Congenital visceral malformations

Congenital visceral malformations develop during organogenesis, which occurs in the first 8 weeks after conception (embryonal period). Common malformations include anorectal malformation, omphalocele, gastroschisis, and biliary atresia. They may occur on their own or together with other malformations and syndromes. An anorectal malformation is characterized by an absent anal opening and failure to pass meconium, which may lead to ileus or the formation of fistulas. An omphalocele is often associated with trisomies and manifests with the herniation of abdominal viscera through the abdominal wall into a hernia sac. In cases of gastroschisis, by contrast, herniated parts of the intestine are not covered by a sac, but exposed. Bladder exstrophy is a rare condition caused by an embryonic malformation resulting in failed closure of the anterior abdominal wall and an exposed urinary bladder. All four conditions are clinical diagnoses and require surgery to prevent infections and further complications. In extrahepatic biliary atresia, the infant presents with prolonged neonatal jaundice, acholic stools, dark urine, and hepatomegaly. Conjugated hyperbilirubinemia and abnormalities on ultrasonography provide valuable clues for diagnosis. If extrahepatic biliary atresia remains undetected or surgery is delayed, the infant may die within the first two years of life, usually as a result of biliary liver cirrhosis.

• Definition: a congenital defect that can occur at any point along the gastrointestinal tract leading to complete (atresia) or incomplete (stenosis) occlusion of the affected lumen
• Epidemiology: approx. 7:10,000 live births ^[1]
• Etiology
  • Often associated with chromosomal anomalies
  • Gastrointestinal atresia is the result of varying mechanisms that lead to a disruption of normal bowel development.
• Clinical features
  • Intrauterine: polyhydramnios
  • Postpartum: signs of intestinal obstruction
    • Abdominal distention
    • Bilious vomiting
    • Failed or delayed meconium passage
• Diagnosis
  • Prenatal ultrasound
  • X-ray of the abdomen
  • Evaluation for associated anomalies (e.g., physical examination; echocardiogram; ultrasound of the brain, abdomen, and spine; newborn screening results)
• Treatment
  • Preoperative: placement of a gastric tube for suction, parenteral nutrition, and fluid replacement
  • Surgery: bypass of the atresia or stenosis

• Definitions
  • Duodenal atresia is the complete occlusion or absence of the duodenal lumen.
  • Duodenal stenosis is an incomplete obstruction caused by narrowing of the lumen.
• Epidemiology
  • Around 1:5000–10,000 live births ^[2]
  • Approx. 50% of cases are associated with further anomalies, e.g., bile duct and VACTERL association. ^[3]
  • 20–25% of cases are associated with chromosomal abnormalities, especially Down syndrome. ^[2]
• Pathophysiology
  • Duodenal atresia occurs when recanalization of the closed duodenum during the embryonic period fails or is only partial (usually between the 8^th and 10^th weeks of gestation).
  • Since the development of the duodenum is connected to the growth of the pancreas and the hepatobiliary system, duodenal atresia is also commonly associated with anomalies of these organs. ^[2]
• Clinical features
  • Intrauterine: polyhydramnios ^[4]
  • Postpartum
    • Vomiting that is typically bilious if the stenosis is distal to the major duodenal papilla ^[4]
      • Atresia or high-grade stenosis: vomiting a few hours after birth ^[2]
      • Mild stenosis: vomiting after a few days
    • Distended upper abdomen; and scaphoid lower abdomen ^[4]
    • Delayed meconium passage
• Diagnostics
  • Prenatal: ultrasound ^[5]
    • Double bubble sign
      • Air and fluid build up proximal to the obstruction and are separated by the pyloric sphincter, which resembles two bubbles on imaging, one in the stomach and one in the duodenum.
      • If present, test for associated anomalies (e.g., karyotyping, microarray) ^[6][7]
      • Associated anomalies may also be investigated with the following methods:
        • Physical examination
        • Ultrasound of the abdomen and kidneys
        • Echocardiography
        • X-ray of the thorax
        • X-ray, ultrasound, and/or MRI of the spine
    • Polyhydramnios
    • Dilation of the stomach and duodenum (proximal to the obstruction) is common.
  • Postnatal: x-ray of the abdomen ; ^[4]
    • Gasless distal bowel
    • Double bubble sign
• Differential diagnoses
  • Jejunal atresia
  • Ileal atresia
  • Hirschsprung disease
  • Meconium ileus
  • Malrotation with volvulus
• Treatment
  • Preoperative management
    • Parenteral nutrition via a central catheter shortly after birth
    • Fluid replacement and restoration of the electrolyte balance
    • Gastric decompression
  • Surgery: bypass of the atresia or stenosis
    • The choice of procedure depends on the anatomical findings and associated anomalies.
    • The most common procedures are duodenoduodenostomy or duodenojejunostomy with a proximal transverse-to-distal longitudinal (diamond-shaped) anastomosis.
• Prognosis: If diagnosis and treatment are quickly established, the survival rate of isolated duodenal atresia (without further anomalies) is 95%.

