Ascites is the pathologic accumulation of fluid within the peritoneal cavity. The word ascites is derived from the Greek askites and askos, meaning bag, bladder, or belly. Ascites can occur at any age and in utero. In children it is usually the result of liver or renal disease. Detection and appropriate treatment of ascites is important to minimize morbidity from its complications.
Anatomy and Physiology
In the normal liver, blood flow from the hepatic artery and portal vein perfuses the hepatic sinusoids and then leaves the liver through the hepatic veins to the inferior vena cava (Fig. 1). Pressure in the sinusoids is normally low, about 2 mmHg, because resistance to afferent flow is considerably greater than efferent resistance. Hepatic lymph is formed by the filtration of sinusoidal plasma into the space of Disse (bordered by hepatocytes on 1 side and sinusoidal lining cells on the other) (1,2). It drains from the liver via the transdiaphragmatic lymphatic vessels to the thoracic duct, which empties into the left subclavian vein. The sinusoidal endothelium is highly permeable to albumin; therefore, the concentration of protein in hepatic lymph is close to that of plasma, and there is no significant osmotic gradient across the sinusoidal membrane.
In the intestines, blood from the mesenteric capillaries drains via the mesenteric veins into the portal vein (Fig. 1). The mean pressure of mesenteric capillaries is normally about 20 mmHg. Intestinal lymph drains from regional lymphatics and ultimately combines with hepatic lymph in the thoracic duct. Unlike the sinusoidal endothelium, the mesenteric capillary membrane is relatively impermeable to albumin; the concentration of protein in mesenteric lymph is only about one-fifth that of plasma, so there is a significant osmotic gradient that promotes the return of interstitial fluid into the capillary. In the normal adult, the flow of lymph in the thoracic duct is about 800 to 1000 mL/day (3,4).
Ascites from portal hypertension occurs when hydrostatic and osmotic pressures within hepatic and mesenteric capillaries produce a net transfer of fluid from blood vessels to lymphatic vessels at a rate that exceeds the drainage capacity of the lymphatics. It is not known whether ascitic fluid is formed predominantly in the liver or in the mesentery. The underlying cause of portal hypertension may dictate where the majority of the ascitic fluid is formed. Animal experiments of hepatic vascular outflow restriction show increased hepatic lymph production. When the hepatic vein is ligated in a dog and the liver is placed within the thorax, pleural fluid accumulates instead of ascites; when it is placed within a bag, fluid accumulates in the bag (5,6). In cirrhotic ascites, however, the protein concentration of the ascitic fluid more closely resembles intestinal lymph than hepatic lymph. This suggests that as hepatic fibrosis progresses to cirrhosis, there is decreased capacity for lymph formation by the liver, and that the majority of cirrhotic ascites may be of splanchnic origin (7).
Ascites is a common complication of cirrhosis (8). Alteration of 3 interrelated pathophysiologic processes contribute to the formation of cirrhotic ascites: portal hypertension, vasodilation, and hyperaldosteronism.
In patients with cirrhotic ascites, there is a nitric oxide–mediated systemic vasodilation causing effective hypovolemia, although the trigger for nitric oxide production is not well understood (9). Renal juxtaglomerular apparatuses sense this effective hypovolemia and stimulate the renin-angiotensin-aldosterone system leading to increased sympathetic activity and antidiuretic hormone (ADH) secretion (10). ADH activity promotes free water retention and expansion of plasma volume (11,12). The usual vasoconstricive effects of angiotensin appear to be blunted in cirrhosis, allowing perpetuation of systemic arteriolar vasodilation (13). Arteriolar vasodilation of the splanchnic bed leads to systemic vascular steal and continued systemic underfilling (14). Thus, compensatory mechanisms are unable to achieve circulatory homeostasis and a hypovolemic response continues.
Portal hypertension also increases the hydrostatic pressure gradient across splanchnic circulation resulting in increased intestinal lymph formation. When lymph formation outpaces lymphatic drainage capacity, it accumulates in the peritoneal cavity. Animal models suggest that there is a 60% increase in hepatic lymph production for each millimeter of mercury increase in portal pressure (15).
The patient with decompensated cirrhosis has a hyperdynamic circulatory state with an expanded blood volume, increased cardiac output, tachycardia, a wide pulse pressure, and peripheral vasodilation. The hypoalbuminemia seen with synthetic liver failure exacerbates ascites formation by decreasing the osmotic gradient drawing interstitial fluid into the vascular space.
Noncirrhotic ascites can develop in multiple ways. Peritoneal carcinomatosis causes ascites by the secretion of proteinaceous material from malignant cells with osmotic forces then favoring movement of fluid into the peritoneum. Tuberculous ascites and other forms of inflammatory ascites develop because of similar fluid shifts in response to proteinaceous secretions (16).
Conditions such as right-sided heart failure, Budd-Chiari syndrome, and portal venous malformations may impair portal blood flow leading to portal hypertension and ascites. When a noncirrhotic liver is exposed to elevated sinusoidal pressures, there is an increase in hepatic lymph formation (Fig. 1). Hydrostatic forces are also transmitted to the splanchnic circulation resulting in increased intestinal lymph formation as described above.
Heart failure and nephrotic syndrome may cause decreased effective arterial blood volume with secondary activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system and ADH, leading to renal sodium and water retention (17). The hypoalbuminemia of advanced nephrotic syndrome results in decreased intravascular oncotic pressure and subsequent movement of plasma into the interstitium.
Pancreatic and biliary ascites are caused by leakage of pancreatic juice or bile into the peritoneal cavity, and may be complicated by fluid shifts caused by the irritant effect of these secretions on the peritoneum.
The causes of ascites vary according to the age of the patient. Different hepatic and nonhepatic causes of ascites have been reported in the fetus, neonate, infant, child, and adult.
Isolated ascites, in the absence of hydrops fetalis, is uncommon. Although examination of the fetus by ultrasound has become common, even in a normal pregnancy, there have been only a small number of reported cases of isolated fetal ascites. It appears that many cases resolve spontaneously before birth, and are not associated with poor outcomes or chronic disease (18,19). A list of described causes of fetal ascites is shown in Table 1.
Cytomegalovirus (CMV) is the most common congenital infection of the fetus and can cause fetal ascites and liver disease (20,21). Ascites is typically detected at a gestational age between 21 and 30 weeks. The presence of ascites in utero does not necessarily indicate severe infection or a poor prognosis (22), but data are sparse because many fetuses with ultrasound manifestations of CMV infection are electively aborted (23). Histologic examination of severely infected fetal livers has shown hepatocellular degeneration with extensive bridging fibrosis and intrahepatic calcifications (24).
Intrauterine meconium peritonitis, a sterile peritonitis caused by fetal bowel perforation, can cause ascites, and in 1 case was associated with intravascular dissemination of meconium and multiorgan infarction (25). Meconium ileus diagnosed by fetal ultrasound is often milder and has a better prognosis than symptomatic cases diagnosed after birth; however, the presence of ascites in utero indicates a more complicated course (26).
Neonatal ascites can be caused by many of the same conditions that cause fetal ascites (Table 2), although many congenital diseases do not typically manifest ascites until after birth. There are also multiple iatrogenic causes of ascites in the newborn such as extravasation of parenteral nutrition from femoral or umbilical venous catheters (27–29) and perforation of the bladder or urachal remnant with extravasation of urine into the peritoneal cavity (30,31).
