician is available tohelp with the onslaught of feelings that many familiesexperience at the time of diagnosis. During disclosure,the clinician should remind the family of the earlier

Table 2. Differential Diagnosis ofPediatric Somatization• Unrecognized physical disease (eg, multiple sclerosis,

endometriosis)• Unrecognized psychiatric disorder (eg, depression,

anxiety)• Factitious disorder/Munchausen by proxy syndrome• Psychological factors affecting a medical condition




conversation referring to the possibility that the symp-toms may be related to stress, temperamental sensitivity,anxiety, or whatever term may be tolerated by the familyto facilitate acceptance of a behavioral intervention oreven a request for psychological or psychiatric consulta-tion.

It is important for pediatricians to recognize their ownresponses to the family resistance and reluctance to layaside the “search for disease” and not inadvertently con-vey by word or body language their own frustrationabout the difficult and time-consuming task they arefacing.

A primary reason that many patients and their parentsare angry and reject the diagnosis of somatization disor-der is that they feel disrespected and not believed: “Youthink it is all in my head, but I know I hurt and that thereis something wrong.” In part, this conception relates tothe unfortunate term “psychosomatic,” which conveysthe mistaken notion of a body-mind duality and for someindividuals still carries the connotation of being crazy(“psycho”). Therefore, it is important to explain that the“functional versus organic” paradigm is old-fashionedand does not reflect current thinking, which suggests amore complex interplay of multiple factors, includinggenetic and biochemical components predisposing to thepatient’s symptoms.

Essentially, the pediatrician must convey an under-standing that the patient’s pain is real; that is, the doctorhas learned and believes that pain is due to a neuralnociceptive component and an affective component,

both processed by the central nervous system and influ-enced by personal experience, genetics, and the environ-ment. To help patients and parents become more open tothe concept of somatization, they can be reminded ofhow themes in everyday language acknowledge the con-nection between emotions and bodily processes. Forexample, we talk about having a “gut reaction,” having“butterflies in my stomach,” feeling “all choked up,” orthat something “makes me vomit.” In addition, embar-rassment can manifest as blushing, fear as cold sweat, andanger as stiffening muscles and clenching teeth, thusfacilitating explanations such as “blushing of the gut”and “spastic colon.” Another way to help patients andparents view somatization is as a sensitivity, a phenome-non of “amplification” of otherwise normal body sensa-tions, similar to the role of the amplifier in the transmis-sion of music. (44)

At the center of any successful program is the untiringeffort to motivate patients and parents toward a partner-ship with the doctor in dealing with the symptoms andcomplaints. Although it could be argued that the risk ofantagonizing patients and parents by presenting a diag-nosis of somatization and causing them to leave thepractice for “doctor shopping” would recommend thepolicy of helping patients by medicating them symptom-atically with analgesics, tranquilizers, anxiolytics, andother agents from the pharmacopeia, such action tendsto be only a short-term solution. Although tempting andcertainly easier, such an approach may only reinforce thesearch for the “magic pill” and a never-ending pursuit ofa technological solution.

At a deeper level, the reason for informing patientsand families about the nature of the disorder involves theprinciple of respect for persons because it is an ethicalduty, with few exceptions, for clinicians to share withpatients their understanding of their situation.

The primary exception to this rule, which allows forjustified paternalism and “face-saving” suggestive thera-pies, may apply to those patients who have conversiondisorders and cannot make use of the information. Thediagnosis of somatization should not lead a patient orparent to the perception that this diagnosis will be raisedas a barrier to preempt future complaints. Instead, itshould become clear that the diagnosis is made in thespirit of offering an interpretation that may call for newerand more effective treatments, such as stress manage-ment and individual or family counseling. Somatoformdisorders do respond to treatment and rehabilitation.Cognitive and behavioral interventions; use of positiveand negative reinforcements; and self-monitoring tech-

Table 3. Principles of PediatricSomatization Treatment• Form an alliance with the patient and family• Be direct; avoid deception in explanations and

treatments• Offer reassurance when appropriate• Use cognitive and behavioral interventions• Use a rehabilitative approach• Use positive and negative reinforcement• Teach self-monitoring techniques (eg, hypnosis,

relaxation, biofeedback)• Consider family and group therapies• Improve communication between clinicians and

school• Consolidate care when possible• Aggressively treat comorbid psychiatric conditions• Consider psychopharmacologic interventions• Monitor outcome

Adapted from Campo and Fritz. (2)




niques such as hypnosis, relaxation, and biofeedbackhave been proven successful. (1)(2)(3)(4)(45)(46)

Many patients miss school because of their symptom-atology. This practice can develop into a full-blownschool avoidance syndrome. This evolution often is notrecognized by the parents because “my child loves schooland wants to go” (which may actually be true, but thechild is unable to do so). Family counseling and goodcommunication between the clinician and the school canaid in addressing this situation. The instruction is that thechild must be brought to school and stay in the building.Class attendance is not mandatory but going to school is.If need be, the child may rest in the school infirmary, aquiet area, or the library. There is no returning homeunless the child is febrile. Class attendance usually fol-lows spontaneously. Parents must be prepared for thedifficult days, which often occur on Sunday evening andthe last vacation day before returning to school. Reach-ing this type of agreement can be facilitated by one of theparents being ready and willing to help the other.

A patient not responding to intensive treatmentshould be evaluated for the possibility of comorbiditysuch as a mood disorder, anxiety disorder, and substanceabuse, which should be identified and treated to assuresuccessful treatment. The presence of comorbid condi-tions is why pediatricians treating children who haverecurrent somatic complaints must become familiar withscreening for anxiety disorder, depression, attention-deficit/hyperactivity disorder, substance use disorder,and conduct disorder.

Judicious use of psychopharmacologic treatment insomatoform disorders may be appropriate when comor-bid depression or anxiety is suspected or the severity ofsymptoms has led to significant and prolonged impair-ment. Once the pediatrician can convince the patient andfamily to seek additional treatments, such as psycholog-ical therapy or evaluation for the use of medication, it isimportant for the consulting mental health professionalto receive a detailed description of what led to theconsultation because that history may be missing fromthe patient’s narrative.

Conversely, the psychiatrist or psychologist must beasked to provide feedback to the pediatrician becausesome families may report that the mental health cliniciansaid there was “nothing wrong, it was all medical.” Theconsultant should be expected to tell the referring pedi-atrician what services will be provided and what thepediatrician is expected to monitor. For pediatricianswho are sophisticated in the use of counseling and psy-chotropic medications, a mental health referral might notbe necessary.

Often, families worry that the diagnosis of somatiza-tion will be followed by abandonment by the physician.This concern can be dispelled by arranging frequentfollow-up visits, which have the potential to “preempt”the frequent emergence of new symptoms, prevent emer-gency department visits, and ease the overall manage-ment of symptoms. It is helpful to emphasize that allforthcoming symptoms will be examined with the atten-tion they deserve because somatizing under stress is verycommon and does not “provide immunity” against ap-pendicitis, flu, pneumonia, and other conditions. Mostfamilies, even when disagreeing with their physicians, canaccept (albeit grudgingly) treatment recommendations ifthey are assured of an attentive, open-minded, and reg-ularly scheduled follow-up.

The payment structure of medical services can con-spire against optimal care for patients who have somati-zation disorders. In part, this situation has evolved be-cause procedural interventions historically have beenvalued by insurance companies above spending time withpatients and in part because many insurers “carve out”these types of disorders exclusively for treatment throughthe mental health insurance coverage. Frequently, such“carve outs” mean that patients must pay their pediatri-cians out of pocket or from their mental health benefits,which rarely is allowed. At other times, services simply gounpaid.

Depending on contractual arrangements, pediatri-cians currently have three less-than-satisfying options:1) accept the rate of reimbursement for their services andbill the rest to the family, 2) refer the family to a consul-tant and coordinate care, or 3) negotiate directly with thepayer about the case. The reason to expend all this effortis that gaining expertise in this type of work can make agreat difference in the life of children, and the effort isrewarded by success and enormous professional satisfac-tion.

PrognosisWith appropriate intervention, the prognosis for mostsomatization disorders in children and adolescents is verygood. On occasion, somatization is the proverbial “tip ofthe iceberg” that calls attention to a psychiatric disordernecessitating mental health consultation and treatment.Unfortunately, many untreated children risk continuoussomatization as adults. (47)(48)(49)(50) The most se-vere form, the undifferentiated somatoform disorder, isrelated to personality disorders, is of long duration, andhas a persistent course.




AdvocacyFrom a professional development perspective, advocacywork must continue to emphasize that change in medicaleconomics is needed, specifically, that the financial im-pact of somatization on utilization must be addressed.(51) Increased funding is needed for both research andtraining in an area that has such great impact on qualityof life. Teaching about this subject needs to be incorpo-rated into the medical education of medical students,residents, subspecialty fellows, and postgraduate stu-dents to increase all clinicians’ level of comfort and senseof effectiveness in dealing with somatization disorders.

References1. Silber TJ, Pao M. Somatization disorders in children and ado-lescents. Pediatr Rev. 2003;24:255–2662. Campo JV, Fritz GL. A management model for somatization.Psychosomatics. 2001;42:467–4763. Rickert VI, Jay MS. Psychosomatic disorders: the approach.Pediatr Rev. 1994;15:448–4544. Reese A, Strasburger VC. Is it “real” or is it “psychosomatic?”Basic principles of psychosomatic medicine in children and adoles-cents. In: Greydanus DE, Wolraich ML, eds. Behavioral Pediatrics.New York, NY: Springer Verlag; 1992:352–3565. Lipowski ZJ. Somatization: the concept and its clinical applica-tion. Am J Psychiatry. 1988;145:1358–13686. American Psychiatric Association. Diagnostic and Statistical

Manual of Mental Disorders. 4th ed, Text Revision (DSM-IV-TR).Washington, DC: American Psychiatric Association; 20047. American Psychiatric Association. Diagnostic and StatisticalManual of Mental Disorders Primary Care Version. 4th ed. Wash-ington, DC: American Psychiatric Press; 20008. Wolraich ML, Felice MD, Drotar D. The classification of childand adolescent mental diagnoses in primary care. In: Diagnostic andStatistical Manual for Primary Care (DSM-PC) Child and Adoles-cent Version. Elk Grove Village, IL: American Academy of Pediat-rics; 19969. Haugland S, Wold B, Stevenson J, Aaroe LE, Woynarowska B.Subjective health complaints in adolescence. A cross-national com-parison of prevalence and dimensionality. Eur J Public Health.2001;11:4–1010. Alfven G. The covariation of common psychosomatic symp-toms among children from socio-economically differing residentialareas. An epidemiological study. Acta Paediatr. 1993;82:484–48711. Campo JV, Fritz GL. Somatization in children and adoles-cents. J Am Acad Child Adolesc Psychiatry. 1994;33:1223–123512. Fritz GK, Fritsch S, Hagino O. Somatoform disorders inchildren and adolescents: a review of the past 10 years. J Am AcadChild Adolesc Psychiatry. 1997;36:1329–133713. Muris P, Meesters C. Children’s somatization symptoms: cor-relations with trait anxiety, anxiety sensitivity, and learning experi-ences. Psychol Rep. 2004;94:1269–127514. Burba B, Oswald R, Grigaliunien V, et al. A controlled study ofalexithymia in adolescent patients with persistent somatoform paindisorder. Can J Psychiatry. 2006;51:468–47115. Torgersen S. Genetics of somatoform disorders. Arch GenPsychiatry. 1986;43:502–50516. Berntsson LT, Gustafsson JE. Determinants of psychosomaticcomplaints in Swedish schoolchildren aged seven to twelve years.Scand J Public Health. 2000;28:283–29317. Friedrich WN, Schafer LC. Somatic symptoms in sexuallyabused children. J Pediatr Psychol. 1995;20:661–67018. Garber J, Van Styke DA, Walker LS. Concordance betweenmother’s and children’s reports of somatic and emotional symp-toms in patients with recurrent abdominal pain or emotional disor-ders. J Abnormal Child Psychol. 1998;26:381–39119. Greene JW, Walker LS. Psychosomatic problems and stress inadolescence. Pediatr Clin North Am. 1997;44:1557–157220. Green M. Vulnerable child syndrome and its variants. PediatrRev. 1986;8:75–8021. Dutta S, Mehta M, Verma IC. Recurrent abdominal pain inIndian children and its relation with school and family environment.Indian Pediatr. 1999;36:917–92022. Kinzl JF, Traveger C, Biebl W. Family background and sexualabuse associated with somatization. Psychother Psychosom. 1995;64:82–8723. Orr D. Adolescence, stress, and psychosomatization. J AdolHealth Care. 1986;7:97S –108S24. Srabstein J, Joshi P, Due P, et al. Prevention of public healthrisks linked to bullying: a need for a whole community approach.Int J Adolesc Med Health. 2008;20:185–19925. Tanaka H, Tamai H, Terashima S, et al. Psychosocial factorsaffecting psychosomatic symptoms in Japanese schoolchildren.Pediatr Int. 2000;42:354–35826. Walker LS, Greene JW. Children with recurrent abdominalpain and their parents: more somatic complaints, anxiety, anddepression than other patient families? J Pediatr Psychol. 1989;14:231–243

Summary• The Diagnostic and Statistical Manual for Primary

Care (DSM-PC) Child and Adolescent Version (8)contains a useful pediatric classification ofsomatization disorders that is based on consensusdue to lack of relevant clinical studies.

• Based on some research evidence, somatizationdisorders occur in children who are geneticallypredisposed and exhibit trait anxiety, anxietysensitivity, and alexithymia. (13)(14) There isconcordance in identical twins.

• Environmental factors are suggested by the presenceof models in the family and the preponderance ofthese conditions among children of families living inlower socioeconomic strata.

• Stress is an important contributory factor; thepossibility of bullying or physical or sexual abusemust be considered.

• Adolescents who have somatoform pain disorders areoften afflicted by alexithymia.

• Agreement on the management of somatizationdisorders outlined in this article is based onconsensus. Patients who do not respond to pediatricintervention may suffer from comorbidity such as ananxiety or mood disorder.




27. Walker LS, Garber J, Grene JW. Somatization symptoms inpediatric abdominal pain patients: relationship to chronicity ofabdominal pain and parent somatization. J Abnorm Child Psychol-ogy. 1991;19:379–39428. Atlas JA, Wolfson MA, Lipschitz DS. Dissociation and soma-tization in adolescent inpatients with and without history of abuse.Psychol Rep. 1995;76:1101–110229. Brown RT. Adolescents with psychosomatic problems. ComprTher. 1996;22:810–81630. Forsyth R, Farrell K. Headache in childhood. Pediatr Rev.1999;20:39–4531. Garralda ME. Psychosomatic illness in children. Practitioner.1992;236:621–62232. Hyams JS, Hyman PE. Recurrent abdominal pain and the bio-psychosocial model of medical practice. J Pediatr. 1998;133:473–47833. Murray KF, Christie DL.Vomiting. Pediatr Rev. 1998;19:23734. Narchi H. The child who passes out. Pediatr Rev. 2000;21:38435. Rudra HS, Park JH, Webbe-Hijazi N, et al. Index of suspicion.Pediatr Rev. 2006;27:107–11236. Selbst SM, Ruddy RM, Clark BJ, et al. Pediatric chest pain: aprospective study. Pediatrics. 1988;82:319–32337. Sherry DD, McGuire T, Mellins E, et al. Psychosomatic mus-culoskeletal pain in childhood: clinical and psychological analyses of100 children. Pediatrics. 1991;88:1093–109938. Willis J. Syncope. Pediatr Rev. 2000;21:20139. Zuckerman B, Stevenson J, Bailey V. Stomach and headachesin a community sample of preschool children. Pediatrics. 1987;79:677–68240. Hogdman CH. Conversion and somatization in pediatrics.Pediatr Rev. 1995;16:29–34

41. Dvonch VM, Bunch WH, Siegler AH. Conversion reactions inpediatric athletes. J Pediatr Orthop. 1991;11:770–77242. Gooch JL, Wolcott R, Speed J. Behavioral management ofconversion disorder in children. Arch Phys Med Rehabil. 1997;78:264–26843. Steinhauer PD. Resistances to the biopsychosocial approach:individual, familial and systemic. Behavior Pediatr. 1990;11:330–33244. Barsy AJ, Goodson JD, Lane RS, Cleary PD. The amplificationof somatic symptoms. Psychosom Med. 1988;50:510–51945. Sugarman LI. Hypnosis: teaching children self-regulation.Pediatr Rev. 1996;17:5–1146. Olness K. Hypnosis and biofeedback with children and adoles-cents: clinical, research, and educational aspects. Introduction.J Dev Behav Pediatr. 1996;17:29947. Cohen P, Pine DS, Must A, Kasen S, Brook J. Prospectiveassociations between somatic illness and mental illness from child-hood to adulthood. Am J Epidemiol. 1998;147:232–23948. Bass C, Murphy M. Somatoform and personality disorders:syndromal co-morbidity and overlapping developmental pathways.J Psychosom Res. 1995;39:403–42749. Berntsson LT, Kohler L. Long-term illness and psychosomaticcomplaints in children aged 2–17 years in the five Nordic countries.Comparison between 1984 and 1996. Eur J Public Health. 2001;11:35–4250. Offord DR, Boyle MH, Szatmari P, et al. Ontario Child HealthStudy. II: Six month prevalence of disorder and rates of serviceutilization. Arch Gen Psychiatr. 1987;44:832–83651. Bernal P, Estroff DB, Aboudarham JF, et al. Psychosocialmorbidity: the economic burden in a pediatric health maintenanceorganization sample. Arch Pediatr Adolesc Med. 2000;154:261–266

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

5. Which of the following statements regarding somatization disorders in children is true?

A. Neurologic symptoms are the most common manifestation in infants.B. Symptoms are generally feigned with a secondary gain in mind.C. They are more common in children who are encouraged to openly display their fear or anger.D. They are more common in children who have a family member with a chronic disease.E. They occur more often in higher socioeconomic groups.

6. You are evaluating a 16-year-old girl who complains of fatigue for the past 3 months. She reports nofever, weight loss, or pain. She has difficulty sleeping at night and decreased appetite, and she has quit herafter-school drama class, which she previously enjoyed. Her family history reveals a mother who hasdepression and fibromyalgia. Except for a flat affect, her physical examination results are normal. Which ofthe following is the most likely diagnosis in this patient?

A. Conversion disorder.B. Depression.C. Somatic complaint problem.D. Somatoform disorder, not otherwise specified.E. Undifferentiated somatoform disorder.




7. A 10-year-old boy comes to your clinic with a 2-month history of intermittent vision loss that lasts forseveral minutes and resolves spontaneously. He describes a complete loss of vision in both eyes, and he hasmissed approximately 20 days of school. He denies other symptoms. His family history reveals agrandmother who lives with them and who has Alzheimer disease. Because of financial strain, he has beenasked to care for his grandmother in the afternoons and evenings. An ophthalmologic evaluation 3 weeksago showed normal findings. On physical examination, he reports normal vision and appears indifferent tohis reported symptoms. Findings on examination are normal, including the neurologic examination. Whichof the following is most likely?

A. Anxiety disorder.B. Conversion disorder.C. Optic neuritis.D. Somatic complaint variation.E. Undifferentiated somatoform disorder.

8. You have diagnosed undifferentiated somatoform disorder in an adolescent girl who has recurrentabdominal pain. Even though she has no weight loss, diarrhea, or other symptoms and her examinationfindings are normal, her parents are concerned that she may have inflammatory bowel disease because hergrandmother has Crohn disease. Which of the following should you do at this time?

A. Arrange a series of follow-up visits to monitor how she is doing and develop a program to help her andexplain the connection between emotions and bodily functions to the patient and her family.

B. Conduct a thorough search for pathologic causes, including endoscopy and upper gastrointestinalradiographic series.

C. Assess whether there is occult blood in stools, obtain a C-reactive protein measurement, and reassurethe family that nothing is wrong and that the pain will resolve.

D. Encourage the girl to ignore her pain because it is not real pain and she needs to learn how to live withit.

E. Refer the girl to a child psychiatrist for a psychopharmacology consultation to consider anxiolytictherapy.





Tomas Jose Silber Somatization Disorders: Diagnosis, Treatment, and Prognosis




ial_issues_problemshttp://pedsinreview.aappublications.org/cgi/collection/psychosoc

Psychosocial Issues and Problemsfollowing collection(s): This article, along with others on similar topics, appears in the







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J. Bryan Carmody Focus on Diagnosis: Urine Electrolytes




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Author Disclosure

Dr Carmody 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.

Urine ElectrolytesJ. Bryan Carmody, MD*

IntroductionAlthough electrolytes in the bloodmust be maintained within narrowlimits for homeostasis, urine is thebody’s waste, and concentrations ofurine solutes vary widely, dependingon the need for the specific solute tobe excreted or retained. However, ina variety of clinical situations, analysisof urine electrolytes can be very in-formative or even diagnostic. Tomaximize the usefulness of such tests(Table), the clinician must possessboth a basic knowledge of renal sol-ute handling and an understandingof the particular instances in whichmeasurement of urine electrolytes isuseful.

Frequently, clinicians are hesitantto obtain urine electrolytes due tothe perceived difficulty in interpret-ing them in the absence of “normal”values. It is critically important torealize that urine electrolytes canonly be interpreted in the context ofthe patient and the clinical situation.For example, a urine potassium con-centration of 35 mEq/L may be ap-propriate for a healthy patient eatinga potassium-rich diet but would indi-cate inappropriate renal potassiumwasting in a patient whose serum po-tassium concentration is 2.0 mEq/L(2.0 mmol/L).

