PEDIATRICS Vol. 114 No. 1 July 2004, pp. 285-290
Meconium Obstruction in the Very Low Birth Weight Premature Infant
Sanjuanita Garza-Cox, MD*,
Susan E. Keeney, MD*,
Carlos A. Angel, MD*,
,
Lauree L. Thompson, MD* and
Leonard E. Swischuk, MD
* Departments of Pediatrics
Surgery
Radiology, University of Texas Medical Branch, Galveston, Texas
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ABSTRACT
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Meconium obstruction of prematurity is a distinct clinical condition that occurs in very low birth weight infants, predisposing them to intestinal perforation and a prolonged hospitalization if not diagnosed and treated promptly. We report a series of 21 infants, including 2 detailed case reports, whose clinical course is indicative of meconium obstruction of prematurity. Specific risk factors are identified along with descriptions of clinical and radiologic findings, disease course, treatment, and outcome. Meconium obstruction of prematurity was more common in infants with a maternal history of pregnancy-induced or chronic hypertension, suggesting the possibility of decreased intestinal perfusion prenatally. Inspissated meconium was located most frequently in the distal ileum, making this disease process difficult to treat. Gastrografin enemas were safe, diagnostic, and therapeutic. Delay in diagnosis and treatment was associated with perforation and delay in institution of enteral feeds.
Key Words: meconium plug • meconium obstruction • premature bowel obstruction • meconium ileus • meconium blockage • inspissated meconium • Gastrografin enema • intestinal perforation
Abbreviations: NEC, necrotizing enterocolitis • SGA, small for gestational age • OR, odds ratio • CI, confidence interval
Clatworthy et al first described meconium plug syndrome in 1956 as "intestinal obstruction due to the inability of the colon to rid itself of the meconium residue of 9 months of fetal life."1 Recently, inspissated meconium has become a recognized cause of functional bowel obstruction in the low birth weight infant.2,3 It has also been called "syndrome of retained meconium,"2 "meconium blockage syndrome,"4,5 "inspissated meconium syndrome,"5,6 and "meconium disease."2,6 We have chosen to designate it as meconium obstruction of prematurity. Meconium intestinal obstruction encompasses a wide spectrum of diseases including meconium ileus, transient functional ileus of the sick newborn infant, and meconium plug syndrome, which occurs in the term infant and is characterized by low intestinal obstruction, lack of meconium passage in the first 24 hours, and simple treatment with rectal stimulation.4,7,8 Meconium obstruction of prematurity is a distinct entity from the diseases described above. It occurs in very low birth weight infants who develop obstructive symptoms several days after having passed some initial meconium.6 We report a series of 21 infants, with specific case reports of 2 premature infants, whose clinical courses are indicative of this increasingly important disorder to redefine the associated risk factors and complications, particularly that of intestinal perforation, and to present our medical and surgical management. Delay in accurate diagnosis and prompt treatment of this condition can result in increased morbidity and mortality in this fragile group of patients. Potential complications include withholding feeds, which consequently postpones the attainment of adequate enteral nutrition and growth, bowel perforation, and unnecessary surgical procedures. Identifying the characteristics and risk factors of infants susceptible to meconium obstruction of prematurity allows clinicians to maintain a higher index of suspicion and therefore diagnose and initiate treatment in an expedient and safe manner.
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MATERIALS AND METHODS
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The medical records of premature infants with a diagnosis of meconium plug syndrome or meconium ileus as well as those who underwent a laparotomy or ileostomy during the 7-year period from January 1995 to July 2002 were reviewed. Only those preterm infants weighing <2000 g at birth were included. Patients were identified by searching the database of infants admitted to the neonatal intensive care unit at the University of Texas Medical Branch in Galveston, Texas.
Medical records were reviewed for demographic data, prenatal risk factors, feeding and stooling patterns, radiographic findings, interventions, complications, and time of resolution. Infants with diagnoses of gastroschisis, intestinal atresia/strictures, Hirschsprung’s disease, and malrotation were not included. Infants with either spontaneous intestinal perforation or necrotizing enterocolitis (NEC) (diagnosed by radiographic/clinical evidence or gross specimen or histologic evaluation) who did not have a history of either delay in passage of meconium or inspissated meconium on pathologic evaluation were eliminated from the study.
