Professional Documents
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Pediatrics in Review - July2011
Pediatrics in Review - July2011
Nazarian, Rochester, NY
Associate Editors: Tina L. Cheng, Baltimore, MD
Joseph A. Zenel, Sioux Falls, SD
Editor, In Brief: Henry M. Adam, Bronx, NY
Consulting Editor, In Brief: Janet Serwint, Baltimore, MD
Editor, Index of Suspicion: Deepak M. Kamat, Detroit, MI
Consulting Editor Online and Multimedia
contents
Projects: Laura Ibsen, Portland, OR
Editor Emeritus and Founding Editor:
Robert J. Haggerty, Canandaigua, NY
PediatricsinReview Vol.32 No.7 July 2011
Managing Editor: Luann Zanzola
Medical Copy Editor: Deborah K. Kuhlman
Editorial Assistants: Kathleen Bernard, Melissa Schroen
Editorial Office: Department of Pediatrics
Articles
University of Rochester
School of Medicine & Dentistry
601 Elmwood Avenue, Box 777
Rochester, NY 14642
267 Breastfeeding: More Than Just Good Nutrition
Robert M. Lawrence, Ruth A. Lawrence
kbernard@aap.org
Editorial Board
Hugh D. Allen, Columbus, OH Hal B. Jenson, Kalamazoo, MI Normal Pubertal Development:
Margie Andreae, Ann Arbor, MI
Richard Antaya, New Haven, CT
Denise Bratcher, Kansas City, MO
George Buchanan, Dallas, TX
Donald Lewis, Norfolk, VA
Gregory Liptak, Syracuse, NY
Michael Macknin, Cleveland, OH
Susan Massengill, Charlotte, NC
281 Part II: Clinical Aspects of Puberty
Brian Bordini, Robert L. Rosenfield
Brian Carter, Nashville, TN Jennifer Miller, Gainesville, FL
Joseph Croffie, Indianapolis, IN
B. Anne Eberhard, New Hyde Park, NY
Philip Fischer, Rochester, MN
Rani Gereige, Miami, FL
Lindsey Grossman, Springfield, MA
Blaise Nemeth, Madison, WI
Mobeen Rathore, Jacksonville, FL
Renata Sanders, Baltimore, MD
Thomas L. Sato, Milwaukee, WI
Sarah E. Shea, Halifax, Nova Scotia
293 Focus on Diagnosis: The D-test
Kamakshya P. Patra
Patricia Hamilton, London, United Kingdom Andrew Sirotnak, Denver, CO
Jacob Hen, Bridgeport, CT
Jeffrey D. Hord, Akron, OH
Publisher: American Academy of Pediatrics
Nancy D. Spector, Philadelphia, PA
*Clinical Associate Professor, Pediatric Immunology and Infectious Diseases, University of Florida Health Science Center,
Gainesville, FL.
Professor, Department of Pediatrics and Obstetrics/Gynecology; Director, Human Lactation Study Center, University of
Rochester School of Medicine, Rochester, NY.
reported that breastfeeding for at least 3 months was produced by the second 24 hours, 400 g by the third
calculated to provide a 27% (95% CI, 8% to 41%) reduc- 24 hours, and 1,100 g/24 hours by the fourteenth day
tion in the risk of asthma in children who had no family (800 to 1,000 mL). Human milk and cow milk differ
history of asthma compared with children who were not substantially in their composition (Table 2).The proteins
breastfed. Children who had a family history of asthma differ in quality and quantity. In its unaltered form, cow
had a 40% risk (95% CI, 18% to 57%) reduction in the milk contains too much protein, too much casein, too
occurrence of asthma before 10 years of age if breastfed much sodium, and too much phosphorus and has too
for 3 months compared with those not breastfed. The high a solute load for a human infant. Formulas have
risk for children older than 10 years is less clear. Exclusive been designed to improve these issues. Cow milk does
breastfeeding for the first 6 months is recommended by not contain any taurine, an amino acid that has high
the American Academy of Pediatrics (AAP) for many concentrations in human milk and is essential to infant
reasons, including reducing the risk of allergy. Further brain growth. The profile of amino acids in cow milk
if supplementation is necessary, an amino acid-based differs significantly from human milk, especially phenyl-
formula is recommended (hypoallergenic formula). alanine and tyrosine, which are at high concentrations
in cow milk and formula and contribute to problems in
Physiologic Consequences of the Differences phenylketonuria.
between Colostrum and Mature Milk The effect of higher protein in infant formula recently
The milk available in the breast after 16 weeks gestation has been questioned by investigators of the obesity epi-
is called prepartum milk. When the infant delivers and is demic. It has been suggested that a constant intake of
placed at the breast (or is allowed to find his or her way) high protein in infancy stimulates the metabolic rate
to suckle, the milk is colostrum for the next few days. and contributes to the long-term obesity of formula-fed
A gradual change from this transition milk to mature infants. After processing, cow milk and infant formulas
milk usually occurs by 14 days. Postpartum colostrum contain no cells, no enzymes, and no antibodies or other
is called the first immunization because it contains active protective agents and do not support the mainte-
high concentrations of antibodies and other infection- nance of physiologic flora of the infants GI tract.
protective elements, including cells. Colostrum is high in Docosahexaenoic acid (DHA) has received consider-
total protein, low in carbohydrate, and lower in fat than able attention because studies in preterm infants have
mature milk. The amount of milk produced in the first demonstrated improved visual acuity and auditory acuity
24 hours after birth is approximately 50 g, with 190 g in those fed human milk compared with those fed regular
preterm formula. When DHA was added to formula, the ulation of B cells for antibody production, and limited
acuity improved but did not reach the scores achieved by numbers of mature functioning T cells. In addition,
breastfed infants. DHA and omega-3 fatty acids derived function of the classical and alternative pathways of com-
from bacterial culture are added to many formulas, plement formation and activation is decreased. Immuno-
although a benefit has not been proven. globulin (Ig) production is limited in amount and reper-
Vitamin concentrations in human and cow milk are toire, including poor isotype switching, limited IgG
comparable, except for vitamin C, which is significantly subclass production, and low serum IgA concentrations
higher in human milk (100 mg/d). Vitamins in infant through 7 to 8 years of age.
formula exceed the concentrations found naturally. Vita-
min D has become an important issue because the vita- Bioactive Factors
min D generated in human skin from exposure to sun- Human milk not only bolsters the infants immature
shine has diminished through the use of sunscreen, immune response by providing numerous bioactive fac-
wearing of clothing to shade from the sun, pollution of tors that dynamically affect the innate, adaptive, and
the air by industrial waste, and migration of dark-skinned mucosal immunity against specific infectious agents but
populations to climates with less sun. Pregnant women also by influencing immune system development and
have been documented in recent decades to pass less maturation of the mucosal barrier. A very clear dose-
vitamin D to the fetus, so newborns lack sufficient stores response relationship has been documented between the
at birth. As a result, breastfed infants now are given amount (full [exclusive], partial, token) and duration of
400 U daily from birth. Investigative work continues on breastfeeding and the benefits gained by the infant and
the benefits of providing pregnant and lactating women mother. (See Table 1 for the definitions.) Most bioactive
with 1,000 U of vitamin D daily. Most, but not all, infant factors exert their effects at the level of the mucosal
formulas contain 400 U of vitamin D in 26 to 32 oz of immune system. Igs are the best recognized and studied
reconstituted formula. bioactive components in human milk. Igs in human milk
Vitamin K content presents an important issue for the are predominantly secretory IgA, with much smaller
newborn who is born with low concentrations, even amounts of IgM and IgG. Colostrum contains higher
when the mother receives extra doses at the time of amounts of Igs and immunologically competent mono-
delivery. Hemorrhagic disease of the newborn, with GI nuclear cells than transitional or mature milk. The Igs
or intracranial hemorrhage and generalized bleeding, can function by binding directly to specific microbial anti-
present early or up to several weeks after birth and is due gens, blocking binding and adhesion to host cells,
to relative deficiencies of vitamin K-dependent coagula- enhancing phagocytosis, and modulating local immune
tion factors. Such deficiency has resulted in all newborns response. Table 3 in the online edition of this article lists
receiving 1 mg of vitamin K intramuscularly at birth, specific antibodies that have been identified in human
regardless of the proposed mode of feeding. If vitamin K milk.
is administered orally, multiple doses should be pro- The actual antibodies against specific microbial agents
vided. Formula has extra vitamin K, so an infant who present in an individual womans milk depends on her
receives 26 to 32 oz per day of formula receives 4 mg of exposure and response to the particular agents. Not
vitamin K orally daily. Concentrations in human milk and every mother has antibodies in her milk against every
cow milk are lower. microbe. The predominant action of Igs in human
milk is seen at the mucosal level of the infants mouth,
Immunologic Considerations of Human Milk nasopharynx, and GI tract, where they bind to and block
Neonates and infants are immunologically immature the infectious entry of microbial agents through the
and at increased risk for infection. Such developmental mucosal barrier. Although best recognized and remem-
immune defects are only some of the factors that place bered in association with specific protection against
infants at greater risk of infection. In the first 6 postnatal individual infectious agents, Igs provide only a small
months, phagocyte function is immature, with limited portion of the overall immunologic benefit of human
ability to migrate to the site of infection, and reserve milk.
production of phagocytes in response to infection is Other important individual bioactive proteins include
limited. Cell-mediated immunity develops throughout lactoferrin, lysozyme, alpha-lactalbumin, and casein.
childhood. Defects are particularly apparent in the first Lactoferrin exerts its effects via iron chelation, which
6 months after birth, including decreased cytokine pro- contributes to limiting bacterial growth, blocking adsorp-
duction, decreased natural killer cell function, poor stim- tion and penetration of viruses and adhesion of bacteria,
and enhancing intestinal cell growth and repair. Lyso- mation of toxic oxygen radicals. Various enzymes in
zyme binds to endotoxin, increases macrophage activa- human milk break down inflammatory molecules: cata-
tion, and contributes to bacterial cell wall lysis. Lactalbu- lase destroys hydrogen peroxide, histaminase destroys
min transports calcium and enhances the growth of histamine, and arylsulfatase degrades leukotrienes. Vari-
Bifidobacterium, and a modified lactalbumin (in the gut) ous soluble receptors in human milk (IL-1Ra, STNF-
affects immune modulation. Casein limits adhesion of alpha R1 and R2) bind to specific cytokines, blocking
bacteria and facilitates the growth of Bifidobacterium. their inflammatory action.
Carbohydrates are an important nutritional component Vitamins A, C, and E, which are present in higher
in human milk, and the specific carbohydrates lactose, concentrations in human milk than in cow milk, scavenge
oligosaccharides, and glycoconjugates act as bioactive oxygen radicals. Catalase and glutathione peroxidase as
factors. Oligosaccharides act as prebiotics, enhancing the well as lactoferrin serve multiple purposes and have anti-
growth of specific probiotic bacteria in breastfed infants, oxidant properties. Prostaglandins in human milk limit
and both oligosaccharides and glycoconjugates bind superoxide production. The sum total of these anti-
specific microbial antigens. inflammatory effects of human milk occurring at the
Lipids in the form of triglycerides, long-chain polyun- mucosal level limits damage to the mucosal barrier and
saturated fatty acids, and free fatty acids (FFAs) have a facilitates its ongoing growth and development to fur-
lytic effect on many viruses and are active against Giardia ther enhance human milks protection of the infant.
as well. Nucleotides, nucleosides, and nucleic acids com-
prise more than 15% of the nonprotein nitrogen in Infant Microflora, Probiotics, and Prebiotics
human milk. Nucleotides serve many crucial roles in The concept that normal intestinal microflora influ-
energy metabolism, nucleic acid production, and signal ence the development of the local mucosal immunity and
transduction, processes of increased importance during even prime systemic immunity is being supported by
the cellular activation and replication related to an active new research. Pathogen-associated molecular patterns in
immune response. Research related to the essential the microflora are recognized by toll-like receptors and
nature of nucleotides in protection against infection has may contribute to the expression of toll-like receptors on
led to the addition of nucleotides to some infant formu- intestinal epithelial cells as well as lead to program-
las. Cytokines and soluble receptors of cytokines are ming of systemic T-helper cell type 1 (TH1), TH2, and
other examples of bioactive factors that serve several TH3-like T-cell responses. Probiotic bacteria are organ-
functions. Cytokines can act as functional growth fac- isms that live symbiotically in the intestine, conferring
tors and have both inflammatory and anti-inflammatory additional benefits on the host, which include competi-
effects in different situations. tion with pathogenic organisms, strengthened tight
Hormones and growth factors, including erythropoi- junctions between cells, production of antimicrobial bac-
etin, epidermal growth factor, insulin, insulin-like teriocidins, increased mucin production, stimulated peri-
growth factor, nerve growth factor, and transforming stalsis, increased production of specific nutrients (argi-
growth factor-alpha, stimulate the growth and matura- nine, glutamine, small-chain fatty acids), and enhanced
tion of the GI tract and, to a degree, systemic growth. development of the mucosal immune system.
