CASTLE CONNOLLY GRADUATE BOARD REVIEW SERIES

Educational Review
Manual in Pediatrics
6th Edition – 2008

Editor-in-Chief
Robert M. Lembo, M.D.
Formerly Associate Professor, Clinical Pediatrics
New York University School of Medicine
Gastroenterology
and Nutrition
Anupama Chawla, MD
Harvey Aiges, MD

Contents

1. Disorders of the Neonatal Period and Infancy

2. Intestinal Disorders of Childhood

3. Acute Pancreatitis

4. Liver Disease in Childhood

5. Nutrition

6. References

7. Questions

GASTROENTEROLOGY AND NUTRITION 391

1. Disorders of the Neonatal
Period and Infancy
Congenital Anatomic Anomalies
Esophageal Atresia and
Tracheoesophageal Fistula
Esophageal atresia (EA) and tracheoesophageal fis-
tula (TEF) may occur alone or concurrently. Proximal
EA with distal TEF is the most common presentation,
occurring in almost 90% of patients who present with
EA.1 The incidence of the other 4 presentations is
illustrated in Figure 1.
Clinical presentation. In utero, polyhydramnios is
often seen in patients with EA, especially when EA is
present without TEF. These infants usually have
symptoms within the first 6 to 12 hours after birth.
They tend to accumulate saliva and fluid in the
esophageal pouch and present with early drooling,
choking, coughing, and significant respiratory diffi-
culties. In contrast, patients who have TEF without
EA may not have these symptoms, and their initial
presentation may be that of pneumonia.
A diagnosis of EA is easy to make. There is often
resistance to the passage of a nasogastric (NG) tube
into the stomach. If there is resistance, the tube should
Figure 1
Esophageal atresia and tracheoesophageal fistula
85%
Proximal
Esophagus Trachea
Distal
Esophagus
2%
392 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
be left in place and plain x-rays (anterior/posterior and
lateral projections) obtained. Small amounts of con-
trast material can then be instilled into the NG tube
and the blind ending of the esophagus can be con-
firmed (Figure 2). Absence of air in the abdomen in
this setting confirms the diagnosis of EA without TEF.
In contrast, if air is present in the gastrointestinal (GI)
tract in the presence of EA, then a TEF may be
present.
There is a high incidence of associated congenital
defects in patients with EA. Congenital anomalies
exist in approximately half the cases of EA, with car-
diac anomalies being the most common, followed by
musculoskeletal, anal and genitourinary anomalies
(Table 1).
Management. Operative correction through a one-
stage procedure is usually preferred. Primary repair of
the EA and division of the TEF are the goals of the
surgery. Primary anastomosis may not be feasible if
there is a long gap between the 2 esophageal ends. A
long gap is usually defined as a length that exceeds 2
cm or two vertebral body spaces, or when the upper
pouch is above the thoracic outlet.2 Significant post-
8% 4%
<1%
very
rare
operative complications have been noted especially in
patients with a long gap. Approximately 20% to 30%
Table 1

of these patients present with complications related to

primary esophageal anastomosis. In the immediate
Complications Associated with Esophageal

postoperative period, leaks may occur at the site of

Atresia and Tracheosophagel Fistula

anastomosis. Conservative management with intra-

venous (IV) nutrition, nonoral (NPO), and IV antibi-
Type Incidence

otics may be all that is required. Strictures may pre-

sent at the site of the anastomosis 2 to 4 weeks after
Cardiovascular 35

surgery. These usually respond to periodic dilations.

In 5% to 10% of the patients, a recurrence of the TEF
Gastrointestinal 15

has been reported. In this case, conservative manage-

ment may be of little benefit. The current recommen-
Neurologic 5

dation is that if recurrent TEF persists after 4 weeks of

conservative management, then surgical correction is
Genitourinary 5

warranted. Skeletal 2

Approximately 40% to 50% of these patients have

been noted to have gastroesophageal reflux, which is
VACTERL 25

attributed to mobilization of the distal esophagus with

a small portion of the stomach being pulled into the
Overall incidence 50-77

thoracic cavity. This can present with severe distal

esophagitis and, at times, distal esophageal or anasto-
VACTERL=vertebral, anal, cardiac, tracheal, esophageal,
renal, and limb syndrome

Figure 2 From Coran A. Clinical Practice of Gastroenterology.

Philadelphia, Pa: Current Medicine; 1999.

motic strictures. Despite all these complications, most

Radiographic investigation of

infants with this condition have an excellent outcome,

esophageal atresia

especially infants without associated cardiac defects.

Duodenal Atresia and Stenosis

The incidence of duodenal atresia is reportedly
between 1:20,000 and 1:40,000 births. Approxi-
mately 25% to 30% of infants with duodenal atresia
have Down syndrome.

Clinical presentation. Duodenal atresia and stenosis

are also associated with other congenital anomalies,
such as EA, malrotation of the midgut, imperforate
anus, and congenital cardiac anomalies.3 More than
50% of duodenal atresia cases are associated with
polyhydramnios. It can often be confirmed in utero by
ultrasonographic examination. However, prenatal
ultrasonography is not always accurate; therefore, the
diagnosis must be confirmed after birth. Neonatal
vomiting may or may not be bilious, depending on the
site of the duodenal obstruction.
The blind upper pouch is outlined with barium. Air is pre-
sent in the stomach, therefore suggesting a T-E fistula in
the distal esophagus.

GASTROENTEROLOGY AND NUTRITION 393


Figure 3
Classic double-bubble sign compatible with
duodenal atresia
In addition, the patient demonstrates esophageal atresia
and cardiomegaly (child with Down syndrome).
Duodenal atresia causes a classic double-bubble sign
with the absence of distal gas on a plain upright
abdominal x-ray (Figure 3). Contrast barium studies
are not necessary. Duodenal stenosis usually causes
only partial obstruction; therefore, the plain x-ray
films are not diagnostic. An upper GI contrast study
confirms the diagnosis.
Management. Surgical correction is warranted for
both duodenal atresia and stenosis. At the time of
surgery, malrotation should be ruled out. An end-to-
side or side-to-side duodenoduodenostomy is the pro-
cedure of choice. In cases of very distal duodenal
lesions, a duodenojejunostomy is performed. In most
cases of neonatal duodenal atresia and stenosis repair,
total parenteral nutrition (TPN) is started within 24
hours of surgery and continued until oral feeding is
established. Delayed emptying of the duodenum may
occur after the surgical repair, but usually improves
over 3 to 4 weeks. In a significant number of infants,
however, duodenal motility problems persist through-
out life.
394 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Hypertrophic Pyloric Stenosis
Hypertrophic pyloric stenosis is the most common
condition requiring abdominal surgery in infants.
Muscular hypertrophy of the circular muscle of the
pyloric canal results in stenosis. In time, the circular
muscle increases in length as well as thickness, result-
ing in partial gastric outlet obstruction.4 The condition
is more common in first-born children, and males are
affected 5 times more frequently than females. There
is an increased risk in siblings and offspring of
affected children. The precise cause of the pyloric cir-
cular hypertrophy remains poorly understood. Lately
systemic erythromycin given in the first 2 weeks of
life has been suggested as a risk factor.5
Clinical presentation. Pyloric stenosis usually pre-
sents between the ages of 2 weeks and 3 months, with
a peak incidence around 3 to 4 weeks. These infants
present with vomiting, which may have been occur-
ring since birth but has become more frequent and
forceful. The emesis is not bilious and is often projec-
tile in nature. Vomiting usually occurs 10 to 15 min-
utes after a feeding, and these infants are often hungry
after these episodes.
The hypertrophic pyloric muscle is often referred to as
the pyloric olive. It is palpable in about 80% of these
infants, feeling like a hard, moveable mass approxi-
mately 1.5 cm in diameter. It is usually palpable in the
upper abdomen to the right of the midline, especially
immediately after a bout of vomiting. Decompression
by a feeding tube also makes it easier to palpate the
olive. Immediately after a feed, peristaltic waves can
be visualized in the upper abdomen, moving from the
right upper quadrant to the left upper quadrant. Elec-
trolyte abnormalities are often encountered due to the
loss of hydrochloric acid in the emesis. These infants
may present with dehydration, hypochloremia, and
metabolic alkalosis. Jaundice is present in about 2%
of these infants. This icterus is of the unconjugated
type. Studies have suggested that these infants have
Gilbert’s disease. The jaundice clears quickly after
surgery.
Diagnosis. Diagnosis of hypertrophic pyloric stenosis
in the majority of infants is usually made on physical
examination. If the pyloric olive is palpable, no fur-
ther diagnostic tests are needed. However, if the his-
tory is suggestive but the physical examination is
inconclusive, imaging studies are recommended.
Ultrasonography of the pyloric channel is diagnostic.
There are strict diagnostic criteria: The pyloric muscle
must be thicker than 5 mm and longer than 2.1 cm. An
upper GI series typically demonstrates abnormal
length of the pyloric canal and narrowing of the lumen
with significantly delayed gastric emptying.
Management. Most of these infants require fluid
resuscitation and correction of electrolytes. Their
metabolic alkalosis is corrected prior to surgery. The
definitive treatment of choice is pyloromyotomy,
which involves splitting the muscle longitudinally
without interrupting the mucosal lining. In the past
few years, several reports have been published on
laparoscopic pyloromyotomy, which has the distinct
advantage of leaving no visible scars.6 Most infants
resume full feeds within 24 to 48 hours after surgery.
Some, however, continue to have emesis. These
infants do well with total volume feeds of lower
caloric strength. Emesis usually resolves over 4 to 5
days.
Table 2
Differentiating Hirschsprung Disease and Functional Constipation
Hirschsprung Disease
Onset of symptoms Infancy
Passage of meconium >24 hours after birth
Rectal examination Empty, snug rectal vault
Explosive liquid stool
Barium enema Shows transition zone (Figure 4)
Rectal suction biopsy Absent ganglion cells/thickened
nerve fibers
Hirschsprung Disease
Hirschsprung disease is a congenital anomaly charac-
terized by the absence of ganglion cells in the colon. It
is a result of the failure of the craniocaudal migration
of ganglion cells along the GI tract. Absence of gan-
glion cells interrupts the inhibitory parasympathetic
nerves in the myenteric plexus, which prevents the
colon from relaxing. This disorder has an incidence of
1:5000 live births, with a male-to-female ratio of
3.8:1. Preganglionic parasympathetic fibers are
hypertrophied. The high concentration of acetyl-
cholinesterase provides a useful means of diagnosing
Hirschsprung disease on rectal suction biopsies. The
extent of aganglionosis varies considerably from
patient to patient. In 75% to 80% of patients, it is lim-
ited to the rectosigmoid area; only 8% of children pre-
sent with total colonic aganglionosis. Reports of
aganglionosis extending to the small bowel have been
extremely rare. Multiple Hirschsprung disease sus-
ceptibility genes are identified.
Clinical presentation. In more than 90% of infants,
symptoms or signs are present during the first 24 to 48
hours of life.7 Approximately 94% of them fail to
pass meconium during the first 24 hours and 57%
during the first 48 hours after birth. Among normal
infants, 25% pass meconium during the first 24 hours
of life and 99% within 48 hours. Any full-term infant
Functional Constipation
After a year of age
< 24 hours of birth
Stool filled, normal/dilated vault
Hard stool
No transition zone
Ganglion cells present/
delicate nerve fibers
GASTROENTEROLOGY AND NUTRITION 395

Figure 4
Hirschsprung disease
On barium enema, a transitional zone (arrow) is seen from
ganglionic proximal bowel that is dilated to an aganglionic
distal bowel that has a normal caliber.
who has not passed meconium by 48 hours after birth
must be evaluated for Hirschsprung disease. During
the neonatal period, these infants typically present
with abdominal distention, vomiting (which is often
bilious), and, infrequently, with enterocolitis. Entero-
colitis is characterized by the presence of abdominal
distention, explosive, watery stools, and, at times,
blood in the stool. Despite the early presentation of
symptoms, only 8% to 10% of patients are diagnosed
within the first month of life and only 40% by 3
months of age. Rectal examination is usually charac-
terized by a snug rectal vault around the finger fol-
lowed by projectile, forceful expulsion of stool after
the finger is withdrawn. Enterocolitis significantly
worsens the outcome for these patients. A mortality
rate of 4% has been reported for those who were diag-
nosed without enterocolitis vs. 33% for those who
developed enterocolitis. Differentiating Hirschsprung
disease from functional constipation is important.
(Table 2)
396 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Diagnosis. A single-contrast barium enema in an
unprepared child is often used to demonstrate a transi-
tion zone between ganglionic and aganglionic bowel.
The use of enemas, laxatives, or manual decompres-
sion of the rectum significantly decreases the sensitiv-
ity of this test. The transition zone can also be missed
if the catheter being used for the barium enema is
placed proximal to it. Early in the neonatal period, the
transition zone is commonly absent because the bowel
proximal to the aganglionic segment has not had time
to dilate.
Anal manometry measures the response of the inter-
nal sphincter to rectal inflation. The rationale for this
test is that distention of the rectum results in relaxation
of the internal anal sphincter in normal individuals. In
patients with Hirschsprung’s disease, this inhibitory
reflex is absent. Three balloons are used to perform
the study—one being placed in the rectal vault,
another within the internal sphincter, and the third
within the external sphincter. The balloon in the rec-
tum is inflated to mimic a fecal bolus, and changes in
the internal and external sphincter are measured by
manometry. In experienced hands, this method is said
to have an accuracy of 95% in the diagnosis of agan-
glionosis. It is particularly useful for children with
ultra-short segment disease (<5 cm). Despite its speci-
ficity and sensitivity, however, it has fallen out of
Rectal biopsy is used as the initial diagnostic study at
centers with a pediatric gastroenterology service. Rel-
atively easy to perform, it provides a definitive diag-
nosis of aganglionosis. Endoscopically obtained for-
ceps biopsies are usually inadequate for diagnostic
purposes. These biopsies are not deep enough to con-
tain adequate amounts of submucosal tissue. Gan-
glion cells are typically present in the myenteric
plexus, as well as in Meissner’s plexus in the submu-
cosal layer. Rectal suction biopsies using instruments
designed for this technique are much more adequate.
Management. Surgical correction is warranted for
patients with Hirschsprung’s disease. In infants,
obstruction is relieved by creating an ostomy proxi-
mal to the aganglionic segment. Definitive surgery is
usually performed at approximately age 1 year or
when the infant weighs approximately 10 kg. In older
children, definitive surgery consists of resection of the
aganglionic segment and pull-through of the gan-

Figure 5
Omphalocele
Anterior abdominal wall defect with congenital herniation
at the umbilicus. Herniated organs are covered by a sac.
Figure 6
Gastroschisis
Anterior abdominal wall defect; the extruded intestine has
no covering sac.
glionic segment to the anal opening. These are usually
performed as a one-stage surgical procedure.
Children with Hirschsprung’s disease often continue
to have some rectal dysmotility following surgery.
They often have symptoms of fecal retention and
require mild laxatives. Some children present with
incontinence after pull-through surgery because of
external anal sphincter dysfunction. Medical manage-
ment—consisting of a high-fiber diet and, at times,
use of loperamide hydrochloride—usually has ade-
quate results.
Imperforate Anus
The term “imperforate anus” refers to the absence of
an anal opening. Imperforate anus anomalies are cate-
gorized as high or low lesions, the dividing line being
the levator ani muscle. An incidence of 1:5000 births
has been reported. More than 85% of male patients
with a high lesion have a fistula between the anus and
the urethra or bladder; 80% of females with high
lesions have a fistula to the vagina. In both males and
females with low lesions, 90% have a fistulous tract to
the perineum that is often mistaken for the anal open-
ing. The imperforate anus is associated with many
other anomalies, the most common involving the
skeletal, cardiac, sacral, central nervous (CNS) and
intestinal systems.
Management. Every patient with a high anomaly
undergoes a diverting colostomy within 48 hours
of birth.8 Definitive surgery—which consists of
bringing down the colon through the puborectalis
portion of the levator sling and then through the
perineum—is performed at a later stage. Low
lesions are usually repaired soon after birth by
anoplasty and resection of perineal fistulae, if pre-
sent. The long-term results for all low lesions are
usually excellent, and patients retain normal conti-
nence. The results are not as successful in the cor-
rection of high lesions, with most patients lacking
the normal sensory innervation of their neoanus,
which results in some degree of incontinence.
Omphalocele and Gastroschisis
Omphalocele is a congenital hernia that occurs at the
umbilicus and is usually covered by a sac formed by
fused layers of peritoneum and amnion (Figure 5).
There is a central defect in the skin and the muscles of
the anterior abdominal wall. Gastroschisis is a full-
thickness defect in the anterior abdominal wall, usu-
ally to the right of a normal umbilicus. In gastroschi-
sis, the extruded intestine has no covering sac
(Figure 6).
Management and prognosis for these patients varies
with the size of the defect and the severity of any
associated anomalies. Most patients with omphalo-
GASTROENTEROLOGY AND NUTRITION 397
cele have associated anomalies, but these are rare
among patients with gastroschisis. Malrotation,
extrophy of the bladder, renal anomalies, and car-
diovascular defects are some of the commonly asso-
ciated anomalies. Even with the return of the bowel
to the abdominal cavity, it can take several months
for the damaged, exposed bowel to regain normal
function. Adhesions presenting with intestinal
obstruction comprise the most frequent complica-
tion of the corrected surgery.
Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC) is usually seen in pre-
mature infants. NEC is characterized by various
lesions, ranging from superficial mucosal ulcerations
with edema and hemorrhage to coagulative transmu-
ral necrosis of the intestine. The incidence rate is 1%
to 5% of all admissions to the neonatal intensive care
unit (NICU).
two-thirds of patients with NEC and is pathognomonic
of NEC. Pneumoperitoneum indicates intestinal perfo-
ration. In the absence of x-ray findings, a high level of
suspicion is enough to initiate therapy.
Management. Treatment is initiated as soon as the
diagnosis is suspected. Oral feedings are withheld.
An NG tube is inserted to provide intermittent suc-
tion for decompression. IV fluids are used to correct
any electrolyte abnormalities. Clinically these
infants are very difficult to distinguish from infants
with sepsis. Because bacteria have been implicated
in the pathogenesis of NEC, broad-spectrum antibi-
otics are initiated.
The patient’s course is monitored closely with fre-
quent cross-table lateral x-rays to evaluate for

Pathology and pathogenesis. Although lesions may

Figure 7

occur throughout the GI tract, the most common sites

of involvement are the distal ileum and the ascending
Necrotizing enterocolitis

colon. Inflammation initially results in mucosal ulcer-

ation and submucosal edema, which progresses to
varying degrees of mucosal or transmural necrosis of
the intestine and leads to perforation. Healing occurs
through epithelialization and fibrosis, which often
leads to stricture formation.