For the comparison of prenatal complications, a control group of infants was matched for the study group. The infant born immediately before and after the study infant weighing ±100 g of the birth weight of the study infant was included (n = 42). Infants were excluded from the control group if they had multiple congenital anomalies, intestinal perforation for any reason, or NEC. Logistic regression was used to examine the association of maternal complications and meconium obstruction.
The study protocol was approved by the Institutional Review Board for Human Subjects at the University of Texas Medical Branch.
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CASE REPORTS
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Case 10
A small-for-gestational-age (SGA) infant boy was born at 28 weeks gestational age with a birth weight of 740 g via primary cesarean section precipitated by absent diastolic flow on ultrasound of the umbilical vein and worsening oligohydramnios. He was intubated, given surfactant, and placed on mechanical ventilation with the diagnosis of respiratory distress syndrome. He passed his first 3 stools on day 2, with a subsequent meconium plug stool on day 3. On day 5, he was noted to have abdominal distention and erythema of the lower abdomen. A plain abdominal radiograph showed generalized intestinal distention, and the infant was placed on low intermittent wall suction. He continued to pass small stools until day 7. A saline enema was given on day 8, producing a small amount of stool. On day 11, a 17% Gastrografin (hypertonic water-soluble solution of sodium diatrizoate and meglumine diatrizoate, Bracco Diagnostics, Inc, Princeton, NJ) enema was performed, disclosing large filling defects throughout the colon, primarily in the cecum (Fig 1). Passage of a meconium plug occurred shortly after. He continued to pass stools after the enema, and on day 15, his obstruction completely resolved clinically and radiographically. Feeds then were initiated successfully, and there were no additional intestinal problems during the subsequent 5 months of hospitalization.
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Fig 1. Contrast enema demonstrates meconium plugs (arrows) in the ascending colon. Smaller fragments of meconium are seen scattered throughout the remainder of the colon.
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Case 14
An appropriate-for-gestational-age infant boy was born at 24 weeks with a weight of 835 g via primary cesarean section secondary to preterm labor, prolonged rupture of membranes, and subsequent chorioamnionitis. He was intubated, given surfactant, and placed on mechanical ventilation with the diagnosis of respiratory distress syndrome. He passed a small stool shortly after birth, and feeds were initiated on day 2 with half-strength 100.45-J formula. On day 3, he was noted to have abdominal distention. A glycerin suppository was given, and feeds were discontinued. An initial plain radiograph showed generalized intestinal distention (Fig 2A). Gastrografin enemas were performed on days 4 and 5, producing small amounts of stool. These studies showed loops of distended, obstructed small bowel and filling defects detected in the terminal small bowel (Fig 2B). On day 6, abdominal distention continued, and an unsuccessful saline enema was given, followed by a 20% Mucomyst enema (N-acetylcysteine, Bristol-Myers Squibb Co, Princeton, NJ). Pneumoperitoneum was evident on plain radiographs immediately after instillation of the Mucomyst enema. At laparotomy, an old jejunal perforation and a new pinpoint perforation in the ileum were present. Thick, inspissated meconium was found in the terminal ileum and irrigated and gently manipulated out of the gut. An ileostomy was performed, with subsequent clinical and radiographic resolution of the obstruction. Feeds were started successfully 7 days later. The patient underwent intestinal reanastomosis before discharge without additional intestinal problems.
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Fig 2. A, Preliminary plain film demonstrates moderate distension of the intestines. B, Contrast enema demonstrates a normal colon, with evidence of a meconium plug (arrows) in the distal small bowel.
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RESULTS
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Seventy-eight infants born between January 1995 and July 2002 with a diagnosis of meconium plug syndrome or meconium ileus and those that underwent a laparotomy or ileostomy were identified through our database. Fifty-seven infants were eliminated from the study, 28 on the basis of diagnosis of NEC, 9 with diagnoses of spontaneous perforation not associated with delayed meconium passage or meconium plug found at laparotomy, and 15 with structural intestinal problems including gastroschisis, intestinal atresia/stricture, tracheoesophageal fistula, Hirschsprung’s disease, and intestinal malrotation. On review of hospital charts, 4 infants identified as having meconium plug through the database did not have any intestinal problem during their hospital stay. One chart was unavailable for review.