These bioactive factors are less specific than Igs, but by Prebiotics usually are nondigestible oligosaccharides
acting in concert with multiple factors, they provide the that, after fermentation, lower the pH of the local envi-
major portion of protective effects from human milk. rons and increase the amount of available FFAs. Prebiot-
ics enhance the growth of probiotic bacteria in the intes-
Anti-inflammatory Factors tine. Oligosaccharides are the third most common
The concept of immune protection without an extensive component in human milk in terms of quantity. Cow
and potentially damaging inflammatory response is gain- milk and formula contain less than one tenth of the
ing in significance in general medicine and in breastfeed- oligosaccharides in human milk by weight. The micro-
ing medicine. Many of the same protective bioactive flora of breastfed infants include Lactobacillus bifidus
factors act at the mucosal level without stimulating and Bifidobacterium, which comprise up to 95% of the
a significant inflammatory response, which indirectly culturable organisms. The remaining small portion of
decreases inflammation and possible local tissue damage. bacteria include Streptococcus, Bacteroides, Clostridium,
Certain factors limit further inflammatory stimulation: Micrococcus, and Enterococcus as well as Escherichia coli
lactoferrin blocks activation of complement, and lyso- and other organisms in even smaller numbers. The
zyme inhibits neutrophil chemotaxis and limits for- microflora of formula-fed infants are composed primarily
of gram-negative organisms (coliforms, Bacteroides, Clos- on transmission have documented approximately a 30%
tridium, Enterobacter, and Enterococcus) in much larger transmission rate in breastfed infants, 10% rate in
numbers than in breastfed infants and include very small mixed-feeding infants, and 0% rate in exclusively
amounts of Lactobacillus and Bifidobacterium. Lactoba- formula-fed infants. Researchers estimate that 1 mL of
cillus and Bifidobacterium ferment oligosaccharides, pro- human milk can contain 1,000 T cells infected with
ducing various acids, including FFAs, which lower the HTLV-1. Epidemiologic studies from areas of Japan that
pH in the intestine and limit the growth of potential have high rates of HTLV-1 have reported significant
pathogens such as E coli, Bacteroides, and Staphylococcus. reductions in transmission of the virus from mother to
New molecular techniques that analyze stool by detect- infant with avoidance of breastfeeding or limiting breast-
ing ribosomal RNA sequences of microbes are expanding feeding to less than 6 months duration.
the understanding of GI microflora and factors influenc- HIV-1 infection in the mother is another chronic
ing intestinal and immunologic development at the level infection that can be transmitted readily via human milk
of the gut. Multiple studies have suggested a protective to the infant. In the United States and other areas of the
role of specific intestinal microflora against the risk of world where HIV perinatal transmission prevention is
developing necrotizing enterocolitis (NEC) in preterm highly successful and safe alternatives to breastfeeding
and very low-birthweight infants. are available, acceptable, feasible, affordable, sustainable,
and safe, mothers who have HIV infection have been
Infectious Disease Considerations advised not to breastfeed their infants. In areas of the
Despite all the evidence for the immunologic benefits of world where there is an increased risk of infectious dis-
human milk and the protection afforded infants against eases, nutritional deficiencies, and significant morbidity
specific organisms and separate clinical illnesses, data also and mortality for infants who are not breastfed and
document the transmission of specific infections through replacement feeding is not available, exclusive breast-
human milk or direct contact with an infected maternal feeding by an HIV-positive mother can afford the infant
breast. Although only a few infections are transmitted the best chance of survival. HIV DNA is detectable easily
easily through human milk (human immunodeficiency in human milk and can be categorized as cell-free and
virus [HIV-1], human T-lymphotrophic viruses 1 and 2 cell-associated virus. Factors associated with an increased
[HTLV-1 and -2], and cytomegalovirus [CMV]), these risk of HIV transmission via breastfeeding include mixed
viruses are important because of their potential for caus- feeding versus exclusive breastfeeding, duration of
ing morbidity or mortality in the infant. In addition, breastfeeding, maternal illness and high viral loads,
other infections that are uncommonly transmitted by lower CD4 lymphocyte counts in the mother, and mas-
human milk or breast contact should be considered in titis or nipple lesions in the mother. Recent studies have
specific situations. documented that effective antiretroviral (ARV) treat-
Transmission of infection through human milk is ment of the HIV-positive mother along with exclusive
exceedingly rare compared with the more common breastfeeding can lead to lower transmission rates for
mechanisms of transmission for neonates and infants. infants and lower mortality for both mothers and infants.
Prenatal infection is congenital, occurring across the Prophylactic ARV treatment of the infant along with
placenta; perinatal infection is due to passage through exclusive breastfeeding also has been associated with
the birth canal; and postnatal infection occurs via air- decreased HIV transmission to the infant. Additional
borne, droplet, or contact transmission other than with carefully controlled research on exclusive breastfeeding,
the breast. The predominant modes of transmission and ARV therapy, and optimizing the infants nutrition and
the usual timing of infection are important consider- growth are needed before an optimal regimen can be
ations in different clinical situations. (2) Review of the devised.
considerations for transmission via human milk for Latent CMV infection or even recent CMV infection
selected organisms can be divided into bacterial, viral, in a breastfeeding mother is not a contraindication to
and other. See Tables 4 and 5 in the online edition of this breastfeeding. Postnatal CMV infection via human milk
article for summaries of the considerations for selected occurs readily, but viral presence is rarely, if ever, clini-
bacteria and viruses. cally significant in the term infant. In fact, breastfeeding
has been described as natural CMV immunization in
Viral Infections the term infant. Preterm, low-birthweight, and very low-
Chronic infection of the mother with HTLV-1 or -2 is birthweight infants are at risk for clinically significant
considered a contraindication to breastfeeding. Studies postnatal CMV infection via breastfeeding. This post-
natal infection is more likely to occur between 3 and mission via respiratory droplets, which is the same for
12 weeks postpartum, when virolactia occurs commonly. breastfeeding or formula-fed infants in contact with their
Pasteurization and freezing-thawing milk can decrease mothers. TB mastitis or TB lesions of the breast are rare.
the CMV load in human milk. A reasonable protocol has Breastfeeding or use of expressed human milk from the
been outlined for protecting susceptible infants while mother who has TB can continue once the mother is
using human milk in nurseries that include preterm and receiving appropriate antituberculous therapy and the
very low-birthweight infants. (3) The protocol includes infant is receiving isoniazid prophylactically.
screening mothers for CMV before providing human Staphylococcus or group A Streptococcus infection of
milk to their infants, pasteurizing or freezing-thawing the breast can interfere with breastfeeding. Breastfeeding
human milk from CMV-positive mothers before its use, or use of expressed human milk can continue when the
and observing infants in the nursery for evidence of acute mother is physically comfortable with the process, after
CMV infection.No prospective, controlled trials docu- a temporary suspension during the mothers initial
ment the protective effects of such a protocol. 24 hours of effective antibacterial therapy. Prophylactic
West Nile virus (WNV) is the only other virus for antibiotic therapy for the infant in conjunction with the
which there has been evidence for transmission via maternal treatment often allays additional fear.
human milk with any frequency. Several studies docu- In general, the same antibiotics used to treat a specific
ment the presence of WNV DNA as well as IgM and IgG infection in the mother are used and are safe in the infant
antibodies against WNV in human milk, but no clear and in the mothers milk. Antibiotics do enter human
evidence documents clinically significant illness in infants milk, but usually in very low concentrations, exposing
exposed through breastfeeding by mothers who have the infant to a daily dose well below the commonly used
WNV infection. The concern about viruses such as her- therapeutic dose prescribed for infants and children. The
pes simplex virus, varicella-zoster virus, vaccinia virus exceptions to this principle are doxycycline or tetracy-
(smallpox vaccine virus), or variola virus (smallpox virus) cline because of a concern for dental staining or altered
is transmission through contact with skin lesions that bone growth in the infant (short duration of therapy in
contain the virus on the mothers nipple or breast, not the mother [3 wk] generally is considered acceptable)
through virus excreted in the milk. Temporary avoidance and erythromycin, which has been associated with the
of breastfeeding and milk from the mothers breast that occurrence of infantile hypertrophic pyloric stenosis in
has an identified lesion due to one of these viruses may be young infants. Quinolone use has been increasing in
reasonable. Prophylactic antiviral treatment for the infant children due to the absence of significant adverse effects,
along with maternal antiviral treatment usually is ade- and the use of levofloxacin or ofloxacin in breastfeeding
quate to allow breastfeeding to continue. mothers appears to be without significant concerns,
Viruses commonly transmitted via the respiratory other than the potential for changing the gut flora of the
route (influenza, respiratory syncytial virus, severe acute infant and perhaps bacterial overgrowth with a resistant
respiratory syndrome-associated coronavirus) are not pathogen.
transmitted through human milk. Most frequently, by Additional considerations for group B Streptococcus
the time a specific respiratory illness is diagnosed in the (GBS) infection or colonization of the mother and trans-
mother, the infant has already been exposed via respira- mission to the infant include adherence to proposed
tory secretions. There is no reason to suspend breastfeed- guidelines for prevention of GBS disease in the infant,
ing or the use of expressed human milk, except when the frequent and back and forth nature of colonization
severe disease in the mother prevents the ability to obtain in mother-infant dyads, the difficulty in eradicating col-
human milk. The numerous bioactive factors (not Igs if onization in the mother or infant, and the fact that
it is early in the maternal infection) in human milk can transmission of GBS from mothers to infants occurs with
provide the infant some ongoing protection. and without evidence of mastitis in the mother. Acquisi-
tion of GBS infection via breastfeeding or human milk
Bacterial Infections remains uncommon compared with transmission via
The concern about bacterial infections in the mother close direct contact between mothers and infants. Close
is infection of the nipple or breast (mastitis or breast adherence to the guidelines for prevention of early GBS
abscess) that introduces the bacteria into the milk or disease in the infant is effective and important.
directly into the infants mouth. (See Table 4 for selected Other recommendations to decrease possible GBS
bacterial infections in the mother.) The risk of pulmo- transmission between mother and infant via human milk
nary tuberculosis (TB) in the mother is related to trans- include careful instruction of mothers and medical staff
on the appropriate techniques for expression, collection, Breastfeeding and Maternal Medications
and storage of expressed milk and on the signs and The risk of maternal medication to the breastfed infant
symptoms of mastitis to facilitate early recognition and is a frequent question for the physician. The answer
initiation of effective interventions. Breastfeeding or the depends on a number of factors that involve the infant,
use of expressed human milk can continue after a tem- including gestational age at birth, current age, weight,
porary suspension during the initial 24 hours of anti- feeding pattern, and total oral intake, and the mother,
bacterial treatment for the mother. Preventive or early such as medication dose and dosing pattern, route of
empiric antimicrobial therapy for the infant may be indi- administration, drug absorption, peak plasma concentra-
cated in specific clinical situations, along with the contin- tion and timing of that peak, volume of distribution,
uation of breastfeeding. molecular size of the drug, degree of ionization, pH,
solubility in water or lipids, degree to which the drug is
Fungal Infections protein bound, and oral bioavailability.
Candida infection of the breast and mucocutaneous A number of questions must be clarified to make an
Candida infection in the infant are the only pertinent informed decision about the use and the potential risk of
fungal infections related to breastfeeding and human the medication. If the drug passes into the milk, what is
milk. In general, antifungal therapy administered simul- the concentration in the milk? Is it absorbed by the infant
taneously to the infant and the mother is the most or is it not orally bioavailable as are many drugs that are
effective and appropriate treatment because of the ease effective only by the intravenous or intramuscular routes?
of colonization or recolonization in both mother and Is the infant able to detoxify and excrete the drug or does
infant. Numerous topical and systemic therapies are
it accumulate in the infants system? The milk/plasma
effective. Occasionally, persistent or recurrent Candida
ratio has been determined for a number of drugs by
infection adversely affects ongoing breastfeeding. Can-
measuring the concentration in the milk and maternal
dida infection of the breast is overdiagnosed. Consulta-
plasma simultaneously. A single point in time milk/
tion with a professional or physician who has extensive
plasma ratio does not give an accurate determination of
experience supporting and caring for the breastfeeding
how much the infant will receive. A concentration mea-
mother-infant dyad can facilitate effective treatment and
sured in the milk at the time of feeding is the only reliable
ongoing breastfeeding.
measure of what the infant receives.