The pathogenesis of this disease is believed to be mul-

tifactorial.9,10 Early initiation of enteral feedings,
intestinal hypoperfusion, and infection have been
implicated as precipitating factors. In addition, the
incidence of NEC is inversely proportional to the
infant’s birth weight and gestational age.

Clinical presentation. Symptoms of NEC usually

begin during the first 2 weeks of life, but may be seen
as late as 10 weeks. The classic symptoms include
abdominal distention, bilious vomiting, and blood in
the stool. The disease can present much more aggres-
sively with severe abdominal distention, peritonitis,
bowel perforation, shock, and rapid progression to
death. It has been reported infrequently in infants who
have never been fed enterally.

Diagnosis. Plain abdominal x-rays may demonstrate

pneumatosis intestinales (Figure 7), which is seen in
Plain abdominal roentgenogram demonstrating the pres-
ence of air in the intestinal wall (pneumatosis intestinales).

398 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS

intestinal perforation. Medical management is suc-
cessful in about 80% of these patients. Surgery is
indicated when they do not respond to medical man-
agement or if intestinal perforation occurs.
Morbidity and mortality from NEC has improved
dramatically. Strictures of the intestine are the most
common sequelae, occurring in almost 25% of these
infants. Short bowel syndrome is seen in infants
when large portions of gangrenous small intestine
have been resected.
Gastroesophageal Reflux Disease (GERD)
Gastroesophageal reflux (GER) is one of the most
common GI problems in children, and especially in
infants. Regurgitation of gastric material into the
esophagus is normally controlled by the tonic pressure
of the lower esophageal sphincter (LES). Some degree
of physiologic reflux occurs in healthy children and
adults, but only in brief episodes and usually during
the postprandial hour. Reflux of gastric contents into
the esophagus is considered pathological if it occurs
with increasing frequency, there is poor clearance of
the reflux material, and it is associated with discomfort
or pain, or with reactive airway disease, apnea, or
bradycardia.
Clinical presentation. Effortless regurgitation is
observed almost universally in all healthy infants.
Even infants with physiological reflux appear to be in
no distress and often smile immediately after regurgi-
tation of the formula. Pathologic manifestations of
GER are considered present when one or more of the
following symptoms is present: irritability, choking
episodes, failure to thrive, apnea, feeding difficulties,
and, rarely, acute life-threatening episodes.11 This
condition may be mistaken for neurologic impair-
ment, because the patients can present with severe
arching, stiffening, and torticollis in conjunction with
severe irritability (Sandifer syndrome). The causal
relationship between GER and respiratory symptoms
is more controversial.12 Respiratory symptoms, such
as reactive airway disease, can induce significant
reflux, although it is increasingly recognized that the
reflux is most likely the underlying cause of the reac-
tive airway disease. The significant improvement in
reactive airway symptoms when affected infants are
treated for reflux provides further evidence of reflux
being the causative factor. Older children may mani-
fest symptoms similar to those seen in adults. They
typically present with substernal burning which is
exacerbated during the postprandial period and usu-
ally relieved by antacids. Odynophagia (pain on swal-
lowing) or dysphagia (characterized by the sensation
of food being stuck in the esophagus) may be the only
clinical symptoms of reflux in an older child.
Diagnosis. During infancy, a diagnosis of pathologic
GER can usually be made clinically by accurate his-
tory taking and clinical observation, especially during
a feed. Infants with GER-associated failure to thrive
should be considered for screening blood tests to rule
out metabolic etiologies. Children with projectile
vomiting or vomiting that results in dehydration
should be evaluated radiographically to rule out par-
tial gastric outlet obstruction (eg, pyloric stenosis,
malrotation, antral web, duodenal stenosis).
Infants without emesis but with other symptoms sug-
gesting GER require further diagnostic tests (eg, 24-
hour intraesophageal pH monitoring, barium esopha-
gogram, and possibly esophagogastroduodenoscopy).
Esophageal pH monitoring is regarded as the gold
standard for diagnosing reflux. It is performed on an
outpatient basis, and children are able to continue with
their usual activities during the study. Analysis of the
pH probe studies can be used to determine the number
of episodes of acid reflux, the average duration of
these episodes, and the total time the esophagus is
exposed to an acidic pH during a 24-hour period. Age-
related normal values for these parameters have been
defined. The limitations of a nasal probe based study
include discomfort and interference with normal feed-
ing and activity. For older children an alternative to
conventional pH monitoring is the wireless Medtronic
Bravo pH System. This wireless system, used widely
in adult patients, endoscopically places a telemetry
capsule in the esophagus. The data signal is transmit-
ted and recorded in a pager-sized device. These
devices are well tolerated and have comparable out-
comes with conventional probe devices.13 More
important than the quantification of reflux is the asso-
ciation of reflux episodes with the presenting symp-
toms. Polysomnography, which allows simultaneous
monitoring of the electrocardiogram (ECG), oxygen
saturation, esophageal pH monitoring, and the pneu-
mogram, is especially helpful for evaluating infants
with clinical apnea and GER. Although the pH probe
can quantify acid reflux, it cannot detect reflux for as
long as 2 hours following infant formula feeds due to
GASTROENTEROLOGY AND NUTRITION 399
their neutral pH and high buffering capacity. Also, a
pH probe does not detect reflux of nonacid material
and, thus, may underestimate reflux frequency. Multi-
channel intraluminal impedance (MII) provides an
alternative method for studying GER, allowing for the
detection of both acid and nonacid reflux events.14 The
intraluminal catheter has a pH sensor. MII detects
bolus movement independent of the pH composition
of the refluxate, whereas the pH sensor characterizes
the acidity of the refluxate. An impedance-detected
reflux event is defined as a retrograde bolus movement
across at least the distal 2 channels with a drop in base-
line impedance of at least 50%. To label the
impedance-detected reflux event as acid, the pH must
fall below 4.0 at any time when the bolus is physically
present in the distal clearance channel. This technol-
ogy can detect the presence of GER refluxate of all
types within the esophagus.
MII-pH was found to be superior to pH monitoring in
correlating a positive symptom index with reflux
events in children.15 That study found that nonacid
reflux was more highly associated with respiratory
symptoms than acid reflux.
There are several imaging studies that are used in the
diagnosis of GER. The barium esophagogram
should be used to rule out any anatomical abnormal-
ity that could result in a partial gastric outlet obstruc-
tion that could precipitate GER. It is a poor choice
for diagnosing reflux itself, however, because of its
brief monitoring time and the inability to use it to
distinguish between physiologic and pathologic
reflux. Gastroesophageal scintigraphy may be help-
ful for evaluating gastric emptying and to rule out
pulmonary aspiration. A high rate of false-negative
results has placed this test in disfavor, however.
Esophagogastroduodenoscopy is used to obtain
esophageal mucosal biopsies under direct vision.
The biopsy is the most sensitive test for the detection
of mild nonerosive esophagitis.
Management. Most infants with symptomatic reflux
should initially be managed with conservative antire-
flux measures. Only if such measures fail should phar-
macologic therapy be initiated. Surgical management
is reserved for serious manifestations of reflux that do
not respond to pharmacological therapy and/or persist
beyond the second year of life.
400 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Antireflux measures include:
Positioning of infants. It is recommended that
infants be kept seated upright for at least 45 minutes to
an hour after each feed. Elevation of the head end of
the crib is also recommended. The prone position has
been shown to enhance gastric emptying and thus
decrease GER and the risk of aspiration.
Diet. Formula thickening has been shown clinically
to decrease the number of reflux episodes and the vol-
ume of the vomitus. Rice cereal may be added to the
formula (0.5 to 1 tsp cereal per ounce formula). Small,
frequent meals may also be beneficial. In older chil-
dren, avoiding certain foods that are known to
increase GER (eg, carbonated beverages, fatty foods,
coffee, alcohol, and cigarettes) may be beneficial.
Pharmacologic measures include:
Acid suppression. Antacids, H2 receptor antagonists,
and proton-pump inhibitors have been used for acid
suppression. If antacid therapy is required several
times a day for symptom relief, most practitioners will
switch to H2 receptor antagonists. Ranitidine 4 to 6
mg/kg per day or nizatidine 4-6 mg/kg/day or famoti-
dine 1 to 2 mg/kg per day in 2 to 3 divided doses is
usually prescribed. If these children continue to have
symptoms despite therapy, proton-pump inhibitors
are recommended, especially for children who have
documented esophagitis.
Prokinetic therapy. If acid suppression alone does
not alleviate the symptoms, or if vomiting is interfer-
ing with caloric intake, then the concomitant use of
prokinetic agents is recommended. Erythromycin has
established itself as a prokinetic agent. Acting as a
motilin receptor agonist, this medication binds to the
receptors on the GI smooth muscle. The induction of
contractions from the stomach to the small bowel
facilitates stomach emptying. This is accomplished
using 10% to 20% of the dose used for its antibiotic
properties (1-3 mg/kg/dose every 6 hours). Metoclo-
pramide, a dopamine antagonist and cisapride—a
noncholinergic, nonantidopaminergic agent that
enhances postganglionic acetylcholine release have
been used for their prokinetic properties. However,
reports of cardiac arrhythmias, prolongation of the QT
interval, and death have led to the withdrawal of cis-
apride from the market. Metoclopramide is prescribed
at a dose of 0.1 mg/kg/dose, given 15 to 30 minutes
before meals, 4 times a day. However, drowsiness,
restlessness, irritability and extrapyramidal effects
make its use less desirable. It also may lower the
seizure threshold, and therefore should be used with
caution in children with seizure disorder.
Surgery. Surgery is reserved for children with severe
intractable symptoms. Nissen fundoplication is the
treatment of choice. A significant reduction in reflux
has been reported for more than 90% of these patients.
However, both short- and long-term complications are
frequent and much more common in children with
neurological problems. Complications include the
inability to burp or vomit, especially during indiges-
tion or a bout of gastroenteritis; severe gas bloat; and
discomfort and dysphagia. Severe retching is espe-
cially noted in severely handicapped children. Most
centers now perform this procedure laparoscopically.
Milk Protein Intolerance
The incidence of cow’s milk protein allergy is approx-
imately 1% to 7% for infants.16 It has been estimated
that almost 50% of infants who are allergic to cow’s
milk protein are also allergic to soy protein. Children
who are allergic to cow’s milk protein may present
with urticaria or anaphylaxis within minutes of
ingesting milk. More often, they present after days of
cow’s milk ingestion with symptoms of vomiting,
diarrhea, blood in the stool, or eczema. They usually
present with gross blood in their stools during the first
3 months of life. The stool is usually well formed and
the blood is bright red in color. The infants usually
appear healthy and gain weight adequately. On
endoscopy, however, the colonic mucosa appears
erythematous and friable, and eosinophilic infiltration
of the mucosa is seen on histology. These patients may
or may not exhibit peripheral eosinophilia. Charcot-
Leyden crystals may be found on microscopic exami-
nation of the stool.
Most of these infants respond to being switched to a
casein hydrolysate formula. The gross blood resolves
within 2 to 3 days of discontinuing cow’s milk protein.
In a small percentage of patients, symptoms persist
despite being switched to a casein hydrolysate for-
mula; occult blood in the stool might persist for 7 to 10
days. Fortunately, most of these infants respond to
amino acid-containing non-milk-based formula.17
Most infants with cow’s milk protein allergy do well,
with 60% of them developing a tolerance for cow’s
milk protein by the time they reach age 1 year and
approximately 85% by age 2 years. Children who pre-
sent with GI symptoms can usually be challenged on
an outpatient basis. However, a child whose initial
presentation was anaphylaxis and respiratory symp-
toms should be challenged in a hospital setting.
Eosinophilic Gastroenteropathy (EG)
EG is a chronic disorder in which eosinophils consti-
tute the predominant cellular infiltrate in the gastroin-
testinal tract. In children with EG the clinical presen-
tation depends on the gastrointestinal segment
affected and the wall layers infiltrated. Eosinophils
have been shown to be an integral member of the gas-
trointestinal mucosal immune system, but their pres-
ence in deeper layers is almost always pathologic. EG
is still a quite rare disease. Patients with EG present
with a variety of clinical problems, most commonly
failure to thrive, abdominal pain, irritability, gastric
dysmotility, vomiting, diarrhea and dysphagia. Severe
cases may present with peripheral edema resulting
from protein losing enteropathy. In children with
colonic involvement hematochezia may be the pre-
sentation. The wide array of non-specific common
gastrointestinal symptoms and laboratory findings
explains why the correct diagnosis is dependent on the
microscopic examination of the biopsy samples.
Eosinophilic esophagitis (EE) appears to be a growing
health problem with an annual incidence of at least 1
in 10,000 children.18 The primary symptoms of EE
(chest and abdominal pain, dysphagia, heartburn,
vomiting, and food impaction) are also observed in
patients with chronic esophagitis including GERD.
However, in contrast to GERD, EE appears to have a
common familial form, has a high rate of associated
atopic disease (70%), and is typically associated with
a normal pH probe recording of the esophagus. Dis-
tinguishing EE from GERD is important since EE
patients do not respond to anti-GERD therapy. They
may respond to allergen elimination and/or anti-
inflammatory therapy. Both GERD and EE are associ-
ated with esophageal eosinophils, however, the level
of eosinophils in EE is much higher, greater than 24
eosinophils per high-power field (hpf) (×400); the
normal esophagus is devoid of eosinophils. Endo-
scopic examination of the esophagus may show gran-
ularity with linear furrows and/or concentric rings.
GASTROENTEROLOGY AND NUTRITION 401
Management: If specific foods are suspected or
known to provoke the characteristic symptoms and
then an elimination diet should be instituted. At times
more global dietary restriction with an elemental diet
may be warranted. Amino acid based formulas have
been shown to significantly reduce intraepithelial
eosinophils. In severe cases or those unresponsive to
dietary restrictions, corticosteroids may be effective.
Oral fluticasone propionate has been shown to be
effective in resolving symptoms of EE.
Disodium cromoglycate given orally may be effective
in controlling symptoms of EG. Kettifen, an H1 anti-
histamine, may be of benefit, to children with EG.
More to recently montelukast (Singulair®), a
leukotriene antagonist, has been shown to be effective
within 2 to 4 weeks of therapy.19
Cystic Fibrosis
Cystic fibrosis (CF) is a multisystem disease with a
highly variable course that may present at any time
from birth through adulthood. A diagnosis is made for
80% of patients with CF by age 2 years.20 It is the
most common debilitating genetic disease affecting
Caucasian children.
Inheritance and Genetic Disorder
CF is an autosomal recessive disorder that affects
1:2000 Caucasians and 1:15,000 children of African
descent. Among Caucasians, 1:20 is a carrier. The
gene responsible for CF has been located on the long
arm of chromosome 7. It gives rise to a protein called
the cystic fibrosis transmembrane conductance regu-
lator (CFTR), which regulates the transport of chlo-
ride and other electrolytes across epithelial cell mem-
branes. A mutation of this gene results in the absence
or malfunction of the CFTR channel, which prevents
chloride ions from moving out of the cell and indi-
rectly allows excess sodium into cells. Although there
are more than 1,300 mutations that have been identi-
fied, 70% of the mutations in CF patients are due to
the loss of a phenylalanine residue at amino acid 508
on the CF gene.21
Clinical Presentation
GI and pulmonary causes are the usual mode of pre-
sentation. GI manifestations may present with intesti-
nal, pancreatic esophageal, hepatobiliary as well as
nutritional symptoms.
402 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Intestinal manifestations. Meconium ileus is the
most common presentation of CF in the newborn. Ten
to twenty percent of infants with cystic fibrosis pre-
sent within the first 48 hours of life with meconium
ileus, an intestinal obstruction caused by an abnor-
mally thick and viscid meconium mass, which usually
forms at the ileocecal valve. The newborn with CF
may also present with obstruction of the small intes-
tine as a result of intestinal stenosis or atresia. Rectal
prolapse occurs in less than 1% of patients with CF
each year, but may be the presenting symptom of CF
in infants. In older children, the distal intestinal
obstruction syndrome formally known as meconium
ileus equivalent can occur. This syndrome consists of
colicky abdominal pain, distention, and a palpable
mass, usually in the right lower quadrant. This mass
represents inspissated stool, which causes partial
obstruction. Omission or inadequate intake of pancre-
atic enzymes may be a contributing cause of this syn-
drome.
Infants with CF may present with failure to thrive with
a history of passing several large, bulky bowel move-
ments a day. Malabsorption in the small intestine as
well as pancreatic enzyme deficiency contribute to
these symptoms. Several studies have shown that the
active transport mechanism for bile acid absorption is
abnormal, resulting in increased loss of fecal bile acid
and impaired absorption of Vitamin B12, free fatty
acids, and fat-soluble vitamins. Decreased intestinal
disaccharidase activity manifesting clinically as lac-
tose intolerance has been reported. Some infants with
CF who are fed breast milk or soy-based formula may
develop significant hypoproteinemia and edema sec-
ondary to the low protein content of breast milk or the
reduced availability of the protein in soy milk. Rectal
prolapse is becoming increasingly rare, fortunately,
because of earlier diagnosis and treatment. Gastroe-
sophageal Reflux is often encountered in patients with
CF. Causes are myriad (eg, respiratory medications
that decrease the lower esophageal sphincter pressure,
or an increased abdominal thoracic pressure gradient
following bouts of severe coughing). Many patients
with CF have gastric acid hypersecretion and pancre-
atic and duodenal bicarbonate hyposecretion resulting
in duodenal pH that is too acidic for optimal dissolu-
tion of the enteric coating of enzyme preparation.
Pharmacologic acid suppression helps these patients
achieve adequate fat absorption.22
Hepatobiliary manifestations. Prolonged neonatal
cholestasis occurs in about 5% to 10% of infants with
Table 3

CF as a result of bile duct obstruction due to inspis-

sated bile and mucous. Approximately 20% to 30% of
Indications for Sweat Testing

children with CF have been noted to have abnormal

liver tests. As their survival age increases, more CF
Gastrointestinal

patients are developing multilobular cirrhosis. It is

estimated that 10% of people over the age of 25 with
Meconium ileus

CF have cirrhosis and portal hypertension. Cholecys-

Unexplained intestinal obstruction

titis and cholelithiasis are also becoming increasingly

(distal intestinal obstruction syndrome)

evident in this patient population as it survives into

Rectal prolapse

adulthood; 60% of young adult patients are noted to

Intussusception over the age of 2 years

have gallbladder disease.