References:^[3]

• Definition: absence of the jejunal or ileal lumen
• Epidemiology: less common than duodenal atresia
• Etiology
  • Associated with cystic fibrosis
  • Risk factors: maternal smoking and/or use of vasoconstrictive agents (e.g., cocaine, MDMA) during pregnancy
• Pathophysiology: vascular accident in utero (usually a disruption of superior mesenteric artery) → ischemic necrosis and reabsorption of the jejunum or ileum → discontinuous bowel → obstruction
• Clinical features: similar to duodenal atresia
  • Polyhydramnios (intrauterine)
  • Bilious vomiting and upper abdominal distention (postpartum)
• Diagnostics: Abdominal x-ray shows a triple bubble sign (dilated small bowel loops and air-fluid levels; the three bubbles correlate with the distended stomach, duodenum, and jejunum proximal to the obstruction) and gasless colon.
• Treatment: Surgical correction with bypass of the occluded part of the bowel is always required.

Colonic atresia

• Definition: a congenital anomaly of the colon that results in either stenosis or a complete absence of a colonic segment
• Epidemiology: rare; accounts for approx. 7% of bowel atresias ^[8]
• Pathophysiology: disruption of vascular supply or a mechanical event (e.g., intestinal volvulus) → ischemic necrosis and reabsorption of the colon → distal microcolon or absence of the distal colonic segment
• Clinical features: Symptoms of intestinal obstruction may appear later than with more proximal lesions.
  • Abdominal distention
  • Bilious vomiting
  • Delayed or failed meconium passage
• Diagnosis
  • Clinical diagnosis
  • X-ray: dilated proximal segment and absence of gas in the rectum
• Treatment: primary anastomosis surgery or temporary colostomy

Anorectal malformation (anal atresia)

• Definition: sporadically occurring malformation of the rectum with absent anal opening
• Epidemiology ^[9]
  • Approx. 1:5,000 live births in the US
  • Sex: ♂ = ♀
• Etiology: associated with a number of conditions
  • Mesodermal defects (e.g., VACTERL association)
  • Down syndrome
  • Maternal diabetes
  • Other malformations (e.g., vaginal or uterine anomalies, renal anomalies, spinal cord or cardiovascular malformations)
• Pathophysiology: failure of the urorectal septum to descend caudally to the cloacal membrane
• Clinical features ^[10][11][12]
  • Absence of anal opening
  • Thin anal membrane in place of anal opening through which meconium is visible
  • Obstipation, ileus
  • Fistulas that complicate defecation (e.g., rectovestibular, rectourethral, rectovaginal)
  • Small or missing anal dimple
  • In some cases, bucket-handle malformation
  • Flat bottom (absent or poorly developed midline groove between buttocks)
• Diagnostics
  • Clinical diagnosis
  • Lateral pelvic radiography or invertogram to determine position of the rectal pouch
  • Investigation of additional malformations (e.g., spinal ultrasonography, sacral x-ray)
  • Fistula screening
    • Examination of the genital area and the urethra (e.g., abdominal ultrasound)
    • Urinalysis: meconium detectable in case of a rectourinary fistula
    • Augmented-pressure distal colostography to assess for fistulas
• Treatment
  • IV hydration, no oral feeding
  • Anal reconstructive surgery (primary anoplasty) or temporary colostomy in more complex malformations

