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Intelligence (IQ) Testing

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DOI: 10.1542/pir.27-11-403 · Source: PubMed

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 Article cognition, language, learning

Intelligence (IQ) Testing

Ellen B. Braaten, PhD,*
Objectives After completing this article, readers should be able to:
Dennis Norman, EdD†
1. Define intelligence quotient (IQ) and what constitutes the “normal” range of IQ scores.
2. Describe the predictive validity of intelligence test scores.
Author Disclosure 3. Discuss the factors that may influence performance on intelligence tests.
Drs Braaten and 4. Recognize the relationship between variability observed in factor scores and the
Norman did not probability of the child having a learning or cognitive disability.
disclose any financial 5. Describe how achievement tests are used in conjunction with IQ tests to determine
relationships relevant eligibility for a learning disability.
to this article.

Introduction
Intelligence tests assess a person’s mental abilities and compare them with the abilities of
other people through the use of numerical scores. Although the term intelligence is used
as if there is agreement on what it means, in reality there is much debate as to how this term
should be and has been defined. For example, debate has surrounded whether intelligence
should be considered an inherent cognitive capacity, an achieved level of performance, or
a qualitative construct that cannot be measured. Psychologists have debated whether
intelligence is learned or inherited, culturally specific or universal, and one ability or several
abilities. While these debates are ongoing, evidence is increasing that traditional intelli-
gence tests measure specific forms of cognitive ability that are predictive of school
functioning, but do not measure the many forms of intelligence that are beyond these
more specific skills, such as music, art, and interpersonal and intrapersonal abilities. (1)
Despite these debates, most experts view intelligence as a person’s problem-solving
abilities, such as adapting to the environment and having vocabulary skills, higher-order
thinking (eg, decision making, reasoning skills, verbal and nonverbal problem-solving
skills), memory, and mental speed. More specifically, for the purpose of this article,
intelligence is discussed as it relates to a child’s score on the intelligence (IQ or “intelli-
gence quotient”) tests that are used most commonly to measure a person’s intelligence for
educational planning or neuropsychological assessment.

Intelligence Tests
Efforts to measure intelligence have long been a part of psychology, and despite contro-
versy over the meaning and scope of intelligence, an IQ score can provide meaningful data
about a child’s cognitive abilities if put within a conceptual framework that does not
overstate its meaning or implications for the child. Intelligence tests are the most studied
and, consequently, the most reliable, valid, and useful tests available for measuring specific
cognitive abilities. Within a particular IQ test, children tend to perform the same on items
designed to assess the same ability, which suggests internal consistency. The tests are
reliable because children generally receive the same score when they retake the same test
years later, although the reliability of the test usually increases with the age of the child.
Test validity is based on numerous studies that have found high correlations between
children’s IQ scores and their performance in school, achievement tests, and tests of
specific intellectual functioning (eg, measures of language, visual motor processing).
An IQ score reflects a child’s performance on an intelligence test relative to that of
children of the same age. In short, a child’s IQ score tells the extent to which his or her

*Psychologist, Massachusetts General Hospital; Assistant Professor, Harvard Medical School, Boston, Mass.
†
Chief of Psychology, Massachusetts General Hospital; Associate Professor, Harvard Medical School, Boston, Mass.

Pediatrics in Review Vol.27 No.11 November 2006 403

cognition, language, learning IQ testing

test children ages 21⁄2 to 6 years of

age. Each of these tests is composed
of subtests that measure a variety of
domains. The WISC-IV contains
15 subtests that are divided into 10
core subtests and 5 supplemental
(ie, optional) subtests, which form
four composites scales (referred to
as “factor scores”): Verbal Com-
prehension (verbal knowledge and
the ability to use verbal skills in new
situations), Perceptual Organiza-
tion (the ability to think about and
Figure. Classification ratings for IQ ranges as they are distributed along the normal curve. organize visual material without the
use of words), Working Memory
performance on the test departs from average. The IQ (the ability to hold information in memory to manipulate
score represents a construct of “intelligence” that in- it or perform calculations with it), and Processing Speed
cludes a combination of verbal and nonverbal processing (the speed at which one can process simple visual infor-
skills, such as vocabulary, information about the world, mation without making errors). The Table lists the
reasoning, short-term memory, and speed of information WISC-IV subtests and factor scores. Although there are
processing; these skills, together, are represented by the tests of infant “intelligence,” such as the Bayley Scales of
IQ score. Nearly all comprehensive psychological evalu- Infant Development, most tests for children younger
ations include some measure of intelligence. For exam- than age 3 years measure abilities, such as sensorimotor
ple, for a child who is being tested to confirm a diagnosis development and early language skills, which are not
of attention-deficit/hyperactivity disorder (ADHD), an highly correlated with later IQ.
intelligence test can confirm that the child’s academic
difficulties do not indicate a specific cognitive weakness Predictive Validity of IQ
or mild mental retardation. Intelligence tests are reasonably accurate at predicting
Most intelligence tests assess a range of verbal, visual- which children will be successful in school and which will
spatial, and problem-solving skills. Because they target
multiple cognitive skills, IQ tests are composed of
subtests that measure specific areas of functioning. Scores WISC-IV Factors and
Table.

on these subtests are combined to yield measures of Subtests

verbal and nonverbal problem-solving abilities, as well as
a full-scale IQ score. IQ scores are assumed to be nor- Verbal Comprehension Factor
mally distributed in the population, with most scores ● Three Core Subtests: Similarities—Vocabulary—
falling in the middle of the distribution and fewer scores Comprehension
● Two Supplemental Subtests: Information—Word
falling at the upper and lower extremes (Figure). The
Reasoning
average IQ score on most IQ tests is 100, with a standard
deviation of 15. Most IQ scores (about 68%) fall within 1 Perceptual Reasoning Factor
standard deviation on either side of the mean (eg, be- ● Three Core Subtests: Block Design—Picture
tween 85 and 115), and almost all scores (99% of popu- Concepts—Matrix Reasoning
lation) fall within 3 standard deviations above or below ● One Supplemental Subtest: Picture Completion

the mean. Working Memory Factor

School-age children most frequently are tested with ● Two Core Subtests: Digit Span—Letter-Number
the Wechsler Intelligence Scale for Children–Fourth Sequencing
Edition (WISC-IV). The Wechsler Adult Intelligence ● One Supplemental Subtest: Arithmetic
Scale, Third Edition (WAIS-III) is the test used most Processing Speed Factor
frequently for adolescents ages 16 and older. The
● Two Core Subtests: Coding—Symbol Search
Wechsler Preschool and Primary Scale of Intelligence – ● One Optional Subtest: Cancellation
Third Edition (WPPSI-III) is used most frequently to

404 Pediatrics in Review Vol.27 No.11 November 2006


have difficulty, with correlations between intelligence
tests and measures of educational achievement averaging
about 0.50. Thus, IQ tests are one of the best single
indices of how well a child will do in school. However,
IQ test scores are not the sole predictive factor of how a
person will perform in school and are not the definitive
indication of how a person eventually will function in
society because other variables, such as intellectual do-
mains not measured by a specific test, parenting, quality
of schooling, motivation, and exposure to culture and
books, also are important determinants of success in life.
Research has shown that IQ constancy increases with
age, although correlations tend to be slightly higher for
elementary students than for high school or college
students. Generally, the correlations with educational
achievement and IQ are highest for verbal subjects, such
as reading. In contrast, the predictive power of IQ test
scores before the first birthday are not very strong for
children who fall in the average to superior range, (2) but
the tests are fairly predictive (ranging in studies from
0.50 to 0.97) for children assessed
at lower IQ levels (ie, below IQs
.result. .in.largemany
of 50). (3)
Overall, the general rule of
thumb is that the older the child,
the more stable the IQ. By age 4
years, the correlation with IQ 12
years later is relatively high
(r⫽0.77). (2) Although many
IQ tests.
older children show little fluctua-
tion in their IQ scores, research
has indicated that a subset of younger children show wide
fluctuation in IQ scores. Finally, even older children may
show some fluctuations in scores in response to major
stressors such as a loss of a parent, divorce, or change in
schools. With these possible exceptions, by around age
10 years, IQ scores generally are relatively stable.
Factors That Influence Performance on IQ
Tests
IQ is influenced by genetic factors (eg, the child’s genetic
makeup), familial factors (eg, parents’ IQs and education
and quality of the home environment), educational fac-
tors (eg, quality of educational opportunities and teach-
ing), and other factors, such as the community in which
the child lives. Environmental influences on the develop-
ment of intelligence include access to stimulating or
enriching experiences, caregivers who help the child
learn problem-solving skills, access to books and sources
of knowledge, good nutrition, a high level of social
support, parental involvement in the child’s learning and
cognition, language, learning IQ testing
education, an enriched language environment, good
school attendance, good schools, and stable neighbor-
hoods. (4)
Cultural and ethnic differences in performance on
intelligence tests also have been documented. For exam-
ple, studies have indicated that the average scores on
standardized intelligence tests of children from African-
American and Latino families often are below those of
children from Caucasian families. However, the available
data do not support a genetic interpretation; (5) rather,
the differences likely reflect a cultural or language bias.
In addition to innate and background factors, an
almost limitless list of intervening variables can affect a
child’s performance on an IQ test. A qualified test ad-
ministrator attempts to minimize such variables as much
as possible, but influencing factors can include the loca-
tion of the evaluation (eg, noisy office), previous testing
experiences that may result in practice effects, the
examiner-examinee interaction, a negative stance on the
part of the child, peer-group pressure to fail, or poor
learning disabilities
verbal-performance splits on
motivation. Other causes of poor performance can in-
clude limited hearing or visual acuity, a lack of profi-
ciency with the English language, situational stressors,
poor attentional skills, or acute emotional difficulties
such as depression or anxiety.
Discrepancies in IQ Test Score Patterns
In general, children’s factor scores on the WISC-IV
should be fairly similar; the more variability observed in
factor scores, the higher the probability that the child has
a learning or cognitive disability. Previous versions of the
WISC provided verbal and performance IQ scores in
addition to a full-scale IQ. Differences greater than 15
points between a child’s verbal comprehension and per-
ceptual reasoning scores are worthy of an explanation
and may be cause for concern because many learning
disabilities result in large verbal-performance splits on IQ
tests. For example, many children who have dyslexia have
lower verbal abilities compared with nonverbal abilities
because dyslexia is a verbally based learning disability.
Pediatrics in Review Vol.27 No.11 November 2006 405
cognition, language, learning IQ testing
Children who have nonverbal learning disabilities, by
definition, have lower perceptual reasoning scores com-
pared with verbal comprehension abilities and frequently
have significantly weak processing speed scores, as well.
However, even a 15-point difference does not necessarily
indicate the presence of a learning disability. This is
because differences in styles of thinking and learning are
common and often are reflected in a child’s pattern of IQ
scores, such as in the case of a child who has superior
intellect and has a verbal comprehension index of
140 and a perceptual reasoning index of 120. That said,
if an extremely large (⬎25-point) verbal comprehension-
perceptual reasoning split is present, and if one of these
scores is below the average range, psychologists fre-
quently refer the child to a neurologist or to a develop-
mental pediatrician to rule out the possibility of neuro-
logic impairment. Even if the difference between a child’s
factor scores on an IQ test is large, the discrepancy
should not be used alone to make a diagnosis of a
learning disability or to predict brain functioning with-
Comparisons
of IQs with tests
of academic achievement frequently are used
in diagnosing specific learning disabilities.
out substantial support from other test data and obser-
vations. Finally, when the differences between a child’s
WISC-IV factor scores are significant, the full-scale IQ
may not be a valid measure of the child’s level of overall
intellectual functioning because the IQ may represent a
forced “average” of very disparate skills.
Using Intelligence Tests to Evaluate Learning
Disabilities
To evaluate specific learning disabilities, such as a reading
disorder, disorder of written expression, or math disabil-
ity, IQ tests typically are used in conjunction with
achievement tests. Achievement tests are designed to
measure what a child has actually learned, including
mathematical problem-solving, reading, spelling, writ-
ing, or an understanding of science concepts. Most
achievement tests focus on a particular subject and mea-
sure a child’s learning with questions of varying difficulty.
The child’s score then either is compared with that of a
child of the same age or grade or measured against an
406 Pediatrics in Review Vol.27 No.11 November 2006
objective standard. When used to diagnose a specific
learning disability, a child’s academic achievement in one
or more areas is compared with his or her intellectual
abilities. If a child’s ability in one or more areas of
achievement, as measured on standardized tests, is sig-
nificantly lower than expectations based on age, educa-
tion, and intelligence, the probability is high that a
learning disability exists. However, these difficulties also
must impede the child’s ability in academic achievement
or activities of daily living. Also, if the child has a sensory
deficit, such as in visual perception, memory, or atten-
tion, the difficulties in math or writing need to be worse
than what would be expected with the sensory deficit
alone. For example, if a child who has ADHD has prob-
lems with math, the math difficulties must be worse than
what would be expected from a child who has attentional
difficulties. Thus, although IQ and achievement tests are
used frequently to diagnose a learning disability, a simple
discrepancy is not sufficient to make the diagnosis be-
cause other issues need to be eliminated.
In addition, the lack of a dis-
crepancy is not necessarily an indi-
cation that a learning disability
does not exist. This is particularly
true for the young child who may
exhibit early signs of a learning
disability, but who does not yet
lag behind to the extent that a
discrepancy exists. In these cases,
the pattern of scores on relevant
tests (eg, reading fluency, phonics
skills, reading comprehension, prereading skills) be-
comes primary in the diagnosis of a learning disability.
Because current federal law recognizes the shortcomings
of a discrepancy approach in determining a learning
disability, school districts are not bound by the discrep-
ancy criteria before children are found to be eligible for
special education services. However, current law also
states that the lack of achievement must not be due to
mental retardation; a visual, hearing, or motor impair-
ment; emotional disturbance; or environmental disad-
vantage. Thus, intelligence tests typically are given to
rule out the possibility that a cognitive deficit underlies
the child’s difficulties with academic skills.
Summary
Intelligence is a multifaceted construct that, for the
purposes of this review, is operationalized as the standard
IQ tests (eg, Wechsler Scales) used by schools and psy-
chologists to measure cognitive functioning in a formal
environment. Intelligence scores predict the ease with

which people learn in formal situations, but do not
necessarily predict success in life or occupations. Mea-
sures of intelligence can be affected by fluency of lan-
guage, access to educational stimulation, educational
resources, motivation, and emotional functioning. Vari-
ability in terms of subtest or factor score performance
may be a sign of a learning disability, but a simple
discrepancy between verbal and nonverbal abilities is not
sufficient to diagnose a learning disability. Comparisons
of IQs with tests of academic achievement frequently are
used in diagnosing specific learning disabilities, but
schools and diagnosticians are not bound by the discrep-
ancy criteria. However, to diagnosis a specific learning
disability, the possibility of a cognitive deficit needs to be
ruled out, which typically is done through the adminis-
tration of an IQ test. Overall, IQ tests are the most
reliable and valid instruments used to measure a person’s
cognitive abilities, but they always should be interpreted
within a conceptual framework that does not overstate its
implications for the child.
References
1. Gardner H. Frames of Mind: The Theory of Multiple Intelligences.
New York, NY: Basic Books; 1983
2. Neisser U, Boodoo G, Bouchard TJ Jr, Boykin AW, Brody N, Ceci
SJ. Intelligence: knowns and unknowns. Am Psychol. 1996;51:77–101
3. Satler JM. Assessment of Children: Behavioral and Clinical Applica-
tions. 4th ed. La Mesa, Calif: Jerome M. Sattler, Publisher, Inc; 2002
4. Spitz HH. Commentary on the contributions to this volume. In:
cognition, language, learning IQ testing
Detterman D, ed. Current Topics in Human Intelligence: Vol. 5. The
Environment. Norwood, NJ: Ablex; 1996:173–177
5. Brooks-Gunn J, Klebanov PK, Duncan GJ. Ethnic differences in
children’s intelligence test scores: role of economic deprivation,
home environment, and maternal characteristics. Child Devel.
1996;67:396 – 408
Suggested Reading
Braaten E, Felopulos G. Straight Talk About Psychological Testing
for Kids. New York, NY: The Guilford Press; 2004
Flanagan DP, Kaufman AS. Essentials of WISC-IV Assessment. New
York, NY: John Wiley & Sons; 2004
Hebben N, Milberg W. Essentials of Neuropsychological Assessment.
New York, NY: John Wiley & Sons; 2002
Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS.
Neuropsychological Assessment. 4th ed. Oxford, England: Oxford
University Press; 2004
Obrzut JE, Hynd GW. Neuropsychological Foundations of Learning
Disabilities: A Handbook of Issues, Methods and Practice. San
Diego, Calif: Academic Press; 1996
Snyder PJ, Nussbaum PD. Clinical Neuropsychology: A Pocket
Handbook for Assessment. Washington, DC: American Psycho-
logical Association; 1998
Spreen O, Strauss E. A Compendium of Neuropsychological Tests:
Administration, Norms and Commentary. Oxford, England:
Oxford University Press; 1998
Wechsler D. Manual for the Wechsler Intelligence Scale for
Children–Revised. New York, NY: The Psychological Corpora-
tion; 1974
Wechsler D. WAIS-R Manual: Wechsler Adult Intelligence
Scale–Revised. New York, NY: The Psychological Corporation;
1981
Pediatrics in Review Vol.27 No.11 November 2006 407
cognition, language, learning IQ testing

PIR Quiz
Quiz also available online at www.pedsinreview.org.

1. Intelligence, as measured by IQ testing, is:

A. Independent of cultural background.
B. Invariant over time.
C. Non-normally distributed.
D. Not assessable in children younger than age 6 years.
E. Predictive of school performance.