Despite these questions, reliable measures of many
Parasitic Infections
common medications have been documented. Consider-
Transmission of parasites through breastfeeding or
human milk is not a significant concern. Although hook- able research has resulted in valuable estimations of the
worm infection occurs commonly in young children, and safety of many, but not all, drugs. The determination of
transmammary spread of helminths has been described the relative infant dose (RID) has been used to standard-
in veterinary medicine, little substantiated evidence sup- ize the method that estimates the amount of a given drug
ports the presence of hookworms in human milk or that the infant receives. The formula is:
significant infection in the infant due to a hookworm RID (%)absolute infant dose (mg/kg per day)
passed via human milk. Giardiasis in infants younger than maternal dose (mg/kg per day 100)
6 months of age is rare, and given the various factors
active against Giardia in human milk, transmission via These calculations assume average metabolism and a
this route is highly unlikely. There is no evidence for maternal dose in the usual therapeutic range. The accept-
transmission of malaria via human milk, but the mother able RID of a drug is 10% or less for term infants, who
and infant both need to be protected from contact with have a clearing capacity about one third that of the adult.
infected mosquitoes. Maternal treatment or prophylaxis Preterm infants are less efficient at clearing drugs, with
for malaria during breastfeeding can be accomplished capacity only 5% of the adult capacity at 24 to 28 weeks
safely with various agents, such as chloroquine, quinine, gestation and only 10% at 28 to 34 weeks gestation.
pyrimethamine-sulfadoxine, tetracycline, mefloquine, After 7 months of age, however, the infant can handle
and primaquine, with some attention to the age of the most drugs at adult concentrations. The RID is avail-
child, the duration of exposure, and short periods of able for many medications from reference data banks
pumping and dumping of expressed milk during the such as the Library of Medicine data bank at http://
use of mefloquine. Transmission of Toxoplasma gondii or toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT. Other
Trichomonas via human milk has not been demonstrated. resources are Medications and Mothers Milk (4) and the
University of Rochester Breastfeeding and Human Lac- in human milk, using a medication in the same classifica-
tation Study Center Drug Line (585/275-0088). tion of drugs that have the lowest RID, avoiding long-
The AAP Committee on Drugs has published catego- acting preparations of medications, scheduling dosing
ries of drugs and their safety for use while breastfeeding. so the medication concentration in the milk is lowest
If the drug is prescribed normally for term or preterm when the infant feeds, taking the medication immedi-
infants, it is considered safe via human milk. If the infant ately after breastfeeding or breastfeeding just before the
also needs a drug such as an antibiotic, it must be next dose when the medication is taken several times a
administered directly to the infant. If the medication is day, and observing the infant for changes in behavior
not bioavailable orally, the infant cannot absorb it from while administering the medication to the mother.
the stomach. Large molecules such as insulin, heparin,
and many Igs do not pass into milk from maternal Use of Human Milk in Preterm Infants
plasma. All of the benefits of human milk are magnified in the
Drugs of abuse or street drugs are considered contra- preterm infant. If the infant can receive oral feeding,
indicated, and breastfeeding is not recommended. For a mothers milk is the safest and best tolerated of all the
mother actively participating in a methadone mainte- available feedings. Human milk can be introduced earlier
nance program, the potential benefits of breastfeeding than the foreign protein of formula. All of the infection
and human milk for the mother and infant should be protection qualities and the antibodies found naturally in
considered strongly. Breastfeeding can be recommended human milk protect against infection, especially NEC.
in certain situations in which there has been good pre- The limitations are the ability of the mother to pump her
natal care, maternal compliance with a drug addiction milk and make it available. Milk banks are available
recovery program before birth, and negative maternal throughout the country that can provide pasteurized
urine toxicology screens for 12 weeks before and at human milk from approved donors. The concerns of the
delivery. Women who have been stable on a methadone neonatologist stem from the inability to measure the
maintenance program should be permitted to breastfeed. volume consumed when the infant is at the breast and the
Evidence suggests that methadone-exposed infants may need for additional calories in the limited volumes toler-
have less severe symptoms of neonatal abstinence syn- ated by extremely immature infants. The quick solution
drome when maintained after delivery on human milk. is to add concentrated formula from powder or liquid
Immunosuppressant drugs, such as methotrexate, are made from bovine milk, known by the misnomer
contraindicated. However, some newer antimetabolites human milk supplementer. This preparation contains
or cancer drugs have very short half-lives. A drug is none of the protective factors of human milk and inter-
considered to clear the body within 5 times the half-life. feres with those present in any human milk provided.
If the half-life is 2 hours, it will clear in 10 hours, during One commercially available supplementer made exclu-
which time the mother can pump and discard her milk. sively from human milk has been shown to promote
The infant can be fed previously pumped milk or a growth in preterm infants as well as protect against
suitable substitute during that interim period. infection, especially NEC.
Radioactive compounds have been studied widely. Because women today commonly are deficient in vita-
The clearance half-life has been measured for most of the min D, even while taking prenatal vitamins during preg-
radioactive compounds used diagnostically or therapeu- nancy, their infants have inadequate stores at birth, espe-
tically. The same formula (5half-lifeclearance time) cially if born preterm. Vitamin D supplementation is
can be used to determine how long a mother needs to required if the preterm infant is receiving mothers milk
pump and discard her milk. However, when the half-life (400 U daily).
is longer than 3 days, it is impractical to have a mother Ideally, preterm nurseries have nursing staff who are
pump and discard for 15 days or longer, although this also certified lactation consultants and can assist mothers
determination is an individual decision. Radioactive iodine who wish to pump and provide their milk. The consul-
falls in this category. Iodine 131 in therapeutic doses takes tants can advocate for the mother who is ready and eager
3 to 5 weeks to clear the maternal system. to feed her preterm infant at the breast. All neonatal
In summary, drugs that are administered routinely to intensive care units should provide electric breast pumps
infants are safe to prescribe for the breastfeeding mother. and private accommodations to pump. Freezers and
Important considerations for minimizing the amount of refrigerators should be designated for sole storage of
medication to which the breastfeeding infant is exposed human milk. Pumped milk should be stored in freezer-
include choosing the drug present in the lowest amount safe containers that can be sealed and labeled with name,
unit number, date, and time of collection, so milk can be age. The Healthy People 2020 goals for breastfeeding were
fed sequentially, beginning with the antibody-rich colos- released in late 2010 (http://www.healthypeople.gov/
trum. Most neonatal intensive care units have feeding 2020/topicsobjectives2020/overview.aspx?topicid26)
protocols geared to the gestational age and weight of the and show some changes. Anticipated rates are changed,
infant. Mothers milk can be used if these guidelines are and methods to reduce barriers are included. The goals
followed. are:
At the time of discharge, some preterm infants still
need added calories, which can be provided by bioen- Infants ever breastfed: 82%
gineering, in which the mother pumps 5 mL of milk Infants breastfeeding at 6 months: 60.6%
from the breast first (and saves it frozen for weeks to be Infants exclusively breastfed through 3 months: 46.2%
used later). She then feeds just the hind milk, which is Infants exclusively breastfed through 6 months: 25.5%
higher in calories and fat than the foremilk. Some nurs-
The WHO multicenter growth reference was conducted
eries have the ability to measure the caloric content of
in six countries (Brazil, Ghana, India, Norway, Oman,
mothers milk from a sample taken from each pumping
and the United States) between 1997 and 2003. The
for 24 hours. The average caloric measure is 20 kcal/oz,
study consisted of a longitudinal follow-up of 882 infants
with a range of 15 to 24 kcal/oz. The milk can be
from birth to 24 months of age and a cross-sectional
supplemented as necessary or, in the case of high-calorie
study of 6,669 children ages 18 to 71 months. Children
producers, not at all. The initial milk produced by moth-
included in the study were healthy infants living in socio-
ers who deliver preterm has been demonstrated to be
economic situations favorable to growth, who were
higher in protein, calcium, sodium, and calories for the
breastfed exclusively for at least 4 months and were
first few weeks. Although an advantage to the infant, lack
introduced to complementary foods at 6 months of age,
of bedside technology does not permit factoring in this
with breastfeeding continuing up through 12 months of
nutrient variation in the feeding orders.
age. The tables and charts (www.who.int/childgrowth/
en) created through this study depict normal human
Current Recommendations
growth under optimal environmental conditions. The
The World Health Organization (WHO), United Nations
curves for the six different countries were virtually super-
Childrens Fund, AAP Section on Breastfeeding, Amer-
imposable on each other for height and weight growth
ican College of Obstetricians and Gynecologists, Amer-
through 60 months of age. These standards now identify
ican Academy of Family Physicians, Academy of Breast-
breastfeeding as the biologic norm for growth and devel-
feeding Medicine, and many other health organizations
opment and add further evidence for the recommenda-
recommend exclusive breastfeeding for the first 6 post-
tions of exclusive breastfeeding through 4 to 6 months
natal months. Numerous obstacles to the initiation and
of age.
continuation of breastfeeding remain within health-care
Pediatricians and other health-care professionals
settings, the workplace, communities, and the media.
across the United States should continue to recommend
The goals for Healthy People 2010 for breastfeeding
the use of human milk for all infants, with few exceptions
in the United States were: 1) initiation of any breastfeed-
(Table 6). A balanced presentation of up-to-date infor-
ing in 75% of infants in the early postpartum period,
mation on the benefits and process of breastfeeding
2) continuation of any breastfeeding in 50% of infants
should be provided to all parents to assist them in making
at 6 months of age, 3) continuation of any breastfeeding
an informed decision for the feeding of their infants.
in 25% of infants at 1 year of age, 4) exclusive breast-
Pediatricians and other health-care professionals should
feeding in 40% of infants at 3 months of age, and 5) exclu-
adopt and promote the Ten Steps to Successful Breast-
sive breastfeeding in 17% of infants at 6 months of age.
feeding in all maternity services and facilities providing
The Centers for Disease Control and Prevention have
care to infants and children (Table 7).
reported preliminary survey data on breastfeeding rates
in the United States for infants born in 2006. Although
rates have improved since 1999, they still fall below the In-hospital Breastfeeding Policies: Early and
Healthy People 2010 goals. For infants born in 2006, Frequent Contact of Mother and Infant
74% initiated breastfeeding, 43% continued breastfeed- Hospital management of the mother-infant dyad who
ing at 6 months, and 23% continued at 12 months of age. plan to breastfeed are clearly spelled out by the WHO-
An estimated 33% of infants were exclusively breastfed UNICEF ten steps that have been endorsed by the AAP
through 3 months of age and 14% through 6 months of (Table 7). The AAP did take exception to the recommen-
PIR Quiz
Quiz also available online at http://pedsinreview.aappublications.org.
1. Skin-to-skin contact between an infant and mother in the first hour after birth has been associated with:
A. Calmer personality.
B. Earlier attachment.
C. Faster infant development.
D. Greater emotional stability.
E. More successful breastfeeding.
2. The most definitive studies showing a reduction in atopic dermatitis following at least 3 months of
breastfeeding involved:
A. Children younger than 10 years of age who had a family history of asthma.
B. Children older than 10 years of age who had with a family history of asthma.
C. Children who had no family history of asthma.
D. Infants who had a family history of atopy.
E. Infants who had no family history of atopy.
3. Vitamin K has been administered routinely to newborns for many years. Which of the following vitamins
has also been recommended for supplementation from birth?
A. A.
B. B.
C. C.
D. D
E. E.
4. In the United States, infection with which of the following viruses is a contraindication to breastfeeding?
A. Cytomegalovirus.
B. Human immunodeficiency virus.
C. Respiratory syncytial virus.
D. Varicella-zoster virus.
E. West Nile virus.
5. The earliest age at which most infants can metabolize drugs at adult rates is:
A. 1 week.
B. 1 month.
C. 4 months.
D. 8 months.
E. 1 year.
*Section of Adult and Pediatric Endocrinology, The University of Chicago Pritzker School of Medicine, Chicago, IL.
orchidometer dimensionsellipsoid of revolution: volume0.52length(0.64length)2.
Figure 4. Relationship of key pubertal stages to pubertal growth velocity. Top panel: After a slight deceleration in growth, female
puberty begins with breast development. Pubic hair development soon follows, and linear growth accelerates. Girls achieve peak height
velocity approximately 1 year before menarche. Note that the current estimates for attainment of pubertal milestones in normal-weight
girls (Table 1) are about 0.25 years (pubic hair stage 3) to 0.5 years (breast stage 2) earlier than these 1985 estimates from Tanner and
Davies (1985). (11) Bottom panel: After a slight deceleration in growth, male puberty begins with testicular enlargement to genital stage
2 (volume >3 mL). Pubic hair development soon follows, and linear growth accelerates. Boys achieve peak height velocity before entering
genital stage 5 (testis volume 12 mL). Note that the current estimates for pubic hair stage 3 milestones (Table 1) are 0.5 year earlier than
these 1985 estimates. Modified from Bock and Rosenfield (18) and Tanner and Davies. (11)
sex hormone production. The condition is five times cation for an evaluation to rule out estrogen excess,
more common in girls than in boys, and 90% of cases in androgen deficiency, or liver dysfunction.
girls are idiopathic. Conversely, complete precocious
puberty is idiopathic in only 50% of boys. Consequently, Puberty Too Late: Delayed Puberty
organic central nervous system disorders, of virtually any Delayed puberty is defined as lack of breast development
cause, are more prevalent in precocious boys than in by age 13.0 years in girls and lack of pubertal testicular
precocious girls. An activating mutation of GPR54, a key development (genital stage 2) by age 14.0 years in boys
factor in the hypothalamic signaling system regulating (Table 1). The delay is accompanied by slowing of linear
pubertal GnRH release, has been reported to cause pre- growth velocity, and sometimes the accompanying short
mature puberty. (39) stature is the primary complaint.
Precocity in the 6- to 8-year age range usually is not Most delayed puberty does not have a serious cause
rapidly progressive and may not require specific treat- because it is due to an extreme variant of normal, known
ment. Overweight and obesity may be the underlying as constitutional delay of pubertal growth and devel-
cause in many such cases. However, rapidly progressive opment, which is seen more commonly in boys. This
precocity, particularly if before 6 years of age or if asso- condition results from unexplained delay in the onset
ciated with vaginal bleeding at breast stage 2, requires of pubertal HPG activation, ie, prolongation of the
investigation and treatment. physiologic gonadotropin deficiency of childhood. Once
Other causes of precocious puberty include puberty begins, its course and tempo are normal, and
gonadotropin-independent precocious puberty, which catch-up growth to target height occurs. If puberty does
results from intrinsic adrenal or gonadal disorders or not begin in a boy by 18 years of age, it is pathologic. In
exogenous hormones. The most common of these con- the meantime, the self-image of many constitutionally
ditions are nonclassic congenital adrenal hyperplasia delayed boys benefits significantly from short physiologic
(which is mildly virilizing), McCune-Albright syndrome (low-dose) courses of androgen replacement therapy
(which typically feminizes girls), and testotoxicosis under the care of a pediatric endocrinologist.