Descriptive information concerning the remaining 21 patients with meconium obstruction is presented in Table 1. All infants were of very low birth weight, with a mean weight of 819 ± 196 g (mean ± SD) and a mean gestational age of 27 ± 2.4 weeks. The control group was well matched for birth weight, gestational age, and gender. Thirty-three percent of the infants with meconium obstruction were SGA, compared with 17% in the control, but the association was not statistically significant. Fifty-seven percent of the infants with meconium obstruction had an identifiable maternal risk factor associated with decreased placental perfusion including preeclampsia, eclampsia, chronic hypertension, diabetes mellitus with arterial involvement, oligohydramnios, and chronic placental abruption. Infants with meconium obstruction were more likely than controls to have associated prenatal complications including maternal treatment with magnesium sulfate (odds ratio [OR]: 3.9; confidence interval [CI]: 1.0, 8.8; P = .048), pregnancy-induced hypertension (OR: 7.2; CI: 1.5, 14.8; P = .007), and maternal chronic hypertension (OR: 7.0; CI: 1.5, 22.7; P = .008). We did not find significant associations between meconium obstruction and SGA, maternal diabetes, oligohydramnios, or chronic placental abruption.
Clinical characteristics and radiologic findings of the 21 patients are presented in Table 2. Obstruction related to inspissated meconium in the small bowel developed between the ages of 1 and 18 days, with a mean of 5.6 ± 4.8 days of life. Eighty percent of infants were >24 hours of age when they developed symptoms of mechanical obstruction. Sixty-five percent of infants passed stool before the clinical development of intestinal obstruction, and the average time of passage of first stool was 4.4 ± 3.6 days. Passage of stools was typically infrequent or in small amounts and often required rectal stimulation with a thermometer or glycerin suppository.
All the infants had abdominal radiographs showing multiple loops of distended bowel with little or no rectal gas and physical findings of abdominal distention with visible and palpable loops of bowel, suggestive of low intestinal mechanical obstruction, except for case 8, who never developed signs of obstruction. Fourteen infants were given a contrast enema, 5 of whom required repeated instillations. All contrast enemas were performed using Gastrografin, except for one, which was a barium enema. Gastrografin enemas were given in the neonatal intensive care unit. Gastrografin was diluted 1:5 with normal saline to make a 17% solution and was instilled through a Foley catheter in aliquots of 5 mL, taking plain radiographs after each instillation to assure safety. If resistance was encountered, the instillation was halted. Up to 20 mL of solution was generally sufficient to outline the colon, distal ileum, and inspissated meconium plugs on plain abdominal radiographs. It was interesting that, on contrast studies, the distal ileum was noted to have inspissated meconium in 10 infants. Five of these infants had either a distal obstruction or multiple filling defects in only the distal ileum, 2 had filling defects in both the colon and distal ileum, and 2 showed a microcolon with a filling defect of the terminal small bowel. An additional 3 infants had filling defects in the colon only. The other 2 infants passed large meconium plugs with instillation of contrast, so that no filling defect was seen on the radiograph. One infant was given oral metrizamide, which showed no passage of contrast past the distal small bowel.
Twenty-four percent of the symptomatic infants experienced resolution of obstruction after glycerine suppositories or saline enemas alone. Eight infants were given a 20% Mucomyst enema, of which 2 were successful in relieving obstruction. In 9 of the 13 patients who were given Gastrografin enemas, Gastrografin not only proved to be diagnostic but also was therapeutic, resulting in passage of tenacious meconium without need for additional medical or surgical intervention. There was only 1 perforation occurring soon after a contrast enema with Mucomyst. Although 2 additional infants who received contrast enemas suffered a perforation, the perforations occurred >24 hours after the contrast enema and were not considered to be related to the enema.
