67: No Stool in 48 Hours

The nurse reports that no stool has been passed in a premature infant that is 36 hours old. Ninety-nine percent of term infants, 100% of post-term infants, and 76% of premature infants (majority are >32 weeks) pass a stool in the first 24 hours of life. The majority of preterm infants have delayed passage (37% in 24 hours, 32% beyond 48 hours, and 99% by 9 days in one study). The time when the first meconium stool passes has been used as a marker for normal gastrointestinal functioning, and a delay can occur because of gestational immaturity, a severe illness, a bowel obstruction, or other cause. Delayed meconium passage can be a predisposing factor for bowel perforation. Males pass stool later than females, and type of feeding does not predict the time to the first stool.

1. Has a stool been passed since birth? If a stool has been passed since birth but not in the last 48 hours, constipation may be the cause. In small bowel obstruction, meconium can be passed and then a decrease or no stools occur. If a stool has never been passed, imperforate anus or some degree of lower intestinal obstruction may be present. Table 67–1 shows the time after birth at which the first stool is typically passed.

2. What is the gestational age and birthweight of the infant? An inverse relationship between gestational age, birthweight, and meconium passage exists. Premature and very low birthweight (VLBW) infants commonly have a delayed passage of stool because of immaturity of interstitial cells of the colon, increased viscosity of meconium (preemies have lack of water in stool), and lack of triggering effect of enteral feeds on gut hormones when the patient is maintained NPO. Studies show the older the gestational age, the shorter time to the first stool. Delayed meconium passage can be as high as 80% in VLBW infants. Remember that failure of a full-term or post-term infant to pass meconium within 24 hours may signify an intestinal obstruction. In preterm infants it may not.

3. Were maternal drugs used that could cause a paralytic ileus with delayed passage of stool? Magnesium sulfate, which is used to slow the premature onset of labor, may cause paralytic ileus. Narcotics for pain control or use of heroin by the mother may also cause delayed passage of stool in the neonate. Antenatal betamethasone exposure leads to earlier stool passage, and antenatal exposure to magnesium sulfate has conflicting results—some studies show it does not affect the timing of the first stool in premature infants and others state it was associated with delayed stool passage.

4. Are there any other congenital abnormalities and associated syndromes? Hirschsprung disease is associated with trisomy 21, neurofibromatosis, Waardenburg syndrome, multiple endocrine neoplasia (MEN) type 2, central hypoventilation syndrome, and cardiac septal defects.

1. Constipation. This is just in infants who have already passed a stool and then fail to pass one. Infants have a mean of 4 stools per day during the first week of life; this gradually decreases to a mean average of 1.7 per day at age 2 years. Some breast-fed infants do not have stools for several days.

2. Bowel obstruction. Infants with distal small bowel (ileum) or colonic obstruction can present with abdominal distension and delayed passage of meconium. Small bowel obstruction usually presents with bilious vomiting with or without abdominal distension, and meconium can be passed, but it usually progresses to a decrease or no stools. Large bowel obstruction usually presents with abdominal distension and no stools.

   1. Large bowel obstruction

      1. Meconium plug syndrome. An obstruction in the lower colon and rectum caused by meconium. It is a transient form of distal colonic or rectal obstruction. Incidence is 1 in 500–1000 newborns. (Note: A rectal biopsy should be considered in all these patients because they have an increased incidence [10–15%] of Hirschsprung disease.) Meconium plug syndrome is more common in infants of diabetic mothers (small left colon syndrome) and in premature infants (microcolon of prematurity).

      2. Small left colon syndrome. A functional distal bowel obstruction in which the plug extends to the splenic flexure, caused by transient dysmotility in the descending colon. Usually seen in term infants. Approximately 50% have a history of maternal diabetes, and most don't pass meconium in the first 24 hours of life. The others have sepsis, hypoglycemia, hypothyroidism, or increased magnesium. Microcolon of prematurity is the preterm equivalent of small left colon syndrome. Functional abnormality with failure of the small bowel contents to pass into the colon in utero. The majority of mothers had toxemia and magnesium sulfate.

      3. Hirschsprung disease (congenital aganglionic megacolon). Accounts for ∽15% of infants who have delayed passage of stool. It occurs in 1 in 4000 live births. A functional obstruction is caused by aganglionosis of cells in Meissner and Auerbach plexus in the rectum and variable amounts of the distal colon. The affected segment of colon and rectum are aperistaltic. Typically the infant is full term and presents with delayed passage of meconium. Sixty to ninety percent of infants with Hirschsprung disease fail to pass meconium in the first 24–48 hours of life. It has a sex-dependent penetrance (4 males to 1 female) and 8% of patients have Down syndrome. It is more common in white males.

