Clinical question
In infants (≤1 y) with crying or irritability attributed to feeds, do proton pump inhibitors (PPIs) improve symptoms without additional harms compared with placebo?
Bottom line
Use of PPIs does not improve crying, fussiness, irritability, or regurgitation attributed to feeds. However, PPIs may increase the risk of serious adverse effects at 4 weeks (12.0% vs 2.5% with placebo), including respiratory tract infections.
Evidence
Results are statistically significant unless indicated. Systematic reviews from the past 10 years were identified.1 As no meta-analyses were available, RCTs were retrieved.2-5
Two placebo-controlled RCTs of PPIs; 4-week duration.2,3
- In 162 infants (median age: 4 months) given lansoprazole after crying within 1 hour of taking 25% or more feed (0.2 to 1.5 mg/kg/d),2 the following were found:
— A 50% or greater reduction in feedings with crying or duration of crying episodes: 54% in each group.
— No differences in crying, regurgitations, stopped feedings, feed refusal, and back arching.
— Serious adverse events (eg, respiratory tract infections): 12.0% versus 2.5% (placebo); number needed to harm of 10.
- An RCT of 30 infants (mean age: 5 months) with frequent crying and reflux (confirmed by biopsy and pH monitoring) taking omeprazole (10 to 20 mg/d)3 found no difference in crying and fussing (minutes per 24 hours), as well as in irritability (0 to 10 visual analogue scale score).
No placebo-controlled RCTs of histamine-2 receptor antagonists were available. Head-to-head comparisons of histamine blockers versus PPIs found no difference.4
In 4 withdrawal RCTs (8 to 268 infants; 1 to 11 months old) of open-label treatment with rabeprazole,5 esomeprazole,6 pantoprazole,7 or famotidine8 for 1 to 4 weeks, responders and compliers were randomized to blinded continued drug use or placebo. At 4 to 5 weeks the following were found:
Context
While PPIs improve esophageal pH in infants,3 they do not improve symptoms.
Implementation
Regurgitation red flags include growth or developmental delay, forceful vomiting, and bile or blood-stained vomit.9 In the absence of red flags, repeated parental reassurance is key.10 Guidance recommends that regurgitation—even with crying, fussiness, or back arching—is normal and common in early infancy (affecting ≥40%), and 90% of infants will have resolution by age 1 or earlier.10 If reassurance is not sufficient for parents, a breastfeeding assessment by trained individuals for breastfed infants can be offered.10 For formula-fed infants, smaller more frequent feeds or thickening feeds with infant cereals can be tried.9-11 Guidelines also suggest that if non–immunoglobulin E–mediated cows’ milk protein allergy is suspected, trials of restricting dairy from the mother’s diet for breastfed infants or switching to a formula with extensively hydrolyzed protein can be considered.9 However, the evidence supporting these guideline-recommended interventions is very limited.
Notes
Tools for Practice articles in CFP are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr G. Michael Allan and Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice{at}cfpc.ca.
Footnotes
Competing interests
None declared
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