Pediatric Gastrointestinal Disorders

Foundations

Bilirubin is formed by the breakdown of heme-containing proteins, primarily hemoglobin. Unconjugated bilirubin binds to albumin and is carried to the liver, where it is conjugated by glucuronyl transferase and excreted into bile. While jaundice in adults is usually a conjugated hyperbilirubinemia, resulting from primary hepatobiliary disease, neonatal jaundice is usually the result of extrahepatic causes and results in an unconjugated hyperbilirubinemia ( Table 166.2 ). There are typically three physiologic factors that contribute to neonatal jaundice: (1) increased bilirubin production, (2) decreased clearance and excretion, and (3) increased enterohepatic resorption. Conjugated hyperbilirubinemia in neonates, on the other hand, is less common and always pathologic.

Nearly every newborn develops an unconjugated serum bilirubin level greater than 1 mg/dL— the normal upper limit in adults—during the first week of life. Jaundice, the yellow discoloration of the skin and sclera, becomes clinically noticeable when the total bilirubin level rises above about 5 mg/dL. Risk factors for the development of severe hyperbilirubinemia in the neonate include prematurity, isoimmune-mediated hemolysis (ABO incompatibility), sepsis, cephalohematomas, dehydration, and inherited abnormalities, such as hereditary spherocytosis and glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Unconjugated bilirubin crosses the blood-brain barrier, where it causes cell death. At levels greater than approximately 20 to 25 mg/dL, there is an increased risk of bilirubin-induced neurologic dysfunction (BIND). Kernicterus refers to the chronic, irreversible, long-term neurologic sequelae of BIND.

Jaundice during the newborn period is usually the result of an immature metabolism of bilirubin. This benign self-limited jaundice is termed physiologic jaundice of the newborn , occurring in approximately 50% of normal newborns. Although it varies based on ethnicity, total bilirubin levels typically peak between two and five days of life, and the yellow discoloration of the skin usually resolves by the first two weeks of life.

Breast milk jaundice is the second most common cause of neonatal jaundice. The exact pathophysiology is uncertain, but it may be hormonally mediated or related to increased enterohepatic resorption of bilirubin. Breast milk jaundice is typically characterized by a mild unconjugated hyperbilirubinemia that peaks a bit later than physiologic jaundice and may persist for several weeks to months. Other causes of jaundice vary significantly (see Table 166.2 )

Clinical Features

Healthy infants are born with normal bilirubin levels that gradually increase to a peak level of 6 mg/dL on approximately the third day of life and then decline to normal levels within 2 weeks. Infants with hyperbilirubinemia usually begin life with similarly low bilirubin levels but exhibit a faster rise in bilirubin levels over the first few days of life. Physiologic jaundice is rarely present on the first day of life, meaning that a total bilirubin level greater than 5 mg/dL within the first 24 hours of life is almost always pathologic. Children with breast milk jaundice typically demonstrate the same gradual increase seen with physiologic jaundice, but levels continue to increase and peak at around 10 to 21 days of life. Elevated levels may persist for 3 to 10 weeks before gradually declining.

Toxic levels of bilirubin (dependent on age, but in general >20 mg/dL) may be associated with neurotoxicity and encephalopathy, termed bilirubin-induced neurologic dysfunction (BIND), and the development of kernicterus. Symptoms of BIND include poor feeding and lethargy, sometimes progressing to muscle rigidity, opisthotonos, seizures, and death. Other potential clinical manifestations are cerebral palsy, sensorineural hearing loss, and gaze abnormalities (usually upward gaze limitations).

Acute bilirubin encephalopathy (ABE) refers to the early and potentially reversible signs and symptoms of the hyperbilirubinemia, including somnolence, poor feeding, hypertonia or hypotonia, and a high-pitched cry. If untreated, symptoms can progress to lethargy, hypertonia, backward arching of the neck and trunk (retrocollis and opisthotonos, respectively), fever, irritability, and apnea. Ultimately, this can lead to seizures and death. Survivors may have chronic, permanent coordination problems, cerebral palsy, hearing loss, and learning disabilities. If treated, some or all of these symptoms may be reversible. Ultimately, the management of neonatal jaundice aims to prevent the development of BIND and kernicterus.

