What is the differential diagnosis and management for spitting up in premature babies?

Differential Diagnosis for Spitting Up in Premature Infants

In premature infants presenting with spitting up, the primary differential includes physiologic gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), cow's milk protein allergy, aspiration with or without swallowing dysfunction, and anatomic abnormalities including bowel obstruction. 1

Distinguishing Physiologic GER from Pathologic GERD

The critical first step is differentiating benign "happy spitters" from infants with complications requiring intervention. 1

Physiologic GER (Benign)

• Regurgitation or spitting up occurs daily in 50% of all infants and is a normal physiologic process 1
• Infant is thriving with adequate weight gain 1
• No respiratory symptoms, feeding refusal, or signs of discomfort 1
• No intervention beyond reassurance is needed 1

GERD (Pathologic - Requires Evaluation)

• Poor weight gain or failure to thrive 1
• Feeding refusal or aversion 1
• Respiratory symptoms: apnea, bradycardia, recurrent pneumonia, chronic cough 1
• Hematemesis or unexplained anemia 1
• Oxygen desaturation during or after feeds 1
• Premature infants are at particularly high risk, especially those with bronchopulmonary dysplasia (BPD) - 18.4% of premature infants with BPD develop significant GERD versus only 1.2% without BPD 2

Cow's Milk Protein Allergy

This diagnosis mimics GERD and must be considered in all premature infants with persistent spitting up. 1

• Mucus or blood-tinged stools are classic findings 3
• Small amounts of cow milk protein from maternal diet pass through breast milk in sufficient quantities to cause symptoms 1, 3
• Implement a 2-4 week trial of maternal elimination diet (restricting milk and eggs) in breastfed infants 1
• Use extensively hydrolyzed protein or amino acid-based formula in formula-fed infants 1
• Symptoms typically improve within 1-2 weeks of strict elimination 3
• This is a transient condition that resolves by 1-2 years of age 3

Aspiration and Swallowing Dysfunction

Premature infants have high rates of aspiration (29-100% in those undergoing videofluoroscopic swallow studies), including silent aspiration without obvious clinical signs. 1

High-Risk Features Requiring Swallow Evaluation

• Cough or persistent oxygen desaturation during feeding 1
• Suspected or confirmed vocal cord paralysis (all premature infants with vocal cord paralysis had silent aspiration in one study) 1
• Other airway anomalies 1
• Failure to wean from oxygen or ventilatory support as expected 1
• Failure to thrive 1
• Chronic pulmonary symptoms out of proportion to viral infections 1
• History of prolonged intubation or multiple intubations 1

Clinical Signs of Aspiration

• Stridor, wheeze, tachypnea, increased secretions 1
• Critical pitfall: Up to one-third of infants with normal clinical feeding evaluations have silent aspiration on formal testing 1

Anatomic Abnormalities and Bowel Obstruction

While less common, anatomic causes must be excluded, particularly with bilious vomiting or failure to pass meconium. 1

Proximal Obstruction

• Nonbilious vomiting occurs in 15% of proximal bowel obstructions 1
• Classic "double bubble" sign indicates duodenal atresia 1
• "Triple bubble" with no distal gas indicates jejunal atresia 1

Distal Obstruction

• Multiple distended bowel loops with absent or decreased distal gas 1
• Requires contrast enema to differentiate meconium plug, ileal atresia, or Hirschsprung disease 1

Management Algorithm

Step 1: Assess Severity and Red Flags

• If bilious vomiting, abdominal distention, or no meconium passage → obtain abdominal radiographs immediately 1
• If hematemesis, unexplained anemia, or recurrent pneumonia → consider upper endoscopy 1
• If respiratory symptoms during feeding → consider swallow evaluation (VFSS) 1

Step 2: Trial of Cow's Milk Protein Elimination

This applies to infants with complications of GER, not "happy spitters" 1

• Breastfed: maternal elimination diet excluding milk and eggs for 2-4 weeks 1
• Formula-fed: switch to extensively hydrolyzed or amino acid-based formula 1

Step 3: Feeding and Positioning Modifications

• Reduce feeding volume while increasing frequency 1
• CRITICAL WARNING: Avoid thickened feedings in premature infants due to association with necrotizing enterocolitis 1
• Upright positioning after feeds 1
• Avoid overfeeding and environmental tobacco smoke 1

Step 4: Avoid Pharmacologic Therapy Unless Absolutely Necessary

• Acid suppression medications lack evidence of effectiveness and have harmful adverse effects including increased risk of pneumonia and gastroenteritis 4
• No pharmacologic therapy has >50% support for effectiveness among pediatric specialists 5
• Erythromycin as a prokinetic is ineffective at standard doses 6

Critical Pitfalls to Avoid

• Never use thickened feedings in premature infants born before 37 weeks gestation - FDA warning regarding association with necrotizing enterocolitis 1
• Do not prescribe acid suppression therapy without clear evidence of esophagitis or failure of conservative management 1, 4
• Do not assume normal clinical feeding evaluation excludes aspiration - formal swallow study may be needed 1
• Do not discontinue breastfeeding prematurely - maternal elimination diet can effectively manage cow's milk protein allergy 3
• Do not use soy formula as alternative - up to 40% cross-reactivity with cow's milk protein allergy 3