What are the differential diagnoses for rectal bleeding in a 4‑day‑old neonate?

Differential Diagnosis for Rectal Bleeding in a 4-Day-Old Neonate

In a 4-day-old neonate with rectal bleeding, the most likely diagnoses are idiopathic neonatal transient colitis (INTC), anal fissures, food protein-induced proctocolitis (FPIPC) from maternal dietary proteins, necrotizing enterocolitis (NEC), and infectious colitis, with INTC being the most common cause in otherwise well-appearing infants. 1

Age-Specific Differential Diagnoses

Most Common Causes in Well-Appearing Neonates

• Idiopathic Neonatal Transient Colitis (INTC) accounts for approximately 87.5% of cases of small, fresh rectal bleeding in not-sick neonates, with spontaneous resolution typically occurring within 4 days (range 1-8 days) 1

• Anal fissures are commonly associated with non-significant rectal bleeding in neonates and represent a benign, self-limiting condition 2, 3

• Food Protein-Induced Proctocolitis (FPIPC) is less common than traditionally suspected, representing only 12.5% of cases in not-sick neonates with rectal bleeding 1. This condition can present as early as day 4 of life in exclusively breastfed infants when maternal dietary cow's milk protein passes into breast milk 4. The American Academy of Allergy, Asthma, and Immunology identifies cow's milk and soy as the most common triggers 5

Serious Conditions Requiring Urgent Recognition

• Necrotizing Enterocolitis (NEC) is the most common gastrointestinal emergency in newborns, typically striking premature infants during the first 2 weeks of life 6. Early signs include abdominal distention, lethargy, and feeding intolerance that may progress to gastrointestinal bleeding and hemodynamic instability 6. The radiographic hallmark is pneumatosis intestinalis (air in the bowel wall), with mortality ranging from 20-40% 6

• Infectious Colitis should be considered in the differential diagnosis, particularly Campylobacter jejuni infection, which can cause rectal bleeding in otherwise healthy neonates 2. Antibiotic treatment is advised for children under three months due to high risk of fulminant disease 2

Critical Diagnostic Approach

Initial Clinical Assessment

• Assess hemodynamic stability first, as approximately 15% of acute presentations can involve hypovolemic shock requiring aggressive fluid resuscitation 5

• Perform digital rectal examination when appropriate to assess for anal fissures, masses, or stool consistency 5

• Evaluate for systemic symptoms including fever, abdominal distention, lethargy, feeding intolerance, weight loss, or failure to thrive, as these suggest serious pathology such as NEC or infectious colitis 5, 6

• Obtain detailed feeding history, including whether the infant is breastfed or formula-fed, and maternal dietary intake if breastfeeding (particularly cow's milk consumption) 4

Laboratory Evaluation

• Check complete blood count to assess for anemia and evaluate severity of bleeding 5

• Obtain hemoglobin and hematocrit to quantify blood loss 7

• Consider coagulation studies (PT/INR, aPTT, platelet count) if there is personal or family history of easy bruising or excessive bleeding 5

• Perform stool culture to exclude infectious etiologies, particularly in cases with systemic symptoms 2

Endoscopic Findings and Histopathology

• Sigmoidoscopy reveals red, fragile, hemorrhagic mucosa with severe inflammation in FPIPC cases 5, 4

• Endoscopic abnormalities are observed in virtually all cases of neonatal rectal bleeding, even when the underlying cause is benign INTC 1

• Rectal biopsy shows marked eosinophilic infiltration with multifocal hemorrhage in FPIPC 4, and increased eosinophils on biopsy according to the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 5

Management Algorithm

For Well-Appearing Neonates with Small, Fresh Rectal Bleeding

1. Observe for spontaneous resolution over 4 days if the infant is clinically stable, as INTC resolves spontaneously in the majority of cases 1

2. If bleeding persists beyond 4 days in the absence of other etiology, consider FPIPC and initiate maternal dietary elimination of cow's milk and soy if breastfeeding, or switch to casein hydrolysate formula (such as Nutramigen) if formula-feeding 4, 1

3. Perform food elimination and challenge test (ECT) to confirm FPIPC diagnosis in cases with persistent bleeding 1

For Ill-Appearing Neonates or Those with Systemic Symptoms

1. Immediately assess for NEC if the infant has abdominal distention, lethargy, feeding intolerance, or hemodynamic instability 6

2. Obtain abdominal radiographs to evaluate for pneumatosis intestinalis 6

3. Initiate aggressive medical therapy including bowel rest, nasogastric decompression, broad-spectrum antibiotics, and fluid resuscitation 6

4. Surgical consultation is required if intestinal gangrene or perforation develops, which occurs in approximately half of NEC cases 6

Common Pitfalls to Avoid

• Do not assume FPIPC without confirmation through food ECT, as clinical findings and histological results may satisfy diagnostic criteria but the actual incidence is much lower than suspected 1

• Do not overlook infectious colitis, particularly Campylobacter, as bacterial colitis is often considered unlikely and diagnostics are not routinely conducted 2

• Do not delay evaluation for NEC in premature infants or those with systemic symptoms, as mortality is high (20-40%) and approximately half require surgical intervention 6

• Always consider child abuse when bleeding presents with other concerning features 5

• Do not attribute bleeding to hemorrhoids, as hemorrhoids are exceedingly rare in neonates and symptoms attributed to them frequently represent other pathology 5