Ascites in Infants and Children
Cirrhosis from chronic liver disease is the most common hepatic cause of ascites in infants and children (Table 3). Inflammatory conditions of the bowel that involve the serosal surface, such as eosinophilic enteropathy (32) and Crohn disease (33), may result in ascites. Vitamin A intoxication may also present with ascites, and measurement of retinol-binding protein is important in establishing the diagnosis (34,35).
Pancreatic ascites occurs rarely in children (36). One-third of cases occur in infants younger than 1 year old (37). Serum amylase and lipase levels may be normal and the diagnosis missed unless ascitic fluid is analyzed (38). Ascites appears to be an accurate independent predictor of severity of pancreatitis and pseudocyst formation (39).
Ascites in Adults
The most common cause of ascites in adults is parenchymal liver disease. Cirrhosis (usually from chronic liver disease resulting from hepatitis C infection, alcoholic hepatitis, or nonalcoholic steatohepatitis) accounts for about 85% of cases. Cardiac disease and malignancy are the next most common causes and together account for about 5% of cases (40). Pancreatitis and tuberculosis are responsible in a minority of patients (41).
Evaluation of the presence, quantity, and etiology of ascites includes the history of the illness, the physical examination, imaging studies, and diagnostic paracentesis.
History and Physical Examination
Patients with ascites typically report increased abdominal girth and recent weight gain (42). There may be a history of chronic liver disease or hepatitis. Physical examination may reveal a protuberant abdomen, bulging flanks, or dullness to percussion. Jaundice, spider angiomas, umbilical collateral veins, clubbing, and palmar erythema are other signs suggestive of liver disease.
The presence of bulging flanks can be caused by free fluid in the peritoneum, organomegaly, or obesity. Percussion of the abdomen can be used to distinguish ascites from obesity. In a supine patient with ascites, gas-filled loops of small intestine float to the top of the mid-abdomen. The percussion note of the mid-abdomen will be tympanitic, whereas the ascites-filled flanks will have dullness to percussion. If the patient is then placed in a lateral position, dullness to percussion will shift to the dependent side. The test for shifting dullness has a sensitivity of 60% to 88% and a specificity of 56% to 90%. It has been estimated that the minimum volume of ascitic fluid required to detect shifting dullness in an adult is 1.5 to 3.0 L (43).
A more sensitive test for ascites, which can be easily done in small children, is the “puddle” sign (44). In this test, a supine patient's abdomen is percussed over the umbilibus. The resonant percussion becomes dull as the patient is moved to a prone position and the ascitic fluid “puddles” in dependent regions. Infants and small children can easily be held prone by a caregiver, whereas the abdomen of older children can be percussed with the patient kneeling on all fours.
The test for a fluid wave requires 2 examiners, 4 hands, and a cooperative supine patient. The sides of the hands of 1 examiner are used to press down the midline of the patient's abdomen, while the other examiner depresses the flank with 1 hand and senses the resultant fluid wave in the contralateral flank with the other hand. The test for a fluid wave is unreliably sensitive (20% to 80%) but highly specific (82% to 100%) (43).
Ultrasound is a sensitive imaging technique for the detection of ascites (Fig. 2). Free fluid can be imaged confidently with ultrasound because it layers in the dependent regions, the hepatorenal recess (Morison pouch) and the pelvic cul-de-sac (45). It has been estimated that in supine infants 10 to 20 mL can be detected by ultrasound in the perivesicle area (46). Limitations to ultrasound include obesity and complex, loculated ascites because sound wave transmission to deeper structures can be limited by adipose tissue and intralumenal gas.
Ascites can also be detected by plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI) (Figs. 3–5) (47). CT demonstrates extrapancreatic fluid collections in children with acute pancreatitis (48) and high-density ascites in tuberculous peritonitis (49). Chylous ascitic fluid has been shown by both CT and ultrasound to develop a unique biphasic fat-fluid level when the patient remains recumbent (50). MRI is an excellent modality for detecting intraperitoneal fluid. With the advent of attempts to reduce ionizing radiation exposure, MRI could play a more important role in the detection of free fluid or loculated fluid collections in the abdominal peritoneal cavity. This may become more applicable in children as scanning times in MRI shorten.
Diagnostic Abdominal Paracentesis
In most children, ascites is readily recognizable as caused by hepatitis, portal hypertension, or nephrotic syndrome. When the cause of ascites is not apparent, however, examination of ascitic fluid can aid in identification of the etiology. Abdominal paracentesis is recommended to detect bacterial peritonitis when ascites accumulates quickly, when patients are hospitalized because of clinical deterioration, or when the patient has fever or abdominal pain (51).
Paracentesis can usually be performed quickly, inexpensively, and, when certain precautions are taken, safely (52). First, the site for needle insertion is selected. With the patient in the semi-recumbent position, the level of dullness is percussed. A site is chosen that is below both the umbilicus and the upper edge of dullness but above the urinary bladder. Scars should be avoided because bowel may be adherent to them. A common needle insertion site is 2 finger breadths medial and cephalad to the anterior superior iliac spine. Ultrasound localization of fluid is typically not necessary but may be warranted if there is difficulty in identifying a safe location.
Following disinfection of the site, a local anesthetic is injected in the skin and subcutaneous tissue. To create a Z-tract (to prevent leakage after the needle is withdrawn) the skin is pushed down about 2 cm over the abdominal musculature and a 22-gauge needle is inserted. The needle is advanced slowly in 5-mm increments, and if blood is seen, the needle is withdrawn. The syringe is aspirated when ascitic fluid is seen in the needle hub. Following aspiration of fluid the needle is withdrawn.
Ascitic fluid collected via paracentesis should be submitted to the laboratory in an anticoagulant tube for a white blood cell count and differential. Bedside inoculation of blood culture bottles with ascitic fluid should be performed (53). In addition, at the time of the first paracentesis, measurement of the albumin concentration is performed. If there is not sufficient fluid to perform all 3 tests, then the white blood cell count and differential is performed first because of its value in deciding whether to treat with antibiotics for possible bacterial peritonitis.
The components of the peritoneal fluid can often help define the etiology of ascites. Amylase elevation indicates pancreatitis or intestinal perforation. Polymicrobial infection is consistent with intestinal perforation, whereas monomicrobial infection suggests spontaneous bacterial peritonitis. Uroascites is present when the concentrations of urea and creatinine are higher in the ascitic fluid than in serum. Elevated ascitic bilirubin indicates perforation of the biliary tree or upper intestine. Chylous ascites is indicated by a milky appearance and a concentration of triglycerides higher in ascitic fluid than in serum.
The concentration of albumin in serum minus the concentration of albumin in ascitic fluid, called the serum-ascites albumin gradient, can reliably separate ascites into 2 categories: high gradient (≥1.1 g/dL) and low gradient (<1.1 g/dL). High-gradient ascites is present when there is portal hypertension, in conditions such as cirrhosis, fulminant hepatic failure, Budd-Chiari syndrome, and portal vein thrombosis. Low-gradient ascites occurs in the absence of portal hypertension in conditions such as peritoneal carcinomatosis, tuberculous peritonitis, pancreatic ascites, biliary leak ascites, nephrotic syndrome, and serositis (54,55).
The exudate-transudate concept, based on the concentration of total protein in ascitic fluid, is unreliable and outmoded (56). In a study of 901 paracenteses, measurement of the ascitic fluid total protein correctly classified the causes of ascites only 56% of the time, whereas the serum-ascites albumin gradient differentiated the causes of ascites resulting from portal hypertension 97% of the time (57).