Malabsorption/failure to thrive
Voracious appetite with poor weight gain

Pancreatic manifestations. Total pancreatic insuffi-

Symptomatic deficiency of vitamins A, D, E and K

ciency has been seen in 80% of infants with CF. The

Prolonged infantile cholestasis

insufficiency is caused by mucous obstruction of the

Cirrhosis/portal hypertension

pancreatic ducts, which prevents the efflux of pancre-

Unexplained cholelithiasis

atic enzymes and results in autolysis of the pancreatic

Pancreatitis in children or adolescents

parenchyma. Diabetes mellitus is a common problem

in these patients when they reach young adulthood.
Pulmonary

CF related diabetes mellitus occurs in as many as 50%

of patients older than 30 years of age. The diabetes is
Recurrent or nonresolving pneumonia

usually nonketotic. Patients who have adequate pan-

Staphylococcal pnuemonia

creatic function are more susceptible to recurrent

Psuedomonas aeruginosa in sputum

bouts of acute pancreatitis than patients with pancre-

Recurrent bronchiolitis

atic insufficiency.
Lobar atelectasis
Chronic bronchitis/chronic cough

Pulmonary manifestations. Abnormally thick

Radiographic evidence of bronchiectasis

mucous secretions and impaired ciliary function pre-

Hemoptysis in childhood

dispose these patients to recurrent lower respiratory

tract infections. Early infections are usually caused by
Miscellaneous

Staphylococcus aureus, but after approximately age 4,

the organism most commonly isolated from the pul-
Family history of cystic fibrosis

monary secretions is Pseudomonas aeruginosa. Clini-

Digital clubbing

cally, patients show signs of chronic obstructive pul-

Hyponatremic dehydration

monary disease with a barrel-shaped, emphysematous

Metabolic alkalosis

chest and digital clubbing. Colonization with

Salty taste of skin

Burkholderia cepacia occurs later, and is especially

Nasal polyps

ominous. Most of these patients finally succumb to

Pansinusitis

compromised respiratory function. In the last stage,

Unexplained hypoproteinemia/

they develop respiratory failure and cor pulmonale.

anasarca in infancy
Azoospermia

Miscellaneous manifestations. Chronic sinusitis

Unexplained delayed menarche

affects almost all CF patients, and 10% to 15% of

them develop significant nasal polyposis. Men with
From Aiges HW. Cystic fibrosis. In: Brandt LJ, ed. Clinical

CF are almost always sterile because of azoospermia

Practice of Gastroenterology. Philadelphia, PA:

and absence of the vas deferens.

Current Medicine; 1999.

GASTROENTEROLOGY AND NUTRITION 403

 DNA analysis in many cases by finding two known
disease-causing mutations in a patient with appropri-
Table 4

Non-Cystic Fibrosis Causes of ate clinical correlates.

Prenatal testing can now be accomplished in most

Abnormal Sweat Tests

families with an affected family member. Newborn

screening of the general population for CF, using heel-
stick testing of immunoreactive trypsinogen levels is
Adrenal insufficiency

gaining popularity and proving valuable.22

Glycogen storage disease, type I
Fucosidosis

Management
Malnutrition/edema

Early diagnosis, nutritional support, enzymatic sup-

Nephrogenic diabetes insipidus

plementation, and, most importantly, an aggressive

Hypothyroidism

approach to pulmonary complications have resulted

Ectodermal dysplasia

in a significantly decreased morbidity and prolonged

Prostaglandin E1 infusion

survival for these patients. With adequate nutrition

and prevention of malabsorption, these children can
From Aiges HW. Cystic fibrosis. In: Brandt LJ, ed. Clinical

gain weight and height adequately. Improved nutri-

Practice of Gastroenterology. Philadelphia, PA: Current

tional status has also been shown to prevent deteriora-

Medicine; 1999.

Diagnostic Tests tion of pulmonary function. In infants, the use of for-

The diagnosis of CF is established by the sweat test—
preferably by the pilocarpine iontophoresis technique,
in which at least 100 mg of sweat is acquired and a
quantitative analysis of chloride and sodium per-
formed. The normal value of sweat chloride is less
than 30 mEq/L. In 98% of patients with CF, the sweat
chloride level is greater than 60 mEq/L. Indications
for a sweat test are outlined in Table 3. Several condi-
tions may produce an elevated sweat electrolyte level,
and these should be considered when analyzing the
sweat test. Non-CF causes of abnormal sweat tests are
listed in Table 4. Diagnosis can now be confirmed by
mulas that contain medium-chain triglycerides pre-
cludes the need for pancreatic lipase. However, as the
child begins to eat solid foods, supplementation with
pancreatic enzymes becomes necessary. Capsules are
given with meals, with the dose titrated to decrease the
bulk and number of stools as well as the degree of
steatorrhea. For infants, capsules are opened and the
microspheres sprinkled in fruit. The toddler requires
about 1000 units of lipase/kg/meal; children aged 5 to
12 years 500 units of lipase/kg/meal.23 High daily
doses of pancreatic enzyme supplements may cause
fibrosing proximal colonic injury, which is character-
ized by inflammation, shortening, and fibrosis of the

Table 5

Fat Soluble Vitamin Recommendations for Patients with Cystic Fibrosis and Cholestasis

Age Vitamin A (IU) Vitamin D (IU) Vitamin E (IU) Vitamin K (mg)

0-12 months 1500 400 40-50 0.3-0.5

1-3 years 5000 400-800 80-150 0.3-0.5

4-8-years 5000-10,000 400-800 100-200 0.3-0.5

>8 years 10,000 400-800 200-400 0.3-0.5

Cystic Fibrosis Foundation, Consensus Guidelines, 2002

404 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS

colon. Enzyme replacement therapy should be limited
to 2500 units/kg of lipase per dose.
Figure 8

Patients with cystic fibrosis are at risk for fat-soluble

Celiac disease

vitamin deficiencies. To avoid the potential of fat-sol-

uble vitamin deficiencies, the patient’s diet should be
supplemented with these vitamins. ABDEK, a rela-
Children with celiac disease typically show a down-

tively new mixture of fat and water soluble vitamins,

ward decline in their weight gain with eventual flatten-

is now available but does not meet 100% of the rec-

ing of their growth curve approximately 3-6 months

ommended needs of these patients (Table 5).

after the introduction of gluten to their diets.

In the adolescent and young adult population, pul-

monary function usually worsens despite aggressive
pulmonary therapy and nutritional support, thereby
increasing metabolic demands. Long-term supple-
mental feedings are feasible and appear to be success-
ful in improving nutrition and at times stabilizing,
even improving, respiratory status. Nocturnal naso-
gastric or gastrostomy feedings are commonly used
for nutrition supplementation.

In patients with hepatic dysfunction, ursodeoxycolic

acid (a hydrophilic bile salt) increases bile flow and
results in an improvement in liver function test results.
However, there is no proof that it prevents the progres-
sion of CF liver disease. Orthotopic liver transplanta-
tion is indicated for patients with signs of hepatic fail-
ure. The results are especially good for patients with
mild to moderate pulmonary disease. Most patients
with CF can now be expected to survive into the third
decade of life. Patients with predominantly GI symp-
toms have a far better course than those with primarily
respiratory manifestations, and men seem to survive
longer than women.

Celiac Disease

Celiac disease (CD), also called gluten sensitive

enteropathy, is a permanent intestinal intolerance to
dietary wheat gliadin and related proteins that result in
a specific histologic lesion of the small intestine. Sig-
nificant regional differences have been noted in the
incidence of this disease. In Europe, an incidence of at
least 1:1000 live births is reported. CD has been well Clinical Features
documented in the Indian subcontinent, North Africa, The clinical features of CD vary considerably with
the Middle East, and in South America. It was thought the age at presentation. Intestinal symptoms are
to be relatively uncommon in the United States, but common in children diagnosed within the first 2
the incidence in the United States is fast approaching years of life. Chronic diarrhea, weight loss, vomit-
the European incidence over the past decade. ing, severe anorexia, and irritability are the present-
ing symptoms in children less than 2 years of age.

GASTROENTEROLOGY AND NUTRITION 405

Symptoms become apparent usually within 2 to 3
months following the introduction of wheat to the
diet. The patient’s history reveals normal growth
during the first few months of life; however, within
months of the introduction of wheat, the patient’s
stools become foul smelling and have oatmeal con-
sistency. At this time, the abdomen becomes dis-
tended and a concomitant loss of subcutaneous fat
and muscle wasting is seen, usually in the buttocks
and proximal extremities. The rate of weight gain
diminishes or weight loss ensues. Eventually the
patient’s growth curve flattens, usually 3 to 6
months after the introduction of gluten to their diets.
The height percentiles begin to decline a few
months later (Figure 8). When the diagnosis has
been missed, the patient presents with signs of mal-
absorption of fat-soluble vitamins, eg, bruising,
rickets, fractures, or tetany. Constipation has also
been reported in up to 10% of toddlers with CD.
Children older than 4 years may present to the
endocrinologist with short stature or in adolescence
with delayed puberty. They may have symptoms of
anorexia, abdominal pain, and lactose intolerance.
Older children may also present with iron deficiency
anemia. Dental abnormalities, which include severe
enamel hypoplasia, have been reported in up to 30%
of untreated CD children. Constipation is reported in
up to 28% of older children.
Associated diseases. Dermatitis herpetiformis is
associated with a pathology in the small intestine that
is histologically indistinguishable from that of CD.
The abnormal small intestine is present in approxi-
mately 50% of the patients who have dermatitis her-
petiformis and responds to a strict, gluten-free diet.
Other diseases that are found to have a higher-than-
expected frequency in patients with CD are insulin-
dependent diabetes mellitus, immunoglobulin A
(IgA) nephropathy, Down syndrome, selective IgA
deficiency, and sarcoidosis. The incidence of intesti-
nal lymphoma is also much higher in patients with
CD, especially patients who have not received treat-
ment or only received partial treatment.
406 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Diagnosis
Tests for malabsorption. Patients with CD may have
iron deficiency anemia and decreased serum albumin,
but red blood cell (RBC) folate level is particularly
sensitive. Quantitative fecal analysis over a 72-hour
period is the best available method for demonstrating
fat malabsorption. A 3-day diet record is maintained
on these patients, and starting on the third day, all
stools are collected over a 72-hour period. This stool
is analyzed for excreted fat. The percentage of malab-
sorbed fat is calculated as follows:
% Malabsorbed fat = [Fat excreted in 24 h (g) / fat
ingested in 24 h (g)] x 100
A value of less than 5% for malabsorbed fat is
considered normal.
Circulating antibodies in CD. Antigliadin,
antireticulin, endomysial, and tissue transglutami-
nase antibodies (TGA) provide an excellent screen-
ing profile for CD. Each of these antibodies can be
measured for their IgG and IgA fractions. The IgG
antigliadin and IgG antireticulin antibody have low
specificity and sensitivity for CD, but the
endomysial24,25 and t-TGA are indeed extremely
sensitive and specific markers. t-TGA is assessed
using the ELISA methodology, making it easier to
perform than the endomysial antibody, which is
assessed by the immunofluorescent technique.
t-TGA showed a sensitivity of 95% and a specificity
of 97% in children. These antibodies are less specific
in the presence of Down syndrome and diabetes mel-
litus and may be absent in children younger than 2
years and in patients with IgA deficiency. It is, there-
fore, recommended that all patients being screened
by these antibodies for suspected CD also be
screened for IgA deficiency. In a healthy population,
2% to 3% are reported to be IgA deficient.
The pathogenesis of CD is firmly rooted in host
genetic factors. This was first evident from clinical
observations of multiple cases of CD within fami-
lies, and the high (approximately 70%-75%) rate of
concordance for CD among monozygotic twins. It is
known that CD is associated with specific MHC
class II alleles that map to the HLA-DQ locus. The
HLA-DQ2 heterodimers that confer susceptibility to
CD are present in at least 90%-95% of patients with
CD. The HLA-DQ8 heterodimer is found in the
remaining 5%–10% of patients with CD. However,
HLA-DQ2 and HLA-DQ8 are present in approxi-
mately 40% of the United States population. Simply
having HLA-DQ2 or HLA-DQ8 and ingesting prod-
ucts made from wheat, rye, and barley does not cause
CD26.
Small intestine biopsy. The small intestine biopsy
remains the gold standard for the diagnosis of CD.
The main histologic findings include absence of villi,
crypt hyperplasia, intra-epithelial lymphocytes, and
infiltration of the lamina propria with plasma cells
and lymphocytes. Current requirements to fulfill the
criteria for the diagnosis of CD are:
Management. The specific therapy for CD is a
gluten-free diet that excludes wheat, barley, oats,
and rye. A strict gluten-free diet usually leads to
improvement within a few days. During infancy,
severe irritability and anorexia are the first symp-
toms to reverse; this is followed by improved stool
consistency. The histologic appearance of the
mucosa usually returns to normal within 6 months to
a year of the gluten-free diet. The current recom-
mendation is to stay on a gluten-free diet for life. In
severe cases or in infants who present with a celiac
crisis—which is characterized by profuse watery
diarrhea with or without vomiting and dehydra-
tion—immunosuppressive therapy is recom-
mended.

• A characteristic histologic appearance of the

mucosa at the time of presentation;

• Resolution of the symptoms following elimination

of gluten from the diet;

• Presence of circulating antibodies at the time of

diagnosis and their disappearance following gluten
withdrawal once the patient is asymptomatic.

A rechallenge is only necessary if these criteria are

not unequivocally fulfilled. Conditions other than
CD may result in total or partial villous atrophy.
These include cow’s milk or soy protein intolerance,
malnutrition, gastroenteritis, chronic Giardia lam-
blia infection, bacterial overgrowth, radiation enteri-
tis and immune deficiency states.

