What are the treatment options for premature infants with symptoms of Gastroesophageal Reflux Disease (GERD)?

Treatment of GERD Symptoms in Premature Infants

Premature infants with GERD symptoms should be managed primarily with conservative, non-pharmacologic interventions, as acid suppression therapy lacks efficacy evidence and carries significant risks including necrotizing enterocolitis, pneumonia, and gastroenteritis in this vulnerable population. 1, 2

Clinical Presentation in Premature Infants

Premature infants with GERD present differently than term infants and require heightened clinical suspicion:

• Respiratory deterioration is a hallmark sign, particularly in infants with bronchopulmonary dysplasia (BPD), where 18.4% develop significant GERD compared to only 1.2% without BPD 3
• Sudden pulmonary decline requiring reintubation after initial extubation, especially in infants previously improving from respiratory distress syndrome 3
• Feeding difficulties, poor weight gain, and refusal to eat are critical warning signs 3, 1
• Apnea and bradycardia episodes may indicate severe reflux requiring intervention 3, 4
• Reflux in premature infants is often nonacidic and typically improves with maturation 1

First-Line Management: Conservative Measures

Feeding Modifications

Start with feeding adjustments before considering any pharmacologic intervention: 1, 5

• Reduce feeding volume while increasing frequency to minimize gastric distension 1
• Consider a 2-4 week trial of extensively hydrolyzed protein or amino acid-based formula in formula-fed infants, as cow's milk protein allergy co-exists with GERD in 42-58% of cases 1, 4
• For breastfed infants, implement a maternal exclusion diet restricting at least milk and egg for 2-4 weeks 1

Critical Warning About Thickened Feedings

Avoid thickened feedings in premature infants due to the association with necrotizing enterocolitis. 1 The FDA specifically warns against using thickening agents in infants born before 37 weeks gestation who are currently hospitalized or discharged within the past 30 days 1

Positioning Strategies

Evidence for positioning in premature infants is limited and contradictory:

• Left lateral positioning after feeding is the only non-pharmacological intervention with evidence for reducing reflux episodes 6
• Upright positioning in caregiver's arms for 10-20 minutes after feeding may decrease GER frequency 1
• Avoid semi-supine positions (car seats, infant carriers) as these exacerbate reflux 1
• Note that prone positioning recommendations apply only to awake, supervised infants, not premature infants in the NICU 1

Pharmacologic Therapy: Use With Extreme Caution

Strong Evidence Against Routine Acid Suppression

Acid suppression therapy should be avoided in premature infants due to lack of efficacy and significant safety concerns: 1, 2

• Proton pump inhibitors (PPIs) and H2 antagonists increase risk of community-acquired pneumonia, gastroenteritis, candidemia, and necrotizing enterocolitis specifically in preterm infants 1, 5
• Lansoprazole was not found to be effective in infants 1-12 months with symptomatic GERD in controlled trials, with 54% response in both treatment and placebo groups 7
• Acid suppression increases the burden of nonacid reflux, which is already predominant in infants and may worsen symptoms 8, 2

When Pharmacologic Therapy Might Be Considered

Only consider acid suppression if there are clear GI symptoms of pathological reflux AND conservative measures have failed for 2-4 weeks: 1, 5

• Must have documented GI features such as recurrent regurgitation, dystonic neck posturing, or evidence of esophagitis [1, @22@]
• Do not use acid suppression solely for chronic cough or respiratory symptoms without GI manifestations [1, @22@]
• If used, PPIs should be dosed 30 minutes before meals, though metabolism differs in infants versus adults 1

Prokinetic Agents

Insufficient evidence supports routine use of prokinetic agents (metoclopramide, domperidone), and adverse effects including drowsiness, restlessness, and extrapyramidal reactions may outweigh benefits 1, 4

Surgical Intervention

Fundoplication is reserved only for premature infants with life-threatening complications who have failed medical management: 3, 4

• In one series, 17 of 22 premature infants with documented GERD required fundoplication, with 15 having initial respiratory distress syndrome 3
• Dramatic improvement in pulmonary status occurred post-fundoplication in infants with severe BPD-associated reflux 3
• Surgery should only be considered after careful exclusion of other etiologies and with realistic parental counseling about outcomes 1, 5

Diagnostic Evaluation

History and physical examination are usually sufficient; avoid routine diagnostic testing: 1

Warning Signs Requiring Further Investigation

Evaluate for alternative diagnoses if the following are present: 1

• Bilious vomiting, GI bleeding, hematemesis, or hematochezia
• Consistently forceful vomiting
• Fever, lethargy, or hepatosplenomegaly
• Abdominal tenderness or distension
• Poor weight gain despite interventions

When Diagnostic Testing May Be Indicated

• Upper endoscopy with biopsy if symptoms persist despite appropriate therapy for 4-8 weeks, to evaluate for esophagitis or exclude other conditions 1, 9, 5
• pH/impedance monitoring can quantify reflux but does not always correlate with symptoms 1, 8
• Upper GI series is useful only to evaluate anatomy, not to diagnose GERD 1

Key Clinical Pitfalls to Avoid

• Do not reflexively prescribe acid suppression for regurgitation or respiratory symptoms without clear GI manifestations of pathological reflux 1, 2
• Recognize that most infant GER resolves spontaneously by 12 months without intervention 1, 4, 8
• Consider cow's milk protein allergy as a mimic or co-existing condition before escalating GERD therapy 1, 4
• Avoid thickened feedings in premature infants due to necrotizing enterocolitis risk 1
• Understand that nonacid reflux predominates in infants and worsens with acid suppression 8, 2