2. An 8-year-old boy is being evaluated for his poor academic performance in third grade. Results from his
WISC-IV reveal:
Full Scale IQ: 100
Verbal Comprehension Factor Score: 85
Perceptual Reasoning Factor Score: 115
Working Memory Factor Score: 95
Processing Speed Factor Score: 105
These test findings are most consistent with a diagnosis of:
A. Dyslexia.
B. Expected variation.
C. Isolated attention-deficit disorder.
D. Math disability.
E. Mental retardation.

3. A 6-year-old girl whose teachers are concerned about her ability to keep up with her classmates is found
to have a WISC-IV IQ of 70 with a verbal comprehension factor score of 65 and a perceptual reasoning
factor score of 75. These results are most supportive of a diagnosis of:
A. Average intelligence.
B. Dyslexia.
C. General cognitive deficit.
D. Isolated attention-deficit disorder.
E. Isolated nonverbal learning disability.

4. An 8-year-old boy without evidence of sensory deficit is having difficulty reading at grade level. In
addition to a significant verbal-performance split on IQ testing, formal diagnosis of a reading disorder
requires:
A. A full-scale IQ of at least 110.
B. A home visit.
C. Grade retention.
D. Neurologic referral.
E. Standardized achievement testing.

408 Pediatrics in Review Vol.27 No.11 November 2006

 Article nutrition

Breastfeeding: The Essential Principles

Latha Chandran, MBBS,
Objectives After completing this article, readers should be able to:
MPH,* Polina Gelfer, MD†
1. Understand the physiology of lactation.
2. Discuss the biologic specificity of human milk.
Author Disclosure 3. Delineate the benefits of breastfeeding for the infant, the mother, and the community.
Drs Chandran and 4. Know relative and absolute contraindications to breastfeeding.
Gelfer did not 5. Describe current recommendations for breastfeeding.
disclose any financial
relationships relevant
to this article. Introduction
Breastfeeding practice is the biologic norm for Homo sapiens and dates back some 40,000
years. Until the last several decades, breastfeeding was the norm, and wet-nursing was the
only alternative to allow infants to survive. Although pediatricians overwhelmingly agree
that breastfeeding is best for babies, in the United States today, only 68% of all new
mothers even attempt it, and at least 50% abandon it quickly. The United States Public
Health Service Healthy People 2010 Initiative calls for an increase in the rate of breast-
feeding to 75% at birth, 50% at age 6 months, and 25% at 1 year of age (Figure). The
presence or absence of breastfeeding affects the economics of the family and the commu-
nity. Multiple studies confirm that the annual cost to the United States health care system
from women not breastfeeding is several billion dollars. Promoting breastfeeding can
decrease costs for public health programs such as The Special Supplemental Nutrition
Program for Women, Infants, and Children, parental employee absenteeism as a result of
decreased infant illness, environmental burden for disposal of formula cans and bottles, and
energy demands for production and transport of artificial feeding products.

Physiology of Lactation
During pregnancy, the breast grows larger, the diameter of the areola increases, pigmen-
tation increases, the nipples become more erect, and the veins become more prominent.
Various hormones stimulate breast growth: prolactin and placental lactogen stimulate
nipple and areolar growth; estrogen facilitates the proliferation and differentiation of the
ductal system; and progesterone promotes an increase in size of the lobes, lobules, and
alveoli. During the first half of pregnancy, the ductal tree grows and proliferates, and
additional lobules form. The second half of pregnancy is characterized by acceleration of
secretory activity and distention of alveoli from accumulating colostrum. After 16 weeks of
pregnancy, lactation occurs, even if the pregnancy does not progress.
The volume of milk secreted by the mammary cells remains small until after the infant
is born. After delivery of the placenta, serum progesterone and estrogen concentrations
fall, and negative feedback by these hormones on pituitary prolactin release is lost.
Prolactin concentrations rise, leading to increased milk synthesis. When the neonate begins
suckling, the posterior pituitary hormone oxytocin is released. Oxytocin causes the
milk-ejection reflex or letdown, a contraction of the myoepithelial cells surrounding the
alveoli necessary for the ejection of milk.
The rate of milk synthesis after each breastfeeding episode varies and is related to the
degree of emptiness or fullness of the breast; an emptier breast makes milk faster than a
fuller one. Thus, breastfeeding is not a major factor for the initiation of lactation, but it is
essential for the continuation of lactation. Lactogenesis also is susceptible to outside

*Editorial Board.
†
Assistant Professor of Clinical Pediatrics, State University of New York at Stony Brook, Stony Brook, NY.

Pediatrics in Review Vol.27 No.11 November 2006 409

nutrition breastfeeding
Figure. Breastfeeding rates in 2003 and United States
Healthy People 2010 breastfeeding objectives. From Centers
for Disease Control and Prevention breastfeeding national
immunization data.
influence. Certain conditions, such as type 1 diabetes
mellitus, obesity, polycystic ovary syndrome, placental
retention, and stress, can delay or diminish lactogenesis.
The reasons for this delay are not clear. Human milk
production is related to an infant’s demand. Infants have
the ability to self-regulate their milk intake.
Composition of Human Milk
Human milk is unique and species-specific. All substitute
feeding preparations differ markedly from it, making
human milk superior for infant feeding. Human milk is
rich in proteins, nonprotein nitrogen compounds, lipids,
oligosaccharides, vitamins, and minerals. In addition, it
contains hormones, enzymes, growth factors, and many
types of protective agents.
Colostrum
The first milk secreted by the postpartum woman is
colostrum. Human colostrum differs from mature milk.
The energy value is about 67 kcal/100 mL compared
with the 75 kcal/100 mL for mature milk. The volume
varies with the parity of the mother and the number of
feedings. The concentrations of sodium, potassium, and
chloride are greater than those of mature milk. Protein,
fat-soluble vitamins, and minerals are present in greater
percentages than in transitional and mature milk. The
high level of antibodies may provide protection against
the bacteria and viruses that are present in the birth canal.
Colostrum facilitates the passage of meconium and es-
410 Pediatrics in Review Vol.27 No.11 November 2006
tablishment of Lactobacillus bifidus flora in the infant’s
gut.
Mature Milk
Mature human milk contains fat, carbohydrates, and
protein as substrates for infant nutrition. The fat of
human milk provides about 50% of its calories. Triglyc-
erides are the primary constituents of the fat. The lipid
fraction provides essential fatty acids. Human milk is
rich in long-chain polyunsaturated fatty acids, including
docosahexanoic acid and arachidonic acid, which are
associated with higher visual acuity and cognitive ability
in the infant. The fats of human milk and cow milk are
qualitatively different, with human milk containing more
of the absorbable triglyceride olein and cow milk con-
taining more volatile fatty acids (butyric, capric, caproic,
and caprylic). These differences may result in the preterm
or sick infant possibly developing steatorrhea after in-
gesting cow milk.
Lactose is the primary carbohydrate in human milk,
although small quantities of galactose and fructose also
are present. Lactose enhances calcium absorption and is
metabolized readily to galactose and glucose, which sup-
ply energy to the infant. Human milk consists predomi-
nantly of whey proteins; cow milk mostly has casein.
Whey protein is composed of five major components:
alpha-lactalbumin, serum albumin, lactoferrin, immuno-
globulins, and lysozyme. The latter three elements play
important roles in immunologic defense. Human milk
also contains free amino acids, including essential amino
acids, as well as nucleotides. Table 1 lists comparisons
between human milk, cow milk, and some infant formu-
las. About one third of infants who are allergic to cow
milk protein may be allergic to soy protein, as well; in
such cases, protein hydrolysate formulas are used. The
standard caloric content for all formulas is 20 kcal/oz.
The amount of vitamins and micronutrients in human
milk varies, depending on the diet and genetic differ-
ences of mothers. Generally, as lactation progresses, the
level of water-soluble vitamins in human milk increases
and the level of fat-soluble vitamins declines. Human
milk is a good source of vitamin A and vitamin E, but has
very little fat-soluble vitamin D. The risk of vitamin D
deficiency rickets is greatest for dark-skinned children
living in inner-city areas and for infants of solely breast-
feeding mothers eating strict vegetarian diets. All breast-
fed infants should receive 200 IU of oral vitamin D drops
daily. (1)
Human milk contains small amounts of vitamin K.
A few days after birth, enteric bacteria produce sufficient
quantities of the vitamin, but until ingestion of copious
 Table 1. Composition of Human Milk, Cow Milk, and Infant Formulas
Cow Milk
Protein-based Soy Protein-based
Ingredients Human Milk Cow Milk Formula Formula Protein Hydrolysate Formula
Carbohydrate Lactose Lactose Lactose Sucrose Sucrose
(g/dL) 7.0 4.8 Corn syrup Corn syrup Corn syrup
3.6 to 3.7 3.6 3.4 to 3.7
Protein Human milk protein, Cow milk protein, whey: Nonfat milk Soy isolate Cow milk protein hydrolyzed
(g/dL) whey: casein ratio casein ratio of 22:78 Demineralized Methionine to reduce allergenicity
of 75:25 Total: 3.3 whey 1.8 to 2.0 1.9
Total: 1.1 1.4
Fat (g/dL) Human milk fat Butterfat Soy oil Palm olein Medium-chain triglyceride
Contains more Contains more volatile Coconut oil Soy oil oil
absorbable fatty acids Palm oil Coconut oil Soy oil
triglyceride 3.7 3.6 to 3.7 3.6 to 3.7 Coconut oil
3.8 3.4 to 3.7
Calcium 280 1,226 530 710 640 to 710
(mg/L) Higher calcium content
due to inhibition of
absorption by
phytates
Phosphorus 147 956 284 to 360 507 to 560 430 to 507
(mg/L)
Iron (mg/L) Vitamin C and 0.5 5.0 12 12
lactose facilitate
absorption
0.4
Suggested Preferred for all Children older than 1 Infants who Infants who have cow Infants who have food
uses infants year of age who have have milk allergy (30% allergies or underlying
normal gastrointestinal normal may have cross- gastrointestinal damage
tract gastrointestinal reactivity), lactose
tract but malabsorption,
cannot be galactosemia
breastfed
nutrition
breastfeeding

Pediatrics in Review Vol.27 No.11 November 2006 411

nutrition breastfeeding

Major Protective and Anti-inflammatory

Table 2. IQ scores nearly 4 points higher
than those who did not receive hu-
Factors in Human Milk man milk, after statistical control of
social and perinatal factors associ-
Factors Function
ated with breastfeeding such as
Immunoglobulins Generate immune response to specific antigens birthweight, multiplicity, gesta-
Secretory IgA, IgM, IgG tional age, maternal age, education,
Lactoferrin Antibacterial effect, especially against Escherichia
coli, inhibition of complement, carries iron and family income. (2)
Lysozyme Bactericidal and anti-inflammatory
Casein Inhibits microbial adhesion to mucosal membranes Anti-infective Properties of
Lipids Protect against enveloped viruses, anti-infective Human Milk
efforts Human milk provides protection
Prostaglandins Cytoprotective
Cytokines Activate the immune system against disease. The high concen-
Glycoconjugates Antiviral, antibacterial protection trations of secretory immunoglob-
Phagocytes Absorb pathogens, release IgA ulin (Ig)A, enzymes, other Igs, and
Lymphocytes Essential for cell-mediated immunity; antiviral leukocytes provide broad-spectrum
activity protection against infections and
Memory T cells give long-term protection
Prolactin Enhances development of B and T lymphocytes chronic conditions. Breastfeeding
Stimulates proliferation of intestinal mucosa helps to prevent infantile diarrhea
Human growth factors Mucosal barrier to antigens and other GI infections. It is now
well established that ingested anti-
bodies from human milk can pro-
amounts of human milk promotes gastrointestinal (GI) vide local GI immunity against specific enteric patho-
bacterial colonization, neonates are susceptible to vita- gens, including Campylobacter jejuni, Clostridium
min K deficiency-induced hemorrhagic disease. To pre- difficile, Escherichia coli, Giardia lamblia, rotavirus, Sal-
vent this condition, 1 mg of vitamin K is administered monella typhimurium, Shigella sp, and Vibrio cholerae.
routinely intramuscularly to infants immediately after The degree of protection is related to the amount of
birth. Mothers consuming strictly vegan diets may pro- human milk an infant receives; exclusive breastfeeding is
duce milk that is deficient in vitamin B12, as well. The associated with greater protection.
total mineral content in human milk is higher in the first Studies of the protective effects of breastfeeding
days after birth and slowly decreases throughout lacta- against respiratory tract infections offer conflicting re-
tion. Although human milk has only a small amount of sults. Several studies suggest that breastfeeding helps to
iron, breastfed babies rarely develop iron deficiency be- prevent respiratory illnesses; (3) others indicate little
cause iron absorption is facilitated by the high lactose and protection. There is, however, strong evidence that hu-
vitamin C concentrations of human milk. man milk protects against respiratory syncytial virus in-
Several anti-inflammatory and protective factors have fection. (4) Similar protection has been established
been identified in human milk and their functions delin- against Haemophilus influenzae bacteremia and menin-
eated (Table 2). gitis as well as pneumonia caused by Streptococcus pneu-
moniae. Breastfeeding also provides protection against
Benefits of Breastfeeding ear infections and atopic disorders.
Child Health Benefits
Human milk provides optimal nutrition to the infant,
facilitating adequate growth and development. Research Protection from Chronic Disease
studies among term and preterm infants have shown Breastfeeding contributes to the prevention of diabetes,
significant improvements in developmental outcomes of celiac disease, childhood cancer, sudden infant death
breastfed infants compared with formula-fed infants. In syndrome, obesity, and many other health problems.
addition, growing evidence suggests small, but signifi- The longer the duration of breastfeeding, the greater is
cant, cognitive benefits for breastfeeding. When tested at its protective effect. The protection by human milk
7 to 8 years of age, children who were breastfed as infants against illness extends beyond infancy to childhood and
for 8 months or longer had mean verbal intelligence adulthood. Exclusive breastfeeding during the first
quotient (IQ) scores 6 points higher and performance months after birth is associated with lower asthma rates