(primary Leydig cell hyperplasia, which causes moderate Delayed puberty also can be caused by a variety of
masculinization in boys); neoplasms are rare possibilities chronic endocrine, metabolic, and systemic disorders.
to consider. Undernutrition underlies the delayed puberty of disad-
Vaginal bleeding in the absence of breast develop- vantaged populations. Screening tests for general health
ment is not likely to be hormonally mediated. Alter- (eg, complete blood count, comprehensive metabolic
nate causes, such as foreign body, abuse, or genital tract panel, erythrocyte sedimentation rate, and thyroid func-
neoplasm, should be explored. tion tests) are indicated, as are gonadotropin concentra-
tions to assess the possibility of hypogonadism.
Puberty Too Much: Sex Steroid Excess
Disorders
Hirsutism, excessive sexual hair development in a female Puberty Too Little: Hypogonadism
(as distinguished from a generalized excess of body hair Hypogonadism is suspected when the patient experi-
or hypertrichosis), is a normal variant when mild and ences too little pubertal development, micropenis, or
isolated. However, when accompanied by menstrual cryptorchidism. Obesity is a common confounder in the
abnormality or when severe, hyperandrogenism must be diagnosis of micropenis because a prominent suprapubic
considered, and PCOS accounts for about 85% of these fat pad obscures penile development (pseudomicro-
cases. (40) PCOS is a disorder of otherwise unexplained penis), but normalcy of penile development is demon-
hyperandrogenic anovulation that manifests typically strable by palpation of the full length of the penile
in the perimenarchal stage of development. PCOS gen- corpus. Failure of the testes to descend is a risk factor for
erally is due to functional ovarian hyperandrogenism. infertility and testicular malignancy. (41) These risks
About 50% of affected girls are obese, and 50% of these appear to increase with the severity of the cryptorchidism
have metabolic syndrome. and time to orchiopexy beyond infancy. Retractile testes
During puberty, most boys develop transient gyneco- were believed to be spared these risks, but recent studies
mastia. However, a mid-adolescent female degree of suggest that about one third of retractile testes ascend to
breast development in a boy (macromastia) can be become cryptorchid and lose germ cells. Accordingly,
expected to persist. Although usually an extreme variant health supervision visits should include assurance of the
of normal, this degree of breast development is an indi- scrotal position of the testes.
21. Rosenfield RL. Essentials of growth diagnosis. Endocrinol Control in Children1987. Task Force on Blood Pressure Control
Metab Clin N Am. 1996;25:743758 in Children. National Heart, Lung, and Blood Institute, Bethesda,
22. Bayley N, Pinneau S. Tables for predicting adult height from Maryland. Pediatrics. 1987;79:125
skeletal age: revised for use with the Gruelich-Pyle hand standards. 34. Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Second-
J Pediatr. 1952;40:432 441 ary sexual characteristics and menses in young girls seen in office
23. American Academy of Pediatrics Committee on Adolescence; practice: a study from the Pediatric Research in Office Settings
American College of Obstetricians and Gynecologists Committee Network. Pediatrics. 1997;99:505512
on Adolescent Health Care, Diaz A, Laufer MR, Breech LL. 35. Lucky AW, Rich BH, Rosenfield RL, Fang VS, Roche-Bender
Menstruation in girls and adolescents: using the menstrual cycle as N. A useful test to discriminate true precocious puberty from
a vital sign. Pediatrics. 2006;118:22452250 premature thelarche and adrenarche. J Pediatr. 1980;97:214 216
24. Zhang K, Pollack S, Ghods A, et al. Onset of ovulation after 36. Pescovitz OH, Hench KD, Barnes KM, Loriaux DL, Cutler
menarche in girls: a longitudinal study. J Clin Endocrinol Metab. GB, Jr. Premature thelarche and central precocious puberty: the
2008;93:1186 1194 relationship between clinical presentation and the gonadotropin
25. Steinberg L, Morris AS. Adolescent development. Annu Rev response to luteinizing hormone-releasing hormone. J Clin Endo-
Psychol. 2001;52:83110 crinol Metab. 1988;67:474 479
26. Finkelstein JW, Susman EJ, Chinchilli VM, et al. Estrogen or 37. Klein KL, Mericq V, Brown-Dawson JM, Larmore KA,
testosterone increases self-reported aggressive behaviors in hypogo- Cabezas P, Cortinez A. Estrogen levels in girls with premature
nadal adolescents. J Clin Endocrinol Metab. 1997;82:24332438
thelarche compared with normal prepubertal girls as determined by
27. Susman EJ, Finkelstein JW, Chinchilli VM, et al. The effect of an ultrasensitive recombinant cell bioassay. J Pediatr. 1999;134:
sex hormone replacement therapy on behavior problems and
190 192
moods in adolescents with delayed puberty. J Pediatr. 1998;133:
38. Rosenfield RL. Identifying children at risk of polycystic ovary
521525
syndrome. J Clin Endocrinol Metab. 2007;92:787796
28. Dewald JF, Meijer AM, Oort FJ, Kerkhof GA, Bogels SM. The
39. Teles MG, Bianco SD, Brito VN, et al. A GPR54-activating
influence of sleep quality, sleep duration and sleepiness on school
mutation in a patient with central precocious puberty. N Engl
performance in children and adolescents: a meta-analytic review.
J Med. 2008;358:709 715
Sleep Med Rev. 2010;14:179 189
29. Feinberg I, Higgins LM, Khaw WY, Campbell IG. The ado- 40. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med.
lescent decline of NREM delta, an indicator of brain maturation, is 2005;353:2578 2588
linked to age and sex but not to pubertal stage. Am J Physiol Regul 41. Thorup J, McLachlan R, Cortes D, et al. What is new in
Integr Comp Physiol. 2006;291:R1724 R1729 cryptorchidism and hypospadiasa critical review on the testicular
30. Mayo Medical Laboratories 2010 Reference Laboratory Services dysgenesis hypothesis. J Pediatr Surg. 2010;45:2074 2086
for Health Care Organizations. Rochester, MN: Mayo Clinic. 42. American Academy of Pediatrics Policy Statement. Iden-
Accessed April 2011 at: www.mayomedicallaboratories.com tifying and treating eating disorders. Pediatrics. 2003;111:
31. Tobiume H, Kanzaki S, Hida S, et al. Serum bone alkaline 204 211
phosphatase isoenzyme levels in normal children and children with 43. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin
growth hormone (GH) deficiency: a potential marker for bone in women with hypothalamic amenorrhea. N Engl J Med. 2004;
formation and response to GH therapy. J Clin Endocrinol Metab. 351:987997
1997;82:2056 2061 44. Southam A, Richart E. The prognosis for adolescents
32. Hickman TB, Briefel RR, Carroll MD, et al. Distributions and with menstrual abnormalities. Am J Obstet Gynecol. 1996;94:
trends of serum lipid levels among United States children and 637 645
adolescents ages 4 19 years: data from the Third National Health 45. Braverman PK, Breech L. American Academy of Pediatrics.
and Nutrition Examination Survey. Prev Med. 1998;27:879 890 Clinical report gynecologic examination for adolescents in the
33. Horan M. Report of the Second Task Force on Blood Pressure pediatric office setting. Pediatrics. 2010;126:583590
PIR Quiz
Quiz also available online at http://pedsinreview.aappublications.org.
6. Normal pubertal development varies according to a childs weight and ethnicity. Which of the following
clinical findings indicates premature pubertal development?
A. Penile enlargement in a 10-year-old African American male of normal weight.
B. Stage 3 pubic hair in a 7-year-old Mexican American girl of normal weight.
C. Testicular enlargement in a 9-year-old white boy who is obese.
D. Thelarche in a 7-year-old African American girl of normal weight.
E. Thelarche in a 9-year-old white girl who is obese.
7. You are seeing a 13-year-old girl who experienced menarche 3 months ago. Her physical examination
shows that the areolae form a secondary mound above the contour of her breasts. Her pubic hair is curly
and coarse and covers the lower portion of her mons pubis. Which of the following is the most accurate
description of her Sexual Maturity Rating?
A. Breast: stage 2, pubic hair: stage 3.
B. Breast: stage 3, pubic hair: stage 3.
C. Breast: stage 3, pubic hair: stage 4.
D. Breast: stage 4, pubic hair: stage 4.
E. Breast: stage 4, pubic hair: stage 5.
9. Which of the following patients should undergo an evaluation to rule out organic pathology as a cause for
abnormal pubertal development at this time?
A. A 6-year-old white girl who has unilateral thelarche, normal growth velocity, and no pubic hair
development.
B. A 7-year-old Mexican American boy who has breast development and testicular enlargement.
C. A 13-year-old African American girl who has a recent growth spurt and no menarche.
D. A 13-year-old white boy who has no testicular enlargement and normal growth velocity.
E. A 16-year-old African American girl who has excessive pubic hair and normal menstrual cycles.
The D-test
Kamakshya P. Patra, MD*
for detection of inducible clindamy- appropriate antibiotic therapy and aureus isolates. J Clin Microbiol. 2006;
cin resistance in all staphylococcal may contribute to avoidable failures 44:24812484
Prunier AL, Malbruny B, Laurans M,
isolates. The recommendation sug- of pharmacotherapy.
Brouard J, Duhamel JF, Leclercq R.
gested that all laboratories report High rate of macrolide resistance in
D-test-positive isolates as being resis- Staphylococcus aureus strains from pa-
tant to clindamycin. CLSI also sug- tients with cystic fibrosis reveals high
Suggested Reading proportions of hypermutable strains.
gested that a comment be added: Frank AL, Marcinak JF, Mangat PD, et al. J Infect Dis. 2003;187:1709 1716
This isolate is presumed to be Clindamycin treatment of methicillin- Sattler CA, Mason EO, Jr, Kaplan SL. Pro-
resistant based on detection of in- resistant Staphylococcus aureus infections spective comparison of risk factors and
ducible clindamycin resistance. Clin- in children. Pediatr Infect Dis J. 2002; demographic and clinical characteristics
21:530 534 of community-acquired, methicillin-
damycin may still be effective in some Lewis JS, Jorgensen JH. Inducible clinda- resistant versus methicillin-susceptible
patients. mycin resistance in staphylococci: Staphylococcus aureus infection in chil-
Despite the above guidelines, use should clinicians and microbiologists be dren. Pediatr Infect Dis J. 2002;21:
of the D-test still is not universal. concerned? Clin Infect Dis. 2005;40: 910 917
280 285 Siberry GK, Tekle T, Carroll K, Dick J.
Physicians in primary care and spe- NCCLS (CLSI). Performance Standards for Failure of clindamycin treatment of
cialty settings must be aware of Antimicrobial Susceptibility Testing. methicillin-resistant Staphylococcus au-
whether a D-test has been performed Wayne, PA: NCCLS (CLSI); 2004: reus expressing inducible clindamycin
to determine the presence of induc- M100 S14 resistance in vitro. Clin Infect Dis. 2003;
Patel M, Waites KB, Moser SA, Cloud GA, 37:12571260
ible clindamycin resistance in S au- Hoesley CJ. Prevalence of inducible clin- Woods CR. Macrolide-inducible resistance
reus isolates. Varying use of the damycin resistance among community- to clindamycin and the D-test. Pediatr
D-test may cause delay in initiating and hospital-associated Staphylococcus Infect Dis J. 2009;28:11151118
Corrections
In the In Brief article entitled Balance and Vertigo in Children in the February issue
(Pediatr Rev. 2011;32:84 85), the next-to-last sentence in the third column on page 84
should read, The attack is induced by head movements or positional changes. This
condition is very similar to benign paroxysmal positional vertigo in adults and may be the
same condition. Current thinking is that the pediatric disorder is a migraine equivalent,
whereas the adult condition is attributed to calcium crystals in the semicircular canals,
although the cause of the pediatric disorder is not clear.
In the Visual Diagnosis case published in the June issue (Pediatr Rev. 2011;32:253255),
the correct designation for the third author is Kenneth Cochran, RN.
