Genetic and clinical profile of neonates with meconium ileus: A case series

Case series

Details of clinical characteristics are shown in Table 1. Four were term neonates, and one a late preterm. All presented within 48 h of life with abdominal distension, bilious vomiting, and failure to pass meconium.

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Table 1.

Clinical characteristics and investigation profile of neonates with MI.

	Case 1	Case 2	Case 3	Case 4	Case 5
Gestation/ Birthweight	Term/3480 g	Term/2080g	Late preterm/2100 g	Term /3500 g	Term/2838 g
Sex	Male	Male	Female	Female	Male
Antenatal USG findings: Dilated small bowel loops / echogenic foci	Present	None	Present	None	None
Barium enema	Contrast filling till cecum	Contrast passage till cecum with filling defects	Contrast filling till cecum, microcolon	Contrast filling till distal ileum, microcolon	Contrast filling seen till cecum
Management	Surgery	Conservative	Conservative, followed by surgery	Conservative, followed by surgery	Surgery
Surgical intervention	Jejuno-ileal anastomosis	Not required	Ileo- ileal anastomosis	Ileo-ileal anastomosis	Adhesiolysis, paracolic gutter drain placement and peritoneal lavage
Outcome	Death	Discharge	Discharge	Discharge	Discharge
Duration of hospital stay	22 days	20 days	13 days	10 days	33 days
Genetic analysis	No abnormality detected	CFTR mutation	CFTR mutation	CFTR mutation	Heterozygous- variant of unknown significance

CFTR: cystic fibrosis transmembrane conductance regulator; ICJ: ileo-cecal junction, NG: nasogastric; MI: meconium ileus; USG: ultrasonography.

Clinical examination revealed a tense abdomen, a patent anal opening, and absent or sluggish bowel sounds. Two neonates demonstrated echogenic bowel and dilated bowel loops on an antenatal ultrasound scan. Initial workup included abdominal radiography, ultrasonography, and contrast enema. All neonates had dilated bowel loops on radiography, with one showing tiny calcifications suggestive of a meconium pseudocyst, confirmed by ultrasonography. Gastro-intestinal contrast studies predominantly revealed the absence of contrast distal to the ileo-caecal junction (Fig. 1), with additional findings of microcolon (Fig. 2) and filling defects. Three presented as simple MI, and the remaining two had peritonitis.

Genetic testing by whole-exome sequencing was done in all five neonates; three had cystic fibrosis transmembrane conductance regulator (CFTR) mutations suggestive of CF, while one showed a heterozygous genetic abnormality of unknown significance.

Initially, the three neonates with simple MI were managed conservatively, which included warm saline bowel wash-outs followed by N-acetyl cysteine enema administration. Of these, two eventually required surgical intervention because of deterioration. At exploratory laparotomy, evacuation of viscous meconium followed by resection of necrotic segments and end-to-end anastomosis of intact bowel segments was performed.

The other two neonates with suggestion of peritonitis ab initio underwent exploratory laparotomy. One had adhesions secondary to meconium peritonitis and underwent adhesiolysis with peritoneal lavage with placement of drains in the pelvic and paracolic gutters as well as a defunctioning ileostomy. The other underwent evacuation of inspissated meconium by diluted Gastrograffin washout. An appendicectomy, T-tube placement at the junction of the ileum and the transitional point, was performed, and the tube brought out in the right lumbar region. However, a revision exploratory laparotomy needed to be done owing to non-passage of meconium despite conservative measures. The proximal ileal loop was re-constructed as an ileostomy, and a mucus fistula was brought out. Intra-operative rectal biopsies were performed in all cases but were not suggestive of aganglionosis.

Postoperatively, enteral nutrition was initiated after signs of functioning bowel appeared. Three of four neonates were started on pancreatic enzyme supplementation after assessing them for the same according to protocol. ⁶ Four neonates survived to discharge, while one succumbed to septic shock.

The diagnosis of CF by genetic testing helped guide nutritional support protocols (viz. more aggressive enzyme supplementation for patients with severe mutations and complicated presentation), as well as more frequent follow-up visits for assessment of growth, family counseling, and screening of siblings.