412 Pediatrics in Review Vol.27 No.11 November 2006


during childhood. (5) Human milk Viruses Identified in Breast Milk and
Table 3.
also may protect preterm infants
against necrotizing enterocolitis. Impact on Breastfeeding
Virus
Benefits for the Mother
Breastfeeding and lactation de- HIV-1, HIV-2
crease postpartum bleeding and HTLV-1, HTLV-2
Hepatitis B virus (HBV)
promote more rapid uterine involu-
tion. They decrease the risk of Hepatitis C virus
breast and ovarian cancer and pos-
sibly decrease the risk of hip frac- Herpes simplex virus
tures and osteoporosis in the post- Cytomegalovirus
menopausal period. They definitely
promote development of bonding Rubella virus
and attachment between the West Nile virus
mother and the infant. HIV⫽human immunodeficiency virus, HTLV⫽human T-cell lymphoma/leukemia virus
Contraindications to
Breastfeeding
Medical Disorders
Breastfeeding is optimal for infants, but there are a few
conditions when breastfeeding is not in the baby’s best
interest. Breastfeeding is contraindicated for infants who
have classic galactosemia, an autosomal-recessive disor-
der in which the liver enzyme galactose-1-phosphate
uridyltransferase is absent. Affected infants are unable to
metabolize lactose or galactose, leading to liver failure
and mental retardation. When this diagnosis is suspected,
abrupt weaning from breastfeeding is necessary.
Mothers who have active untreated tuberculosis dis-
ease should be separated from their infants and advised to
suspend breastfeeding until the mother and infant are
receiving appropriate antituberculosis therapy. The
mother should wear a mask and adhere to infection
control measures. Separation is no longer necessary once
the infant is started on isoniazid. However, if multidrug-
resistant tuberculosis is suspected, the infant should re-
main separated from the mother even after he or she is
started on isoniazid. (6)
Viruses
Human milk can transmit certain viral diseases. The
viruses that can be identified in human milk and their
impact on breastfeeding are listed in Table 3.
The World Health Organization recommends avoid-
ance of all breastfeeding by human immunodeficiency
virus (HIV)-infected mothers when replacement feeding
is acceptable, feasible, affordable, sustainable, and safe.
Women in developed countries who are HIV-positive
should not breastfeed their offspring, but in the develop-
ing world when replacement feeding is not feasible or
nutrition breastfeeding
Impact on Breastfeeding
Contraindicated
Contraindicated
Not contraindicated, especially if infant receives HBV
vaccine and HBV immune globulin
Not contraindicated. Nipple cracks or fissures may pose
a risk for transmission.
Contraindicated only if active breast lesions are present
Not contraindicated. Some experts recommend stopping
breastfeeding of preterm and immunosuppressed
infants if mother becomes infected during lactation.
Not contraindicated
Not contraindicated
safe, exclusive breastfeeding is recommended during the
first postnatal months. (7) The exact risk of transmission
is unknown, but risk is probably higher in mothers who
have higher viral loads.
The human lymphotropic virus HTLV-1, associated
with adult T-cell leukemia and lymphoma, is uncommon
in the United States. HTLV-2 is a related retrovirus.
Mothers who are HTLV-1- or -2-positive should not
breastfeed.
Women who have herpetic lesions on their breasts
should refrain from breastfeeding. In the absence of
breast lesions, the newborn can breastfeed and room-
in, but scrupulous hand washing and covering of any
lesions is recommended to prevent possible cross-
contamination.
Medications
Almost all drugs are excreted into human milk to some
degree, but only a very few are unsafe for the infant.
Table 4 lists medications that are contraindicated when
breastfeeding. Mothers who are receiving radioactive
isotopes, antimetabolites, or chemotherapeutic agents
should not breastfeed until the medications no longer are
excreted in the milk. Individual drugs that preclude
breastfeeding include lithium, atropine, chlorampheni-
col, cyclosporine, bromocriptine, ergot alkaloids, and
iodides. Long-term maternal ingestion of drugs that
have sedative effects can cause sedation in breastfeeding
infants and withdrawal symptoms on interruption of
breastfeeding. (8) Although most drugs can be used
safely by breastfeeding women, physicians should make a
Pediatrics in Review Vol.27 No.11 November 2006 413
nutrition breastfeeding
Medications Contraindicated During
Table 4.
Breastfeeding
Drug/Class Possible Adverse Effects in Infant
Antineoplastic agents Fetal death, congenital anomalies, organ system
toxicity
Immunosuppressants Potential suppression of the immune system
Lithium High potential for toxicity
Chloramphenicol Blood dyscrasias, aplastic anemia
Ergot alkaloids Ergotism poisoning
Radiopharmaceuticals Potential toxicity; brief to full interruption of
breastfeeding recommended
Bromocriptine Suppresses prolactin secretion; hyperprolactinemic
mothers taking drug can breastfeed successfully
Iodides Thyroid suppression
risk versus benefit assessment prior to the use of any
drugs during lactation. (8)
Conditions That Are Not Contraindications to
Breastfeeding
Breastfeeding is not contraindicated for infants born to
mothers who are hepatitis B surface antigen-positive. All
such infants should receive hepatitis B immunoglobulin
(HBIG) and hepatitis B virus (HBV) vaccine within
12 hours after birth. Multiple studies have shown that
breastfeeding does not appear to increase the rate of
infection among neonates; moreover, in areas of high
HBV prevalence, lack of breastfeeding places the infant
at greater risk of contracting the disease.
Maternal hepatitis C virus (HCV) infection is not a
contraindication for breastfeeding. (1) The overall rate of
maternal-infant HCV transmission among breastfed in-
fants is similar to that of formula-fed infants. It has been
suggested, but not shown, that the presence of cracks or
fissures in the nipple poses a risk for transmission of
HCV. Some experts believe that mothers should be
counseled about potential risks.
Although transmission of cytomegalovirus (CMV)
through breastfeeding has been established, no serious
illness or clinical symptoms in neonates fed CMV-
positive human milk have been reported. Breastfeeding is
not contraindicated for healthy term infants whose
mothers have CMV infection. However, decisions about
breastfeeding of preterm and immunosuppressed infants
should be made with consideration of the potential ben-
efits of human milk versus the risk of CMV transmission.
Freezing and pasteurization can decrease the CMV viral
load in milk significantly.
Maternal tobacco smoking is not a contraindication
to breastfeeding. Clinicians, however, should advise
414 Pediatrics in Review Vol.27 No.11 November 2006
mothers to avoid smoking within
the home and to make every effort
to wean themselves from tobacco.
Women who have a history of
breast reduction are at risk of insuf-
ficient lactation. Those diagnosed
with breast cancer can continue
breastfeeding. However, when che-
motherapy begins, the infant must
be weaned. Inverted nipples should
not impede breastfeeding. Usually
the degree of inversion lessens as
breastfeeding continues. Women
who have acute mastitis should
continue frequent breastfeedings.
Breastfeeding Considerations in Normal and
Special Situations
American Academy of Pediatrics (AAP)
Recommendations on Breastfeeding for
Healthy Term Infants
In its most recent recommendations, the AAP has taken
a very strong position on promoting breastfeeding. (1)
Recommendations include exclusive breastfeeding for
the first 6 postnatal months and continuation of breast-
feeding for at least the first year and beyond, as long as
desired by mother and child. Complementary foods rich
in iron and supplementary fluoride should be introduced
beginning around 6 months of age. The AAP suggests
enthusiastic support of breastfeeding by all health-care
professionals as well as recognition and sensitivity to
cultural differences regarding breastfeeding attitudes and
practices. Pediatricians should recommend human milk
for all infants in whom breastfeeding is not contraindi-
cated. When direct breastfeeding is not possible, ex-
pressed human milk should be provided. Education of
both parents before and after delivery is an essential
component of successful breastfeeding.
Healthy infants should be in direct skin-to-skin con-
tact with their mothers immediately after birth. After the
recovery period, mother and infant should sleep in prox-
imity to each other to facilitate breastfeeding. Water and
other fluids should not be given to breastfeeding infants
unless specifically ordered by the physician.
During the first weeks of breastfeeding, the infant
should have 8 to 12 feedings every 24 hours. After
breastfeeding is well established, the frequency of feed-
ing may decline to about eight times per 24 hours. The
mother should offer both breasts at each feeding for as
long as the infant remains at the breast. In the early weeks
after birth, infants should be aroused to feed if 4 hours

Markers of Successful
Table 5.
Breastfeeding
● 7% or less weight loss in first few days after birth
● Return to birthweight by at least 2 weeks
● Weight gain per day of 20 to 30 g during first 3
postnatal months
● Lactation established in mother by 2 to 4 days after
birth
● At least eight breastfeeding events every 24 hours
● Baby is latching onto breast easily
● Three to six stools and four to six voids by 5 to 7
days of age
have passed since the last feeding. It is recommended
that trained medical personnel in the hospital evaluate
breastfeeding at least twice daily, including observation
of position, latch, and milk transfer.
Follow-up of breastfeeding infants after hospital dis-
charge is critically important. The AAP recommends
early follow-up within 2 days of discharge for any infant
sent home when he or she is younger than 72 hours of
age. An infant who has many risk factors might need to
be seen earlier (within 24 h of discharge). The health-
care professional should evaluate the infant’s weight,
hydration status, and the presence or absence of jaun-
dice. Markers of successful breastfeeding are listed in
Table 5. The next ambulatory visit can be scheduled at
2 to 3 weeks of age so the physician can monitor weight
gain and provide additional support. Exclusive breast-
feeding is one of several risk factors for worsening hyper-
bilirubinemia in the infant.
Nursing While Pregnant
Pregnancy can occur while lactating. There is no need to
wean the first infant from the breast. It is possible to
lactate throughout pregnancy and to have both infants at
the breast postpartum. This feeding pattern can be used
without any apparent ill effects on the nourishment of
the new infant. The mother should be provided with
psychological support as well as adequate rest and nour-
ishment.
Breastfeeding Newborns Who Have Special
Needs
PRETERM OR ILL INFANTS. In this situation, breast-
feeding may be delayed for days or weeks. Medical per-
sonnel should advise mothers to begin expressing milk
within hours of giving birth. Mother-infant skin-to-skin
contact and direct breastfeeding should be encouraged as
nutrition breastfeeding
early as possible. If the respiratory status of the infant
precludes direct breastfeeding, gavage feedings with ex-
pressed human milk may be considered. Fortified human
milk is recommended for many low-birthweight infants.
Banked human milk can be a suitable alternative for
infants whose mothers are unable or unwilling to breast-
feed.
MULTIPLE INFANTS. Most mothers of multiple infants
are capable of producing most or all of the milk required
for two to four infants. These mothers need substantial
help and support with early feedings. Simultaneous feed-
ing saves time, but it is important to assess each infant
initially at the breast separately.
DOWN SYNDROME. Hypotonia, abnormal anatomic
structure of the oral cavity, and significant congenital
heart disease may affect breastfeeding of infants who have
Down syndrome. Large, flattened tongues cause diffi-
culty latching on. In addition, affected infants may have
difficulty swallowing and are at increased risk of pulmo-
nary aspiration. Feeding usually improves as the infant’s
muscle tone improves. Despite these challenges, the
prevalence of breastfeeding among patients who have
Down syndrome is similar to that of the general popula-
tion. Very close monitoring of growth and development
is imperative for children who have Down syndrome and
are breastfed exclusively.
CLEFT LIP AND PALATE. Studies reveal that approxi-
mately 25% of infants who have cleft lip and palate have
early feeding problems, leading to poor weight gain over
the first few postnatal months. Patients who have isolated
cleft lip have better feeding records and faster weight
gain compared with those who have isolated cleft palate.
Common feeding problems include inability to generate
negative sucking pressure in the oral cavity, excessive air
intake, nasal regurgitation, and fatigue. However, for
patients who have cleft lip/palate, breastfeeding offers
several benefits over bottle-feeding. It allows a better seal
due to pliability of the human breast, promotes develop-
ment of oral and facial muscles, and decreases the risk of
ear and respiratory infections. After repair of the cleft,
experts recommend resumption of nursing as early as
possible, if not in the immediate postoperative period.
Practical Issues in Breastfeeding
Guidelines for Collection and Storage of
Expressed Human Milk
It is very important to maintain cleanliness to minimize
bacterial contamination in the process of collection. The
Pediatrics in Review Vol.27 No.11 November 2006 415
nutrition breastfeeding
mother should be instructed in washing her hands, her
breasts, and pumping equipment. Many hospitals, phar-
macies, and local rental companies have electric pumps
that are very time-efficient. Human milk can be stored in
either glass or plastic containers. Glass or flexible bottles
(polypropylene containers) have significant advantages in
maintaining the stability of the components of human
milk, particularly IgA.
Freshly expressed human milk can be used safely for
up to 8 hours at room temperature, but the potential for
contamination is greater when milk is not refrigerated.
Various studies support storing milk in a refrigerator
(4°C/39°F) for up to 5 days without increasing the risk
of bacterial contamination and to facilitate retaining
some cell viability. Because refrigerated milk separates,
the container should be shaken vigorously before feeding
the baby. Milk can be kept for 3 months in a self-
defrosting freezer and for 12 months in a freezer that has
no defrost cycle that maintains a temperature of 0°F
(⫺20°C). The milk should be thawed in the refrigerator
and used within 24 hours. Defrosting in the microwave is
not recommended.
Banking Human Milk
The Human Milk Banking Association of North America
was established in 1985. It supervises collection, screen-
ing, processing, storing, and distribution of donated
human milk for infants who are prescribed human milk.
Donors are screened carefully and are taught how to
express their milk by using sanitary collecting methods.
Donated milk is treated by heat to destroy any bacteria or
viruses. Common reasons for prescribing donor milk
include allergies and formula intolerance, prematurity,
failure to thrive, immunologic deficiencies, and postop-
erative nutrition.
Conclusion
Breastfeeding ensures the best possible physical health as
well as developmental and psychosocial outcomes for
infants. Overwhelming evidence supports strong recom-
mendations to increase and sustain breastfeeding in the
population. The biologic and immunologic markers in
human milk, such as the specific antibodies and cellular
factors as listed in Table 2, are very important to infant
health, as are the various nutrients. There are very few
416 Pediatrics in Review Vol.27 No.11 November 2006
absolute contraindications to breastfeeding. It is imper-
ative that pediatricians and other medical care practitio-
ners have an in-depth understanding of the innumerable
benefits of breastfeeding. Breastfeeding should become a
cultural norm among all women, regardless of education
and socioeconomic status.
References
1. AAP Section on Breastfeeding Policy Statement. Breastfeeding
and the use of human milk. Pediatrics. 2005;115:496 –506
2. Horwood LJ, Darlow BA, Mogridge N. Breast milk feeding and
cognitive ability at 7– 8 years. Arch Dis Child Fetal Neonatal Ed.
2001;84:F23–F27
3. Lopez-Alarcon M, Villalpando S, Fajardo A. Breastfeeding low-
ers the frequency and duration of acute respiratory infection and
diarrhea in infants under six months of age. J Nutrition. 1997;127:
436 – 443
4. Holberg CJ, Wright AL, Martinez FD, Ray CG, Taussig LM,
Lebowitz MD. Risk factors for respiratory syncytial virus-associated
lower respiratory illnesses in the first year of life. Am J Epidemiol.
1991;133:1135–1151
5. Oddy WH, Peat JK, de Klerk NH. Maternal asthma, infant
feeding and the risk of asthma in childhood. J Allergy Clin Immu-
nol. 2002;110:65– 67
6. American Academy of Pediatrics, Committee on Infectious Dis-
eases. Management of newborn infant whose mother has tubercu-
losis. 2006 Red Book, Report of the Committee on Infectious Diseases.
27th ed. Elk Grove Village, Ill: American Academy of Pediatrics;
2006:694 – 695
7. World Health Organization. New data on the prevention of
mother to child transmission of HIV and their policy implications.
Conclusions and recommendations. Technical consultation on be-
half of the UNFPA/ UNICEF/WHO/UNADIS Inter-Agency
Task Team on Mother-Child Transmission of HIV. Geneva, Swit-
zerland: October 2000. Available at: http://www.who.int/
reproductive-health/stis/mtct/kesho_bora.htm. Accessed 8/26/06
8. Hale T. Medications and Mother’s Milk. 11th ed. Amarillo, Tex:
Pharmasoft Publishing; 2004
Suggested Reading
Cahill JB, Wagner CL. Challenges in breastfeeding. Contemp Pedi-
atr. 2002;19:94 –138
Churchill RB, Pickering LK. The pros (many) and cons (a few) of
breastfeeding. Contemp Pediatr. 1998;15:108 –119
Lawrence RA. Breastfeeding: A Guide for the Medical Profession. 5th
ed. St Louis, Mo: Mosby-YearBook, Inc; 1999
Philipp BL, Cadwell K. Fielding questions about breastfeeding.
Contemp Pediatr. 1999;16:149 –164
Riordan J. Breastfeeding and Human Lactation. 3rd ed. Sudbury,
Mass: Jones and Bartlett Publishers; 2005
 nutrition breastfeeding

PIR Quiz
Quiz also available at www.pedsinreview.org.

5. You are discussing the physiology of lactation with a medical student. Which of the following statements is
true?
A. After delivery, the prolactin concentration drops, leading to increased milk synthesis.
B. Lactation does not occur if pregnancy does not progress beyond 20 weeks.
C. Obesity does not interfere with lactogenesis.
D. Oxytocin causes the milk-ejection reflex or letdown.
E. The rate of milk synthesis is not related to the degree of emptiness or fullness of the breast.

6. Compared with mature human milk, colostrum contains more:

A. Calories.
B. Carbohydrate.
C. Fat.
D. Protein.
E. Vitamin C.

7. Of the following pathogens, breastfeeding is most likely to protect against infection caused by:
A. Escherichia coli.
B. Hepatitis C virus.
C. Herpes simplex virus.
D. Human immunodeficiency virus.
E. Mycobacterium tuberculosis.

8. You are evaluating a healthy breastfed newborn. In which of the following conditions would you strongly
advise against breastfeeding?
A. The mother has a history of positive purified protein derivative test with negative chest radiograph and
is currently receiving isoniazid treatment.
B. The mother is a chronic hepatitis C carrier.
C. The mother is cytomegalovirus-positive.
D. The mother is hepatitis B surface antigen-positive.
E. The mother is receiving chemotherapeutic agents for breast cancer treatment.

Pediatrics in Review Vol.27 No.11 November 2006 417

consultation with the specialist

Cardiovascular Preparticipation
Sports Screening
Anoop Singh, MD,* Michael Silberbach, MD†

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

1. Describe the key cardiac elements of the preparticipation examination.

Author Disclosure
Drs Singh and Silberbach did not
disclose any financial relationships
relevant to this article.
To view a sample preparticipation
evaluation form, visit
www.pedsinreview.org and click on
Consultation with the Specialist.
2. Identify red flags in a patient’s cardiac history and physical examination
that warrant consultation with a cardiologist.
3. Characterize the cardiovascular findings of the well-trained athlete.
4. Recognize the common causes of sudden cardiac death on the playing field.
5. Discuss the absolute and relative contraindications to athletic participation.
Background
In the United States, the prepartici-
pation examination (PPE) has be-
come a standard for athletic clearance
of high school students in nearly ev-
ery state. This screening serves many
purposes, but a primary goal is to
restrict athletic participation of those
who may be predisposed to dying on
the playing field.
The death of a high school athlete
devastates the child’s family, signifi-
cantly affects the local community,
and often generates extensive media
coverage. Fortunately, sudden death
remains a rare phenomenon; best es-
timates predict an incidence of 1 per
200,000 high school athlete-years.
In 75% of such cases, cardiovascular
disease is the cause. Accordingly,
medical professionals must have a
keen sense for detecting silent cardiac
disease in young athletes.
History Taking
The medical history is the most im-
portant part of the cardiovascular
PPE. It is best to ask open-ended
questions of the patient. A volun-
teered complaint warrants greater at-
*Fellow, Pediatric Cardiology, Department of
Pediatrics, Oregon Health & Science University,
Portland, Ore.
†
Editorial Board.
tention than a “yes/no” response.
A checklist of questions that probes
for potential cardiac disease is also
helpful (see the form available in the
online version of this article only).
Family concerns or observations
complement the picture of the ado-
lescent’s health. Indeed, the Ameri-
can Heart Association recommends
that a parent verify all elements of the
history.
The personal history focuses on
symptoms such as chest pain, chest
tightness, dyspnea, near-syncope,
syncope, dizziness, exercise intoler-
ance, and fatigue. The setting in
which symptoms occur is very impor-
tant. Symptoms in the context of ath-
letic activity may be a harbinger of
cardiovascular disease. For example,
a history suggestive of vasovagal syn-
cope is less concerning than one of
exercise-related syncope. On the
other hand, palpitations may be
more noticeable and worrisome
when they occur at rest.
A detailed medication history in-
cludes both prescribed medications
and supplements. When asking about
illicit drug use, particular attention
should be given to performance-
enhancing drugs such as androgenic
steroids, human growth hormone, and
amphetamines.
Important components of the