Disease
Negative Test
c d
Result
ac bd
Sensitivity a/(ac)
Specificity d/(bd)
LR for a positive test [a/(ac) b/(bd)] or sensitivity (1-specificity)
LR for a negative test [c/(ac) d/(bd)] or (1-sensitivity) specificity.
rectal temperature of 35.2C, scleral sodes, with chills before the onset of tinal parasites performed before en-
icterus, and jaundice to the lower fevers. Recurrent fever episodes have doscopy were negative. The serum
abdomen. He does not have hepato- been so debilitating that he has immunoglobulin E (IgE) concentra-
splenomegaly, and he has normal missed many school days, prompting tion was normal, and radioimmune
male genitalia. an investigation for neglect. He has absorption studies for a panel of food
His serum glucose concentration had many evaluations in the past, allergens were negative. Evaluation
is 36 mg/dL (2.0 mmol/L), total none of which have determined the for celiac disease (duodenal biopsy,
bilirubin is 13.3 mg/dL (227.5 cause of his fevers. antigliadin, and antitransglutaminase
mol/L), and direct bilirubin is His weight and height are at 95th antibodies) was negative. Results of
3.1 mg/dL (53.0 mol/L). Results percentile. His temperature is the inflammatory bowel disease
of additional laboratory tests are as 40.3C, heart rate is 81 beats/min, (IBD) serology 7 panel were strongly
follows: negative full sepsis evalua- respiratory rate is 22 breaths/min, indicative of Crohn disease (CD).
tion (blood, urine, and CSF cul- blood pressure is 110/58 mm Hg, The boy was treated with balsalazide,
tures); negative urine and serum and oxygen saturation is 98% in room calcium, vitamin D, and pred-
studies for cytomegalovirus; normal air. He appears well but tired. Physi- nisolone, which resulted in resolu-
CBC, peripheral smear, and reticulo- cal findings are unremarkable except tion of the symptoms, weight gain,
cyte count; normal serum electrolyte for enlarged bilateral posterior cervi- and normalization of abnormal labo-
values; nonreactive hepatitis A, B, cal lymph nodes, with the largest be- ratory values.
and C studies; normal serum gamma ing 1 cm.
glutamyl transpeptidase, total pro- Laboratory results show a WBC Differential Diagnosis
tein, albumin, alkaline phosphatase, count of 9.6103/L (9.6109/L) Hypocalcemia at this age has myriad
ammonia, and lactic acid values; nor- (69% neutrophils, 19% lymphocytes, causes, including hypovitaminosis D,
mal urine organic and amino acids; 10% monocytes, and 2% eosino- malabsorption, hyperphosphatemia,
and normal plasma amino acids. phils). Liver function tests and hypomagnesemia, hypoparathyroid-
Maximal concentrations of serum urinalysis results are normal. The an- ism, and poor diet as well as disorders
AST and ALT are 249 and 139 U/L, tinuclear antibody as well as Epstein- of liver and kidney. Hypoalbumine-
respectively. Abdominal ultrasonog- Barr virus and human immunodefi- mia, anemia, and gastrointestinal
raphy yields normal results. Addi- ciency virus antibodies are negative. symptoms were clues suggesting ma-
tional imaging and laboratory studies ESR is 24 mm/hr and C-reactive labsorption. This boys clinical pre-
reveal the cause of his hypoglycemia, protein is 9.52 mg/dL. Additional sentation and laboratory evaluation,
hypothermia, and hyperbiliru- laboratory evaluation reveals his including serologic markers, led to
binemia. diagnosis. the diagnosis of CD.
The Condition
Case 3 Presentation Case 1 Discussion CD is an idiopathic chronic inflam-
A 7-year-old boy is transferred from Abdominal CT scan was obtained matory disease of the bowel that can
another facility to rule out lymphoma because of abdominal pain of long affect any part of the digestive tract,
because of a 2-day history of temper- duration and showed thickening of from mouth to anus, and has an an-
atures up to 40.6C and an enlarged the wall of the terminal ileum (Fig. nual incidence of approximately 3 to
posterior cervical lymph node. He 1). Endoscopy revealed hypertro- 5 per 100,000. Around 30% of pa-
does not have runny nose, cough, phied mucosa at the greater curva- tients are diagnosed before 20 years
nausea, vomiting, or diarrhea. He has ture of the stomach, rectosigmoid of age. As per the Montreal classifica-
had recurrent episodes of high fever junction, and distal splenic flexure. tion, patients may be classified by
(temperatures of 40.0 to 40.6C) Biopsies from the esophagus, stom- age, location (ileum, colon, ileocolic,
over the past 6 years, beginning at 6 ach, duodenum, jejunum, and termi- or upper GI tract), and disease be-
months of age, occasionally accom- nal ileum yielded numerous eosino- havior (inflammatory, stricturing, or
panied by abdominal pain. The fre- phils (15/high-power field) (Fig. 2). penetrating). (1) Fewer than one
quency of fever has been increasing Gastric and duodenal biopsies were third of patients present with the
over the past 3 years, now occurring negative for Helicobacter pylori, and triad of abdominal pain, diarrhea,
nearly every month. He is usually there was no evidence of cryptitis or and weight loss. Extraintestinal
drowsy and sleepy during fever epi- abscess. Serial stool analyses for intes- symptoms are more common in CD
type or enzyme activity should be (Kamakshya P. Patra, MD, Vedanta ties (such as agenesis of the corpus
evaluated before beginning therapy Dariya, MD, Wanda Thomas, MD, callosum and absence of the septum
with thiopurines because this status John Herbst, MD, Louisiana State pellucidum), and pituitary hypopla-
can affect response and toxicity. University Health Sciences Center, sia with associated hypopituitarism.
Methotrexate is used in patients who Shreveport, LA) Generally, two of the three condi-
develop resistance or toxicity to aza- tions must be present for diagnosis.
thioprine and 6-mercaptopurine. The disorder is equally prevalent in
Infliximab (a monoclonal anti- Reference males and females. Most cases are
body to tumor necrosis factor) is 1. Silverberg MS, Satsangi J, Ahmad T, et sporadic, but familial cases have been
al. Toward an integrated clinical, molecular
used in patients who have suboptimal described. For unknown reasons,
and serological classification of inflamma-
responses to conventional therapy. tory bowel disease: report of a working party cases occur more often in infants
Adverse reactions include infusion of the 2005 Montreal World Congress of born to young mothers.
reaction, reactivation of latent tuber- Gastroenterology. Can J Gastroenterol. Clinical features in infancy may
culosis, opportunistic infections, de- 2005;19(suppl A):536 include respiratory distress on the
myelinating disease, development of first postnatal day, metabolic acido-
autoantibodies, and T-cell lym- sis, hypotonia, severe hypoglycemia,
phoma. Metronidazole or cipro- Case 2 Discussion hypogenitalism, and midline CNS
floxacin is used as initial therapy for Additional laboratory test results in- defects. As many as two of three pa-
perirectal fistulas. Nonhealing cases cluded the following: serum cortisol tients develop endocrine deficits
require thiopurines or infliximab. at 10:20 PM was 1.1 g/dL ranging from isolated GHD to pan-
Surgery is indicated when there is (30.3 nmol/L) (normal PM range, hypopituitarism; progressive loss of
perforation, stricture, intractable 2 to 10 g/dL [55.2 to 275.9 nmol/ endocrine function may occur over
bleeding, abscess, or disease refrac- L]), thyroid-stimulating hormone time. Both cholestatic and nonchole-
tory to medical treatment. Nutri- was 6.25 mIU/mL (normal range, static jaundice have been associated
tional rehabilitation and psychosocial 0.6 to 10.0 mIU/mL), and free with the condition. Hyperbiliru-
therapy are important adjunctive thyroxine was 0.8 ng/dL (10.3 binemia resolves in most cases once
treatments. pmol/L) (normal range, 0.6 to hormonal replacement therapy is ini-
CD is a chronic disorder that in- 1.75 ng/dL [7.7 to 22.5 pmol/L]). tiated. Neurologic deficits are com-
volves remissions and intermittent Brain MRI revealed an ectopic poste- mon but highly variable, ranging
disease flares. Onset before 20 years rior pituitary gland and pituitary from severe intellectual disability to
of age is associated with a poorer gland hypoplasia, absence of the an- mild focal deficits.
prognosis. Because extensive and terior portion of the septum pelluci-
long-standing disease increases the dum, and hypoplasia of the left optic Diagnosis
risk for malignancy, screening is rec- nerve and optic chiasm. These find- Hypoglycemia and hypothermia
ommended for older patients. ings are consistent with septo-optic (with or without hyperbilirubinemia)
dysplasia (SOD), also known as De in the newborn period always should
Lessons for the Clinician Morsier syndrome. raise concern for sepsis, and a thor-
Tetany can be an initial presenta- The patient was treated initially ough evaluation and appropriate
tion of CD. A high degree of sus- with hydrocortisone, and levothy- treatment should ensue.
picion is required because CD has roxine was added subsequently. Be- Causes of hypoglycemia in the
protean manifestations. cause of persistent hypoglycemia, newborn period include hyperinsu-
Diagnosing CD can be a challenge growth hormone deficiency (GHD) linemia (as occurs in infants born
because often endoscopy and bi- was diagnosed clinically, and growth to mothers who have toxemia or ges-
opsy may not yield characteristic hormone treatment was instituted. tational diabetes mellitus), limited
findings. A combination of clinical glycogen stores (from prematurity,
manifestations, laboratory studies The Condition intrauterine growth restriction, star-
that include serologic markers, and SOD is a rare condition occurring in vation, and perinatal stress), in-
imaging studies may help establish 1 in 10,000 live births. It is highly creased glucose use (seen in hypo-
the diagnosis. heterogeneous and defined loosely thermia, polycythemia, and sepsis),
Gastrointestinal eosinophilia can by the triad of optic nerve hypoplasia, endocrinopathies (such as adrenal
be a histologic finding in CD. midline neuroradiologic abnormali- insufficiency or GHD), decreased
glycogenolysis, diminished gluco- outcome in infants who have biliary consider the diagnosis when evalu-
neogenesis, and inborn errors of atresia. ating an infant who has hypoglyce-
metabolism. mia and hypothermia.
Evaluation for hypoglycemia Management Unexplained hypoglycemia should
should be performed when the pa- Once the diagnosis of SOD is con- be evaluated. Urgent treatment is
tient is symptomatic (blood glucose firmed, appropriate treatment should essential to prevent adverse neuro-
50 mg/dL [2.8 mmol/L]) and be initiated. Urgent treatment of hy- logic outcomes.
should include assessment of serum poglycemia may require intravenous It is essential that treatment with
glucose and insulin, cortisol, growth dextrose. Therapy with hydrocorti- glucocorticoid be initiated before
hormone, lactic acid, free fatty acids, sone and growth hormone may be thyroid hormone replacement so
and beta-hydroxybutyrate as well as a necessary for long-term maintenance adrenal crisis is not precipitated.
complete metabolic panel that in- of euglycemia. Thyroid hormone re- Treatment with other pituitary
cludes liver function tests. In addi- placement must be instituted as soon hormones, such as growth hor-
tion, plasma concentrations of am- as the diagnosis of thyroid hormone mone and antidiuretic hormone,
monia, an acyl-carnitine profile, and deficiency is established; long-term then can be instituted as needed.
urine organic acids should be mea- treatment with thyroid hormone, in- Hyperbilirubinemia (cholestatic and
sured. The newborn screen results volving careful monitoring of con- noncholestatic) often is present in
should be reviewed. centrations and titration of dosage, infants who have hypopituitarism.
At 2 weeks of age, any infant who offers the best outlook for physical Neonatal cholestasis is always
has jaundice should be evaluated by growth and neurodevelopmental pathologic and requires further
measuring total serum bilirubin and progress. Because treatment with evaluation.
conjugated bilirubin. Elevation of thyroid hormone can precipitate ad-
conjugated bilirubin in infancy is renal crisis in patients who have un- (Julie Martin, MD, Marcie Drury-
defined as a serum concentration treated adrenal insufficiency, replace- Brown, MD, Ivor Hill, MD, Wake
greater than 1.0 mg/dL (17.1 ment of glucocorticoid must precede Forest University Health Sciences,
mol/L) if the total bilirubin is less thyroid hormone treatment. Contin- Winston-Salem, NC; James Kerri-
than 5.0 mg/dL (85.5 mol/L) or ued assessment and appropriate gan, MD, East Tennessee Childrens
more than 20% of the total bilirubin treatment of other hormonal defi- Hospital, Knoxville, TN)
if the total bilirubin is greater than ciencies, such as diabetes insipidus
5.0 mg/dL (85.5 mol/L). and hypogonadism, is essential. Af-
Although a large number of con- fected infants also need evaluation by Case 3 Discussion
ditions are associated with conju- specialists in ophthalmology, neurol- The boys immune evaluation showed
gated hyperbilirubinemia, relatively ogy, and childhood development. serum IgA of 84 mg/dL (840 mg/L)
few account for the majority of cases. This patient was treated with thy- (normal, 33 to 202 mg/dL [330 to
Idiopathic neonatal hepatitis syn- roid hormone, hydrocortisone, and 2,020 mg/L]), IgG of 669 mg/dL
drome and biliary atresia account for growth hormone. His hypoglycemia, (6.7 g/L) (normal, 633 to
70% to 80% of cases, and alpha-1- hypothermia, and hyperbiliru- 1,280 mg/dL [6.3 to 12.8 g/L]),
antitrypsin deficiency accounts for binemia resolved, and the serum and IgM of 62 mg/dL (620 mg/L)
another 5% to 15%. The initial step in transaminase values normalized. His (normal, 48 to 207 mg/dL [480 to
evaluation should be to identify growth is being monitored, as are his 2,070 mg/L]). His IgD concentra-
treatable disorders of neonatal developmental progress, visual func- tions, however, were significantly el-
hepatitis syndrome, such as sepsis, tion, and signs of possible diabetes evated at 335 mg/dL (3,350 mg/L)
other neonatal infections (such as insipidus and hypogonadism. The (normal, 4 to 41 mg/dL [40 to
TORCH infections), hypothyroid- latter condition typically is not diag- 410 mg/L]). Thus, a diagnosis of
ism, panhypopituitarism, and in- nosed until the expected time of pu- hyperimmunoglobulin D syndrome
born errors of metabolism (galac- bertal development. (HIDS) was established.