• Definition
  • Ventral wall defect that results in congenital herniation of abdominal viscera through the abdominal wall at the umbilicus.
  • The hernia sac is covered by the amniotic membrane and the peritoneum.
• Epidemiology
  • Approx. 1:4,000 live births in the US
  • Sex: ♂ > ♀
• Etiology
  • Frequently observed in trisomies (trisomy 21, trisomy 18, and trisomy 13) and Beckwith-Wiedemann syndrome
  • Often associated with additional malformations (e.g., cardiac, gastrointestinal, genitourinary, and neural tube defects)
• Pathophysiology: persistent herniation of the midgut derivatives due to impaired closure of the lateral umbilical folds
• Clinical features
  • Most commonly affects premature infants
  • Umbilical hernia sac (may contain intestine, liver, and gall bladder)
  • Features of associated conditions
• Diagnosis ^[13]
  • Clinical diagnosis at birth
  • Can be detected prenatally
    • Ultrasonography: polyhydramnios in utero
    • ↑ Maternal serum alpha-fetoprotein (MSAFP)
• Treatment
  • Cesarean delivery to prevent rupture of the sac of large omphalocele; especially if the liver is contained in the hernia sac
  • Vaginal delivery is possible in cases with small omphalocele
  • Wrapping of the hernia sac with sterile saline dressings covered with plastic wrap
  • Nasogastric suction
  • IV fluids to avoid abdominal distention and to compensate fluid loss
  • Surgery (within the first 24 hours of life)
    • Usually primary abdominal wall closure
    • Alternatively, secondary closure following:
      • Staged silo repair
      • Skin graft or dermal patch
• Complications
  • Rupture of hernia sac with infection (peritonitis)
  • Secondary intestinal wall atresia as a result of injury
• Prognosis
  • Dependent on the size of the defect and birth weight
  • Survival rate over 90% in the absence of additional malformations

• Definition: a ventral wall defect that results in paraumbilical herniation of the intestine through the abdominal wall without formation of a hernia sac
• Epidemiology: approx. 1:2,000 live births in the US
• Pathophysiology
  • Failed formation of a sufficiently large peritoneal cavity → growing bowel leads to rupture of the anterior abdominal wall at its weakest point → herniation of bowel sections
  • Because the malformation occurs relatively late in development, additional anomalies are rarely present (in contrast to omphalocele)
• Clinical features
  • Protrusion of intestinal content usually on the right side of the umbilicus
  • The intestine is not contained in a hernia sac and appears edematous, erythematous, and dull.
  • Shortened bowel
  • Malabsorption caused by mucosal damage
  • Peritonitis
  • Seen especially in premature infants and associated with cryptorchidism and gastrointestinal stenoses or atresia
• Diagnosis
  • Usually clinical diagnosis
  • Can be detected prenatally (see “Diagnosis” of omphalocele above)
• Treatment
  • Cesarean delivery has no advantage over vaginal delivery.
  • See “Treatment” of omphalocele above
  • Emergency surgery
    • Primary abdominal wall closure (success rate of 70%)
    • Alternative: staged silo repair (see “Treatment” of omphalocele above)
• Prognosis
  • Survival rates are generally high (> 90%).
  • Short bowel syndrome is a common complication.
  • 20% of children develop necrotizing enterocolitis. ^[14]

Unlike in cases of omphalocele, gastroschisis does not manifest with a hernia sac.

Omphalocele keeps your gut O-sealed (covered with peritoneum), but in Gastroschisis, the Gut freezes (herniates through the abdominal wall without being covered by peritoneum).