      4. Anorectal malformations (1 in 4000–8000 infants) such as imperforate anus (or anal atresia), which can be high or low type with a fistula or anal stenosis. An infant with an imperforate anus may pass meconium if a fistula exists. There are a high percentage of associated anomalies with anal atresia (70%). One example is the VATER/VACTERL (vertebral defects, anal atresia, tracheoesophageal fistula, and radial or renal dysplasia/vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal defects and radial upper limb hypoplasia) association. Anal stenosis can occur and may present with a small, tight anus, sometimes with a dot of meconium present.

   2. Small bowel obstruction

      1. Meconium ileus. Occurs when meconium becomes obstructed in the terminal ileum. It can present with a failure to pass meconium. It occurs in 15% of newborns with cystic fibrosis (CF); 90% of patients with meconium ileum have CF and thus should be tested for it. It is the most common presentation of CF in the neonatal period.

      2. Intestinal atresias. Atresias most commonly occur in the ileum, followed by the duodenum, jejunum, and then colon. Bilious emesis, abdominal distension, and failure to pass meconium are seen; jaundice is possible.

      3. Other small bowel obstructions. (Duodenal atresia, malrotation and volvulus, and meconium peritonitis.) Usually meconium is passed and then they progress to a decrease or no stools.

   3. Adhesions. Postoperatively, such as after surgery for necrotizing enterocolitis (NEC), there is a 30% chance of having adhesions.

   4. Rare causes. Colonic stenosis/atresia: The colon is the least common site of stenosis and atresia. See dilated proximal intestine on radiograph. Hypoganglionosis: a reduced number of ganglion cells; presents with symptoms similar to Hirschsprung disease and can occur with Hirschsprung disease. Neuronal intestinal dysplasia type A is hypoplasia or aplasia of the sympathetic innervation of the myenteric plexus and mucosa, with inflammation of the mucosa; it presents with symptoms similar to Hirschsprung disease. Megacystis-microcolon intestinal hypoperistalsis syndrome (Berdon syndrome) has urinary retention, dilated small bowel, microcolon, megacystis (giant bladder), and hydronephrosis. Pathology reveals that ganglion cells are present.

3. Other causes/associations

   1. Prematurity/VLBW infants. (See Section II.B.) Delayed passage of meconium is common. Immature colon and delayed first feeding with patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), mechanical ventilation, and uteroplacental insufficiency is associated with delayed passage in VLBW infants. These infants usually do not have abdominal distension or bilious nasogastric aspirates.

   2. Infection. Sepsis is the most common infection causing delayed passage. Other infections that can result in intestinal dysfunction include pneumonia/enterovirus infection/omphalitis/peritonitis.

   3. Respiratory distress syndrome. Infants with RDS can have delayed gastric emptying which can cause dysmotility of the intestine.

   4. Electrolyte abnormalities. Hypokalemia, hyponatremia, hypercalcemia, and hypermagnesemia. Fetal hypoglycemia can also impair neonatal intestinal motility.

   5. Maternal medications. Magnesium sulfate, ganglionic blocking agents or illicit drugs (opiates, heroin), neuroleptics, antidepressants.

   6. Infant medications. Theophylline, opiates, narcotic analgesic therapy.

   7. Hypothyroidism (most common). Other endocrinopathies—adrenal insufficiency, hyperparathyroidism, adrenal bleeding.

   8. Ileus. This can cause a delayed passage of stool.

   9. Idiopathic.

   10. Other less common causes. Congestive heart failure, hyperbilirubinemia, renal vein thrombosis, hypovolemia, PDA, embolism/thrombosis.

1. Prenatal history may reveal abnormalities on the fetal ultrasound. Polyhydramnios can be seen in jejuno-ileal atresia. Extraluminal meconium calcifications can be seen with meconium ileus. The classic double bubble of duodenal atresia can be seen on prenatal ultrasound.

2. Physical examination. Special attention to the abdomen is important. First, inspect the anus (eg, 5th digit probe, rectal thermometer, or soft feeding tube). If patency is in question, consult with surgery on the best way to further evaluate. Check for abdominal distention or rigidity, bowel sounds, and evidence of a mass. A rectal examination will also determine whether muscle tone is adequate, and it may reveal hardened stool in the rectum. Infants with Hirschsprung disease typically have a distended abdomen (63–91% of neonates) and bilious vomiting (19–37%).