tosemia). The next step is directed Hereditary periodic fever syn-
at evaluation of possible extrahepatic Lessons for the Clinician dromes (HPFSs), or human auto-
biliary atresia because surgical in- Hypopituitarism in infancy is a po- inflammatory syndromes, represent a
tervention within the first 2 post- tentially life-threatening but treat- group of disease processes that result
natal months results in improved able condition. It is important to in recurrent episodes of fever, usually
caused by a disturbance in the mech- headache. Other common symptoms condition may be that episodes are
anisms that control and mediate in- include abdominal pain, diarrhea, nau- precipitated by vaccinations and mild
flammation. These disorders typically sea, vomiting, and arthralgia. Up to viral infections.
are suspected after infectious causes 90% of patients have lymphadenopa- HIDS can be diagnosed when the
have been ruled out. thy during fever episodes, usually in patient presents with the previously
HPFSs are inherited disorders. Pa- the cervical region. Among the cutane- described symptoms and has an ele-
tients usually present with high tem- ous manifestations are erythematous vated serum IgD concentration
peratures, along with nonspecific con- macular rashes, papules, and urticaria. (13 mg/dL [130 mg/mL]). Be-
stitutional symptoms such as joint More than two thirds of patients expe- cause IgD values sometimes can be
pain, fatigue, abdominal pain, and rience the first episode of fever before normal in the condition, if the pa-
rash. Symptoms usually resolve on res- their first birthdays. tient presents with clinical features
olution of fever, which may take days The most common characteristic strongly suggestive of HIDS, genetic
to weeks without any medical inter- of HIDS is significantly elevated se- testing can be performed. During the
ventions. Familial Mediterranean fever rum IgD concentrations. However, attacks, patients usually have elevated
(FMF) is by far the most common serum IgD values may be normal un- acute-phase reactants. Some patients
HPFS. til age 3 years. The prevalence of can present with elevated serum IgA
FMF is an autosomal recessive dis- HIDS is higher in individuals of values. Because patients have an in-
order caused by a mutation in the Dutch or French origin, but the dis- ability to metabolize mevalonic acid,
Mediterranean fever (MEFV) gene on order can be found in individuals of mevalonic acid can be detected in the
chromosome 16, which encodes the other European ethnic groups. urine. This situation can be assessed
protein pyrin. Pyrin is involved in reg- HIDS follows an autosomal reces- by determining the ratio of meval-
ulating interleukin-1-beta (IL-1). sive inheritance pattern, and the ge- onic acid to creatinine in urine.
Affected patients usually present with netic defect is found on chromosome However, this finding should not be
abdominal, chest, and joint pains, 12, specifically in the q24 chromo- used as a confirmatory test; rather, it
symptoms that sometimes lead to un- some region. Patients who have should be considered as supporting
necessary laboratory and radiographic HIDS have reduced activity of me- evidence for the diagnosis. Cur-
evaluation and even laparotomy. valonic kinase, an enzyme that me- rently, studies are evaluating leuko-
Amyloidosis is a common complica- tabolizes mevalonic acid, an interme- triene E4 concentrations in urine as
tion of FMF, sometimes resulting in diate product of cholesterol and another diagnostic tool for HIDS.
renal failure. isoprenoid biosynthesis. It is pro-
Another periodic fever syndrome is posed that the decrease in isoprenoid Treatment
tumor necrosis factor (TNF) receptor- end-products leads to increased pro- There is no known definitive therapy
1-associated periodic fever (TRAPS), duction of IL-1, leading to in- for HIDS. However, colchicine, non-
which is also known as familial Hiber- creased inflammation and fever. Al- steroidal anti-inflammatory drugs,
nian fever. The mode of transmission is though patients who have FMF and immune globulin intravenous, cyclo-
autosomal dominant with incomplete TRAPS develop amyloidosis, pa- sporine, glucocorticoids, statins, and
penetrance. The defect occurs in the tients who have HIDS very rarely anticytokine therapies such as IL-1
gene encoding for the TNF receptor. develop this complication. receptor antagonists and TNF- an-
Affected patients usually present with tagonists have been tried with some
fevers for at least 5 days and up to Diagnosis success.
2 weeks. The fever typically is accom- The median period from onset of
panied by conjunctivitis and periorbital disease to diagnosis is usually 10 Lessons for the Clinician
edema, sometimes with joint pain, years because the disease is not sus- An accurate and detailed history in
rash, and abdominal pain. pected until the history reveals a cy- patient who experiences prolonged
clical pattern of fever over time. It is fever may prevent unnecessary lab-
The Condition important, however, to diagnose the oratory evaluation.
HIDS was described first in 1984 by condition earlier rather than later be- It is important to consider heredi-
Jos van der Meer in the Netherlands. cause early detection can prevent un- tary fever syndromes in the differ-
(1) HIDS is characterized by recurrent necessary extensive evaluations and ential diagnosis when a patient
temperatures up to 39.0C, accompa- missed school days for patients and presents with frequent unexplained
nied by chills, lymphadenopathy, and workdays for parents. A clue to the episodes of fever.
Early diagnosis of periodic fever Harbor-UCLA Medical Center, Da- periodic fever: a new syndrome. Lancet.
syndromes is important to monitor vid Geffen UCLA School of Medicine, 1984;323:10871090
In Brief
Tumor Markers in Infancy and Childhood
Rosanna Ricafort, MD Tumor markers are substances found in neoplastic conditions are associated
The Childrens Hospital abnormal amounts in the blood, urine, with an elevation in serum bHCG, most
at Montefiore or tissues that can be used in the commonly, chronic renal insufficiency.
Bronx, NY diagnosis, staging, treatment, and sur- The use of bHCG as a tumor marker is
veillance of patients who have cancer. based on its association with tropho-
The two most common tumor markers blastic differentiation in malignant
Author Disclosure in pediatric oncology, -fetoprotein germ cell tumors such as choriocarci-
Drs Ricafort and Adam have (AFP) and -human chorionic gonado- nomas and embryonal carcinomas.
disclosed no financial relationships tropin (bHCG), can aid in the treatment Although evidence-based clinical
relevant to this In Brief. This of children who have either known practice guidelines exist for using tu-
cancer or genetically predisposed can- mor markers as screening tools for sev-
commentary does not contain a
cer syndromes. eral cancers in adults, most notably,
discussion of an unapproved/ AFP is a glycoprotein normally syn- breast and colorectal cancers, such
investigative use of a commercial thesized by the fetal yolk sac, liver, and mass screening guidelines do not exist
product/device. intestine that serves as a fetal type of for the pediatric population. Cancer
binding protein. Reference values for surveillance protocols in pediatrics are
serum AFP in the neonatal period and limited to patients who have genetic
Alpha 1-Fetoprotein (AFP) Reference infancy up to 2 years of age have been syndromes that predispose to cancer.
Values in Infants up to 2 Years of established from normal term babies Beckwith-Wiedemann syndrome, the
Age. Blohm ME, Vesterling-Horner D, who did not have additional factors best described of several overgrowth
Calaminus G, Gobel U. Pediatr associated with AFP elevation. Espe- syndromes that are associated with an
Hematol Oncol. 1998;15:135142 cially in the first few postnatal months, increased incidence of childhood can-
Alpha-Fetoprotein and Beta-Human the range of values is broad. Initially, cer, carries about an 8% risk of intra-
Chorionic Gonadotropin: Their Clini- AFP has a half-life of less than 1 week; abdominal cancers in early childhood,
cal Significance as Tumour Markers. later, the half-life appears to be longer. most commonly, Wilms tumor and
Gregory JJ, Jr, Finlay JL. Drugs. 1999; Elevations of serum AFP can be seen in hepatoblastoma. Although surveillance
57:463 467 association with certain nonneoplastic guidelines vary, the general practice is
Diagnostic Value of Alpha 1-
conditions, most commonly in acute to screen with abdominal/pelvic ultra-
Fetoprotein and Beta-Human Chori-
liver disease, such as extrahepatic bili- sonography and serum AFP measure-
onic Gonadotropin in Infancy and
Childhood. Schneider DT, Calaminus ary atresia and hepatitis. In addition, ments every 3 to 4 months until age 4
G, Gobel U. Pediatr Hematol Oncol. hereditary disorders such as ataxia tel- years for hepatoblastoma, with pelvic
2001;18:1126 angiectasia and tyrosinemia can be as- ultrasonographic imaging continued
The Prognostic Value of Tumor Markers sociated with serum AFP elevation. The until age 8 years for Wilms tumor.
in Newly Diagnosed Patients With use of AFP as a tumor marker is based Initial diagnostic evaluation of chil-
Primary Central Nervous System on its association with epithelial liver dren in whom a malignant germ cell
Germ Cell Tumors. Kim A, Ji L, Bal- tumors (hepatoblastoma and hepato- tumor or liver tumor is suspected in-
maceda C, et al. Pediatr Blood Can- cellular carcinoma) and certain malig- cludes quantitative measurement of se-
cer. 2008;51:768 773 nant germ cell tumors (yolk sac tumors rum AFP and bHCG. Liver function tests
Timing and Magnitude of Decline in
[also known as endodermal sinus tu- always should accompany AFP assess-
Alpha-Fetoprotein Levels in Treated
mors] and embryonal carcinomas). ment to exclude nonmalignant hepatic
Children with Unresectable or Met-
astatic Hepatoblastoma are Predic- bHCG is a glycoprotein produced diseases that can be associated with
tors of Outcome: A Report from the physiologically by the trophoblasts of elevated AFP concentrations. For a child
Childrens Cancer Group. Van Torn- the placenta to stimulate hormonal who has a liver mass, quantification of
out JM, Buckley JD, Quinn JJ, et al. production and maintain pregnancy. serum AFP aids in the diagnosis. The
J Clin Oncol. 1997;15:1190 1197 Aside from pregnancy, only a few non- most common primary malignant liver
tumor in childhood, hepatoblastoma, is mount. A patient who has an intracra- Serum tumor marker surveillance is
associated with higher AFP values than nial germ cell tumor associated with a valuable tool in assessing patients for
hepatocellular carcinoma, which is elevated AFP or bHCG in the serum or relapse of malignant germ cell tumors
more common in adolescents. Liver me- CSF should be treated, even in the and liver tumors. In general, low-risk
tastases from other malignant tumors, presence of contradicting histology, for patients who are treated with surgery
such as neuroblastoma, or benign con- a nongerminomatous germ cell tumor, alone are followed more frequently
ditions, such as hepatic hemangioma, which has a poorer prognosis than a than those who receive adjuvant che-
are not associated with elevated AFP pure germinoma and, thus, requires motherapy, with the aim of detecting
concentrations. more aggressive therapy. relapse early to allow timely interven-
When a young child who has a liver Although the initial concentration tion. A consistent increase in serum
mass is unable to undergo a diagnostic of tumor markers at diagnosis has been tumor markers in some cases can pre-
biopsy because of respiratory compro- investigated as a prognostic indicator, a cede a clinically apparent relapse. Most
mise, abdominal compartment syndrome, more common trend is to follow tumor practice guidelines advocate for at
or uncorrectable coagulopathy, a mark- marker rate and magnitude of decline least monthly serum tumor marker
edly elevated serum AFP value is specific as an indicator of response to therapy. screening during the first year after
enough to allow for hepatoblastoma- Persistence, a secondary increase, or therapy, followed by more extended
directed emergent therapy. Of note, consistent prolongation beyond the es- intervals thereafter for approximately
hepatoblastoma accompanied by low AFP timated half-life of tumor marker se- 5 years.
values (100 ng/mL) is associated with rum values may indicate residual or Unlike in the adult population,
the presence of unfavorable small cell recurrent malignancy. The half-life of population-wide tumor marker screen-
undifferentiated histology and a poor AFP is estimated at 7 days and bHCG at ing of pediatric patients for malignant
prognosis. Also, although hepatocellular 3 days. A transient elevation in AFP may tumors is not appropriate. Elevations in
carcinoma typically is associated with not necessarily herald persistent active AFP and bHCG need to be evaluated in
lower AFP values than hepatoblastoma, a tumor; liberation of AFP from dying clinical context to distinguish malig-
less common fibrolamellar variant of tumor cells may cause a reversible in- nant from nonmalignant sources. In
hepatocellular carcinoma secretes high crease immediately following the initi- pediatric oncology practice, these tu-
amounts of AFP. ation of chemotherapy. Liver dysfunc- mor markers aid in the prognosis and
AFP and bHCG measurements from tion related to therapy also may cause treatment of patients who have secret-
serum, cerebrospinal fluid (CSF), or se- an increase in AFP. In hepatoblastoma, ing malignant tumors, most commonly,
rous effusions can aid in establishing serum AFP values generally normalize intracranial and peripheral malignant
the diagnosis of germ cell tumors. In within 4 to 6 weeks following a com- germ cell tumors and the primary liver
certain well-defined clinical settings, plete surgical resection; persistence of tumors hepatoblastoma and hepatocel-
elevated tumor markers can allow for elevated AFP beyond this period war- lular carcinoma.