Complications of paracentesis are uncommon. In a prospective study of 125 adults with 229 paracenteses, there were no deaths attributable to paracentesis (52). Large intraabdominal hemorrhages occurred in 3 patients, 1 of whom required a blood transfusion. Paracentesis can be performed despite prolongation of the prothrombin time, except in cases of frank disseminated intravascular coagulation, and routine administration of fresh frozen plasma or platelets is not necessary.
The benefits of treatment, primarily patient comfort, must be weighed against the discomfort of treatment and potential complications. Small amounts of ascitic fluid that do not produce symptoms or clinical sequelae may require little or no treatment. Tense ascites causing respiratory compromise, severe pain, or other major clinical problems should be treated promptly.
Mobilization of ascitic fluid is accomplished by creating a negative sodium balance until ascites has diminished or resolved; then sodium balance is maintained so that ascites does not recur. In most patients treatment of ascites consists of restriction of dietary sodium and administration of diuretics. On occasion, fluid restriction is also used. Patients who are resistant to diuretics in the setting of sodium restriction can be treated with large-volume paracentesis or transjugular intrahepatic portosystemic shunting (TIPS). Ultimately, orthotopic liver transplantation may be required.
Restriction of Dietary Sodium
Unrestricted intake of dietary sodium exacerbates ascites because of marked renal sodium retention. Ingestion of <10 mEq of sodium daily prevents ascites formation; however, such a diet is unpalatable and few patients will adhere to it. It is recommended that dietary sodium be limited to 44 to 88 mEq (1–2 g) per day in adults, or approximately 17 to 35 mEq (0.4–0.8 g) per thousand calories. Most pediatric hepatologists recommend restriction of sodium intake: either a diet with no added sodium or a maximum of 2 mEq/kg of body weight per day. Restriction of dietary sodium by itself will be sufficient for only a minority of patients, and treatment with diuretics is usually required. Restriction of water intake is usually not recommended unless serum sodium falls below 125 mEq/L.
Supine positioning causes a decrease in sympathetic adrenergic tone and a reduction in the stimulation of renin, angiotensin, and aldosterone, with subsequent diuresis. Bed rest has a small effect on natriuresis in most patients with cirrhosis; it is not considered necessary and, particularly for pediatric patients, it is impractical.
Spironolactone is the most effective single diuretic because of its ability to block the marked hyperaldosteronism that is characteristic of cirrhotic ascites. Metabolites of spironolactone act on the cortical and medullary collecting tubules by inhibiting the binding of aldosterone. Because it acts distally, spironolactone can normally inhibit the reabsorption of only 2% of the filtered sodium. In patients with cirrhosis, the bioactive metabolites of spironolactone have prolonged half-lives, ranging from 24 to 58 hours. As a result it often requires >5 days of treatment to achieve steady-state conditions and administration more than once daily is unnecessary (58).
A randomized comparative study demonstrated that 95% of nonazotemic cirrhotic patients with avid sodium retention responded to spironolactone treatment, but only 52% responded to furosemide. Patients who did not respond to furosemide had higher levels of renin and aldosterone, and upon subsequent treatment with spironolactone, 90% responded (59). Cirrhotic patients with ascites who do not respond to spironolactone treatment have a lower fractional sodium delivery to the distal renal tubule because of enhanced sodium reabsorption in the proximal tubule (60).
Furosemide is a loop diuretic that prevents sodium and chloride reabsorption in the thick ascending limb of the loop of Henle; it has no effect on the distal and collecting tubules (Fig. 6). Because 20% to 50% of filtered sodium is reabsorbed in the loop of Henle, furosemide can increase sodium excretion by as much as 30%. It should be used cautiously, however, because it reduces effective circulating volume in patients who are already intravascularly hypovolemic.
Diuretic treatment is begun with spironolactone, either alone or, in more severe cases, in combination with furosemide (61). One approach is to begin treatment with spironolactone 2 to 3 mg/kg of body weight (up to 100 mg) as a single morning dose; if there is no response, the dose is increased by 2 mg/kg (up to 100 mg) every 5 to 7 days until a maximum dose of 4 to 6 mg/kg (up to 400 mg) is reached. The adequacy of spironolactone dosing can be monitored with random urine sodium levels; values >50 mEq/L are desired. If there is still no response, then oral furosemide 1 mg/kg (up to 40 mg) daily is added, increasing the dose by 1 mg/kg (up to 40 mg) every 5 to 7 days if necessary until a maximum dose of 2 to 4 mg/kg (up to 160 mg) is reached. An alternative approach that may hasten the onset of diuresis is to begin treatment with both spironolactone 2 mg/kg (up to 100 mg) and furosemide 1 mg/kg (up to 40 mg) as a single morning dose. If necessary, the dosages of both spironolactone and furosemide are increased every 5 to 7 days until maximum doses of 4 to 6 mg/kg (up to 400 mg) and 2 to 4 mg/kg (up to 160 mg), respectively, are reached, maintaining a spironolactone to furosemide ratio of about 2.5 to 1 (62).
A gradual approach to diuretic therapy is preferred to decrease the likelihood of adverse effects. The goal of therapy is to reduce the body weight by approximately 0.5% to 1% (up to 300 to 500 g) each day until the ascites is gone, and to prevent the reaccumulation of ascites. No more than 900 mL of ascites can be reabsorbed in 1 day in an adult, so weight loss of >900 g will be associated with contraction of plasma volume (63). Spironolactone treatment can lead to hyperkalemic acidosis, and furosemide treatment can lead to hypokalemic alkalosis. When both drugs are used together, disturbances of potassium and pH occur less commonly. Oral potassium salts should not be administered as a sodium salt substitute when spironolactone is used as monotherapy because of the danger of hyperkalemia. Complications of diuretic therapy also include renal failure secondary to intravascular volume depletion, hyponatremia, hepatic encephalopathy, antiandrogenic effects, and muscle cramps. Nonsteroidal anti-inflammatory agents reduce the diuretic effect of furosemide (64). Intravenous furosemide can cause a potentially hazardous sudden decrease in glomerular filtration rate, and hence must be used cautiously (54).
When ascites results from portal hypertension as a complication of chronic liver disease, hypoalbuminemia is commonly present because of hepatic synthetic dysfunction. As discussed earlier, hypoalbuminemia will exacerbate ascites due to low vascular oncotic pressure. Hence, when serum albumin levels are <2.5 g/dL, supplemental albumin administration may aid ascitic fluid mobilization (65,66). Twenty-five percent albumin may be dosed at 1 g/kg IV up to 3 times per day until serum levels are >2.5 g/dL.
Therapeutic paracentesis of diuretic-resistant tense ascites has been shown to be a safe, rapid, and effective treatment of ascites (67,68). Large volumes of ascitic fluid can be removed without increasing the risk of adverse alterations of hemodynamics, electrolytes, renal function, or mortality. Repeated removal of 4 to 6 L/day of ascitic fluid has become a standard treatment in adults; however, repeated large-volume paracentesis can lead to protein and complement depletion.
When large-volume paracentesis is performed, there is a significant increase in blood urea nitrogen, elevation of plasma renin activity and plasma aldosterone concentration, and reduction of serum sodium. These changes, which indicate a physiological response to the contraction of blood volume, are not usually manifested clinically by symptoms or signs (69–72).
