A 3-month-old boy was admitted from his pediatrician’s office for failure to thrive and vomiting. On admission, he weighed barely more than his birth weight and was cachectic with muscle wasting. His abdomen was grossly distended but soft and nontender. A trial of nasogastric feeds resulted in a worsening of his clinical status. He was transferred to the ICU, and diagnostic imaging was concerning for a distal bowel obstruction. Surgical pathology revealed a surprising diagnosis, which is described in detail in the following case.
- Upper GI —
- upper gastrointestinal tract radiograph
- NG —
This case discusses a 3-month-old boy who presented with chronic poor weight gain, emesis, and progressively worsening abdominal distention. The pregnancy was complicated by infertility requiring in vitro fertilization, and the male infant was delivered via vacuum-assisted vaginal delivery at 37 weeks’ gestation. Birth weight was 3118 g (31st percentile for gestational age). During his newborn stay, he required phototherapy for unconjugated hyperbilirubinemia. He was discharged on the third day of life and was producing multiple wet diapers at that time. Stool output was recorded within 24 hours of birth. He was readmitted 2 days later for persistent jaundice. He was again started on phototherapy, and formula supplements were added. Prenatal screening, including parental genetic testing for cystic fibrosis, was all normal. His newborn metabolic screen was also normal.
The patient was exclusively breastfed for the first month of his life. His mother reported that he nursed every 2 hours and spent 10 to 15 minutes on each breast during feeds. During that time period, he was producing multiple wet diapers and stools daily. When he followed up with his pediatrician at 1 month of age, his weight was 3770 g (10th percentile for age). At ∼6 weeks of age, he developed a gastrointestinal illness with fever; nonbloody, nonbilious emesis; and loose stools. His mother was sick with a similar illness at that time. After this, his diarrhea and fevers resolved, but he continued to have frequent, small-volume emesis with almost every feed.
At his 2-month well-child visit, his weight was 3388 g (less than third percentile for age). He was started on ranitidine and simethicone and scheduled for a follow-up weight check and screening laboratory studies, but at this point, his parents decided to switch pediatricians. The family followed up with the new pediatrician at age 3 months. At this visit, he had lost 128 g (now weighing 3260 g) and was continuing to have frequent emesis that his parents described as intermittently “yellow-tinged.” He was also producing fewer wet diapers and stools. On examination, he was cachectic with significant abdominal distention. Further review of systems yielded negative results for fevers, blood in stools, cyanosis, and diaphoresis with feeds. At this point, he was admitted to the inpatient unit for further management.
For the hospitalist: What are your initial thoughts? What additional information is it important to ascertain from the history in a patient with failure to thrive?
Allayne Stephans, MD:
For any patient with failure to thrive, a thorough history and physical examination are essential parts of the evaluation. The focus in this patient should be on the feeding history because the vomiting and abdominal distention indicate a gastrointestinal etiology of his poor weight gain. It is also important to determine the degree of malnutrition because a patient with moderate to severe malnutrition necessitates a more comprehensive initial evaluation. In any patient, contributing social factors should also be considered.
Case Discussion Continued
Social history revealed that he lived at home with his parents and 14-year-old stepbrother. His vaccines were up to date. He was not exposed to smoke and did not attend day care. Family history was negative for Hirschsprung disease, inflammatory bowel disease, metabolic disorders, and cystic fibrosis. He was meeting most developmental milestones but still could not fully support his head.
On admission physical examination, temperature was 36.9ºC, heart rate was 144, respiratory rate was 40, blood pressure was 91/63, and oxygen saturation was 98% on room air. Weight was 3215 g (less than third percentile), length was 55.5 cm (first percentile), and head circumference was 38 cm (second percentile). He was awake and not in any obvious distress but cachectic with temporal wasting. He appeared small for his age. The anterior fontanelle was open, soft, and flat, measuring ∼2 cm. He had underdeveloped muscle bulk and poor head control but was noted to have minimal head lag. His abdomen was soft, moderately distended, tympanitic on percussion, but nontender and without detectable hepatosplenomegaly. The anus was patent. Skin was loose with mild tenting. The remainder of the physical examination was normal.