GASTROENTEROLOGY AND NUTRITION 407

2. Intestinal Disorders of
Childhood
Infectious Diarrhea
Diarrheal disease remains a leading cause of infant
mortality throughout the world. In Latin America,
Asia, and Africa it is estimated that each child has at
least 2 to 3 episodes of diarrhea a year. According to
the World Health Organization (1982), approximately
4 million children worldwide die from diarrhea each
year. Acute infectious diarrhea can be caused by either
viral or bacterial infections.
Viral Gastroenteritis
Viral agents cause diarrhea more frequently than bac-
terial agents, both in developed and underdeveloped
nations. Rotavirus, Norwalk virus, enteric adenovirus,
calicivirus, and astrovirus are among the causative
agents.27 They usually affect infants and toddlers.
Cytomegalovirus has also been associated with enteri-
tis and colitis, but this seems to occur almost exclu-
sively among immunocompromised patients.
Pathogenesis. Viral agents invade the villous entero-
cytes along the entire length of the small bowel. The
infected cells are shed, resulting in blunted villi.
Hyperplasia of the crypt cells occurs, but these imma-
ture cells are deficient in lactase and sucrase. Lack of
these enzymes results in significant protracted
osmotic diarrhea, at times lasting for 4 to 6 weeks.
Clinical manifestations. Rotavirus infection is
more commonly seen in the winter, whereas enteric
adenovirus usually causes diarrhea during the sum-
mer. Illness typically begins with the sudden onset of
diarrhea and vomiting. Vomiting may precede the
diarrhea by 24 hours. The stools are usually watery.
With rotavirus infection, gross or occult blood may
rarely be present in the stool. The acute watery diar-
rhea usually results within 2 to 5 days. Watery diar-
rhea resolves, but some degree of osmotic diarrhea
persists till the villous pattern of the small intestine is
restored. Diagnosis of rotavirus typically is accom-
plished by using enzyme-linked immunosorbent
assays that detect rotaviral agents.
Treatment. Supportive therapy with oral or IV rehy-
dration is the mainstay of care. Early onset of feeding,
regardless of the diarrheal stools, is recommended.
For a short period, rotavirus oral vaccine was being
408 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
administered, but has been withdrawn because of
increased incidence of associated intussusception.
Bacterial Gastroenteritis
Bacterial pathogens that commonly cause diarrhea
are Campylobacter, Salmonella, Shigella, and
pathogenic Escherichia coli. Yersinia, Aeromonas,
Hydrophila and Plesiomonas species can also cause
diarrhea. Diarrhea associated with Clostridium
difficile is most commonly seen after antibiotic ther-
apy. Campylobacter infection is acquired via the
fecal-oral route or from contaminated foods, espe-
cially poultry. Güillain-Barré syndrome has been
documented as a complication of this infection.
Children can present with acute abdominal pain and
bloody or nonbloody diarrhea. It may be self-limit-
ing. In patients with persistent symptoms, ery-
thromycin is an effective antimicrobial agent.
Salmonella infection is usually acquired from the
ingestion of contaminated foods, especially meats and
eggs. Salmonella can be differentiated into several
serotypes. Serotypes that cause gastroenteritis are
grouped together as Salmonella enteritis. Serotypes
that cause a systemic illness commonly referred to as
typhoid fever are grouped together as S typhi. These
patients present with acute onset of fever, abdominal
pain, vomiting, and diarrhea. Their stools are typically
watery, although in 5% to 10% of cases they contain
gross blood. Typhoid fever occurs much less often
than Salmonella gastroenteritis. It is characterized by
high spiking fevers, nausea, vomiting, diarrhea, and,
at times, splenomegaly. Numerous sequelae are
reported with all forms of Salmonella infection,
including septicemia, meningitis, osteomyelitis,
myocarditis, hepatitis, and pneumonia. In most cases,
Salmonella gastroenteritis requires only supportive
therapy. Infants younger than 6 months, children with
bacteremia, or children who are immunosuppressed
should be treated with antimicrobial therapy. Ampi-
cillin or trimethoprim-sulfamethoxazole therapy is
recommended. All patients with S typhi infection
should be treated.
Only the pathogenic strains of E coli cause diarrheal
illness. These are divided into 4 major groups:
enteropathogenic, enterotoxigenic, enteroinvasive,
and enterohemorrhagic E coli. The first 2 pathogens
usually cause diarrhea in infants in underdeveloped
countries. Enteroinvasive pathogens usually cause
dysentery. Enterohemorrhagic pathogens, including E
coli 0157:H7, cause grossly bloody diarrhea. Under-
cooked meats are the most frequent source of this
pathogen. It is particularly important, because it can
result in hemolytic uremic syndrome (HUS), which is
characterized by hemolytic anemia, uremia, and
thrombocytopenia. Some studies have estimated a 5%
to 10% mortality rate in these patients.
Shigella presents most commonly with bloody diar-
rhea. Significant mucosal inflammation, leukocytosis,
and the presence of high fever is pathognomonic of
Shigella infection. Seizures often complicate this
infection. It remains unclear if these occur secondary
to the neurotoxic effect of the Shigella toxin or fever.
Most of the children with this infection remain symp-
tomatic and require antimicrobial therapy. Ampicillin
or trimethoprim-sulfamethoxazole are the treatments
of choice.
Patients with Yersinia infections can present with a
gastroenteritis that is indistinguishable from other bac-
terial infections, although in older children the signs
and symptoms can mimic appendicitis. It causes
mucosal thickening and aphthous ulcerations in the
ileum, making it virtually indistinguishable from
Crohn’s ileitis. Most cases are self-limiting.
Antibiotic use may allow the luxuriant growth of
C difficile and its toxin. Symptoms range from self-
limiting diarrhea to life-threatening pseudomembra-
nous colitis with significant systemic symptoms.
Diagnosis is made by the presence of the toxin in the
feces. In cases of pseudomembranous colitis, the typi-
cal endoscopic findings suggest the diagnosis. Treat-
ment, therefore, has to be individualized for each
patient. Usually the discontinuation of antibiotics and
gradual restoration of the intestinal flora will eradicate
the infection. However, in severe cases, metronidazole
therapy is recommended. Vancomycin should only be
used in resistant cases.
The most common parasitic infections encountered in
children in the United States are Giardia lamblia,
Entamoeba histolytica, and Cryptosporidium. Giardia
infection can present as an acute illness or with
chronic symptoms that are indistinguishable from
malabsorption syndromes. Giardiasis can be picked up
on microscopic examination of the stools. Currently,
the Giardia antigen can be detected in the stool, and
this has much higher sensitivity than direct stool
examination. Metronidazole is the treatment of
choice. E histolytica infection is seen particularly in
children after foreign travel or contact with a care-
taker who is an asymptomatic carrier. Metronidazole
treatment is recommended.
The workup of a child with infectious diarrhea
remains frustrating, because the causative pathogen
cannot be identified in more than 50% of these
patients.28
Functional Constipation and Encopresis
The normal frequency of bowel movements varies
with age. Infants usually have about 4 stools a day
during the first few weeks of life, although breast-fed
babies can go for several days without having a bowel
movement. The stool frequency decreases to approxi-
mately 2 stools a day at age 2 years and 1 stool a day
at approximately age 4 years. Constipation is usually
defined as fewer than 3 bowel movements per week
or significant discomfort with bowel movements.
Unresolved constipation may lead to significant fecal
retention, with overflow incontinence causing soiling
or encopresis. Soiling and encopresis signifies the
passage of stool into the underwear in children older
than 4 years. Encopresis occurs in 1% to 5% of chil-
dren between the ages of 4 and 7 years. Boys have a
significantly higher incidence.
In children, constipation is usually functional, the
most common cause being intentional stool withhold-
ing.29 Initiation of toilet training, starting school, inter-
current illnesses, and other stressful events (eg, the
birth of a sibling) can result in stool-withholding
behavior. This leads to the feces staying in the colon
for longer periods and significant absorption of fluids
and consequent hard stools. The subsequent passage
of large, hard stools is extremely painful. The child
begins to associate pain with defecation, resulting in
fear of having a bowel movement. Diet seems to be a
contributing factor in a small percentage of these chil-
dren. Some children are constantly drinking milk or
formula from a bottle, and this significantly limits the
intake of high roughage foods. In a recent study, milk
protein allergy has been determined to be the cause in
some of these infants.
GASTROENTEROLOGY AND NUTRITION 409
Clinical Presentation
Children with functional constipation present with a
history of severe discomfort when they have to defe-
cate.30 Parents describe them as stiffening their lower
extremities, turning red in the face, holding onto furni-
ture, or hiding under tables and in corners for hours
before eventually having a bowel movement. This is
often interpreted by the parents as the child straining
to defecate. Over months of this repetitive behavior,
the rectum becomes dilated from storing a large
amount of fecal matter. At this stage, the rectal vault
requires larger and larger stool for the walls to be
stretched enough to trigger the urge to defecate. Chil-
dren can go for several days without having a bowel
movement; during that time, they are usually
described as very irritable, experiencing abdominal
cramping, and reducing their oral intake significantly.
The diagnosis of functional constipation is usually
based solely on the patient’s history and the absence
of physical abnormalities. Radiological and labora-
tory studies are not necessary in these children.
Although stool withholding is initially a voluntary
behavior, the subsequent soiling from overflow incon-
tinence is involuntary, occurring secondary to a mega-
colon impacted with large amount of hard, rocklike
stool and the leakage of liquid stool around the
impaction. The physical examination is usually nor-
mal, except for a dilated rectum filled with firm stool
or, in more severe cases, a large mound of hard stool.
Anal fissures are often present secondary to the pas-
sage of large-caliber stools. The fissures may be
excruciatingly painful and only reinforce the child’s
association of severe discomfort and pain with
defecation.
Hirschsprung disease must be considered in the dif-
ferential diagnosis of functional constipation.31 Chil-
dren with Hirschsprung disease usually pass soft,
small-caliber stools and do not exhibit the stool-
withholding behavior described above. The rectum
is usually empty and not dilated, in contrast to that of
children with functional constipation. History of
constipation dates back to early infancy with
Hirschsprung disease, in contrast to approximately a
year of age for children with functional constipation.
Table 2 differentiates Hirschsprung disease from
functional constipation.
Neurologic abnormalities and thyroid disorders must
also be considered when managing a patient with con-
410 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
stipation. Hypothyroidism and hypotonia play a sig-
nificant role in enhancing the constipation in children
with Down syndrome. Urinary tract infections are
more common in children with constipation,
particularly girls.
Management
Education. Education of the family, with an explana-
tion of the pathogenesis of the constipation, is the first
step in the treatment of functional constipation and
encopresis. Parents are often fearful of missing an
underlying organic etiology as they interpret their
child’s behavior of pushing hard to have a bowel
movement as an indication that something is obstruct-
ing the rectum.
Disimpaction. Disimpaction of the large amount of
stool seen either on rectal examination or throughout
the colon—as seen on an abdominal x-ray—is neces-
sary prior to starting maintenance therapy. Usually a
combination of rectal and oral therapy is effective in
disimpaction of these children. Rectal disimpaction is
carried out with the use of phosphate soda enemas,
saline enemas, or use of bisacodyl suppositories. The
use of soap suds, tap water, and magnesium enemas is
not recommended because of their toxicity. Disim-
paction with oral medication is usually initiated
simultaneously or after 24 hours of rectal therapy.
Oral senna preparations or bisacodyl and magnesium
citrate preparations have also been used effectively for
oral disimpaction. In patients with severe impaction,
oral Fleets phosphate soda or polyethylene glycol iso-
tonic electrolyte solutions(PEG-ELS) can be used ini-
tially. PEG-ELS is composed of polyethylene glycol
and a physiologic electrolyte solution. The elec-
trolytes in PEG-ELS are used to prevent electrolyte
losses during large-volume lavage. However, the elec-
trolyte solution has a salty taste that most children find
unpleasant. PEG is now available without added elec-
trolytes in the form of a tasteless powder. It is highly
soluble and minimally absorbed in the GI tract. PEG
acts as an osmotic agent increasing fecal water con-
tent. This medication has recently been found to be
safe and effective in doses of 1-1.5 g/kg for disim-
paction and 0.8 g/kg for maintenance therapy in
children.32, 33
Maintenance Therapy
Once the impaction has been removed, the aim is to
have the child passing stool regularly without any dis-
comfort. The majority of these children require ongo-
ing laxative therapy. Osmotic laxatives—eg, lactulose
and magnesium hydroxide preparations and now PEG
solution, are preferred over long-term use of stimulant
laxatives, such as senna preparations and bisacodyl.
Usually after the initial disimpaction, stimulant laxa-
tives are used for 2 to 4 weeks and are followed by
long-term use of osmotic laxatives. The laxative dose
is increased to produce a daily bowel movement with-
out stool-withholding behaviors. At this stage behav-
ior modification with the use of calendar and stickers
may be used to provide positive reinforcement. Main-
tenance therapy may be necessary for several months,
sometimes years. Parents should be warned of this at
is not always confirmed on endoscopy or histologi-
cally, however. The 13C urea breath test has been
demonstrated to be much more sensitive and specific
for H pylori infection. This test takes advantage of the
high concentration of endogenous urease in this
organism. The recovery of 13C-labeled carbon diox-
ide in exhaled air following the ingestion of 13C-
labeled urea is indicative of infection. This is now
commercially available. At present, it is the most sen-
sitive and specific noninvasive test for the detection
of H pylori infection.
Secondary Peptic Ulcer Disease

the initiation of treatment, as well as of the possibility Secondary peptic ulcer disease usually occurs sec-
of relapses, particularly during stressful situations. A ondary to stress and the use of drugs, particularly the
balanced diet that includes grains, fruits, and vegeta- nonsteroidal anti-inflammatory drugs (NSAIDs).
bles as well as adequate fluid intake is recommended
as part of the treatment for constipation in children.
However, forceful implementation is discouraged.
Table 6

Antacid Interference with Drug Absorption

Peptic Ulcer Disease

Peptic ulcer disease encompasses primary and secondary

Binding by Magnesium or Aluminum

ulceration of either the gastric or the duodenal wall.34 Digoxin

Tetracycline
Primary Peptic Ulcer Disease Ferrous sulfate

When an identifiable etiology can be determined for

Aspirin

the peptic ulceration, it is termed primary peptic ulcer

NSAIDs

disease. In children, duodenal ulcers are far more

Cimetidine

prevalent than gastric ulcers. Helicobacter pylori and

Ranitidine

diseases associated with stimulation of gastric secre-

Phenytoin

tion are usually determined to be the etiology of pri-

Quinidine

mary peptic ulcer disease.

Chloroquine
Warfarin

H pylori infection. The majority of duodenal ulcers in

Isoniazid

children are related to H pylori infection.35,36 This spi-

ral bacillus inhabits the gastric mucosa and usually
Effect of Decreased Activity

results in acute gastritis and duodenal ulcer disease.

The definitive diagnosis of H pylori-associated dis-
Decreased Absorption

ease requires the recovery of bacteria from biopsy

Tetracycline

specimens. Most children with H pylori have a nodu-

Indomethacin

lar gastric mucosa. This organism is rarely, if ever,

Chlorpromazine

recovered from histologically normal gastric tissue.

Ketoconazole

Noninvasive diagnostic techniques for H pylori peptic

ulcers are now available. Children develop an IgG
Increased Absorption

antibody response to the organism; thus, a positive

Aspirin

IgG antibody against H pylori in children with acid

Furosemide

peptic symptoms strongly suggests an infection. This

Diazepam

GASTROENTEROLOGY AND NUTRITION 411

This disease is far more prevalent in the stomach than
in the duodenum. In infants, stress ulcers are related to
septic shock, traumatic delivery, and respiratory or
cardiac insufficiency. In older children, they are seen
more often in patients with severe trauma, extensive
burns, or severe head injury.
Clinical presentation. These children usually pre-
sent with abdominal pain that is localized to the epi-
gastric area, as well as dyspepsia and postprandial
discomfort. GI bleeding may sometimes be the only
manifestation of ulcer disease in the absence of pain;
this is especially true for children with duodenal
ulcers. The physical examination is nonspecific,
with only half of these children having epigastric
tenderness on palpation. A definitive diagnosis is
made by endoscopy, which will confirm the presence
of ulcers and rule out an H pylori infection. Barium
studies have a significantly lower sensitivity and
have fallen out of favor.
In the clinical setting of recurrent or persistent peptic
ulceration that is refractory to medical management,
other evaluations are indicated. A baseline fasting
serum gastrin can be used to identify patients with
hypergastrinemia. Diseases that are associated with
high levels of serum gastrin and marked gastric hyper-
secretion and peptic ulceration include antral G-cell
hyperplasia (Zollinger-Ellison syndrome secondary to
gastrinoma or non-␤ islet cell tumor of the pancreas),
systemic mastocytosis, chronic renal disease, and
hyperparathyroidism. A secretin infusion test is used
to confirm the diagnosis. After secretin infusion,
serum gastrin and gastric acidity increase signifi-
cantly. Serum gastrin levels rise to more than 500
pg/mL, whereas in normal individuals there is little or
no change in the gastrin levels.
Management. The goal of therapy for peptic ulcer is
generally to prevent acid-related damage and thus
allow the ulcer to heal. Effective acid neutralization is
achieved with antacids. The most commonly used
preparations consist of a combination of magnesium
and aluminum hydroxide. Antacids are generally well
tolerated, but require frequent administration. They
also interfere with the absorption of several other
drugs, either directly by binding to the drug or by
decreasing gastric acidity (Table 6). Gastric acid pro-
duction can be reduced by inhibiting the histamine
receptors with H2 receptor antagonists. Proton-pump
412 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
inhibitors are generally used when patients fail to
respond to H2 antagonists. Some centers are now
using this as first-line medication for patients with
established ulcer disease. For patients with docu-
mented H pylori infection, triple therapy—typically
with clarithromycin, amoxicillin, and a proton-pump
inhibitor—is used concurrently for 2 weeks.
Metronidazole and tetracycline are among the other
antibiotics that have been found to be effective. Cur-
rent medications and modalities to achieve endo-
scopic hemostasis at the ulcer site have significantly
reduced the need for surgical intervention. Current
indications for surgery in peptic diseases are perfora-
tion of the stomach or duodenum.
Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) includes Crohn’s
disease and ulcerative colitis and chronic indetermi-
nate colitis. The causes of these diseases remain
unknown. Hypotheses regarding the etiology of IBD
support the multifactorial theory encompassing
genetic predisposition, internal and external environ-
mental influences and immune system dysfunction.37
Clinical Presentation
Ulcerative colitis (UC) is limited to the colon, whereas
in patients with Crohn’s disease, the inflammation can
occur throughout the GI tract. In 75% of children with
Crohn’s disease, there is involvement of the terminal
ileum. Abdominal pain, diarrhea, and weight loss are
the most common features of both diseases, although
bloody diarrhea is more characteristic of ulcerative
colitis. Some patients with Crohn’s disease might pre-
sent with only growth retardation. Many of these
patients have anorexia, fatigue, low grade fevers,
arrested sexual development, and arthralgias.38,39
Extra-intestinal manifestations are seen in both dis-
eases. Perianal disease with abscesses or fistulas is
seen more commonly in patients with Crohn’s dis-
ease; sclerosing cholangitis occurs more commonly in
patients with ulcerative colitis. Chronic uveitis,
arthralgias, arthritis, erythema nodosum, and pyo-
derma gangrenosum are seen in both conditions.
Osteoporosis is increasingly being recognized to be
inherent to the disease process. Intestinal obstruction
or intestinal perforation is seen in patients with
Crohn’s disease. Fulminant bloody diarrhea and toxic
megacolon are more common in patients with ulcera-
tive colitis.
Table 7

Differentiation Between Ulcerative Colitis and Crohn’s Disease

Ulcerative Colitis Crohn’s Disease

Site of Disease Colon only Any part of gastrointestinal tract

Symptoms
Bleeding +++ +
Diarrhea +++ ++
Abdominal pain ++ +++
Growth failure + +++
Tenesmus +++ ±
Perianal disease - +

Endoscopic Findings
Rectal involvement +++ +
Inflammation Continuous Discontinuous
Diffuse erythema Patchy lesions
Ulceration in inflamed mucosa Discrete ulcers in normal mucosa

Complications
Fistulas Exceedingly uncommon Frequent
(Crohn’s?)
Strictures Uncommon (malignancy?) Common

Cancer Risk (>10 years) Increased Increased

Diagnosis disease. The markers include perinuclear staining

These children should be screened for markers of
chronic inflammation, eg, anemia, thrombocytosis,
and elevated erythrocyte sedimentation rate (ESR) or
C-reactive protein (CRP). Hypoalbuminemia is often
present, reflecting protein losses from the inflamed GI
tract. Liver function tests, if abnormal, may reflect the
concomitant presence of sclerosing cholangitis or
autoimmune hepatitis. An upper GI series with small-
bowel follow-through—especially with spot films of
the ileum—is especially helpful in identifying small-
bowel disease and, therefore, helps distinguish
Crohn’s diseases and ulcerative colitis. Endoscopy of
the upper and lower GI tract is recommended for all
children with suspected inflammatory bowel disease.
Endoscopic and histologic findings can be used to fur-
ther distinguish Crohn’s disease from ulcerative coli-
tis. Serological testing can be helpful in evaluating
children for IBD, and distinguishing UC from Crohn’s
antineutrophil cytoplasmic antibody (pANCA) for
chronic ulcerative colitis and anti-saccharomyces
cerevisiae antibody (ASCA) for Crohn’s disease. The
sensitivity and specificity of combined pANCA and
ASCA has been reported to be 68% and 92% respec-
tively. However, serological markers have a low sen-
sitivity to be used as a potential screening tool for
patients with suspected inflammatory bowel disease40
(Table 7). A relatively new tool, the wireless capsule
endoscopy, has made it possible to acquire images of
the entire small bowel and is proving to be a valuable
additive tool to flexible endoscopy.
Treatment
The aim of therapy is to suppress inflammation and,
thus associated symptoms. In children, special atten-
tion should also be focused on promoting normal
growth and sexual development, because the disease