the diagnosis of malignant germ cell rants careful evaluation for residual or
tumors without the need for histologic metastatic disease. Comment: Urine vanillylmandelic
confirmation. In mixed germ cell tu- Among children who have initially acid and homovanillic acid, metabolites
mors, the presence of elevated serum unresectable or metastatic hepatoblas- of norepinephrine and dopamine, are
AFP or bHCG concentrations should toma at diagnosis in whom primary tumor markers for neuroblastoma, the
elicit a careful, meticulous review of surgery is delayed, the decline of tumor most common cancer of infancy and
the histology for elements of yolk sac markers following neoadjuvant chemo- the most common extracranial solid
tumor or choriocarcinoma, respectively. therapy before surgical resection has tumor of childhood. Studies in Japan,
In large immature teratomas that lack been demonstrated to have prognostic Great Britain, Germany, and Canada
morphologic evidence of yolk sac tu- value. An decline of at least 1 log from have investigated screening programs,
mor, elevated serum AFP values should baseline is associated with improved usually at 6 months of age, to detect
prompt immunohistochemistry analysis survival. In malignant nonseminoma- undiagnosed neuroblastomas. The Na-
of the tumor for microscopic foci of tous germ cell tumors, AFP and bHCG tional Cancer Institute has determined
malignant yolk sac elements. are excellent tumor markers for moni- that such screening does not result in
Because biopsy technique may allow toring the response to therapy. Tumor decreased mortality. Aside from false-
for only a small sampling of an intra- marker decline has been evaluated as a positive results, most tumors identified
cranial germ cell tumor, serum and CSF potential prognostic marker to guide by mass screening programs are early-
assessment for AFP and bHCG is para- further therapy in such patients. stage neuroblastomas, which have a
high likelihood of spontaneous regres- ten to treatment that is more likely to prostate-specific antigen as a screen
sion. In other words, most of the tumors be toxic than beneficial. The ability to for prostate cancer.
found would have disappeared without screen does not mean that all screening
ever becoming symptomatic, but their should be undertaken, an issue raising
identification leads to the enormous controversy for our colleagues in adult Henry M. Adam, MD
anxiety associated with cancer and of- medicine about the use, for example, of Editor, In Brief
In Brief
Pheochromocytoma
Sadiqa Edmonds, MD Pheochromocytoma, a rare disease oc- The Table summarizes four familial
Daniel M. Fein, MD curring more often in adults than in syndromes commonly associated with
Alison Gurtman, MD children, accounts for only about 1% of pheochromocytoma. Von Hippel-Lindau
Childrens Hospital at Montefiore pediatric hypertension and often is as- syndrome (VHL), a neurocutaneous syn-
Bronx, NY sociated with a variety of genetic syn- drome associated with 20% of all
dromes. The National Registry of Child- pheochromocytomas, carries a 10% to
Author Disclosure hood Cancers reports an incidence of 20% risk of developing pheochromo-
Drs Edmonds, Fein, Gurtman, and 0.11 benign and 0.02 malignant pheo- cytoma. The tumors can be bilateral or
chromocytomas per 1 million children. extra-adrenal, but only 5% associated
Adam have disclosed no financial
Eighty-five percent of pheochromocy- with VHL are malignant.
relationships relevant to this In Brief.
tomas are located in the adrenal Multiple endocrine neoplasia (MEN)
This commentary does not contain a glands; the rest develop in the extra- types IIA and IIB are associated with
discussion of an unapproved/ adrenal parasympathetic and sympa- pheochromocytoma. MEN IIA manifests
investigative use of a commercial thetic paraganglia. Most tumors are with parathyroid hyperplasia, adrenal
product/device. less than 5 cm in size, and 25% to 33% medullary hyperplasia or pheochromo-
are bilateral. Approximately 10% of cytoma, and medullary thyroid car-
intra-adrenal and 40% of extra-adrenal cinoma. MEN IIB is characterized by
Phaeochromocytoma in Children.
Armstrong R, Sridhar M, Greenhalgh pheochromocytomas are malignant. In neuromas, medullary carcinoma, and
KL, et al. Arch Dis Child. 2008;93: childhood, these tumors are more prev- pheochromocytoma. The risk of pheo-
899 904 alent in boys than girls, but during chromocytoma in MEN IIA is about
Clinical Problem Solving: A Crisis in adolescence this trend reverses, possi- 50% and in MEN IIB is higher.
Late Pregnancy. Desai AS, Chutkow bly because of hormonal influences. Neurofibromatosis type 1, an auto-
QA, Edelman E, et al. N Engl J Med. In children 18 years of age and somal dominant syndrome associated
2009;361:22712277 younger, about 60% of pheochromo- with cafe au lait macules, Lisch nod-
Adrenal Dysfunction. Speiser PW. In: cytomas have an associated germline ules, neurofibromas, optic gliomas, and
McInerny TK, Adam HM, Campbell mutation, and in children younger than axillary or inguinal freckling, carries a
DE, Kamat DM, Kelleher KJ, eds. 10 years, this number increases to 70%. 1% risk of pheochromocytoma. In fa-
American Academy of Pediatrics Familial genetic syndromes predispose milial paraganglioma syndrome, which
Textbook of Pediatric Care. Elk Grove to the development of pheochromocy- is also autosomal dominant, paragan-
Village, IL: American Academy of
toma by altering sympathetic neuronal gliomas develop in the head, neck,
Pediatrics; 2009:1808 1818
cell precursor apoptosis. A family his- chest, abdomen, and pelvis; about 20%
A Current Review of the Etiology, Di-
agnosis and Treatment of Pediatric tory of genetic syndromes is common of affected patients develop a pheo-
Pheochromocytoma and Paragangli- but not equivocal in affected children. chromocytoma.
oma. Waguespack SG, Rich T, Grubbs Many associated syndromes are auto- Pheochromocytomas become symp-
E. J Clin Endocrinol Metab. 2010;95: somal dominant, but spontaneous mu- tomatic from the increased secretion of
20232037 tations occur. norepinephrine (predominant in chil-
high likelihood of spontaneous regres- ten to treatment that is more likely to prostate-specific antigen as a screen
sion. In other words, most of the tumors be toxic than beneficial. The ability to for prostate cancer.
found would have disappeared without screen does not mean that all screening
ever becoming symptomatic, but their should be undertaken, an issue raising
identification leads to the enormous controversy for our colleagues in adult Henry M. Adam, MD
anxiety associated with cancer and of- medicine about the use, for example, of Editor, In Brief
In Brief
Pheochromocytoma
Sadiqa Edmonds, MD Pheochromocytoma, a rare disease oc- The Table summarizes four familial
Daniel M. Fein, MD curring more often in adults than in syndromes commonly associated with
Alison Gurtman, MD children, accounts for only about 1% of pheochromocytoma. Von Hippel-Lindau
Childrens Hospital at Montefiore pediatric hypertension and often is as- syndrome (VHL), a neurocutaneous syn-
Bronx, NY sociated with a variety of genetic syn- drome associated with 20% of all
dromes. The National Registry of Child- pheochromocytomas, carries a 10% to
Author Disclosure hood Cancers reports an incidence of 20% risk of developing pheochromo-
Drs Edmonds, Fein, Gurtman, and 0.11 benign and 0.02 malignant pheo- cytoma. The tumors can be bilateral or
chromocytomas per 1 million children. extra-adrenal, but only 5% associated
Adam have disclosed no financial
Eighty-five percent of pheochromocy- with VHL are malignant.
relationships relevant to this In Brief.
tomas are located in the adrenal Multiple endocrine neoplasia (MEN)
This commentary does not contain a glands; the rest develop in the extra- types IIA and IIB are associated with
discussion of an unapproved/ adrenal parasympathetic and sympa- pheochromocytoma. MEN IIA manifests
investigative use of a commercial thetic paraganglia. Most tumors are with parathyroid hyperplasia, adrenal
product/device. less than 5 cm in size, and 25% to 33% medullary hyperplasia or pheochromo-
are bilateral. Approximately 10% of cytoma, and medullary thyroid car-
intra-adrenal and 40% of extra-adrenal cinoma. MEN IIB is characterized by
Phaeochromocytoma in Children.
Armstrong R, Sridhar M, Greenhalgh pheochromocytomas are malignant. In neuromas, medullary carcinoma, and
KL, et al. Arch Dis Child. 2008;93: childhood, these tumors are more prev- pheochromocytoma. The risk of pheo-
899 904 alent in boys than girls, but during chromocytoma in MEN IIA is about
Clinical Problem Solving: A Crisis in adolescence this trend reverses, possi- 50% and in MEN IIB is higher.
Late Pregnancy. Desai AS, Chutkow bly because of hormonal influences. Neurofibromatosis type 1, an auto-
QA, Edelman E, et al. N Engl J Med. In children 18 years of age and somal dominant syndrome associated
2009;361:22712277 younger, about 60% of pheochromo- with cafe au lait macules, Lisch nod-
Adrenal Dysfunction. Speiser PW. In: cytomas have an associated germline ules, neurofibromas, optic gliomas, and
McInerny TK, Adam HM, Campbell mutation, and in children younger than axillary or inguinal freckling, carries a
DE, Kamat DM, Kelleher KJ, eds. 10 years, this number increases to 70%. 1% risk of pheochromocytoma. In fa-
American Academy of Pediatrics Familial genetic syndromes predispose milial paraganglioma syndrome, which
Textbook of Pediatric Care. Elk Grove to the development of pheochromocy- is also autosomal dominant, paragan-
Village, IL: American Academy of
toma by altering sympathetic neuronal gliomas develop in the head, neck,
Pediatrics; 2009:1808 1818
cell precursor apoptosis. A family his- chest, abdomen, and pelvis; about 20%
A Current Review of the Etiology, Di-
agnosis and Treatment of Pediatric tory of genetic syndromes is common of affected patients develop a pheo-
Pheochromocytoma and Paragangli- but not equivocal in affected children. chromocytoma.
oma. Waguespack SG, Rich T, Grubbs Many associated syndromes are auto- Pheochromocytomas become symp-
E. J Clin Endocrinol Metab. 2010;95: somal dominant, but spontaneous mu- tomatic from the increased secretion of
20232037 tations occur. norepinephrine (predominant in chil-
the tumor and immediately after tumor who have no underlying genetic condi- and pathology classes hearing about
removal. Adjunctive therapy, such as tion, annual follow-up is likely to be pheochromocytoma than essential hy-
high-dose 131I-MIBG, may be used in sufficient after the first 6 months. How- pertension. Although pheochromo-
patients who develop metastatic disease. ever, lifelong follow-up is required be- cytoma is in the differential diagnosis,
Removal of a benign pheochromo- cause tumors can recur, particularly we hope that in the midst of an epi-
cytoma should result in resolution of with familial pheochromocytomas that demic of childhood obesity and associ-
symptoms. Hypertension beyond 24 hours are part of a genetic syndrome. ated hypertension, it is not still topping
after resection raises concern for re- the list.
tained tumor. Initial follow-up consists of Comment: When I was in medical
monthly blood pressure and urinary cat- school (granted, a long time ago), we Henry M. Adam, MD
echolamine measurements. In patients actually spent more time in physiology Editor, In Brief
important. If the child is expected to should be discontinued in the brain- and social attention, it is important
die following withdrawal of LSMT, it dead child. LSMT should not be to the parent to remain undiscov-
is possible that a legal charge of as- continued in any dead patient, re- ered. If FDBP is discovered, the par-
sault may be changed to manslaugh- gardless of the circumstances leading ent may face separation from his or
ter or murder. Thus, the outcome of to death. Parents, however, may be her child and loss of attention.
the parents decision may alter the compassionately offered some input Therefore, most perpetrators of
legal charges filed against them, a as to when and under what circum- FDBP are careful not to be discov-
guardian, relative, or acquaintance. stances such LSMT is discontinued. ered. FDBP is most likely to occur at
(2)(3) Parents desire to decide in the Because the chance of criminal pros- home, but when it occurs in the hos-
best interest of the severely abused ecution is so high in death following pital, it happens when no health-care
child may, therefore, be compro- child abuse, the AAP recommends professional is present.
mised by an attempt to protect them- that the medical examiner be in- Because this condition is so diffi-
selves or others from increased legal volved before forgoing LSMT. (2) cult to diagnose unequivocally,
prosecution. health-care professionals have used
If health-care practitioners sus- Organ and Tissue Donation covert surveillance to aid in making
pect that parents are experiencing a State and federal laws require that the diagnosis. Principal methods of
conflict of interest in deciding about parents or legal guardians be given covert surveillance include hidden
their childs best interest, additional the opportunity to donate their dead video cameras as well as one-way mir-
resources may be sought. The hospi- childs organs or tissues. Even par- rors in the hospital room. Arguments
tal ethics committee, attorneys, ad- ents suspected of abuse retain the against and for covert surveillance are
ministrators, social workers, and cul- right to make this decision on behalf ethically charged.
tural and religious leaders may be of their dead child, unless their legal
helpful in resolving the conflict. Be- rights as parents have already been Arguments Against Covert
cause stripping parents of their legal removed. The AAP recommends Surveillance
custody and decision-making rights, that the medical examiner be encour- Covert surveillance may reveal sensi-
even when they are no longer physi- aged to attend the organ/tissue pro- tive information irrelevant to the
cally caring for their child, may be curement procedure to have the op- childs illness. Such disclosure may
time-consuming and require court portunity to collect any possible cause shame or harm to the involved
intervention, the American Academy additional criminal evidence. (2) parties. If the parent learns that he or
of Pediatrics (AAP) recommends she has been observed secretly and
that a guardian ad litem be appointed Covert Surveillance for his or her privacy violated without
to assist with medical decision- Factitious Disorder by Proxy consent, he or she may lose all trust in
making in each case of child abuse Factitious disorder by proxy the physician as well as in health-care
requiring LMST in which the parent (FDBP), a type of child abuse in professionals in general. Such loss of
may have conflict of interest in decid- which a caretaker, usually a parent, trust may cause the parent to avoid
ing whether to continue LSMT. (2) takes action so a child appears to be health-care professionals in the fu-
Thus, in the field of child abuse, pa- or actually becomes ill, results in ture, setting up the child for subse-
tient (parental) autonomy can be eventual death in up to 10% of chil- quent insufficient care. The parent
outweighed by beneficence and non- dren as well as in significant long- may question the physicians honesty
maleficence toward the child. (4) term physical and psychological mor- and whether the physicians actions
bidity for the child. are in the best interest of the child or
Brain Death FDBP may be suspected when a of the child-parent dyad. Deteriora-
If a child is determined to be brain reasonable medical evaluation reveals tion in the parent-physician relation-
dead, whether abused or not, prepa- no primary disease in the child, but ship may make the parent unwilling
ration should be made to remove the the child has events requiring medi- to participate in any physician-
childs body from LSMT because cal attention, usually occurring solely mandated program designed to re-
brain death is recognized as legally in the presence of the parent, which duce risk to children suspected of
and ethically equivalent to cardiopul- cannot be explained otherwise. On being abused. Thus, the use of covert
monary death. Parental agreement removal from the parent, signs of surveillance to try to diagnose FDBP
should not be sought with regard to FDBP disappear. To continue to may indirectly threaten the parent-
whether mechanical life support reap the benefits of extensive medical child relationship by limiting paren-
tal commitment to a healing pro- best interests. When they enlist the is encroaching on the resources of
gram. Subsequent removal of the help of a physician, they are seeking the health-care system. Such a parent
child from the home may result in a attention for themselves rather than a clearly is not aligned with the physi-
long trail of foster homes and associ- cure for the childs condition. They cian in serving as a fiduciary for the
ated risks. have not sought the physicians child.