For the hospitalist: Was it appropriate to admit this patient to the hospital? Are there any laboratories or imaging studies that might be helpful?
At this point, this patient’s history and examination do not provide an explanation for his condition, and therefore, he merits an extensive evaluation, including laboratory studies and abdominal imaging. This patient likely met admission criteria at his 2-month visit when he was noted to have severe malnutrition with persistent vomiting. With his current presentation, which included weight loss and not just poor weight gain, admission was absolutely appropriate.
The differential for significant weight loss in this infant is broad and includes a genetic or metabolic condition, a malabsorptive process, renal tubular acidosis, thyroid disease, congenital cardiac disease, and inadequate intake. Differentiating between these conditions begins with assessing a patient’s blood counts and electrolytes, as well as thyroid and hepatic function. Inflammatory markers may suggest a preference for categories of the differential. Imaging studies of the abdomen would allow for assessment of a primary gastrointestinal etiology of failure to thrive. It is also important to involve social work early to identify possible psychosocial contributors to poor weight gain.
Case Discussion Continued
Initial laboratory evaluation demonstrated anemia with hemoglobin at 8.6 g/dL and thrombocytosis of 502 × 109/L with a normal white blood cell count and differential. Electrolytes, hepatic function panel, and his ammonia level were normal other than an albumin of 1.9 g/dL. Urinalysis was normal. Inflammatory markers were significant only for a mildly elevated C-reactive protein of 2.95 mg/dL. Iron studies, amylase, and lipase were normal. Thyroid function testing was also appropriate for age.
An abdominal radiograph demonstrated distended loops of bowel throughout the abdomen with a small amount of gas overlying the rectum (Fig 1). An upper gastrointestinal tract radiograph (upper GI) was performed and showed a low-lying duodenal-jejunal junction but no evidence of malrotation (Fig 2). A nasogastric (NG) tube was placed, and continuous enteral feeds of breast milk were attempted. However, the patient had worsening abdominal distention and continued emesis, which became consistently bilious in nature, so feeds were held. A peripherally inserted central catheter line was placed, and total parenteral nutrition was started. His abdominal distention improved somewhat with NG decompression. A nutritionist, gastroenterologist, and surgeon were consulted.
For the nutritionist: How would you classify this patient’s nutritional status at the time of admission?
Melani DeSapri, MS, RD:
During his initial assessment, this patient was classified as severely malnourished because of inadequate intake and feeding difficulties, as evidenced by a weight z score of −3.89, a 510 g (13.5%) weight loss over the 2 months before admission, and depletions in fat stores on physical examination.
For the gastroenterologist: What is your differential diagnosis for an infant with bilious emesis? How do you typically proceed with diagnostic evaluation? Does the degree of malnutrition in this patient change your differential?
Jonathan Moses, MD:
Given the history of persistent vomiting, an anatomic issue such as intestinal malrotation is a consideration. An upper GI is a useful imaging study to rule this out, as done by the medical team, because 90% of patients with intestinal malrotation will be symptomatic by 1 year of age. Prompt diagnosis is imperative to avoid midgut volvulus, which can be a devastating complication. The upper GI can also detect other anatomic abnormalities, such as pyloric stenosis or duodenal atresia.1 Hirschsprung disease could be considered, and querying the parents about passage of first meconium is a high-yield screening tool because the vast majority of healthy infants pass first meconium within their first 48 hours of life.2 Less common causes of persistent emesis in this age group include necrotizing enterocolitis and intussusception. A malabsorptive process could be considered given the poor weight gain, but typically, there is more diarrhea present. As Dr Stephans noted, a comprehensive nutritional assessment is paramount given the increased mortality associated with moderate to severe malnutrition.3 With this degree of malnutrition, more benign conditions (such as infantile gastroesophageal reflux or colic, which are self-resolving issues) are less likely, and further evaluation is warranted.
