• The delayed passage of meconium may be the result of a mechanical or functional bowel obstruction.
  
• Virtually all infants, term and preterm, will have passed meconium by 48 h of age.
  
• The evaluation of any infant with delayed passage of meconium should begin with a thorough physical examination and history.
  
• For infants who are unstable, the infant must first be stabilized before the investigation begins as to the cause of delayed stooling.

• The evaluation of any infant with GI bleeding should begin with a thorough physical examination and history.
  
• For infants who have massive bleeding and are unstable, the infant must first be stabilized before the investigation begins.

• Serial hematocrits can be followed to track the severity of blood loss.
  
• Transfuse PRBCs as indicated (see Chapter 37 chapter for further information).
  
• Direct visualization with endoscopy may have to be undertaken to evaluate and possibly treat the cause of bleeding.

• The evaluation of any infant with GI bleeding should begin with a thorough physical exam and history.
  
• For infants who have massive bleeding and are unstable, the infant must first be stabilized before the investigation begins as to the cause of GI bleeding.

• Serial hematocrits can be followed to track the severity of blood loss.
  
• Transfuse PRBCs as indicated (see Chapter 37 chapter for further information).
  
• Direct visualization with endoscopy may have to be undertaken to evaluate and possibly treat the cause of bleeding.

• GER is defined as passage of gastric contents into the esophagus.
  
• GER is very common in term and preterm neonates.
  
• A very large majority of infants exhibit no signs of clinical compromise and hence do not warrant specific treatment (GER) vs. infants who experience feeding difficulties, poor weight gain, failure to thrive, etc as a direct result of reflux (GERD).
  
• For infants who have persistent “spitting up,” care must be taken to ensure that there is no true underlying pathology as a cause.
  
• Apnea and GER are common occurrences in premature infants, but studies have shown no temporal relationship between the two.

Risk Factors

• Congenital diaphragmatic hernia
  
• Esophageal atresia repair
  
• Gastroschisis
  
• Omphalocele
  
• Short bowel syndrome (SBS)
  
• Bronchopulmonary dysplasia
  
• Neurologic deficits

Differential Diagnosis

• Differential diagnosis for GER should include:
  
  
  
  • GI tract anatomic abnormalities: Esophageal webs or stenosis, duodenal web or stenosis, malrotation, gastric outlet obstruction
    
  • Inborn errors of metabolism
    
  • Renal dysfunction
    
  • Neurologic deficits
    
  • Bronchopulmonary dysplasia

Clinical Presentation

• Dysphagia
  
• Odynophagia
  
• Arching of the back with feeds
  
• Irritability
  
• Failure to thrive
  
• Hematemesis

Management

• Initial management should be aimed at nonpharmacologic maneuvers (eg, GERD precautions):
  
  
  
  • Positioning of the infant with the head of the bed elevated.
    
  • Changing the rate of feeding (slow rate of bolus feeds to 60-90 minutes, feed less volume more frequently).
    
  • Consider thickening feeds with commercially available thickeners.
    
  • Discontinuation of caffeine for apnea of prematurity may ameliorate symptoms of GER.
  
  
• Pharmacologic therapy can be used if the above measures fail, but data on efficacy in this patient population are very limited.
  
  
  
  • Use of H2 blockers or PPIs to decrease gastric acid release have been reported with mixed results
    
  • Use of promotility agents is not advocated because of potentially serious side effects (eg, Parkinsonian reaction and tardive dyskinesia with the use of metoclopramide, may not be reversible).
    
  • Infants with severe symptoms as above have GERD.
    
  • Infants with GERD often have true esophagitis or gastritis and have been shown to benefit from gastric acid reduction.
  
  
• Surgical intervention with fundoplication may be considered for infants who fail to respond to pharmacologic therapy and continue to display signs of GERD.

• 25%–50% of term neonates and a larger percentage of preterm neonates will develop clinical jaundice.
  
• Clinical exam is not a reliable tool to estimate serum bilirubin level.
  
• The major source of bilirubin is from the breakdown of hemoglobin in the RES.
  
• Bilirubin is also produced from other heme-containing proteins in the peripheral tissues (eg, cytochromes, myoglobin)
  
• Bilirubin, a nonpolar, water-insoluble molecule, is transported to the liver cells bound to serum albumin.
  
  
  
  • The bound form of bilirubin is unable to cross into the CNS.
    
  • Any factors that increase the free fraction (unbound form) of bilirubin potentially increase the amount of bilirubin that is able to cross into the CNS (ie, hypoalbuminemia, drugs, acidosis).
  
  
• On arrival to the hepatocyte, bilirubin crosses the plasma membrane bound to the cytoplasmic protein ligandin → transported to the endoplasmic reticulum for conjugation by the enzyme UDPG-T. Inherited deficiencies or polymorphisms of the conjugation enzymes can predispose an infant to developing severe hyperbilirubinemia.
  
• Conjugated bilirubin is excreted via the biliary tree into the GI tract, and eventually passed in the stools. A small fraction of conjugated bilirubin is converted back to unconjugated bilirubin via the action of β-glucuronidase, reabsorbed, and sent to the liver for re-conjugation (process of enterohepatic recirculation)
  
• The majority of fetal unconjugated bilirubin is cleared via the placenta to the maternal circulation.

Physiologic Unconjugated Hyperbilirubinemia

• Generally, whereas bilirubin peaks in term neonates at 3–4 d, it peaks at 4–5 d in preterm neonates.
  
• Physiologic hyperbilirubinemia occurs for several reasons:
  
  
  
  • Increased bilirubin production caused by decreased RBC survival in the neonate compared with adults
    
  • Increased enterohepatic recirculation caused by ↑ levels of β-glucuronidase and decreased gut motility
    
  • Decreased hepatic ligandin leading to decreased bilirubin uptake in the liver
    
  • Decreased UDPG-T activity leading to decreased conjugation of bilirubin
    
  • Decreased hepatic excretion