Urine Sodium ConcentrationSodium is the body’s primary extra-cellular cation. Because water move-ment follows solute movement, so-dium has a major physiologic role inmaintaining extracellular volume,and the kidney actively varies reab-sorption of sodium to maintain ap-

propriate effective circulating vol-ume. Therefore, the major use of theurine sodium concentration (UNa) isto assess a patient’s volume status.When the effective circulating vol-ume is decreased (hypovolemia), thekidney avidly retains sodium in aneffort to maintain circulating vol-ume, and the UNa is low, generallyless than 20 mEq/L. Without thisstimulus, sodium excretion parallelsdietary intake and generally is morethan 40 mEq/L. (1)

Although assessment of a pa-tient’s volume status is useful in avariety of situations, measurement ofthe UNa is particularly useful in theevaluation of two specific states: hy-ponatremia and acute renal failure.Hyponatremia is caused by excessiveretention of free water out of propor-tion to solute. In clinical practice,this state is due either to the syn-drome of inappropriate antidiuretichormone secretion (SIADH) or tothe appropriate secretion of ADHthat occurs in response to hypovole-mia. It is important to note that thelatter situation occurs not just in sit-uations in which the total body wateris decreased such as gastroenteritisor adrenal insufficiency but also inedematous states such as cirrhosis,congestive heart failure, and ne-phrotic syndrome. In these cases, al-though total body water is increased,the effective circulating volume is de-creased, triggering the appropriaterelease of ADH. In volume-depletedhyponatremic states, the renal tubulesreclaim as much sodium as possible,and the UNa is low at less than20 mEq/L. In SIADH, however, pa-tients experience euvolemia, and so-dium is excreted in the urine at thenormal rate, making the urine sodiumconcentration greater than 40 mEq/L

*The Children’s Hospital of the King’s Daughters,Norfolk, VA.

Abbreviations

ATN: acute tubular necrosisFENa: fractional excretion of

sodiumFEurea: fractional excretion of ureaNH4

�: ammonium ionRTA: renal tubular acidosisSIADH: syndrome of inappropriate

antidiuretic hormonesecretion

TTKG: transtubular potassiumgradient

UAG: urine anion gapUCl: urine chloride concentrationUK: urine potassium concentrationUNa: urine sodium concentrationUurea: urine urea nitrogen

concentration

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when the patient is consuming a nor-mal diet. (1)

For similar reasons, the UNa is alsovaluable in the assessment of a pa-tient who has acute renal failure.Here, the differential diagnosis typi-cally is between prerenal azotemiaand intrinsic renal failure caused byacute tubular necrosis (ATN). If thefailure is prerenal, the kidney retainssodium aggressively in response tohypovolemia and the UNa is low.However, in patients who have ATN,the UNa is greater than 40 mEq/Ldue to tubular damage that impairsmaximal reabsorption of sodium. (1)

In most situations, only a singlerandom or “spot” measurement of so-dium is adequate to provide diagnosticinformation. However, because theconcentration of sodium in the urine isdependent on the amount of free wa-ter in the urine, measuring a randomUNa alone can be misleading in cases ofimpaired renal concentrating ability orexcess free water in the urine. Thus, itmay be preferable to calculate the frac-tional excretion of sodium (FENa),which is calculated as

FENa�

(UNa�plasma creatinine/plasma

Na��urine creatinine)�100%

By expressing the percentage of thefiltered sodium that is excreted, theFENa provides a measure of the so-dium handling that is independent ofhow dilute or concentrated the urinemay be. Appropriate sodium conser-vation (as might be seen in prerenalazotemia) results in an FENa of lessthan 1%; patients who have ATN haveFENa measurements greater than 2%.

The FENa must be interpretedslightly differently in infants, whohave diminished ability to reabsorbsodium due to their immature tubules.Thus, in term neonates, the FENa is lessthan 3% in a volume-depleted state, (2)and in critically ill preterm infants,FENa less than 4% indicates maximalsodium retention. (3)

Calculating the FENa requires si-multaneous measurement of bloodand urine sodium and creatinine. Inyounger children who are unable tovoid on command, the most practicalmeans of obtaining samples is to

place a urine collection bag, thendraw blood for chemistries immedi-ately after the child voids.

Urine PotassiumConcentrationThe kidney has an extraordinary abilityto vary potassium excretion, depend-ing on dietary intake and the serumpotassium concentration. The majorvalue of the urine potassium concen-tration (UK) is in cases of hypo- orhyperkalemia to determine whetherthe kidney is responding appropriatelyto these stimuli. Although spot mea-surements of UK may be helpful, uri-nary potassium handling is assessedbest by calculating the transtubular po-tassium gradient (TTKG).

TTKG�

(UK)/(plasma K�)�(plasma

osmolarity)/(urine osmolarity)

For patients eating normal diets, theTTKG typically is 8 to 9. However,when hypokalemia occurs due to gas-trointestinal losses or inadequate po-tassium intake, the kidney should

Table. Common Electrolyte MeasurementsUrine Electrolyte Clinical Situation Interpretation

UNa Hyponatremia <20 mEq/L: Volume depletion>40 mEq/L: SIADH

Acute renal failure <20 mEq/L or FENa <1%*: Prerenal azotemia>40 mEq/L or FENa >2%*: ATN

UK Hypokalemia TTKG <2 to 3: Nonrenal lossesTTKG >2 to 3: Renal potassium wasting

Hyperkalemia TTKG <6 to 7: Defective potassium secretion(hypoaldosteronism or renal failure)

TTKG >11: Increased potassium intake or transcellular shiftUCl Metabolic alkalosis <20 mEq/L: “Saline-responsive” alkalosis/volume depletion

with vomiting, nasogastric suctioning>20 mEq/L: “Saline-resistant” alkalosis/renal chloride

wasting with diuretic use, Bartter/Gitelman syndromesUAG Hyperchloremic (normal anion gap)

metabolic acidosisPositive UAG: Renal tubular acidosisNegative UAG: Gastrointestinal bicarbonate loss (diarrhea)

Uurea Acute renal failure FEurea <35%: Prerenal azotemiaFEurea >50%: ATN

*Because immature tubules have a reduced reabsorptive capacity for sodium, the FENa is higher in younger or preterm infants.ATN�acute tubular necrosis, FENa�fractional excretion of sodium, FEurea�fractional excretion of urea, SIADH�syndrome of inappropriate antidiuretichormone secretion, TTKG�transtubular potassium gradient, UAG�urine anion gap, UCl�urine chloride concentration, UK�urine potassium concentra-tion, UNa�urine sodium concentration, Uurea�urine urea nitrogen concentration

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conserve potassium and the TTKGfalls to less than 3. Higher values inthe face of hypokalemia indicate re-nal potassium wasting. (4)

Conversely, in patients who de-velop hyperkalemia (especially chronichyperkalemia), a TTKG less than 7 in-dicates defective potassium secretionbecause the appropriate renal responsewould be to maximize potassium ex-cretion. Because potassium excretiondepends on the presence of aldoste-rone and adequate fluid and solute de-livery to the site of aldosterone activityin the distal tubule, this finding sug-gests hypoaldosteronism or renal fail-ure. (5)

Urine Chloride ConcentrationThe major use of the urine chlorideconcentration (UCl) is in the evalua-tion of a metabolic alkalosis. Typi-cally, sodium and chloride are re-absorbed together throughout thenephron. Accordingly, the UNa andUCl are usually approximately equal.However, in some cases of metabolicalkalosis, the kidney’s need to ex-crete bicarbonate may require so-dium to be excreted with bicarbon-ate, making the UCl low (typically�20 mEq/L). This response occurswith vomiting or nasogastric suc-tion or following hypercapnia. Clas-sically, such situations were knownas “saline-responsive” metabolic al-kaloses because the administrationof saline and repletion of chloridewould correct the alkalosis.

Alternately, metabolic alkalosiscan be caused by a primary inabilityto reabsorb chloride, forcing sodiumto be reabsorbed with another anionsuch as bicarbonate. In such cases,which include genetic defects ofchloride reabsorption such as Bartteror Gitelman syndromes as well as di-uretic use or abuse, the UCl is ele-vated (�20 mEq/L). Here, the alka-losis is “saline-resistant,” and

administration of chloride will haveminimal impact on the alkalosis be-cause the administered chloride willbe lost in the urine. (1) For morecomplicated reasons, profound hy-pokalemia also leads to impairedchloride transport and can causemetabolic alkalosis. (6)

Urine Anion GapThe value of the urine anion gap(UAG) stems from the understand-ing that the total number of cationsin the urine must necessarily equalthe number of excreted anions. Cal-culating the UAG can provide infor-mation about urine compositionwithout directly measuring everypossible solute. The UAG is calcu-lated by subtracting the commonlymeasured anions from the commonlymeasured cations in urine:

UAG�UNa�UK�UCl

Unlike the serum anion gap, which isalways positive, the UAG can be pos-itive or negative, depending on thepresence of excess unmeasured cat-ions or anions in the urine. Knowingthat the gap is positive (indicatingthe presence of excess anions) ornegative (indicating the presence ofexcess cations) is clinically sufficientand more important than the magni-tude of the gap.

The UAG is most useful in theevaluation of a normal anion gap (hy-perchloremic) metabolic acidosis. Inthis situation, the clinician must dis-tinguish between gastrointestinallosses of bicarbonate (such as diar-rhea) and renal tubular acidosis(RTA).

In metabolic acidosis, the appro-priate renal response is to excrete acidto return the serum pH to normal.Thus, with diarrhea or other gastro-intestinal losses of bicarbonate, theUAG is negative (Fig. 1), indicatingthe excess cations in the urine due to

the excretion of protons, which aretypically excreted as ammonium ion(NH4

�).In contrast, the various RTAs are

characterized as an impaired abilityto excrete acid. The UAG, thus, ispositive (Fig. 2), indicating an inabil-ity to secrete NH4

� and impairedrenal response to acidosis. Furtherhistory and diagnostic testing are re-quired to distinguish among thethree types of RTA. (7)

Urine Urea NitrogenAs described previously, measure-ment of the UNa is an excellent indi-cator of a patient’s volume status.

Figure 1. A graphic illustration of theprinciple underlying the urine aniongap. UC�unmeasured cations, UA�unmeasured anions. Because the totalcationic charge must necessarily equalthe total anionic charge, a change in thesize of one “compartment” must be ac-companied by a corresponding change inanother compartment. In the situationdepicted, the anion gap is negative be-cause the number of unmeasured cationsexceeds the number of unmeasured an-ions (the area indicated by the arrow).Because the major unmeasured cation isammonium, this indicates an appropri-ate renal response to metabolic acidosis.

focus on diagnosis



However, in cases of acute diureticuse, drug-induced natriuresis may

make the measurement of the UNa

unreliable. In such cases, measure-ment of the urine urea nitrogen con-centration (Uurea) and calculation ofthe fractional excretion of urea (FEurea)(analogous to the calculation of theFENa) can provide similar informationin the evaluation of acute renal failure.

In low-flow states, the kidney re-tains urea due to the need to reab-sorb sodium maximally (leading tothe out-of-proportion rise of bloodurea nitrogen to serum creatininethat occurs in prerenal azotemia).Thus, if the kidney senses decreasedeffective circulating volume, the FEurea

is less than 35%; in cases of ATN, theFEurea exceeds 50%. (8)

ConclusionUrine electrolytes can be analyzedcheaply and quickly on standard lab-oratory equipment, and becausethere is no requirement that theurine be completely sterile, samplescan be obtained painlessly, even frominfants, by using a urine collectionbag.

References1. Rose BD. Meaning and application ofurine chemistries. In: Clinical Physiology ofAcid-Base and Electrolyte Disorders, 4th ed.New York, NY: McGraw-Hill; 1994:3802. Ellis EN, Arnold WC. Use of urinaryindexes in renal failure in the newborn. Am JDis Child. 1982;136:615–6173. Tapia-Rombo CA, Velasques-Jones L,Fernandes-Celis JM, et al. Usefulness offractional excretion of sodium in critically illpre-term newborns. Arch Med Res. 1997;28:253–2574. Joo KW, Chang SH, Lee JG, et al. Trans-tubular potassium concentration gradient(TTKG) and urine ammonium in differen-tial diagnosis of hypokalemia. J Nephrol.2000;13:120–1255. Choi MJ, Ziyadeh FN. The utility of thetranstubular potassium gradient in the eval-uation of hyperkalemia. J Am Soc Nephrol.2008;19:424–4266. Garella S, Chazan JA, Cohen JJ. Saline-resistant metabolic alkalosis or “chloride-wasting nephropathy.” Ann Intern Med.1970;73:31–387. Kamel KS, Ethier JH, Richardson RM,et al. Urine electrolytes and osmolality:when and how to use them. Am J Nephrol.1990;10:89–1028. Carvounis CP, Nisar S, Guro-RazumanS. Significance of the fractional excretion ofurea in the differential diagnosis of acuterenal failure. Kidney Int. 2002;62:2223–2229

Figure 2. A graphic illustration of apositive urine anion gap, with the num-ber of unmeasured cations exceeding thenumber of unmeasured anions. Whenthis situation occurs in the context ofmetabolic acidosis, it is consistent withrenal tubular acidosis, indicating an im-paired ability to excrete protons in theurine as ammonium.

focus on diagnosis




J. Bryan Carmody Focus on Diagnosis: Urine Electrolytes



Supplementary Material

DC1http://pedsinreview.aappublications.org/cgi/content/full/32/2/65/Supplementary material can be found at:


trolyte_metabolismhttp://pedsinreview.aappublications.org/cgi/collection/fluid_elec

Fluid and Electrolyte Metabolism rdershttp://pedsinreview.aappublications.org/cgi/collection/renal_diso

Renal Disordersfollowing collection(s): This article, along with others on similar topics, appears in the

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CorrectionsThe caption for Figure 2 in the article entitled “Focus on Diagnosis: Urine Electrolytes” inthe February issue of the journal (Pediatr Rev. 2011;32:65–68) is incorrect. The correctcaption should read, “A graphic illustration of a positive urine anion gap, with the numberof unmeasured anions exceeding the number of unmeasured cations. When this situationoccurs in the context of metabolic acidosis, it is consistent with renal tubular acidosis,indicating an impaired ability to excrete protons in the urine as ammonium.” We regret theerror.

The caption for Figure 1 in the article entitled “Sacral Dimples” in the March issue ofthe journal (Pediatr Rev. 2011;32:109–114) is incorrect. The correct caption should read,“Solitary dimple whose location is greater than 2.5 cm above the anus indicated the needfor further evaluation. . . .” We regret the error.

5. A 7-year-old girl presents with a 3-day history of bruising and an episode of epistaxis lasting 30 minutes.On physical examination, the only abnormalities are scleral icterus, widespread bruising, and cutaneous aswell as mucosal petechiae. Laboratory results include a platelet count of 3�103/�L (3�109/L), hemoglobinof 7.8 g/dL (78 g/L), white blood cell count of 12.9�103/�L (12.9�109/L), absolute neutrophil count of8.8�103/�L (8.8�109/L), and mean corpuscular volume of 86 fL. Urinalysis is negative for red blood cells.The most appropriate next study is:

A. Antiplatelet antibodies.B. Bone marrow aspirate.C. Direct antiglobulin (Coombs) test.D. Flow cytometry on peripheral blood.E. Serum blood urea nitrogen and creatinine assessment.

hematology thrombocytopenia

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Robert Macauley Ethics for the Pediatrician: Ethical Issues in Organ Donation







Author Disclosure

Dr Macauley has disclosed no






Ethical Issues in Organ DonationRobert Macauley, MD*


1. Define the dead donor rule and identify current controversies surroundingit.

2. Describe the concept of donation after cardiac death (DCD).3. Identify the requirements for children to serve as living hematopoietic stem

cell and solid organ donors.4. Discuss ethical issues related to organ donation that are specific to

pediatrics.

IntroductionThe primary ethical issues in organdonation involve procurement of vi-tal organs (ie, organs necessary forlife) from deceased donors, procure-ment of nonvital organs from livingdonors, and subsequent allocation ofthese organs. When children are in-volved (either as donors or recipi-ents), each of these issues has an ad-ditional layer of complexity.

Cadaveric Donation of VitalOrgansThe fundamental principle of vitalorgan donation is the “dead donorrule,” which states that donors mustnot be killed to obtain their organs(1) (or, alternatively, that personsmust be dead before their organs aretaken). (2) The matter of when apatient is considered dead, however,is rather complex. Before the adventof mechanical ventilation—whencessation of brain function would in-evitably cause a patient to stopbreathing—determination of deathdepended solely on cardiorespiratoryparameters. Ventilators made it pos-sible to sustain cardiorespiratoryfunction even when a patient was in

what was once termed “irreversiblecoma,” which later came to be knownas “brain dead.” The Uniform Deter-mination of Death Act (1981) estab-lished an all-encompassing definition:a patient is dead if he or she has sus-tained either “irreversible cessation ofcirculatory and respiratory functions”(cardiorespiratory criteria) or “irrevers-ible cessation of all functions of theentire brain, including the brain stem”(neurologic criteria).

The debate about brain deathcontinues, however, with such deter-minations more complex in pediat-rics, especially for younger children.(3) In addition, some critics arguethat the current definition of “braindeath” is too restrictive, instead ad-vocating a “higher brain” definitionof death, which would allow patientswho have brainstem (but no cortical)function to be declared dead. (4)Other critics have questioned whethera patient who meets “whole brain”brain death criteria is truly dead (basedon, for example, continued neurohor-monal regulation in the presence of aflat electroencephalographic tracing(5)). Although this perspective couldmean that vital organs cannot be re-trieved from such patients, some haveused this consideration as an occasionto question whether the dead donorrule is even necessary, instead focusing

*Medical Director of Clinical Ethics, Fletcher AllenHealth Care; Associate Professor of Pediatrics,University of Vermont College of Medicine,Burlington, VT.

ethics for the pediatrician



on the primacy of informed consentfor vital organ donation from neuro-logically devastated or imminentlydying patients. (6) (These poignantquestions are addressed in greater de-tail in another article in the Ethics forthe Pediatrician series: AntommariaAHM. Conceptual and ethical issues inthe declaration of death: current con-sensus and controversies. Pediatr Rev.2010;10:427–430.)

A specific example of the debateover the dead donor rule was thebrief endorsement by the AmericanMedical Association (AMA) of ante-mortem vital organ retrieval from in-fants who had anencephaly. Despitethe American Academy of Pediatrics(AAP) statement in 1992 that“[counseled] extreme caution beforeadopting a policy permitting organretrieval from anencephalic infantswho retain brain stem function,” (7)the AMA defended the practice in1994 as ethically permissible becausethese infants have “never experi-enced and will never experience con-sciousness.” (8) This stance waswidely criticized, largely based on theslippery slope argument: If one couldretrieve organs from anencephalic in-fants because they would never expe-rience consciousness, why not takeorgans from patients in a vegetativestate? The AMA rescinded its opin-ion the following year, and since thattime there has been little discussionof retrieving vital organs from suchinfants.

Cardiorespiratory criteria for de-termination of death have also beendebated, largely because of the re-newed interest in retrieving organsfrom nonheart-beating donors. Be-fore the codification of brain death,DCD was the only method of pro-curing vital organs. Protocols forcontrolled DCD were first designedin the 1990s as a response to an in-sufficient supply of organs availablefrom patients declared dead by neu-

rologic criteria. Controlled DCDtypically involves patients who haveexperienced profound neurologic in-jury (but who do not meet the ac-cepted definition of brain death) andwho are expected to die soon aftercessation of life-sustaining treatment(LST). Once the patient (or surro-gate decision maker) decides to with-draw LST and consents to DCD, adefined period of pulselessness pre-cedes the declaration of death, atwhich point the transplant team ini-tiates organ retrieval. (UncontrolledDCD is relatively rare and refers to asituation in which a potential donorexperiences cardiopulmonary arrestbefore informed consent for organretrieval is obtained.)

Ethical issues related to DCD in-clude the required length of time ofpulselessness, the propriety of inter-ventions intended solely to maximizeorgan viability (such as anticoagula-tion and large-vessel cannulation),and the involvement of the organprocurement team only after deathhas been declared. (9) It also is criti-cal that the decision to withdraw LSTbe made independent of the decisionto donate organs to avoid dividedloyalties. The full range of palliativecare must be available to DCD do-nors, and medications should be ad-ministered for the patient’s comfortalone and not with any intention ofhastening death to maximize organviability.

The cardiorespiratory definitionof death and the dead donor rulewere major considerations in a recentdebate concerning pediatric hearttransplantation following DCD. (10)Critics assert that there could not be“irreversible” cessation of cardiacfunction because such function wassuccessfully reestablished in the re-cipients. (11) Defenders of the pro-cedure draw a distinction between“‘permanent’ (will not reverse) and‘irreversible’ (cannot reverse) cessa-

tion” of cardiorespiratory function,arguing that the transplanted heartswould not function in the donors(because external resuscitationwould not be offered) but could stillfunction in the recipients with medi-cal assistance. (12) In light of thesenuanced distinctions, it is not sur-prising that a recent survey of pedia-tricians found that most were notconfident that DCD donors weretruly dead. (13)

Living DonationAlthough vital organs can be pro-cured only from deceased donors,hematopoietic cells and solid organs(such as kidneys and sections of lungand liver) may be procured from liv-ing donors. The former is less con-troversial than solid organ transplan-tation because the risks to the donor“can be characterized as more thanminimal, but they are nonethelessgenerally modest.” (14) Parents haveturned not only to existing siblings assources of hematopoietic stem cellsfor an affected child, but also to thepurposeful conception of additionalchildren in the hopes of finding anideal match. In some cases, parentshave even used prenatal diagnosis toproduce a human leukocyte antigen-matched donor (so-called “saviorsiblings”). The AAP does not opposethis practice as long as the youngersibling is loved and cared for in his orher own right (and, thus, is not usedsolely as a means to an end). TheAAP identifies five necessary condi-tions for a minor to serve as a hema-topoietic stem cell donor: (14)

1. There are no other donor op-tions (ie, no willing, able, and medi-cally equivalent histocompatibleadult relative).

2. There is a strong and positiverelationship between donor and re-cipient.

3. The recipient is likely to bene-fit from the transplant.




4. Risks to the donor are mini-mized.

5. Parental permission and (whereappropriate) child assent are obtained.

Solid organ donation entailsgreater risks to the donor, both phys-ical (including a mortality risk of 2 in10,000 for kidney donation (15) andthe chance of the donor eventuallysuffering from the same disease thatnecessitated the transplant for the af-fected sibling) and psychological (in-cluding guilt if the transplant is notsuccessful and a loss of attention if itis). Given that the transplant is per-formed for the benefit of someoneelse, there can be no physical benefitsfor the donor. There may be psycho-logical benefits, however, such asgreater self-esteem and potentiallymore attention if the recipient subse-quently requires less intense care.Thus, although it would be impossi-ble to argue that it is in the donor’smedical best interest, it could be inhis or her overall best interest. Thiswould only be the case, however, ifthe recipient were a close relative(most often a minor sibling).