The need for intravenous albumin after paracentesis is a controversial subject (73). Albumin infusions theoretically can produce an undesirable downregulation of albumin synthesis. Other plasma expanders that have been studied, including dextran 70 and polygeline, have not been proven to be as effective as albumin in the prevention of postparacentesis circulatory dysfunction. Patients who receive albumin following total paracentesis have a longer time before rehospitalization and longer survival than patients who received other plasma expanders (70). Postparacentesis administration of terlipressin, a vasopressin analogue, was shown in a study to be as effective as albumin in preventing hemodynamic changes following large-volume paracentesis (74).
There is little published about large-volume paracentesis in children. Infants and young children can develop ascites rapidly. Without gradual accommodation of the abdominal wall, they are subject to respiratory distress and other sequelae of rapidly increasing intraabdominal pressure. In such situations paracentesis is performed to provide symptomatic relief (75). Intravenous albumin is often administered after therapeutic paracentesis in children at a dose of 1 g/kg.
The peritoneovenous shunt was invented to create a conduit for ascites in the peritoneum to return to the vascular space in the superior vena cava (76). The LeVeen and Denver shunts consist of a perforated tube in the abdomen connected with a 1-way pressure-sensitive valve to a catheter that extends subcutaneously into a jugular vein. Peritoneovenous shunting often results in a reduction or elimination of ascites, with restoration of effective blood volume (77,78). Complications are frequent and include coagulopathy, shunt obstruction, superior vena caval thrombosis and obstruction, pulmonary embolism, and sepsis. Technical modifications have not been able to prevent these complications, and pediatric use is generally limited to palliative care (79).
TIPS placement lowers portal pressure and prevents rebleeding from esophageal varices (80). It can also effectively alleviate cirrhotic ascites (81). It induces a delayed natriuresis and improves proximal renal tubular reabsorption of sodium, renin-angiotensin-aldosterone activity, and central blood volume despite continued arterial vasodilation (82). However, it is associated with complications such as hepatic encephalopathy and worsening liver failure, especially in patients with severe liver dysfunction (83). Vascular malformations and patient size may limit application in some pediatric patients (84).
Attempts to develop techniques to ultrafilter ascites and re-infuse it, either into blood or into the peritoneum, have not been superior to other approaches in either adults (85–87) or children (56,88,89). If a child has symptomatic and intractable ascites because of liver disease, then referral for liver transplantation should be arranged.
SPONTANEOUS BACTERIAL PERITONITIS
Bacterial peritonitis is a complication of ascites with a high mortality rate if treatment is delayed. Spontaneous bacterial peritonitis (SBP) is defined as an infection of ascitic fluid without evidence of an abdominal source. Secondary bacterial peritonitis is defined as an intraabdominal infection caused by a condition that requires surgical treatment, such as intestinal perforation, a perirenal abscess, or gallbladder empyema.
The incidence of spontaneous bacterial peritonitis in children is not known (90). In a report of 321 children with chronic liver disease, there were 12 episodes of SBP in 11 patients; all 11 had ascites (91). Patients presented with rapid-onset abdominal distension, fever, malaise, and abdominal pain; some patients also had vomiting, diarrhea, and worsening jaundice. Diffuse rebound tenderness was present and encephalopathy had developed or worsened in most of the patients. Cultures of ascitic fluid detected a single organism in 11 of the episodes; Streptococcus pneumoniae was isolated in 73%, Klebsiella pneumoniae in 18%, and Hemophilus influenzae in 9%. A more recent report examined 13 culture-positive cases of SBP in 12 pediatric patients. Isolated organisms were S pneumoniae (39%), Escherichia coli (15%), S viridans (15%), K pneumoniae, H influenzae, Enterococci, and nontypable Streptococcus(92). The declining prevalence of Streptococcus and Haemophilus in this pediatric series likely reflects contemporary vaccination protocols. Adult series indicate that 60% of SBP episodes are caused by Gram-negative enteric bacilli (93).
An estimated 10% of SBP cases are not accompanied by symptoms suggestive of peritonitis (94). It is recommended that diagnostic paracentesis be performed when ascites first appears, at the time of a hospitalization, or when there is clinical deterioration, unexplained fever, abdominal pain, or other suspicious symptoms.
The concentration of bacteria in infected ascites is often low. Bedside inoculation of blood culture bottles with ascitic fluid is more sensitive than agar plating in detecting bacterial peritonitis, improving sensitivity from 43% to 93% (53). Gram stains of ascitic fluid are only 10% sensitive; however, they can rapidly identify the polymicrobial infections that are worrisome for intestinal perforation.
Samples of ascitic fluid that contain a leukocyte count >500 cells/mm3 and an absolute polymorphonuclear cell (PMN) count >250 cells/mm3 are assumed to be infected (54). In SBP, the PMN count is elevated and the ascites culture is positive. When the PMN count is elevated but the ascetic fluid culture is negative, it likely indicates a false-negative culture. When the PMN count is normal but the culture is positive, it may represent contamination of the culture, early SBP, or transient bacterascites (a condition that resolves in most cases without antibiotics). A repeat paracentesis is often helpful in interpreting these results.
If SBP is diagnosed by paracentesis or culture, then antibiotic treatment should be initiated. A non-nephrotoxic broad-spectrum antibiotic with Gram-negative coverage, such as a third-generation cephalosporin, is generally recommended. In most cases of SBP, treatment is continued for a total of 5 to 7 days, and the ascitic fluid becomes sterile after 48 hours. Despite advances in supportive care, SBP remains an indicator of poor prognosis. Although pediatric data are not available, adult in-hospital mortality remains between 10% and 30% (95).
Prophylaxis for primary or recurrent SBP has been recommended in certain clinical situations. Ciprofloxacin, norfloxacin, and trimethoprim-sulfamethoxazole have been used in adults (96,97), but not reported in children. A meta-analysis of adults with cirrhosis and ascites indicates that β-blockers may also decrease the risk of SBP (98).
Understanding of the pathophysiology and possible etiologies of pediatric ascites is critical in making a rapid diagnosis of this condition. Laboratory and radiographic investigations may provide clinically important information because prompt and appropriate treatment of ascites is warranted to prevent related morbidity and mortality.
1. Millward-Sadler GH, Jezequel AM. Normal histology and ultrastructure. In: Wright R, Alberti KGMM, Karran S, et al. Liver and Biliary Disease
. London: WB Saunders; 1979.
2. Colletti RB, Krawitt EL. Ascites. In: Wyllie R, Hyams JS, editors. Pediatric Gastrointestinal Disease: Pathophysiology
. Philadelphia: WB Saunders; 1999. pp. 104–115.
3. Dudley FJ. Pathophysiology
of ascites formation. Gastroenterol Clin North Am 1992; 21:215–235.
4. Gil Z, Beni-Adani L, Siomin V, et al
. Ascites following ventriculoperitoneal shunting in children with chiasmatic-hypothalamic glioma. Childs Nerv Syst 2001; 17:395–398.
5. Freeman S. Recent progress in the physiology and biochemistry of the liver. Med Clin North Am 1953; 1:109–124.
6. Hyatt RE, Smith JR. The mechanism of ascites, a physiologic appraisal. Am J Med 1954; 16:434–438.
7. Arroyo V, Gines P. Mechanism of sodium retention and ascites formation in cirrhosis. J Hepatol 1993; 17(Suppl 2):S24–S28.
8. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44:217–231.
9. La Villa G, Gentilini P. Hemodynamic alterations in liver cirrhosis. Mol Aspects Med 2008; 29:112–118.
10. Leiva JG, Salgado JM, Estradas J, et al
of ascites and dilutional hyponatremia: contemporary use of aquaretic agents. Ann Hepatol 2007; 6:214–221.
