Small Intestinal Atresia and Stenosis

The pathophysiology of duodenal stenosis and atresia differs from that of obstructions located more distally in the jejunoileal area; the importance of this difference cannot be overstated. In duodenal atresias, a failure of recanalization of the intestinal tube occurs at 8-10 weeks' gestation after the obliteration of the lumen by epithelial proliferation at 6-7 weeks; it usually occurs in the second part of the duodenum. Incomplete recanalization can lead to duodenal stenosis or the presence of a duodenal web. ^{[5, 6]}

Atresias of the jejunum and ileum (ie, JIA) are classified together and occur in about 1 in 10,000 births annually. The underlying process is an ischemic injury to the gut resulting in segmented blood supply to the intestines, usually secondary to malrotation with volvulus or intestinal strangulation with the umbilical ring, intestinal perforations, or vasoconstrictive drugs (eg, cocaine, ephedrine, and nicotine). Jejunoileal atresias occur after intestinal development because of bile droplets, meconium, or lanugo distal to the atresia. ^[7]

In 1998, Dalla Vecchia et al performed a 25-year retrospective review and found 277 neonates with intestinal atresia. ^[8] The level of obstruction was duodenal in 138 patients, jejunoileal in 128, and colonic in 21. Of the 277 neonates, 10 had obstructions at more than one site. JIA was associated with intrauterine volvulus (27%), gastroschisis (16%), and meconium ileus (11.7%). Postoperative mortality was 4% for neonates with duodenal atresia and 0.8% for those with JIA.    

In atresias of the small intestine, the jejunum and ileum are equally affected. ^{[9, 10]}  It was suggested by Grosfeld that the proximal jejunum is the site of atresia in 31% of cases, the distal jejunum in 20%, the proximal ileum in 13%, and the distal ileum in 36%. In more than 90% of patients, the atresia is single; however, multiple atresias are reported in 6-20% of cases. ^{[10, 11, 12]}

Stollman et al published a sizable series of JIA as a retrospective review at a large pediatric referral center in the Netherlands. ^[13] Between 1974 and 2004, they found 114 infants with JIA. In all, 62% of atresia and stenosis cases were noted in the jejunum, 30% in the ileum, and 8% in both the jejunum and the ileum; 7% of patients had intestinal stenosis, 16% had type I atresia, 21% had type II, 24% had type IIIa, 10% had type IIIb, and 22% had type IV (see Classification below).

Heij et al performed a retrospective analysis of 21 patients with jejunal atresia and 24 with ileal atresia and found more differences than similarities between the groups (see Table 1 below). ^{[14, 15, 16, 2, 17]}

Table 1. Differences Between Jejunal and Ileal Atresia ^{[14, 15, 16, 2, 17]} (Open Table in a new window)

In this analysis, mean birth weight and gestational age were significantly lower in patients with jejunal atresia than in those with ileal atresia. ^[14] In most cases of jejunal atresia, multiple atresias were found, whereas in most cases of ileal atresia, only a single atresia was found. Antenatal perforation was frequent (10 cases) in ileal atresia but infrequent (two cases) in jejunal atresia. The postoperative course was often prolonged, and mortality increased in patients with jejunal atresia, three of whom died (all of them patients with apple-peel deformity); by comparison, one patient with ileal atresia died.

Heij et al suggested that a difference in bowel-wall compliance between the jejunum and the ileum might explain some of their findings. ^[14] The compliant jejunal wall allows massive dilatation with subsequent loss of peristalsis, accounting for the prolonged postoperative course and the relatively high perforation rate in ileal atresia.

Classification

Duodenal atresia has several basic morphologies, as follows:

• Type I atresia - Luminal webs or membranes, some of which contain a central defect or fenestration of variable size, and result in a marked size discrepancy with mural continuity
• Type II atresia - Dilated proximal and diminutive distal segments connected by a fibrous cord
• Type III atresia - Complete discontinuity between the segments
• Type IV atresia - Blockage of multiple segments of the intestine; this may result in a cvery short length of useful intestine

Infants with any of the four types of JIA usually vomit green bile on the day of their birth; however, those with obstructions farther down in the intestine may have a swollen belly and vomit until 2 to 3 days later.