Parents are the presumeddecision-makers for their children,for whom they must make choicesbased on what is in their child’s bestinterest. Because the parents are alsoconcerned with that sibling’s best in-terest, their loyalty is divided, whichcan make it extremely difficult to de-cide whether to proceed with dona-tion. There is also the matter of theassent of the child and his or hersusceptibility to coercion, given thecharged emotional family landscape.This dilemma has been highlightedin the popular press in Jodi Picoult’snovel My Sister’s Keeper and the sub-sequent motion picture.

Whereas the Amsterdam Consen-sus Panel determined that minorsshould not be permitted to donatesolid organs, (15) both the UnitedStates Live Organ Donor Consensus

Group and the AAP argue that chil-dren may do so in certain situations.The AAP cites a lower age limit of11 to 14 years to provide meaningfulassent (in light of the increased riskcompared with hematopoietic stemcell donation). The five necessaryconditions are analogous to those forhematopoietic stem cell transplant,with the following modifications:(16)

1. Both the recipient and the do-nor are highly likely to benefit (whichessentially requires the recipient tobe an immediate family memberwhile also excluding donors whohave severe cognitive disabilities be-cause they could not appreciate thebenefit to their relative).

2. Surgical risk for the donor isextremely low.

3. The minor freely assents to do-nate without coercion (establishedby an independent advocacy team).

Although much of the ethical de-bate surrounding transplantationand pediatrics involves children asdonors, there are also ethical issuesinvolving children as recipients. Anexample is the discovery of misattrib-uted paternity through screening thepresumed father as a potential donor,an issue identified in up to 0.5% ofliving kidney donations. (17) Argu-ments in favor of disclosure includethe duty of truth-telling and the re-quirement of informed consent;those opposed cite family preserva-tion and patient confidentiality. Atpresent, there does not appear to beconsensus as to the appropriate re-sponse. At a minimum, transplantprograms should formulate a policyfor responding to such situations,and this potential discovery shouldbe disclosed to prospective donorsbefore testing.

Allocation of OrgansEquitable distribution of scarce re-sources is a matter of justice, one of

the core principles of biomedical eth-ics. Initial attempts at determiningwho would benefit from the limitedsupply of transplantable organs in-cluded “social worth” criteria, suchas religious observance and commu-nity involvement. It quickly becameapparent that such criteria were notappropriate in a pluralistic society,and prioritization for organs nowgenerally takes into account time onthe waiting list, tissue or blood-typematching, level of current need, andgeographic region.

Over time it has become clear thatsome of these factors could place chil-dren at a competitive disadvantage, de-spite the child’s life expectancy follow-ing transplant being greater than anequivalent adult’s. Children currentlymake up 1.6% of the national waitinglist, with more than 70% of such chil-dren waiting for either a kidney orliver. (18) Recognizing their uniqueneeds, Congress passed the Children’sHealth Act in 2000, which requiredthe Organ Procurement and Trans-plant Network (OPTN) to formulatepediatric-specific criteria for organ al-location. Rather than relying exclu-sively on length of time on the waitinglist, subsequent OPTN criteria priori-tize children for pediatric donor lungs,adolescent donor hearts, and kidneysprocured from donors younger thanthe age of 35 years. Children youngerthan the age of 11 years receive furtherprioritization for kidney transplant inlight of the effects of renal failure ondevelopment. (19)

Obviously, a child cannot receive anorgan unless the parent or guardianhas the patient listed for transplant andgives permission for the procedure.This situation raises the ethical ques-tions of whether failure to seek trans-plant constitutes medical neglect onthe part of the parents and whether anadolescent may refuse a potentially life-saving transplant. Answering these




questions depends largely on the typeof transplant, the likelihood of success,and any comorbidities that may affectthe child’s quality or duration of life. Inthe case of the adolescent, the patient’slevel of understanding and maturity aswell as state laws regulating emanci-pated or “mature” minors are relevant.

References1. Robertson J. The dead donor rule. HastCent Rep. 1999;6:62. Arnold RM, Youngner SJ. The dead do-nor rule: should we stretch it, bend it, orabandon it? Kennedy Inst Ethics J. 1993;3:263–2783. Task Force for the Determination ofBrain Death in Children. Guidelines for thedetermination of brain death in children.Arch Neurol. 1987;44:587–5884. Veatch RM. The impending collapse ofthe whole-brain definition of death. HastCent Rep. 1993;23:18–245. Halevy A, Brody B. Brain death: recon-ciling definitions, criteria, and tests. AnnIntern Med. 1993;119:519–5256. Truog RT, Robinson WM. Role of braindeath and the dead-donor rule in the ethicsof organ transplantation. Crit Care Med.2003;31:2391–23967. Committee on Bioethics. Infants withanencephaly as organ sources: ethical con-siderations. Pediatrics. 1992;6:11198. American Medical Association. Opinion2.162: Anencephalic infants as organ do-nors. Code of Medical Ethics. Chicago, IL:American Medical Association; 1994:309. Antommaria AHM. Conceptual andethical issues in the declaration of death:current consensus and controversies. Pedi-atr Rev. 2010;10:427–43010. Boucek MM, Mashburn C, Dunn SM,et al, Denver Children’s Pediatric HeartTransplant Team. Pediatric heart transplan-tation after declaration of cardiocirculatorydeath. N Engl J Med. 2008;359:709–714

11. Veatch RM. Donating hearts after car-diac death: reversing the irreversible. N EnglJ Med. 2008;359:672–67312. Bernat JL. How the distinction be-tween “irreversible” and “permanent” illu-minates circulatory–respiratory death deter-mination. J Med Phil. 2010;35:242–35513. Joffe AR, Anton NR, deCaen AR. Sur-vey of pediatricians’ opinions on donationafter cardiac death: are the donors dead?Pediatrics. 2008;122:e967–e97414. American Academy of Pediatrics. Policystatement: children as hematopoietic stem celldonors. Pediatrics. 2010;125:392–40415. Delmonico F; Council of the Trans-plantation Society. A report of the Amster-dam Forum on the care of the live kidneydonor: data and medical guidelines. Trans-plantation. 2005;79:S53–S6616. Ross LF, Thistlethwaite JR, and theCommittee on Bioethics. Minors as livingsolid-organ donors. Pediatrics. 2008;122:454–46117. Young A, Kim SJ, Gibney EM, et al. forthe Donor Nephrectomy Outcomes Re-search (DONOR) Network. Discoveringmisattributed paternity in living kidney do-nation: prevalence, preference, and practice.Transplantation. 2009;87:1429–143518. Organ Procurement and TransplantNetwork website. Accessed November2010 at: http://optn.transplant.hrsa.gov19. American Academy of Pediatrics. Policystatement: pediatric organ donation andtransplantation. Pediatrics. 2010;125:822–828

Summary• Vital organs may be procured

only from patients declareddead (dead donor rule).

• Increasing numbers of organsare being procured frompatients declared dead bycardiorespiratory criteriafollowing withdrawal of life-sustaining treatment (DCD).

• The AAP holds that childrenmay serve as livinghematopoietic stem cell andsolid organ donors as long ascertain conditions are met.

• Recent modifications to theOPTN allocation schemeprioritizes children for organsprocured from other children(and, in some cases, youngadults).





Robert Macauley Ethics for the Pediatrician: Ethical Issues in Organ Donation




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

Ethics for the Primary Care Pediatricianfollowing collection(s): This article, along with others on similar topics, appears in the







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Sharon R. Ghazarian ValuePImportance: The Value of the

Research and Statistics: Distinguishing Statistical Significance from Clinical







Author Disclosure

Dr Ghazarian has disclosed no






Distinguishing Statistical Significancefrom Clinical Importance: The Valueof the P ValueSharon R. Ghazarian, PhD*

Case PresentationYou have been providing handouts oninfant massage to your families whohave newborns for several years. Youhad read about the benefits of infantmassage, including increased bondingbetween parent and child, improvedinfant digestion, facilitation of at-tachment, improved sleep, and betterinfant weight gain. (1) However, yourecently read an article showing theresults of a comparative panel designstudy in which the association betweeninfant massage and weight gain wasstatistically significant at 2 monthsbut not at 4 months of age for mothersand their infants in Santiago, Chile.(2) You now wonder whether infantmassage is as beneficial as you oncethought and whether you should con-tinue to provide the information toparents of newborns.

IntroductionMany practitioners wonder whethera lack of statistical significance meansa lack of clinical importance for theirpatients. If a study finds an associa-tion to be statistically significant,does it mean that the finding also isclinically important? Alternatively, ifa study finds that an association is notstatistically significant, does it meanthat the finding is not clinically im-portant for the families in a practitio-ner’s practice? Statistical significancedemonstrates the likelihood that adifference or relationship really existsand did not just occur by chance. We

often are excited by a significant Pvalue, but that value does not neces-sarily mean that the finding is impor-tant or useful.

Determining statistical signifi-cance involves hypothesis testing andcomparison of study results to a pre-determined level or P value. The levelof significance is the probability ofreporting an incorrect association orcommitting a type I error. Conven-tional P values usually are set at either0.05 or 0.01. A P value of 0.05 indi-cates that the researcher is 95% surethat the finding is a true associationand not just due to chance. A P valueof 0.01 indicates that the researcheris 99% sure that the finding is a trueassociation and that the findingcould be due to chance only 1% ofthe time. Thus, if a study reports thatan association between infant mas-sage and infant weight gain is signif-icant at the 0.05 level, the associationcan be considered as true 95% of thetime and possibly due to chance 5%of the time. (3)

Although P values measurechance of association, they do notmeasure strength of association orclinical importance. P values tend tobe smaller when there is a larger nu-meric difference between the twogroups, a larger sample size, or lessvariability within treatment groups.(4) Values are also affected by theproportion of those exposed and theproportion who have the targetedoutcome. In fact, because of the lim-itations and misuses of P values, theInternational Committee of MedicalJournal Editors suggests that “whenpossible, quantify findings andpresent them with appropriate indi-cators of measurement error or un-

*Director, Bayview Biostatistics, Epidemiology andData Management Core, Department of Pediatrics,Johns Hopkins University, Baltimore, MD.

research and statistics



certainty (such as confidence inter-vals). Avoid relying solely onstatistical hypothesis testing, such asthe use of p-values, which fails toconvey important quantitative infor-mation.” (5)

The authors of the infant massagestudy (2) found a statistically signifi-cant association between infant mas-sage and infant weight gain at 2months of age (5,537 g for the mas-sage group versus 4,672 g for thecontrol group) with a P value of0.0016. Because the P value is lessthan 0.01, there is less than a 1%likelihood that the findings are sim-ply due to chance. Accordingly, thereprobably is an association at 2months. Is this degree of weightchange important? The study alsoshows that the association betweeninfant massage and weight gain at 4months was not statistically signifi-cant (7,044 g for the massage groupversus 7,119 g for the controlgroup). Although there was a statis-tically significant association betweenmassage and weight gain at 2

months, the clinical importance isunclear. What does the statistical dif-ference in weight gain suggest andwhat does the nonstatistical differ-ence in weight gain at 4 months sug-gest?

In addition, the study used a sampleof 100 newborns in a low-incomeneighborhood of Santiago, Chile. Un-less a practitioner has a practice withthe same demographic characteristicsof the study sample, study results maynot be generalizable to other children.To ascertain whether infant massage isbeneficial, numerous studies wouldneed to be examined with samples offamilies possessing a variety of demo-graphic characteristics, including vari-ous levels of income, education, familystructure, race/ethnicity, parity, mari-tal status, and more.

ConclusionPractitioners should consider clinicalimportance independent from statis-tical significance, in this case askingwhether broader literature, beyondthe single study demonstrating lim-

ited statistical significance, suggeststhat infant massage is beneficial forparents and newborns. Final deci-sions about what to recommend tofamilies should be based on broadliterature searches, studies generaliz-able to a clinician’s patient popula-tion, and careful consideration ofwhat is statistically and clinically im-portant to the families being served.

References1. Lorenz L, Moyse K, Surguy H. The ben-efits of baby massage. Paediatr Nurs. 2005;17:15–182. Serrano MSC, Doren FM, Wilson L.Teaching Chilean mothers to massage theirfull-term infants. J Perinat Neonat Nurs.2010;24:172–1793. Howell DC. Statistical Methods for Psy-chology. Pacific Grove, CA: Duxbury; 20024. Cummings P, Koepsell TD. P values ver-sus estimates of association with confidenceintervals. Arch Pediatr Adolesc Med. 2010;164:193–1965. International Committee of MedicalJournal Editors. Uniform Requirements forManuscripts Submitted to Biomedical Jour-nals: Writing and Editing for BiomedicalPublication. Accessed November 2010 at:http://www.icmje.org

research and statistics




Sharon R. Ghazarian ValuePImportance: The Value of the

Research and Statistics: Distinguishing Statistical Significance from Clinical




tatisticshttp://pedsinreview.aappublications.org/cgi/collection/research_s

Research and Statisticsfollowing collection(s): This article, along with others on similar topics, appears in the







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Moustafa, Shira Rosenberg, Ryan P. Flanagan and Neil Mullen John D.A. Campagna, Minela Fernandez, Lance Yamashiroya, Ronen Zipkin, Marwa

3: Ecchymotic Lesions on the Backs of Asian Boys2: Fever, Rash, Headache, Myalgia, and Arthralgia in an 11-year-old Boy • Case Index of Suspicion • Case 1: Nonbilious Projectile Vomiting in a Neonate • Case







The reader is encouraged to writepossible diagnoses for each case beforeturning to the discussion. We invitereaders to contribute case presentationsand discussions. Please inquire first bycontacting Dr. Deepak Kamat [email protected].

Author Disclosure

Drs Campagna, Fernandez,

Yamashiroya, Zipkin, Moustafa,

Rosenberg, Flanagan, and Mullen

have disclosed no financial

relationships relevant to these cases.

This commentary does not contain a

discussion of an unapproved/

investigative use of a commercial

product/device.

Case 1: Nonbilious Projectile Vomiting in aNeonate

Case 2: Fever, Rash, Headache, Myalgia, andArthralgia in an 11-year-old Boy

Case 3: Ecchymotic Lesions on the Backs of AsianBoys

Case 1 PresentationA 16-day-old boy is evaluated in theED for 5 days of projectile vomiting.Thirty minutes after breastfeeding,he vomits milk at distances up to 2 ft.He also has been having difficultyfeeding, staying on the breast foronly 5 minutes, and is sleepy. Thefrequency of emesis has been increas-ing to after almost every feeding.Urine output and stooling frequencyhave decreased.

The infant was born at term to a37-year-old G2P2 woman after anuncomplicated pregnancy. His new-born screening results were normal.He developed icterus on postnatalday 2, with a peak bilirubin value of22 mg/dL (376.3 �mol/L) and apositive direct antiglobulin test. Thehyperbilirubinemia responded tophototherapy within 24 hours.

Physical examination reveals an ic-teric, nondysmorphic infant in no ap-parent distress. His temperature is36.6°C, heart rate is 132 beats/min,respiratory rate is 48 breaths/min,and oxygen saturation is 99%. He haslost more than 10% of his birth-weight. His fontanelle is open, soft,and flat. His lungs are clear, and hisabdomen is soft and nondistended,without any organomegaly, but hisbowel sounds are hypoactive.

Laboratory studies reveal a WBCcount of 13.0�103/mcL (13.0�109/L) with a normal differentialcount, Hgb of 17.6 g/dL (176 g/L), Hct of 50.7% (0.51), and plateletcount of 528�103/mcL (528�109/L). His C-reactive protein (CRP)measures less than 0.1 mg/dL. A ba-

sic metabolic panel yields normal re-sults. He has an indirect hyperbili-rubinemia of 17.3 mg/dL (295.9�mol/L). Blood, CSF, and urinecultures are sent.

Ultrasonography of the abdomenshows a normal pylorus. Chest radio-graphs as well as CT scan of the chestand abdomen reveal the diagnosis.

Case 2 PresentationAn 11-year-old boy presents to theED with a 9-day history of tempera-ture to 40.2°C and a 2-day history ofa nonpruritic rash that began on histrunk and spread to all four extremi-ties. The rash is most prominentwhen he is febrile. He has headaches,myalgias, and joint pain, whichworsen with his fevers. Animal expo-sures include stray cats, turtles, and arat infestation in his backyard. He hasa history of bipolar disorder, seizures,and hypothyroidism, for which hetakes lithium, levetiracetam, andlevothyroxine sodium, respectively.

In the ED, his temperature is40.0°C, heart rate is 133 beats/min,respiratory rate is 20 breaths/min,and blood pressure is 88/43 mmHg. Physical examination reveals awell-nourished, well-developed boyin no acute distress. He has a faint,blanching, macular exanthem on histrunk, all four extremities, and bothpalms and soles. There are severalnonblanching macules on his anklesand left wrist.

Laboratory evaluation reveals aWBC count of 5.29�103/mcL(5.29�109/L), with 22% neutrophils,

index of suspicion



50% bands, 21% lymphocytes, and6% monocytes; Hgb of 11.8 g/dL(118 g/L); and platelet count of109�103/mcL (109�109/L). HisCRP is 19.8 mg/dL, ESR is 18 mm/hr, AST is 89 U/L, and ALT is53 U/L. Results of a chemistry paneland a urinalysis are normal. Addi-tional testing reveals the diagnosis.

Case 3 PresentationTwo Asian boys, ages 9 and 11 years,who are neighbors, present to theED 1 day apart complaining of sorethroat, fever, headache, and abdom-inal pain for about 1 week. Both boysare otherwise healthy and have noknown chronic illnesses, medicationuse, or previous hospitalizations.

Physical examination reveals nor-mal vital signs in both boys. How-ever, both boys exhibit an erythema-tous oropharynx, exudates ontonsils, and bilateral submandibularlymphadenitis. The findings on der-matologic examinations are of con-cern. The 9-year-old boy has numer-

ous ecchymotic lesions on his backthat are approximately 3�10 cm(Fig. 1), and the 11-year-old boyhas numerous round areas of ecchy-mosis approximately 8 cm in diame-ter across his back (Fig. 2). All otherphysical findings are normal.

On further questioning, neitherboy has a history of epistaxis, bruis-

ing, petechiae, hemoptysis, hema-tochezia, fatigue, or weight loss.When questioned directly about thelesions, neither boy makes eye con-tact or provides an explanation ofhow the lesions occurred. Additionalhistory reveals the cause for the find-ings.

Case 1 DiscussionThe patient was hospitalized for fluidmanagement. His chest radiographshowed a radiopaque mass betweenthe right cardiac border and rightdiaphragm (Fig. 3). CT scan of thechest showed a gastric volvulus in thethoracic cavity (Fig. 4). He was takento the operating room, where alarger-than-average paraesophagealhernia with proximal bowel hernia-tion was found. The volvulus wasreduced surgically. His hyperbiliru-binemia resolved within 48 hours ofhospitalization, and urine, CSF, andblood cultures were negative.

Differential DiagnosisNonbloody, nonbilious (NBNB)vomiting in an infant (0 to 3 monthsof age) has a broad differential diag-nosis. Nonbilious vomitus suggeststhat the lesion lies proximal to theampulla of Vater. Bilious vomitingoften connotes a serious condition.

The most common cause of non-bilious vomiting in this patient’sage group is gastroesophageal reflux(GER), which results from abnormalfunction of the lower esophagealsphincter (LES). In infants, this dys-function usually stems from immatu-rity of the LES. GER resolves as thechild ages. Infants who have GERusually gain weight properly andhave normal physical examinationfindings. Vomiting tends to occurwithin 30 minutes of feeding.

Milk protein allergy is anothercommon cause of NBNB vomiting.The condition represents hypersensi-

Figure 1. Numerous ecchymotic linearlesions on the back.

Figure 2. Numerous round areas of ec-chymosis approximately 8 cm in diame-ter across the back.

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



tivity to milk protein and occurs withhuman, cow, and soy milk feedings.Affected patients often are irritable,have feeding intolerance, and canhave hematochezia. In the most se-vere cases, the children fail to thrive.Vomiting can occur at any time.

Another important cause ofNBNB vomiting is pyloric stenosis,which occurs due to hypertrophy ofpyloric smooth muscle, resulting inblocked passage of gastric contents.Pyloric stenosis frequently occurs inboys between 2 and 6 weeks of age,but girls also are affected. Vomitingusually occurs soon after feeding andoften is projectile. History usually re-veals a progressively increasing inten-sity and frequency of emesis. Patients

tend to present with weight loss andhypochloremic, hypokalemic meta-bolic alkalosis.