Six infants suffered intestinal perforations. The average time of perforation was 6.2 ± 3.8 days after diagnosis of obstruction. Interestingly, the average time to diagnosis of obstruction was later in infants who perforated (7 ± 5 days), compared with those who did not (5 ± 4.9 days). Table 3 presents the procedures performed in the 7 infants who required surgery. Overall, a third of the infants underwent laparotomies, 5 due to intestinal perforation, 1 for NEC with perforation, and 1 for progressive distention with microcolon. All operations were performed in the neonatal intensive care unit through limited transverse right-lower-quadrant incisions with minimal manipulation of the gut. Resections were conservative, because after the meconium plugs were removed, intestinal viability was excellent. All but 1 infant received an ostomy. Primary anastomosis and closure was performed in the remaining infant. In several instances, gentle irrigations with warm saline or 10% Mucomyst were used in the postoperative period to clear residual plugs from the proximal stomas. Of note, case 8 never developed abdominal distention and had a gasless abdomen on plain radiograph. Laparotomy was performed for presumed NEC and intestinal perforation after the patient developed a large pneumoperitoneum. A single perforation was found proximal to a distal jejunal segment of inspissated meconium; otherwise, the bowel appeared healthy. Case 11 developed a pneumoperitoneum after 3 days of abdominal distention. Laparotomy revealed a perforation of the distal ileum, NEC of the cecum, and multiple meconium plugs in the sigmoid colon.
In those infants managed medically, resolution of obstruction occurred 6 ± 2.6 days after diagnosis of obstruction (range: 2–10 days), but institution of successful feedings was delayed by 8.6 ± 4 days from development of obstruction (range: 3–16 days). In those infants who required surgical intervention, starting successful feedings was delayed by 20.5 ± 15 days from development of obstruction (range: 7–50 days). Despite the prolonged hospital stay caused by consequences of premature birth, the survival rate to discharge of this cohort of infants was 95%. One patient died at 11 months of life secondary to complications from his extensive respiratory problems. None of these infants developed additional gastrointestinal problems during their prolonged hospitalization except for 1, who developed NEC at 45 days of life and was treated medically. Of note, the 2 patients who showed a microcolon on contrast studies demonstrated normal bowel size on relief of obstruction on subsequent films.
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DISCUSSION
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Meconium obstruction in the low birth weight infant was not reported until 1979 in a case report of 3 patients by Siegel et al.5 Vinograd et al6 later described it as "meconium disease" in 1983 in a report of 7 patients. Krasna et al3 reported meconium obstruction in the low birth weight infant in a report of 20 infants in 1996. All these reports described a mild form of the disease not requiring surgery. However, in 1996, Greenholz et al9 reported 12 infants with inspissated meconium syndrome requiring surgery, 8 cases of which were caused by intestinal perforation. Our present report is of 21 patients, all of whom were premature and of very low birth weight (<1250 g), with patient characteristics resembling those reported previously.6,9 Symptoms occurred late in the first week and up to 2 1/2 weeks of life, with 29% progressing to perforation and a total of 33% of the infants requiring surgery. Medical management was successful in two thirds of the infants. Gastrografin enema was the most effective medical therapy, and our procedure in the neonatal intensive care unit without fluoroscopic visualization proved to be safe. Seventy percent of the infants who were given Gastrografin passed tenacious green meconium during or shortly after instillation, with subsequent relief of the intestinal obstruction. Contrary to other reports, none of these infants developed symptoms of dehydration10 or suffered a perforation due to the procedure.11 One perforation occurred soon after enema with Mucomyst, but we think it unlikely that the type of enema solution used was etiologic. Use of oral agents is a potential adjunct to enemas. Greenholz et al9 reported use of 10% oral acetyl-cysteine for 2 weeks in an infant after Gastrografin enema.