Colonic atresia develops in 1 in 20,000-66,000 births and occurs in fewer than 15% of babies with intestinal atresia. ^[18] The bowel becomes massively dilated, and patients develop signs and symptoms like those of JIA. Colonic atresia may occur with small-bowel atresia, Hirschsprung disease, or gastroschisis.

The maximal dilatation of the proximal segment occurs at the point of obstruction. This segment is commonly aperistaltic, of questionable viability, or both. ^[3] Grosfeld et al modified Louw’s original classification into the following description of intestinal atresia, which is currently the most commonly used classification scheme ^[10] :

• Type I – Membrane
• Type II – Blind ends joined by a fibrous cord
• Type IIIa – Disconnected blind end
• Type IIIb – Apple-peel deformity
• Type IV – Multiple, string-of-sausages appearance

Stenosis

The proximal dilated intestine is in continuity with the distal nondilated bowel, and the mesentery is intact. A narrow, semirigid segment with a minute lumen is present between these portions. The small-bowel length is normal. This lesion might simulate a type I atresia (see the image below).

Atresia type I

Type I is a mucosal (septal) atresia with an intact bowel wall. The proximal dilated intestine is continuous with the distal narrow one. The mesentery is intact, and the intestinal length is normal. The pressure generated on the internal membrane may elongate it as a windsock, giving a conical appearance to the transition. The distal intestine is collapsed (see the image below) but may contain meconium.

Atresia type II

In type II, a fibrous cord separates the proximal bowel from the distal segment. The mesentery is usually intact, but a small V-shaped defect may be present. Intestinal length is normal. The proximal blind pouch is grossly dilated, often aperistaltic and cyanotic. Perforations may be noted in patients who present late. Dilatation usually extends 10-15 cm proximally, after which point the intestine appears relatively normal. The distal blind pouch may be mildly distended because of retained cellular debris (as in fetal intussusception) (see the image below).

Atresia type IIIa

Type III atresias are the most common. ^{[9, 19]} Intrauterine resorption of fetal gut subjected to a vascular insult explains the reduced bowel length commonly seen in this atresia type. The distal bowel is small and decompressed.

In type IIIa atresia, the two blind ends are completely separated without a fibrous cord between them. The atresia has a V-shaped mesenteric gap, and the intestine is shortened (see the images below). The proximal dilated pouch may have questionable viability and undergo torsion.

Atresia type IIIb

In type IIIb atresia (Christmas-tree or apple-peel deformity), the two intestinal segments are separated as in type IIIa, and the mesenteric defect is large. The proximal atretic segment is in the upper jejunum, near the ligament of Treitz; the pouch is distended and lacks dorsal mesentery. The superior mesenteric artery distal to the middle colic branch is absent. The collapsed distal intestine helically encircles a small vessel (marginal artery) arising from the ileocolic or right colic arcades, or the inferior mesenteric artery, and its vascularity may be impaired.

Type I and type II atresia may coexist in the distal segment. The intestine is always substantially shortened (see the image below). Many patients with this variant have low birth weight (70%) and were born premature (70%); they may also have malrotation (54%), multiple atresias, and an increased number of other associated anomalies that raise the prevalence of complications (63%) and increase the mortality (54-71%). ^{[20, 21]}

Atresia type IV

Type IV atresia refers to any number and combination of type I, II, or III atresias that present simultaneously, creating a string-of-sausages appearance (see the image below). A possible cause is intrauterine inflammation. However, findings of this type of atresia in family members suggest possible autosomal recessive transmission. ^{[22, 11, 23]}

The presence of multiple GI atresias with cystic dilatation of the bile duct is rare; the association has been described in only a few dozen patients, with no recorded survivors in the world literature. ^{[24, 25]} The dilatation of the bile duct seems to be due to normal bile drainage into a closed-loop duodenal obstruction. Patients present with multiple atresias and die of short-bowel syndrome and complications related to total parenteral nutrition (TPN).