Infants who have inborn errorsof metabolism, increased intracranialpressure, and nonaccidental traumaoften present with NBNB vomiting.

The ConditionCongenital paraesophageal hernia isa rare condition that is distinctivelydifferent from a sliding hiatal hernia.Sliding hiatal hernias occur when thegastroesophageal junction slides intothe thorax. In contrast, paraesopha-geal hernia is characterized by a por-tion of the stomach itself, usuallythe fundus, dislocating into the tho-racic cavity. Congenital paraesopha-geal hernias result from two distinctabnormalities in the development ofthe diaphragm. In one abnormalitythat occurs in the development ofthe right pneumoenteric recess, therecess becomes flattened and elon-gated, which allows the gastric fun-dus to move through the diaphragm.The second abnormality occurs inthe development of mesodermal cellsaround the aorta. In all cases, thegastric fundus is surrounded by aperitoneal sac, and the mass residesposterior to the heart and anterior tothe esophagus.

In both abnormalities, the gastricbody migrates into the thoracic cav-ity. Depending on the size of thehernia, bowel can follow. Paraesoph-ageal hernias become symptomaticwhen herniated stomach musclesare unable to pass gastric contentsthrough the pylorus effectively.There is evidence that the herniatedviscus can obstruct the esophagus,leading to vomiting that may be in-termittent.

As the herniation progresses, therisk of gastric volvulus increases. Theabnormal position of the stomachweakens the ligamentous anchors ofthe normal stomach, and the fundus

is free to rotate in the thoracic cavity.Such twisting can lead to furthervomiting and may progress to stran-gulation and infarction. This out-come is rare because gastric volvulustends to resolve spontaneously.

Paraesophageal hernia usually canbe seen as an abnormality on chestradiograph, as in this patient. Themost common finding is a cystic massin the posterior mediastinum. Ap-proximately one third of radiographsshow an air-fluid level. An upper GIradiographic series can help establishthe cystic mass as a part of the GItract. CT scan generally is not indi-cated but does show the details ofabnormal anatomy.

Treatment and PrognosisTreatment of paraesophageal herniais surgical correction. The stomach isemptied by nasogastric suctioning,the hernial sac is excised, and thediaphragm is repaired by crural ap-proximation. Because it has been es-tablished that there is significant dis-ruption of the normal anatomy, mostpediatric surgeons perform an anti-reflux procedure simultaneously.Surgical correction is relatively safe,and corrected hernias are associatedwith minimal morbidity. Usually,long-term complications are limitedto GER.

Paraesophageal hernias in chil-dren are less likely to strangulate thanin adults, even if there is radiographicevidence of volvulus.

This patient tolerated his surgicalprocedure well. He had no furtherepisodes of emesis and gained weightnormally.

Lessons for the Clinician

● NBNB vomiting in an infant iscommon and usually representsGER, but the clinician must beaware of more serious conditions,

Figure 3. Chest radiograph shows a ra-diopaque mass between the right cardiacborder and right diaphragm.

Figure 4. CT scan of the chest shows agastric volvulus in the thoracic cavity.

index of suspicion



such as gastric volvulus, and actquickly.

● Early diagnosis improves the suc-cess of surgical intervention andoverall prognosis considerably.

(John D.A. Campagna, MD, MPH,TM, Minela Fernandez, MD, LanceYamashiroya, MD, Tripler ArmyMedical Center, Honolulu, HI)

Case 2 DiscussionWhile in the hospital, the boy’s feverpersisted, with a maximum tempera-ture of 40.4°C. He was started em-pirically on intravenous cefotaximeand doxycycline. With ongoing my-algias associated with limited rangeof motion in his shoulders, rheuma-tology was consulted to evaluate forsystemic-onset juvenile idiopathic ar-thritis (JIA). Laboratory results werenegative for Mycoplasma titers; Bar-tonella titers; parvovirus and adeno-virus polymerase chain reaction test-ing; and blood, urine, and stoolcultures. His rickettsial typhus im-munoglobulin M titer was positiveat 1:512, supporting the diagnosisof murine typhus. He defervescedwithin 72 hours of starting cefo-taxime and doxycycline and was dis-charged from the hospital to com-plete a 10-day course of doxycyclinemonotherapy. His rash and com-plaints of myalgias were no longerpresent on discharge.

Differential DiagnosisAlthough the differential diagnosisof fever and rash is broad, the typeof rash and its location can be help-ful in narrowing the possibilities.Maculopapular rashes that start onthe trunk and extend to the extrem-ities, palms, and soles (ie, centrifugalrash) include rickettsial diseases suchas infection with louse-borne Rprowazekii, R felis, and flea-borne Rtyphi. Patients who have Rocky

Mountain spotted fever (RMSF),caused by R rickettsii, often have arash that begins on the wrists andankles and spreads centrally to in-volve the trunk and extremities.Blanching macules and papulesevolve into petechiae over time andcan include the palms and soles.RMSF is a life-threatening illness andrarely has a benign course when leftuntreated. Ehrlichiosis may presentwith a maculopapular rash similar toRMSF but rarely is petechial and of-ten has a variable distribution.

Salmon-pink macules or copper-colored papules on the palms andsoles are suggestive of secondarysyphilis and typically appear 4 to8 weeks after the primary infection.The rash associated with measles be-gins on the face and spreads in acephalocaudal distribution, occur-ring 2 to 4 days after the initial pro-drome of cough, coryza, and con-junctivitis. The measles rash typicallyis erythematous and can includepurple-red macules or papules. Ru-bella can have a similar distributionand may be scarlatiniform or morbil-liform, at times being confused withacne. Neither rash typically involvesthe palms or soles.

Dengue fever also can presentwith a distinct rash, often seen in twoseparate phases, and is associatedwith headache and myalgias. The firstrash is transient, macular, and ap-pears within 1 to 2 days of the onsetof fever. The second rash occurs 1 to2 days after defervescence, can bemaculopapular or morbilliform, andtypically spares the palms and soles.

Stevens-Johnson syndrome (SJS)should be considered among patientstaking mood-stabilizing medicationssuch as lithium. SJS more often isassociated with the use of antiepilep-tic agents such as phenytoin, carbam-azepine, and valproic acid as well asnonsteroidal anti-inflammatory agentsand sulfa-containing medications.

Less often, infectious causes such asMycoplasma infection have been im-plicated. The rash of SJS typicallyinvolves mucous membranes (con-junctivitis, urethritis, oral ulcers) andcan include bullae associated with apositive Nikolsky sign.

This patient’s persistent fever andcomplaints of joint pain and myalgiasraised the possibility of systemic JIA.However, children who have JIAtypically demonstrate joint stiffnessafter periods of prolonged inactivityrather than unremitting myalgias andjoint pain. Fevers classically involvetemperatures greater than 39.0°Cand occur in one to two peaks at thesame time each day. Fever must bepresent for more than 2 weeks tomeet diagnostic criteria. The rash of-ten is characterized as salmon pink,nonpruritic, and primarily affectingthe trunk and extremities.

The ConditionMurine typhus (flea-borne typhus)is caused by R typhi and typicallyconstitutes a less severe illness thanepidemic typhus (louse-borne Rprowazekii). Rats are the primary res-ervoir for R typhi, although cats in-fested with fleas also can serve as areservoir. The rat flea XenopsyllaCheopis is the vector usually respon-sible for rodent-to-human transmis-sion. After feeding on infected ro-dents, fleas become carriers for life.Humans become infected when con-tact with flea feces occurs througha compromised skin barrier. Mostcases have been reported in Califor-nia, Texas, and Hawaii.

Laboratory findings can includeleukopenia, elevated inflammatorymarkers, and slightly elevated livertransaminases. Symptoms can resem-ble other rickettsial infections andcan include fever, chills, headaches,and myalgias. The rash occurs in ap-proximately 60% of patients andgenerally presents 4 to 7 days after

index of suspicion



the onset of symptoms. The rash typ-ically is macular or maculopapularand often remains discrete withsparse lesions. The illness rarely lastslonger than 2 weeks, although severecases that are not treated can be fatal.

TreatmentThe drug of choice for murine ty-phus is doxycycline (2.2 mg/kg ev-ery 12 hours to a maximum of300 mg/day). The duration of fe-brile illness averages 12 days, with amedian time to defervescence of2 days. Therapy often is continuedfor 3 days after resolution of fever.Although most patients appear welland do not require intensive care,complications can include renal fail-ure, meningoencephalitis, respira-tory failure, and myocarditis. Prompttreatment can shorten the durationof fever, and relapses are very rarewhen patients are treated properly.Postexposure prophylaxis is not indi-cated, but R typhi infections shouldbe reported to local or federal publichealth agencies.

Lessons for the Clinician● The combination of fever and rash

is a common presenting complaintin children, and most patients whohave these signs have a benign, self-limited illness.

● A subset of patients have pro-longed symptoms that require amore thorough history and physi-cal examination, including a travelhistory as well as a detailed historyof animal exposures.

● Narrowing the differential diagno-sis according to physical findingscan lead to a more cost-effectiveevaluation and quicker resolutionof symptoms.

(Ronen Zipkin, MD, MarwaMoustafa, MD, Shira Rosenberg, MD,Children’s Hospital of Los Angeles, LosAngeles, CA)

Case 3 DiscussionBoth boys had positive rapid strepto-coccal latex agglutination tests andwere started on penicillin therapy.Because of concern about the ecchy-moses, screening coagulation studieswere performed, and results werewithin normal limits. Both boys wereinterviewed without adult supervi-sion and still were not willing to pro-vide an explanation for the bruis-ing on their backs. Child protectiveservices (CPS) was contacted to ini-tiate an evaluation for nonaccidentaltrauma in both cases.

DiagnosisOn further questioning of the par-ents, it was learned that an Asian folkhealer had treated both boys earlierthat week. The 9-year-old boy wastreated with coining and the 11-year-old boy with cupping.

The ConditionThe practices of cupping and coiningare believed to heal individuals af-fected by respiratory and febrile ill-nesses. Coining (cao gao) is per-formed by massaging the back orchest with mentholated oil, then ag-gressively scraping the edge of a coinback and forth linearly until bruisingor petechiae develop. Coining is notintended to cause permanent bodilyharm and is a widespread practicethroughout much of Vietnam andparts of Southeast Asia. Althoughcoining typically does not inflict seri-ous harm, there is a reported case of arenal contusion with hematuria fol-lowing coining.

Cupping is a traditional folk heal-ing practice rooted in Latin Ameri-can, Asian, and Eastern Europeanbeliefs. For cupping, a small amountof alcohol is ignited within a glass cupto heat the air inside the container.The cup is then placed on the bareskin of the affected individual. As theair within the cup cools, a vacuum is

created between the cup and theskin, resulting in bruising of the skin.

Several cultural healing methodsare mistaken for child abuse, themost common being cupping, co-ining, moxibustion, and spooning.Moxibustion is a Southeast Asianpractice considered to be a variationof acupuncture in which a Chineseherb (Artemisia vulgaris) is burnedonto the skin using an instrumentsuch as yarn or incense near the af-fected area to draw out “the evil.”Spooning is a practice in China thatis similar to coining.

Asian folk healers have been prac-ticing these techniques in major met-ropolitan cities that have large Asianpopulations. In both these cases, theED physicians taking care of theseboys were not aware of these healingmethods, despite practicing medi-cine in an institution where many oftheir patients came from ethnic andcultural populations that practicesuch faith-healing methods. Becausethe patients had physical findingsof bruising in unusual patterns overthe back without explanation, theED physicians suspected nonacci-dental trauma, thereby warrantingreports to CPS, which determinedthat the bruising was the result ofnonharmful attempts to heal the pa-tients.

These procedures had parentalconsent and, therefore, did not con-stitute nonaccidental trauma. Inboth cases, the intent behind thetreatment methods was based on cul-turally accepted traditional beliefs.Thus, it was determined that the in-juries were not a result of physicalabuse, and CPS released the boys totheir parents.

Most bruising in children is dueto accidental trauma, and 93% ofaccidental bruises occur over bonyprominences. In the ambulatorychild, accidental bruises generally oc-cur on the extensor surfaces of the

index of suspicion



lower leg, the anterior thigh, and theforehead. Accidental bruising on thechest, abdomen, back, buttocks, softtissue of the face, ears, and “pro-tected areas” such as the neck, genitalarea, and inner thighs is uncommonin children of all ages. The presenceof a bruise in any of these uncommonlocations may signal intentional in-jury and possible serious underly-ing pathology such as intracranialinjury, skeletal fracture, or intra-abdominal trauma, particularly in achild younger than 2 years of age.

Bruises due to intentional traumaoften assume a pattern that reflectsthe shape of the impacting object.Common “patterned” inflicted inju-ries include pinch marks; humanbites; hand slaps; ligature marksaround the neck or extremities; andmarks from electrical cords, belts,brushes, shoes, and kitchen utensils.

In the case of a child younger than2 years of age who has suspiciousbruises, the clinician should considerfurther evaluation for abuse (such asimaging studies) because 43% of allinflicted skeletal fractures are unsus-pected clinically at the time of the

child’s evaluation, and approximately50% of children in whom an inflictedfracture is diagnosed have more thanone fracture at the time of diagnosis.For children older than 2 years ofage, further evaluation for underly-ing injuries should be initiated if thepatient is symptomatic.

The differential diagnosis forbruising includes Mongolian spots,phytophotodermatitis, coagulopathy,Henoch-Schonlein purpura, Ehlers-Danlos syndrome, erythema multi-forme, and cultural practices suchas “coining” and “cupping.” Most ofthese diagnoses can be distinguishedbased on the history and physical andlaboratory evaluation to rule outbleeding disorders.

Because of the high morbidity andmortality associated with child abuse,health-care personnel need to besensitive to the possibility of abuse.Although reporting suspected childabuse might cause discomfort for thefamily, not reporting child abuse maycause significant harm to the child.However, the clinician should beaware of cultural practices that mayappear to hurt a child but do not.

Lessons for the Clinician● Health-care practitioners must

consider the possibility of physicalabuse when faced with a child whohas suffered an unexplained trau-matic injury.

● Lack of awareness of the culturaland traditional healing practicesused by various communities canlead a health-care professional tosuspect potential physical abusewhen encountering certain physi-cal findings.

● Although the stigma of suspectedchild abuse can be painful for fam-ilies, it is extremely important toinvestigate fully any suspected non-accidental trauma to prevent fur-ther harm to children.

(Ryan P. Flanagan, MD, Chil-dren’s Hospital of Pittsburgh HeartCenter, Pittsburgh, PA; Neil Mullen,MD, Department of Pediatrics, Ma-digan Army Medical Center, FortLewis, Tacoma, WA)

To view Suggested Reading lists forthese cases, visit http://pedsinreview.aappublications.org and click on“Index of Suspicion.”

index of suspicion




Moustafa, Shira Rosenberg, Ryan P. Flanagan and Neil Mullen John D.A. Campagna, Minela Fernandez, Lance Yamashiroya, Ronen Zipkin, Marwa

3: Ecchymotic Lesions on the Backs of Asian Boys2: Fever, Rash, Headache, Myalgia, and Arthralgia in an 11-year-old Boy • Case Index of Suspicion • Case 1: Nonbilious Projectile Vomiting in a Neonate • Case



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Karen M. Davenport and Archana A. Patel Cataracts







In BriefCataractsKaren M. Davenport, MDArchana A. Patel, MDUniversity of Arizona College of

MedicineTuscon, Arizona

Author Disclosure

Drs Davenport, Patel, and Serwint

have disclosed no financial

relationships relevant to this In Brief.

This commentary does not contain a



product/device.

Eye Examination in Infants, Childrenand Young Adults by Pediatricians.American Academy of Pediatrics,Committee on Practice and Ambula-tory Medicine and Section on Oph-thalmology. Pediatrics. 2003;111:902–907

Preferred Practice Pattern Guidelines:Pediatric Eye Evaluations. AmericanAcademy of Ophthalmology PediatricOphthalmology/Strabismus Panel. SanFrancisco, CA: American Academy ofOphthalmology; 2007:1–39

Infantile Cataracts. Krishnamurthy R,VanderVeen DK. Int Ophthalmol Clin.2008;48:175–192

Pediatric Cataract: The TorontoExperience-Etiology. Lim Z, Rubab S,Chan YH, Levin A. Am J Ophthalmol.2010;149:887–892

Advances in the Management ofCongenital and Infantile Cataract.Lloyd IC, Ashworth J, Biswas S, AbadiRV. Eye. 2007;21:3101–1309

Evaluation of Screening Procedures forCongenital Cataracts. Magnusson G,Jakobsson P, Kugelberg J, et al. ActaPaediatr. 2003;92:1468–1473

Cataracts are a leading cause of pre-ventable blindness, responsible for 5%to 20% of childhood blindness casesworldwide. In the United States, the prev-alence of cataracts in children youngerthan 18 years of age ranges from 1 to 6per 10,000. A cataract is an opacity ofthe lens and is considered visually sig-nificant when greater than 3 mm andcentrally located. The World Health Or-ganization (WHO) defines cataract as acause of blindness in which sight canbe restored through tertiary prevention.Provision of quality surgery within anoptimal time frame is one of the WHO’stargets for Vision 2020, a global initia-tive to eliminate preventable causes ofblindness.

Cataracts may occur at any age.Approximately 50% of congenital cat-aracts are idiopathic; the remainderare due to congenital infections, ter-atogens, genetic or metabolic disease,and ocular disorders. Despite improvedprenatal care and immunizations, con-genital infections remain a major sourceof cataracts, particularly in developingnations. Although rubella is the mostcommon infectious cause of congenitalcataracts, other congenital infections,such as cytomegalovirus, varicella, her-pes simplex, toxoplasmosis, and syphi-lis, may cause them. Teratogens, suchas alcohol and corticosteroids, may alsocause congenital cataracts.

Bilateral cataracts are more com-monly identified with genetic disease,often related to autosomal dominanttraits. Cataracts are associated with nu-merous genetic syndromes, the mostcommon being trisomies 13, 18, and 21.Although less frequent, cataracts mayalso be seen in WAGR syndrome (Wilmstumor, aniridia, genital abnormalities,retardation), neurofibromatosis type 2,

CHARGE (coloboma, heart defects,choanal atresia, retardation of growth,genital abnormalities, ear abnormali-ties) syndrome, Alport syndrome, Lowesyndrome, and Sturge-Weber syndrome.Unilateral cataracts are generally causedby primary ocular disorders in the ab-sence of trauma. These abnormalitiesinclude posterior lenticonus, aniridia,microphthalmos, persistent hyperplas-tic primary vitreous, and anterior seg-ment dysgenesis.

Multiple metabolic diseases are as-sociated with cataracts, the most com-mon being galactosemia. Cataracts ininfants born with galactosemia canresolve if the infant is changed to alactose-free formula soon after birth.Other metabolic conditions that causecataracts are associated with hypopar-athyroidism, hypoglycemia, and coppermetabolism disorders. Hence, it is es-sential to perform an eye examinationon children who exhibit failure to thriveand have suspected metabolic disease.After infancy, most cataracts occurfrom trauma, systemic disease (such asjuvenile idiopathic arthritis), or thera-peutic intervention (ie, corticosteroid useand radiation).

The major cause of cataract-associated blindness is deprivation am-blyopia. There appears to be a latentperiod during which visual deprivationis reversible before final vision is af-fected. Therefore, timely identificationand treatment of cataracts is essential.Optimally, surgical intervention for con-genital cataracts should occur within6 weeks of birth for unilateral cataractsand 10 weeks for bilateral cataracts.Unfortunately, this time frame often isnot met. This short window for inter-vention makes it crucial for pediatricclinicians to identify and refer any chil-

in brief



dren who have abnormal eye findingspromptly to a pediatric ophthalmolo-gist. Studies have emphasized the im-portance of nursery screenings in timelydiagnosis and treatment of cataracts.The nursery examination, combined withthe American Academy of Pediatricsrecommended newborn visit at 3 to5 days, offers at least two opportunitiesfor diagnosis within the recommendedtime frame for surgical intervention.

Physical findings that should promptreferral to an ophthalmologist includeabnormal red reflex, structural abnor-malities, or any irregularity or asymme-try of the pupils. Ideally, the red reflexexamination should be performed in adarkened room, with each eye exam-ined individually from a distance of 1 to2 feet. Immediate referral is warrantedfor the findings of an absent red reflex,dark spots in the red reflex, or a whitereflex. The Bruckner test should followthe red reflex examination. In this eval-uation, both eyes are viewed simulta-neously using an ophthalmoscope froma distance of 2 to 3 feet, allowing theviewer to note asymmetry of the redreflex that may suggest amblyopia.

After age 3 months, it is importantalso to test a child’s ability to fix and

follow objects. The presence of nystag-mus or squinting warrants a referral. At3 years of age, it is reasonable to begintesting visual acuity. In addition, paren-tal observation of any ocular abnormal-ities and a family history of childhoodcataracts are valuable determinants ofan infant’s risk.

In general, the operative outcomeof congenital cataracts is good. Manychildren can achieve a visual acuity of20/60. Complications of surgery in-clude, but are not limited to, visual axisopacifications, glaucoma, retinal detach-ment, and strabismus. Children shouldhave close follow-up evaluation by anophthalmologist following surgery toensure optimal visual outcome.