Differential Diagnoses

Once the diagnosis of neonatal jaundice is established based on physical exam and laboratory confirmation of an elevated unconjugated bilirubin level, focus should be directed to identifying and managing the physiologic factors contributing to the derangement. The birth history may reveal prematurity or a history of birth trauma–related cephalohematomas. Review of the maternal and infant perinatal records may identify maternal-child blood type (ABO) incompatibility or other risk factors for isoimmune-mediated hemolysis. A detailed history of feeding patterns, urine output, and stool appearance may identify poor nutritional intake, poor weight gain, and dehydration. The presence of hyper- or hypothermia may suggest the presence of infection/sepsis. The family history may identify siblings or other relatives with a history of jaundice or genetic or metabolic disorders. Table 166.2 presents additional differential considerations for jaundiced infants.

Diagnostic Testing

Physiologic and breast milk jaundice are the most common causes of neonatal jaundice; pathologic causes and indications for evaluation of hyperbilirubinemia are listed in Box 166.1 . Transcutaneous bilirubin meters can be used to quickly measure bilirubin levels through the skin in otherwise well-appearing neonates who are beyond 24 hours, but within 7 days, of life. Infants who have previously undergone phototherapy, those with known risk factors for hemolysis, and those with high transcutaneous levels (based on the meter manufacturer’s recommended product range) should also have serum levels sent. Initial serum testing can also determine fractionated levels of total versus direct (conjugated) bilirubin.

We recommend that further laboratory evaluation include a complete blood count (CBC) with a peripheral smear and Coombs test to determine immune-mediated major blood group incompatibility, if not previously known. Diagnostic testing in ill-appearing infants includes finger stick blood glucose measurement, electrolyte panel, urine assay for reducing substances, serum ammonia levels, ketones, lactate and evaluation for infection. Conjugated hyperbilirubinemia is always pathologic, resulting from biliary atresia, other biliary obstructive pathology, severe infections, toxins, or inborn errors of metabolism.

Management

The treatment of infants with unconjugated hyperbilirubinemia centers on the prevention of kernicterus. Because oral intake stimulates enterohepatic circulation and decreases bilirubin levels, feeding (including breast-feeding) should be encouraged. Phototherapy is the initial intervention used to reduce the total bilirubin level in affected infants. Guidelines for the use of phototherapy, based on age, risk factors for developing BIND, and bilirubin level, have been established and recommended by the American Academy of Pediatrics (AAP) ( Fig. 166.1 ). BiliTool ( www.bilitool.org ) is an additional online resource that utilizes the same AAP guidelines to help clinicians assess the risk of developing hyperbilirubinemia in late preterm and full term infants.

Infants with severely elevated bilirubin levels are at greatest risk for developing BIND. Exchange transfusions are the most effective and rapid way to remove bilirubin. Indications for exchange transfusion include bilirubin level above age-specific threshold recommended by the AAP guidelines (see Fig. 166.1 ), failure of phototherapy (i.e., the bilirubin level continues to rise despite intensive phototherapy), and jaundiced infants with signs and symptoms of BIND. The procedure is time-consuming and should be performed in a pediatric or neonatal intensive care unit (NICU), where the infant’s hemodynamic status may be closely monitored. A double-volume transfusion (180 to 190 mL/kg packed red blood cells) replaces approximately 85% of an infant’s blood volume and reduces the total bilirubin level by at least 50%. It is performed by serially removing small aliquots of the infant’s blood, typically no more than 5 to 10 mL/kg and replacing it with a similar volume of packed red blood cells until the total transfusion volume is achieved.

Disposition

Infants with bilirubin levels greater than established age- and risk factor-specific levels should receive phototherapy ( Fig 166.1A ). Infants who appear ill, are below their expected weight for day of life, cannot maintain oral intake, or require exchange transfusion ( Fig 166.1B ) should undergo hospital admission for phototherapy, IV hydration, and on-going evaluation. Home phototherapy is an option for infants who are otherwise well-appearing, have reliable caregivers with access to emergency care, and can receive follow-up within 24 hours. All infants with direct hyperbilirubinemia should be admitted to the hospital for evaluation of the cause, treatment of sepsis or other treatable cause, and consultation with subspecialist (e.g., pediatric gastroenterology) as indicated.