That associated congenital malformations are more prevalent with duodenal atresia than with JIA suggests that proximal obstructions occur earlier in fetal life. ^{[8, 26]}  Unlike duodenal atresia, JIA involves separation by a cordlike segment or a V-shaped mesenteric gap. This definition, plus the usual finding of bile pigments and lanugo distal to the atretic segment, indicate that an in-utero vascular accident occurring relatively late in gestation (>11-12 wk) is the likely origin of these atresias, rather than a failure of GI tract recanalization. A localized intrauterine vascular accident with ischemic necrosis of the bowel and subsequent reabsorption of the affected segment has been the favored theory. ^{[27, 15, 28]}

De Chadarévian et al reported on an infant with inherited thrombophilia that created a hypercoagulable state, favoring a segmental intestinal thrombosis and resulting in terminal ileal atresia. ^[29] This patient was also found to have Hirschsprung disease, which is rarely associated with intestinal atresia.

The localized nature of a vascular insult explains the low (10%) prevalence of coexisting conditions. Intestinal atresia associated with in-utero intussusception or perforation, malrotation, volvulus, internal hernias, gastroschisis, and omphalocele further corroborates a vascular event as the etiology of most JIAs. ^{[30, 28, 31, 32]} Only one case of a newborn patient has been reported with multiple intestinal atresias associated with multifocal angiodysplasia of the intestinal wall. ^[33] Antenatal diagnosis requires tertiary care with both pediatric and neonatal expertise available.

Sweeney et al examined 38 patients with jejunal atresia and 45 patients with ileal atresia at the Children's Research Center in Dublin, Ireland. ^[26] Compared with patients with ileal atresia, patients with high jejunal atresia had a higher rate of associated congenital malformations (42% vs 2%), a higher rate of multiple or apple-peel (type IIIb) atresia (53% vs 9%), and a higher mortality. These results suggest that jejunal atresia may also develop from a malformation process.

In a collaborative study in France, Gaillard et al reviewed 102 cases from 42 induced abortions and 22 stillborn and surgical findings in 38 neonates. ^[34] Abnormalities such as meconium ileus (associated with cystic fibrosis) and chromosomal aberrations (eg, Down syndrome) were present during the second trimester of gestation. The authors detected intestinal atresia and stenosis in the third trimester of pregnancy, which were associated with ischemic conditions.

Although most infants have only one atretic segment, multiple atresia has been described in infants of mothers who ingested ergotamine and caffeine or pseudoephedrine (alone or with acetaminophen) during pregnancy. ^{[35, 36]} Other vasoconstrictive factors (eg, cocaine abuse and smoking during pregnancy) are linked with increased risk for intestinal atresia. ^[36] The risk is also higher in patients with graft-versus-host disease and immunosuppression and those with malformation processes that are likely due to autosomal recessive transmission. ^{[23, 37]} Multiple intestinal atresias have been reported in rare association with pyloric atresia and pylorocholedochal fistula. ^[38]

In a study of 114 cases of JIA in the Netherlands, Stollman et al found other GI anomalies in 24% of patients, genitourinary malformations in 9%, cystic fibrosis in 9%, neurologic abnormalities in 6%, and congenital heart disease in 4%. ^[13]

Duodenal obstructions of congenital origin are often associated with other congenital anomalies, which account for most of the morbidity and mortality in these patients. Various publications have reported a 50-80% incidence of associated conditions. Congenital heart disease and trisomy are the most common related conditions in about 30% of cases. ^{[39, 40]} All three states may coexist in the same patient. ^[41]

In a study of patients with trisomy 21 who underwent antenatal US, about 4% showed antenatal evidence of duodenal atresia. ^[42] Other associated anomalies include intestinal malrotation (20%), esophageal atresia, ^[43] imperforate anus (10-20%), thoracoabdominal heterotaxia, and gallbladder agenesis.

One of the most important factors to remember is that in duodenal atresia, as in other neonatal diseases, the outcome for patients depends more on the severity of the associated anomalies and the ease with which they can be corrected than on the surgical management of the obstruction itself.

Familial cases of various types of atresia have been described. ^[44] Familial type I jejunal atresia affected three members from two generations in one family. Proximal atresia was associated with renal dysplasia. Knowledge of the familial form of the disease indicates that most cases of JIA result from disruption of a normal embryologic pathway, most likely the development of the superior mesenteric artery and its branches. They should be considered true embryologic malformations rather than acquired lesions.