Comment: I still remember readingin college biology class about the ex-periments in which a cat’s eye wassutured shut to identify the criticaltime for visual development and theresultant harm to visual acuity fromlight deprivation. Cataracts cause asimilar light deprivation. Because theearly identification and treatment ofcataracts can prevent blindness, pedia-tricians have an incredibly importantrole in ensuring that an eye examina-

tion is performed in the newborn nurs-ery and in the first postnatal week. Attimes, seeing the red reflex in a new-born can be a challenge, but strategiessuch as darkening the room or liftingan infant from a horizontal to verticalposition result in the infant opening hisor her eyes. Most causes of unilateralcataracts are idiopathic, but when thecataracts are bilateral, it is prudent tosearch further for a cause, whethergenetic, metabolic, or infectious. Ofinterest, the first genetic mapping ofan autosomal disease in humans wasaccomplished for congenital cataracts.Although congenital cataracts fromrubella infection have decreased in fre-quency in developed countries, they stillpresent a problem in countries wherethe measles, mumps, rubella vaccine isnot universally administered. Research-ers are investigating best practices forintraocular lenses and approaches todecrease the postoperative morbiditiesfrom cataract surgery, such as glau-coma and the inflammatory response.

Janet R. Serwint, MDConsulting Editor, In Brief

in brief




Karen M. Davenport and Archana A. Patel Cataracts




dershttp://pedsinreview.aappublications.org/cgi/collection/eye_disor

Disorders of the Eye dysmorphologyhttp://pedsinreview.aappublications.org/cgi/collection/genetics_

Genetics/Dysmorphologyfollowing collection(s): This article, along with others on similar topics, appears in the







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Jacques Benun Balance and Vertigo in Children







In BriefBalance and Vertigo in ChildrenJacques Benun, MDWarren Alpert Medical SchoolBrown UniversityProvidence, RI

Author Disclosure

Drs Benun and Serwint havedisclosed no financial relationshipsrelevant to this In Brief. Thiscommentary does not contain adiscussion of an unapproved/investigative use of a commercialproduct/device.

Vertigo. MacGregor DL. Pediatr Rev.2002;23:10–15

Idiopathic Benign Paroxysmal Vertigoin Children, A Migraine Precursor.Ralli G, Atturo F, deFilippis C.Int J Pediatr Otorhinolaryngol.2009;73(suppl):S16–S18

Various Causes and Clinical Character-istics in Vertigo in Children WithNormal Eardrums. Choung YH,Park K, Moon SK, Kim CH, Ryu SJ.Int J Pediatr Otorhinolaryngol.2003;67:889–894

Etiology of Vertigo in Children.Balatsouras DG, Kaberos A,Assimakopoulos D,Katatomichelakis M, Economou NC,Korres SG. Int J Pediatr Otorhino-laryngol. 2007;71:487–494

Too Young to Talk of Vertigo?Miyahara M, Hirayma M, Yuta A,Takeuchi K, Inoki T. Lancet.2009;373:516

Meniere’s Disease in Childhood. Akagi H,Yuen K, Maeda Y, et al. Int J PediatrOtorhinolaryngol. 2001;61:259–264

Syncope. Delgado CA. In: Fleisher GR,Ludwig S, eds. Textbook of PediatricEmergency Medicine. 6th ed. Phila-delphia, PA: Lippincott Williams &Wilkins, a Wolters Kluwer business;2010:589–595

Balance is a motor function that en-ables a person to control coordinatedmovements. Any dysfunction of theneuroaxis that commands this controlresults in a disturbance of balance,leading to symptoms of dizziness. Ver-tigo is included under the subcategoryof dizziness.

The definition of vertigo is a sensa-tion of movement that may be rota-tional or moving forward and can in-clude tilting. Vertigo may result fromabnormalities of the labyrinth system orthe central nervous system that spansfrom the vestibular nerve to the brain-stem and cerebellum. As with any dys-function, the key to correct diagnosisis performing a complete history, phys-ical examination, and further testingbased on clinical indications.

Obtaining an accurate history inyoung children may be difficult be-cause they may not have the vocabu-lary to describe the sensation of vertigo.However, some authors suggest usingplayground terms such as “spinning,swinging, sliding, or being on the merry-go-round.” Symptoms associated withvertigo include nausea, vomiting, pal-lor, and perspiration but not loss ofconsciousness. Additional historical ques-tions should address head trauma, fe-ver, infections, and family history ofvertigo or migraines.

The physical examination focuses onevaluation of the external and middleear; ophthalmologic assessment for signsof nystagmus; and neurologic exami-nation of the cranial nerves, cerebellarfunction, and gait. Additional testing toconsider includes hearing testing andaudiometry. Brain imaging, such as mag-netic resonance imaging, is only neededif the history and physical findingssuggest an intracranial process.

The most common cause of vertigoin children is middle ear disease, whichmay lead to balance disorders in walking.The external and middle ears should beexamined for evidence of effusion, acuteotitis media, or malformations such ascholesteatoma or perilymphatic fistula.Perilymphatic fistula may follow minorhead trauma, resulting from a ruptureof the round or oval window of themiddle ear into the vestibule, creating afistula. Symptoms from middle ear dis-ease tend to improve after appropriatemedical treatment. These diseases arevery familiar to pediatricians and caneasily be diagnosed by otoscopic exam-ination.

It is more challenging to develop adifferential diagnosis of vertigo in chil-dren who have normal tympanic mem-branes. Potential causes include:

● Benign paroxysmal vertigo (BPV)● Migraine● Vestibular neuritis due to viral infec-

tions● Head trauma● Meniere disease● Cerebellar and brainstem tumors

After middle ear disease, BPV is themost common cause of vertigo in chil-dren. The age of onset ranges between2 and 12 years, with an average age ofonset of 6 years. The condition is morecommon in females and typically pre-sents as a sudden onset of vertigo thatlast seconds to minutes, with completeresolution of symptoms between epi-sodes. The attack is not induced by headmovements or positional changes. As-sociated symptoms may include nauseaand vomiting, and abnormal eye move-ments such as nystagmus may bepresent, but there are no neurologicchanges or altered state of conscious-

in brief



ness. The diagnosis is based on thebrevity of the symptoms, presence ofnystagmus during the episodes,symptom-free intervals, and frequentlya family history of migraines. BPV isincluded among the periodic syndromesof childhood and may be considered amigraine equivalent. The prognosis isgood and the symptoms disappearspontaneously before adolescence, al-though a subset of patients may de-velop migraines in the future. Migrainesmust also be considered as a potentialcause of vertigo.

Vestibular neuritis is caused byviruses such as herpes simplex, varicella-zoster, and influenza. Symptoms of nau-sea and vomiting develop suddenly andmay persist for weeks.

Head trauma with or without tempo-ral bone fracture can cause labyrinthineconcussion. Affected patients developsymptoms immediately after the trauma.The child is unsteady and tends to falltoward the affected side. The symptomsusually improve after 4 to 6 weeks.

Meniere disease is another con-sideration when evaluating vertigo. Al-though rare in children, the prevalenceranges from 1.5% to 4% among chil-dren in whom vertigo is diagnosed, andcases have been described as young as4 years of age. The key symptoms aretinnitus, vertigo, and progressive hear-ing loss.

Cerebellar and brainstem tumors arerare causes of vertigo. Associated find-ings include headache, emesis, gait dis-turbance, and papilledema. Brain imag-ing is indicated.

Treatment of vertigo depends on thecause and duration of symptoms. Foracute symptoms that resolve quickly,reassurance may be all that is needed.Medications to suppress symptoms in-clude promethazine and diazepam. Per-sistent severe nausea or vomiting canbe treated with antiemetics such asmetoclopramide or prochlorperazine. Ifthe vertigo becomes chronic or recur-rent, clonazepam or carbamazepinemay be indicated. Symptoms of anxiety,

panic attacks, and depression maypresent as a result of prolonged vertigoand should be treated accordingly.

Comment: Vertigo can be challeng-ing to diagnose, especially in youngchildren. Pediatricians need to be awarethat the causes of vertigo in childrendiffer from those in adults. Vertigo maybe diagnosed infrequently in youngchildren because symptoms may be in-correctly attributed to their develop-mental status and lack of coordinationrather than to a balance dysfunction,and young children may have difficultydescribing their symptoms. Pediatri-cians must be skilled in differentiatingthe common causes of vertigo, such asmiddle ear disease, which is easilytreated, and BPV, which resolves, fromrarer but more serious conditions thatmay be progressive and require morethorough testing and imaging.


in brief




Jacques Benun Balance and Vertigo in Children




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

Ear, Nose and Throat Disorders c_disordershttp://pedsinreview.aappublications.org/cgi/collection/neurologi

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Elizabeth A. Van Dyne Issues in Chemotherapy







In BriefIssues in ChemotherapyElizabeth A. Van Dyne, MDKaiser Permanente Medical CenterLos Angeles, CA

Author Disclosure

Drs Van Dyne and Serwint have

disclosed no financial relationships

relevant to this In Brief. This

commentary does contain a



product/device.

Immunizations in Special Clinical Cir-cumstances. American Academy ofPediatrics. In: Pickering LK, Baker CJ,Kimberlin DW, Long SS, eds. RedBook: 2009 Report of the Committeeon Infectious Diseases. 28th ed. ElkGrove Village, IL: American Academyof Pediatrics; 2009:72–86

Varicella-Zoster Infections. AmericanAcademy of Pediatrics. In: PickeringLK, Baker CJ, Kimberlin DW, Long SS,eds. Red Book: 2009 Report of theCommittee on Infectious Diseases.28th ed. Elk Grove Village, IL:American Academy of Pediatrics;2009:714–727

Fever and Neutropenia in PediatricPatients with Cancer. Meckler G,Lindemulder S. Emerg Med ClinNorth Am. 2009;27:525–544

2002 Guideline for the Use of Anti-microbial Agents in NeutropenicPatients with Cancer. Hughes WT,Armstrong D, Bodey GP, et al.Clin Infect Dis. 2002;34:730–751

Children who have cancer may be se-verely immunocompromised by theoncologic process and the immuno-suppression that results from chemo-therapy. Their increased susceptibility

to infection directs the scheduling ofvaccine administration and the urgenttreatment of the febrile child.

Live (attenuated) vaccines shouldnot be given to patients undergoingimmunosuppressive therapy, specificallychemotherapy and radiation treatment.Live vaccines include those manufac-tured to protect against Salmonellatyphi; influenza (live intranasal vac-cine); measles, mumps, rubella (MMR);varicella; rotavirus; polio (oral vaccine);yellow fever; and smallpox. The recom-mendation is to wait at least 3 monthsafter completion of the last immuno-suppressive treatment before adminis-tering live vaccines, and many oncolo-gists wait 6 to 12 months. Because thetime to immune reconstitution de-pends on the type of chemotherapygiven, the dosage, and the patient’sdegree of responsiveness to treatment,the recommendations must be tailoredto the individual patient and his or hercircumstances. Vaccination with in-activated vaccines can be completedwithout increased risk of infectiouscomplications, but the timing is impor-tant because the immune response maybe inadequate in immunocompromisedpatients. An adequate response is usu-ally achieved from 3 months to 1 yearfollowing the discontinuation of theradiation or chemotherapy. Inactivatedinfluenza vaccine is recommended be-fore each influenza season for patients6 months of age and older. If possible,influenza vaccination should be post-poned until no sooner than 3 to4 weeks after a chemotherapy course iscompleted and when the granulocyteand lymphocyte counts are greater than1,000 cells/�L.

Varicella infection can be severe inimmunocompromised children, result-

ing in encephalitis, hepatitis, pneumo-nia, and, in some cases, death. Anextended period of vesicular eruptionsmay occur. Immunocompromised pa-tients who have well-documented ex-posure to varicella and no history ofvaricella infection or serologic titersshould receive varicella-zoster im-mune globulin (under the brand nameVariZIGTM). (Note: VariVIG is distributedin the United States by FFF Enterprises,Temecula, CA, and can be requested atany time by calling 800-843-7477.)Varicella virus replicates rapidly, ceas-ing replication within 24 hours of theonset of rash, at which time treatmentwith immunoglobulins is less effec-tive. It is crucial to treat the infectionas soon as possible, at the latest by96 hours after exposure, and not basetreatment on presentation of the rash.Some experts recommend treatmentwith VariZIG whether or not there is apast history of varicella infection be-cause immunologic responses are lowand serologic tests can be unreliable inimmunocompromised children. VariZIGis a new investigational drug and some-what difficult to obtain but preferableto immune globulin intravenous becauseit contains concentrated immunoglob-ulin specific to varicella. If VariZIG isunavailable, one dose of immune glob-ulin intravenous can be administeredinstead. If neither is available or 96 hourshas passed, chemoprophylaxis withacyclovir should be initiated specificallyat 7 to 10 days postexposure to atten-uate or prevent infection.

Another major concern for the im-munocompromised child who has can-cer is fever in the setting of neutrope-nia. Patients must present emergentlyfor rapid triage, evaluation, and promptadministration of antibiotics. Increased

in brief



risk of morbidity and mortality due toinfection correlates with the severityand duration of neutropenia. Bone mar-row suppression, impaired immunologicresponses, the presence of a vascularaccess device, and the breakdown ofmucocutaneous barriers from chemo-therapy all contribute to the risks forthe immunocompromised child.

A thorough physical examinationmust be performed on the child whohas neutropenia, assessing vital signs;evaluating potential sites of infection;and paying special attention to all areasof the skin, mucous membranes, gastro-intestinal tract (eg, mouth, rectum),and vascular access devices. A patientwho has neutropenia may not mountan inflammatory response, resulting inminimal erythema, exudate, or pain atinfected sites. A complete blood countwith differential count and blood cul-tures from all lumens of vascular ac-cess devices are recommended. Patientswho have an absolute neutrophil countless than 500 cells/mm3 or who appearill are at greatest risk. Although a micro-biologic diagnosis is made in 10% to30% of pediatric patients who haveneutropenia, most do not have an ob-vious source of fever or clear infection.Further evaluation with chest radiogra-phy, urinalysis, urine cultures, or addi-tional cultures is warranted, based onthe patient’s symptoms.

Aggressive intravenous hydration andurgent antibiotic administration is im-

perative for the febrile neutropenic pa-tient because infection can progressrapidly. Frequent monitoring of vitalsigns and surveillance of urine outputis essential because tachycardia anddecreased urine output may be theinitial signs of compensated shock.After drawing cultures, immediate anti-biotic coverage for gram-positive and-negative organisms (including Pseudo-monas) should be administered. Indi-viduals who appear toxic should receivedual gram-negative coverage. Consid-eration must also be given to fungal,viral, and other opportunistic infec-tions and appropriate therapy tailoredto the patient. Oral antibiotics are notappropriate in pediatric patients whohave fever and neutropenia.

The child undergoing treatment forcancer presents the additional concernfor life-threatening infections. Practi-tioners must be aware of establishedguidelines and consultative resourcesto provide the highest quality of care.

Comment: This In Brief reviews im-portant concepts for all who providemedical care to children who have can-cer. Provision of care requires collabo-ration and consultation among thepatient’s primary care clinician, emer-gency department staff, the patient’soncologist, and an infectious diseasespecialist, along with the patient andfamily. The immunization of householdcontacts and siblings is imperative to

minimize disease transmission to thepatient. Family members and householdcontacts should not be given smallpoxor oral polio vaccines because of poten-tial transmission to the patient butshould receive MMR, varicella, androtavirus vaccines, which have a verylow risk of transmission to the patient.If a household member develops a rashfollowing the varicella vaccine, thechild who has cancer should avoidcontact with that person, but no otherprecautions are currently warranted.Inactivated influenza vaccine should begiven to household contacts 6 monthsof age and older, and age-appropriateinactivated vaccines are important toadminister. The universal administra-tion of varicella vaccine hopefully hasdecreased the risk exposure for patientswho have cancer. For those who haveneutropenia and fever, urgent evalua-tion and administration of antibioticsis imperative. Specific antibiotic andantifungal choices must be guided byindividual risk factors and local micro-biologic profiles and tailored to theindividual patient. Hence, the coordi-nated care of the cancer patient withoncology and infectious disease con-sultation is important to provide indi-vidualized care and demonstrates theimportance of true medical home prin-ciples.


in brief




Elizabeth A. Van Dyne Issues in Chemotherapy




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

Disorders of Blood/Neoplasms _diseaseshttp://pedsinreview.aappublications.org/cgi/collection/infectious









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DOI: 10.1542/pir.32-2-e18 2011;32;e18-e24 Pediatr. Rev.

Elaine Z. Galicia-Connolly, Larissa Shamseer and Sunita Vohra Disabilities

Complementary, Holistic, and Integrative Medicine: Therapies for Learning

http://pedsinreview.aappublications.org/cgi/content/full/32/2/e18located on the World Wide Web at:




http://pedsinreview.aappublications.org/cgi/content/full/32/2/e18


Complementary, Holistic, and IntegrativeMedicine: Therapies for Learning DisabilitiesElaine Z. Galicia-

Connolly, MD,* Larissa

Shamseer, MSc,† Sunita

Vohra, MD†

Author Disclosure

Dr Galicia-Connolly

and Ms Shamseer

have disclosed no

financial relationships

relevant to this

article. Dr Vohra has

disclosed receiving

salary support from

the Alberta Heritage

Foundation for

Medical Research and

Canadian Institutes of

Health Research. This

commentary does


of an unapproved/


commercial

product/device.

BackgroundBetween 5% and 10% of schoolchildren have learning disabilities (LD), and up to 80% ofsuch children have some form of dyslexia. (1) The diagnosis is based on significantly loweracademic achievement than the intelligence quotient (IQ) would suggest. (2) Althoughdisorders of learning and attention frequently occur together, this review specificallyexamines the effectiveness of complementary and alternative medicine (CAM) interven-tions for children who have LD. The studies might include children who have comorbidconditions such as attention-deficit/hyperactivity disorder (ADHD).

Existing interventions for LD focus on remedial teaching in the early years and offeringcompensatory mechanisms and lifestyle adjustments at later ages. The most robustpredictive factors correlating with the success of LD interventions are attention andbehavior, general verbal ability, prior level of component reading skills, and total IQ. (1) Ina survey of 148 schoolchildren who had dyslexia, Bull found that 55.4% had used CAM fordyslexia, most commonly nutritional supplements or special diets, homeopathy, andosteopathy or chiropractic manipulation. (3)

MethodsWe conducted a search for articles related to learning disabilities and CAM therapies onMEDLINE, Embase, AMED, PsycInfo, the Cochrane Database of Systematic Reviews,and Cochrane’s Central Register of Controlled Trials. Search terms were: (learningdisorders OR learning disabilities) AND (complementary therapies), with terms varying bydatabase and no limits on language or date. Studies were included if they examined astrictly pediatric population (0 to 18 years) of individuals who had LD and who experi-enced CAM as the intervention.

ResultsEleven articles were relevant to this review (Table).

Nutritional SupplementsPOLYUNSATURATED FATTY ACIDS (PUFAS). The PUFAs eicosapentaenoic acids (EPA)

and docosahexaenoic acid (DHA) are believed to be critical for brain developmentand function. (16) Kairaluoma and associates (4) conducted a double-blind, placebo-controlled, randomized, controlled trial (RCT) evaluating the effects of single dailysupplementation with 500 mg EPA and 400 mg carnosine over a 3-month period on thereading-related skills of 61 children (mean age, 10.6 years) who had dyslexia. They foundno significant differences in the two groups in measures of reading accuracy or speed,spelling, decoding, fluency, arithmetic skills, reading-related language skills, and attentionor behavioral problems.

A double-blind RCT evaluated the effect of supplementation of highly unsaturated fattyacids on ADHD symptoms of 41 children (mean age, 10.25 years; standard deviation[SD]�0.74 years) who had both literacy problems and features of ADHD. (5) Althoughthe authors reported that the studied children were not formally diagnosed as havingADHD, the Connors Parent rating scale for ADHD was employed as the primary endpoint

*Former Clinical Fellow, University of Alberta, Stollery Children’s Hospital CARE Program, Edmonton, Alberta, Canada.†Complementary and Alternative Medicine Research and Education (CARE) Program, Department of Pediatrics, Faculty ofMedicine, University of Alberta on behalf of the American Academy of Pediatrics Section on Complementary and IntegrativeMedicine.NOTE: The agents discussed in this series are designated as dietary supplements rather than drugs. Although dietarysupplements are regulated by the United States Food and Drug Administration (FDA), their manufacturers may make claimswith little evidence and need not prove safety prior to marketing. The burden is on the FDA to monitor safety after theproduct is on the market. Readers are referred to the 1994 Dietary Supplement Health and Education Act (www.cfsan.fda.gov/�dms/dietsupp.html).

Article complementary medicine

e18 Pediatrics in Review Vol.32 No.2 February 2011. Provided by Pakistan:AAP Sponsored on February 1, 2011 http://pedsinreview.aappublications.orgDownloaded from


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n•

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blin

ding

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port

ing

bias

with

pare

ntas

sess

men

ts•

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drop

out

(n�

2)

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tinue

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complementary medicine learning disabilities

Pediatrics in Review Vol.32 No.2 February 2011 e19. Provided by Pakistan:AAP Sponsored on February 1, 2011 http://pedsinreview.aappublications.orgDownloaded from


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and measured at 12 weeks. PUFA supplementation ap-peared to alleviate ADHD-related symptoms in dyslexia.

An open-label pilot study of 24 children who haddyslexia and whose mean age was 12 years evaluated apatented single daily supplement containing tuna fish oil(480 mg DHA, 108 mg EPA) and primrose oil over a5-month period. (6) The authors reported that 76% ofchildren showed significant improvement in word-chaintests (P�0.04), with 60% improvement in reading speed(P�0.01) and 23% improvement in motoric-perceptualspeed (P�0.05) at the end of the study. Both parents andchildren reported improvement in speed of reading andschoolwork. Although this treatment appears promising,it would benefit from more rigorous study with a placebocontrol group to reduce potential bias.