Foundations

Hypertrophic pyloric stenosis is the most common cause of infantile GI obstruction beyond the first month of life. This condition occurs in 1 of every 250 live births, although rates and trends vary significantly by region. Boys are affected at four times the rate of girls. Approximately one-third of cases occur in first-born children. Prematurity and infant exposure to macrolide antibiotics are additional risk factors. Hypertrophic pyloric stenosis tends to have familial patterns, but the exact pattern of inheritance is unclear.

Affected infants are born with a normal sized pylorus that enlarges as time progresses. The exact cause is unknown, although hypertrophy seems to be stimulated by feeding. As the pylorus enlarges, a progressive gastric outlet obstruction develops, and vomiting ensues. Vomiting causes loss of fluid and gastric acid (hydrogen and chloride ions). As dehydration and electrolyte derangements worsen, the kidney attempts to retain hydrogen ions in exchange for potassium, resulting in the classic hypochloremic-hypokalemic metabolic alkalosis.

Clinical Features

Infants classically present at 2 to 6 weeks of chronologic age, with gradually progressive vomiting that becomes projectile but remains nonbilious. Early in the disease process, infants remain vigorous, with a ravenous appetite. They rapidly finish an entire feeding, only to regurgitate the entire volume in a projectile fashion. In the later stages of the disease, infants may exhibit poor weight gain, clinical dehydration, and malnutrition, along with visible waves of abdominal peristalsis in response to intense contractions against the obstruction.

Diagnostic Testing

Infants may have a palpable pylorus in the right epigastrium on abdominal examination, commonly referred to as an “olive.” Because access to ultrasound is now readily available in the developed world, pyloric stenosis is generally diagnosed earlier compared to decades ago, and the “olive” is now palpated in only a minority of infants who present later in the disease course. Laboratory derangements reflect a state of dehydration and electrolyte loss through vomiting—a hypochloremic metabolic alkalosis (serum bicarbonate [HCO ₃ ] levels ≥29 mmol/dL and chloride levels ≤98 mmol/dL), although these abnormalities may be absent early in the disease course.

Hypertrophic pyloric stenosis may be confirmed by ultrasonography or fluoroscopic upper GI series (UGI). Ultrasonography is often the first diagnostic modality of choice because it is simple, readily available, and without serious complications such as aspiration. Upper GI series may be preferred when there is bilious vomiting and concern for more distal bowel obstruction. With both modalities, reported accuracy is greater than 95%. On ultrasound, the pylorus appears thickened (pyloric muscle thickness > 4 mm; pyloric diameter > 14 mm) and elongated (>19 mm), which is diagnostic ( Fig. 166.2 ). On UGI series, a characteristic string sign, reflecting passage of contrast material through the narrowed pyloric sphincter, may also be evident. In advanced stages with complete obstruction at the pylorus, plain films may reveal a distended, air-filled stomach.

Management

Treatment consists of fluid and electrolyte replacement and surgical consultation. Hypertrophic pyloric stenosis is not a true surgical emergency but may be a fluid and electrolyte emergency. Fluid resuscitation should begin with repeated boluses of 20 mL/kg of normal saline as necessary to treat dehydration and hypovolemic shock. Potassium supplementation (KCl, 0.5 to 1 mEq/kg IV over 1 to 2 hours) is often necessary. Definitive management is surgery. The corrective procedure, called a pyloromyotomy, may be performed open, referred to as the Ramstedt pyloromyotomy, or laparoscopically. Associated mortality is rare.

Disposition

Most children are best managed with hospital admission for rehydration and correction of electrolyte abnormalities in conjunction with urgent imaging and surgical consultation.

Foundations

Malrotation of the intestines occurs in 1 in 500 live births and has a male predominance of at least 2 : 1. Among infants with malrotation, symptomatic volvulus of the midgut occurs in the first month of life in approximately one-third, in the first year of life in approximately one-half, and before the age of 5 years in 75% of children. Rarely, patients born with intestinal malrotation develop midgut volvulus later in life as adults. Some remain asymptomatic. When midgut volvulus does occur, the mortality rate may be as high as 10% with surgical intervention.