418 Pediatrics in Review Vol.27 No.11 November 2006


past medical history include rheu-
matic fever, Kawasaki disease, myo-
carditis, arrhythmias, congenital
heart disease, heart murmurs, or hy-
pertension. Essential hypertension,
increasingly common in the adoles-
cent population, always warrants an
evaluation for secondary causes. Fi-
nally, unexplained seizures or near-
drowning raise the possibility of car-
diac ion channel defects, such as the
long QT syndrome (LQTS).
The family history is an integral
part of the screening process because
it may initiate additional evaluation
of an asymptomatic patient. Perti-
nent family history includes congen-
ital heart disease, Marfan syndrome
or other connective tissue disorders,
cardiomyopathy, and LQTS or other
arrhythmias. Searching for silent car-
diac disease entails asking specifically
about unexplained sudden death in
the family, such as unexplained
drowning, near-drowning, seizures,
or an automobile fatality, especially
involving a family member younger
than 50 years of age.
Physical Examination
Vital signs are an important aspect of
the physical examination. The heart
rate and blood pressure are com-
pared with age-specific norms. Hy-
pertension in children is defined as a
blood pressure greater than the 90th
percentile for age, height, and sex.
Hypertension warrants, at a mini-
mum, four extremity blood pressure
measurements and another measure-
ment at a separate office visit.
The general examination of the
patient includes an overall assess-
ment for features suggestive of
Marfan syndrome, such as kyphosco-
liosis, pectus deformity, arm span
greater than height, joint hypermo-
bility, arachnodactyly, and a tall and
thin body habitus.
Auscultation of the chest focuses
on heart sounds, clicks, and cardiac
Red Flags in the History or Physical
Table 1.
Examination
● Syncope or near-syncope on exertion
● Chest pain/discomfort on exertion
● Palpitations at rest
● Excessive shortness of breath or fatigue with activities
● Family history of Marfan syndrome, cardiomyopathy, long QT syndrome, or
clinically significant arrhythmias
● Family history of premature, sudden death
● Irregular heart rhythm
● Weak or delayed femoral pulses
● Fixed, split second heart sound
● Any systolic murmur graded 3/6 or greater
● Any diastolic murmur
● Stigmata of Marfan syndrome
● Chest pain in Turner syndrome
murmurs and is performed with the
patient in both the supine and stand-
ing positions. The standing position
accentuates the dynamic obstruction
murmur of hypertrophic cardiomy-
opathy. The abdomen must be pal-
pated to detect organomegaly. Fi-
nally, the physical examination must
include assessment of femoral pulses
to screen for aortic coarctation.
When to Refer
Referring a patient to a pediatric car-
diologist depends on the experience
and comfort level of the primary care
practitioner. Although each case has
its own nuances, there are “red flags”
in the history and examination that
usually prompt consultation with a
pediatric cardiologist (Table 1).
Cardiology Evaluation
A patient referred to a pediatric car-
diologist may or may not require any
testing, depending on the results of
the history and physical examination.
When more information is needed, a
chest radiograph and electrocardio-
gram (ECG) often are obtained.
However, left ventricular hypertro-
phy is difficult to diagnose on a plain
film, and as many as 15% of those
who have cardiac hypertrophy have a
consultation with the specialist
completely normal 12-lead ECG
tracing. Accordingly, an echocardio-
gram is often part of the primary
investigation in referred patients. Ad-
ditional tests at the cardiologist’s
disposal include ambulatory ECG
monitoring, 30-day ECG-event mon-
itoring, exercise stress testing, electro-
physiology studies, stress echocardio-
grams, cardiac magnetic resonance
imaging, cardiac catheterization, and
angiography.
The responsibilities of the pediat-
ric cardiologist are threefold: 1) find-
ing cardiovascular disease in undiag-
nosed patients and initiating therapy,
2) identifying those patients at risk
for sudden cardiac death, and
3) clearing healthy individuals for full
athletic participation.
There is, however, a gray area be-
tween healthy-appearing and diseased
hearts. The well-trained athlete’s heart
falls into this indeterminate category.
The Athlete’s Heart
Just as aerobic and isometric exercise
have visible effects on skeletal mus-
cle, athletic training remodels cardiac
muscle. Such morphologic changes
present a challenge to the clinician,
who must distinguish between be-
Pediatrics in Review Vol.27 No.11 November 2006 419
consultation with the specialist
nign adaptation to exercise and car-
diac disease.
Endurance training normally re-
sults in enlargement of the left ven-
tricular cavity due to an increased
stroke volume. Basal cardiac output
is unaffected because the well-
conditioned athlete’s resting heart
rate is decreased. However, the de-
gree of left ventricular enlargement
can approach dimensions seen pri-
marily in diseased hearts.
Another conundrum is presented
by left ventricular hypertrophy. Stud-
ies have shown that 2% of highly
trained male athletes demonstrate
significant increases in left ventricular
wall thickness. Thus, echocardio-
graphically determined cardiac mea-
surements may overlap with diagnostic
criteria for hypertrophic cardiomyopa-
thy. In these patients, the suspicion
increases if there is a positive family
history for cardiomyopathy, an asym-
metry between the septal and poste-
rior left ventricular wall thickness by
echocardiography, a lack of concur-
rent left ventricular cavity enlarge-
ment, an abnormal ECG tracing, or
no decrease in thickness with decon-
ditioning.
In addition to structural changes,
the athlete’s heart displays unusual
ECG patterns, arrhythmias, and con-
duction abnormalities. An Italian
study showed that 40% of athletes
had abnormal electrical patterns on
ECG recordings in a population in
whom only 5% had a cardiovascular
abnormality. Ambulatory ECG mon-
itoring in normal athletes may show
junctional rhythm at rest, frequent
premature ventricular beats, ventric-
ular couplets, or nonsustained ven-
tricular tachycardia that can be con-
fused with ventricular irritation from
myocarditis.
Athletes who have left ventricular
enlargement or hypertrophy and are
deemed otherwise healthy should be
cleared to participate in sports. How-
420 Pediatrics in Review Vol.27 No.11 November 2006
ever, it should be noted that such
physiologic changes cannot be la-
beled definitively as benign. One
long-term echocardiographic study
following elite athletes showed that
cardiac chamber enlargement per-
sisted despite deconditioning in 20%
of the retired athletes. Thus, the sig-
nificance of exercise-induced ventric-
ular remodeling remains undefined.
Sudden Death
The exact number of young athletes
dying during competitive sports is
uncertain. Incidence estimates range
from 1 per 44,000 to 1 per 200,000
athlete-years. Approximately 75% of
all sudden deaths are due to cardio-
vascular disease, with hypertrophic
cardiomyopathy being the most
common cause. Fatal events due to
commotio cordis comprise the bulk
of sports-related deaths not due to
underlying cardiovascular disease.
Knowing that the presenting event of
previously undetected cardiovascular
disease may be death makes a com-
pelling case for the importance of the
PPE.
Hypertrophic Cardiomyopathy
(HCM)
HCM is the most common cause of
sudden cardiac death in young ath-
letes. HCM has an autosomal domi-
nant inheritance pattern, with more
than 400 mutations on 12 genes de-
scribed thus far. The prevalence in
the general population is estimated
to be 0.2%. Clinical features that may
raise suspicion for the disease include
symptoms of left ventricular outflow
obstruction, a heart murmur, family
history of HCM, or an abnormal
ECG tracing. Echocardiography
demonstrates left ventricular hyper-
trophy that classically is asymmetric.
However, absence of cardiac hyper-
trophy does not rule out the presence
of HCM. At the cellular level, myo-
fibrillary disarray creates a substrate
for electrical instability. Sudden
death is likely the result of re-entrant
ventricular arrhythmias.
Congenital Coronary Artery
Anomalies
Coronary arteries arising from the
wrong sinus are the second leading
cardiac cause of death on the playing
field. Of these congenital malforma-
tions, a left main coronary artery
originating from the right sinus of
Valsalva and traveling between the
aorta and main pulmonary artery is
the most common. Affected patients
may experience chest pain on exer-
tion. However, findings on physical
examination and ECG are usually
normal. The exact mechanism of
sudden death is debated. The abnor-
mal coronary vessel often arises at an
acute angle from the sinus of Val-
salva; this precipitous origin may pre-
dispose to ischemia when myocardial
demands increase with exercise.
Marfan Syndrome
Marfan syndrome is an autosomal
dominant disorder caused by muta-
tions in the gene encoding the pro-
tein fibrillin, a key component of
connective tissue. The estimated
prevalence ranges from 1 per 5,000
to 1 per 10,000. Clinical features in-
clude kyphoscoliosis, pectus defor-
mities, arm span greater than height,
joint hypermobility, arachnodactyly,
pes planus, lens dislocation, myopia,
and a history of spontaneous pneu-
mothorax. Cardiac manifestations in-
clude aortic root dilatation, aortic
dissection, and mitral valve prolapse.
The diagnosis is based on the family
history and clinical criteria. Sudden
cardiac death is due to dissection and
rupture of the aorta.
Congenital LQTS
LQTS involves the generation of an
abnormal myocardial action poten-
tial due to defects in cell membrane-
 consultation with the specialist

Figure. A. 12-lead electrocardiogram tracing from a 10-year-old who has long QT syndrome, demonstrating a prolonged QTc of 590
msec. B. Rhythm strip from a 14-year-old during an episode of polymorphic ventricular tachycardia (torsades de pointes).

Pediatrics in Review Vol.27 No.11 November 2006 421

consultation with the specialist
associated ion channel proteins. The
diagnosis is considered when a pro-
longed QTc interval [Bazett formula
(QT in msecs and RR in secs):
QTc⫽QT/公RR] accompanies a
history of syncope. Sensorineural
deafness, present in the autosomal
recessive form of LQTS (Jervell and
Lange-Nielsen syndrome), may be
an additional clue. Syncope is due to
self-limited episodes of polymorphic
ventricular tachycardia called tor-
sades de pointes (Figure). Prolonged
QTc interval and a positive family
history are important risk factors for
sudden death. Although the arrhyth-
mia may occur at any age, there is a
predilection for cardiac events in ad-
olescence. Sudden death occurs
when the arrhythmia degenerates
into ventricular fibrillation.
Commotio Cordis
Commotio cordis causes 20% of all
sudden deaths in young athletes. It
occurs when blunt, nonpenetrating
trauma to the chest produces ventric-
ular fibrillation. The blow often is
neither excessive nor associated with
structural injury. Arrhythmias may
be induced by enhanced energy
transfer to the heart through the
child’s compliant chest wall coincid-
ing with a vulnerable period of car-
diac repolarization. Projectiles such
as baseballs and hockey pucks have
been implicated most often in com-
motio cordis. Survival is less than
15% but improves if prompt cardio-
pulmonary resuscitation and defibril-
lation occur.
Eligibility and
Disqualification From Sports
Young athletes who have cardiovas-
cular disease are at greater risk for
sudden death than are nonathletes
who have cardiac disease. Perhaps ex-
treme exercise stress triggers rare
events such as malignant arrhythmias
that otherwise would remain hidden.
422 Pediatrics in Review Vol.27 No.11 November 2006
Thus, the rationale for athletic dis- contraction, resulting in an increas-
qualification is that the cessation of ing pressure load on the heart. Static
athletic activity may be protective. exercise should be avoided by pa-
The current recommendations for tients who have left heart obstructive
sports eligibility are based on the disease, regurgitant aortic valves, or
consensus opinion outlined in the connective tissue disorders where
36th Bethesda Conference guide- aortic dilation is a risk. However, it
lines. Although the recommenda- may be appropriate to recommend
tions generally are conservative, only moderate dynamic and low static ac-
a handful of cardiovascular condi- tivities for these individuals. Dy-
tions require disqualification from all namic exercises, on the other hand,
sports (Table 2). The Bethesda eligi- require isotonic muscle contraction
bility criteria do not apply to non- and typically result in increasing the
competitive, recreational activities. cardiac output. High-intensity dy-
The American Heart Association has namic exercises may be stressful for
published separate guidelines. patients who have even mild ventric-
The clinician must consider mul- ular dysfunction. Such patients
tiple factors, both physical and psy- might be restricted to low dynamic/
chological, before disqualifying a low static competitive sports.
particular patient. In many cases, the
activities may be limited and not Conclusion
eliminated. For example, individuals The PPE is the optimal tool available
who have Marfan syndrome or an im- to primary care practitioners for pre-
plantable cardioverter-defibrillator are venting heart disease-related deaths
cautioned to avoid sports that carry a on the playing field. However, there
risk of bodily collision. is considerable variability in the de-
Because different sports carry dif- tails of the screening process, and
ferent risks, it may be possible to many states have either no or inade-
tailor recommendations to an indi- quate examination forms. Standard-
vidual patient. It is possible to cate- izing the history and physical form
gorize various activities into static and creating accreditation criteria for
and dynamic exercise components, clinicians who perform the examina-
permitting classification in terms of tion would be two good steps toward
the type of stress (Table 3). Static optimizing the PPE. The cost/
exercise involves isometric muscle benefit ratio of obtaining an ECG or
Absolute Contraindications to Sports
Table 2.
Participation
● Pulmonary vascular disease with cyanosis and large right-to-left shunt
● Severe pulmonary hypertension
● Severe aortic stenosis or regurgitation
● Severe mitral stenosis or regurgitation
● Cardiomyopathies
● Vascular form of Ehlers-Danlos syndrome
● Coronary anomalies of wrong sinus origin
● Catecholaminergic polymorphic ventricular tachycardia
● Acute phase of pericarditis
● Acute phase of myocarditis (at least 6 mo)
● Acute phase of Kawasaki disease (at least 8 wk)
 consultation with the specialist

Classification of Sports According to

Table 3. and an ECG in addition to the his-
tory and physical examination. In
Type of Exercise this month’s Internet-only pages of
PIR, Dr Renato Vitiello cites data
Low Dynamic Moderate Dynamic High Dynamic
suggesting that sudden death from
Low Static Billiards Baseball Badminton HCM in athletes can be reduced by
Bowling Softball Field hockey this approach. The Italian perspec-
Cricket Fencing Racquetball
Golf Table tennis Soccer tive may soon be adopted by all of
Riflery Volleyball Tennis Europe. – Michael Silberbach, MD
Track (long distance)
Moderate Archery Field events Basketball
Static Auto racing Figure skating Ice hockey
Diving Football/Rugby Lacrosse
Equestrian Rodeo Track (middle distance) Suggested Reading
Motorcycling Surfing Swimming Corrado D, Pelliccia A, Bjornstad HH, et al.
Track (sprinting) Cross-country skiing Cardiovascular pre-participation screen-
High Static Bobsledding Bodybuilding Boxing ing of young competitive athletes for
Field (throwing) Downhill skiing Canoeing/Kayaking prevention of sudden death: proposal
Gymnastics Skateboarding Cycling for a common European protocol. Con-
Sailing/Windsurfing Snowboarding Rowing sensus Statement of the Study Group of
Sport climbing Wrestling Speed skating Sport Cardiology of the Working Group
Weight lifting Triathlon/Decathlon of Cardiac Rehabilitation and Exercise
Physiology and the Working Group of
Modified from Task Force 8; classification of sports. J Am Coll Cardiol. 2005;5:1366. Copyright Myocardial and Pericardial Diseases of
2005. The American College of Cardiology Foundation and American Heart Association, Inc. the European Society of Cardiology.
Permission granted for one time use. Additional reproduction is not permitted without permission of
the ACC/AHA. Eur Heart J. 2005;26:516 –524
Glover DW, Maron BJ. Profile of prepartici-
pation cardiovascular screening for high
school athletes. JAMA. 1998;279:
focused cardiac ultrasonography to 1817–1819
accidents, homicide, and suicide are
Maron BJ. Sudden death in young athletes.
rule out hypertrophic cardiomyopa- far more prevalent problems, causing N Engl J Med. 2003;349:1064 –1075
thy continues to be debated in the 10,000 deaths a year in 15- to 19- Maron BJ, Shirani J, Poliac LC, Mathenge
United States. A recent consensus year-olds. Although the primary care R, Roberts WC, Mueller FO. Sudden
statement from Europe has advo- practitioner assiduously seeks to death in young competitive athletes.
Clinical, demographic, and pathological
cated the use of 12-lead ECGs based identify heart disease during the
profiles. JAMA. 1996;276:199 –204
on the 25-year experience in Italy screening visit, it is equally important Moss AJ. Long QT syndrome. JAMA.
where electrocardiography has been to promote a physically active life- 2003;289:2041–2044
an integral part of the PPE. (See style that encourages both mental Pelliccia A, Maron BJ, Culasso F, et al.
commentary by Dr Renato Vitiello in and cardiovascular health. Clinical significance of abnormal elec-
trocardiographic patterns in trained ath-
the Internet-only pages.)
letes. Circulation. 2000;102:278 –284
This article has focused on identi- EDITORIAL BOARD NOTE. In the Pelliccia A, Maron BJ, De Luca R, Di Paolo
fying silent cardiovascular disease United States, medical evaluation FM, Spataro A, Culasso F. Remodeling
and defining criteria for determining prior to participation in sports is stan- of left ventricular hypertrophy in elite
sports eligibility in young athletes. It dard practice, but national guidelines athletes after long-term deconditioning.
Circulation. 2002;105:944 –999
is important to remember that the for the PPE are not established. In
36th Bethesda Conference: eligibility rec-
incidence of sudden cardiac death Italy, a federal law sets a single, high ommendations for competitive athletes
during sports participation is ex- standard for the entire country that with cardiovascular abnormalities. J Am
tremely low. In the United States, requires certification for screeners Coll Cardiol. 2005;45:1312–1375

Pediatrics in Review Vol.27 No.11 November 2006 423

consultation with the specialist

PIR Quiz
Quiz also available online at www.pedsinreview.org.

9. A pediatrician is conducting a history and preparticipation physical examination on a teenager. In the

medical history, the event that would be most suspicious for an inherited cardiac ion channel defect, such
as the long QT syndrome, is:
A. Extreme weight loss.
B. History of narcolepsy.
C. Near-drowning.
D. Status asthmaticus.
E. Episodes of vertigo.