For the surgeon: What is your initial approach to a patient like this?
Anne Kim, MD, MPH:
After examining this patient and reviewing the abdominal radiograph, our immediate concern was for a complete or partial small bowel obstruction. Our initial approach would be to place an NG tube for decompression. Because the upper GI was not diagnostic, we would consider a contrast enema to look for causes of distal obstruction. Given his late presentation, Hirschsprung disease was our primary concern. Other congenital causes of obstruction include meconium ileus or jejunoileal atresia with a web causing partial obstruction, colonic atresia, internal hernia, or an adhesive obstruction related to an in-utero perforation.
A computed tomography scan or ultrasound of the abdomen would also have been imaging studies to consider, but they are suboptimal when evaluating for primary bowel obstruction, especially in this patient. Infants have limited intraabdominal fat, which makes delineation of different loops of bowel on a computed tomography scan difficult. An abdominal ultrasound would also have been difficult to interpret because of this patient’s extensive bowel dilation. Because our primary concern was for Hirschsprung disease, we recommended the barium contrast study first.
Case Discussion Continued
On hospital day 2, the patient became increasingly sleepy and difficult to arouse, with persistent bilious emesis. He was tachycardic and tachypneic with a blood pressure appropriate for age, and the tachycardia did not resolve with administration of a fluid bolus. His abdominal examination showed persistent, marked distention. Given his vital sign abnormalities, he was transferred to the PICU for further management.
For the critical care attending physician: What was your initial impression of this patient? What further evaluation was warranted at this time?
Karen Lidsky, MD:
When this patient arrived in the PICU, he was irritable but awake and more responsive than he had been on the floor. He improved after receiving an additional fluid bolus, which suggested a degree of intravascular volume depletion possibly related to abdominal third spacing versus early sepsis. His heart rate and respiratory rate were elevated, but his blood pressure was acceptable for his age. At this point, his abdomen was markedly distended, with palpable loops of bowel, so we (like the consultants) were concerned for some type of bowel obstruction. He did not have significant rebound tenderness or guarding, which lessened but did not eliminate our concern for acute peritonitis.
Our first goal was to maintain hemodynamic stability and make sure that previous measures taken to decompress the abdomen were working. There were concerns about the patency of the Salem sump, so this was replaced and put on low, intermittent suction. Electrolytes were repeated and still unremarkable. We followed serial blood gases to monitor for the development of a metabolic acidosis, which did not occur. We agreed with surgery and gastroenterology that the next diagnostic study should be a barium enema.
Case Discussion Continued
Barium enema was performed and showed a normal caliber colon with no transition zone. The contrast did not progress beyond the midascending colon, prompting concern for proximal colonic obstruction of unclear etiology (Fig 3). With this finding and his worsening clinical status, he was taken to the operating room for an exploratory laparotomy.
For the surgeon: What are the common causes of intestinal obstruction in infants? How common is it to see intestinal obstruction with only intermittent bilious emesis?
Common causes of intestinal obstruction include those associated with nonbilious emesis (reflux, overfeeding, and pyloric stenosis) and those associated with bilious emesis (malrotation with or without volvulus, intestinal atresia [especially antral or duodenal webs], Hirschsprung disease, incarcerated hernias, and adhesions from previous surgery or intraabdominal infection). Intussusception and necrotizing enterocolitis are much less likely in an infant of this age but can also be considered. Ileus is a functional obstruction that can occur in response to any intraabdominal or systemic infection in pediatric patients and is more common in infants. Ileus can present with abdominal distention alone or with emesis that can be either nonbilious or bilious. Intermittent bilious emesis, like this patient had, is rare in cases of complete obstruction but can be seen in partial obstruction.