GASTROENTEROLOGY AND NUTRITION 413

itself and certain anti-inflammatory medications will
suppress linear growth. Oral corticosteroids may be
used in moderate to severe cases to help induce remis-
sion. Rectal corticosteroid preparations, in the form of
foams and enema, are especially useful in children
with rectal and left-sided disease. The 5-amino salicy-
lates are used extensively either as first-line therapy or
as an adjunct to corticosteroid therapy. Corticos-
teroids should be used very sparingly in children
because of their tendency to retard linear growth as
well as other serious side effects. 6-Mercaptopurine
(6-MP) has become a more extensively used agent in
children because of its steroid-sparing effect. Close
monitoring for neutropenia and hepatitis is necessary
when on 6-MP therapy, however. Cyclosporin and
tacrolimus are reserved for severe fulminant disease.
Infliximab, a chimeric monoclonal antibody directed
against tumor necrosis factor is now approved by the
FDA for use in patients with Crohn’s disease and
ulcerative colitis. More recently cases of hep-
atosplenic T cell lymphoma have been reported in
patients with IBD who had received infliximab and
who notably, were also exposed to a purine ana-
logue.41
Nutritional support. The objectives of nutritional
support are to enhance linear growth and sexual matu-
ration, as well as to promote a positive nitrogen bal-
ance, which will aid in decreasing bowel inflamma-
tion. Oral supplements are recommended, but their
unpleasant taste limits their intake. In children and
adolescents with growth failure and poor oral intake,
enteral feedings should be considered. Enteral feeding
via NG tube or a percutaneous endoscopic gastros-
tomy tube over several months results in positive
weight and height velocity and progression of sexual
maturation. For patients with extensive small-bowel
disease who are unable to tolerate enteral feeds or fail
to respond to enteral feeding, parenteral hyperalimen-
tation is recommended.
Surgical intervention. Complications of Crohn’s dis-
ease—eg, perforation and intestinal obstruction—
usually dictate surgical intervention. Clinical recur-
rence after resection is seen in almost 50% of these
patients. In ulcerative colitis, surgical intervention
may be necessary because of massive GI bleeding,
acute fulminant colitis, or toxic megacolon.
414 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Intestinal Polyps
Most intestinal polyps in children are juvenile
(inflammatory) polyps. Hamartomatous and adeno-
matous polyps are also seen throughout the GI tract in
children as inherited polyposis syndromes.
Juvenile Polyps
Juvenile polyps, which are also called inflammatory
polyps, are the most common polypoid lesions of the
colon in children. They were thought to be solitary
polyps, but the use of colonoscopy has made it clear
that more than half of patients with this condition have
more than one polyp, with a fourth of these located
proximal to the transverse colon. The peak incidence
of juvenile polyps is between ages 4 and 6 years.
These children usually present with painless hema-
tochezia; rarely, constipation, diarrhea, tenesmus, or
prolapse of the rectal polyp is the presenting symp-
tom. Some believe that these polyps outgrow their
vascular supply and eventually are autoamputated.
However, because of persistent bleeding and the pos-
sibility of adenomatous change, it is recommended
that all polyps be removed by means of colonoscopy.
The general consensus is that if a patient has fewer
than 5 juvenile polyps, no further evaluation is neces-
sary, provided these polyps have been successfully
removed.
Juvenile Polyposis
This condition is characterized by the presence of
multiple inflammatory polyps and is subdivided into 3
groups: 1) juvenile polyposis coli, in which the polyps
are localized to the colon; 2) generalized juvenile
polyposis, in which the polyps are found throughout
the GI tract; and 3) juvenile polyposis of infancy, in
which the polyps may be present throughout the GI
tract. Infants with juvenile polyposis usually have
associated congenital anomalies and also present with
severe failure to thrive, bloody diarrhea, and protein-
losing enteropathy.
Inherited Hamartomatous Polyposis Syndromes
These syndromes are characterized by the presence of
multiple hamartomatous polyps of the GI tract and
have an autosomal dominant mode of inheritance.
Peutz-Jeghers syndrome. This syndrome is charac-
terized by the presence of hamartomatous polyps in
the GI tract and mucocutaneous pigmentation around
the mouth and lips. Polyps are usually multiple and
can occur throughout the GI tract. Ovarian tumors,
sex cord tumors, and breast cancer have been reported
with increasing frequency among patients with this
syndrome. Once the diagnosis of Peutz-Jeghers syn-
drome is suspected on clinical grounds, the GI tract
must be investigated thoroughly. Upper and lower
endoscopy to the furthest point possible is recom-
mended. A relatively new tool, the wireless capsule
endoscopy has made it possible to acquire images of
the entire small bowel and is proving to be a valuable
additive tool. Endoscopic or surgical removal of all
polyps is recommended. Patients with this condition,
especially females, should be followed closely for
associated cancers.
Cowden’s syndrome. This syndrome is characterized
by multiple hamartomatous lesions. Polyps can be
present throughout the GI tract, and mucocutaneous
hamartomas are often present, especially on the lips.
These lesions have the potential for malignant trans-
formation and, therefore, should be removed.
Inherited Adenomatous Polyposis Syndromes
These syndromes are characterized by the presence of
multiple adenomatous polyps. Three syndromes are
well recognized: familial polyposis coli, Gardner’s
syndrome, and Turcot’s syndrome. Turcot’s syndrome
has an autosomal recessive pattern of inheritance; the
other 2 syndromes have an autosomal dominant mode
of inheritance. Inherited adenomatous polyposis syn-
dromes have recently been shown to be associated
with the adenomatous polyposis coli gene (APC),
which is caused by a mutation on the long arm of
chromosome 5; 70% of patients with these syndromes
are positive for this gene. Genetic testing for the gene
is now commercially available.
Familial polyposis coli. This syndrome occurs in
1:8000 births. Patients with a positive family history
are usually identified on routine surveillance. Symp-
toms may develop as early as age 10 years. Diarrhea
and rectal bleeding are common. Polyps have also
been reported in the ileum and duodenum, especially
around the ampulla and antrum. A diagnosis is made
by family history and endoscopic appearance of mul-
tiple polyps present throughout the colon. Adenocar-
cinoma develops in all patients by age 50 years. Ade-
nocarcinoma has been reported in several children,
the youngest aged 9 years.
Gardner’s syndrome. The GI findings in patients
with this disorder are identical to those seen in patients
with familial polyposis coli. Significant extra-intesti-
nal manifestations, eg, mandibular osteomas, lipo-
mas, fibromas, desmoid tumors, and pigmentation of
the retinal epithelium—are seen in most patients with
Gardner’s syndrome.
Turcot’s syndrome. This syndrome is also character-
ized by multiple colonic adenomatous tumors with a
marked potential for malignant transformation. Brain
tumors, especially medulloblastoma and glioma,
characterize the extra-intestinal manifestations.
Management
All children with a family history of familial poly-
posis coli should be screened. If the affected adult
has the APC gene, the children should undergo
screening for the gene. If the affected adult does not
have the APC gene, then surveillance colonoscopy
should be done, beginning at approximately age 10
years. Once the polyps are present, a total colec-
tomy is the treatment of choice, because the lesions
undergo malignant transformation in all patients
with this condition.42
Meckel’s Diverticulum
Meckel’s diverticulum is a remnant of the
omphalomesenteric duct. The diverticulum is located
on the antimesenteric border of the distal ileum. Its
incidence is reported to be approximately 2%. The
diverticulum is typically located 40 to 50 cm from the
ileocecal valve in a full-grown child. It is typically 3 to
6 cm in length. The majority of these diverticula are
lined with ileal mucosa, although gastric, duodenal,
and rarely bile duct mucosa and ectopic pancreatic tis-
sue have been demonstrated.
Clinical Presentation
Studies have shown that 80% of symptomatic Meck-
el’s diverticula contain ectopic tissue (gastric mucosal
or pancreatic tissue). Intermittent and painless bleed-
ing from the rectum is the most common presentation
of a symptomatic patient with Meckel’s diverticulum.
Bleeding is actually from peptic ulceration, which
occurs most commonly at the edge of ectopic gastric
mucosa and normal ileal mucosa. The bleeding can be
severe, resulting in a significant drop in hematocrit
and orthostatic changes in the child. The stool is typi-
cally burgundy in color, but can be bright red with
GASTROENTEROLOGY AND NUTRITION 415
very rapid bleeding. Usually bleeding is self-limiting
due to contraction of splanchnic blood vessels in
response to hypovolemia. A diverticulum can become
the site of acute inflammation, with a clinical presen-
tation that is indistinguishable from acute appendici-
tis. Perforation occurs in approximately one third of
patients with diverticulitis. Meckel’s diverticulum
might present as intussusception, with the diverticu-
lum being the lead point. The index of suspicion for
the presence of a lead point is higher if intussusception
occurs in children older than 3 years and recurs after
reduction with air or barium enemas.43
Diagnosis
For children presenting with lower GI bleeding, a
99m-technetium pertechnetate scan, commonly
referred to as a Meckel scan, is used to visualize
ectopic gastric mucosa. The mucous-secreting cells of
the gastric mucosa are responsible for the uptake of
this isotope. The sensitivity of the scan can be
increased with the use of pentagastrin, glucagon, or an
H2 blocker. Studies were initially reported with cime-
tidine, which decreases peptic secretion but does not
affect radionuclide uptake. A dose of 20 mg/kg before
the study is recommended. In patients with very active
rapid bleeding, angiography or technetium 99M-
labeled RBCs may be of some use. However, as most
of the bleeding from Meckel’s diverticulum is self-
limiting, these studies are rarely utilized.
Treatment
A Meckel’s diverticulum should always be removed
from a symptomatic patient. If that patient has a posi-
tive scan, surgery is definitely indicated. If the clinical
presentation suggests Meckel’s diverticulum but the
scan is negative, the scan should be repeated using H2
antagonists, if that was not initially done. However, if
the diagnostic studies are persistently negative but
lower GI bleeding recurs, then surgical exploration is
still warranted. During surgery, the diverticulum is
excised, usually without the need to resect the ileum.
A V-shaped incision made at the base of the remnant
with transverse closure avoids ileal stenosis.
GI Duplications
Intestinal duplications occur on the mesenteric site of
the bowel and share a common blood supply between
the duplicated segment and the adjacent intestinal
tract. The duplicated segment is termed spherical if it
416 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
has no communication with the normal intestinal tract
or tubular if its lumen communicates with the adjacent
gut. Duplications occur throughout the GI tract, but
small-bowel duplications are the most common.
These are usually limited to a small segment of the ter-
minal ileum. Small-bowel duplications often contain
gastric mucosa. Gastric duplications are the rarest.
Clinical Presentation
The clinical features vary with the site of the duplica-
tion and whether it is spherical or tubular. Patients
usually present with complications associated with
duplications, including intestinal obstruction, intus-
susception, ulceration, GI bleeding, perforation, pan-
creatitis, or an abdominal mass. Most duplications are
symptomatic, but there have been reports of them
being identified as incidental findings on laparotomy
for other causes.44
Diagnosis
The diagnosis is often difficult. A Meckel’s scan has
been utilized to identify ectopic gastric mucosa within
the duplication. However, this is only helpful in
detecting intestinal duplications that contain ectopic
gastric mucosa. Barium studies may occasionally
delineate a tubular duplication. However, their speci-
ficity is too poor to use them to distinguish duplicated
bowel from normal intestine. CT scanning is espe-
cially helpful in picking up cystic lesions.
Management
The surgical treatment of choice is resection of the
duplication followed by end-to-end anastomosis.
Most of these patients do well, with very little morbid-
ity or intestinal dysfunction.45
Appendicitis
Acute appendicitis is the most common ailment
requiring emergency abdominal surgery during child-
hood.46 The rate of appendicitis is estimated at approx-
imately 4:1000 children each year. It rarely occurs in
children younger than 2 years, and the peak incidence
is during adolescence. Acute appendicitis is almost
always caused by obstruction of the appendiceal
lumen; appendiceal fecaliths are frequently the cause.
Rarely, torsion of the appendiceal mesentery or edema
due to infection may lead to obstruction of the lumen.
Nonobstructive appendicitis is rare.
Clinical Presentation
Abdominal pain is almost always the presenting
symptom. Initially, the pain is crampy in nature and
localized to the periumbilical area. After a few hours,
the patient begins to vomit; usually a few hours after
that, the periumbilical pain shifts to the right lower
quadrant. Physical signs usually begin to appear at this
stage. The most reliable diagnostic sign is localized
tenderness in the right lower quadrant. As peritoneal
irritation progresses, voluntary rigidity of the abdomi-
nal muscles is detected in the right lower quadrant.
Rebound tenderness is elicited by the examiner gently
pressing down in this area and then quickly releasing
the pressure. Patients can be asked to hop on one foot
at a time; if they can do this without pain, it is highly
unlikely that they have appendicitis.
Diagnosis
The white blood cell (WBC) count is usually elevated
due to an increase in the number of neutrophils. A uri-
nary tract infection (UTI) must be ruled out, because it
can mimic the signs and symptoms of appendicitis. A
radiologic investigation can be a helpful adjunct to the
physical examination for making the diagnosis. Plain
x-rays might demonstrate a calcified appendiceal
fecalith. In experienced hands, an ultrasound exami-
nation is very specific, but, unfortunately, not very
sensitive. A CT scan will clearly delineate a thick-wall
obstructed appendix.
Differential Diagnosis
Gastroenteritis (especially caused by
Y enterocolitica), Crohn’s disease of the ileum, intus-
susception, mesenteric adenitis, and UTIs can all
mimic acute appendicitis.
Management
Emergency appendectomy is required for acute
appendicitis without complications. Children with this
disorder recover quickly and are usually back to their
normal routine within 3 to 4 days. The child with gen-
eralized peritonitis or an appendiceal abscess is best
treated initially with broad spectrum IV antibiotics.
Some surgeons prefer to perform an appendectomy at
this stage with debridement of the abscess cavity; oth-
ers prefer to have the patient complete a
10- to 14-day course of antibiotics and perform an
interval appendectomy 4 to 6 weeks later.
Intussusception
Intussusception—which is the invagination of a prox-
imal segment of bowel (intussusceptum) into a more
distal segment (intussuscipiens)—is a frequent cause
of bowel obstruction in children younger than 2 years.
This process leads to compromise of the mesenteric
blood flow, resulting in venous congestion of the
involved bowel.
Clinical Presentation
This condition is characterized by the sudden onset of
intermittent, crampy abdominal pain, which causes
the infant to “double over.” The infant is totally
asymptomatic between the initial attacks. These
episodes may be accompanied by severe listlessness
and pallor. Bilious emesis usually ensues. A typical
palpable, sausage-shaped abdominal mass is
described in these patients, but is only palpable in
about 50% of them. These patients may present with
mucous, currant-jelly stools or have only microscopic
blood on guaiac testing.
Diagnosis
Standard procedure for the diagnosis and treatment of
patients with ileocolic intussusception remains the
hydrostatic barium or air enema. An NG tube is
inserted and IV resuscitation is initiated prior to per-
forming the study. Whenever feasible, the surgeon
should be present during the study in case a reduction
fails. Perforation is the main risk of the procedure,
occurring in 1% to 3% of these patients. The presence
of an intraluminal mass and the “coiled-spring” sign
of the involved area confirm the diagnosis. Reduction
of the intussusception is successful in 50% to 80% of
cases with the hydrostatic barium enema. The success
rate is highest if the symptoms have been present for
less than 24 hours. Hydrostatic reduction of the intus-
susception under ultrasound guidance approaches
100% sensitivity in experienced hands. However,
false-positive results occur when there is thickening
of the bowel wall.
Treatment
Hydrostatic contrast studies are usually performed for
therapeutic reduction of the intussusception as well as
for its diagnosis. Some centers use air under pressure
as the contrast material. If radiologic reduction is
unsuccessful or results in perforation, surgical inter-
vention is recommended. Intraoperatively, manual
GASTROENTEROLOGY AND NUTRITION 417
reduction is attempted with the intussusceptum being
carefully milked proximally. If the mass cannot be
removed, then bowel resection becomes necessary in
up to 25% of these patients. Recurrent intussusception
is noted in 8% to 12% of patients following radiologic
reduction, and may occur within hours of the initial
reduction or months later. Recurrence after surgical
reduction is less than 3%. As a rule, if intussusception
recurs more than twice, surgery is recommended
because of the increased likelihood of there being a
lead point, eg, an intestinal polyp or a Meckel’s
diverticulum.
Foreign Body Ingestion
In 1995, the American Association of Poison Control
reported over 75,000 incidents of foreign body inges-
tion by children in the United States, two-thirds of
them younger than 6 years. Approximately 1500
deaths are estimated to occur annually from foreign
body ingestion. The esophagus is the most common
site in which foreign bodies get lodged. An object that
clears the esophagus usually passes through the
remainder of the GI tract without difficulty. Other
physiological sites in which foreign bodies may
become lodged are the pylorus, ileocecal valve, and
anus. Coins are by far the most commonly swallowed
objects. Batteries, pieces of toys, safety pins, marbles,
and crayons are among the others. Odynophagia, dys-
phagia, persistent choking, and vomiting are common
symptoms. An x-ray will often help the clinician iden-
tify the foreign body and its location. However, sev-
eral plastics and toys are radiolucent and not identifi-
able on plain x-rays.
Once foreign body ingestion has been diagnosed
and the object is verified as being lodged in the
esophagus, immediate attention is recommended,
especially if the patient is symptomatic. Endoscopic
removal is the treatment of choice. Objects with
blunt margins—such as coins—located in the distal
esophagus will usually pass spontaneously and,
therefore, in asymptomatic patients, a 24-hour
period of observation is recommended. Children are
usually asymptomatic when the object is in the
418 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
stomach. The family needs to be reassured and
advised to screen all stools for the passage of the
coin. If the coin does not pass in 4 weeks, the x-ray
should be repeated; if the coin is still lodged in the
stomach, then it is removed under endoscopy.
If a battery becomes lodged in the esophagus, it
should be removed immediately, because batteries
contain potassium hydroxide, which can be caustic to
the esophageal mucosa. However, if the battery has
passed into the stomach, one can wait 48 hours; if at
that time it is still lodged in the stomach, it should be
removed. Other objects that should be removed are
any objects longer than 6 cm or greater than 2.5 cm in
diameter. Children with foreign body ingestion of
unknown material, especially metal toys, should be
carefully observed for signs of lead toxicity.47
Caustic Ingestion
Caustic ingestion occurs predominantly in toddlers.
Sodium hydroxide (lye) is a strong alkaline solution
and by far the one with the most catastrophic out-
come. It causes liquefaction necrosis and deep tissue
injury to the esophagus. Acid ingestion, on the other
hand, produces superficial lesions. Symptoms after
caustic ingestion usually develop immediately. Oral
burns are often noted. Odynophagia is noted soon
after ingestion. If caustic ingestion is suspected,
endoscopy is recommended, usually between 12 and
24 hours after ingestion. In children with severe
esophageal burns, a tube or a string may be placed at
the time of endoscopy to maintain patency; it may also
be helpful for future dilations in case severe scarring
and stenosis of the esophagus occur. The use of IV
antibiotics and corticosteroids remains controversial.
If the child is febrile or develops pneumonia or perfo-
ration, IV antibiotics is warranted.
The most common late complication is the formation
of esophageal strictures. Dilation may be effective in
these patients. Most of them require significant long-
term nutritional support. A significant number may
require esophageal resection, with colonic replace-
ment of the esophageal segment.
Table 8

Causes of Acute Pancreatitis in Childhood

Trauma Vasculitis
Abdominal trauma Systemic lupus erythematosus
Child abuse Henoch-Schönlein purpura
Kawasaki disease
Multisystem Disease Pancreatic Disorders
Reye’s syndrome Cystic fibrosis
Shock Diabetes
Hemolytic-uremic syndrome Pancreas divisum
Crohn’s disease Duplications
Sarcoidosis Anomalies of ducts
Kawasaki disease
Biliary Disorders
Drugs Gallstones
Chlorthalidone Choledochal cyst
L-Asparaginase Biliary tree anomalies
Azathioprine Duodenal obstruction
Sulfonamides Parasites
Sulfasalazine After endoscopic retrograde
Thiazides Cholangiopancreatography
Furosemide
Estrogens Gastrointestinal Disorders
Tetracycline Duodenal ulcer, penetrating
Valproic acid Duplications
Phenformin
Procainamide Nutritional Problems
Corticosteroids Malnutrition
Ethacrynic acid Rapid refeeding
Bulimia
Infections
Sepsis Toxic Conditions
Viruses (measles, mumps, Alcohol
Epstein-Barr virus, Organophosphates
coxsackie B, rubella, Carbamates
hepatitis A and B, Borates
influenza, Yellow scorpion bite
echovirus
Mycoplasma pneumoniae Transplantations
Renal transplantations
Metabolic disorders Graft-versus-host disease
Hypercalcemia
Hyperlipidemia Miscellaneous
Uremia Hereditary
␣1-antitrypsin deficiency Idiopathic
Postoperative

GASTROENTEROLOGY AND NUTRITION 419

3. Acute Pancreatitis

Acute pancreatitis occurs less frequently in children treatment or image-guided drainage is often necessary
than in adults.48 The most common etiologic factors if there are persistent symptoms or internal complica-
are direct abdominal trauma, multisystem disease, and tions. In patients with recurrent or chronic pancreati-
drug ingestion. Several other causes have been impli- tis, pancreatic enzyme supplementation has been
cated (Table 8). Pancreatitis is increasingly reported in shown to be beneficial.
patients infected with the human immunodeficiency
virus (HIV) and in children with the opportunistic
infections associated with acquired immune defi-
ciency syndrome (AIDS). Drugs used for the treat-
ment of HIV—eg, pentamidine and didanosine
(ddI)—have also been shown to induce pancreatitis.