The differential diagnosis of meconium obstruction of prematurity includes NEC, meconium ileus, Hirschsprung’s disease, and intestinal atresia. In unusual cases, NEC may clinically resemble inspissated meconium syndrome, especially if small bowel gas is forced into the colon and mixes with meconium, causing the appearance of pneumatosis intestinalis.7 After perforation occurs, distinguishing meconium obstruction from NEC is very challenging and may only be possible with pathologic examination of the intestinal region involved. Concurrent NEC and intestinal perforation due to meconium obstruction may occur, as noted in case 11 of our series. It is possible that severe, prolonged distention proximal to the meconium obstruction causes ischemia to the antimesenteric portion of the intestine, resulting in pathologic findings of NEC. Meconium ileus presents with inspissated meconium in the ileum, but symptoms are typically persistent and/or recurrent. Although cystic fibrosis and Hirschsprung’s disease have very similar initial clinical and radiologic findings, they were not excluded in our study infants with additional testing because complete resolution of symptoms was observed over their lengthy hospitalization. To our knowledge, none have subsequently developed recurrence of intestinal problems, Hirschsprung’s disease, or cystic fibrosis. Furthermore, in regard to cystic fibrosis, previous investigators have reported that none of their very low birth weight infants with meconium obstruction have positive sweat chloride tests.6,9 Finally, meconium obstruction of prematurity can be misdiagnosed as intestinal atresia, resulting in unnecessary surgery. Before the time period used in this report, 2 very low birth weight infants were wrongly diagnosed as having intestinal atresia at our institution. At laparotomy, inspissated meconium was found as the only cause for the intestinal obstruction.
A major complication of meconium obstruction of prematurity is perforation, which can occur rapidly if the obstruction is not relieved. Perforation occurred more commonly in infants diagnosed later. Because it may be assumed that inspissated meconium was present from birth in most infants, this would suggest that prolonged obstruction with distention of small bowel predisposes to perforation. Inspissated meconium in the distal ileum seemed to be a common factor in the infants who developed perforations. Of the 6 infants who had spontaneous perforations, 5 of them had filling defects in the distal ileum on contrast radiography or were found to have inspissated meconium in the distal ileum at surgery. We postulate that standard medical therapy is less effective in such infants because of the difficulty of reaching the obstructed area via enema. Two of these infants with distal ileal obstruction also had microcolon, and both required surgery, 1 for perforation and the other for obstruction refractory to medical therapy. Although we cannot be definitive, it would seem that microcolon is a poor prognostic sign for successful medical management, which has been reported previously.9 Indications for surgery were worsening clinical condition with increasing abdominal distention and/or intestinal perforation. Although primary repair is a viable option in infants with intestinal perforations, we recommend diversion, particularly in those infants who present with pneumoperitoneum without a previous contrast study that rules out obstruction distal to the site of perforation.
At this point an etiology for meconium obstruction of prematurity is conjectural. Prenatal and perinatal risk factors may include any etiology causing perinatal intestinal hypoperfusion as well as factors associated with dysmotility and stasis.2,9 A premature colon and weak peristalsis have also been associated with meconium developing into an inspissated and tenacious plug because of increased water reabsorption.8 Hypermagnesemia has been associated with functional obstruction in premature infants as a result of intestinal smooth muscle depression and delayed peristalsis.12 Another risk factor that has been associated with functional colonic obstruction is maternal diabetes.13 It is hypothesized that fetal hypoglycemia causes excess glucagon production, which in turn decreases bowel motility.7,14 Our findings of the association of meconium obstruction with maternal pregnancy-induced and chronic hypertension would support the hypothesis of prenatal intestinal hypoperfusion. Our failure to detect a significant association of meconium obstruction with SGA and maternal diabetes may have been related to low numbers of study patients.
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CONCLUSIONS
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We report a group of 21 preterm infants with meconium obstruction of prematurity. These very low birth weight infants had initial spontaneous passage of meconium followed by signs and symptoms of low intestinal obstruction. They were more likely to have prenatal histories of maternal hypertension. Inspissated meconium in the distal ileum was noted in 57% of the infants. In infants who have the classic findings of meconium obstruction of prematurity, such meconium in the ileum is not associated with cystic fibrosis. Gastrografin enemas proved to be safe, diagnostic, and the best therapeutic method in our patient population. However, one third of infants required surgical management because of spontaneous intestinal perforation or worsening obstructive symptoms secondary to inspissated meconium in the distal ileum. Delay in diagnosis was associated with perforation and postponement in attaining adequate enteral nutrition. Because meconium plug syndrome is becoming a more prevalent and important diagnosis, prompt recognition of this disease and its risk factors with early and aggressive medical management is essential to prevent the need for surgical intervention.
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FOOTNOTES
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Received for publication Apr 15, 2003; Accepted Feb 6, 2004.
Reprint requests to (S.E.K.) Division of Neonatology, Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0526. E-mail: skeeney{at}utmb.edu
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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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ABSTRACT
MATERIALS AND METHODS