An open-label pilot study examined administration ofthe same supplement to 15 children who had dyspraxiaover a 4-month period. (7) Motor skills using the Move-ment Assessment Battery for Children were measured asthe primary outcome at 4 months. The authors reportedstatistically significant differences in all the children’smovement skills. Unfortunately, in the absence of acontrol group, the potential for biased estimates of treat-ment effect is high.

GINGKO BILOBA. Gingko biloba has traditionally beenused in Chinese medicine as a memory “booster.” Anopen-label trial examined the effect of a single morning80-mg dose of gingko biloba over a 34-day period in 15children (mean age, 10.8 years, SD�2 years) who had aDiagnostic and Statistical Manual of Mental Disorders,4th edition, text revision (DSM-IV-TR) diagnosis of“dyslexia not taking psychotropic medications or under-going rehabilitative treatment.” (8) The authors found asignificant improvement in reading accuracy but notreading speed. A double-blind, placebo-controlled RCTwould be helpful to confirm these preliminary results.

NeurofeedbackChildren who have LD have higher values of theta activ-ity on encephalography (EEG) than unaffected children,(17) and neurofeedback has been described as an “oper-ant conditioning procedure” that allows an individual tolearn to modify the electrical activity of his or her ownbrain. (18) Quantitative EEG evaluation attests to theheterogeneity of children who have LDs, and studies onthe efficacy of neurofeedback remain sparse, needinglarger sample sizes to replicate their findings. (19)

A double-blind RCT evaluated neurofeedback in 10children ages 7 to 11 years who had a diagnosis of LD.(9) Participants were assigned to either 40 45-minute

biweekly neurofeedback sessions during which partici-pants were “trained” to inhibit their brain’s theta activityover 10 to 12 weeks or to placebo sessions that werecomprised of similar sessions but with random and non-contingent feedback. Tests of variables of attention(TOVA) and EEG were obtained after 20 sessions andthe Weschler Intelligence Scale for Children (WISC) wasreadministered after 6 months. The authors reported asignificant improvement in WISC performance, with nocorresponding significant changes in the EEG readingsof the treatment group.

Nine of the 10 children from the previously men-tioned cohort were subsequently followed for 2 years toexamine the long-term effects of neurofeedback. (10)The authors reported a significant increase in global IQand performance scores and a remission of LD symptomsin four of the five children who had undergone neuro-feedback. In contrast, all of the children in the controlgroup continued to exhibit LD. Further studies withlarger sample sizes would be helpful.

One RCT evaluated the efficacy of 40 45-minuteneurofeedback sessions given over 6 months to enhancebeta activity and suppress theta activity in 18 treatment-naıve children ages 5 to 15 years who had received adiagnosis of LD or ADD/ADHD. (11) Fifty percent ofthe children on a wait list acted as a control group. Therewas a significant improvement in IQ scores (P�0.02) andparent-reported inattention (P�0.04) in the childrenwho underwent neurofeedback, but there were no dif-ferences in parent-reported oppositional behavior be-tween groups. The authors attributed the improvementin the children’s IQ scores to enhanced attention.

Chiropractic TherapiesAn RCT evaluated an intervention called “sunflowertherapy” (described as a integrative course of treatmentthat combines applied kinesiology, osteopathic manipu-lation, massage, herbal remedies, homeopathy, and neu-rolinguistic programming) administered over 15 weeksby using cognitive, literacy, and self-esteem tests in 70children ages 6 to 13 years who had dyslexia. (12)Participants were randomized to either eight 40-minutesessions of sunflower therapy or a control group andwere retested within a mean of 15.7 weeks (SD 2.3).The author found no differences between groups incognitive or literacy tests but noted statistically signifi-cant improvements in academic self-esteem (P�0.001)and reading self-esteem (P�0.001) scores within thetreatment group. We concur with the author that acontrol group with sham treatment to exclude placeboeffects would be helpful. This study has been criticized




for too short of a treatment period to detect treatmenteffects. (13)

Applied kinesiology is a chiropractic diagnosticmethod that evaluates muscle function using manualmuscle testing, based on the premise of a link betweenmotor impairments and developmental delay. A caseseries of 157 children ages 6 to 13 years who had devel-opmental delay syndromes, including children who hadADHD, involved psychometric testing that monitoredcognitive function, including patient- or parent-reportedimprovements in school performance, social interaction,and sporting activities before and after chiropractic treat-ment. (14) The authors reported enhanced cognitiveperformance in this group of children based on 6.6% to33.2% improvement between scores from psychometrictests that were administered within 5 days to 18 monthsafter 2 to 50 chiropractic sessions. These promisingresults would benefit from further rigorous study, ideallyincluding a less heterogeneous sample, a randomizedcontrol group, and blinded outcome assessment.

Music TherapyThe effect of music in enhancing reading skills of second-grade students and students who had reading disabilitieswas examined in a prospective interventional study. (15)A class of eight children who had reading disabilityunderwent a specially designed 4-week curriculum usingmusic to target reading comprehension and vocabularyskills. The authors used two intact second-grade classesfor comparison. One participated in their normal readingprogram as a control class and the other underwent boththe music-augmented reading program and their normalreading program as a treatment class.

The authors reported significant improvements inword decoding (P�0.04), word knowledge (P�0.01),and reading comprehension (P�0.01) in the childrenwho had LD and attributed these findings to increasedattention and more active participation because of thesmaller class size. For second graders, the treatmentgroup had significantly greater gains in word knowledgecompared with the control group. The music/readingcurriculum appeared to be an effective supplement to thecurrent reading program. It would be more compelling ifchildren who had a reading disability had been includedin the control group for better assessment of the effect ofmusic therapy in this population.

Adverse EventsOf the 11 studies included in this review, only fourexplicitly reported on the presence or absence of adverseevents during the study. Adverse events associated with

PUFAs include nausea, nosebleeds, and mild fever. (20)(21)(22) Other potential adverse events are gastrointes-tinal upset, altered immune response, reduced bloodpressure, and increased risk of bleeding at high doses.(23)(24) Potential drug interactions may occur withanticoagulants and antiplatelet drugs. (25)(26)

The use of gingko biloba generally has been associ-ated with mild and transient effects, the most commonbeing headache. Reported serious adverse effects includeseizures, spontaneous bleeding, and intracerebral hem-orrhage. (27)(28)(29)

None of the studies (9)(10)(11) reported adverseeffects during neurofeedback. However, with 20 or moresessions, reported adverse effects have included head-aches, dizziness, increased irritability, moodiness, loss ofattention, and hyperactivity in children who were beingconcomitantly treated with stimulants. (30)

A systematic review on the safety of pediatric spinalmanipulation identified 14 serious adverse events thatresulted in hospitalization, permanent disability, ordeath. Others involved delayed diagnosis or inappropri-ate provision of chiropractic care. (31) The estimated riskof a serious adverse event is 0.13% in adults, (32) but anaccurate estimate from high-quality pediatric studies isnot available. (33)

ACKNOWLEDGMENTS. The authors would like to ac-knowledge the invaluable assistance of Connie Wintherand Soleil Surette in the literature search for this manu-script.

References1. Lagae L. Learning disabilities: definitions, epidemiology, diag-nosis, and intervention strategies. Pediatr Clin North Am. 2008;55:1259–12682. Ewen JB, Shapiro BK. Disorders of attention or learning inneurodevelopmental disorders. Semin Pediatr Neurol. 2005;12:229–2413. Bull L. Survey of complementary and alternative therapies usedby children with specific learning difficulties (dyslexia). Int J LangCommun Disord. 2009;44:224–2354. Kairaluoma L, Narhi V, Ahonen T, Westerholm J, Aro M. Dofatty acids help in overcoming reading difficulties? A double-blind,placebo-controlled study of the effects of eicosapentaenoic acid and

Summary• Preliminary evidence suggests possible positive

effects of neurofeedback, PUFA, gingko biloba,chiropractic, and music in the treatment of LD, butmore rigorous data are needed.




carnosine supplementation on children with dyslexia. Child CareHealth Dev. 2009;35:112–1195. Richardson AJ, Puri BK. A randomized double-blind, placebo-controlled study of the effects of supplementation with highlyunsaturated fatty acids on ADHD-related symptoms in childrenwith specific learning difficulties. Prog Neuropsychopharmacol BiolPsychiatry. 2002;26:233–2396. Lindmark L, Clough P. A 5-month open study with long-chainpolyunsaturated fatty acids in dyslexia. J Med Food. 2007;10:662–6667. Stordy BJ. Dark adaptation, motor skills, docosahexaenoic acid,and dyslexia. Am J Clin Nutr. 2000;71(1 suppl):323S–326S8. Donfrancesco R, Ferrante L. Ginkgo biloba in dyslexia: a pilotstudy. Phytomedicine. 2007;14:367–3709. Fernandez T, Herrera W, Harmony T, et al. EEG and behavioralchanges following neurofeedback treatment in learning disabledchildren. Clin Electroencephalogr. 2003;34:145–15210. Becerra J, Fernandez T, Harmony T, et al. Follow-up study oflearning-disabled children treated with neurofeedback or placebo.Clin EEG Neurosci. 2006;37:198–20311. Linden M, Habib T, Radojevic V. A controlled study of theeffects of EEG biofeedback on cognition and behavior of childrenwith attention deficit disorder and learning disabilities. BiofeedbackSelf. 1996;21:35–4912. Bull L. Sunflower therapy for children with specific learningdifficulties (dyslexia): a randomised, controlled trial. ComplementTher Clin Pract. 2007;13:15–2413. Mathews MO, Thomas E, Yeung A. Rebuttal paper to “Sun-flower therapy for children with specific learning difficulties (dys-lexia): a randomised, controlled trial.” Complement Ther Clin Pract.2009;15:44–4614. Cuthbert SC, Barras M. Developmental delay syndromes: psy-chometric testing before and after chiropractic treatment of 157children. J Manipulative Physiol Ther. 2009;32:660–66915. Register D, Darrow AA, Standley J, Swedberg O. The use ofmusic to enhance reading skills of second grade students andstudents with reading disabilities. J Music Ther. 2007;44:23–3716. Brulotte J, Bukutu C, Vohra S. Complementary, holistic, andintegrative medicine: fish oils and neurodevelopmental disorders.Pediatr Rev. 2009;30:e29–e3317. Chabot RJ, di Michele F, Prichep L, John ER. The clinical roleof computerized EEG in the evaluation and treatment of learningand attention disorders in children and adolescents. J Neuropsychi-atr Clin Neurosci. 2001;13:171–18618. Monastra VJ. Electroencephalographic biofeedback (neuro-therapy) as a treatment for attention deficit hyperactivity disorder:rationale and empirical foundation. Child Adolesc Psychiatr ClinNorth Am. 2005;14:55–82

19. Cantor DS, Chabot R. QEEG studies in the assessment andtreatment of childhood disorders. Clin EEG Neurosci. 2009;40:113–12120. Amminger GP, Berger GE, Schafer MR, Klier C, FriedrichMH, Feucht M. Omega-3 fatty acids supplementation in childrenwith autism: a double-blind randomized, placebo-controlled pilotstudy. Biol Psychiatry. 2007;61:551–55321. Emsley R, Niehaus DJ, Oosthuizen PP, et al. Safety of theomega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatricpatients: results from a randomized, placebo-controlled trial. Psy-chiatry Res. 2008;161:284–29122. Sinn N, Bryan J, Wilson C. Cognitive effects of polyunsatu-rated fatty acids in children with attention deficit hyperactivitydisorder symptoms: a randomised controlled trial. ProstaglandinsLeukotrienes Essent Fatty Acids. 2008;78:311–32623. Goodnight SH Jr, Harris WS, Connor WE. The effects ofdietary omega 3 fatty acids on platelet composition and function inman: a prospective, controlled study. Blood. 1981;58:880–88524. Wensing AG, Mensink RP, Hornstra G. Effects of dietary n-3polyunsaturated fatty acids from plant and marine origin on plateletaggregation in healthy elderly subjects. Br J Nutr. 1999;82:183–19125. Buckley MS, Goff AD, Knapp WE. Fish oil interaction withwarfarin. Ann Pharmacother. 2004;38:50–5326. Woodman RJ, Mori TA, Burke V, et al. Effects of purifiedeicosapentaenoic acid and docosahexaenoic acid on platelet, fi-brinolytic and vascular function in hypertensive type 2 diabeticpatients. Atherosclerosis. 2003;166:85–9327. Haemorrhage due to ginkgo biloba? Prescrire Int. 2008;17(93):1928. Hasegawa S, Oda Y, Ichiyama T, Hori Y, Furukawa S. Ginkgonut intoxication in a 2-year-old male. Pediatr Neurol. 2006;35:275–27629. Yagmur E, Piatkowski A, Groger A, Pallua N, Gressner AM,Kiefer P. Bleeding complication under gingko biloba medication.Am J Hematol. 2005;79:343–34430. Monastra VJ, Lynn S, Linden M, Lubar JF, Gruzelier J,LaVaque TJ. Electroencephalographic biofeedback in the treat-ment of attention-deficit/hyperactivity disorder. Appl PsychophysiolBiofeedback. 2005;30:95–11431. Vohra S, Johnston BC, Cramer K, Humphreys K. Adverseevents associated with pediatric spinal manipulation: a systematicreview. Pediatrics. 2007;119:e275–e28332. Carnes D, Mullinger B, Underwood M. Defining adverseevents in manual therapies: a modified Delphi consensus study.Man Ther. 2010;15:2–633. Humphreys BK. Possible adverse events in children treated bymanual therapy: a review. Chiropr Osteopat. 2010;18:12





Elaine Z. Galicia-Connolly, Larissa Shamseer and Sunita Vohra Disabilities

Complementary, Holistic, and Integrative Medicine: Therapies for Learning


http://pedsinreview.aappublications.org/cgi/content/full/32/2/e18including high-resolution figures, can be found at:


ntary_holistic_integrativehttp://pedsinreview.aappublications.org/cgi/collection/compleme

Holistic, and Integrative MedicineComplementary, _language_learning_attention_disorders

http://pedsinreview.aappublications.org/cgi/collection/cognition Disorders of Cognition, Language, Learning, and Attention

following collection(s): This article, along with others on similar topics, appears in the






http://pedsinreview.aappublications.org/cgi/collection/cognition_language_learning_attention_disorders

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Donna Denno Global Child Health

http://pedsinreview.aappublications.org/cgi/content/full/32/2/e25located on the World Wide Web at:




http://pedsinreview.aappublications.org/cgi/content/full/32/2/e25


Global Child HealthDonna Denno, MD, MPH*

Author Disclosure

Dr Denno has




commentary does not


of an unapproved/


commercial

product/device.


1. State the current annual number of child deaths globally and percentage of thesedeaths occurring in developing countries.

2. List the seven leading causes of childhood deaths worldwide and the interventionsrecommended by international guidelines to prevent these deaths.

3. Be aware of the percentage of childhood deaths that could be prevented throughwidespread implementation of these interventions.

4. Describe Millennium Development Goal 4 and progress toward its achievement.5. Discuss the socio-political-economic factors and policies that affect child health.6. Identify specific ways in which child health professionals in the United States can

affect child health globally.

IntroductionEach year, millions of children die, the vast majority in poor countries. Tragically, mostof these deaths are preventable with technologies that are currently available and recom-mended for universal implementation. Progress is being made: 8.1 million childrenyounger than the age of 5 years died in 2009, down from 12.4 million in 1990.Unfortunately, rates of reduction in child mortality are much less than what can beaccomplished realistically with available technology. Furthermore, progress lags far behindwhat was expected when 189 nations committed to reduce poverty and improve health anddevelopment via the Millennium Development Goals (MDGs). The MDGs consist ofeight specific goals, including MDG4, which explicitly relates to child health and aims toreduce child mortality by two thirds between 1990 and 2015. The world is not on track tomeet MDG4, although several developing countries are demonstrating that substantial

improvements in child health can be made by focusing onmaking key lifesaving interventions available to children whoneed them the most.

This article explores the scope and causes of childhoodmortality, interventions to combat these killers, trends inchild health, potential reasons for these trends, and oppor-tunities for progress in improving global child health.

Scope of the ProblemHealth is more than just survival, but as a starting point, it ishard to avoid the fact that more than 22,000 childrenyounger than age 5 years are estimated to die each day.Ninety-nine percent of these deaths occur in developingcountries, with 92% in Africa and Asia. A child born insub-Saharan Africa faces a 1 in 8 chance of dying before his orher fifth birthday compared with 1 in 130 for a child born inthe United States and an average of 1 in 167 for developedcountries.

“Child,” as used in this article and as typically defined inthe global health field, includes persons younger than 5 yearsof age because of their particular biologic and social vulner-

*Department of Pediatrics, Department of Global Health, University of Washington, Seattle, WA.

Abbreviations

ACT: artemisinin combination therapyAIDS: acquired immune deficiency syndromeCHW: community health workerHib: Haemophilus influenzae type bHIV: human immunodeficiency virusIMCI: integrated management of childhood illnessIPT: intermittent presumptive treatmentITN: insecticide-treated netMDG: Millennium Development GoalORS: oral rehydration saltsORT: oral rehydration therapyPCP: Pneumocystis jiroveci pneumoniaU5MR: under-five mortality rateUNICEF: United Nations Children’s FundVA: vitamin AWHO: World Health Organization

Article preventive pediatrics



ability. Age-specific mortality rates decline appreciablybeyond 5 years. Under 5 mortality rates (U5MRs) arecommonly used as indicators to assess the health of ageneral population. If conditions favor the health andwelfare of this vulnerable group, the situation generallycan be considered favorable for the overall society.

Statistics from developing countries can carry a widemargin of uncertainty due to lack of resources to supportsurveillance and registry systems and limited availabilityof diagnostics for precise determination of causes ofillness and death. Furthermore, many important health-related events take place outside of health facilities, lim-iting the acquisition of information in centralized datasources. For example, parents often seek care for child-hood illnesses from pharmacy shops or street vendors.Most births and neonatal deaths occur at home and oftenare unrecorded.

However, there are additional sources of helpful data,including nationally representative surveys, such as De-mographic and Health Surveys (largely funded byUnited States Agency for International Development)and the United Nations Children’s Fund (UNICEF)Multiple Indicator Cluster Surveys. Expert panels such asthe Inter-agency Group for Child Mortality Estimationand the Child Health Epidemiology Reference Grouphave been working on improving estimation methodol-ogies and standardizing reporting of estimates. Despiteless-than-desirable margins of certainty, these collectivesources of information allow for examination of trends

and help to set priorities withinprograms and policies to improvechild survival.

Major Causes of ChildMortalityEighty-four percent of global childdeaths are due to seven major caus-es: neonatal problems, pneumonia,diarrhea, malaria, measles, humanimmunodeficiency virus (HIV)/acquired immune deficiency syn-drome (AIDS), and injuries (Fig. 1).

Undernutrition is an enormousrisk factor for childhood mortalityand morbidity. As defined in recentresearch that estimates it contrib-utes to 35% of all child deaths, un-dernutrition includes: 1) lack ofsufficient macronutrient (eg, pro-tein) and caloric intake; 2) micro-nutrient deficiencies, especially vi-

tamin A (VA), zinc, iron, and iodine; and 3) lack of earlyinitiation of breastfeeding and exclusive breastfeeding inthe first 6 months after birth. Undernutrition increasessusceptibility to infectious diseases and is associated withlong-term cognitive impairment and poor school perfor-mance as well as with poor health consequences in adult-hood and into the next generation (eg, low-birthweightoffspring among affected women).

It is worth noting that undernutrition and the com-mon direct causes of child deaths are not exotic tropicaldiseases, but rather diseases of poverty. Many are thesame diseases that killed children in the United States andother developed countries 100 years ago: neonatal prob-lems, diarrhea, pneumonia, and measles. These scourgeswere largely controlled even before the advent of antimi-crobials and vaccinations by social changes addressingcrowding, sanitation, nutrition, and basic living condi-tions. Medical breakthroughs such as antibiotics, immu-nizations, and insecticides (to prevent malaria, a vector-borne disease that was endemic in parts of the UnitedStates) further accelerated gains in controlling diseaseand preventing childhood mortality.

An overview of causes of childhood mortality wouldnot be complete without mention of less proximate, butperhaps even more important underlying causes: thesocial determinants of health. Children living in absolutepoverty have limited access to the basics necessary tosupport survival (eg, essential medicines and health care,water, sanitation, adequate nutrition, education). Nearly

Figure 1. Causes of death among children younger than age 5 years. Reproduced fromUNICEF ChildInfo website: http://www.childinfo.org/mortality.html and based on Black R,Cousens S, Johnson H, et al. Global, regional, and national causes of child mortality in2008: a systematic analysis. Lancet. 2010;375:1969–1987.

preventive pediatrics global child health



1.4 billion people live on less than $1.25/day, the in-ternational poverty line. Another 1.2 billion live on$1.25 to $2.00/day, which is closer to a practical povertyline, especially in middle-income countries. Altogether,approximately 40% of the world’s population lives on lessthan $2.00/day, an extreme hardship that reduceschances for survival and optimal health.

Relative poverty is also an important determinant ofhealth, as borne out by research in both developed anddeveloping countries. Large gaps between rich and poorwithin a society are associated with worse health out-comes among the poorer compared with the wealthierstrata within the society (Fig. 2). This phenomenon ofpoor health among those living in material deprivationcompared with those around them who are better off hasbeen documented from New York to Glasgow toUganda. Unfortunately, income gaps between rich andpoor have increased dramatically over the past few de-cades, along with increases in health disparities. Forexample, in 21 developing countries where U5MRs haverecently decreased, gaps in mortality rates between therich and the poor increased.