During embryologic development, the GI tract rotates around the superior mesenteric artery. As it completes the rotation, the duodenum forms a C-loop and is fixed to the retroperitoneum in the left upper quadrant at the ligament of Treitz. The cecum becomes similarly fixed in the right lower quadrant. Thus, the duodenum and cecum normally come to lie widely separated and are firmly fixed in position by peritoneal attachments called Ladd bands. They are only loosely connected by a broad-based mesentery. In cases of malrotation, the duodenum and cecum do not rotate completely, remain closely positioned, and are suspended in the midgut region by the mesenteric vascular stalk. This unusually close proximity results in a short stalk of mesentery that easily twists on itself, resulting in obstruction of the distal duodenum and bowel ischemia and necrosis secondary to compression of the superior mesenteric artery.

Clinical Features

The hallmark presentation of acute midgut volvulus associated with intestinal malrotation is sudden-onset bilious emesis and abdominal distention in an infant. Affected infants usually appear quite ill and may present in shock. Any yellow or green pigmented staining of the vomitus suggests the presence of bile. When bile is initially produced, it is bright yellow and turns green only with time and oxidative exposure. Therefore, differential coloring of bile-stained emesis, yellow versus green, is not predictive of a surgical condition.

Diagnostic Testing

Plain radiographs may demonstrate nonspecific signs of a small bowel obstruction, including dilated loops of proximal small bowel with air-fluid levels and a paucity of bowel gas distally ( Fig. 166.3 ). The diagnostic procedure of choice to identify midgut volvulus is a limited upper GI contrast series, revealing an abnormal position of the duodenal C-loop, which fails to normally cross the midline from right to left ( Fig. 166.4 ), and a characteristic corkscrew appearance of the more distal small bowel ( Fig. 166.5 ).

Ultrasonography, usually performed to evaluate for hypertrophic pyloric stenosis, may reveal an abnormal orientation of the superior mesenteric artery and vein (the vein is abnormally positioned anteriorly or to the left of the artery ( Fig. 166.6 ) or a whirlpool sign caused by the vessels twisting around the mesenteric stalk, causing an echogenic twisting pattern. CT is usually not recommended because it carries the risk of additional radiation without benefit of improved diagnostic ability over upper GI series.

Differential Diagnoses

Vomiting in childhood, especially infants, is common and occurs across a wide spectrum of illnesses (see Table 166.3 ). Causes vary by age, progression of symptoms, and vomitus appearance. In children less than one year old, sudden onset of bilious vomiting is an ominous sign and should prompt emergent evaluation for acute bowel obstruction, including malrotation with midgut volvulus. Gastroesophageal reflux disease (GERD) and hypertrophic pyloric stenosis typically cause nonbilious emesis in relatively well-appearing infants. NEC may also present with obstructive signs and symptoms, including bilious emesis and abdominal distention. However, unlike malrotation with volvulus, NEC is characterized radiographically by diffusely dilated loops of small bowel and the presence of air within the bowel walls, termed pneumatosis intestinalis .

Management

Emergent pediatric surgical consultation should be obtained for any neonate or infant with bilious vomiting, even before diagnostic studies have been completed. In acute midgut volvulus, operative intervention should be rapid to save the bowel from necrosis.

Intravenous (IV) access should be obtained, and laboratory studies should include blood glucose level, a CBC with differential, electrolyte values, and renal and liver function tests. If there are clinical signs of shock, repeated fluid boluses of 20 mL/kg of normal saline or lactated Ringers solution should be given until adequate circulation has been established. Ill-appearing infants should receive empirical broad-spectrum antibiotic coverage for enteric bacterial pathogens ( Box 166.2 ). A nasogastric or orogastric tube should be placed to decompress the proximal bowel and stomach. A limited upper GI series should also be emergently obtained but should not delay resuscitation and surgical consultation.

Disposition

Patients with a confirmed or equivocal diagnosis should be admitted with emergent surgical consultation.

Foundations

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates. However, because most affected infants are premature and acquire the condition in the NICU, NEC usually is not usually encountered in the ED setting. NEC does occur in a small subset of late preterm and full-term infants, although most of them have other underlying illnesses and rarely are discharged from the NICU prior to the onset of disease. Complications in children who survive NEC, which are often encountered in the ED, include strictures, fistulas, and short gut syndrome.

