Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disorder in whites. Neonatal intestinal obstruction caused by meconium ileus is the earliest clinical manifestation of CF. Other causes of intestinal obstruction in the neonate with CF have also been reported, including jejunoileal atresia and meconium plug syndrome (1–3). Herein, we describe the first known case of a newborn with CF presenting with neonatal intestinal obstruction caused by colonic atresia.
A newborn term baby girl (birth weight 2.96 kg) was born to a healthy gravida 2, para 1, mother following an uncomplicated pregnancy. She developed abdominal distension associated with failure to pass meconium at 36 hours of life. An abdominal radiograph showed dilated loops of bowel. Enteral feeding was ceased and intravenous fluids and broad-spectrum antibiotics were commenced before transfer to a tertiary hospital for further investigation and management.
Upon arrival, she had an urgent barium enema, which showed a distal microcolon and no contrast advancing proximal to the splenic flexure, suggesting the presence of colonic atresia (Fig. 1A). On laparotomy, at 4 days of age, a type I colonic atresia (membranous atresia with serosal continuity) was identified, with dilated proximal colon filled with thick meconium and a small-caliber distal colon (Fig. 1B). In addition, she was noted to have thick viscous meconium plugging in the terminal ileum with dilated loops of small bowel proximally. The atretic segment was resected, and an end-to-end anastomosis was performed. The terminal ileum was opened for washout of the thick meconium, and a double-barrel ileostomy created. A suction rectal biopsy was performed to exclude Hirschsprung disease.
Postoperatively, she received total parenteral nutrition for 5 days before expressed breast milk was reintroduced and upgraded. Parenteral nutrition was weaned off by postoperative day 10. Despite increasing the volume of her feeds and energy density to 50 mL · kg−1 · day−1 and 28 kcal/30 mL, respectively, she failed to gain weight. Ileostomy output was <30 mL · kg−1 · day−1. On examination, she had mild peripheral edema, reduced subcutaneous fat, and muscle bulk, but no ascites or organomegaly. By day 18 postoperatively, her serum albumin had dropped to 12 g/dL (reference range 28–44 g/dL).
Further investigations for failure to thrive were performed. Urinalysis, microscopy, culture, and urine metabolic screen for inborn errors of metabolism were normal. She had a normal complete blood count, electrolytes, renal and liver biochemistry, immunoglobulin G, and coagulation screen. Stools were collected for microscopy and culture, α1-antitrypsin, and elastase-1. Large amounts of fat globules in her stools and abnormal elastase-1 level of <15 μg/g (normal >200 μg/g) were found. Concurrently, at 4 weeks of age, her newborn screening result became available and was positive for CF. Her immunoreactive trypsin level was elevated at 84 μg/L (normal <75 μg/L), and genotyping revealed homozygosity for F508del genotype. Her sweat chloride concentration was elevated at 92 mmol/L (abnormal >60 mmol/L). Pancrelipase at 5000 U · kg−1 · day−1 and fat-soluble vitamins were commenced, resulting in significant weight gain and normalization of her serum albumin. Her stoma output decreased to 10 mL · kg−1 · day−1. She was discharged at 54 days old and continued to thrive after stoma closure at 4 months old.
To our knowledge, this is the first case of neonatal intestinal obstruction in CF caused by colonic atresia. Approximately 20% of patients with CF present with neonatal intestinal obstruction caused by meconium ileus. Rarely, a diagnosis of CF can be made in association with other causes of neonatal intestinal obstruction, including meconium plug syndrome and jejunoileal atresia (1–3).
It is unclear whether the association between colonic atresia and CF is related (directly or indirectly) to CF transmembrane conductance regulator protein absence/dysfunction or is purely coincidental. Colonic atresia is a rare cause of neonatal bowel obstruction, accounting for <10% of all forms of gastrointestinal atresia and has a frequency of 1/20,000 births (4). Colonic atresia has been associated with Hirschsprung disease, gastroschisis, but not CF. Previous reports of intestinal atresia in CF were limited to the jejunum and ileum. The cause of intestinal atresia is thought to be related to intrauterine intestinal ischemia in “watershed” areas of vascular supply, which includes the splenic flexure. It is plausible that distension by thick meconium in the affected colon led to a localized area of ischemia resulting in atresia in our case. Alternatively, heavy meconium-filled bowel may twist to develop a splenic flexure volvulus causing ischemic injury in the watershed area of the splenic flexure. Although intestinal obstruction by inspissated meconium typically occurs in the terminal ileum, it may also occur elsewhere in the intestine. Indeed, acute intestinal obstruction caused by adherent meconium-like fecal material in the colon has been previously reported in CF-affected infant and adult (5,6). Furthermore, potentially related colonic pathologies such as colonic perforation and cecal diaphragm have been reported in patients with CF (7,8).
Although an isolated case of colonic atresia associated with CF is insufficient to justify routine testing for CF in all cases of colonic atresia, we advise a high index of suspicion for CF in all forms of intestinal atresia. Moreover, we suggest careful examination of the terminal ileum during laparotomy. The finding of meconium plugging in the terminal ileum should warrant early evaluation for CF. Furthermore, unexplained failure to thrive/malnutrition in the postoperative period should also prompt testing for CF.
In conclusion, this is the first report of neonatal intestinal obstruction in CF caused by colonic atresia. A high index of suspicion for the diagnosis of CF is necessary in any newborn who presents with intestinal atresia including colonic atresia.
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