What is the next best step for a 4-month-old formula-fed baby with constipation, presenting with hard, goat-like stools, who has been unresponsive to lactulose (a laxative) syrup 2.5 ml twice daily for 1 month?

Next Step for Refractory Infant Constipation

Switch from lactulose to polyethylene glycol (PEG) at an appropriate dose for age, as lactulose has failed after one month of treatment and PEG demonstrates superior efficacy in infants over 6 months of age.

Immediate Management Algorithm

Step 1: Age-Appropriate Laxative Selection

• For infants under 6 months: Lactulose/lactitol are the authorized medications, but since lactulose has failed at 2.5 mL twice daily (5 mL total daily), the dose is likely inadequate 1, 2
• For infants 6 months and older: Switch to polyethylene glycol (PEG), which is authorized and more effective than lactulose 2, 3
• The current lactulose dose (5 mL/day total) is below the FDA-recommended range of 2.5-10 mL daily in divided doses for infants 1

Step 2: Optimize Current or Switch Therapy

Since this infant has been on inadequate lactulose dosing:

If under 6 months old:

• Increase lactulose to the upper end of the dosing range (up to 10 mL daily in divided doses) 1
• The goal is to produce 2-3 soft stools daily 1
• If diarrhea occurs, reduce dose immediately 1

If 6 months or older (preferred approach):

• Switch to PEG, which produces significantly more stools per week than lactulose (mean difference 0.70 stools/week, with better tolerability and less need for additional therapies) 3
• PEG reduces the need for rescue laxatives by 45% compared to lactulose (18% vs 31% requiring additional therapy) 3
• PEG is superior to placebo with a mean increase of 2.61 stools per week 3

Step 3: Concurrent Dietary Modifications

While adjusting pharmacotherapy, implement these evidence-based dietary changes:

• Add fruit juices containing sorbitol (prune, pear, or apple juice) at 10 mL/kg body weight daily 4
• For formula-fed infants: Consider switching to lactose-free or lactose-reduced formula, as cow's milk can promote constipation in some children 4, 5
• Avoid foods high in simple sugars and fats if the infant has started solids 4

Step 4: Rule Out Red Flags

Before escalating therapy, ensure none of these concerning features are present:

• Failure to thrive 4
• Abdominal distension 4
• Bloody stools 4
• Vomiting 4
• Abnormal neurological findings 4
• Delayed passage of meconium beyond 48 hours at birth 4

If any red flags are present, refer for specialist evaluation to rule out Hirschsprung's disease, hypothyroidism, or other organic causes 5, 6

Evidence Quality and Clinical Reasoning

The recommendation to switch to PEG (if age-appropriate) is based on:

• Cochrane systematic review (25 RCTs, 2310 participants) demonstrating PEG superiority over lactulose 3
• French pediatric guidelines confirming PEG authorization for infants over 6 months 2
• The current lactulose dose is subtherapeutic according to FDA labeling, which may explain treatment failure 1

Common Pitfalls to Avoid

• Underdosing laxatives: The current 2.5 mL twice daily is at the lower end of the recommended range; many providers fail to titrate adequately 1
• Premature discontinuation: Treatment often requires months to years, not weeks 5, 3
• Misdiagnosing lactose intolerance: Do not diagnose based solely on stool pH or reducing substances without clinical worsening upon lactose introduction 7
• Expecting immediate results: Improvement may take 24-48 hours or longer with lactulose 1

Alternative if PEG Unavailable or Not Tolerated

• Liquid paraffin (mineral oil) shows significant efficacy with a mean difference of 4.94 more stools per week compared to lactulose 3
• However, this is less commonly prescribed and has specific administration considerations 2, 3