11. Bichet D, Szatalowicz V, Chaimovitz C, et al
. Role of vasopressin in abnormal water excretion in cirrhotic patients. Ann Intern Med 1982; 96:413–417.
12. Gentilini P, Laffi G, La Villa G, et al
. Pathogenetic factors and clinical elements in ascites and hepatorenal syndrome during liver cirrhosis. Ann Ital Med Int 1999; 14:264–284.
13. Hennenberg M, Trebicka J, Kohistani AZ, et al
. Vascular hyporesponsiveness to angiotensin II in rats with CCl(4)-induced liver cirrhosis. Eur J Clin Invest 2009; 39:906–913.
14. Cichoz-Lach H, Celinski K, Slomka M, et al
of portal hypertension. J Physiol Pharmacol 2008; 59(Suppl 2):231–238.
15. Laine GA, Hall JT, Laine SH, et al
. Transsinusoidal fluid dynamics in canine liver during venous hypertension. Circ Res 1979; 45:317–323.
16. Goodman GM, Gourley GR. Ascites complicating ventriculoperitoneal shunts. J Pediatr Gastroenterol Nutr 1988; 7:780–782.
17. Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2). N Engl J Med 1988; 319:1127–1134.
18. Zelop C, Benacerraf BR. The causes and natural history of fetal ascites. Prenat Diagn 1994; 14:941–946.
19. El Bishry G. The outcome of isolated fetal ascites. Eur J Obstet Gynecol Reprod Biol 2008; 137:43–46.
20. Sun CC, Keene CL, Nagey DA. Hepatic fibrosis in congenital cytomegalovirus infection: with fetal ascites and pulmonary hypoplasia. Pediatr Pathol 1990; 10:641–646.
21. Stocker JT. Congenital cytomegalovirus infection presenting as massive ascites with secondary pulmonary hypoplasia. Hum Pathol 1985; 16:1173–1175.
22. Binder ND, Buckmaster JW, Benda GI. Outcome for fetus with ascites and cytomegalovirus infection. Pediatrics 1988; 82:100–103.
23. Lipitz S, Achiron R, Zalel Y, et al
. Outcome of pregnancies with vertical transmission of primary cytomegalovirus infection. Obstet Gynecol 2002; 100:428–433.
24. Yamashita Y, Iwanaga R, Goto A, et al
. Congenital cytomegalovirus infection associated with fetal ascites and intrahepatic calcifications. Acta Paediatr Scand 1989; 78:965–967.
25. Patton WL, Lutz AM, Willmann JK, et al
. Systemic spread of meconium peritonitis. Pediatr Radiol 1998; 28:714–716.
26. Dirkes K, Crombleholme TM, Craigo SD, et al
. The natural history of meconium peritonitis diagnosed in utero. J Pediatr Surg 1995; 30:979–982.
27. Spriggs DW, Brantley RE. Thoracic and abdominal extravasation: a complication of hyperalimentation in infants. AJR Am J Roentgenol 1977; 128:419–422.
28. Shareena I, Khu YS, Cheah FC. Intraperitoneal extravasation of total parental nutrition infusate from an umbilical venous catheter. Singapore Med J 2008; 49:e35–e36.
29. Mohan MS, Patole SK. Neonatal ascites and hyponatraemia following umbilical venous catheterization. J Paediatr Child Health 2002; 38:612–614.
30. Dmochowski RR, Crandell SS, Corriere JN Jr. Bladder injury and uroascites from umbilical artery catheterization. Pediatrics 1986; 77:421–422.
31. Hepworth RC, Milstein JM. The transected urachus: an unusual cause of neonatal ascites. Pediatrics 1984; 73:397–400.
32. Zegarra A, Garcia C, Piscoya A, et al
. Eosinophilic enteritis as a rare cause of ascites: case report. Rev Gastroenterol Peru 2009; 29:272–275.
33. Tekin F, Vatansever S, Ozutemiz O, et al
. Severe exudative ascites as an initial presentation of Crohn's disease. Turk J Gastroenterol 2005; 16:171–173.
34. Mendoza FS, Johnson F, Kerner JA, et al
. Vitamin A intoxication presenting with ascites and a normal vitamin A level. West J Med 1988; 148:88–90.
35. Rosenberg HK, Berezin S, Heyman S, et al
. Pleural effusion and ascites: unusual presenting features in a pediatric patient with vitamin A intoxication. Clin Pediatr (Phila) 1982; 21:435–440.
36. D'Cruz AJ, Kamath PS, Ramachandra C, et al
. Pancreatic ascites in children. Acta Paediatr Jpn 1995; 37:630–633.
37. Athow AC, Wilkinson ML, Saunders AJ, et al
. Pancreatic ascites presenting in infancy, with review of the literature. Dig Dis Sci 1991; 36:245–250.
38. Saps M, Slivka A, Khan S, et al
. Pancreatic ascites in an infant: lack of symptoms and normal amylase. Dig Dis Sci 2003; 48:1701–1704.
39. Maringhini A, Ciambra M, Patti R, et al
. Ascites, pleural, and pericardial effusions in acute pancreatitis. A prospective study of incidence, natural history, and prognostic role. Dig Dis Sci 1996; 41:848–852.
40. Runyon BA. Ascites and bacterial peritonitis. In: Sleisenger MH, Fordtran JS, editors. Gastrointestinal Disease: Pathophysiology
. 9th ed. Philadelphia: Saunders Elsevier; 2010.
41. Aiza I, Perez GO, Schiff ER. Management
of ascites in patients with chronic liver disease. Am J Gastroenterol 1994; 89:1949–1956.
42. Williams JW Jr, Simel DL. The rational clinical examination. Does this patient have ascites? How to divine fluid in the abdomen. JAMA 1992; 267:2645–2648.
43. Chongtham DS, Singh MM, Kalantri SP, et al
. Accuracy of clinical manoeuvres in detection of minimal ascites. Indian J Med Sci 1998; 52:514–520.
44. Tanner S. Assessment of the liver. In: Aynsley-Green AC, ed. Paediatric Hepatology
. London: Churchhill Livingstone; 1989: 4.
45. Nguyen KT, Sauerbrei EE, Nolan RL. The peritoneum and the diaphragm. In: Rumack CM, Wilson SR, Charboneau JW, editors. Diagnostic Ultrasound. St Louis: Mosby-Year Book; 1991.
46. Dinkel E, Lehnart R, Troger J, et al
. Sonographic evidence of intraperitoneal fluid. An experimental study and its clinical implications. Pediatr Radiol 1984; 14:299–303.
47. Heiken JP. Abdominal wall and peritoneal cavity. In: Lee JKT, Sagel SS, editors. Computed Body Tomography. New York: Raven Press; 1989.
48. King LR, Siegel MJ, Balfe DM. Acute pancreatitis in children: CT findings of intra- and extrapancreatic fluid collections. Radiology 1995; 195:196–200.
49. Epstein BM, Mann JH. CT of abdominal tuberculosis. AJR Am J Roentgenol 1982; 139:861–866.
50. Hibbeln JF, Wehmueller MD, Wilbur AC. Chylous ascites: CT and ultrasound appearance. Abdom Imaging 1995; 20:138–140.
51. Runyon BA. Care of patients with ascites. N Engl J Med 1994; 330:337–342.
52. Runyon BA. Paracentesis of ascitic fluid. A safe procedure. Arch Intern Med 1986; 146:2259–2261.
53. Runyon BA, Canawati HN, Akriviadis EA. Optimization of ascitic fluid culture technique. Gastroenterology 1988; 95:1351–1355.