A plethora of studies have documented the strongcorrelation between child survival and the mother’s ed-ucation level (Fig. 3). In Bolivia, for example, babiesborn to women who have no education are 2.5 timesmore likely to die before their first birthdays comparedwith those whose mothers have completed secondaryschool. Rural residence, slum dwelling, race, and ethnic-ity are other important social determinants of health.

Interventions to Reduce Child MortalityThe following section reviews current recommendationsfor preventing deaths from leading childhood killers. Theterm intervention is used to describe “a biologic agent oraction intended to reduce morbidity or mortality.” (1)

Neonatal CausesMore than one third of children who die do so during thefirst month after birth, accounting for more than 3.2 mil-lion deaths annually. Three major causes comprise 80%of deaths: prematurity and low birthweight, neonatalinfections, and asphyxia. Most deaths occur at home andin the first postnatal week. A large proportion of neonataldeaths can be prevented if babies and their mothersreceive known, effective interventions that span theante-, intra-, and postpartum periods. Examples includeantenatal screening and care, delivery by skilled birthattendants, promotion of early and exclusive breastfeed-ing, hygienic skin and umbilical cord care, keeping babieswarm and dry (eg, skin-to-skin contact), family recogni-tion of signs of illness requiring prompt medical atten-tion, and early assessment of newborns by trained healthworkers. Unfortunately, coverage rates in developingcountries for recommended neonatal interventions arepoor (Fig. 4).

Widespread implementation of a package of inexpen-sive, simple, and effective interventions could cut neona-tal deaths in half and bring global neonatal death rates tolevels comparable with those of industrialized countriesthat were recorded just before the widespread availabilityof neonatal intensive care.

Acute Respiratory InfectionsPneumonia is the leading cause of death after the neona-tal period, killing more than 1 million children annually.Although data on the microbiologic causes of pneumo-nia are limited, pneumococcus and Haemophilus influen-zae type b (Hib) are the leading causes of childhoodpneumonia deaths globally. This predominance is notunlike the causes of pneumonia deaths in industrializedcountries, especially before Hib and pneumococcalvaccine introduction. Other causes include viruses (eg,respiratory syncytial virus); other bacteria (eg, Staphylo-coccus aureus); and where HIV prevalence is high, Pneu-mocystis jiroveci pneumonia (PCP). PCP is responsiblefor 5% of childhood pneumonia deaths worldwide, de-spite the availability of effective prophylaxis and treatment.

Preventive measures are important in reducing theincidence of pneumonia and case fatality rates. Under-nourished children lack adequate immunity and havemore difficulty in clearing secretions due to weakened

Figure 2. Under 5 mortality rate (per 1,000 live births) bywealth group. Reproduced from Closing the Gap in a Gener-ation: Health Equity Through Action on the Social Determi-nants of Health. Final Report of the Commission on SocialDeterminants of Health. Geneva, Switzerland: World HealthOrganization; 2008.




respiratory muscles. Furthermore, children younger than6 months of age who are exclusively breastfed and chil-dren who continue to breastfeed through the secondpostnatal year are less likely to develop acute respiratoryinfections. Micronutrients (especially zinc) play an im-portant role in immune function and respiratory infectionprevention.

Hib and pneumococcal vaccines were incorporatedinto routine vaccination schedules in industrialized

countries toward the end of the20th century. However, despite thefact that the largest burden of Hiband pneumococcal disease has beenand continues to be in developedcountries, serotype coverage inpneumococcal vaccine has largelyfocused on markets in high-incomecountries. Furthermore, cost hasbeen a major impediment for Hiband pneumococcal vaccine intro-duction in poor countries. Since1997, Hib vaccine has graduallybeen incorporated into at least 115national childhood vaccine sched-ules. Pneumococcal vaccine rolloutis in its infancy in the developingworld. At the time of this writing,South Africa, Rwanda, and Gambiaare the only sub-Saharan Africancountries to have introduced thevaccine nationally, although othercountries have plans to do so in the

near future. Measles vaccine plays an important preven-tive role because pneumonia is a common sequela ofmeasles infection. Cotrimoxazole prophylaxis is impor-tant for PCP prevention among HIV-infected individu-als.

Indoor air pollution is associated with a 1.8-fold riskof contracting pneumonia and is largely caused by burn-ing of solid fuels (eg, dung, wood, charcoal) in dwellingsfor heat and cooking. These polluting fuels are used

primarily by poor households thatare unable to afford stoves that usecleaner burning fuels. Efforts tomitigate this exposure are ongoingthrough research to develop afford-able and acceptable clean energysystems and through increasing theutilization of existing methods,such as solar cookers.

Although prevention plays animportant role in pneumonia con-trol, treatment with a full courseof appropriate antibiotics remainsa critical intervention to reducerates of fatal pneumonia. The termpneumonia, as used in this articleand customarily in the global childhealth field, actually refers to “sus-pected pneumonia.” Diagnostic

Figure 3. Infant mortality rates by mother’s education in multiple countries. Reproducedfrom Closing the Gap in a Generation: Health Equity Through Action on the SocialDeterminants of Health. Final Report of the Commission on Social Determinants of Health.Geneva, Switzerland: World Health Organization; 2008.

Figure 4. Coverage of key neonatal survival interventions in the developing world.Reproduced and modified from UNICEF ChildInfo website: http://www.childinfo.org:80/newborncare.html.




test availability, including radiography, is extremely lim-ited in resource-poor settings. Diagnosis of suspectedpneumonia hinges on clinical assessment, based espe-cially on tachypnea or retractions in a child who hascough or cold symptoms.

Despite increasing resistance to first-line antibiotics(amoxicillin and cotrimoxazole), clinical trials continueto demonstrate the efficacy of these inexpensive oraldrugs, even in the treatment of severe pneumonia. Theyremain the mainstay of recommended treatment in theWorld Health Organization (WHO) and UNICEFguidelines. Prompt and appropriate treatment is criticalto reducing pneumonia deaths and hinges on: 1) parent/caretaker recognition of tachypnea and retractions assigns for which prompt care should be sought, 2) abilityto access appropriate health care without delay (ie, ser-vices are available, geographically proximate, affordable,of good quality, and nondiscriminatory), 3) accuratediagnosis and treatment by health workers, and 4) avail-ability and affordability of treatment and completion of afull therapeutic course. However, fewer than one fifth ofparents/caregivers recognize that fast breathing and re-tractions require urgent medical attention. Only 54% ofchildren who contract pneumonia in developing coun-tries are taken for appropriate health care. An evensmaller percentage actually receives antibiotics. Tragi-cally, there has been little improvement in these coveragestatistics over the past decade, especially in sub-SaharanAfrica.

Hundreds of thousands of lives could be saved ifpneumonia prevention and treatment interventions wereuniversally available. Universal treatment with antibioticsalone could reduce pneumonia mortality by approxi-mately 40%. To make this treatment a reality, implemen-tation strategies must focus on getting treatment tochildren in the communities where they live. Studies haveconsistently shown that community health workers(CHWs) trained in pneumonia case management canaccurately identify and effectively treat childhood pneu-monia. However, a recent study (2) demonstrated thatonly 27 of 54 countries that have a high pneumoniaburden have implemented some type of community-based pneumonia case management program. One thirdof countries have policies that restrict community casemanagement of pneumonia (eg, prohibitition of CHWsin dispensing or prescribing antibiotics). Policies andprograms that are conducive to getting interventions tochildren who need them the most (eg, the poor, ruraldwellers), efforts to educate families about danger signsof pneumonia, and improved access to and quality of care

in clinics and hospitals are critical in increasing the num-ber of patients who receive pneumonia treatment.

Diarrheal DiseaseDiarrhea is the second leading cause of child death afterthe neonatal period and accounts for nearly 4 billion

Glossary of Terms• U5MR�under five mortality rate, also referred to as

child mortality rate�number of deaths before5 years of age/1,000 live births

• Infant mortality rate�number of deaths before1 year of age/1,000 live births

• Neonatal mortality rate�number of deaths before28 days of age/1,000 live births

• Absolute poverty�living below a minimum level ofincome or wealth that is necessary for attainment ofbasic needs (eg, adequate shelter and nutrition) andservices (access to education and essential healthcare)

• Relative poverty�in a society with large differencesbetween rich and poor, living at an income orwealth level significantly less than the societalaverage, so those living in relative poverty areexcluded from the ordinary way of living of mostpeople around them

• Skilled birth attendant�a health professional suchas a midwife, doctor, or nurse who has been trainedto manage normal pregnancies, childbirth, and theimmediate postnatal period and can identify, manage,and refer complications in women and newborns

• Community health workers (CHWs)�persons livingin a community and selected by their community toreceive basic training to provide preventive healthservices, offer counseling on prevention and care-seeking practices, identify common illnesses, and inmany countries, provide basic health services forcommon problems. CHWs are referred to with avariety of names in different settings, includingcommunity health volunteers or village healthworkers in Africa, health promoters in Latin America,and lady health workers in Pakistan

• Improved water sources are those that are protectedfrom fecal contamination and include piped water,public taps, standpipes, boreholes, protected wells,protected spring, and rainwater

• Improved sanitation facilities are those thathygienically separate human waste from humancontact, including units that flush or pour-flush intosewer or septic systems or pit latrines, ventilatedimproved pit latrines or pit latrines with slab, andcomposting toilets

For more information, see WHO/UNICEF JointMonitoring Programme for Water Supply andSanitation http://www.wssinfo.org/definitions-methods/introduction




cases (all ages) and 1.1 million child deaths annually.Microbiologic causes vary by locale and have not beenwell elucidated, especially in developing countries wherethe incidence and mortality rates are highest. A variety ofbacteria (eg, Campylobacter, Salmonella, Escherichia coli,and Shigella), viruses (especially rotavirus), and parasites(eg, Cryptosporidium, Giardia) cause infectious diarrheaand are spread via water, food, utensils, flies, and hands.Deaths are due largely to fluid and electrolyte losses.Undernourished children are at greater risk of contract-ing and dying from diarrheal disease. Furthermore, re-peated and persistent infections can lead to or exacerbateunderlying undernutrition (Fig. 5).

The incidence of diarrhea and its mortality could bedramatically reduced by widespread implementation ofcurrently available prevention and treatment interven-tions. Access to “improved” (see Glossary of Terms)water sources and sanitation facilities as well as sufficientquantities of water to facilitate improved hygiene couldreduce diarrhea-related mortality by up to 88%. Further-more, widespread coverage of these interventions couldreduce the impact of other water-related diseases. Forexample, access to improved sanitation facilities reducesthe risk of acquisition of helminth infections (eg, hook-worm, whipworm, roundworm) from contact with con-taminated soil (eg, walking shoeless in at-risk environ-ments) or ingestion of contaminated food. Theseparasites are responsible for significant morbidity, includ-ing intestinal blood loss and reduced nutrient absorp-tion. Availability of a sufficient water supply for adequate

hygiene could also contribute tocontrol of diseases such as Guineaworm, trachoma, and respiratoryinfections.

Slightly more than 50% of theworld’s population has access topiped water (going into their dwell-ing or yard), while 87% have access toany type of improved water sources,up from 77% in 1990. Furtherprogress is still needed, especially insub-Saharan Africa, where only 58%of the population have access to im-proved water sources. Much slowerprogress has been made in sanitationcoverage. Only 62% of people glo-bally have access to improved sanita-tion facilities (compared with 54% in1990), and coverage in southernAsia and sub-Saharan Africa is abys-mally poor at less than 33%.

Adequate nutrition, including breastfeeding and ade-quate micronutrients, also plays an important role inpreventing diarrhea. In addition, new immunizations,such as rotavirus vaccine, hold promise for preventingdiarrhea due to specific agents.

Key treatment interventions are oral rehydration ther-apy (ORT) and zinc. For more than 2 decades, ORT hasbeen the cornerstone of treatment for preventing andtreating dehydration and electrolyte losses. ORT is esti-mated to save the lives of 1 million children annually.ORT employs prepackaged oral rehydration salts (ORS)mixed with water or the use of appropriate other fluidssuch as homemade solutions. Most recently, the compo-sition of internationally used ORS has been reformulatedto a lower osmolarity, which has been found to shortenthe duration of diarrhea and decrease the need for un-scheduled intravenous fluids compared with the olderformulation. International treatment guidelines also rec-ommend a 10- to 14-day course of oral zinc for allchildren who contract diarrhea and live in areas that havea presumed high prevalence of zinc deficiency (ie, mostdeveloping countries). Treatment with zinc reduces theseverity and duration of illness and decreases the likeli-hood of subsequent diarrheal episodes in the following2 to 3 months.

Because it is a relatively new recommendation, dataon zinc coverage are limited. However, progress in ORTcoverage has been sluggish. In 2008, only 38% of chil-dren who had diarrhea in developing countries (data

Figure 5. The vicious cycle of infectious diarrhea, malabsorption, and undernutrition.




exclude China) received recommended fluid therapycompared with 32% in 2000.

The unacceptable toll of deaths from diarrhea is atragic reminder of the work that remains in deliveringknown, effective prevention and treatment to those chil-dren most in need.

MalariaAlmost 50% of the world’s population lives in areas wheremalaria is endemic. The Plasmodium parasites that causemalaria are transmitted by the bite of the Anophelesmosquito. Infection with any of the four malaria-causingspecies (P falciparum, P vivax, P malariae, and P ovale) isassociated with significant morbidity, although the vastmajority of malaria deaths are due to P falciparum. Thegeographic distribution of Plasmodium species varies;Figure 6 depicts all areas where transmission from any ofthe species occurs and specifically denotes areas where Pfalciparum resistance to conventional antimalarials hasbeen reported.

People living in malaria-endemic areas frequently ex-perience asymptomatic and “uncomplicated” malariathat primarily presents with the flulike symptoms of fever,headache, and vomiting. Malaria parasites replicate inand lyse hematocytes, causing anemia, which exacts a tollon physical and mental development in children andeconomic productivity in adults. Untreated uncompli-cated malaria can rapidly lead to life-threatening “com-

plicated” malaria in pregnantwomen and young children (due torelative immunosuppression andlack of acquired immunity, respec-tively) in areas where P falciparumcause disease. Severe hemolyticanemia and cerebral malaria (pre-senting with altered mental status,convulsions, or coma) are the mostcommon forms of complicated ma-laria and are associated with highfatality rates. Malaria parasites in-fect the placenta and contribute tolow birthweight, a major cause ofneonatal mortality.

Reduction in malaria mortalityrequires a multipronged approachconsisting of prevention and treat-ment interventions. Insecticidetreated nets (ITNs) are one of themost effective methods of prevent-ing transmission. Studies havedemonstrated a 17% reduction in

all causes of child mortality in malaria-endemic areasassociated with regular ITN use. Not only do ITNsprotect sleeping individuals with a physical barrieragainst mosquitoes, but the insecticide also offers protec-tion to nonusers up to several hundred meters away.Initially, ITN implementation strategies focused on cre-ating demand for ITN purchase. However, even at sub-sidized prices, nets were not affordable to those in mostneed and at highest risk, and coverage rates were low.A recent shift to a mass distribution strategy (eg, throughantenatal care and immunization clinics) has increasedcoverage multifold, although much more progress isrequired to move current 20% coverage rates to 80%coverage goals (set by the WHO World Health Assemblyin 2005) by 2010.

Malaria parasites can become resistant to antimalarialdrugs quickly; conventional therapies (eg, chloroquine,sulfadoxine-pryimethamine) are no longer effective inmany areas (Fig. 6). Artemisinin combination therapy(ACT), once deemed too costly for wide-scale use, isnow the recommended first-line treatment for uncom-plicated malaria in areas characterized by high resistanceto conventional therapies. Artemisinin is an effectiveantimalarial, and when used in combination with anotherantimalarial agent, progression to resistance is sloweddramatically. To prevent rapid development of artemisi-nin resistance, the WHO recommends against the pro-duction, marketing, or use of artemisinin oral mono-

Figure 6. Malaria transmission areas and reported P falciparum resistance, 2004.Reproduced from Guidelines for the Treatment of Malaria. Geneva, Switzerland: WorldHealth Organization; 2006.




therapy, especially because there are no effectivetreatment alternatives on the market. Unfortunately, oralartemisinin monotherapy is available in many countries,and resistance has recently been reported in Cambodia.Furthermore, even in countries that have adopted ACTas first-line treatment, few children who have malariasymptoms are receiving the agent. In fact, recent datafrom sub-Saharan Africa demonstrated that fewer than60% of children who have had malaria symptoms havereceived any type of antimalarial. Updated WHO treat-ment guidelines recommend that all children presentingwith fever and living in malaria-endemic countries betested for malaria infection (by microscopy or rapiddiagnostic tests) and treated accordingly. In settingswithout testing capacity, febrile children should betreated for malaria presumptively.

Malaria infection among pregnant women is com-mon, even when asymptomatic. Intermittent presump-tive treatment (IPT) during pregnancy is effective inreducing maternal (eg, anemia) and neonatal (eg, lowbirthweight) complications of infection by clearing par-asites from the bloodstream and placenta. IPT, consist-ing of two doses of oral sulfadoxine-pyrimethamine, isrecommended during pregnancy for those residing inendemic areas. IPT for young children holds greatpotential for reducing malaria mortality. Research is

ongoing to identify IPT drugsthat have fewer current and po-tential resistance issues.

Other Major Causes of ChildMortality

Measles is a leading cause ofvaccine-preventable mortality,contributing to 1% of child deaths.Two doses of vaccine are recom-mended. The first dose is usuallyadministered at 9 months of age inendemic settings. Approximately80% of 12- to 23-month-old chil-dren have received at least onedose. Children infected with mea-sles are at high risk for secondarycomplications, including cornealulceration, diarrhea, and pneumo-nia. Concomitant VA deficiency isassociated with increased morbid-ity and mortality. VA plays an im-portant role in immune and epithe-lial tissue function. VA deficiency iscommon in developing countries,

and measles infection further depletes VA stores. Treat-ment with high-dose VA reduces measles-related mor-bidity and mortality and is recommended for all childrenwho have measles living in areas with high VA deficiency.Much recent progress has been made in reducing measlesmortality: deaths have declined by 74% and 89% world-wide and in sub-Saharan Africa, respectively, between2000 and 2007.

AIDS and injuries account for 2% and 3% of childhoodmortality globally, respectively, but represent higher pro-portions of deaths, depending on geographic setting. Forexample, injuries account for higher proportions ofdeaths in middle-income countries where infectious dis-eases are better controlled. Most deaths due to injuriesare preventable with interventions that employ a multi-disciplinary approach to the problem. AIDS is responsi-ble for a high proportion of child deaths in many sub-Saharan African countries. Transmission from mother tochild accounts for 90% of childhood HIV acquisition andhas been virtually eliminated in industrialized countries.This progress is not the case in developing countries dueto poor access to antiretrovirals and less-than-optimalsubstitutes for breastfeeding due to cost and sanitationissues. Furthermore, only a small fraction of childrenmeeting criteria for treatment of HIV/AIDS are receiv-ing treatment.

Figure 7. Trends in U5MR from 1970 to 2008.




Child Health Intervention ImplementationWithin the Health SystemIn the 1990s, in response to programs focused solely oncontrolling and treating single diseases, WHO andUNICEF developed the Integrated Management ofChildhood Illness (IMCI), a strategy that focuses oncaring for the whole child. IMCI includes preventive andcurative elements, such as monitoring growth, develop-ment, and immunization status during all childhood sickvisits. Effective IMCI implementation includes threecomponents: 1) improving health worker case manage-ment skills, 2) improving health practices within familiesand communities, and 3) improving overall health sys-tems. Nonpediatric physicians and nonphysician provid-ers of care are trained in IMCI clinical algorithms. Thesetypes of HCWs, particularly nonphysician providers (eg,nurses, mid-level providers), provide the bulk of childhealth services in resource-poor settings. IMCI algo-rithms focus on identification of common causes of mor-tality, appropriate treatment, and referral for more spe-cialized or hospital-based care when necessary. Thecommunity and family practices component encom-passes education to increase key preventive practices inthe household and community and to ensure that parentsknow symptoms for which to seek health care. Last, butnot least, a functioning health system is critical for train-ing and regular supervision of health workers and forensuring timely access to referred care and steady stocksof drugs, vaccines, equipment, and supplies.

Evaluations of the IMCI strategy conducted inmultiple countries have demonstrated improved per-formance by health workers and improved clinical careby those who have taken the IMCI course. However,the evaluations also showed that less attention hasbeen focused on implementing the family/community

and health systems components. To achieve any sig-nificant reduction in child mortality through the IMCIstrategy, full attention to all three components isneeded as well as implementation of services on alarger scale.

Efforts are being made, including by the WHO, torevitalize the Primary Health Care movement, first ad-vanced in the 1970s. This movement encourages inte-grated care but additionally focuses on universal access toessential medicines and health services and a comprehen-sive approach to health that includes addressing under-lying environmental (eg, water and sanitation) and socialdeterminants of health (eg, education).

Trends in Child MortalityTracking of health data globally started in the 1960s.There has been a continual decline in U5MRs and inabsolute numbers of child deaths annually over theintervening decades. Remarkable gains were seen inreducing child mortality in the first couple of decadesafter commencement of data monitoring, followed bya marked diminution in progress, even stagnating andsometimes reversing course, with increased U5MRsin some countries. Worldwide, U5MRs dropped 20%in each decade between 1970 and 1990, but theydropped only 12% in the 1990s. Data to date from thefirst decade of the 21st century indicate modest im-provements in reducing U5MRs compared with theprevious decade (Fig. 7).

Sociopolitical and economic factors and policies caninfluence child health profoundly. An examination oftrends in global health would not be complete withoutexamination of some important sociopolitical and eco-nomic issues affecting these trends:

Figure 8. Vila Manica District Hospital, Mozambique, 1991.Reproduced with permission from Stephen Gloyd.