3. Laboratory findings

   1. Complete blood count (CBC) with differential and blood culture to rule out sepsis. A urine culture under sterile conditions should also be done.

   2. Urinary drug screening on both mother and infant to detect maternal use of narcotics.

4. Imaging and other studies

   1. Plain film abdominal radiographs. A flat plate and upright film of the abdomen should be obtained to look for ileus or bowel obstruction in any infant who has not passed a stool within 48 hours of birth. The radiograph does not tell if it is small or large bowel obstruction. Typically, dilated loops of bowel, air-fluid levels, and no air in the rectum will be seen. With Hirschsprung disease or meconium plug, distention of the colon with multiple air-fluid levels is seen.

      1. Hirschsprung disease. Gas and stool in the colon.

      2. Meconium plug. Distension of the small and large intestine, usually no air-fluid levels are seen. Distal obstruction with absence of air in the rectum can be seen.

      3. Meconium ileus. Distended bowel, some air-fluid levels. Right lower abdomen: meconium and air with ground glass appearance.

      4. Small left colon syndrome. Dilated intestinal loops and air-fluid levels.

   2. Contrast enema. Abdominal radiographs with contrast enema should be obtained in all cases of delayed passage of stool if the patient is symptomatic. These will help define the disease process and may be therapeutic. Microcolon is a radiologic finding of an abnormally small caliber of colon and usually means distal ileal obstruction: ileal atresia, colonic atresia, colon aganglionosis, volvulus, duplication.

      1. Hirschsprung disease. A transition zone is seen with marked dilatation, presence of barium after 24 hours.

      2. Meconium plug syndrome. The contrast enema is a diagnostic test for meconium plug syndrome because it shows the outline of meconium and meconium plugs.

      3. Meconium ileus. Microcolon is seen.

      4. Meconium obstruction of prematurity. Meconium plugs are seen in a small microcolon, with distal ileum obstruction. Can see distal ileum impacted with meconium.

      5. Small left colon syndrome. Short colon with lack of tortuosity. A transition zone can be seen.

   3. Anorectal manometry (ARM). Using an anorectal micromanometric sleeve assembly, it records changes in anal pressure during and after rectal distension. If ganglion cells are present, a fall in anal pressure is seen. In Hirschsprung disease there is absent rectosphincteric reflex. Use of this test is difficult to perform and time-consuming, and requires patience in neonates. Serial manometry may prevent the need for rectal biopsy. Premature infants after 30 weeks' gestation have normal anorectal pressures and have a normal anorectal reflex.

   4. Full-thickness rectal biopsy/renal suction biopsy. Either by suction anal biopsy or transanal wedge resection is the gold standard for diagnosis of Hirschsprung disease. Histology demonstrates the absence of ganglion cells and presence of acetyl cholinesterase–positive hypertrophic nerve fibers.

   5. Rectosigmoid index (RSI). The diameter of the rectosigmoid colon and can be used to help diagnose Hirschsprung disease.

   6. Serum proteins. Three specific protein markers have been identified for Hirschsprung disease, which will allow for early screening and diagnosis, but are not in use yet.

1. Rule out and treat any underlying etiologies such as electrolyte abnormalities, infection, hypothyroidism, respiratory distress syndrome, medications in the mother or infant, and others.

2. Premature infants. Need to rule out pathologic cause versus normal delayed passage of stool. As meconium passage can be delayed in infants who are premature and have a low birthweight, delayed passage of stool does not always predict gastrointestinal (GI) disease. It is best to only do a diagnostic workup for intestinal obstruction in those premature infants with other signs of GI disease (eg, progressive abdominal distension and vomiting).

3. Term infants with delayed passage need to be evaluated earlier as failure to pass meconium in a term infant is highly suspicious for intestinal obstruction.

4. Specific treatment plans

   1. Constipation

      1. Digital rectal stimulation is the first step.

      2. Glycerin suppositories can be used if digital rectal stimulation is unsuccessful. Enemas are not recommended. Mineral oil or stimulant laxatives are also not recommended. Saline irrigation is used in some NICUs.

