In an 8‑week‑old infant with 10 days of vomiting, recent formula change, and now two episodes of grossly bloody stools, what additional laboratory studies and differential diagnoses should be considered?

Urgent Evaluation for Bloody Stools in an 8-Week-Old Infant

This 8-week-old infant with 10 days of vomiting, recent formula change, and now bloody stools requires immediate assessment for intussusception and other surgical emergencies, followed by evaluation for cow's milk protein allergy (CMPA) if surgical causes are excluded. 1, 2

Immediate Red-Flag Assessment

Determine if the vomiting is bilious or non-bilious immediately—this single distinction drives your entire diagnostic pathway. 1, 2

• Bilious vomiting at any age is a surgical emergency until proven otherwise, with midgut volvulus and intussusception being the most critical time-sensitive diagnoses that must be excluded urgently 1, 3
• Assess for signs of severe dehydration: prolonged skin tenting >2 seconds, cool extremities, decreased capillary refill, lethargy—these mandate immediate IV fluid resuscitation 2
• Evaluate for toxic appearance, altered mental status, or signs of sepsis (fever with lethargy), which require urgent workup for meningitis, sepsis, or urinary tract infection 2, 4
• Check for abdominal distention, tenderness, palpable mass, or absent bowel sounds—these suggest obstruction or intussusception 1, 2

Critical Differential Diagnoses

Surgical Emergencies (Must Exclude First)

Intussusception:

• Peak incidence is 6–18 months but can occur at 8 weeks 1, 2
• Classic triad: intermittent crampy abdominal pain (manifested as inconsolable crying or drawing up legs), progression to bilious vomiting, and "currant jelly" stools indicating mucosal damage 1, 2
• A palpable abdominal mass may be present 2
• Obtain abdominal ultrasound immediately if clinical features suggest intussusception—this is the initial imaging modality of choice 2

Malrotation with Midgut Volvulus:

• Accounts for 20% of bilious vomiting cases in early infancy 3
• Can present with bloody stools due to intestinal ischemia 1, 3
• If vomiting is bilious, obtain an abdominal radiograph immediately as the first imaging study, followed by upper GI series if obstruction is confirmed 1, 2

Incarcerated Hernia:

• Less common but must be examined for during physical exam 2

Non-Surgical Causes (After Excluding Surgical Emergencies)

Cow's Milk Protein Allergy (CMPA):

• This is the most common cause of bloody stools in infants, accounting for 53.3% of cases 5
• The recent formula change from one brand to another (both likely cow's milk-based) is highly suggestive 5, 6
• Typically presents with non-bilious vomiting, feeding intolerance, irritability, and bloody stools 5, 6
• Diagnosis is clinical; no specific lab test confirms it 6
• The only definitive way to confirm FPIAP is through elimination diet followed by oral food challenge 6

Necrotizing Enterocolitis (NEC):

• Primarily affects premature infants (<1500g), but can occur in term infants 7, 5
• Presents with feeding intolerance, bilious emesis, bloody stools, abdominal distention, and systemic signs (apnea, lethargy, temperature instability) 7, 5
• Preterm neonates have higher incidence of NEC and later onset of bloody stools compared to term infants 5

Swallowed Maternal Blood:

• Accounts for 10% of bloody stools in neonates 5
• Less likely at 8 weeks of age but can be excluded with Apt test (alkali denaturation test) 8

Viral Enteritis:

• Accounts for 9.7% of bloody stools in neonates 5
• Presents with watery diarrhea, vomiting, and mild fever 2, 4

Anal Fissure:

• Accounts for 5% of bloody stools 5
• Blood typically streaks the outside of formed stool; examine perianal area carefully 5

Essential Laboratory Studies

Immediate Labs (if any red-flag signs present):

• Complete blood count with differential—look for leukocytosis/leukopenia (infection), thrombocytopenia (NEC), and eosinophilia (CMPA, though not diagnostic) 7, 6
• Procalcitonin—significantly elevated in NEC compared to FPIAP or benign causes 6
• Basic metabolic panel—assess for dehydration, electrolyte abnormalities, and metabolic alkalosis (if pyloric stenosis considered) 2, 4
• Blood gas—metabolic acidosis suggests ischemia or severe dehydration 2, 4
• Blood culture if sepsis suspected 2, 4

Stool Studies:

• Stool culture and white blood cells if bloody diarrhea, recent antibiotic use, daycare exposure, or immunodeficiency present 2
• Apt test (alkali denaturation) to distinguish maternal from fetal blood if swallowed blood suspected 8

Additional Labs if NEC Suspected:

• Coagulation studies (PT/PTT)—coagulopathy occurs in NEC 7
• Liver function tests—may be abnormal in NEC 7

Imaging Studies

Abdominal Radiograph (First-Line for Bilious Vomiting or Suspected Obstruction):

• Obtain immediately if vomiting is bilious or if obstruction is suspected 1, 2
• Look for dilated bowel loops, air-fluid levels, pneumatosis intestinalis (air in bowel wall—pathognomonic for NEC), portal venous gas, or free air (pneumoperitoneum) 9, 2, 7

Abdominal Ultrasound:

• First-line imaging for suspected intussusception—shows "target sign" or "pseudokidney sign" 1, 2
• NOT appropriate for pyloric stenosis at 8 weeks if vomiting is bilious—pyloric stenosis causes non-bilious projectile vomiting and typically presents at 3–6 weeks 2
• Can detect bowel wall thickening, increased vascularity, or free fluid suggesting NEC 6

Upper GI Series:

• Indicated for any bilious vomiting to rule out malrotation with volvulus, even if plain radiograph is normal—plain films miss up to 7% of malrotation cases 2
• Sensitivity of 96% for detecting malrotation 1

Management Algorithm

Step 1: Stabilize and Assess Severity

• Ensure airway, breathing, circulation are stable 4
• Assess hydration status and initiate IV fluids if severe dehydration present 2
• Stop oral feeds immediately if bilious vomiting or surgical emergency suspected 2, 4
• Place nasogastric tube for decompression if bilious vomiting or obstruction present 4

Step 2: Determine Vomiting Character

• If bilious: Obtain abdominal radiograph immediately, followed by upper GI series; consult pediatric surgery urgently 1, 2
• If non-bilious with bloody stools: Obtain abdominal ultrasound if intussusception suspected based on clinical features (crampy pain, lethargy, palpable mass) 1, 2

Step 3: Exclude Surgical Emergencies

• If imaging confirms intussusception, malrotation, or NEC with pneumoperitoneum: Immediate pediatric surgery consultation 1, 2, 7
• If imaging is normal or shows only mild non-specific findings: Proceed to evaluate for non-surgical causes 2, 5

Step 4: Evaluate for CMPA (Most Likely Diagnosis if Surgical Causes Excluded)

• Switch to extensively hydrolyzed protein formula (e.g., Nutramigen, Alimentum) or amino acid-based formula (e.g., Neocate, EleCare) for a 2–4 week trial 9, 5, 6
• If breastfed, recommend maternal elimination diet excluding cow's milk and egg for 2–4 weeks 9
• Resolution of symptoms within 2–4 weeks supports CMPA diagnosis 9, 6
• Oral food challenge can confirm diagnosis but should be done under medical supervision 6

Step 5: Consider Other Diagnoses if CMPA Trial Fails

• Viral enteritis—supportive care with oral rehydration therapy 2, 4
• Anal fissure—stool softeners and topical barrier cream 5
• Rare causes: metabolic disorders, coagulation disorders, vascular malformations—consult pediatric gastroenterology 2, 4

Critical Pitfalls to Avoid

• Never dismiss bilious vomiting as "just gastroenteritis"—it is a surgical emergency until proven otherwise 1, 2, 3
• Do not rely on antidiarrheal agents (loperamide, kaolin-pectin)—they are contraindicated in infants, do not reduce symptoms, and can cause severe complications including ileus and death 2
• Do not perform upper GI series for non-bilious projectile vomiting at 8 weeks—this suggests pyloric stenosis, which requires ultrasound, not upper GI 2
• Do not delay imaging if red-flag signs are present—bloody stools with bilious vomiting or toxic appearance require immediate evaluation 1, 2
• Eosinophil count and imaging cannot reliably distinguish FPIAP from idiopathic transient colitis—only elimination diet and oral food challenge confirm CMPA 6
• Procalcitonin is significantly higher in NEC than FPIAP—use this to help differentiate when clinical picture is unclear 6
• Overall operation rate for bloody stools in neonates is only 1.7%—most cases are benign and self-limiting, but you must exclude the 1.7% that require surgery 5