Clinical Presentation
The predominant symptom of pancreatitis is abdomi-
nal pain, which is often epigastric in location. The
pain is described as sharp and constant, and is often
associated with nausea and vomiting. Localized ten-
derness is often elicited in the upper abdomen.

Diagnosis
If pancreatitis is suspected, plasma levels of amylase
and lipase should be obtained. These are not specific,
however, as serum amylase levels are elevated in
patients with conditions other than acute pancreatitis,
eg, acute abdomen due to intestinal perforation or
obstruction, appendicitis, and peritonitis, as well as
liver abnormalities (hepatitis or cirrhosis) and renal
failure. Serum lipase assay is utilized in conjunction
with serum amylase levels because of its greater pan-
creatic specificity. However, the degree of plasma
lipase elevation does not reflect the severity of acute
pancreatitis. Abdominal sonogram, CT scan, and
magnetic resonance imaging (MRI) are helpful in
identifying pancreatitis. In patients with recurrent
pancreatitis or persistent elevation of pancreatic
enzymes, imaging studies of the pancreatic and biliary
duct system are recommended. Endoscopic retro-
grade cholangiopancreatography or magnetic reso-
nance cholangiopancreatography have been used to
delineate the pancreatic and biliary duct systems.

Management
Treatment of acute pancreatitis consists of aggressive
fluid and electrolyte management, bowel rest, pain
management, and nutritional support.49 In most
patients, the disease is self-limited and subsides
within a few days. Blunt pancreatic trauma that
involves the pancreatic ducts tend to require operative
intervention. Patients with pancreatic pseudocysts
may be managed conservatively as well, but surgical

420 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS

4. Liver Disease in Childhood
Neonatal Cholestasis
An infant with jaundice that persists past the first 2
weeks of life or with onset of jaundice after the first
week of life should be investigated for direct (conju-
gated) hyperbilirubinemia, which implies cholestasis.
Neonatal cholestasis is defined as a direct fraction of
the total bilirubin being greater than 20% or a direct
fraction of 2 mg/dL. The causes of neonatal cholesta-
sis are numerous50 (Table 9).
Idiopathic Neonatal Hepatitis
In patients with idiopathic neonatal hepatitis, no spe-
cific etiology is identified, but giant-cell hepatitis is
demonstrated on histology. Idiopathic neonatal hep-
atitis appears to be associated with low birth weight.
More than 50% of affected neonates develop jaundice
within the first week of life. The liver is usually
enlarged. Serum bilirubin and amino transaminase
levels are mildly to moderately elevated. Most of
these infants thrive and experience complete resolu-
Table 9
Relative Frequency of the Various Forms of Cholestasis*
Clinical Form
Idiopathic neonatal hepatitis
Extrahepatic biliary atresia
␣1-Antitrypsin deficiency
Intrahepatic cholestasis syndromes
(Alagille, Byler, etc.)
Bacterial sepsis
Hepatitis
Cytomegalovirus
Rubella, herpes
Endocrine (hypothyroidism, panhypopituitarism)
Galactosemia
+ Per 10,000 live births
* Based on several published series encompassing greater than 500 cases. Modified from Balistreri. 6,7
tion by age 2 to 3 months. However, in children with a
family history of neonatal hepatitis, the prognosis is
less favorable.
Extrahepatic Biliary Atresia
Biliary atresia accounts for approximately one third of
all cases of neonatal cholestasis. Studies indicate an
incidence of 1:8000 to 1:25,000 live births. Two dis-
tinct phenotypes are recognized: embryonic and peri-
natal. The embryonic type accounts for approximately
10% of cases. These infants have an early onset of
cholestasis, and associated malformations are often
present. The perinatal type is characterized by a later
onset of jaundice and is usually not associated with
other congenital anomalies. The birth weight of
infants with biliary atresia is normal. Jaundice can
present from birth until after age 3 to 5 weeks. Stools
become acholic. Serum bilirubin levels are mildly to
moderately elevated. Alkaline phosphatase levels are
markedly elevated. Polysplenia/asplenia syndrome,
malrotation, and situs inversus and immotile cilia syn-
Cumulative Estimated
Percent Frequency+
35-40 1.25
25-30 0.70
7-10 0.25
5-6 0.14
2 <0.1
3-5 <0.1
1 <0.1
1 <0.1
1 <0.1
GASTROENTEROLOGY AND NUTRITION 421
drome are among the other congenital anomalies that
have been reported in patients with biliary atresia.
Liver biopsy remains the gold standard for diagnosis.
Early in the disease, features of extrahepatic obstruc-
tion dominate, with varying degrees of canalicular
and cellular bile stasis and bile duct proliferation. As
time progresses, total and perilobular fibrosis is
observed, with progression to cirrhosis.51 An early
diagnosis is essential, as the outcome of surgical inter-
vention is significantly better during the first 3 months
of life. Surgical palliation with hepatoportoenteros-
tomy (Kasai procedure) is attempted to establish bile
drainage from the liver.
The life expectancy for a patient with untreated biliary
atresia is approximately 2 years, with death occurring
secondary to liver failure. In a series of 149 patients,
survival rates ranged from 75% for patients who were
operated on at less than 2 months of age to 10% in
those who were 3 months or older at the time of
surgery. Despite surgery, most of these patients even-
tually require liver transplantation.
␣1-Antitrypsin Deficiency
This disorder is the most common metabolic etiology
of cholestatic disease in infancy. A mutation in the
␣1-antitrypsin gene, located on chromosome 14,
results in severe deficiency in serum ␣1-antitrypsin
levels. The most common allele associated with
␣1-antitrypsin deficiency is protease inhibitor (PiZ).
Figure 9
Alagille syndrome
Characteristic facies: prominent forehead, deep set eyes,
pointed chin and a saddle shaped nose.
422 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
In individuals homozygous for the Z allele (PiZZ),
serum ␣1-antitrypsin levels are only 10% to 15% of
normal. The incidence of the homozygous deficiency
state (PiZZ) in the Caucasian population is approxi-
mately 1:8000 people.
The risk of liver disease for a child with PiZZ geno-
type is about 3%.52 Infants with liver disease usually
demonstrate cholestatic jaundice and hepatomegaly
within the first 3 to 4 months of life. They are often
small for gestational age. In rare cases, the initial
neonatal manifestation of ␣1-antitrypsin deficiency
may be life-threatening hemorrhage. The clinical and
biochemical manifestations of liver disease resolve
during the first year of life. However, recurrence has
been reported for these infants. Infants with ␣1-anti-
trypsin deficiency, in whom jaundice does not resolve,
may progress to cirrhosis and fulminant liver failure.
Children may present for the first time later in child-
hood or during the teen years with asymptomatic
hepatosplenomegaly and elevated hepatic transami-
nase levels. Any child with an unexplained elevation
in hepatic transaminase levels should be screened for
this disorder. Diagnosis is made by obtaining serum
␣1-antitrypsin levels and doing Pi typing.
Kidney disease. Patients with ␣1-antitrypsin defi-
ciency, especially those with severe liver disease, may
develop nephropathy. These patients must be
screened periodically with urinalysis.
Pulmonary disease. Children rarely manifest the
emphysematous changes common in adults with
␣1-antitrypsin deficiency. Twenty percent of children
with this liver disease have been reported to have reac-
tive airway disease, and approximately 5% may have
pulmonary shunting with some degree of hypoxia.
Management. The management of cholestasis and
liver disease in ␣1-antitrypsin deficiency is no differ-
ent than that for any other infants with cholestatic liver
disease. No specific therapy is available. The only
proven therapy for ␣1-antitrypsin deficiency is liver
transplantation. After the liver transplant, donor hepa-
tocytes provide normal serum levels of the ␣1-antit-
rypsin. Normal levels protect these infants against the
development of emphysema in later years. Exposure
to cigarette smoking should be prohibited.53,54
Alagille Syndrome
Alagille syndrome is characterized by a marked
Table 10

decrease in the number of interlobular bile ducts

(paucity of interlobular bile ducts – PIBD) and
Neonatal Cholestasis: Differential Diagnosis

cholestasis occurring in conjunction with typical

facies, cardiac, skeletal, ocular, renal and develop-
mental abnormalities. The incidence of this syndrome
Idiopathic neonatal hepatitis 10%

has been estimated at 1:100,000 births. An autosomal

dominant pattern of inheritance has been demon-
Extrahepatic biliary atresia 30%-35%

strated, although a large number of cases appear to

occur sporadically.55 The genetic defect is a mutation
␣1-Antitrypsin deficiency 10%

of the Jagged1 gene (chromosome 20p12). This gene

is a ligand in the Notch signaling pathway, which
Familial cholestasis syndromes

plays a role in embryogenesis. This is a potentially

(Byler, etc.) 5%-6%

important finding in the understanding of the

development of multisystem defects from one genetic
Anatomical

mutation.
(Paucity of Intrahepatic ducts) 25%

Clinical presentation. Symptomatic patients usually

Bacterial sepsis 2%

present with cholestasis during the first 3 months of

life. It may present in older children as chronic hepatic
Hepatitis

disease or it may remain undiagnosed until adulthood,

when a related child is identified with the disease.
Cytomegalovirus 3%-5%

There is extreme variability in clinical manifestations

in these patients. Some demonstrate progressive cir-
Rubella, herpes 1%

rhosis or liver failure necessitating liver transplanta-

tion; others have few or no symptoms and remain
Endocrine (hypothyroidism,

undiagnosed until adulthood.

panhypopituitarism) 1%

Diagnosis. The diagnosis is made when a characteris-

Galactosemia 1%

tic liver histology in a cholestatic patient is accompa-

nied by characteristic facies (Figure 9), cardiac mur-
mur, vertebral anomalies, and ocular anomalies. The
facies consist of a prominent forehead, moderate
hypertelorism with deep-set eyes, a small pointed
chin, and a saddle-shaped nose. Cardiac lesions usu-
ally account for most of early mortality; these vary
from insignificant peripheral pulmonary artery steno-
sis to major intracardiac anomalies. Tetralogy of Fal-
lot occurs in approximately 10% of these patients. The
most common skeletal anomaly is the presence of
hemivertebrae (“butterfly vertebrae”). Posterior
embryotoxon is the most common ocular abnormality,
occurring in up to 85% to 90% of cases. It can be diag-
nosed by routine slit-lamp examination. It can be pre-
sent in up to 15% of the general population.
Management and prognosis. The hepatic presenta-
tion of Alagille syndrome is managed by general sup-
portive measures. Early mortality is usually due to
complex cardiac disease, while hepatic complications
account for most of the later morbidity and mortality.
Liver transplantation may be required for patients
with chronic liver failure, severe portal hypertension,
or intractable pruritis.56
Galactosemia
Galactose-1-phosphate uridyltransferase catalyzes the
metabolism of galactose-1-phosphate to uridine
diphosphate-galactose. The absence of this enzyme
leads to rapid accumulation of galactose-1-phosphate,
galactose, and galactitol as soon as lactose-containing
formula is ingested. Symptoms appearing during the
first week of life include poor feeding, irritability,
vomiting, jaundice, and hepatomegaly. Cataracts
appear within days or weeks because of galactitol
accumulation. Newborns with galactosemia are diag-

GASTROENTEROLOGY AND NUTRITION 423

nosed by mass screening of neonatal blood spots for
elevated galactose, provided they have been fed lac-
tose-containing formula prior to the test. Reducing
sugars may be found in the urine. Diagnosis is con-
firmed by assaying enzyme activity in the blood. If
untreated, patients often die undiagnosed with gram-
negative sepsis within weeks. If the infants survive,
cirrhosis develops by 3 to 6 months of age. Manage-
ment with lactose-free diets results in resolution of
cholestasis.
Parenteral Nutrition-Associated Cholestasis
An association between parenteral nutrition and liver
disease is well established in neonates, children, and
adults. No single etiology has been shown responsi-
ble, although possible causes include toxicity or defi-
ciency of components of parenteral nutrition solu-
tions, lack of enteral feeding, infections, surgery, and
prematurity. Discontinuation of parenteral nutrition is
the single most effective intervention. Initiation of
very low-dose enteral feedings will help stimulate
enteral hormone production and improve bile flow.
Table 11
Definitions and Significance of Serologic Markers of Hepatitis B
HBsAg HBV surface antigen
HBcAg HBV core antigen
HBeAg HBV e antigen,
cleavage product of HBcAg
HBV DNA DNA of HBV
anti-HBs Antibody to surface Ag
anti-HBc Total antibody to HBcAg
anti-HBc IgM IgM antibody to HBcAg
anti-HBe antibody to HBeAg
424 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Concomitant use of ursodeoxycholic acid or pheno-
barbital to improve bile flow may also be of some
benefit.
Evaluation of Neonatal Cholestasis
Any neonate with hyperbilirubinemia after the first 2
weeks of life should be evaluated for cholestasis.
Serum bilirubin should be fractionated and the diag-
nosis of cholestasis established if the conjugated frac-
tion is either greater than 20% of the total bilirubin or
greater than 2 mg/dL. Various disorders should be
ruled out by specific tests to distinguish diseases that
require immediate treatment from those that would
benefit from therapeutic intervention (Table 10). The
diagnosis of extrahepatic biliary obstruction must be
made within the first 6 to 8 weeks of life if surgery is to
be worthwhile.
Medical Management of Chronic Cholestasis
Most infants with intrahepatic cholestasis or biliary
atresia (even with surgical correction) require sup-
portive therapy for clinical consequences of persis-
tent cholestasis.
Indicates acute or chronic HBV infection
Not detectable in serum
Indicates active HBV infection, correlates
With HBV replication, signifies high infectivity
Indicates HBV replication
Indicates clinical recovery from HBV and
immune status. May indicate passive immunity
from HBIG
Indicates active HBV infection
(acute and chronic)
Early index of HBV infection,
not present in chronic HBV
Seroconversion to anti-HBe indicates
resolution of hepatitis
Pruritis. Pruritis can be very debilitating for patients
with chronic cholestasis. Cholestyramine and pheno-
barbital, which reduce the concentration of bile acids,
may be of benefit in some patients. Ursodeoxycholic
acid alters the bile acid composition, which has been
shown to be beneficial.57 The recommended dose is
20 to 30 mg/kg per day. Other beneficial agents
include rifampicin and Narcan.
Xanthomas. Xanthomas are cutaneous depositions
of cholesterol that are seen in patients with cholesta-
sis. Cholestyramine, ursodeoxycholic acid, and phe-
nobarbital increase bile flow and may be of some ben-
efit as treatment for xanthomas.
Fat malabsorption. Fat malabsorption is related to a
decreased flow of bile acids into the intestinal lumen,
which leads to the malabsorption of long-chain fatty
acids. However, medium-chain triglycerides (MCT)
are readily absorbed, even with decreased concentra-
tions of bile acids in the intestinal lumen. MCT-con-
taining formulas are recommended for these infants.
Vitamin malabsorption. The fat-soluble vitamins
(vitamins A, D, E, and K) require bile acids for their
incorporation into mixed micelles. In the absence of
bile acids, these vitamins are significantly malab-
sorbed. The recommended oral vitamin supplemen-
tation is outlined in Table 5. ABDEK, a relatively
new mixture of fat and water soluble vitamins, is
now available. Clinical signs, vitamin levels, cal-
Table 12
Serologic Diagnosis of Hepatitis B Viral Status
Acute HBV Carrier HBV
HBsAg + +
HBeAg + -
Anti-HBe - -/+
Anti-HBc -/+ + +
Anti-HBs - -
HBV-DNA + -
cium and phosphate levels, and prothrombin time
(PT) should be monitored periodically to assess
adequate supplementation.
Portal hypertension. Portal hypertension is a conse-
quence of progressive fibrosis and cirrhosis secondary
to the hepatotoxic effects of cholestasis. It often mani-
fests as variceal bleeding and ascites. Salt restriction
and diuretics may be of benefit in the medical man-
agement of ascites. Acute variceal bleeds are man-
aged by use of IV fluids, blood products, and vaso-
pressin or somatostatin infusion. Endoscopic scle-
rotherapy or banding of the varices has become popu-
lar for controlling variceal bleeding. Orthotopic liver
transplantation has become a life-saving modality for
infants and children who progress to end-stage liver
disease.
Viral Hepatitis
Patients with hepatitis viruses A, B, C, D, E, and G
present with predominantly hepatic dysfunction.
Epstein-Barr, herpes, cytomegalovirus, and aden-
ovirus account for approximately 10% of the cases of
viral hepatitis.
Hepatitis A
Hepatitis A virus (HAV) is an RNA virus that is trans-
mitted via the fecal-oral route. It is found in the blood
and stool of an infected individual for up to 3 weeks
before the onset of clinical symptoms and persists for
Postinfection Chronic HBV Vaccinated
- + -
- + -
+/- -/+ -
-/+ -
+ - +
- + -
GASTROENTEROLOGY AND NUTRITION 425
 Hepatitis B
Hepatitis B virus (HBV) is a DNA-containing virus
Figure 10

that is found in all body fluids and secretions in

infected individuals. Transmission occurs by means
Course of acute hepatitis B

of parenteral exposure or an exchange of infected

secretions. All infants born to HBV-infected mothers
Clinical presentation

are at risk for infection through vertical transmission.