54. Pare P, Talbot J, Hoefs JC. Serum-ascites albumin concentration gradient: a physiologic approach to the differential diagnosis
of ascites. Gastroenterology 1983; 85:240–244.
55. Harjai KJ, Kamble MS, Ashar VJ, et al
. Portal venous pressure and the serum-ascites albumin concentration gradient. Cleve Clin J Med 1995; 62:62–67.
56. Rector WG Jr, Reynolds TB. Superiority of the serum-ascites albumin difference over the ascites total protein concentration in separation of “transudative” and “exudative” ascites. Am J Med 1984; 77:83–85.
57. Runyon BA, Montano AA, Akriviadis EA, et al
. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis
of ascites. Ann Intern Med 1992; 117:215–220.
58. Sungaila I, Bartle WR, Walker SE, et al
. Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology 1992; 102:1680–1685.
59. Perez-Ayuso RM, Arroyo V, Planas R, et al
. Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin-aldosterone system. Gastroenterology 1983; 84(5 Pt 1):961–968.
60. Gatta A, Angeli P, Caregaro L, et al
. A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients. Hepatology 1991; 14:231–236.
61. Arroyo V, Gines P, Planas R. Treatment of ascites in cirrhosis. Diuretics, peritoneovenous shunt, and large-volume paracentesis. Gastroenterol Clin North Am 1992; 21:237–256.
62. Yachha SK, Khanna V. Ascites in childhood liver disease. Indian J Pediatr 2006; 73:819–824.
63. Shear L, Ching S, Gabuzda GJ. Compartmentalization of ascites and edema in patients with hepatic cirrhosis. N Engl J Med 1970; 282:1391–1396.
64. Planas R, Arroyo V, Rimola A, et al
. Acetylsalicylic acid suppresses the renal hemodynamic effect and reduces the diuretic action of furosemide in cirrhosis with ascites. Gastroenterology 1983; 84:247–252.
65. Gentilini P, Casini-Raggi V, Di Fiore G, et al
. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol 1999; 30:639–645.
66. Trotter J, Pieramici E, Everson GT. Chronic albumin infusions to achieve diuresis in patients with ascites who are not candidates for transjugular intrahepatic portosystemic shunt (TIPS). Dig Dis Sci 2005; 50:1356–1360.
67. Gines P, Arroyo V, Quintero E, et al
. Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. Gastroenterology 1987; 93:234–241.
68. Salerno F, Badalamenti S, Incerti P, et al
. Repeated paracentesis and i.v. albumin infusion to treat ‘tense’ ascites in cirrhotic patients. A safe alternative therapy. J Hepatol 1987; 5:102–108.
69. Simon DM, McCain JR, Bonkovsky HL, et al
. Effects of therapeutic paracentesis on systemic and hepatic hemodynamics and on renal and hormonal function. Hepatology 1987; 7:423–429.
70. Gines A, Fernandez-Esparrach G, Monescillo A, et al
. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology 1996; 111:1002–1010.
71. Gines P, Tito L, Arroyo V, et al
. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988; 94:1493–1502.
72. Luca A, Garcia-Pagan JC, Bosch J, et al
. Beneficial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis. Hepatology 1995; 22:753–758.
73. Forouzandeh B, Konicek F, Sheagren JN. Large-volume paracentesis in the treatment of cirrhotic patients with refractory ascites. The role of postparacentesis plasma volume expansion. J Clin Gastroenterol 1996; 22:207–210.
74. Lata J, Marecek Z, Fejfar T, et al
. The efficacy of terlipressin in comparison with albumin in the prevention of circulatory changes after the paracentesis of tense ascites—a randomized multicentric study. Hepatogastroenterology 2007; 54:1930–1933.
75. Baden HP, Morray JP. Drainage of tense ascites in children after cardiac surgery. J Cardiothorac Vasc Anesth 1995; 9:720–721.
76. Leveen HH, Christoudias G, Ip M, et al
. Peritoneo-venous shunting for ascites. Ann Surg 1974; 180:580–591.
77. Tobe SW, Morali GA, Greig PD, et al
. Peritoneovenous shunting restores atrial natriuretic factor responsiveness in refractory hepatic ascites. Gastroenterology 1993; 105:202–207.
78. Arroyo V, Gines P, Gerbes AL, et al
. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology 1996; 23:164–176.
79. Fulenwider JT, Smith RB 3rd, Redd SC, et al
. Peritoneovenous shunts. Lessons learned from an eight-year experience with 70 patients. Arch Surg 1984; 119:1133–1137.
80. Conn HO. Transjugular intrahepatic portal-systemic shunts: the state of the art. Hepatology 1993; 17:148–158.
81. Ochs A, Rossle M, Haag K, et al
. The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites. N Engl J Med 1995; 332:1192–1197.
82. Wong F, Sniderman K, Liu P, et al
. Transjugular intrahepatic portosystemic stent shunt: effects on hemodynamics and sodium homeostasis in cirrhosis and refractory ascites. Ann Intern Med 1995; 122:816–822.
83. Sanyal AJ, Genning C, Reddy KR, et al
. The North American Study for the Treatment of Refractory Ascites. Gastroenterology 2003; 124:634–641.
84. Heyman MB, LaBerge JM, Somberg KA, et al
. Transjugular intrahepatic portosystemic shunts (TIPS) in children. J Pediatr 1997; 131:914–919.
85. Lai KN, Leung JW, Vallance-Owen J. Dialytic ultrafiltration by hemofilter in treatment of patients with refractory ascites and renal insufficiency. Am J Gastroenterol 1987; 82:665–668.
86. Rossaro L, Graziotto A, Bonato S, et al
. Concentrated ascitic fluid reinfusion after cascade filtration in tense ascites. Dig Dis Sci 1993; 38:903–908.
87. Zaak D, Paquet KJ, Kuhn R. Prospective study comparing human albumin vs. reinfusion of ultrafiltrate-ascitic fluid after total paracentesis in cirrhotic patients with tense ascites. Z Gastroenterol 2001; 39:5–10.
88. Assadi FK, Gordon D, Kecskes SA, et al
. Treatment of refractory ascites by ultrafiltration-reinfusion of ascitic fluid peritoneally. J Pediatr 1985; 106:943–946.
89. Noble-Jamieson G, Jamieson N, Barnes ND. Ultrafiltration for intractable ascites after liver transplantation. Arch Dis Child 1991; 66:988–989.
90. Clark JH, Fitzgerald JF, Kleiman MB. Spontaneous bacterial peritonitis. J Pediatr 1984; 104:495–500.
91. Larcher VF, Manolaki N, Vegnente A, et al
. Spontaneous bacterial peritonitis in children with chronic liver disease: clinical features and etiologic factors. J Pediatr 1985; 106:907–912.
92. Haghighat M, Dehghani SM, Alborzi A, et al
. Organisms causing spontaneous bacterial peritonitis in children with liver disease and ascites in southern Iran. World J Gastroenterol 2006; 12:5890–5892.
93. Caruntu FA, Benea L. Spontaneous bacterial peritonitis: pathogenesis, diagnosis
, treatment. J Gastrointestin Liver Dis 2006; 15:51–56.
94. Parsi MA, Atreja A, Zein NN. Spontaneous bacterial peritonitis: recent data on incidence and treatment. Cleve Clin J Med 2004; 71:569–576.