10. Sudden death during competitive sports remains a tragic phenomenon in athletes. The percent of these
deaths attributable to underlying cardiovascular disease is estimated to be:
A. 20%.
B. 40%.
C. 50%.
D. 75%.
E. 100%.

11. You have been asked to help at the local sports clinic day for your community. Your assignment is the
cardiovascular station for the high school football team. In examination of the athletes, the physical
finding most suggestive of hypertrophic cardiomyopathy is:
A. A continuous murmur heard on auscultation.
B. A pectus deformity.
C. A systolic murmur accentuated in the standing position.
D. Joint hypermobility.
E. Weak or delayed femoral pulses.

12. You are examining a cross country runner who has had occasional episodes of chest pain. His daily
training includes running 10 miles a day. There is a family history of sudden death of an uncle at a young
age while playing football, raising your concern about cardiomyopathy. You schedule him for
echocardiography. The information on this study that would most suggest hypertrophic cardiomyopathy is:
A. Asymmetric thickness between the septal and posterior left ventricular wall.
B. Bicuspid aortic valve.
C. Left ventricular cavity enlargement.
D. Left ventricular thickening that normalizes with a month of deconditioning.
E. The presence of a patent foramen ovale.

For the following questions, match the specific condition with the way this condition might cause a fatal
event.

13. Commotio cordis

14. Congenital coronary artery anomalies

15. Hypertrophic cardiomyopathy

16. Long QT syndrome

17. Marfan syndrome

A. Aortic dissection.
B. Blunt trauma to the chest wall producing ventricular fibrillation.
C. Electrically unstable myocardium as substrate for ventricular arrhythmias.
D. Myocardial ischemia leading to ventricular fibrillation.
E. Torsades de pointes degenerating into ventricular fibrillation.

424 Pediatrics in Review Vol.27 No.11 November 2006


The reader is encouraged to write
possible diagnoses for each case before
turning to the discussion. We invite
readers to contribute case
presentations and discussions.
Please inquire first by contacting Dr.
Nazarian at LFredN@aol.com.
Author Disclosure
Drs McPeak, Guerra, Nefcy, LaShell,
Wolf, and Algon did not disclose any
financial relationships relevant to
these cases.
To view Suggested Reading lists for these
cases, visit pedsinreview.org and click on
Index of Suspicion.
Frequently Used Abbreviations
ALT: alanine aminotransferase
AST: aspartate aminotransferase
BUN: blood urea nitrogen
CBC: complete blood count
CNS: central nervous system
CSF: cerebrospinal fluid
CT: computed tomography
ECG: electrocardiography
ED: emergency department
EEG: electroencephalography
ESR: erythrocyte sedimentation
rate
GI: gastrointestinal
GU: genitourinary
Hct: hematocrit
Hgb: hemoglobin
MRI: magnetic resonance imaging
WBC: white blood cell
Case 1 Presentation
A 10-month-old boy is brought to a
community ED because he started
vomiting last night and “has not
been the same since.” This morning,
his mother noted that he was breath-
ing fast. He had a low-grade fever
this morning, but none prior. He has
had no weight loss or diarrhea and
has not been exposed to illness. In-
travenous access is obtained, and the
child is intubated because of respira-
tory distress and is flown to a chil-
dren’s hospital.
On examination, the boy’s tem-
perature is 37.6°F (99.7°C), heart
rate is 158 beats/min, and blood
pressure is 90/44 mm Hg. His respi-
ratory rate had been 60 breaths/min
prior to being intubated. He is a
plump, robust infant who is sedated
on the ventilator. Faint crackles are
audible in his lungs. His skin is warm
and well perfused. The rest of his
findings are normal.
Laboratory findings include glu-
cose, 176 mg/dL (9.8 mmol/L); so-
dium, 140 mEq/L (140 mmol/L);
potassium, 3.1 mEq/L (3.1 mmol/);
chloride, 115 mEq/L (115 mmol/L);
bicarbonate, 10 mEq/L (10 mmol/
L); calculated anion gap, 15 mEq/L
(15 mmol/L); BUN, 5 mg/dL
(1.8 mmol/L); and creatinine,
0.3 mg/dL (26.5 mcmol/L).
A blood gas reveals a pH of 7.29 with
a bicarbonate level of 14 mEq/L
(14 mmol/L), a carbon dioxide con-
centration of 14 torr, and a base deficit
of ⫺18.6 mEq/L. His WBC count is
14.9⫻103/mcL (14.9⫻109/L) with
71% neutrophils and 2% bands. He is
started on vasoactive medication for
hypotension and treated for sepsis,
but the clinicians are concerned that
he has had minimal fever and no rash,
and the laboratory findings are puz-
zling. An additional blood test re-
veals the diagnosis.
index of suspicion
Case 2 Presentation
A 4-year-old boy is brought to the
clinic because of a chest deformity.
Born at term, his birthweight was 3.8
kg, and his perinatal course was un-
remarkable. When he was 1 year old,
his mother first noticed a concavity in
his mid-chest region. Two years ago,
he developed mild intermittent
asthma that has been well controlled
with allergen avoidance and occa-
sional inhaled bronchodilator ther-
apy. His weight is 17 kg (50th per-
centile) and his height is 112 cm
(99th percentile). His development
is consistent with his age, except for
moderate language delays, for which
he receives speech therapy.
On physical examination, a
marked pectus excavatum deformity
is evident, as well as thoracic spine
scoliosis and bilateral pes planus. Ad-
ditional clinical findings lead to sus-
picion of a specific syndrome.
Case 3 Presentation
A 14-year-old boy is sent to the ED
by his pediatrician because of a
2-month history of increasing fa-
tigue, dyspnea on exertion, and an
8-lb weight loss. A chest radiograph
performed yesterday shows bilateral
patchy infiltrates. He denies fever,
vomiting, diarrhea, changes in appe-
tite, or feeling lightheaded. The boy
recently visited Puerto Rico for
10 days and works in a dog kennel on
weekends. He has had no significant
past illnesses and does not take any
medications on a regular basis.
On physical examination, his tem-
perature is 97.6°F (36.5°C), heart
rate is 102 beats/min, respiratory
rate is 20 breaths/min, and blood
pressure is 114/68 mm Hg. There
are diminished breath sounds bilater-
ally throughout his lung fields, but
he has no respiratory distress. His
oxygen saturation is 92% on room
air.
Pediatrics in Review Vol.27 No.11 November 2006 425
index of suspicion
The boy’s WBC count is
6.8⫻103/mcL (6.8⫻109/L), Hgb
value is 16.1 g/dL (160 g/L), Hct
is 45.6% (0.456), and platelet count
is 283⫻103/mcL (283⫻109/L).
Electrolyte concentrations, liver
function tests, and protein and albu-
min concentrations are within nor-
mal limits. Blood glucose concentra-
tion is 92 mg/dL (5.1 mmol/L),
calcium is 12.4 mg/dL (3.1 mmol/
L), and ionized calcium is 5.6 mg/
dL (1.4 mmol/L). His ESR is 3 mm/
h. A CT scan of his chest reveals
bilateral ground-glass opacities with
prominent mediastinal and hilar
lymph nodes bilaterally. He is admit-
ted to the hospital for intravenous
hydration, treatment of his hypercal-
cemia and oxygen requirement, and
additional evaluation of his pulmo-
nary disease.
Case 1 Discussion
The child had an anion gap acidosis,
but no evidence of a disorder that
would cause lactic acidosis. Although
he had been vomiting for 12 hours,
he had no other insensible losses to
explain the rapid deterioration. Dia-
betic ketoacidosis seemed unlikely
because his glucose level never ex-
ceeded 200 mg/dL (11.1 mmol/L).
The wide anion gap acidosis
prompted measurement of salicylate
concentrations, although there was
no history of ingestion. Salicylates
were present at a toxic level of
60 mg/dL (4.3 mmol/L). The pa-
tient was alkalinized immediately and
dialyzed. In 24 hours, he was extu-
bated and was doing well.
Laboratory Clues
Severe dehydration from vomiting or
diarrhea can cause a significant lactic
acidosis due to tissue hypoxemia and
hypoperfusion. However, this child
had only a brief history of vomiting.
The rapid breathing and respiratory
426 Pediatrics in Review Vol.27 No.11 November 2006
distress that required intubation led
the clinicians to consider an underly-
ing metabolic derangement. Other
disorders to consider in this case are
methanol toxicity, uremia, diabetic
ketoacidosis, paraldehyde ingestion,
iron and isoniazid toxicities, lactic ac-
idosis, and ethylene glycol ingestion.
The addition of salicylism to the list
creates the “MUDPILES” mne-
monic.
In this case, the child’s mother
later discovered that one of the sib-
lings had given the infant several
adult aspirin tablets. Although the
ingestion history was not known at
the time of admission, a thorough
investigation of the child’s wide an-
ion gap acidosis led to the diagnosis.
Other supporting laboratory findings
included the potassium concentra-
tion of 3.1 mEq/L (3.1 mmol/L) and
serum bicarbonate level of 10 mEq/L
(10 mmol/L).
The Disorder
Aspirin toxicity remains one of the
most serious ingestions in the pediat-
ric population. Despite the recent
declining incidence, there still are ap-
proximately 16,000 cases yearly of
aspirin overdose in this country, re-
sulting in 30 to 35 deaths. An acute
toxic dose for a child is greater than
150 mg (approximately one half of a
325-mg adult tablet) per kg. Al-
though overall use of aspirin has de-
creased, most households in the
United States still contain salicylates
in one form or another (tablets, bis-
muth compounds, keratolytic agents).
Pathophysiology
Salicylates have a broad scope of ac-
tion, especially in toxic doses, be-
cause of their ability to uncouple ox-
idative phosphorylation, inhibit
amino acid synthesis, and inhibit
Krebs cycle enzymes. The emesis and
nausea that patients experience after
aspirin ingestion are related to direct
gastric irritation. Other effects in-
clude altered hearing (usually tinni-
tus), fever, and altered mental status
that can range from agitation to sei-
zures to stupor and coma.
In the initial phase of aspirin over-
dose, patients experience respiratory
alkalosis due to direct stimulation of
the CNS respiratory drive. To correct
this alkalosis, bicarbonate is excreted
in the urine, causing alkaluria. Ini-
tially, potassium also is excreted in
the urine, leading to global hypoka-
lemia. In the next phase of salicylate
toxicity, the kidneys attempt to pre-
serve the potassium level by an ex-
change for hydrogen ions in the
urine. This paradoxic aciduria in the
face of a respiratory alkalosis is a hall-
mark of aspirin toxicity.
In the final stages of aspirin over-
dose, hyperpnea continues as a re-
sponse to the primary metabolic aci-
dosis. This exaggerated breathing
contributes further to insensible wa-
ter losses. Although adults tend to
have a mixed respiratory alkalosis and
metabolic acidosis, acidosis often
predominates in young children. Fi-
nally, as in this infant, salicylates in-
crease pulmonary vasculature perme-
ability, leading to noncardiogenic
pulmonary edema.
Laboratory Evaluation
Several studies should be ordered in
cases of suspected salicylate toxicity.
Electrolytes, BUN, creatinine, arte-
rial blood gases, complete blood
count, and liver function tests should
be checked immediately. Hypokale-
mia is common and can be severe.
Salicylate levels should be checked
immediately if ingestion is suspected
and subsequently checked every 2 to
4 hours until decreasing or reaching
less than 30 mg/dL (2.2 mmol/L).
Although levels typically peak 4 to
6 hours after aspirin ingestion and
correlate poorly with clinical symp-
toms, prolonged peaking of salicy-

lates occurs with ingestion of enteric-
coated tablets or in the presence of
any obstruction in the GI tract, such
as a pill bezoar or pylorospasm.
As in this patient, if the diagnosis
is uncertain, additional laboratory
testing should be undertaken to rule
out other causes of anion gap acido-
sis. Serum lactate, osmolarity, and a
urinalysis looking for ketones can be
helpful. It also may be useful to mea-
sure iron and alcohol levels (looking
for methanol and ethylene glycol).
As always, a thorough history is indi-
cated, particularly focusing on all
medications, including over-the-
counter items, in the household.
Treatment
If the patient is alert, activated char-
coal should be administered. Gastric
lavage usually is not recommended
unless the ingestion is believed to
have been a large, life-threatening
dose and has been brought to medi-
cal attention within 1 hour. Most
important in the treatment of salicyl-
ism is the correction of multiple met-
abolic derangements and dehydra-
tion. Initially, fluid boluses should be
considered in the face of severe dehy-
dration. Caution must be exercised
in the presence of pulmonary edema
or renal failure.
Alkalinization enhances salicylate
elimination and should be instituted
promptly. A goal for serum pH
should be approximately 7.5, with a
goal for urinary pH of greater than
7.5. Standard recommendations sug-
gest using a 1 to 2-mEq/kg bolus of
bicarbonate followed by a sodium bi-
carbonate drip. Because persistent
hypokalemia may interfere with alka-
linization of the urine and salicylate
excretion, it is critical to add potas-
sium to fluids in patients who do not
have renal failure.
Dialysis should be instituted if the
serum salicylate level is greater than
100 mg/dL (7.2 mmol/L) in acute
toxicity or if there are signs of pulmo-
nary edema, renal failure, persistent
altered mental status, worsening vital
signs such as fever, or congestive
heart failure.
Intubation might be considered
in the most seriously ill patients. Cli-
nicians should realize, however, that
intubation of the patient poisoned by
salicylates can be dangerous. The pa-
tient’s own ability to hyperventilate
and regulate acidosis is suppressed,
and he or she may develop worsening
acidosis.
Rarely do long-term sequelae re-
sult from salicylate toxicity. When
recognized and treated early, most
pediatric patients do very well.
Lessons for the Clinician
It is important to consider salicylism
in the differential diagnosis of a child
who has an anion gap acidosis. In this
case, a careful review of the initial
history, physical findings, and labora-
tory studies narrowed the differential
diagnosis significantly. Early recogni-
tion and treatment can be life-saving.
(Katie E. McPeak, MD, Children’s
Hospital of Pittsburgh, Pittsburgh,
Pa.)
Case 2 Discussion
On further examination, the boy’s
arm span was 114 cm and arm span-
to-height ratio was 1.01 (upper limit
of normal, 1.05). His lower segment
measured 59 cm, upper segment was
53 cm, and upper-to-lower segment
ratio was 0.9 (normal, ⬎1). A scoli-
osis series showed a 25-degree devi-
ation of the thoracic spine to the
right.
The presence of major skeletal
features of Marfan syndrome (MS)
prompted referral for cardiac and
ophthalmologic evaluation. An
echocardiogram showed dilatation of
the sinuses of Valsalva as well as aor-
index of suspicion
tic, pulmonary, and mitral valve re-
gurgitation.
Ophthalmologic examination re-
vealed bilateral astigmatism. CT scan
of the chest showed a severe pectus
excavatum deformity.
Although no history of MS was
recorded in the family, the patient
was diagnosed as having emerging
MS based on the presence of major
skeletal and cardiovascular findings,
and he was referred for additional
management.
The Condition
MS is an autosomal dominant disor-
der that affects 1 in 10,000 individu-
als in the United States. Thirty per-
cent of cases represent a new
mutation. A mutation in the gene
that encodes fibrillin-1 (FBN1) is the
genetic basis of this disorder, and
more than one mutation has been
noted. Defective connective tissue is
the mechanism through which ab-
normalities develop.
The diagnosis of MS relies on the
recognition of both major and minor
clinical manifestations. In the ab-
sence of a family history of the disor-
der, the diagnosis is made by noting
one major manifestation from two
different systems and involvement of
a third system with either a major or
minor criterion (Table). If a muta-
tion known to cause MS has been
identified in a member of the family,
the diagnosis requires one major cri-
terion and involvement of a second
organ system.
There is great clinical variability
among individuals as to when mani-
festations of the disorder develop.
The most serious problem is aortic
enlargement, which may involve
multiple levels of the aorta, including
the sinus of Valsalva, the ascending
aorta, and beyond. Aortic root en-
largement can progress to cata-
strophic dissection. Cardiovascular
abnormalities manifest during child-
Pediatrics in Review Vol.27 No.11 November 2006 427
index of suspicion

Table. Diagnostic Criteria for Marfan Syndrome

System Major Criteria Minor Criteria
Skeletal System Presence of at least four of the following ● Pectus excavatum of moderate severity
manifestations: ● Joint hypermobility
● Pectus carinatum ● Highly arched palate with crowding of
● Pectus excavatum requiring surgery teeth
● Reduced upper-to-lower segment ratio ● Facial appearance (dolichocephaly, malar
or arm span-to-height ratio greater hypoplasia, enophthalmos, retrognathia,
than 1.05 down-slanting palpebral fissures)
● Wrist (distal phalanx protrudes beyond
border of clenched fist) and thumb
(thumb and fifth digit overlap circling
the wrist) signs
● Scoliosis >20° or spondylolisthesis
● Reduced extention at the elbows
(<170°)
● Medial displacement of the medial
malleolus causing pes planus
● Protrusio acetabulae of any degree
(ascertained on radiographs)
Ocular System ● Ectopia lentis (dislocated lens) ● Abnormally flat cornea (as measured by
keratometry)
● Increased axial length of globe (as
measured by ultrasonography)
Cardiovascular System ● Dilatation of the ascending aorta with ● Mitral valve prolapse with or without
or without aortic regurgitation and mitral valve regurgitation
involving at least the sinuses of ● Dilatation of the main pulmonary artery,
Valsalva in the absence of valvular or peripheral
OR pulmonic stenosis or any other obvious
● Dissection of the ascending aorta cause, below the age of 40 y
● Calcification of the mitral annulus below
the age of 40 y
● Dilatation or dissection of the descending
thoracic or abdominal aorta below the
age of 50 y
Pulmonary System None ● Spontaneous pneumothorax
● Apical blebs (ascertained by chest
radiography)
Skin and Integument None ● Stretch marks not associated with
marked weight changes, pregnancy, or
repetitive stress
● Recurrent incisional hernias
Dura ● Lumbosacral dural ectasia by CT or None
MRI
Family/Genetic ● Having a parent, child, or sibling who None
History meets these diagnostic criteria
independently
● Presence of a mutation in FBN1 known
to cause the Marfan syndrome
● Presence of a haplotype around FBN1,
inherited by descent, known to be
associated with unequivocally
diagnosed Marfan syndrome in the
family
CT⫽computed tomography, MRI⫽magnetic resonance imaging
From De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet.
1996;62:417– 426. Published with permission of The American Journal of Medical Genetics.