Case Discussion Continued
He underwent exploratory laparotomy on hospital day 3, which demonstrated perforated appendicitis. Pathology was consistent with chronic ischemic changes of the ileum and cecum with diffuse adhesions and marked periappendicitis (Fig 4). In addition to the perforated appendix, he had adhesions causing distal bowel obstruction. An ileocecectomy was done, and ∼10 cm of bowel was resected because of ischemia and damage from adhesiolysis. The bowel wall was noted to have severe inflammation, so a primary anastomosis was not attempted. A Hartmann (blind-ended distal) pouch was created for eventual ileostomy closure
For the surgeon: Walk us through your findings. This seems inconsistent with an acute appendicitis.
These are unusual pathologic findings in a patient with acute appendicitis but are consistent with chronic appendicitis. This patient likely had undiagnosed acute appendicitis at 6 weeks of age, which then led to chronic inflammatory changes and later bowel obstruction. If appendicitis is not diagnosed in a timely manner, which is often the case with neonatal patients, the risk for perforation is high. An undiagnosed perforation of the appendix can lead to chronic inflammatory changes and adhesions. It is not uncommon for older patients to present with distal small-bowel obstructions from appendicitis, but to my knowledge, this is one of the few neonatal cases in the literature.
For the surgeon: Was there an unnecessary delay in taking this patient to the operating room?
Symptoms of bowel obstruction will often improve with NG decompression alone, especially in cases of ileus, so it not unreasonable to try this before proceeding with operative management. This patient was also severely malnourished and dehydrated, so we agreed with the primary team’s attempts to try to optimize his nutritional and fluid status. His clinical deterioration, along with findings on further imaging, necessitated operative management although he was a poor surgical candidate at the time of the operation.
For the critical care attending physician: What were some of the concerns regarding post-operative management of this patient?
We agreed with the surgeons that an emergent procedure was necessary because of his clinical deterioration but that he was not an optimmal surgical candidate give his nutritional status and hypoalbuminemia. When the patient returned to the PICU from the operating room, he remained intubated and was edematous. Postoperatively, he was subject to fluid shifts, which led to pulmonary and peritoneal infiltrates as well as hemodynamic instability. He developed acute respiratory distress syndrome and required prolonged support on the ventilator. Additional central access had been obtained in the operating room, which gave us the ability to monitor his central venous pressures closely.
Case Discussion Continued
After his surgical procedure, the patient was noted to have persistent distention of his abdomen. An abdominal ultrasound was obtained and showed a large amount of peritoneal fluid. Fluid was drained via ultrasound-guided paracentesis, which yielded 150 cc of hazy, yellow-brown ascites fluid (1074 nucleated cells per µL, 60% neutrophils), consistent with an exudative effusion. Although all culture results were negative, he was treated with a prolonged course of cefotaxime and metronidazole for presumed bacterial peritonitis.
The patient was discharged from the hospital at almost 4 months of age on a combination of NG and parenteral feeds. Twice weekly, weights were monitored as an outpatient via home nursing.
For the nutritionist: What sort of catch up growth would you expect for this patient recovering from such a prolonged illness at this age? What must be monitored to ensure that his weight gain occurs safely?
When this patient was restarted on feeds, he was monitored for refeeding syndrome with frequent measurements of electrolytes (with particular attention to magnesium, phosphorus, and potassium) because of the degree of his malnutrition.
Once a patient of this age has adequate caloric intake, we expect weight gain of at least 25 g per day. We calculated his catch-up calorie requirements to be 135 to 140 kcals/kg per day, including 2.5 to 3 g of protein/kg per day. At the time of discharge, he was receiving 16 hours of total parenteral nutrition daily in addition to 16 oz per day via NG feeds of expressed breast milk fortified to 22 kcal/oz. His catch-up growth in the first few weeks after discharge averaged 42 g per day, which is excellent.