The exact pathophysiologic mechanism of NEC is unclear but is likely multifactorial. The primary pathophysiologic event is inflammation or injury to the intestinal wall. Prematurity is the most common and universally accepted risk factor, as 90% of all affected infants are born prematurely.

Clinical Features

Infants with NEC usually first develop feeding intolerance and bilious or nonbilious emesis. In the more advanced stages of the disease, infants may appear extremely ill with hematemesis, hematochezia, fever, and shock. Abdominal radiographs may show intestinal dilation, pneumatosis intestinalis, or intestinal perforation.

Differential Diagnoses

Feeding intolerance and vomiting are common and nonspecific findings in neonates. However, unlike most infants with GERD, pyloric stenosis, and other relatively benign or self-limited causes of vomiting, infants with NEC are usually quite ill-appearing. GERD classically begins shortly after birth and remains relatively constant in character. Pyloric stenosis–related vomiting does not begin until 2 to 3 weeks of age and then gradually increases in severity and forcefulness, but these infants rarely appear acutely toxic. Bilious vomiting, while common in NEC, requires careful consideration to rule out other obstructive pathology, including malrotation with midgut volvulus, especially in children born at or near full term. The appearance of the plain radiographs may help differentiate NEC and volvulus. Volvulus is associated with dilated, air-fluid loops of small bowel proximally and a paucity of bowel gas distally, whereas the hallmark of NEC is diffusely dilated loops of small bowel and pneumatosis intestinalis.

Diagnostic Testing

Plain abdominal radiographs are the imaging study of choice in NEC. Radiographs may show nonspecific signs reflecting the presence of small bowel obstruction (dilated, air-fluid filled loops of bowel), bowel ischemia (intramural bowel wall gas, called pneumatosis intestinalis, or air within the portal system and biliary tract), or bowel perforation (pneumoperitoneum). Pneumatosis intestinalis ( Fig. 166.7 ) is pathognomonic for NEC and is present in 75% of patients. No individual laboratory test is diagnostic or specific for NEC, but may reflect dehydration, electrolyte derangements, and sepsis.

Management

Patients suspicious of having NEC should receive nothing by mouth (NPO), with placement of an orogastric or nasogastric tube for decompression of the stomach and small bowel. Because these patients are frequently hemodynamically unstable and may have periods of apnea or significant respiratory distress, intubation may be needed. IV or intraosseous access should be established; laboratory studies should include a CBC with differential, electrolyte panel, glucose, renal and liver function tests, and type and screen. Blood and urine cultures should be obtained. Fluid resuscitation with 20 mL/kg boluses of normal saline or lactated Ringers solution should be repeated until adequate circulatory volume has been reestablished. Vasoactive agents such as epinephrine, or norepinephrine are indicated for patients in refractory shock. Broad-spectrum antibiotic coverage is indicated (see Box 166.2 ). Emergent pediatric surgery consultation should be obtained in all cases because perforation and bowel necrosis may not be immediately evident on plain radiographs. Mortality is very high (30% to 50%) despite appropriate management.

Disposition

Children thought to have NEC require admission to an ICU and should have emergent pediatric surgical consultation.

Foundations

Gastroesophageal reflux (GERD) refers to the symptomatic regurgitation of stomach contents into the esophagus, with or without vomiting. Reflux occurs as a result of an incompetent lower esophageal sphincter. Reflux is a normal physiologic event in infants, and essentially all infants experience intermittent reflux during at least the first six months of life. When reflux causes troublesome symptoms or complications, it is referred to as GERD. Chronic reflux of gastric contents into the esophagus may result in esophagitis, chronic cough, aspiration, and failure to thrive if severe.

Clinical Features

Reflux and GERD generally begin shortly after birth and resolve with time, usually by the age of one year. Clinical manifestations occur along a wide spectrum of disease, ranging from asymptomatic to occasional episodes of spitting up to severe persistent vomiting and failure to thrive. Sandifer syndrome, although rare, refers to the stereotypical opisthotonic movements highly suggestive of severe GERD. Chronic GERD may cause chronic cough, recurrent stridor, and persistent wheezing. GERD may even be implicated in infants who experience “brief resolved unexplained events” that include symptoms of respiratory distress or apnea, transient color change (i.e., pallor, cyanosis), and possibly a change in muscle tone (flaccidity or rigidity), although evidence of this direct causation is lacking.