± Jaundice Serologic

These infants have few if any clinical manifestations

window
ALT Elevation

of the disease, but develop serologic evidence of the

Anti-HBs

disease by 3 months of age. Definitions and signifi-

HBV DNA Anti-HBe

cance of various serologic markers of hepatitis B are

Anti-HBc IgM

outlined in Table 11. These serologic markers help

determine the status of HBV infection in patients
HBsAg
Infection
HBeAg

(Table 12). The course of acute and chronic HBV is

outlined in Figures 10 and 11, respectively. Age at
0 4 8 12 16 20 24 28

acquisition of primary HBV infection is a major deter-

Time after infection, wk

minant of chronicity. As many as 95% of infected

Course of acute hepatitis B. (From Hoofnagle JH,

neonates, 20% of acutely infected children, and

DiBesceglie AM [5]; with permission.)

2%-6% of adults develop chronic HBV infection.

Hepatocellular carcinoma appears to be more preva-
lent in patients who acquire HBV infection early in
Figure 11

life. The clinical course of acute and chronic HBV are

outlined in the schematic diagrams.
Course of chronic hepatitis B

Treatment. No specific therapy is recommended for

± Symptoms

acute HBV infections. These patients should be fol-

Variable ALT elevation

lowed by serial serological studies to determine

whether they have chronic carrier status or chronic
HBV DNA

hepatitis. All chronic HBV carriers and their house-

Anti-HBc IgM transition to IgG

hold contacts should be immunized to prevent hori-

Anti-HBe

zontal transmission. These patients should be

HBsAg
Infection

screened for hepatocellular carcinoma. Annual

HBeAg

alfa-fetoprotein and hepatic sonography are recom-

mended. HBV-associated chronic hepatitis should be
0 4 8 12 16 20 24 52 260 520

treated. Peginterferon alfa-2a has proved useful as

Time after infection, wk

treatment for chronic HBV.58 Predictors of the

Course of chronic hepatitis B, including remission with

patient’s response to Peginterferon alfa-2a include a

seroconversion from HBeAg to anti-HBe. (From Hoofnagle JH,
DiBesceglie AM [5]; with permission.)

high histologic grade of liver biopsies before treat-

up to 2 weeks after the onset of disease. It is usually an
ment, high serum alanine aminotransferase (ALT)
acute, self-limited illness. Progression to fulminant
and aspartate aminotransferase (AST) levels, and
hepatitis is extremely rare. Chronic Hepatitis A does
serum HBV-DNA exceeding 1 ng/mL. Currently,
not occur. The diagnosis of HAV infection is usually
double-blind controlled studies to evaluate the effec-
made serologically by the detection of the Ig M anti-
tiveness of lamivudine for the treatment of chronic
body to HAV (IgM anti-HAV). No specific therapy is
HBV in children are being carried out. Children who
available. Hepatitis A caccination immunoprophy-
acquire the infection perinatally have a relatively
laxis is in 2 doses. The vaccination is close to 100%
poor response when compared with children who
effective and lasts for up to 20 years. A single vaccina-
develop the infection later in life.
tion is recommended for one-time travelers to
endemic areas.
Immunization. The current recommendation of the
American Academy of Pediatrics is to immunize all

426 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS

children born after April 1, 1992 with the HBV vac-
cine as part of their routine childhood immunization
schedule. Those born before this date are immunized
at approximately age 12 years. Postexposure prophy-
laxis using hepatitis B immune globulin (HBIG) is
recommended. In infants with perinatal exposure,
HBIG should be given within 12 hours after birth,
with concomitant use of HBV vaccination. HBIG is
also recommended after sexual exposure to an
HBsAg-positive partner, exposed household contacts,
or accidental exposure to mucosal or percutaneous
materials that are HBsAg positive. These individuals
should receive HBIG within 14 days of exposure.
Hepatitis C
Hepatitis C virus (HCV) is an RNA virus that is pre-
dominantly transmitted via the parenteral route, simi-
larly to HBV. Perinatal transmission has been docu-
mented. The diagnosis of chronic HCV involves con-
firmation of the presence of HCV infection and liver
disease. Enzyme immunoassay is the most practical
screening test. However, it has a high rate of false-pos-
itive results. If the enzyme immunoassay is positive
and there is evidence of chronic liver disease, then no
further serological testing is necessary. Asymptomatic
patients—eg, blood donors who test positive by
enzyme immunoassays—should be tested by recom-
binant immunoblot assay (RIBA) or polymerase chain
reaction (PCR) assay for HCV-RNA. If a patient is
positive by RIBA and/or PCR with normal ALT, there
is a 30% to 70% chance of finding chronic hepatitis on
liver histology. Most patients remain asymptomatic
with no obvious liver disease during the first 2 decades
with chronic HCV infection; thus, this disease is less
likely to be encountered in the pediatric population.
Patients who have antibodies to HCV with detectable
serum HCV RNA, abnormal ALT levels, and moder-
ate to severe chronic hepatitis on liver biopsy should
be considered for treatment. Peginterferon alfa-2b rib-
avirin ribavirin therapy are found to be of benefit.59
Patients who fail to respond after 3 months should
have treatment discontinued.
Hepatitis D
Hepatitis D (HDV) virus can produce infection and
clinical illness only in the presence of active HBV
infection. Acute HDV may present as a co-infection
(simultaneous acquisition of HBV and HDV) or as a
super-infection (infection superimposed on a chronic
HBV patient). The severity of hepatocellular injury
may be increased significantly by the co-infection.
Treatment is directed towards the eradication of HBV
infection.
Hepatitis E
Hepatitis E virus (HEV) is transmitted by the fecal-
oral route60 and is usually contracted through contam-
inated water. This infection seems to be an acute, self-
limited illness. Persistent viremia and chronic hepati-
tis have not been documented.
Hepatitis G
Hepatitis G virus (HGV) is transmitted parenterally.
Diagnosis of HGV infection relies on the detection of
HGV-RNA by PCR assays. Data suggest that HGV
infection rarely causes acute hepatitis and little or no
liver disease during chronic infection.
Miscellaneous Liver Diseases
Autoimmune Hepatitis
Clinical features of autoimmune hepatitis (AIH) can
vary from being asymptomatic, to a patient with
hepatosplenomegaly on routine examination, to
patients with elevated serum amino acid transferases,
severe acute hepatitis, and even fulminant hepatic
failure.61 Two types of AIH are recognized in children.
Type 1 is characterized by the presence of smooth
muscle antibodies (SMA) and/or antinuclear anti-
body (ANA) associated with very high levels of
Immunoglobulin G. Type 2 is characterized by the
presence of liver-kidney microsomal antibody type 1
(LKM-1). Two thirds of the pediatric population with
autoimmune hepatitis fall into the Type 1 category.
Immunosuppressive therapy should be instituted as
soon as possible. Patients with AIH rarely enter
remission spontaneously. In most cases, low-dose
immunosuppression must be continued indefinitely.62
Wilson Disease
Wilson Disease is an autosomal recessive genetic dis-
order of copper metabolism that affects approxi-
mately 1:30,000 people. The gene associated with
Wilson Disease is ATP7B on chromosome 13. It is
involved on copper transport. Patients with Wilson
Disease accumulate copper in the liver, which eventu-
ally spills over into the brain, eyes, and kidneys.
GASTROENTEROLOGY AND NUTRITION 427
Patients with this disease may have asymptomatic
chronic hepatitis with liver test abnormalities or pre-
sent with fulminant hepatic failure. They nearly
always develop liver disease before age 20 years. The
diagnosis is made on the basis of a combination of
physical and biochemical findings, most notably a
decrease in circulating levels of ceruloplasmin, the
presence of Kayser-Fleischer rings on eye examina-
tion, and a hepatic copper content exceeding 250
mg/g dry liver weight. If left untreated, patients
develop hepatic insufficiency, neurologic and psychi-
atric symptoms, and ultimately liver failure. Lifelong
treatment with metal chelating agents or alternatively
with zinc salts results in excellent survival. Fulminant
hepatic failure and hepatic insufficiency that is unre-
sponsive to medical therapy are best treated by ortho-
topic liver transplantation.
Neonatal Iron Storage Disease
Neonatal iron storage disease, also called neonatal
hemochromatosis, is rare and presents with severe
liver failure during the first few days of life. Serum
ferritin is markedly elevated and coagulation factors
markedly depressed. The most characteristic histo-
logic feature is the extensive deposition of iron within
the residual hepatocytes. This condition must be con-
sidered in neonates presenting with hepatic failure.
Diagnosis can be made by MRI showing large iron
depositions. Treatment with iron chelation and antiox-
idants can prolong life until a liver transplant can be
performed. The transplanted liver does not
reaccumulate iron.
Hereditary Tyrosinemia
Hereditary tyrosinemia is an autosomal recessive dis-
order caused by a deficiency in fumarylacetoacetate
hydrolase deficiency.63 This enzyme is utilized in the
tyrosine degradation pathway, and its deficiency leads
to an accumulation of hepatotoxic metabolites. These
patients may present with acute liver failure with
bleeding diathesis in the first few weeks of life or with
asymptomatic hepatomegaly during the second
decade of life. Hepatocellular carcinoma is a common
complication that may occur as early as 1 year of age,
but more often occurs later in childhood or adoles-
cence. Diagnosis is made by the presence of elevated
levels of succinyl acetone in the urine. A new and
exciting treatment consists of NTBC, an herbicide
that blocks the pathway before toxic metabolites are
formed, given by mouth twice a day along with a diet
very low in phenylalanine and tyrosine. This regimen
428 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
can markedly diminish the complications of tyrosine-
mia (hepatic, renal, and neurologic). If begun early
enough in life, it may also prevent the development of
hepatocellular carcinoma.
Breast Milk Jaundice
Breast-fed infants have higher serum bilirubin levels
than formula-fed babies. The unconjugated hyper-
bilirubinemia continues to rise for 4 weeks, but
promptly resolves when breast-feeding is discontin-
ued. This is thought to be secondary to an inhibitor of
bilirubin glucuronosyltransferase (UGT) in maternal
milk. This enzyme is necessary for the conversion of
bilirubin to a water-soluble form that is essential for its
elimination by the liver and kidney and for its
detoxification.
Gilbert Syndrome
Gilbert Syndrome is the mildest form of inherited,
nonhemolytic, unconjugated hyperbilirubinemia.
Serum bilirubin concentrations in persons with
Gilbert Syndrome generally range from 1 to 5 mg/dL.
The serum bilirubin level of affected persons fluctu-
ates with time and increases during fasting. It is esti-
mated that this syndrome affects 4% to 7% of the pop-
ulation. Gilbert Syndrome is conventionally diag-
nosed in individuals with mild unconjugated hyper-
bilirubinemia without evidence of hemolysis or liver
disease.64
Crigler-Najjar Syndrome
Crigler-Najjar syndrome Type I is a rare disorder
characterized by severe lifelong unconjugated hyper-
bilirubinemia with undetectable hepatic bilirubin-
UGT. It is inherited as an autosomal recessive trait and
presents during the first few days of life. Unconju-
gated bilirubin concentrations usually range from 20
to 40 mg/dL, but may be as high as 50 mg/dL. Pheno-
barbital therapy does not reduce serum bilirubin levels
significantly. Phototherapy is effective for the first 3 to
4 years; thereafter, it loses its effectiveness. Liver
transplantation is the only definitive treatment for
Crigler-Najjar syndrome Type I. Crigler-Najjar syn-
drome Type II is characterized by a severe, incom-
plete reduction of hepatic bilirubin-UGT activity, with
serum bilirubin levels ranging from 7 to 20 mg/dL.
Patients are responsive to phenobarbital therapy, and
this helps distinguish them from Crigler-Najjar syn-
drome Type I.
Toxic Hepatitis
Toxic hepatitis in children may develop secondary to
an idiosyncratic reaction to a drug or drug overdose.
Acetaminophen is the drug most often involved in
drug overdoses in children. When an overdose occurs,
toxic metabolites accumulate causing hepatocellular
injury. Treatment of acetaminophen overdose with N-
acetylcysteine has significantly reduced morbidity
and mortality. Liver transplantation is the treatment of
choice for irreversible fulminant hepatic failure.
Acetylsalicylic acid is also known to cause dose-
related toxicity. Symptoms and biochemical abnor-
malities usually resolve with discontinuation of the
drug. Antibiotics usually cause hepatotoxicity
because of idiosyncratic hypersensitivity reactions.
Erythromycin, trimethoprim-sulfamethoxazole, and
amoxicillin-clavulanic acid have all been associated
with hepatotoxicity. Antiepileptic drugs—especially
valproic acid, phenobarbital, and carbamazepine—
also have the potential to result in significant liver
damage. Immunosuppressive drugs—eg, azathio-
prine, 6-mercaptopurine and cyclosporin—can result
in a clinical presentation that is consistent with hepati-
tis. Anesthetic agents, such as halothane, may cause
hepatotoxicity. Vitamin A toxicity may result in hep-
atic dysfunction. Iron doses greater than 60 mg/kg
usually result in severe hepatotoxicity. Recently,
ibuprofen was associated with liver toxicity.65

Table 13

Organic Causes of Failure to Thrive

Oropharyngeal Chronic diarrhea Congenital infections

Palatal anomaly Celiac disease Syphilis
Pierre Robin syndrome Cystic fibrosis Cytomegalic inclusion virus
Giardiasis Rubella
Central nervous system Microvillus inclusion disease Toxoplasmosis
Cerebral palsy Abetalipoproteinemia HIV infection
Fetal alcohol syndrome Inflammatory bowel disease
Intracranial tumors, cysts Short bowel syndrome Metabolic disorders
Hematoma

Cardiac Chronic liver disease Malignancies

Congenital heart defects
Selective enzyme deficiency Iatrogenic
Pulmonary Enterokinase Prolonged use of steroids
Bronchopulmonary dysplasia Isomaltase
Chronic infection (eg, sec- Sucrase Chromosomal disorders
ondary to cystic fibrosis) Turner’s syndrome
Genitourinary
Gastrointestinal Renal tubular acidosis Immunodeficiency disease
Decreased intake Fanconi syndrome Severe combined
Oropharyngeal disorders immunodeficiency
Cerebral palsy Endocrine DiGeorge syndrome
Hypothyroidism HIV infection
Chronic vomiting Hypopituitarism
Gastroesophageal reflux Diabetes mellitus
Malrotation Diabetes insipidus
Pseudo-obstruction Congenital adrenal hyperplasia
Increased intracranial pressure Growth hormone deficiency

From Chawla A. Failure to thrive. In: LJ Brandt, ed. Clinical Practice of Gastroenterology. Philadelphia, Pa: Current
Medicine; 1999.

GASTROENTEROLOGY AND NUTRITION 429

5. Nutrition
Failure to Thrive
Failure to thrive is common in infancy. Nonorganic
failure to thrive accounts for 50% of all cases, organic
diseases for 25%, and a combination of both play a
role in approximately 25%.66,67
For a child to be labeled as having failure to thrive, the
assessment must be based on several growth points
plotted on the standard age- and sex-appropriate growth
charts. If characterized as having failure to thrive, a
child must meet at least 2 of the following criteria:
1. weight progressing in a downward deviation across
at least 2 major percentile lines on the standard
chart;
2. weight less than 90% of the expected rate for mea-
sured length;
3. weight below the 3rd percentile of expected weight
for age;
4. actual weight loss.
Organic Failure to Thrive
The differential diagnosis of organic failure to thrive
encompasses almost every pediatric subspecialty
(Table 13).
Nonorganic Failure to Thrive
Nonorganic failure to thrive, also described as envi-
ronmental failure to thrive, is the result of psychoso-
cial factors, most commonly, impaired interaction
between the caregiver and infant.68
Evaluation
History. The child with failure to thrive should have a
detailed history, primarily to determine one of the fol-
lowing reasons that have led to malnutrition:
1. Not being offered adequate calories;
2. Inability to consume adequate calories;
3. Difficulty retaining adequate calories;
4. Increased caloric demands that exceed otherwise
adequate caloric intake for child’s age.
In infants less than 5-6 months of age, in whom for-
430 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
mula is the only source of calories, it is easy to ascer-
tain the caloric intake. The majority of infant formu-
las, if prepared properly, provide 20 calories per
ounce. However, improper formula preparation is
common, often providing diluted formula which
eventually results in failure to thrive. Therefore, tech-
nique of formula preparation must be an integral part
of history-taking in all infants with failure to thrive.
In older infants and children, a 3- to 5-day detailed
diet record maintained by the child’s caretaker should
be analyzed to determine the daily caloric intake.
Calories per kilogram required at a particular age are
noted in Table 14.
The medical history should include a review of vari-
ous organ systems. Vomiting, usually due to underly-
ing gastrointestinal etiology, may at times be sec-
ondary to increased intracranial pressure. A neuro-
logic cause should be suspected if there has been asso-
ciated developmental delay, loss of achieved mile-
stones, or deviation of head circumference across 2
percentile lines. Abnormalities of respiratory status
should make one suspicious of underlying cardiac dis-
ease or chronic pulmonary conditions. Cystic fibrosis
Table 14
Caloric Requirements/kg Body Weight
Age Kcal
0 – 6 months 110
6 – 11 months 90-95
1 – 3 years 100
4 – 6 years 90
7 – 10 years 70
11 – 14 years 55
Tanner Stage V 35
Table 15

Assessment of Infants with Failure to Thrive

Document Failure to Gain Weight

Obtain history and perform physical examination

Note any specific abnormality:
Oropharyngeal disorder
Cardiac defect
Hepatomegaly
Cerebral palsy
Chronic vomiting
Chronic diarrhea

If Suspicious of Nonorganic Failure to Thrive

Perform 3-day calorie counts

Consider hospitalization to document weight gain
with adequate nutrition

If Suspicious of Organic Failure to Thrive

Perform laboratory studies: To screen for:

Complete blood count, leukocyte differential, Anemia, inflammatory causes
platelet count, erythrocyte sedimentation rate
Serum electrolytes, bicarbonate, arterial blood Renal and hepatic disease
pH, liver profile
Urine pH, specific gravity, glucose, protein, Tubular acidosis, diabetes mellitus, diabetes insipidus,
microscopic examination urinary tract infection
Serum immunoglobulins Immunodeficiency
Sweat chloride test Cystic fibrosis
Antigliadin and antiendomysial antibodies Celiac disease
Somatomedin C/bone age, thyroid function tests Endocrine disease
Serum amino acids/urine organic acids Metabolic defects