It may be ethically inexcusable to counsel to have him or her spy on If the parent-physician relation-
use the child as bait during covert them covertly in an attempt to ship has been formed with a goal of
surveillance in the case of suspected achieve a diagnosis. It is unfortunate, providing health care in the best in-
FDBP, due to the risk of harm to the in the parents eyes, that the consci- terest of the child, but the parent is
child during the actual surveillance. entious physician is obligated, legally secretly acting against the best inter-
If health-care professionals suspect and ethically, to investigate any sus- est of the child, the relationship be-
FDBP so strongly that they consider picions. tween the parent and the physician is
the use of covert surveillance, it As society leaders, physicians fraudulent. Therefore, covert surveil-
might be preferable to remove the should hold themselves to high stan- lance of parental activities will not
child immediately from the likely dards and not stoop to deceitful cause much more damage than al-
source of abuse to guarantee his or means of making diagnoses. Accep- ready has affected the parent-
her safety. Physicians willing to per- tance of such behavior may under- physician relationship, which is built
form covert surveillance have been mine the virtue of being a physician. on a precarious structure of parental
criticized as being so focused on falsehoods.
catching the parents in the process of Arguments for Covert If FDBP occurs in the hospital
perpetrating FDBP that they lose Surveillance under surveillance, not only is the
sight of their fiduciary responsibility Covert surveillance is consistent with child subject to less severe and
to protect the child at all times. (5) the physicians role as a fiduciary, en- lengthy trauma than if he or she were
Many parents involved in FDBP trusted with the care of another. As enduring these events at home, but
are wary of video cameras and one- primary fiduciaries, parents usually the diagnosis is determined. (7) Ben-
way mirrors and are unlikely to per- enlist and entrust physicians to cure efits to the child from diagnosing
form their actions in a hospital. and protect the best interests of their FDBP include immediate protection
Therefore, practically speaking, use children by treating their ailments. from further events and minimizing
of secret surveillance bears great risk Parents who abuse their children may the subsequent risk of death or mor-
and lends little benefit. FDBP may be not be capable of making important bidity from parental actions. Despite
treated based on clinical suspicion decisions regarding the childrens suspicions of FDBP, most clinicians
without the deleterious effects of di- best interests. Therefore, the physi- generally require evidence of paren-
agnosis via covert surveillance. The cian whom the parents have enlisted tal attempts to harm their child be-
clinician may simply tell parents sus- to care for their children may be the fore barring them access to the child.
pected of being involved in FDBP only fiduciary. (7) Thus, covert surveillance helps to
that their only options are to partici- Under the guise of promoting the protect the long-term interests of the
pate in a recovery program or to refer childs best interests, the parent in- child.
the child to Child Protective Ser- volved in FDBP may have sought Although covert surveillance of
vices. The physician who positions medical assistance for the child to call parents interacting with their chil-
himself or herself on the side of attention to himself or herself. A par- dren violates their right to privacy,
working with the parent to keep cus- ent who commits FDBP has, thus, may extinguish the trust they have
tody of the child, rather than as an established a false relationship with for the physician, and may not yield
adversary willing to spy on the fami- the physician. Although he or she any answers regarding the cause of
lys activities, demonstrates respect appears to have enlisted and is sup- the childs illness, such surveillance
for the parents, maintains their trust, porting the physician in trying to de- does not disrespect the parents. In-
and minimizes risk to the child of termine the source of the childs stead, it may identify the abusing
another FDBP event. (6) illness, this parent actually is with- parent as needing help. The applica-
Parents who practice FDBP are holding information from the physi- tion of covert surveillance is justified
not appropriate surrogate decision- cian that could help determine why because of the physicians fiduciary
makers for their children and are not the child is ill. In addition, the parent responsibility to protect the best in-
attempting to protect their childrens is manipulating the childs health and terest of the child. Protecting the
child should be the priority, and diatrician and the childs family, may the abused child to the parental
making a diagnosis is germane to that need to decide whether it is in the home for more abuse.
function. childs best interest to remain in such
an environment, whether the envi- Foster Care Placement
Violence ronment can be improved, or Child abuse and neglect frequently
Children who witness physical vio- whether the child should be up- result from such adversities as pov-
lence between their parents have rooted and placed in a foster home erty, mental illness, caregiver sub-
psychological outcomes similar to free of the predilection for violence. stance abuse, transitions between
those of children who have been The physician is legally and ethi- caregivers, and domestic violence.
physically abused. Even when there is cally mandated to report violence di- For each household referred to the
no direct physical abuse of children rected against children to protect child welfare authorities, it must be
being raised in a violent household, them. (14) The pediatrician may sus- determined whether the childs in-
such children have physiologic neuro- pect abuse based on physical find- terests are served best by his or her
endocrine alterations that result in ings; the adverse psychosocial effects remaining at home or by placement
elevated resting heart rate, elevated of a violent environment that does in foster care. The key ethical di-
blood pressure, other findings consis- not cause obvious physical findings lemma in choosing whether a child
tent with a chronic fight-or-flight in the child may be more difficult to should be in foster placement or re-
response, (8) and somatic symptoms recognize. The pediatrician may be main at home with his or her parents
such as headache. Similarly, such chil- less inclined to report these cases, lies in balancing beneficence and
dren have a high risk of adverse even if he or she is aware of the nonmaleficence to the child. A sec-
psychosocial outcomes, including ad- presence of violence in the childs ondary dilemma is determining allo-
justment disorders and posttraumatic environment. Physicians may fail to cation of social resources, such as fos-
stress disorder. report violent households, which ter care, to optimize community
Adverse outcomes may be inter- may harm the child, due to their own outcomes.
nalized within the child in the form desire not to damage the patient- Depending on the individual fam-
of social isolation, lack of emotional physician relationship and to con- ilys circumstances, the childs best
attachment, and cognitive inatten- tinue to provide treatment for the interest may be met by remaining at
tion with poor academic perfor- child and family. Failure to report home, provided certain dangerous
mance. Children may present with violence affecting children allows conditions are corrected. If the par-
externalized, aggressive, and violent more opportunities for children to ents are willing to correct the envi-
behavior. Very young children have experience adverse effects. ronment within their home, benefits
limited understanding of conflict and In the emergency department, the could include stability in terms of the
fewer strategies for coping with it. physicians office, or court, often child maintaining psychological at-
(9) Therefore, it is the youngest chil- within earshot of the parent, the tachments, consistency of rules and
dren exposed to violence at home child may be asked questions about expectations of behavior, consistency
who are at greatest risk for adverse being the deliberate or inadvertent of provision of physical care, mainte-
psychosocial outcomes. target of violence. The child may be nance of familial and ethnic identity,
Violence affecting children also inclined to deny that any violence and more effective use of social re-
may occur in the form of teen dating occurs at home to appease his or her sources. Therefore, reasonable ef-
violence; bullying; and exposure to parent and avoid later punishment. forts should be exerted, when appro-
firearms, (10) television shows, mov- He or she should be allowed to an- priate, to preserve and repair families
ies, (11) video games, and music. swer without the parent being pres- to make the parental home as ideal as
(12) Media violence has been ent. He or she should be assured that possible for the child. (15)
strongly associated with aggressive honest answers are in his or her own When the parental home is not
behavior, desensitization to violence, best interest and that he or she will be remediable and continues to be dan-
fear of being harmed, and night- protected from parental retaliation. gerous for a child, foster care must be
mares. (13) Once abuse is reported, lawyers rep- used, even on a temporary basis. Fos-
When a child is exposed to re- resenting the alleged abusive parents ter care is intended to provide the
peated violence at home, and if the may be aware of the abuse, but still child with safety as well as psycholog-
violence cannot be eliminated, au- may argue in favor of the innocence ical, physical, and cognitive nurtur-
thorities, in conjunction with the pe- of their clients, thus risking return of ing to allow the child to heal. How-
ever, foster care is associated with ment may be less attentive in relative developmentally appropriate and less
certain risks. Due to the high work- foster care than in nonrelated foster cognitively stimulating than that
force turnover in the child welfare care. Relative foster caregivers have a which they would have received in
system, youth in foster care may suf- high incidence of incomplete high the parental home. (17) This differ-
fer adverse effects such as lack of sta- school education, similar to that of ence may occur because the average
bility and loss of trusting relation- the investigated parents, increasing foster family provides care for five or
ships with child welfare workers. (16) the risk of poor academic achieve- more children simultaneously,
Insufficient numbers of suitable fos- ment of the child. Both related and stretching both financial resources
ter homes result in placement with nonrelated foster caregivers have a and time available for each childs
relatives, (15) a delay of long-term higher incidence of serious physical care. Without adequate knowledge
placement, or frequent changes of illness compared with investigated of and skills in child development,
foster homes for any given child. (17) parents, often due to their greater enough time to attend to the childs
Repeated foster home and school age, which may impede their ability physical and developmental needs,
changes compound the adverse con- to care for the foster child in an ex- good mental and physical health, and
sequences that previous stress and emplary manner. financial and other resources neces-
inadequate parenting had on the Although nonrelated foster par- sary to build a safe and nurturing
childs neurodevelopment and ability ents generally are older and have environment for the child, foster care
to cope. Repeated separation of the higher levels of education, higher in- may not be superior to the high-risk
child from his or her primary pillars comes, a spouse to help with child- home being investigated.
of psychological support (first, the care, and better mental health, they The authorities of the child wel-
parents and later, a variety of foster generally provide a learning environ- fare and judicial systems have the dif-
parents) may result in attachment ment for the foster child that is less ficult role of weighing the alterna-
disorders and an inability to trust and
love. Frequent school changes and
the termination of foster care at 18 Summary
years of age may leave the child un-
prepared for adult life (inadequate Multiple ethical dilemmas in the field of child abuse create challenges to
independent living skills, inadequate making decisions that are in the best interest of the child. The clinician
must have command of these ethical issues to render the most appropriate
employment skills and plans, inade-
and compassionate care to the child.
quate coaching regarding the pursuit Withdrawal of LSMT may be ethically permissible, with the intention of
of higher education, lack of financial allowing death to occur, for the child who has suffered severe and
aid). (15) permanent brain damage and who may have no interest in whether he or
Placement of a child in the foster she lives or dies or who is expected, if medical technology is continued, to
live a life of pain and suffering.
care of a relative offers the advantages
Parents may have conflicts of interest regarding whether to continue LSMT
of maintaining his or her family and because if the child dies, they may be legally charged with manslaughter or
ethnic roots and having a more con- murder. Therefore, the clinician must listen to the reasoning process that
sistent group of caregivers. Such fac- parents use in reaching their decision.
tors could ease the childs transition Appointment of a guardian ad litem, as well as use of ethics consultants
and other resources, can help to ensure that the treatment decision is in the
back to the parental home when its
best interest of the child.
deficiencies are corrected. A lower A brain-dead child is legally and ethically indistinguishable from a child
incidence of untreated mental illness who suffers a cardiorespiratory death.
is seen in foster caregivers who are Covert surveillance in suspected factitious disorder by proxy has been
relatives compared with parents criticized for revealing irrelevant and embarrassing information as well as
being deceitful and deleterious to the parent-physician relationship,
whose homes have been investigated
potentially dangerous to the child, likely to be nondiagnostic, not serving
by child welfare workers. Foster care the purpose for which the parents sought the physicians counsel, and
with a relative, however, may result harmful to the role of the physician. However, its use is justifiable because
in unplanned, inadvertent, and po- of the physicians fiduciary responsibility to protect the best interest of the
tentially unsafe return of the child to child.
Although the intention of foster care is to place children in a safe, healing
his or her parental home. Social sup-
home, certain risks inherent in foster placement create a challenge in
port resources may be less available, determining which home situation is in the best interest of the child.
and supervision of the home environ-
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