Case Discussion Continued
Parenteral nutrition was discontinued 1 week after discharge, when he followed up with gastroenterology. The patient was slowly transitioned back to oral feeds over the next several weeks, and by 5 months of age, he was tolerating full volume oral feeds, had consistent catch-up growth, and was meeting appropriate developmental milestones. His ileostomy was reversed ∼6 months after his initial surgery, and he continues to do well.
Acute appendicitis is a common diagnosis in older children, but it is a rare cause of persistent abdominal symptoms in young infants. Of appendicitis cases, <5% are reported in children <5 years of age, and it is even less common in children <3 months old. Historically, neonatal appendicitis has been seen in former preterm infants, and male infants are more commonly affected than female infants,4 although these trends are becoming less significant over time.5
Commonly reported symptoms in this age group are nonspecific and include abdominal distention, irritability, lethargy, poor feeding, and leukocytosis.5 These symptoms can easily be mistaken for many other systemic conditions. Abdominal wall cellulitis or right-lower quadrant erythema is a distinguishing feature of infantile appendicitis and has been noted in approximately one-quarter of reported cases. Additionally, the finding of pneumoperitoneum, especially when it is localized to the right-lower quadrant, should raise suspicion for acute appendicitis.5 However, even these specific findings can overlap with other, more common diagnoses, including malrotation with volvulus and necrotizing enterocolitis. There is some thinking that neonatal appendicitis may represent a form of localized necrotizing enterocolitis5–9 because of common risk factors (including congenital heart disease and perinatal asphyxia), and it has been associated with Pseudomonas aeruginosa infection in some series.10
It has been hypothesized that appendicitis is rare in this population because of the immature structure of the appendix during the neonatal period. Typically, the appendix has an overall funnel shape with a wider opening at the cecum, which differs from the more tubular structure seen in older patients. This structural variation may decrease the likelihood of obstruction. Additionally, because infants are fed a liquid diet and generally remain in a supine position when either awake or asleep, they are less likely to develop symptomatic abdominal obstruction from any cause.5,6,10 Neonates are also less likely to be infected with adenoviruses or other infections that may cause lymphoid hyperplasia, which is thought to be a contributing factor to the development of appendicitis in older patients.5
Because of the difficulties in correctly identifying cases of neonatal appendicitis early, the risk of perforated appendicitis is higher, as was manifested in our patient's case. Additionally, anatomic features of a neonate’s appendix, including the thin appendiceal wall, may predispose it to perforation at any point throughout the illness.5,6,11 Historically, mortality for neonatal appendicitis has been much higher than in the pediatric and adult populations and is likely due to the delay in diagnosis as well as neonates’ relatively poor physiologic reserve, particularly in relation to their nutritional status. One recent study found that nearly one-fourth of patients died in the setting of neonatal appendicitis, although this is markedly improved from previous mortality rates of approximately three-fourths of patients.5 Those who presented without sepsis and no free air on abdominal imaging had lower mortality, as did those with earlier surgical treatment.5,12
Any young infant with appendicitis should be evaluated for other related conditions that may have predisposed the infant to developing this condition (including Hirschsprung disease,12 cystic fibrosis, and meconium plugs)4 because these conditions are associated with increased intracanalicular pressure in the appendiceal lumen. However, analysis of case series of patients with neonatal appendicitis do not bear out these theoretical associations with clinical data.5
Obstructive processes should be high on the differential for any patient who presents with persistent emesis and abdominal distention. In neonates and young infants, other, more common diagnoses (including pyloric stenosis, malrotation with or without volvulus, necrotizing enterocolitis, and gastroenteritis) should always be considered. Any patient with severe malnutrition should undergo a comprehensive evaluation for underlying pathology.
- Accepted June 6, 2017.
- Address correspondence to Allayne Stephans, MD, Division of Pediatrics, General Academic Pediatrics, UH Rainbow Babies and Children’s Hospital, 11100 Euclid Ave, Mail Stop 6019, Cleveland, OH 44106. E-mail:
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2016-4267.
- Copyright © 2017 by the American Academy of Pediatrics