From Chawla A. Failure to thrive. In: Brandt LJ, ed. Clinical Practice of Gastroenterology. Philadelphia, Pa: Current
Medicine; 1999.

should be suspected in children with repeated
episodes of bronchitis or pneumonia, especially
occurring in conjunction with failure to thrive. The
majority of children with cystic fibrosis also have
maldigestion/malabsorption, often reflected by the
presence of large, oily, foul-smelling stools. A his-
tory of recurrent bacterial infections should make
one suspicious of an underlying immunodeficiency.
Increased anion gap and persistent acidosis warrant
screening for defects of amino acid or fatty acid
metabolism. Persistent acidosis with normal anion
gap should raise the suspicion of renal tubular
acidosis.
Social history should be reviewed carefully, espe-
cially concerning the child’s specific caretakers.
Within the last couple of decades, as more families
have needed to have 2 working parents, and single-
parent families have increased, this has led to involve-
ment of either multiple caretakers or the use of day
care centers. This makes it far more difficult to assess
the caloric intake, behavioral issues, and inconsisten-
cies in feeding techniques.
Examination
Congenital abnormalities should be assessed. Even
minor congenital anomalies such as body asymmetry,
low-set ears, and extra digits may be associated with
developmental delay, mental retardation, and conse-

GASTROENTEROLOGY AND NUTRITION 431


Figure 12
How to calculate ideal weight for age and
weight age based on a child’s actual weight
18
16
14
12
Weight, kg
10
8 Actual weight
Weight age
6
4
2
B 3 6 9 12 15 18 21 24 27 30 33 36
Age, mo
Chawla A. Failure to thrive. In: LJ Brandt, ed. Clinical Prac-
tice of Gastroenterology. Philadelphia, PA: Current
Medicine;1999.
quent poor caloric intake with failure to gain weight.
Congenital heart disease, especially acyanotic heart
disease, can often be missed in infancy. Anthropomet-
ric measurements must be obtained from previous
health records and carefully plotted. Weight usually
declines before height. Weight loss in the presence of
normal height and head circumference suggests the
recent onset of malnutrition, whereas an absolute
decline in weight associated with a decline in height
velocity indicates a more chronic nutritional depriva-
tion. Height velocity usually begins to decline 4-6
months after the decline in weight gain.
In addition to a search for an underlying organic
abnormality, one must evaluate these infants, irre-
spective of their background, for signs of neglect. The
neglected, malnourished child often appears apa-
thetic, and lacks interest in his/her environment.69
432 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
Laboratory Evaluation
The history and physical examination usually help to
determine the necessary laboratory studies that should
be ordered. Table 15 offeres guidelines to assist in the
evaluation of children with failure to thrive. In chil-
dren with persistent vomiting, a barium study should
be obtained to rule out anatomic abnormalities such as
malrotation or the presence of an antral web.
95
90
In the absence of an anatomic gastrointestinal abnor-
75
mality, and especially if vomiting is associated with
50
developmental delay or deviation of head circumfer-
25
ence across 2 percentile lines, then an intracranial
10
space-occupying mass should be considered. A mag-
Ideal weight 5
for age
netic resonance image of the brain is recommended in
this setting.
If the child’s height is more significantly affected than
his/her weight, an endocrine abnormality is more
likely. If non-organic failure to thrive is suspected,
confirmation of the diagnosis is based on exclusion of
an underlying organic condition and a positive growth
response to better nutrition and caloric intake.
Management
Nutritional management is the keystone of therapy
for these infants in both organic and nonorganic fail-
ure to thrive. For a child with organic failure to
thrive, specific measures are directed at controlling
the major medical problem, while making every
attempt to correct the infant’s nutritional status by
providing a disease-appropriate modified diet with
increased calories.
In the setting of nonorganic failure to thrive, manage-
ment must also focus on improving the interaction
between the infant and the caretaker. A more global
approach addressing the social, emotional, and finan-
cial support system for the family is warranted.
The goal of nutritional treatment is to promote catch-
up growth in weight and height. Catch-up growth is
defined as acceleration of growth that occurs when a
period of growth retardation ends, and measured
parameters begin to climb across percentile lines
towards the expected height and weight percentiles.70
The following formula, to calculate the calories
needed for catch-up growth, is suggested by Farrell.7
 Caloric needs can often be met, especially in
infants, by increasing the caloric density of the for-
Figure 13

mula with the addition of either glucose polymers

or medium- or long-chain triglycerides. In older
Body mass index-for-age percentiles:

children, ready-to-feed, higher-calorie formulas

Boys, 2 to 20 years

can be used for supplementation. The use of naso-

gastric feeds becomes necessary occasionally,
BMI

especially in the setting of underlying organic dis-

34

ease, eg, cyanotic heart disease.

32 97th

Childhood and Adolescent Obesity

95th
30

Obesity is the most widespread and severe nutri-

90th

tional problem of children in the United States, with

28

prevalence rates that vary greatly by ethnic group.73,74

85th
26

Weights are generally higher for Hispanic and

75th

American Indian children of both sexes, and for

24
50th

African-American girls. The body mass index

22

(BMI), the index of weight over height squared

25th

(BMI = [wt (kg)]/[ht (m)]2, better reflects the amount

20 10th
5th

of body fat compared with the amount of muscle or

18 3rd

bone, and is used for a proxy for measurement of

body fatness. BMI measurements are now an inte-
16

gral part of the standard growth chart. The BMI is the

14

preferred method of expressing body fat percentile

from clinical measurements. An example of a body
12

mass index chart is in the attached figure (Figure 13).

kg/m2
2 4 6 8 10 12 14 16 18 20

The definition of being overweight or the more

Age (years)

acceptable term, at risk for obesity in children is the

85th percentile of BMI for age and gender. Obesity
in children is defined as the 95th percentile of BMI
Source: Developed by the National Center for Health
Statistics in collaboration with the Center for Chronic Dis-

for age and gender. In adults, a BMI of 25 is consid-

ease Prevention and Health Promotion (2000).

calories required for weight ered overweight, and a BMI of more than 30 is con-
Energy requirement for
sidered obese. The BMI has good specificity, so that
catch-up (kcal/kg/day)
age x ideal weight for age (kg) it seems to exclude subjects who are not overweight
=

x actual weight in kg or obese. However, it misses some that are obese,

The growth chart in Figure 12 illustrates how to cal-
culate the ideal weight for age and weight age based
on the child’s actual weight. Ideal weight for age is
the 50th percentile weight for that age. Weight age
is the age at which the child’s current weight would
be on the 50th percentile. However, in children with
severe malnutrition, calories should be increased
gradually over a 2- to 3-week period until the goal
for energy requirement for catch-up growth is met.72
Severely malnourished children, if fed too rapidly,
may develop re-feeding syndrome, often character-
ized by hypocalcemia, hypophosphatemia, and at
times, cardiac failure.
and therefore has poorer sensitivity. BMI might not
provide an accurate reflection of the nutritional sta-
tus in a stunted child, suggesting better nutritional
status than is actually the case.
Multiple factors have been implicated as the cause
for obesity. A complex mixture of environmental
and genetic influences usually determines an indi-
vidual’s body weight. Obviously, the recent
changes in population averages for a marked
increase in BMI demonstrates the environmental
influences. More recently, though, genetic basis for
obesity is being more extensively explored. An

GASTROENTEROLOGY AND NUTRITION 433

obesity gene is a gene with natural variants (alleles)
that cause monogenic obesity in human families;
that is, the presence of the mutation predicts the pres-
ence of obesity. Most new understanding of mecha-
nisms that cause obesity has come from studies of
animal models such as mice. Genes have been iden-
tified that cause spontaneous obesity on any diet,
irrespective of its caloric density (such as the leptin
and leptin-receptor genes). Many of these genes
have been shown to have human homologues that
cause human obesity.76 Overall, 7 genes are known to
cause human obesity, and at least 20 genes are
known to influence fat accumulation in mice.77 How-
ever, molecular genotyping is not currently possible
commercially.
For years, people have debated whether it is the genes
or family environmental factors that result in more
overweight parents having overweight children than
non-overweight parents having overweight children.
Although there are physiologic and genetic influ-
ences on the various components of energy
metabolism and body weight regulation, it seems
unlikely that the increased global prevalence of obe-
sity has been driven by a dramatic change in the gene
pool. It is more likely and more reasonable that acute
changes in behavior and environment have con-
tributed to the rapid increase in obesity, and that
genetic factors may be important in the differing
individual susceptibilities in these changes. Today,
children living in an obesogenic food environment
that provides ready availability of inexpensive,
energy-dense palatable foods in large portions are
consuming diets that are too high in carbohydrates
and fat, and contain very few servings of fresh fruits,
vegetables, and grains.78
The more sedentary lifestyle is caused by an increased
reliance on technology and labor-saving devices,
which have reduced the need for physical exertion for
everyday activities. Excessive television viewing, and
over the past 4-5 years, the use of computers for both
entertainment and communication, has significantly
contributed to a sedentary lifestyle in our children.
Obesity in childhood provides an independent fac-
tor to the development of adult morbidity. Strong
434 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS
epidemiologic and causal links between obesity in
the young and early onset Type 2 diabetes have been
illustrated.79
Treatment of the Overweight
Pediatric Patient
Dietary approaches. A low-fat, calorie-restricted diet
has been the standard dietary approach in the treat-
ment of overweight pediatric patients. However, this
approach has not resulted in any demonstrable suc-
cess. In a recent study, the dropout rate exceeded
90%.80 Despite poor long-term sustained weight
reduction on low-calorie diets, it remains a prevalent
practice, especially in female adolescents. The con-
sensus of clinicians taking care of this population is to
instill better eating habits, which would not only result
in decreased caloric consumption, but also well-bal-
anced dietary intake. Significant increases in the con-
sumption of soft drinks are well documented among
children and adolescents. For example, soft drinks
contribute 4.3% of the energy intake of children age
2-18 years, but do not contribute significant amounts
of any other nutrients. Reducing soft drink consump-
tion has the potential to be nutritionally beneficial.
The USDA Center for Nutrition Policy and Promotion
issued a report card on the diet quality of children,
stating “the dietary quality of children and adolescents
steadily declines as they get older.”81 Using the
healthy eating index to evaluate the diets of children,
they recommended substantial improvement in the
diets of children by increasing fruits, vegetables, and
milk products.
Dietary fiber intake has been extensively studied with
regard to its role in weight management. Several
short-term studies suggest that high-fiber foods
induce greater fat satiation (lower meal energy con-
tent) and satiety (longer duration between meals).
Fiber, especially viscous soluble fiber, may increase
intraluminal viscosity and slow gastric emptying, and
provide a mechanical barrier to the enzymatic diges-
tion of starch in the small intestine. As a consequence,
carbohydrate absorption rate and postprandial blood
glucose concentration tend to be lower after high-
fiber, compared with low-fiber foods or meals. As a
result of these lower postprandial blood glucose lev-
els, insulin secretion is reduced. These changes pro-
mote satiety and favor oxidation of fat.
Behavioral therapy. Some view behavioral change in
obesity treatment as being passé and it is often over-
looked, especially in commercial weight reduction
programs. Global family counseling is frequently
more effective than individual counseling of the child.
The simultaneous intervention of a pediatric child
psychologist is often beneficial.
Exercise. Evidence suggests that reduced physical
activity and sedentary behaviors, such as television
viewing and computer games, are primary causes of
the current worldwide obesity epidemic. Exercise
promotion and treatment recommendations for child-
hood obesity include reductions in sedentary behav-
iors and participation in activities with high caloric
cost, ie, school sports and walking programs. Once
again, family participation can play a crucial role in
achieving these goals.
ing satiety. Fenfluramine decreases appetite by stim-
ulating the release of serotonin and dopamine. Phen-
termine is another orally active controlled substance
that affects appetite by increasing the release of
norepinephrine and dopamine from nerve terminals,
and inhibiting their re-uptake. The potential risks of
fenfluramine-induced cardiac valvulopathies led to
the withdrawal of this medication in 1998. The side
effect profile of phentermine includes insomnia,
restlessness, euphoria, palpitations, hypertension,
cardiac arrhythmias, dizziness, blurred vision, and
ocular irritations, therefore not making it a very pop-
ular choice of pharmacotherapy. Silbutramine, an
inhibitor of synaptic re-uptake of norepinephrine,
serotonin, and dopamine, is currently undergoing
clinical trials in older adolescents.

Intensive therapy for morbid obesity. Intensive

treatment is reserved for children and adolescents who
Figure 14

have a BMI greater than the 95th percentile for age

and sex, who also have developed a demonstrable
Roux-en-Y gastric bypass

medical complication that may be remedied through

weight reduction. The comorbid complications of
obesity that may be observed during childhood
Proximal stomach

include hypercholesterolemia, dyslipidemia (elevated

Jejunum

low-density lipoprotein cholesterol and low high-den-

sity lipoprotein); glucose intolerance to frank Type II
diabetes; hepatic steatosis; hypertension; sleep apnea;
and orthopedic complications such as slipped capital
femoral epiphysis and Blount disease.82
Staple line

Intensive diet restriction. The most commonly used

very low-calorie diet is the protein-sparing modified
Distal stomach

fast (PSMF). While cutting the calories, protein intake

is maintained at around 1.5-2.5 g/kg of ideal body
weight. It remains unclear whether these regimens of
PSMF are superior at inducing long-lasting weight
changes for the treatment of pediatric obesity, com-
pared with long-term outcomes of moderate calorie-
restricted diets. When patients use a PSMF, daily vita-
min and mineral supplementation, and consumption
of adequate free water to provide maintenance fluids,
Duodenum

is recommended.

Pharmacotherapy. Very few studies in children

have examined the efficacy of medications that
reduce food intake by decreasing appetite or increas-

GASTROENTEROLOGY AND NUTRITION 435

There are medications now available that reduce the As the problem of obesity becomes an epidemic, not
absorption of nutrients by blocking the action of only in the United States, but worldwide, several orga-
digestive enzymes, or directly blocking the absorption nizations have issued guidelines or policy statements
of nutrients from the gastrointestinal tract. Orlistat is regarding treatment.86 Various organizations are
an inhibitor of gastrointestinal lipases, therefore caus- emphatic about the need for multidimensional
ing maldigestion and malabsorption of ingested fats. approaches targeting families of obese children, and
Side effects of Orlistat include decrease in fat-soluble focusing on encouraging and supporting long-term
vitamin levels, primarily vitamin D; steatorrhea; and behavioral changes, both in their eating habits and
increased frequency of defecation.83 physical activity patterns. All groups acknowledge
the need to promote self-esteem among these chil-
Surgical intervention. Water-filled balloons have dren, and setting realistic expectations with regard to
been placed within the stomach to induce a sense of their eventual goal with their body size and shape.
fullness, but have been shown not to be an effective
measure in decreasing the BMI in morbidly obese
children. Roux-en-Y gastric bypass (RYGB) has
become the most commonly performed bariatric
surgery (Figure 14). RYGB involves dividing the
stomach to create a small stomach pouch. Next a Y-
shaped section of the small intestine is attached to
the pouch to allow food to bypass the duodenum
and the first portion of the jejunum. This causes
reduced calorie and nutrient absorption. There is
limited pediatric data with regard to this surgery in
children. In a recent study, severely obese adoles-
cents who underwent the RYGB procedure were
followed for a mean of 69 months.84,85 Ninety per-
cent had weight losses of more than 30 kg, compris-
ing >65% of their excess body weight. Patients also
had improvements in comorbid conditions.

Complications, however, included iron deficiency

anemia in 50% of the patients, a transient folate defi-
ciency in 30% of the patients, and 40% required surgi-
cal intervention (cholecystectomy in 20%, small
bowel obstruction in 10%, and incisional hernia in
10%). Therefore, the authors suggest that gastric
bypass should be used a last resort option for severely
obese adolescents.

436 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS

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7. Questions

Section on Bacterial Gastroenteritis A. Typhoid fever

1. A 2-year-old boy is admitted to the hospital B. Ulcerative colitis

because of a generalized seizure. His temperature
was 37.8°C (100°F). Within 1 hour of admission, C. Pseudomembranous enterocolitis
he passes loose, watery stools that contain blood.
The most likely diagnosis is: D. Regional enteritis

A. Shigellosis E. Irritable bowel syndrome

B. Salmonellosis
4. The parents of an 18-month-old boy bring the
C. Giardiasis infant to you as a new patient. They state that he
has been “constipated” since early infancy. He has
D. Staphylococcal enteritis been managed with fair success with glycerin
suppositories and laxatives. Physical examination
E. Rotavirus infection discloses no distention of the abdomen. A copious
amount of fecal material is palpated in the large
bowel. The rectal ampulla is empty. The manage-
Section on Failure to Thrive ment of choice would be to:

2. For a term infant, the caloric requirement for ade- A. Continue the present treatment regimen
quate growth during the first month of life is
approximately: B. Continue the present treatment regimen but
add more bulk to the diet
A. 75 to 90 kcal/kg/day
C. Order a barium enema examination
B. 100 to 120 kcal/kg/day
D. Prescribe mineral oil
C. 140 to 175 kcal/kg/day
E. Discontinue all medications and observe the
D. 180 to 200 kcal/kg/day patient

E. >200 kcal/kg/day Section on Congenital Anatomic Abnormalities

Section on Bacterial Gastroenteritis 5. The most common form of esophageal atresia:

3. You are asked to see a 14-year-old girl who was A. Has no associated tracheoesophageal fistula
admitted to the hospital because of a sudden onset
of profuse diarrhea, which was blood tinged. Her B. Has a fistula between upper esophageal seg-
mother states the girl has had no previous health ment and trachea
problem, with the exception of moderate acne
vulgaris for which she was being treated with C. Has a fistula between the lower esophageal
applications of benzoyl peroxide and oral clin- segment and trachea
damycin. Physical examination reveals a temper-
ature of 39.0ºC. Her abdomen is distended, and D. Has fistulas between both lower and upper
there is slight diffuse tenderness. Laboratory stud- esophageal segments and trachea
ies disclose a hemoglobin of 11.2 g/dL and leuko-
cyte count of 3400/mm3. The most likely diagno-
sis for this patient is:

GASTROENTEROLOGY AND NUTRITION 441

Section on Childhood and Adolescent Obesity

6. An obese child has a body mass index of

more than:

A. 50th percentile

B. 75th percentile

C. 85th percentile

D. 95th percentile

Answers

1. A.
2. B.
3. C.
4. C.
5. C.
6. D.

442 EDUCATIONAL REVIEW MANUAL IN PEDIATRICS