This association is an autosomal dominant condition. Matsumoto et al reported a case in Japan and reviewed the literature, finding six other cases of small intestinal atresia in twins. ^[45] All published instances, except for one, involved identical twins. Three pairs of twins had different types of atresia, and the fourth set had no other anomalies. The other family members were unaffected; this may suggest that such cases may be due to environmental influences during gestation.

Another report of different intestinal atresias in identical twins suggested them to be either the consequence of the linkage of two genes or a pleiotropic expression of a single gene. ^[46] Pleiotropy reflects the fact that most proteins have multiple roles in distinct cell types. The genetic change that alters gene expression or function can potentially have wide-ranging effects in various tissues. ^[47] In some instances, the influence of a single gene may be direct and cause single-gene traits. ^[48]

Congenital duodenal obstruction may be complete or partial, intrinsic or extrinsic. Intrinsic obstruction occurs in about 1 of 7000 live births and accounts for about half of all small-bowel atresias. Extrinsic obstruction has many causes, including malrotation with Ladd bands, other congenital bands not associated with malrotation, ^[49] preduodenal portal vein, gastroduodenal duplications, cysts or pseudocysts of the pancreas and biliary tree, and anular pancreas (which is commonly associated with a duodenal web, an intrinsic cause of duodenal obstruction ^[50] ).

Boys and girls are equally affected. ^[9]  In most studies, JIAs seem to be more common than duodenal atresias, and colonic atresias account for the fewest cases.

In West Africa, intestinal atresia is the fourth most common cause of neonatal intestinal obstruction, after anorectal malformations, Hirschsprung disease, and strangulated inguinal hernias. ^[51] In an 11-year retrospective review of 500 children in India, Ranan et al found intestinal atresias to be the most common cause of intestinal obstruction in newborns and the second most common cause (11.8%) after intussusception (20.8%) in all age groups. ^[52]

Unlike duodenal atresia, JIA is not commonly seen in association with Down syndrome. Patients with intestinal atresia are epidemiologically characterized by young gestational age and low birth weight. In addition, the atresia is associated with twinning, the parents are more often consanguineous compared with parents of healthy neonates, and vaginal bleeding frequently complicates the pregnancies.

No correlation between JIA and parental age or disease has been proved. ^{[16, 15, 2]} However, one study from France reported an increased prevalence of intestinal atresia in infants born to teenagers. ^[16] Some maternal infections may be associated with ileal atresia. ^[15]

Infants with atresia often have short-bowel syndrome, a spectrum of malnutrition problems resulting from inadequate bowel length. This may occur in patients born with multiple atresias or those with apple-peel deformity. It is a cause of intestinal failure, together with other congenital diseases of enterocyte development and severe motility disorders (total or subtotal aganglionosis or chronic intestinal pseudo-obstruction syndrome). ^[53]

Also a common causes of short-bowel syndrome in premature infants is necrotizing enterocolitis (NEC), ^[54]  which generally resulting from a perforation in the baby's intestines and bacterial translocation. NEC affects 1 in 1000 premature babies and 1 in 10,000 full-term babies. The most significant risk is for premature infants weighing less than 2 lb (0.9 kg). ^{[55, 56, 57, 58, 59, 60]}

Midgut volvulus is another common cause of short-bowel syndrome. This results from bowel malrotation in neonates and infants who present with proximal small-bowel obstruction and bilious vomiting. About 75% of cases occur within 1 month of birth, but the condition can occur at any age.

Of the 114 patients previously discussed in the study by Stollman et al, 28% developed early postoperative complications, whereas 17% experienced late postoperative complications; mortality was 11%. ^[13] Short-bowel syndrome seems to be the biggest problem, resulting in more extended hospital stays, more feeding problems, and higher morbidity and mortality.