428 Pediatrics in Review Vol.27 No.11 November 2006


hood in about 25% of cases and are
progressive in about 33% of affected
individuals. Dilatation of the mitral
annulus is a common cause of mitral
valve regurgitation in these patients.
The chordae tendineae also can
lengthen and rupture spontaneously.
Heart disease presenting in in-
fancy typically is mitral valve pro-
lapse, whereas aortic disease usually is
identified during later childhood and
adolescence, when the characteristic
body habitus calls attention to the
general diagnosis of MS.
Dislocated lenses commonly de-
velop by the age of 10 years. The
skeletal features can become more
pronounced during periods of rapid
growth. Dural ectasia tends to de-
velop in adulthood, although this
feature can occur at an earlier age.
The phenomenon of partial ex-
pression of MS in a child in whom the
full criteria are suspected to appear at
an older age has been termed
“emerging Marfan syndrome.”
Differential Diagnosis
Mutations in the fibrillin gene FBN1
may result in overlapping pheno-
types, including the MASS pheno-
type (mitral valve prolapse, mild aor-
tic enlargement, nonspecific skin and
skeletal features), familial thoracic
aortic aneurysms, familial ectopia
lentis, isolated skeletal features, and
mitral valve prolapse syndrome.
Other syndromes that have similar
clinical features include homocystin-
uria, Ehlers-Danlos syndrome, Stick-
ler syndrome, Klinefelter syndrome,
and congenital contractural arachno-
dactyly.
The tall, thin teenager who has
long fingers presents a challenge to
the clinician, who might suspect MS
but is not sure of how extensive an
evaluation should be undertaken. If
the history is suggestive of any ge-
netic disorders or the physical exam-
ination reveals abnormalities, addi-
tional investigations are required. It
is particularly helpful to perform an
extended skeletal examination, with
additional measurements beyond the
usual height and weight.
Management
If diagnostic criteria for MS are met,
the affected child should be referred
for evaluation by a multidisciplinary
medical team that includes a geneti-
cist and a cardiologist who has expe-
rience in the management of MS.
All children who have MS require
frequent assessment of the aortic
root. Most patients afflicted with
aortic enlargement are treated with
medications such as beta blockers to
reduce hemodynamic stress. This
treatment can slow the growth rate
of the aortic root. Standard subacute
bacterial endocarditis prophylaxis
should be implemented in those hav-
ing valve disease. Musculoskeletal
abnormalities of the chest or spine
are the most common cause of chest
pain. However, the diagnosis of aor-
tic dissection always should be con-
sidered in these cases. The combina-
tion of dysphonia caused by traction
of the recurrent laryngeal nerve and
chest discomfort is rare, but highly
suggestive of aortic dissection. If aor-
tic dissection is suspected, cardiac
MRI is the best imaging modality.
Progression of skeletal abnormal-
ities can be dramatic in periods of
rapid growth. Evaluation and
follow-up by an orthopedist is indi-
cated in these cases.
Many of the medical problems
seen in conditions such as emerging
MS, MASS phenotype, and familial
aortic dilatation are the same as those
seen in patients who have MS. Thus,
regardless of the diagnosis, it is im-
portant to adhere to the treatment
regimen prescribed for the particular
characteristics that do exist and be
conscientious about follow-up to en-
index of suspicion
sure that additional complications do
not result.
Children at risk for aortic enlarge-
ment or dissection should refrain
from collision and contact sports,
competitive sports, and exercises that
involve muscle straining, such as
weight lifting.
Lessons for the Clinician
It is important to recognize that al-
though tall stature, scoliosis, anterior
chest deformity, arachnodactyly,
joint laxity, and flat feet are common
in the general population, diagnostic
importance increases dramatically
when such findings are prominent
and found in combination. The pur-
pose of the diagnostic evaluation of
tall stature is to distinguish the com-
monly occurring, normal, familial
constitutional variant from the rare
pathologic conditions. Often, when
the history suggests familial tall stat-
ure and the findings on physical ex-
amination are entirely normal, no
laboratory tests are indicated.
Early diagnosis and management
of MS and overlapping conditions
can save lives. Pediatricians need to
be aware of the early manifestations
of MS so prompt evaluation and
management can be instituted. (Abel
Guerra, MD, Christine Nefcy, MD,
Mark LaShell, MD, 374th Medical
Group, Yokota Air Base, Japan)
The views expressed in this case
are those of the authors and do not
reflect the official policy of the De-
partment of Defense or other depart-
ments of the United States govern-
ment.
Case 3 Discussion
An extensive infectious evaluation re-
vealed no evidence of bacterial infec-
tion, Mycoplasma or Legionella infec-
tion, or viral infection, including
Epstein-Barr virus, cytomegalovirus,
and human immunodeficiency virus.
Pediatrics in Review Vol.27 No.11 November 2006 429
index of suspicion
An endocrinologic evaluation failed
to identify a cause for his hypercalce-
mia. No evidence of malignancy was
found.
The boy’s pulmonary function
tests (PFTs) showed a restrictive pat-
tern, including a forced expiratory
volume in 1 second (FEV1) and
forced vital capacity (FVC) at 58% of
predicted value. The FEV1/FVC ra-
tio was 100%, correlating with his
restrictive pattern. His angiotensin-
converting enzyme (ACE) level was
elevated at 196 IU/L (normal, 18 to
90 IU/L), and a bronchial biopsy
obtained during bronchoscopy
showed multiple noncaseating coa-
lescing granulomas suggestive of sar-
coidosis. He was started on oral
prednisone (1 mg/kg per day). He
required a short stay in the intensive
care unit to control his hypercalcemia
(ionized calcium level rose to
7.9 mg/dL [2 mmol/L]) and oxy-
gen requirement.
Repeat PFTs showed significant
improvement less than 1 week after
the initiation of corticosteroids. The
FVC and FEV1 improved to 72% and
68% of predicted values, respectively,
and the FEV1/FVC ratio was 94% of
its predicted value. He was dis-
charged from the hospital on hospital
day 11 and instructed to follow up
with pediatric pulmonology and pe-
diatric rheumatology. He will con-
tinue daily steroids while having his
PFTs monitored serially. The goal is
to taper his maintenance steroid dos-
ing to an every-other-day regimen.
Pulse high-dose steroids along with
methotrexate was considered, but it
was decided to pursue the more clas-
sic treatment of corticosteroids
dosed conventionally.
The Condition
Sarcoidosis is a generalized inflam-
matory process that most often af-
fects the lungs but can involve almost
any body system, including the skin,
430 Pediatrics in Review Vol.27 No.11 November 2006
eyes, kidneys, lymphatics, and heart.
In one series, 75% of patients had
multisystem involvement. In infants,
sarcoidosis typically presents with
skin involvement (including ery-
thema nodosum) and joint and eye
disease. In older children, sarcoidosis
tends to affect the pulmonary system,
lymphatics, and eyes (uveitis) more
frequently.
Clinical features of sarcoidosis
vary and depend on the specific or-
gan systems involved. This patient
displayed the classic findings of a re-
strictive pattern on PFTs, although
he had no eye findings typical of uve-
itis or rash characteristic of cutaneous
sarcoidosis.
Sarcoidosis can be staged by the
following criteria: Stage I is defined
as the presence of hilar lymphade-
nopathy on radiographs without pa-
renchymal infiltrates, stage II in-
cludes pulmonary infiltrates, and
stage III is defined as infiltrates with-
out lymphadenopathy.
The pathogenesis of sarcoidosis
remains obscure, primarily because
of the variety of manifestations it can
produce. Both environmental and
genetic factors have been linked to
the condition. Infectious agents,
chemicals, drugs, autoimmune fac-
tors, and genetic factors all have been
explored as potential causes of the
disease. The current belief is that sar-
coidosis represents the exposure of a
genetically susceptible individual to a
specific environmental agent that
triggers an exaggerated cellular im-
mune response. Sarcoidosis most
commonly affects young adults and
in the United States occurs more fre-
quently in African-Americans.
Pathologic Findings
Sarcoidosis is characterized by a fo-
cused, overwhelming inflammatory
response to an unknown antigen.
The noncaseating granuloma is the
classic pathologic finding. The
pathogenesis of the granuloma in-
cludes accumulation of mononuclear
inflammatory cells in the target or-
gan, following which macrophages
aggregate and differentiate into epi-
thelioid and multinucleated cells. Ac-
tivated lymphocytes and macro-
phages within the granuloma release
mediators, including interleukin-1
(IL-1), IL-2, interferon, and other
cytokines that promote and maintain
the granulomatous lesion. During
active disease, lymphocytes in the
granulomas are predominantly
helper T (CD4) lymphocytes.
Three processes have been identi-
fied in the initiation of sarcoidosis:
exposure to antigen, cellular immu-
nity directed against the antigen me-
diated through antigen-presenting
cells and antigen-specific T lympho-
cytes, and the appearance of immune
cells that produce a nonspecific im-
mune response. This extensive in-
flammation often results in fibrosis,
as with pulmonary sarcoidosis.
Differential Diagnosis
Sarcoidosis is a diagnosis of exclu-
sion. Because no specific test con-
firms the diagnosis, other causes of
granulomatous disease must be ruled
out. Tuberculosis, chronic beryllium
disease, hypersensitivity pneumoni-
tis, pulmonary alveolar proteinosis,
Wegener granulomatosis, and other
conditions must be considered when
evaluating a patient who has granu-
lomatous disease with diffuse pulmo-
nary involvement. Clues to the diag-
nosis of sarcoidosis include an
elevated ACE level, hypercalcemia
(33% of patients), uveitis, elevated
ESR, hyperproteinemia, eosino-
philia, and a diffuse pulmonary pro-
cess.
Treatment
The mainstay of treatment is oral cor-
ticosteroids, with the dose and dura-
tion of treatment tailored to the in-

dividual because absolute guidelines
regarding steroid use are not avail-
able. Initial dosing is 1 mg/kg per
day and may be tapered according to
clinical response. Duration of ther-
apy is based on an individual patient’s
response to therapy. Corticosteroid
therapy has been associated with im-
provements in dyspnea, PFTs, and
the appearance of the chest radio-
graph as well as suppression of gran-
uloma formation. However, evi-
dence that corticosteroids can
prevent long-term pulmonary fibro-
sis does not exist, and adverse effects
often limit their usefulness.
Second-line therapy is with im-
munosuppressants and cytotoxic
agents, including methotrexate, hy-
droxycholorquine, azothioprine, and
antitumor necrosis factor drugs (en-
tanercept and infliximab). Of these
agents, methotrexate is the best stud-
ied and has been found to reduce the
need for corticosteroid therapy as
well as to delay the decline in PFT
parameters, such as the FEV1 and
diffusing capacity of carbon monox-
ide. One limitation of methotrexate
is hepatotoxicity, which is minimized
when folic acid supplementation is
provided.
Other therapies are useful in treat-
ing specific symptoms of sarcoidosis:
nonsteroidal anti-inflammatory drugs
for erythema nodosum, joint in-
volvement, and fevers; topical corti-
costeroids for mild cases of erythema
nodosum; ophthalmic corticoste-
roids for prevention of permanent
damage in suspected cases of uveitis;
hydroxychloroquine for cutaneous
sarcoidosis unresponsive to steroids
and for hypercalcemia; and implant-
able defibrillators for cardiac se-
quelae. In general, therapy for a pa-
tient who has sarcoidosis requires a
multidisciplinary approach, which
can involve primary care clinicians,
pulmonologists, rheumatologists, der-
matologists, ophthalmologists, cardi-
ologists, and neurologists.
Prognosis
More than 60% of patients afflicted
with sarcoidosis have a good progno-
sis; they do not require therapy and
their disease remits spontaneously.
Poor prognostic indicators include
advanced staging by chest radio-
graphs, cardiac or neurologic disease,
and pulmonary hypertension. Of
these, the initial stage is the most
important prognostic factor: 95% of
patients who have stage I disease are
asymptomatic at 5 years compared
with 25% of patients who have stage
III disease. In general, asymptomatic
patients undergo spontaneous reso-
lution of their disease, while symp-
tomatic patients tend toward multi-
system involvement and chronic
disease, with irreversible sequelae in
up to 20% of cases.
Sarcoidosis in children usually car-
ries a better prognosis than in adults.
However, children who have early-
onset sarcoidosis with eye, joint, or
index of suspicion
skin involvement carry a guarded
prognosis; most experience a chronic
course and multiple irreversible se-
quelae. Determining the prognosis
for a patient who has sarcoidosis
must involve screening for multior-
gan disease, using scales such as the
ACCESS Organ Assessment Instru-
ment, (1) as well as determining the
effect of pulmonary, systemic, and
cutaneous symptoms on the patient’s
perceived quality of life.
Lessons For The Clinician
Sarcoidosis remains an unusual dis-
ease in children but must be consid-
ered when evaluating a patient who
has a diffuse pulmonary process that
cannot be explained by other causes.
Sarcoidosis can present with involve-
ment of almost any organ system but
most commonly involves the lungs,
lymphatics, eyes, and skin in chil-
dren. Consultation with a pediatric
pulmonologist, rheumatologist, and
ophthalmologist should be consid-
ered when the diagnosis is a possibil-
ity. (Michael Wolf, MD, Sibel Algon,
MD, Bristol Myers Squibb Children’s
Hospital/UMDNJ - Robert Wood
Johnson University Hospital, New
Brunswick, NJ)
Reference
1. ACCESS Research Group. Design of a
case control etiologic study of sarcoidosis
(ACCESS). J Clin Epidemiol. 1999;52:
1173–1186
Pediatrics in Review Vol.27 No.11 November 2006 431