Bladder exstrophy

• Definition: embryological defect of ventral abdominal wall due to an overdeveloped cloacal membrane
• Epidemiology ^[15]
  • Prevalence is 3 per 100,000 live births
  • More common in males
• Clinical features
  • Bladder and urethra herniated through a defect in the abdominal wall
  • Incontinence
  • Genital abnormalities
    • Males: shortened penis with dorsal penile curvature and epispadias
    • Females: bifid clitoris with labia separated anteriorly and epispadias
  • Widely separated pubic symphysis
  • Associated malformations
    • Omphalocele
    • Often a low set umbilicus, indirect inguinal hernia , and anteriorly displaced anus
    • Possibly hip dysplasia, bicornuate uterus, cardiac dysplasia
• Diagnostics
  • Largely a clinical diagnosis
  • Prenatal ultrasound with inability to visualize bladder, lower abdominal wall mass, low set umbilical cord, abnormal genitalia, and pubic bone diastasis
• Treatment
  • Staged or primary surgical repair and reconstruction
    • Timing depends on surgeon preference and infant's anatomy: within first 2–3 days of life (immediate) or between 6–12 weeks of age (delayed)
  • Iliac osteotomy may be required if the diastasis is extreme or after first 2–3 days of life as pelvis becomes less malleable
• Complications
  • Persistent incontinence
  • Urinary tract infections (UTIs), epididymitis
  • Bladder stones, fistulas
  • Vesicoureteral reflux
  • Vaginal and rectal prolapse
  • Possible infertility in males
  • Bladder adenocarcinoma
• Prognosis: life-long management necessary with focus on bladder and renal function, psychological status, and sexual function and fertility

Biliary atresia

• Definition: obliteration or discontinuity of the extrahepatic biliary system, most commonly of the common bile duct
• Epidemiology
  • Approx. 1:10,000–15,000 live births in the US
  • ♀ > ♂
• Etiology
  • Exact etiology unknown, most likely an embryonal malformation or acquired lesion
  • Approx. 10–35% of cases involve additional anatomical malformations (e.g., situs inversus, asplenia, polysplenia, cardiac anomalies)
• Pathophysiology: discontinuity of the biliary system due to obliteration or fibrosis → obstruction of bile flow (cholestasis) → secondary biliary cirrhosis and portal hypertension
• Clinical features
  • Jaundice
    • Prolonged neonatal jaundice (> 2 weeks)
    • Onset 2 weeks after birth is possible.
  • Acholic stools, dark urine
  • Hepatomegaly
• Diagnosis
  • Laboratory analysis
    • Conjugated hyperbilirubinemia
    • ↑ Aminotransferases and alkaline phosphatase
    • ↑ GGT
  • Ultrasonography
    • Absence of the gallbladder
    • No dilatation of the biliary tree
  • Liver biopsy
    • Active inflammation with bile duct degeneration and fibrosis
    • Bile duct proliferation
    • Portal stromal edema
  • Hepatobiliary scintiscanning (HBSS): failed excretion of the tracer into the bowel
  • Intraoperative cholangiography to confirm diagnosis
• Treatment
  • Kasai procedure (hepatoportoenterostomy): a connection is created between the liver and the small intestine to allow for bile drainage.
  • In cases of liver cirrhosis: liver transplantation (primary reason for liver transplantation in children)
• Complications
  • If undetected
    • Early biliary liver cirrhosis (at approx. 9 weeks of age)
    • Children may die within the first 2 years of life
  • Postoperative
    • Cholangitis in 50% of cases
    • Portal hypertension in > 60% of cases

Alagille syndrome

• Description: a genetic condition that is characterized by intrahepatic biliary duct aplasia or hypoplasia
• Epidemiology: Approx. 1:30,000–45,000 live births in the US
• Etiology
  • Autosomal-dominant inheritance
  • Mutation in the JAG1 gene on chromosome 20 in 90% of patients
• Clinical features
  • Hepatic manifestations
    • Cholestasis
    • Jaundice
    • Pruritus
    • Cirrhosis
  • Facial dysmorphism
    • Triangular face
    • Deep set eyes
    • Broad nasal bridge
  • Congenital heart defects (e.g., peripheral pulmonary stenosis)
  • Butterfly vertebrae
  • Posterior embryotoxon
  • Renal dysplasia
• Diagnosis
  • Laboratory findings
    • Conjugated hyperbilirubinemia
    • ↑ Serum aminotransferases
    • ↑ γ-GT
  • Liver biopsy: decreased number of interlobular bile ducts
  • Confirmation via genetic testing: detection of JAG1 gene mutation
• Treatment
  • Depends on the affected organ systems
  • Conservative management of cholestasis and pruritus (e.g., ursodeoxycholic acid, cholestyramine)