95. Garcia-Tsao G. Current management
of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology 2001; 120:726–748.
96. Rolachon A, Cordier L, Bacq Y, et al
. Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial. Hepatology 1995; 22(4 Pt 1):1171–1174.
97. Krag A, Wiest R, Gluud LL. Fluoroquinolones in the primary prophylaxis of spontaneous bacterial peritonitis. Am J Gastroenterol 2010; 105:1444–1445.
98. Senzolo M, Cholongitas E, Burra P, et al
. Beta-blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. Liver Int 2009; 29:1189–1193.
99. Son M, Walsh CA, Baxi LV. Prenatal diagnosis
of urinary ascites in a fetus with meningomyelocele. Fetal Diagn Ther
100. Achiron R, Gindes L, Kivilevitch Z, et al
. Prenatal diagnosis
of congenital agenesis of the fetal portal venous system. Ultrasound Obstet Gynecol 2009; 34:643–652.
101. Suzumori N, Obayashi S, Hattori Y, et al
. Prenatal diagnosis
of persistent cloaca. Congenit Anom (Kyoto) 2009; 49:116–117.
102. Ben-Haroush A, Yogev Y, Levit O, et al
. Isolated fetal ascites caused by Wolman disease. Ultrasound Obstet Gynecol 2003; 21:297–298.
103. Patel MS, Callahan JW, Zhang S, et al
. Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up. Am J Med Genet 1999; 85:38–47.
104. Blaakaer J. Ultrasonic diagnosis
of fetal ascites and toxoplasmosis. Acta Obstet Gynecol Scand 1986; 65:653–654.
105. Maconochie IK, Chong S, Mieli-Vergani G, et al
. Fetal ascites: an unusual presentation of niemann-pick disease type C. Arch Dis Child 1989; 64(10 Spec No):1391–1393.
106. Manning DJ, Price WI, Pearse RG. Fetal ascites: an unusual presentation of Niemann-Pick disease type C. Arch Dis Child 1990; 65:335–336.
107. Singh S, Sills JH, Waffarn F. Interesting case presentation: neonatal hemochromatosis as a cause of ascites. J Perinatol 1990; 10:214–216.
108. McDuffie RS Jr, Bader T. Fetal meconium peritonitis after maternal hepatitis A. Am J Obstet Gynecol 1999; 180:1031–1032.
109. Ling PY, Fang SB, Liao WC, et al
. Fetal ascites and second trimester maternal hepatitis C virus infection. Taiwan J Obstet Gynecol 2006; 45:260–263.
110. Hertel J, Pedersen PV. Congenital ascites due to mesenteric vessel constriction caused by malrotation of the intestines. Acta Paediatr Scand 1979; 68:281–283.
111. Woodall DL, Birken GA, Williamson K, et al
. Isolated fetal-neonatal abdominal ascites: a sign of intrauterine intussusception. J Pediatr Surg 1987; 22:506–507.
112. Yang JI, Kim HS, Chang KH, et al
. Intrauterine intussusception presenting as fetal ascites at prenatal ultrasonography. Am J Perinatol 2004; 21:241–246.
113. Voss LM, Hadden W, Pease PW, et al
. Neonatal ascites due to congenital jejunal obstruction. Aust Paediatr J 1988; 24:260–261.
114. Adams MC, Ludlow J, Brock JW 3rd, et al
. Prenatal urinary ascites and persistent cloaca: risk factors for poor drainage of urine or meconium. J Urol 1998; 160(6 Pt 1):2179–2181.
115. Wax JR, Blakemore KJ, Baser I, et al
. Isolated fetal ascites detected by sonography: an unusual presentation of turner syndrome. Obstet Gynecol 1992; 79(5 Pt 2):862–863.
116. Greenberg F, Stein F, Gresik MV, et al
. The Perlman familial nephroblastomatosis syndrome. Am J Med Genet 1986; 24:101–110.
117. Akduman EI, Luisiri A, Launius GD. Fetal abuse: a cause of fetal ascites. AJR Am J Roentgenol 1997; 169:1035–1036.
118. Agrawala G, Predanic M, Perni SC, et al
. Isolated fetal ascites caused by bowel perforation due to colonic atresia. J Matern Fetal Neonatal Med 2005; 17:291–294.
119. Noreldeen SA, Hodgett SG, Venkat-Raman N. Midgut volvulus with hemorrhagic ascites: a rare cause of fetal anemia. Ultrasound Obstet Gynecol 2008; 31:352–354.
120. Heaton FC, Vaughan R. Intrauterine supraventricular tachycardia: cardioversion with maternal digoxin. Obstet Gynecol 1982; 60:749–752.
121. Griscom NT, Colodny AH, Rosenberg HK, et al
. Diagnostic aspects of neonatal ascites: report of 27 cases. AJR Am J Roentgenol 1977; 128:961–969.
122. Shweni PM, Kambaran SR, Ramdial K. Fetal ascites. A report of 6 cases. S Afr Med J 1984; 66:616–618.
123. Machin GA. Diseases causing fetal and neonatal ascites. Pediatr Pathol 1985; 4:195–211.
124. Ojala TH, Hornberger LK. Fetal heart failure. Front Biosci (Schol Ed) 2010; 2:891–906.
125. Keller M, Scholl-Buergi S, Sergi C, et al
. An unusual case of intrauterine symptomatic neonatal liver failure. Klin Padiatr 2008; 220:32–36.
126. Ghishan FK, Younoszai MK. Congenital hepatic fibrosis: a disease with diverse manifestations. Am J Gastroenterol 1981; 75:317–320.
127. Ghishan FK, Gray GF, Greene HL. Alpha 1-antitrypsin deficiency presenting with ascites and cirrhosis in the neonatal period. Gastroenterology 1983; 85:435–438.
128. Deckelbaum RJ, Weizman Z, Bauer CR. Ascites in the newborn associated with hepatitis. Clin Pediatr (Phila) 1980; 19:374–376.
129. Gilsanz V, Emons D, Hansmann M, et al
. Hydrothorax, ascites, and right diaphragmatic hernia. Radiology 1986; 158:243–246.
130. Jaffe R, Yunis EJ. Congenital Budd-Chiari syndrome. Pediatr Pathol 1983; 1:187–192.
131. Piersigilli F, Auriti C, Marcellini M, et al
. Isolated fetal ascites due to Budd-Chiari syndrome. Ultrasound Obstet Gynecol 2008; 31:222–223.
132. George JC, Cohen MD, Tarver RD, et al
. Ruptured cystic mesenchymal hamartoma: an unusual cause of neonatal ascites. Pediatr Radiol 1994; 24:304–305.
133. Puvabanditsin S, Garrow E, Vizarra R. An unusual cause of congenital ascites. Acta Paediatr 1995; 84:829–830.
134. Abdelbasit OB, Shaheed MM, Al-Omari MS, et al
. Gastric perforation. An unusual cause of ascites in a newborn baby. Saudi Med J 2000; 21:1085–1087.
135. Garrett RA, Franken EA Jr. Neonatal ascites: perirenal urinary extravasation with bladder outlet obstruction. J Urol 1969; 102:627–632.
136. Gurgoze MK, Yildirmaz S, Dogan Y, et al
. A rare cause of ascites in a newborn: posterior urethral valve. Pediatr Int 2010; 52:154–155.