Technical Tip
Corneal Abrasions
Ann U. Stout, MD*
Author Disclosure
Dr Stout did not disclose any
financial relationships relevant to
this tip.
The father of a healthy 16-month-old
boy brings him in to “check his eye.” The
evening before, which had been rather
windy, he had taken the child for a walk
in the stroller. During the walk, the boy
began fussing and rubbing one eye. The
father noticed that the eye was watery
and red but could not see anything in
the eye. He gave the boy some acet-
aminophen, and he slept well. Today,
however, the eye is still teary and
irritated, and the boy is fussy. You
inspect the eye and find no foreign
body.
Fluorescein staining viewed with a
Wood lamp shows a 2-mm corneal
abrasion and fine linear vertical streak
defects. You suspect a hidden foreign
body because the abrasion probably
occurred yesterday and should have
healed overnight. Upon eversion of the
upper lid, you see a small black particle
stuck to the tarsus that is removed
easily with a cotton swab (Fig. 1). You
prescribe analgesics as needed, topical
antibiotic ointment, and reassurance.
The next day, the father reports that his
son’s eye is back to normal.
Corneal abrasions (Fig. 2) occur of-
ten in children of all ages. The cornea is
one of the most richly innervated tis-
*Casey Eye Institute, Oregon Health & Science
University, Portland, Ore.
sues of the body, so discomfort may
range from mild to severe, depending
on the size of the defect. Symptoms
include photophobia, tearing, and in-
termittent sharp pain due to ciliary
body spasm. Physical findings include
irritability, blurry vision, conjunctival
injection, blepharospasm, irregular red
reflex, dulled corneal light reflex, and
fluorescein staining of the epithelial
defect.
Examination is facilitated by the use
of topical anesthetics (proparacaine or
tetracaine), which provide temporary
pain relief. Fluorescein helps define the
size of the defect, although large de-
fects may be seen without any dye.
Fluorescein strips can be moistened and
touched to the lower fornix to apply
the stain or combination anesthetic/
fluorescein drops can be used. The dye
stains the exposed corneal stroma, but
washes off of intact epithelium. The
yellow dye is visible with regular white
light, although blue or ultraviolet light
(Wood lamp) may make it more visible
and be better tolerated by a child who
has photophobia.
The conjunctival cul de sac and
upper tarsus should be examined to rule
out retained foreign bodies, which may
cause persistent abrasions, unless the
cause of the abrasion is known to be
Figure 1. Foreign body in the eye.
technical tip
external. The upper lid can be everted
over a cotton-tip applicator or a finger-
tip to examine the tarsus. Abrasions
that involve the entire cornea, such as
after chemical exposure, may be over-
looked because no normal epithelium
remains for comparison.
Corneal abrasions heal rapidly, often
within 24 hours, although larger de-
fects may take longer. Antibiotic oint-
ment may help lubricate the surface
until healing occurs, but aminoglyco-
sides should be avoided because they
may delay epithelial regrowth. The
chance of secondary infection is low,
unless foreign matter is retained.
Therefore, a course of topical antibiot-
ics is not requisite. Tight patching with
two eye pads may help with comfort by
blocking light and preventing the irri-
tation of repetitive blinking. The patch
must be tight enough to prevent inad-
vertent lid opening under the patch,
which could result in subsequent addi-
tional abrasions from the patch mate-
rial. Patching is not believed to speed
healing unless the defect encompasses
more than 75% of the corneal surface
area. Most younger children dislike the
patch, so it can be applied in the office
Figure 2. Corneal abrasion.
Pediatrics in Review Vol.27 No.11 November 2006 433
in brief
and removed by the family if it is poorly
tolerated. The family should not reapply
it because it might be too tight or not
tight enough.
Over-the-counter analgesics or co-
deine may be used for pain manage-
ment if needed. The pain of an abrasion
should not be underestimated, and
treatment should be tailored to the
child’s comfort level. Pupillary dilation
with a cycloplegic agent (tropicamide
1% or cyclopentolate 1%) may help to
block ciliary spasm and relieve pain.
In Brief
Ampicillin and Amoxicillin
Zainab A. Malik, MD
Nathan Litman, MD
Children’s Hospital at Montefiore
Bronx, NY
Author Disclosure
Drs Malik, Litman, and Adam did not
disclose any financial relationships
relevant to this In Brief.
The Use of Antibiotics. Kucers A. In:
Crowe KS, Grayson ML, Hoy J, eds.
The Use of Antibiotics: A Clinical
Review of Antibacterial, Antifungal
and Antiviral Drugs. 5th ed. Oxford,
United Kingdom: Butterworth-Heine-
mann Publishing; 1997:108 –143,
192–208
Penicillins. Chambers HF. In: Mandell
GL, Bennett JE, Dolin R, eds. Princi-
ples and Practice of Infectious Dis-
eases. Vol 1. 6th ed. Philadelphia, Pa:
Elsevier Churchill Livingstone; 2005:
281–293
Diagnosis and Management of Acute
Otitis Media. Subcommittee on
Management of Acute Otitis Media.
American Academy of Pediatrics and
American Academy of Family Physi-
434 Pediatrics in Review Vol.27 No.11 November 2006
Topical nonsteroidal drops (ketorolac)
may provide additional relief, but may
delay healing. Topical anesthetics
NEVER should be dispensed because
they not only retard healing but can
lead to corneal melting and perforation.
Most small abrasions heal overnight.
The patient can be seen the next day as
needed or feasible. If symptoms and
signs have resolved, it can be assumed
that the abrasion has healed. A small
group of patients are at risk of devel-
oping recurrent erosions from poor ini-
cians. Pediatrics. 2004;113:
1451–1465
Management of Sinusitis. Subcommit-
tee on Management of Sinusitis and
Committee on Quality Improvement.
American Academy of Pediatrics.
Pediatrics. 2001;108:798 – 808
Ampicillin and amoxicillin are amino-
penicillins derived from the penicillin
nucleus. Their basic structure consists
of the beta-lactam ring and a side
chain. The ring structure confers anti-
microbial activity, and the side chain
determines the antibacterial spectrum
and pharmacologic properties. The an-
tibacterial activity of aminopenicillins
is similar to that of other penicillins via
inhibition of bacterial cell wall synthe-
sis. Penicillin-sensitive reactions in
bacterial cell wall synthesis are cata-
lyzed by a class of proteins called
penicillin-binding proteins (PBPs),
which are inhibited by beta-lactam
antibiotics.
The antibacterial spectrum of amino-
penicillins includes nonbeta-lactamase-
producing gram-positive cocci, anaer-
obes, and gram-negative cocci, including
Neisseria and Enterobacteriacae that
tial healing. During the night, the lid
sticks to the new epithelial cells and
pulls them loose upon awakening.
These small abrasions are symptomatic
upon awakening and often improve
throughout the day. Nightly lubrication
with ointment sometimes can break
this cycle. Patients who have nonheal-
ing abrasions should be referred
promptly for additional evaluation be-
cause such abrasions can be due to
secondary infections, occult foreign
bodies, or lacerations.
do not produce beta-lactamase. These
agents are not active against Pseudo-
monas sp and are hydrolyzed by beta-
lactamases, making them ineffective
against beta-lactamase-producing strains
of bacteria.
Ampicillin is effective in treating
upper and lower respiratory tract infec-
tions caused by Streptococcus pneu-
moniae, beta-hemolytic streptococci, and
nonbeta-lactamase-producing strains of
Haemophilus influenzae. It also is ef-
fective in the treatment of meningitis
caused by group B streptococci, Listeria
monocytogenes, N meningitidis, and all
except highly resistant strains of S
pneumoniae. Ampicillin previously was
a first-line agent for treating urinary
tract infections (UTIs) caused by Esch-
erichia coli and gastroenteritis caused
by Salmonella enterica or Shigella sp.
However, due to the rising prevalence
of beta-lactamase-producing strains of
these organisms, ampicillin no longer is
the agent of choice for UTIs unless
susceptibility has been documented.
The in vitro activity of amoxicillin is
similar to that of ampicillin. Ampicillin
usually is given intravenously (IV) or

intramuscularly (IM), whereas amoxicil-
lin is the preferred oral agent because it
is less likely to cause diarrhea and can
be administered less frequently than
oral ampicillin. Amoxicillin is indicated
in the treatment of otitis media, sinus-
itis, pneumonia, and susceptible UTIs.
Among the oral penicillins and ceph-
alosporins, amoxicillin can achieve
therapeutic minimum inhibitory con-
centrations in body tissues for nonmen-
ingeal infections caused by penicillin-
resistant pneumococci, except highly
resistant strains. Amoxicillin is not use-
ful in the treatment of shigellosis be-
cause it is well absorbed in the small
intestine. Oral ampicillin is indicated for
this purpose; its poor intestinal absorp-
tion allows significant levels of the
antibiotic to reach the site of infection
in the large intestine.
Ampicillin can be given IV or IM in
the form of its sodium salt. For neo-
nates weighing more than 2,000 g and
younger than 7 days old, a dose of
25 mg/kg every 8 hours is recom-
mended for mild-to-moderate infec-
tions. With serious infections such as
meningitis, the dose should be in-
creased to 50 mg/kg every 8 hours.
Neonates older than 7 days and weigh-
ing more than 2,000 g who have mild
infections can receive a dose of
25 mg/kg every 6 hours; for meningitis,
the dose should be increased to
200 mg/kg per day divided every
6 hours. For older infants and children,
doses of 100 to 400 mg/kg per day,
divided every 4 to 6 hours, are recom-
mended. Because ampicillin is relatively
nontoxic, dose adjustment is not imper-
ative in mild-to-moderate renal failure,
although it may be required for patients
who have severe renal dysfunction.
Ampicillin is well distributed
throughout the body. Although the
peak interstitial tissue concentrations
are lower than those achieved in serum,
the drug persists in the interstitium for
a longer period of time. It achieves
therapeutic concentrations in septic
joint effusions, ascitic fluid, and para-
pneumonic effusions. Very low concen-
trations of ampicillin can be detected in
normal cerebrospinal fluid, but higher
levels are achieved in patients who
have bacterial meningitis due to ongo-
ing meningeal inflammation.
The serum half-life of ampicillin de-
clines with increasing postnatal age. In
neonates 2 to 7 days old, the serum
half-life is 4 hours; in 8- to 14-day-old
neonates, it is 2.8 hours; and in 15- to
30-day-old neonates, it is 1.7 hours. In
older children and adults, ampicillin has
a serum half-life of 1 hour. After par-
enteral administration, 75% of the dose
is excreted in the urine and 0.1% of the
dose is excreted unchanged in bile.
Because high concentrations of ampi-
cillin are excreted in the urine, it was an
agent of choice for UTIs prior to the
emergence of microbial resistance.
The major adverse effects associated
with ampicillin use are rashes, which
tend to occur more commonly than
with other penicillins (7.7% versus
2.75%). Ampicillin rashes may be urti-
carial or macular, resembling measles
or rubella. The macular rashes usually
appear 4 to 5 days after therapy has
begun, without any other associated
signs of allergy, and often subside with
ongoing treatment. The nonurticarial
rashes do not indicate true ampicillin
hypersensitivity. Parenteral ampicillin
therapy also can cause nausea and
diarrhea, which are more common in
younger children. Ampicillin and
amoxicillin can both be responsible for
Clostridia difficile-associated pseudo-
membranous colitis. Very large doses
that achieve serum levels of 800 mcg/mL
may cause central nervous system toxic-
ity, resulting in convulsions.
Amoxicillin is available in the trihy-
drate preparation for oral use. The stan-
dard dose is 45 mg/kg per day in two
divided doses or 80 to 90 mg/kg per day
in two divided doses for indications
that require high-dose amoxicillin. It is
well absorbed after oral administration,
in brief
and food does not alter its absorption.
Almost 60% of an oral dose of amoxi-
cillin is excreted unchanged in urine
within the first 6 hours. It has a tissue
distribution similar to that of ampicil-
lin, and tissue levels are 40% of serum
levels. Because amoxicillin achieves
high levels in the gastric mucosa, it is a
good antibiotic for treating Helicobac-
ter pylori infections in combination
with other agents. Oral amoxicillin is
not indicated for treating central ner-
vous system infections.
Amoxicillin is relatively nontoxic
and may be given in the usual recom-
mended dose to patients who have mild
renal failure. The dose should be re-
duced for patients whose renal failure
is moderate to severe. Amoxicillin is the
drug of choice for treating acute bac-
terial sinusitis and acute otitis media.
Factors that justify its use as a first-line
agent include its narrow antimicrobial
spectrum, pleasant taste, low cost, ac-
tivity against susceptible and interme-
diately resistant pneumococci, and ac-
ceptable safety profile in children.
There is a high prevalence of beta-
lactamase-producing strains of H influ-
enzae and Moraxella catarrhalis in up-
per respiratory tract isolates in the
United States, making them resistant to
amoxicillin. Of the S pneumoniae iso-
lates from the upper respiratory tract,
an average of 30% are resistant to
penicillin. Some 50% of these organ-
isms are highly resistant, reflected in
their lack of response to standard-dose
amoxicillin therapy. Penicillin resis-
tance among S pneumoniae results not
from the production of an enzyme, but
from an alteration in PBPs on the bac-
terial cell wall, which confers resistance
to penicillins and cephalosporins.
Conventional doses of amoxicillin
(45 mg/kg per day) are effective against
all susceptible strains of S pneumoniae
and most strains that are intermediate
in resistance to penicillin. Highly resis-
tant strains are not susceptible to con-
ventional doses of amoxicillin. High-
Pediatrics in Review Vol.27 No.11 November 2006 435
in brief
dose amoxicillin (80 to 90 mg/kg per
day) achieves high middle ear and sinus
fluid levels, making it effective against
all intermediately resistant strains and
some, but not all, highly resistant
strains. In practice, the response rate to
high-dose amoxicillin among children
who have acute otitis media is approx-
imately 80%.
Risk factors for the presence of in-
termediate or highly resistant S pneu-
moniae necessitating the use of high-
dose amoxicillin include child care
attendance and having received antibi-
In Brief
Cocaine
Christine Rizkalla, MD
Young-Jin Sue, MD
Children’s Hospital at Montefiore
Bronx, NY
Author Disclosure
Drs Rizkalla, Sue, and Adam did not
disclose any financial relationships
relevant to this In Brief.
History of Cocaine. Petersen RC. NIDA
Res Monogr. 1977;13:17–34
Cocaine: History, Use, Abuse. Karch S.
J R Soc Med. 1999;92:393–398
Cocaine Use: 2002–2003. The NSDUH
Report. 2005. Available at: http://
www.oas.samhsa.gov/2k5/cocaine/
cocaine.htm
Intersecting Epidemics—Crack Cocaine
Use and HIV Infection among Inner-
city Young Adults. Edlin BR, Irwin
KL, Faruque S, et al. Multicenter
Crack Cocaine and HIV Infection
Study Team. N Engl J Med. 1994;
331:1422–1427
Cocaine and the Critical Care Chal-
lenge. Shanti C, Lucas C. Crit Care
Med. 2003;31:1851–1859
436 Pediatrics in Review Vol.27 No.11 November 2006
otics in the preceding 3 months, partic-
ularly among children younger than 2
years of age.
Amoxicillin and ampicillin are cross-
allergenic with other penicillins and are
contraindicated in penicillin-allergic
patients. Amoxicillin generally is well
tolerated, although it has a propensity
to cause rashes and results in a morbil-
liform rash if given to a patient acutely
infected with Epstein-Barr virus. The
maculopapular eruptions produced by
amoxicillin are similar to those seen
with ampicillin. Amoxicillin also may
TOX-ACLS: Toxicologic-oriented
Advanced Cardiac Life Support.
Albertson T, Dawson A, de Latorre F,
et al. Ann Emerg Med. 2001;
37(4 suppl):S78 –S90
Cocaine, Amphetamines and Other
Sympathomimetics. Rao R, Hoffman
R. In: Marx JA, Hockberger RS, Walls
RM, eds. Rosen’s Emergency Medi-
cine: Concepts and Clinical Practice.
5th ed. St. Louis, Mo: Mosby; 2002:
2386 –2392
Body Packing: The Internal Conceal-
ment of Drugs. Traub S, Hoffman R,
Nelson L. N Engl J Med. 2003;349:
2519 –2526
According to one legend, before it was
a plant, coca was a beautiful woman,
executed for adultery. Evidence of hu-
mans consuming Erythroxylon coca, a
South American shrub from which co-
caine (benzoylmethylecgonine) is de-
rived, dates to more than 1,000 years
ago. Regarded as divine in the northern
Andes of Peru and Bolivia, cocaine
played a role in religious ceremonies
and inspired colorful mythology regard-
ing its origin. Chewing coca leaves was
promoted for its healing powers, to
cause nausea and diarrhea, although
less commonly than ampicillin.
Comment: Despite newer and newer
(and more expensive) antimicrobial
agents, amoxicillin remains the drug of
choice for both otitis media and sinus-
itis in most children. It’s nice when
oldies are still goodies.
Henry M. Adam, MD
Editor, In Brief
ease hunger and thirst, and to improve
the stamina required for daily labors
and life at great altitudes. Spanish col-
onists of the region introduced the leaf
to Europe, and the pure and far more
potent chemical, cocaine, ultimately
was extracted. The mid-1800s saw the
production of coca-infused wines and
tonics. Early surgeons discovered its
utility for local anesthesia. Sigmund
Freud praised the drug for its multiple
medicinal uses. In 1886, Dr John Pem-
berton produced a new beverage
named Coca Cola, combining coca and
caffeine from the African kola nut
plant, touting it as tonic for multiple
ailments and nervous disorders, partic-
ularly for the elderly. Gradually, more
products contained greater amounts,
and consumption increased. Sir Arthur
Conan Doyle described his celebrated
fictional detective Sherlock Holmes us-
ing cocaine when occupied by boring
cases. By the advent of the 20th cen-
tury, increasing prevalence and nonme-
dicinal use of pure cocaine brought
with it the awareness of its toxic and
addictive potential. Beginning with the