Figure 9. Laboratory technician, Somalia, 1983. Reproducedwith permission from Stephen Gloyd.




• Conflict: Most countries experiencing U5MR in-creases are embroiled in conflict. Since World War II,civilian deaths, including those of women and chil-dren, outnumber combatant deaths, accounting for90% of conflict-related deaths and half among thoseyounger than 18 years. Most civilian deaths are non-trauma-related; rather, they are due to disruptions incivilian infrastructure, including health services. Forexample, pneumonia, diarrhea, and undernutritionrates typically increase during conflict.

• Global free trade policies: Free trade policies havelargely been negotiated to the benefit of rich coun-tries. The United Nations estimates that trade rulesthat are unfair to poor countries deny them $700billion in income every year. For example, subsidies tofarmers in rich countries have shut many farmers inpoor countries out of markets, including in their owncountries. Other policies have encouraged privatiza-tion of health care, which leaves the poor with feweraccess options. Trade policies on drug patents haveresulted in limited access to medicines.

• Debt: Many poor countries are servicing debt burdensfrom high-interest rate loans owed to internationallending agencies, such as the International MonetaryFund and World Bank. African countries pay more indebt than they receive in donor aid.

• International economic policies: Structural adjust-ment policies (now often incorporated as part of “pov-erty reduction initiatives”) are conditions imposed byinternational lending institutions on loaning money orforgiving debt and are intended to rein in borrowergovernment spending. As such, these conditionalitiescall for reduced subsidies for public services that di-rectly affect those who most need the services. Forexample, as many sub-Saharan countries went fromfree to fee-based health care and education, utilizationsubsequently declined. Many Latin American coun-tries privatized water sources, with resultant decreasesin water access among the poor. These policies alsoinclude reductions in civil service workforces (eg,health professionals, teachers) through layoffs. Salarycaps have effectively reduced buying power becausepay cannot keep pace with high inflation rates of manycountries. Slashed funds for improvement and evenupkeep have resulted in crumbling health facilities(Fig. 8), lack of even basic equipment (Fig. 9), andreduction in quality of services.

• Unmet development aid promises: High-incomecountries have recognized that to attain developmentgoals, low-income countries require at least $50 bil-lion in external funds in addition to what is currently

being given. (For the purposes of context, $16 billiona month has been spent by the United States on thedirect costs of the wars in Iraq and Afghanistan, andrecent United States stimulus and financial institutionbailout packages were allocated more than $700 bil-lion each.) The Millennium Declaration is a compactbetween poor and rich countries whereby the lattercommitted to supporting poor countries to meetMDGs. Extending back to 1970, wealthy countrieshave pledged and reiterated their pledge to give 0.7%of their gross national income as donor aid to helpdeveloping countries achieve basic development goals.However, only five countries (Denmark, Luxem-bourg, the Netherlands, Norway, and Sweden) haveactually met this pledge. The United States gives themost in terms of total dollars, but the least in relationto the pledge, donating 0.18% of gross national in-come (compared with 0.3% for 22 Western donorcountries overall).

• Aid effectiveness and priority setting: There is increas-ing recognition that more donor aid* without aideffectiveness measures can translate to wasted dollars,or worse, negative impact. Donor aid is often allocatedto countries not on the basis of need but on the basisof strategic interests. For example, less than one thirdof United States donor aid goes to the least developedcountries. In 2007, the top five recipients of UnitedStates donor aid (Iraq, Afghanistan, Sudan, Columbia,and Egypt) received approximately one third ofUnited States donor funds.

Other problems can translate to less effective donoraid. For example, aid is increasingly being giventhrough nongovernmental organizations (both for-profit and not-for-profit) based in donor countriesinstead of directly to developing countries. These or-ganizations often have high overhead costs, using upto 50% of project funding. Furthermore, internation-ally run projects often draw away indigenous talentwith substantially higher salaries, leaving local institu-tions further understaffed. It is also not unusual tohave hundreds of internationally run projects workingin the same country and not communicating with eachother or with local structures. They often work outsideof national health systems, but this practice only di-verts from and weakens existing systems. Moreover,

*The term donor aid refers to funds that are for the purpose of development toresource-poor countries. Foreign assistance includes donor aid but may alsoinclude military assistance, for example. Health expenditures comprise only 15%of total donor aid, with the remaining going to other areas of development,emergency aid, and debt repayment.




funders determine where, how, and on what prioritiestheir money will be spent.

Donor aid often mandates that recipient countriesbuy donor goods in return. It is not uncommon formore than half of donor aid to funnel right back todonor countries, diminishing the “effectiveness” ofaid dollars in producing intended outcomes. Projectstend to concentrate in capital cities and at national-level hospitals and less commonly reach underfunded,understaffed, more outlying district hospitals, clinics,and communities.

The last few years have seen an influx of funding forhigh-profile diseases, especially AIDS, tuberculosis,and malaria, scourges certainly worthy of global atten-tion. However, funding for more common maternaland childhood killers has been abysmal. For example,pneumonia kills more children than AIDS, tuberculo-sis, and malaria combined and yet receives far lessattention and funding than any of them. The same canbe said for diarrhea and neonatal problems.

• Unmet government commitment to health: Gov-ernments of developing countries have also pledgedto prioritize health, including by providing re-sources for the health sector. For example, Africanheads of state have agreed to devote 15% of domes-tic expenditures to the health sector. Malawi hasmade substantial increases in health funding, andZambia has met the pledge. Most other countrieslag far behind their pledges, and many have de-creased the proportion of funds going to the healthsector.

• Skewed research priorities: In 1998, the term“10/90 gap” was coined by the Global Forum forHealth Research to express that only 10% of healthresearch funding was directed toward the 90% of thedisease burden that affects the poor globally. Theterm continues to be used to express the continuedwide gaps, despite recent increases in global healthresearch spending that have largely focused onHIV/AIDS, to a lesser extent on tuberculosis andmalaria, and relatively little on neonatal problems,pneumonia, or diarrhea, which cause more than halfof all child deaths. Furthermore, 97% of child healthresearch funding goes toward the development ofnew technologies (eg, new drugs or immunizationsto prevent or treat disease) that have the potential toreduce child mortality by 22%. Only 3% of childhealth research dollars are spent on research todetermine how to increase coverage rates of inter-ventions and get effective services delivered to chil-dren who need them the most. Increasing delivery

and coverage could reduce child mortality by 63%.• Inequity: Although the recent financial crisis has

struck developing countries even harder than devel-oped countries, it takes a few years before theimpact of such events on child survival is exactedand measured. The economic boom that precededthe current financial crisis, however, did not neces-sarily result in improved child health. In fact, Indiaexperienced unprecedented economic growth butonly weak reductions in child mortality. This out-come is in contrast to neighboring Bangladesh,which simultaneously made weak economic stridesbut strong improvements in child survival. Al-though national economic stability is an importantelement in the ability to provide resources to healthsystems and programs, studies have indicated thatnational wealth and economic growth in the ab-sence of equity-oriented strategies do not translateto improved child health, especially among thepoor.

• Global food crisis: Even before the onset of theeconomic crisis, soaring food prices resulted in100 million more people joining the ranks of the 1billion people living with hunger. Reasons for in-creased food prices are multifactorial and includedecreased food production due to climatic causes,diversion of crops for biofuel, and an increasingshare of grains going to feed domestic animals tomeet growing worldwide consumer demand formeat among those in better-off strata of society.Although there are alarming predictions of a futurelack of sufficient food supplies to meet an increasingglobal population, global food supplies currentlyare adequate to meet global nutrition needs. How-ever, sharp price increases have dramatically affectedthe amount of food that the poor are able to pur-chase, and global rates of hunger have increased.The full impact on undernutrition rates have yet tobe measured.

What Will it Take to Meet MDG4?MDG4 is based on earlier trends in U5MRs and datademonstrating that two thirds of child deaths can beaverted with interventions that are already available andare recommended for full implementation. MDG4 isnot “pie in the sky”; it is an achievable goal. However,examination of current trends in child health demon-strates that the world is alarmingly far from meeting itsMDG4 commitment (Fig. 10). Perhaps most distressingis that of 64 countries with the highest U5MRs, onlynine are on track to meet MDG4.




MDG4 is attainable, even in the poorest countries,as evidenced by remarkable progress in several high-mortality countries: Nepal, Bangladesh, Eritrea, LoaPeople’s Democratic Republic, Mongolia, Bolivia, andMalawi. (3) Malawi, for example, has reduced itsU5MR by 53% over a 17-year period. Resource-poorcountries making great strides in child health are doingso through equity-oriented national policies orthrough targeting of simple, effective, inexpensive in-terventions (such as antibiotics for pneumonia, ORTfor diarrhea, improved home care for newborns, andITNs to prevent malaria) to those who need them themost, especially poor children and those living in ruralareas. These real-world case studies provide optimismthat dramatic improvements in child survival can beattained. Long-term inroads in promoting child healthadditionally require addressing the underlying deter-minants of health.

Opportunities for ProgressAmerican pediatricians can and do play an importantrole in improving the lives of children in poor coun-tries, which is the majority of children in the world.Many pediatricians are working to improve child sur-vival and health through overseas work or are support-ing organizations that are on the ground in resource-limited settings. On-site work can contribute greatly(eg, through training and clinical work), especiallywhen services are delivered to those in the greatest

need and are consistent with in-country priorities and interna-tional care guidelines. Throughcareful consideration of ethicalengagement in participatory andsustainable global health work toaddress local needs and build lo-cal health institution and healthprofessional capacity, individualsand organizations can avoid un-intended negative consequencesand provide maximal benefit.

The contribution of Americanpediatricians to improving globalhealth is not limited to work onforeign soil. Pediatricians can advo-cate for much needed accountabil-ity among the growing number ofplayers in global health, makingcertain that: 1) major causes ofchildhood morbidity and mortalityare no longer neglected; 2) re-

search agendas expand to determine how best to deliveravailable, effective interventions and services to those inmost need; 3) international initiatives have a more com-prehensive and participatory outlook and are less ori-ented toward single diseases; and 4) research and serviceprograms avoid contributing to the further collapse ofhealth systems, but rather work in conjunction withministries of health and their clinical institutions, such asdistrict hospitals and clinics, to facilitate the strengthen-ing of health systems.

Perhaps the most effective approach for Americanpediatricians to make an impact is by supporting policiesthat address poverty, the major underlying cause of childdeaths globally. Such policies include meeting UnitedStates donor aid pledges and effectively allocating aidbased on need, debt relief, elimination of structural ad-justment policies, and transparent trade proceedings andtrade policies that are fair to poor countries. Surveys havedemonstrated that most Americans are concerned aboutglobal child health, but there are many misconceptionsabout the nature of global health problems and activities.Pediatricians can play an important educational role toaid community members in becoming better informedadvocates.

Just as American pediatricians have played and continueto play a vital role in advocacy for American children, we cansupport children everywhere through advocacy on theirbehalf.

Figure 10. Accelerated improvements in child mortality are needed to meet MDG4.




ACKNOWLEDGMENTS. Grateful thanks to Drs TessaWardlaw and Cynthia Boschi-Pinto for assistance withepidemiologic data; Drs Charles Mock and Elinor Gra-ham for thoughtful manuscript review; and ElizabethWolf for manuscript preparation.

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9. Schell CO, Reilly M, Rosling H, Peterson S, Ekstrom AM.Socioeconomic determinants of infant mortality: a worldwide studyof 152 low-, middle-, and high-income countries. Scand J PublicHealth. 2007;35:288–29710. Victora CG, Wagstaff A, Schellenberg JA, Gwatkin D, ClaesonM, Habicht JP. Applying an equity lens to child health and mortal-ity: more of the same is not enough. Lancet. 2003;362:233–24111. Bhutta ZA, Ahmed T, Black RE, et al. What works? Interven-tions for maternal and child undernutrition and survival. Lancet.2008;371:417–44012. Darmstadt GL, Bhutta ZA, Cousens S, Adam T, Walker N, deBernis L. Evidence-based, cost-effective interventions: how manynewborn babies can we save? Lancet. 2005;365:977–98813. World Health Report: Make Every Mother and Child Count.Geneva, Switzerland: World Health Organization; 200514. De Vogli R, Birbeck GL. Potential impact of adjustmentpolicies on vulnerability of women and children to HIV/AIDS insub-Saharan Africa. J Health Pop Nutr. 2005;23:105–12015. Labonte R, Schrecker T. Globalization and social determinantsof health: promoting health equity in global governance (part 3 of3). Global Health. 2007;3:716. Labonte R, Schrecker T. Globalization and social determinantsof health: the role of the global marketplace (part 2 of 3). GlobalHealth. 2007;3:617. Labonte R, Schrecker T. Globalization and social determinantsof health: introduction and methodological background (part 1 of3). Global Health. 2007;3:518. O’Hare BA, Southall DP. First do no harm: the impact ofrecent armed conflict on maternal and child health in Sub-SaharanAfrica. J R Soc Med. 2007;100:564–57019. Impact of Armed Conflict on Children. New York, NY:UNICEF; 1996

Suggested Reading

General References on Global Child Health:

2003 Lancet Child Survival Series:Bryce J, el Arifeen S, Pariyo G, Lanata C, Gwatkin D, Habicht JP.

Reducing child mortality: can public health deliver? Lancet.2003;362:159–164

Black RE, Morris SS, Bryce J. Where and why are 10 millionchildren dying every year? Lancet. 2003;361:2226–2234

Claeson M, Gillespie D, Mshinda H, Troedsson H, Victora CG.Knowledge into action for child survival. Lancet. 2003;362:323–327

Jones G, Steketee RW, Black RE, Bhutta ZA, Morris SS. How manychild deaths can we prevent this year? Lancet. 2003;362:65–71

Victora CG, Wagstaff A, Schellenberg JA, Gwatkin D, Claeson M,Habicht JP. Applying an equity lens to child health and mortality:more of the same is not enough. Lancet. 2003;362:233–241

The State of the World’s Children 2010: Child Rights. New York, NY:UNICEF; 2009. UNICEF publishes an annual State of theWorld’s Children Report that includes indicators on child healthand development. Each report covers a special theme. The 2008report focused on child survival, the 2009 report on maternaland newborn care, and the 2010 special edition on the UNConvention on the Rights of the Child. Accessed November2010 at: http://www.unicef.org/sowc/

Summary• Approximately 8 million children die annually (based

on 2009 data), and 99% of child deaths occur indeveloping countries. (3)

• Eighty-four percent of global child deaths are due toseven major causes: neonatal problems, acuterespiratory infections, diarrhea, malaria, measles,injuries, and HIV/AIDS. (4)

• Undernutrition is an underlying cause in 35% ofchild deaths. (5)

• Determinants of child mortality include lack ofaccess to improved water sources and sanitationfacilities, lack of access to care, lack of maternaleducation, absolute poverty, and relative poverty.(6)(7)(8)(9)(10)

• Two thirds of child deaths could be prevented withinterventions that are currently available, effective,and feasible for widespread implementation (1)(11)(12) as well as consistent with MDG4. However,trends in decreasing child mortality have slowed,(13) and based on current trends, the world is noton track to meet MDG4.

• Sociopolitical and economic factors and policies have atremendous influence on health and the determinantsof health (6)(13)(14)(15)(16)(17)(18)(19)




World Health Report: Make Every Mother and Child Count. Geneva,Switzerland: World Health Organization; 2005

General Clinical Information:Managing Newborn Problems: A Guide for Doctors, Nurses, and Mid-

wives. Geneva, Switzerland: World Health Organization; 2003.Pocket Book of Hospital Care for Children: Guidelines for the Man-

agement of Common Illnesses With Limited Resources. Geneva,Switzerland: World Health Organization; 2005

Disease-specific References:Diarrhea: Why Children are Still Dying and What Can Be Done About

It. Geneva, Switzerland: World Health Organization, UNICEF;2009

Guidelines for the Treatment of Malaria. 2nd ed. Geneva, Switzer-land: World Health Organization; 2010

Wardlaw T, Johansson E, Hodge M. Pneumonia: The ForgottenKiller of Children. Geneva, Switzerland: World Health Organi-zation, UNICEF; 2006

World Report on Child Injury Prevention. Geneva, Switzerland:World Health Organization; 2008

UNICEF ChildInfo website. http://www.childinfo.org/index.html

2005 Lancet Neonatal Survival series:Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: When?

Where? Why? Lancet. 2005;365:891–900Darmstadt GL, Bhutta ZA, Cousens S, Adam T, Walker N, de

Bernis L. Evidence-based, cost-effective interventions: howmany newborn babies can we save? Lancet. 2005;365:977–988

Knippenberg R, Lawn JE, Darmstadt GL, et al. Systematic scalingup of neonatal care in countries. Lancet. 2005;365:1087–1098

Martines J, Paul VK, Bhutta ZA, et al. Neonatal survival: a call foraction. Lancet. 2005;365:1189–1197

2008 Lancet Maternal and Child Undernutrition series:Bhutta ZA, Ahmed T, Black RE, et al. What works? Interventions

for maternal and child undernutrition and survival. Lancet.2008;371:417–440

Black RE, Allen LH, Bhutta ZA, et al. Maternal and child under-nutrition: global and regional exposures and health conse-quences. Lancet. 2008;371:243–260

Bryce J, Coitinho D, Darnton-Hill I, Pelletier D, Pinstrup-Andersen P. Maternal and child undernutrition: effective actionat national level. Lancet. 2008;371:510–526

Morris SS, Cogill B, Uauy R. Effective international action againstundernutrition: why has it proven so difficult and what can bedone to accelerate progress? Lancet. 2008;371:608–621

Victora CG, Adair L, Fall C, et al. Maternal and child undernutri-tion: consequences for adult health and human capital. Lancet.2008;371:340–357

Determinants of Health:Closing the Gap in a Generation: Health Equity Through Action on

the Social Determinants of Health. Final Report of the Commis-sion on Social Determinants of Health. Geneva, Switzerland:World Health Organization; 2008

IMCI:World Health Organization Child and Adolescent Health and

Development Department website on IMCI. Accessed Novem-ber 2010 at: http://www.who.int/child_adolescent_health/topics/prevention_care/child/imci/en/index.html

IMCI Clinical Algorithms:Integrated Management of Childhood Illness – Standard Chart

Booklet. Geneva, Switzerland: World Health Organization; 2008Integrated Management of Childhood Illness for High HIV Settings

Chart Booklet. Geneva, Switzerland: World Health Organiza-tion; 2008

Primary Health Care:Declaration of the 1978 Alma-Ata International Conference on

Primary Health Care. Accessed November 2010 at: www.who.int/publications/almaata_declaration_en.pdf

World Health Report: Primary Health Care: Now More than Ever.Geneva, Switzerland: World Health Organization; 2008

Socio-political-economic Issues and Policies Affecting GlobalHealth:

Farmer P. Pathologies of Power: Health, Human Rights, and the NewWar on the Poor. Berkeley, CA: University of California Press; 2003

Fort MP, Mercer MA, Gish O, eds. Sickness and Wealth: TheCorporate Assault on Global Health. Cambridge, MA: SouthEnd Press; 2004

Global Health Watch 2: An Alternative World Health Report.London, United Kingdom: People’s Health Movement; 2008

Kim JY. Dying for Growth: Global Inequality and the Health of thePoor. Monroe, ME: Common Courage Press; 2000

Ethical Considerations in Global Health and Development andResearch:

Leroy JL, Habicht JP, Pelto G, Bertozzi SM. Current priorities inhealth research funding and lack of impact on the number ofchild deaths per year. Am J Public Health. 2007;97:219–223

NGO Code of Conduct for Health Systems Strengthening. AccessedNovember 2010 at: http://ngocodeofconduct.org/

Organisation for Economic Co-operation and Development. TheParis Declaration and Accrea Agenda for Action on Aid Effec-tiveness. 2005. Accessed November 2010 at: http://www.oecd.org/document/18/0,2340,en_2649_3236398_35401554_1_1_1_1,00.html

Suchdev P, Ahrens K, Click E, Macklin L, Evangelista D, GrahamE. A model for sustainable short-term international medicaltrips. Ambul Pediatr. 2007;7:317–320

Tracking MDGs:Countdown to 2015: Maternal, Newborn and Child Survival

website. Accessed November 2010 at: http://www.countdown2015mnch.org/index.php

United Nations Development Programme MDGs website. Ac-cessed November 2010 at: http://www.undp.org/mdg/

Opportunities for Involvement in Global Child Health:American Academy of Pediatrics Section on International Child

Health (SOICH) “is committed to improving the health andwell-being of the world’s children. . .through education, advo-cacy, research, service, and the facilitation of effective globalpartnerships.” The website lists opportunities and informationrelated to these areas. Accessed November 2010 at: http://www.aap.org/sections/ICH/default.cfm

Dueger C, O’Callahan C, eds. Working in International ChildHealth. 2nd ed. Elk Grove Village, IL: American Academy ofPediatrics Section on International Child Health; 2008. A prac-tical guide for volunteering and working overseas





Donna Denno Global Child Health


http://pedsinreview.aappublications.org/cgi/content/full/32/2/e25including high-resolution figures, can be found at:


born_infanthttp://pedsinreview.aappublications.org/cgi/collection/fetus_new

Fetus and Newborn Infant _pediatricshttp://pedsinreview.aappublications.org/cgi/collection/preventive

Preventive Pediatrics _disordershttp://pedsinreview.aappublications.org/cgi/collection/nutritional

Nutrition and Nutritional Disorders _diseaseshttp://pedsinreview.aappublications.org/cgi/collection/infectious








http://pedsinreview.aappublications.org/cgi/collection/nutritional_disorders

http://pedsinreview.aappublications.org/cgi/collection/preventive_pediatrics

http://pedsinreview.aappublications.org/cgi/collection/fetus_newborn_infant




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