137. El-Messidi A, Fleming NA. Congenital imperforate hymen and its life-threatening consequences in the neonatal period. J Pediatr Adolesc Gynecol 2006; 19:99–103.
138. Murphy D, Simmons M, Guiney EJ. Neonatal urinary ascites in the absence of urinary tract obstruction. J Pediatr Surg 1978; 13:529–531.
139. Morrell P, Coulthard MG, Hey EN. Neonatal urinary ascites. Arch Dis Child 1985; 60:676–678.
140. Gillan JE, Lowden JA, Gaskin K, et al
. Congenital ascites as a presenting sign of lysosomal storage disease. J Pediatr 1984; 104:225–231.
141. Vyas ID, Variend S, Dickson JA. Ruptured ovarian cyst as a cause of ascites in a newborn infant. Z Kinderchir 1984; 39:143–144.
142. Schultz RB, Kocoshis S. Cutis marmorata telangiectatica congenita and neonatal ascites. J Pediatr 1979; 95:157.
143. Woods AG, Woods CW. Hemophagocytic lymphohistiocytosis in the premature neonate: a case study. Adv Neonatal Care 2009; 9:274–278.
144. Martone WJ, Williams WW, Mortensen ML, et al
. Illness with fatalities in premature infants: association with an intravenous vitamin E preparation, E-Ferol. Pediatrics 1986; 78:591–600.
145. Purohit DM, Lakin CA, Othersen HB Jr. Neonatal pseudoascites: an unusual presentation of long tubular duplication of small bowel. J Pediatr Surg 1979; 14:193–194.
146. Akgur FM, Tanyel FC, Akhan O, et al
. The place of ultrasonographic examination in the initial evaluation of children sustaining blunt abdominal trauma. J Pediatr Surg 1993; 28:78–81.
147. Miller SF, Seibert JJ, Kinder DL, et al
. Use of ultrasound in the detection of occult bowel perforation in neonates. J Ultrasound Med 1993; 12:531–535.
148. Caine Y, Deckelbaum RJ, Weizman Z, et al
. Congenital hepatic fibrosis—unusual presentations. Arch Dis Child 1984; 59:1094–1096.
149. Cohen HA, Amir J, Frydman M, et al
. Infection with the hepatitis A virus associated with ascites in children. Am J Dis Child 1992; 146:1014–1016.
150. Gurkan F. Ascites and pleural effusion accompanying hepatitis A infection in a child. Clin Microbiol Infect 2000; 6:286–287.
151. Chau TN. Hepatitis E: a potential vaccine-preventable disease needs global concern. J Gastroenterol Hepatol 2008; 23:827–828.
152. Levy I, Shohat M, Levy Y, et al
. Recurrent ascites in an infant with perinatally acquired cytomegalovirus infection. Eur J Pediatr 1989; 148:531–532.
153. Rajwal S, Davison S, Wyatt J, et al
. Primary Epstein-Barr virus hepatitis complicated by ascites with Epstein-Barr virus reactivation during primary cytomegalovirus infection. J Pediatr Gastroenterol Nutr 2003; 37:87–90.
154. Klein MD, Philippart AI. Posttraumatic Budd-Chiari syndrome with late reversibility of hepatic venous obstruction. J Pediatr Surg 1979; 14:661–663.
155. Banani SA, Bahador A, Nezakatgoo N. Idiopathic perforation of the extrahepatic bile duct in infancy: pathogenesis, diagnosis
, and management
. J Pediatr Surg 1993; 28:950–952.
156. Stringel G, Mercer S. Idiopathic perforation of the biliary tract in infancy. J Pediatr Surg 1983; 18:546–550.
157. So SK, Lindahl JA, Sharp HL, et al
. Bile ascites during infancy: diagnosis
using disofenin tc 99m sequential scintiphotography. Pediatrics 1983; 71:402–405.
158. Chase GJ, O'Shea PA, Collins E, et al
. Protein-losing enteropathy in systemic lupus erythematosus. Hum Pathol 1982; 13:1053–1055.
159. Eldor J, Olsha O, Farkas A. Over-transfusion ascites. Resuscitation 1991; 21:289–291.
160. West GA, Berger MS, Geyer JR. Childhood optic pathway tumors associated with ascites following ventriculoperitoneal shunt placement. Pediatr Neurosurg
161. Diluna ML, Johnson MH, Bi WL, et al
. Sterile ascites from a ventriculoperitoneal shunt: a case report and review of the literature. Childs Nerv Syst 2006; 22:1187–1193.
162. Fernbach SK. Ascites produced by peritoneal seeding of neuroblastoma. Pediatr Radiol 1993; 23:569.
163. Mecrow IK, Miller V, Lendon M, et al
. Mesenteric fibromatosis presenting with ascites in childhood. J Pediatr Gastroenterol Nutr 1990; 11:118–122.
164. Berry PJ, Favara BE, Odom LF. Malignant peritoneal mesothelioma in a child. Pediatr Pathol 1986; 5:397–409.
165. Duncan KA, King SE, Ratcliffe JF. Intraperitoneal fluid collections following liver transplantation in a paediatric population. Clin Radiol 1995; 50:40–43.
166. Gane E, Langley P, Williams R. Massive ascitic fluid loss and coagulation disturbances after liver transplantation. Gastroenterology 1995; 109:1631–1638.
167. John TG, Plevris JN, Redhead DN, et al
. Massive ascitic fluid loss after liver transplantation. Gastroenterology 1996; 111:564–565.
168. Rossi TM, Cumella J, Baswell D, et al
. Ascites as a presenting sign of peritonitis in chronic granulomatous disease of childhood. Clin Pediatr (Phila) 1987; 26:544–545.
169. Richer O, Ulinski T, Lemelle I, et al
. Abdominal manifestations in childhood-onset systemic lupus erythematosus. Ann Rheum Dis 2007; 66:174–178.
170. Chu YT, Chiou SS. Painless massive ascites and hypoalbuminemia as the major manifestations of systemic lupus erythematosus. J Microbiol Immunol Infect 2006; 39:78–81.
171. Axelsson CK, Knudsen FU. Catheter-induced ascites—an unusual complication of parenteral feeding. Intensive Care Med 1978; 4:91–92.
172. Beshay VE, Beshay JE, Rosenberg AJ. Chylous ascites: a case of child abuse and an overview of a rare condition. J Pediatr Gastroenterol Nutr 2001; 32:487–489.
173. Novak RW, Boeckman CR. Pyloric duplication presenting with hemorrhagic ascites. Clin Pediatr (Phila) 1983; 22:386–388.
174. Granot E, Deckelbaum RJ. “Pseudoascites” as a presenting physical sign of celiac disease. Am J Gastroenterol 1983; 78:730–731.
175. Gyves-Ray K, Hernandez RJ, Hillemeier AC. Pseudoascites: unusual presentation of omental cyst. Pediatr Radiol 1990; 20:560–561.
176. Joshi N, Yadav S, Singh B, et al
. Omental cyst presenting as tubercular ascites. J Infect Dev Ctries 2010; 4:183–186.
177. Shafi SM, Malla MA, Reshi FA. Giant primary omental cyst mimicking a pseudoascites. Afr J Paediatr Surg 2009; 6:58–60.
178. Kaya M, Sakarya MH. Pseudoascites: report of three cases. Turk J Gastroenterol 2009; 20:224–227.
179. McCullagh M, Keen C, Dykes E. Cystic mesothelioma of the peritoneum: a rare cause of ‘ascites’ in children. J Pediatr Surg 1994; 29:1205–1207.