Harrison Act of 1914, the United States
government passed legislation to at-
tempt to control its availability, but
public demand remained.
Far from myth and legend, cocaine
now is popularly known as bazooka,
white lady, Charlie, snow, tornado,
kryptonite, dust, bones, sugar, and
blow, among other names. Estimates in
both 2002 and 2003 were that more
than 5.9 million people in the United
States older than age 12 years (2.5% of
the population) had used cocaine
within the past 12 months, primarily
within the 18- to 25-year-old group.
Cocaine is abused by several routes.
Water-soluble cocaine hydrochloride is
snorted as a powder or injected as an
aqueous solution. Alkaloid preparations
are smoked as “free-base” or as the
precipitated crystal form known as
crack. As a base, cocaine is highly
purified, heat-stable, and lipid-soluble,
thereby readily crossing the blood-brain
barrier and yielding an intense and
immediate “high.” Both smoking and
intravenous (IV) injection produce a
high within seconds to minutes that
lasts 15 to 30 minutes unless repeated
hits are delivered. The effects of insuf-
flated cocaine peak at 20 to 30 minutes
(due to local vasoconstriction, which
slows its absorption) and last approxi-
mately 1 hour. Cocaine may be adulter-
ated to augment its mass (eg, with
sugars or talc) or to enhance its effects
(eg, with heroin— known as a
“speedball”—phencyclidine, lidocaine,
or strychnine). Use with alcohol pro-
duces the metabolite cocaethylene,
which may augment its toxicity.
The physiologic effects of cocaine
result from the release of norepineph-
rine from adrenergic nerve terminals
and from inhibited reuptake of dopamine,
epinephrine, serotonin and norepineph-
rine. Sympathetic overstimulation man-
ifests as mydriasis, diaphoresis, tachy-
cardia, hypertension, and hyperthermia.
This may be followed by the complica-
tions of myocardial infarction, stroke,
seizure, pulmonary hemorrhage, gastro-
intestinal ischemia, rhabdomyolysis,
and renal failure. Use in pregnancy may
lead to placental abruption or fetal
demise. Behavioral manifestations of
this sympathetic overstimulation in-
clude euphoria, confidence, agitation,
aggression, and hallucinations (“coke
bugs”).
Cocaine blocks sodium transport
across cell membranes, slowing nerve
impulses, which accounts both for its
anesthetic properties and for its poten-
tial to induce fatal ventricular arrhyth-
mias and cardiac arrest. IV use carries
the additional risks of local infection,
sepsis, and endocarditis. Human immu-
nodeficiency virus transmission is an
additional risk of IV drug use, both from
needle-sharing and because high-risk
sexual encounters are associated with
drug-seeking behavior.
Chronic use of cocaine is associated
with cachexia, poor nutrition, and
“crack dancing” (choreoathetotic move-
ments from decreased dopamine
stores). Upregulation of dopaminergic
receptors exacerbates tolerance as well
as the drug craving and dysphoria that
follow each high. With greater intake
needed to achieve the same effects,
cocaine users increase their potential
for morbidity and mortality.
Cocaine users may not be forthcom-
ing about their drug taking. Urine
screening is widely available, employing
a highly specific immunoassay for the
metabolite benzoylecgonine, which is
excreted for 24 to 48 hours. However,
depending on the chronicity of use,
urine may remain positive for several
days.
As with all medical emergencies,
individuals who present with symptoms
of toxicity should be evaluated for air-
way stability. The most rapidly fatal
complications in cocaine use are re-
lated to hyperthermia, hypertension,
and cardiac dysrhythmias. Benzodiaz-
epines and aggressive external cooling
are the foundation of management of
in brief
such complications. Potentially life-
threatening hyperthermia results from
agitation, increased motor tone, and
vasoconstriction, interrupting the
body’s cooling mechanisms. Once iden-
tified, hyperthermia must be addressed
emergently with: benzodiazepines to
decrease agitation; paralysis and airway
stabilization if indicated; IV access for
aggressive fluid management; and rapid
cooling with ice.
The clinician also must monitor lev-
els of creatine kinase, electrolytes, cre-
atinine, coagulation parameters, and
urine myoglobin because rhabdomyoly-
sis may be an associated complication.
A direct-acting alpha-adrenergic an-
tagonist such as phentolamine and a
vasodilator, usually nitroprusside, are
used to treat critical hypertension. Beta
blockers should be avoided because re-
sultant unopposed alpha-adrenergic
stimulation may exacerbate the hyper-
tension. Computed tomography (CT)
scanning of the brain and lumbar punc-
ture should be strongly considered for
patients who have persistent headache
or altered mental status.
Evaluation of chest pain in associa-
tion with cocaine use requires radio-
graphs of the chest (for pneumothorax,
widened mediastinum, and pneumonia),
electrocardiography (ECG), measure-
ment of cardiac enzymes and electro-
lytes, a complete blood count, and
blood cultures. Acute coronary syndromes
due to cocaine should be managed ini-
tially with nitrates and benzodiazepines,
with use of alpha-adrenergic antagonists
considered in refractory cases. Sodium
bicarbonate is appropriate for treating
the sodium channel blockade that re-
sults in ventricular dysrhythmias, man-
ifested as a widened QRS interval on
ECG. Class 1A and 1C antidysrhythmic
agents generally are contraindicated in
such situations because exacerbation of
sodium channel blockade may ensue.
A unique set of problems arises with
individuals who have ingested densely
contained, well-sealed packets of the
Pediatrics in Review Vol.27 No.11 November 2006 437
in brief
drug for transport (body packers) or
who have hastily swallowed poorly
sealed aliquots to conceal them from
law enforcement officers (body
stuffers). Body packers may harbor up
to 100 packages, each containing a
lethal quantity of the drug. Body
stuffers, while concealing a lesser
amount of drug, may be at greater risk
for toxicity from rupture of poorly se-
cured packets. Plain radiographs may
reveal air trapped between the wrap-
pers (often condoms) used for packag-
ing (“double-condom sign”), and con-
trast CT scans may demonstrate foreign
Correction
For question #11 on page 345 in the September 2006 issue of Pediatrics in Review,
the answer should be D rather than E.
438 Pediatrics in Review Vol.27 No.11 November 2006
bodies surrounded by gas. Bowel perfo-
ration is an additional concern. Because
of the potential for lethal overdosing, a
positive urine assay accompanied by
symptoms of cocaine toxicity in such
individuals should prompt rapid surgi-
cal decontamination, with treatment of
associated toxicity as described previ-
ously. Stable individuals should be
managed with whole bowel irrigation,
using polyethylene glycol to facilitate
gut emptying, and observation until
passage of all packages.
With considerable numbers of ado-
lescent users and accidental toddler
exposures, cocaine continues to present
a complex and sometimes fatal public
health challenge that includes the pe-
diatric population. Familiarity with the
manifestations and management of co-
caine intoxication is imperative for
practitioners who work with children
and adolescents.
Comment: So, at least initially,
there really was a difference between
Coke and Pepsi!
Henry M. Adam, MD
Editor, In Brief
Pediatrics in Review Vol.27 No.11 November 2006 439

A Child Who Has Acute
Onset of Unusual Skin
Lesions and Edema
Figure 1. Purplish-red, slightly raised macules on the face and
trunk.
Figure 2. Purplish-red, slightly raised macules on the face and
ear.
Author Disclosure
Drs Acun, Ustundag, Sogut, Koca, and Numanoglu did not
disclose any financial relationships relevant to this case.
visual diagnosis
Ceyda Acun, MD,* Gonca Ustundag, MD,* Ayhan Sogut, MD,*
Rafet Koca, MD,† Gamze Numanoglu, MD‡
Presentation
A 13-month-old boy presents to the emergency depart-
ment with a 1-day history of rash on his face, medial
thighs, and upper trunk and swelling of his face, ears,
hands, and feet. He has a 3-day history of an upper
respiratory tract infection. There is no recent history of
immunization or drug intake.
The physical examination reveals an alert child who
has a widespread rash over his peroral area, chin, cheeks,
and ears, with sparing of the mucous membranes (Figs.
1, 2). His vital signs are appropriate for his age. The rash
appears in a rosette pattern of 1 to 2-cm diameter,
purplish-red, slightly raised macules. A milder rash ap-
pears on his medial thighs and upper trunk. Both his face
and ears are significantly swollen, and the flexor surfaces
of the hands and feet are mildly swollen. The patient is
admitted for observation and evaluation.
Over the next 3 days, the rash spreads to his arms and
legs (Figs. 3, 4). However, apart from a transient mild
fever, the child appears well, having no obvious systemic
symptoms.
The laboratory examination reveals a normal com-
plete blood count, serum immunoglobulins, C3 and C4
levels, circulating immune complexes, antistreptolysin
titers, coagulation studies, urinalysis, renal function tests,
and liver function tests. Stool samples are negative for
ova and parasites, and blood cultures show no growth.
A skin biopsy reveals the diagnosis.
*Department of Pediatrics.
†
Department of Dermatology.
‡
Department of Pathology, Karaelmas University, School of Medicine, Zonguldak,
Turkey.
Pediatrics in Review Vol.27 No.11 November 2006 e71
visual diagnosis

Figure 3. Rash over extremities.

Figure 4. Rash over legs and buttocks.

e72 Pediatrics in Review Vol.27 No.11 November 2006


Diagnosis: Acute Hemorrhagic Edema of
Infancy
The patient has acute hemorrhagic edema of infancy
(AHEI), a diagnosis based on the clinical presentation
and the skin biopsy demonstration of leukocytoclastic
vasculitis.
AHEI is a rare, benign form of leukocytoclastic vas-
culitis that occurs in children younger than 2 years of age.
Originally reported by Snow in 1913, case reports in the
European literature have labeled this disorder Finkelstein
disease, Seidlmayer syndrome, medallion-like purpura,
and infantile postinfectious iris-like purpura and edema.
Epidemiology
Although uncommon, AHEI appears throughout the
world. The disease frequency is unknown, and no racial
predilection is reported. AHEI may be slightly more
common among male infants than among female infants.
Affected children are usually 4 to 24 months of age.
Cause
The cause of AHEI is unknown, although in approxi-
mately 75% cases, AHEI is preceded by viral infection
(usually upper respiratory tract infection), bacterial infec-
tion (streptococcal pharyngitis, pulmonary tuberculosis,
bronchopneumonia, urinary tract infection), immuniza-
tion (measles, diphtheria-pertussis-tetanus), or drug ex-
posure (penicillin, cephalosporins, trimethoprim-
sulfamethoxazole, acetaminophen). AHEI may be
immune-mediated, but only a few cases demonstrate
immune complexes in biopsy specimens.
Definitions
Leukocytoclastic vasculitis—A histopathologic term for
small-vessel vasculitis, also known as hypersensitivity
vasculitis, allergic vasculitis, and allergic angiitis.
Deposition of immune complexes along the
postcapillary venules activates the complement
cascade, leading to neutrophil migration, vessel wall
destruction, fluid leakage, and red blood cell
extravasation. Palpable purpura is the most sensitive
clinical sign for leukocytoclastic vasculitis.
Purpura—A red-purple, nonblanchable discloration,
greater than 0.5 cm in diameter, that represents
hemorrhage into the skin.
visual diagnosis
Clinical Features
The clinical hallmark of AHEI is the sudden appearance
and spread of a purpuric rash and edema over the face and
extremities in an otherwise healthy infant. Fever may be
present. The rash first appears as red macules or urticarial
lesions that dramatically evolve into large (1 to 5 cm diam-
eter) ecchymotic papules, characteristically arranged in a
cluster of circular lesions (sometimes described as a rosette
or cockade pattern). The face, ears, scrotum, and extremi-
ties are affected commonly, with sparing of the trunk and
mucous membranes. Edema develops early in the course of
the disorder and appears over the face, scalp, the dorsa of
the hands and feet, and the proximal extremities. Approxi-
mately 50% of patients complain of arthralgias.
Complications are rare and include purpuric lesion
necrosis (especially of the ears) and gastrointestinal vas-
culitis followed by intussusception. Transitory renal
problems (microscopic hematuria, mild proteinuria)
have been described infrequently, with spontaneous re-
covery within days to 3 weeks.
Spontaneous and complete healing of AHEI occurs
within 1 to 3 weeks, but relapses may occur up to 15
months after initial presentation. Only necrotic areas may
leave a scar.
Suggested diagnostic criteria for AHEI include:
● Patient age younger than 2 years
● Purpuric or ecchymotic targetlike lesions, with
edema of the face, ears, and extremities, with or
without mucosal involvement
● Lack of systemic disease or visceral involvement
● Spontaneous recovery within a few days or weeks
Laboratory Features
Laboratory findings are nonspecific and include mild
leukocytosis, lymphocytosis, thrombocytosis, and in
some cases, eosinophilia. Immune complexes may be
present in some cases, but serum complement and im-
munglobulin (Ig) values generally are within normal limits.
Skin biopsy demonstrates fibrinoid necrosis, pupura, neu-
trophil and mononuclear cell infiltration, and leukocytocla-
sis. Direct immunoflourescence may reveal vascular depos-
its of C1q, C3, and fibrinogen. One series of case reports
found that 80% of patients had vessel deposits of IgM, 30%
had IgA, 30% had IgE, and 20% had IgG.
Differential Diagnosis
AHEI is similar to Henoch-Schönlein purpura (HSP) in
presentation. Some clinicians postulate that AHEI is a
variant of HSP. However, HSP generally affects children
ages 3 to 6 years and, unlike AHEI, presents with sys-
Pediatrics in Review Vol.27 No.11 November 2006 e73
visual diagnosis
temic symptoms such as abdominal pain and vomiting.
Frequently, renal disease (proteinuria, hematuria, tran-
sient azotemia) also is present in HSP. Most cases of HSP
demonstrate vascular IgA deposition; only a minority of
cases of AHEI do so. Furthermore, although AHEI may
demonstrate C1q perivascular deposition, HSP does not.
Other important differential diagnoses include me-
ningococcemia, erythema multiforme, urticaria with
hemorrhage, Kawasaki disease, purpura due to septice-
mia, and drug eruption.
Management
There is no specific treatment for AHEI. Spontaneous,
complete resolution without complications usually oc-
curs within 5 to 14 days, but the disease may endure as
long as 35 days. Antibiotics should be administered if
there is concurrent bacterial infection.
Case reports suggest that systemic corticosteroids and
antihistamines do not alter the course of the disease,
although some authors recommend treating AHEI with
corticosteroids if the ears or joints appear compromised.
Patient Course
The patient was treated with prednisolone (1 mg/kg per
day) because of rapid disease progression. Within 48 hours,
his condition had improved, and by 7 days, the skin lesions
had resolved completely. Prednisolone was tapered gradu-
ally over the next 2 weeks. The disease has not recurred.
e74 Pediatrics in Review Vol.27 No.11 November 2006
Summary
AHEI is a benign variant of leukocytoclastic vasculitis
that occurs in children younger than 2 years of age.
Respiratory tract infection, drug intake, or immunization
frequently precedes AHEI. Striking clinical features in-
clude acute appearance of the cutaneous lesions in oth-
erwise healthy young infants and children, lack of visceral
involvement, and self-limited progression. Laboratory
tests, except for punch biopsy of the skin lesions, are non-
diagnostic. Differential diagnoses include HSP and other
potentially serious disorders such as meningococcemia, er-
ythema multiforme, and Kawasaki disease. No effective
therapy exists for AHEI, and treatment is supportive.
Suggested Reading
Barkai G, Sinai L. Index of suspicion: acute hemorrhagic edema of
infancy. Pediatr Rev. 2003;24:349 –353
Caksen H, Odabas D, Kosem M, et al. Report of eight infants with
acute infantile hemorrhagic edema and review of the literature.
J Dermatol. 2002;29:290 –295
da Silva Manzoni AP, Viecili JB, de Andrade CB, et al. Acute
hemorrhagic edema of infancy: a case report. Int J Dermatol.
2004;43:48 –51
Garty BZ, Ofer I, Finkelstein Y. Acute hemorrhagic edema of
infancy. IMAJ. 2002;4:228 –229
Smitt JH, Vermeer MH, Faber WR. Acute hemorrhagic edema of
infancy (AHEI). Clin Dermatol. 2002;20:2–3

Commentary
The Value of the ECG in the Preparticipation Sports Physical
Examination: The Italian Experience
Editor’s note: This commentary by Dr
Vitiello addresses cardiovascular prepar-
ticipation sports screening by describ-
ing the extensive Italian protocol aimed
at preventing cardiovascular deaths in
athletes. Presented data indicate the
value of the protocol, and extending
the practice across Europe has been
proposed. Readers not only will find this
information to be educational but also
will appreciate the value of viewpoints
and experiences from other countries.
We hope to present more of these
contributions from outside of North
America in the near future.—LFN
In 1982, the Italian Ministry of Health
mandated required screening for every-
one who participates in competitive
sports. (1) The law states that every 1 to
2 years, all competitive athletes must
be certified for participation. The defi-
nition of a competitive athlete includes
students in secondary schools, members
of sports clubs, and professional ath-
letes. By law, the screenings are per-
formed at designated “Centers for Sport
Medicine” and are conducted by sports
medicine specialists. The evaluation in-
cludes a comprehensive family and per-
sonal history, a physical examination, a
12-lead electrocardiogram (ECG), and a
urinalysis. Furthermore, athletes partic-
ipating in certain high-intensity sports
also must undergo exercise testing and
pulmonary function testing (Table).
Those in whom abnormalities are found
on the initial screening studies are
referred for additional tests, including
echocardiography, 24-hour Holter moni-
toring, and others as necessary. (1)
In Italy, there has been considerable
interest in preventing sudden death in
commentary
young athletes by preparticipation cases of sudden death in young people
screenings because there is a high in- and observed a significant reduction of
cidence of catastrophic deaths caused HCM-caused sudden death from the
by cardiomyopathy in young athletes. expected 24% to 2% (one case). Further-
(2)(3)(4)(5) more, recognition of the relatively more
The Italian preparticipation screen- rare disease, arrhythmogenic right ven-
ing program, by requiring ECG studies, tricular (RV) cardiomyopathy, as a cause
might reduce mortality. The thinking is of death increased. Thus, it appears that
that the ECG is an excellent screening the ECG has been an extremely valuable
test for hypertrophic cardiomyopathy addition to the Italian program.
(HCM), (6) the leading cause of sports- Besides HCM, other causes of car-
related cardiac death. (7)(8)(9)(10) diac arrest in athletes may manifest
Burke and associates (8) found that ECG abnormalities at the preparticipa-
24% of sudden deaths during compet- tion cardiovascular screening. These
itive sporting events were caused by disorders include arrhythmogenic RV
HCM. After the institution of the Italian cardiomyopathy, long QT syndrome, di-
law, Corrado and colleagues (11) pro- lated cardiomyopathy, and Brugada
spectively studied 269 consecutive syndrome. With this knowledge in
Classifications of Sport According to Type
Table.
of Screening
Screening: Clinical Visit,
Screening: Clinical Visit, 12-lead ECG, Exercise Testing,
12-lead ECG, Urinalysis Spirometry, Urinalysis
Sport Frequency (y) Sport Frequency (y)
Auto racing 1 Soccer 1
Badminton 2 Baseball 1
Bobsled 1 Boxing 1
Golf 2 Canoeing/Kayaking 1
Motorcycling 1 Rowing 1
Diving 1 Speed skating 1
Riflery 1 Hockey 1
Archery 2 Skiing 1
Table tennis 2 Rugby 1
Karting 2 Tennis 1
Cycling 1
Swimming 1
Basketball 1
Biathlon/Pentathlon 1
Gymnastics 1
Modified from Decree of Italian Ministry of Health (1).
Pediatrics in Review Vol.27 No.11 November 2006 e75
 commentary
mind, it is critical to characterize the
ECG findings in these diseases fully and
to disseminate this information con-
cisely to those administering the pre-
participation screenings.
We believe that the Italian screen-
ing system, which by national law re-
quires examinations and also routinely
employs the ECG, results in a significant
reduction in sport-related cardiac
deaths. Accordingly, there has been
great interest in the Italian model from
the greater European medical commu-
nity. Recently, the Study Group of Sport
Cardiology of the Working Group of
Cardiac Rehabilitation and Exercise
Physiology and the Working Group of
Myocardial and Pericardial Diseases of
the European Society of Cardiology
presented a consensus document, in
which the key role of the 12-lead ECG
for identification of cardiac diseases
leading to sudden death was empha-
sized. (12) This same study group is
working on updated European guide-
lines to be published soon, although
there may be problems for the differ-
ent health organizations in the Euro-
pean countries.
e76 Pediatrics in Review Vol.27 No.11 November 2006
View publication stats
Renato Vitiello, MD
Unità Operativa Complessa di
Pediatria e Neonatologia
Ospedal Civile Torre Annunziata
Torre Annunziata, Italy
References
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