   2. Anorectal abnormality. Imperforate anus.

      1. Obtain immediate pediatric surgical consultation.

      2. Insert a double-lumen nasogastric (NG) tube for decompression.

      3. Look for other congenital anomalies. Genitourinary tract abnormalities are frequently seen with imperforate anus.

   3. Bowel obstruction

      1. Meconium plug

         1. Contrast enema. Performed using an agent such as Omnipaque 240 to verify meconium plug. In infants with this problem, the study usually reveals a normal-sized colon with filling defects.

         2. If meconium plug is verified by contrast enema. Repeated water-soluble enemas are usually given every 4–6 hours.

         3. Acetylcysteine (Mucomyst) enema. If water-soluble enemas are ineffective, a dilute 4% solution of acetylcysteine and water can be used as an enema to break down the meconium so the plug can be passed.

         4. If normal stooling occurs. Monitor closely.

         5. If an abnormal pattern of stooling recurs. Further workup (eg, rectal biopsy) is necessary to rule out Hirschsprung disease, which ultimately will be diagnosed in half of these patients.

      2. Meconium ileus

         1. Contrast enema may reveal microcolon. Evidence of perforation, volvulus, or atresia may also be seen.

         2. Obstruction can be treated with Mucomyst enemas (see Section V.D.3a.iii). Adequate fluid and electrolyte replacement must be given.

         3. Antegrade agents in NG tube (N-acetylcysteine [NAC] or Gastrografin) have been entertained by some, but there is a potential for side effects and a lack of studies.

         4. Operative management may be necessary in patients not relieved by enemas with passage of meconium within several hours.

      3. Hirschsprung disease

         1. Fluid resuscitation, rectal irrigation, and antibiotics are important to initially treat the enterocolitis and decrease the risk of mortality.

         2. Initial radiograph shows marked gaseous distension of colon with undilated rectum.

         3. Contrast enema usually shows a distal narrowed, aganglionic segment leading to a dilated proximal segment. A transition zone, irregular colonic contractions, irregular mucosa, and an abnormal rectosigmoid index (RSI) all suggest Hirschsprung disease.

         4. Rectal biopsy, the definitive diagnosis, is performed to confirm aganglionosis.

         5. Surgical repair with a 2- or 3-stage procedure. Colostomy is usually indicated once the diagnosis is confirmed.

      4. Adhesions. Surgery is usually necessary to lyse the adhesions if a trial of nasogastric decompression fails.

      5. Incarcerated hernia. This is a surgical emergency.

      6. Malrotation

         1. Contrast enema reveals an abnormally placed cecum.

         2. Surgical correction is necessary.

      7. Volvulus

         1. Contrast enema reveals obstruction at the midtransverse colon.

         2. Surgery should be an immediate intervention.

      8. Intussusception. Hydrostatic reduction is attempted. If unsuccessful, surgery with operative reduction or resection is done.

      9. Duodenal atresia. Decompression with nasogastric suction and surgery.

      10. Small left colon syndrome. Contrast enema is done and is usually diagnostic and therapeutic. Surgery is indicated if the obstruction is recurrent or if there is a perforation.

      11. Microcolon of prematurity. Contrast enema examination, close observation of infants with possibility of surgical intervention if there are complications.

      12. Meconium obstruction of prematurity. Diluted contrast enema is the gold standard for diagnosis and treatment. Surgical management may be necessary if spontaneous intestinal perforation occurs or worsening of symptoms.

      13. Ileus caused by sepsis

          1. Broad-spectrum antibiotics are initiated after a sepsis workup is performed (see Chapter 130). Intravenous ampicillin and gentamicin are usually recommended. Vancomycin may be substituted for ampicillin if staphylococcal infection is suspected (for dosages, see Chapter 148).

          2. A nasogastric tube should be placed to decompress the bowel. The infant should not be fed enterally.

      14. Ileus caused by NEC. See Chapter 113.

      15. Ileus caused by hypokalemia

          1. Treat underlying metabolic abnormalities. Correct potassium levels if low (see Chapter 63).

          2. Place a nasogastric tube to rest the bowel.

      16. Prematurity. Conservative treatment is usually recommended in infants who are not vomiting but have progressive abdominal distention, even if microcolon is seen. Treatment consists of a low osmolality water-soluble contrast enema for passage of the stool. Consult a pediatric radiologist for appropriate contrast enema to be used.

      17. Hypothyroidism. If the serum T₄ and TSH levels confirm the presence of hypothyroidism, thyroid replacement therapy is indicated. Consult with an endocrinologist before starting therapy. See Chapter 140.