A study comparing postoperative outcomes of 50 patients with complete congenital duodenal obstruction (CCDO; n = 27) or incomplete congenital duodenal obstruction (ICDO; n = 23) found that outcomes in these two groups differed significantly. ^[61] CCDO’s overall antenatal detection rate was 49%; however, the rate for CCDO was substantially higher than that for ICDO (88% vs 4%). Despite the high detection rate, the CCDO group was significantly associated with the following:

• Lower gestational age at birth
• Lower age and weight during the operation
• Higher rate of associated congenital heart disease (CHD)
• More extensive preoperative radiologic diagnostics
• Higher morbidity according to the Clavien-Dindo classification
• Higher comprehensive complication index

In addition, CCDO patients had a more extended hospital stay, which was associated with more adverse events. ^[61] On the other hand, patients with ICDO often experience considerable delays in diagnosis and operative repair of their congenital malformation. Although this study focused specifically on CCDO and ICDO postoperative outcomes, it also identified essential factors during the antenatal and postnatal periods that could significantly impact prognosis.

Lack of sufficient residual bowel is responsible for considerable morbidity or poor quality of life. In most instances, maximal intestinal adaptation occurs within 6-12 months, but it may take longer. ^[28] The use of the longitudinal intestinal lengthening and tailoring (LILT) procedure, proposed by Bianchi and modified by Aigrain, can allow the child to be weaned from parenteral nutrition. ^[62]

As a consequence of advances in medical care (eg, improved surgical techniques and parenteral nutrition), the survival of neonates with intestinal atresia improved dramatically in the 20th century. ^[63]  Before the mid-20th century, the mortality associated with small-bowel atresia was prohibitive (>90%). By the late 1950s, survival had risen to 78%. Survival rates improve with distal atresia, whereas mortality is high in instances of multiple atresias (57%); apple-peel deformity (54-71%); and atresia associated with meconium ileus (65%), meconium peritonitis (50%), or gastroschisis (66%). ^{[20, 5, 21, 28]}

Currently, overall survival rates (including preterm babies) have reached 90%, with a surgical mortality of less than 1%. ^{[20, 8, 21]} Mortality is related to sepsis, associated anomalies, prematurity, malrotation, meconium peritonitis, and long-term TPN complications in patients with short-bowel syndrome.

The most common cause of death in infants with JIA is an infection related to pneumonia, peritonitis, or sepsis. ^[9] Sato et al reported on an infant with ileal atresia and meconium peritonitis after a perforation who presented with pylephlebitis (air in the portal system) and a pulmonary gas embolism. ^[64] The patient had respiratory distress, shock, disseminated intravascular coagulation, and intractable diarrhea but eventually recovered and was discharged from the hospital after four months.

The most critical surgical complications are anastomotic leaks and functional obstruction at the level of the anastomosis; these occur in as many as 15% of patients. ^{[9, 19]} In 84 patients with congenital JIA or colonic atresia who were treated in New South Wales, Australia, mortality was higher in infants who underwent stoma formation than in those who received a primary anastomosis. ^[65] Reoperation may be required to prevent complications. ^[66]

Today, the survival rate for patients with short-bowel syndrome is 80-94%. ^[67] The presence or absence of the ileocecal valve does not affect mortality. Still, it does affect the length of time for which TPN is required and thus affects the complications related to its use (eg, predisposition to infection, central line sepsis, and TPN-related cholestasis). ^{[8, 67]} Malabsorption and steatorrhea are most severe in patients with terminal ileal resection, particularly when the ileocecal valve is excised. Vitamin B supplements are helpful for such patients. These children's long-term recovery is often remarkably normal, but there is a 10-15% incidence of neurologic and developmental defects. ^[67]

The presence of multiple intestinal atresias necessitates repeated surgical interventions and sometimes small-bowel transplantation; the development of short-bowel syndrome in these patients is associated with an increased risk of cholestasis, liver cirrhosis, and hepatic failure. The prognosis is poor, with most infants dying early in life. ^[68] Patients with this condition often have immunodeficiency. ^[69] Thymic dysplasia and lymphoid depletion are key findings in patients with mutations in the TTC7A gene who have multiple intestinal atresias. Multiple and recurrent intestinal atresia is extremely uncommon and can lead to intrauterine death. ^[70]

Overall mortality due to intestinal atresia does not seem to depend on the location of the obstruction. Prematurity, birth weight less than 2 kg, and associated anomalies are independent risk factors for prolonged hospital stay and higher mortality. ^{[71, 72]}