PPIs no benefit to crying infants

Proton pump inhibitors (PPIs), given to crying infants with the thinking that the discomfort of gastroesophageal reflux (GER) explains the babies' tears, do not decrease crying or irritability, according to a systematic review.

Dorota Gieruszczak-Bialek, MD, from the Department of Pediatrics, Medical University of Warsaw, Poland, and colleagues report the findings of their review online December 30 in the Journal of Pediatrics.

In July 2104, Dr Gieruszczak-Bialek and colleagues searched two registries and three databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials) for randomized controlled trials involving infants with GER or gastroesophageal reflux disease (GERD) that examined the effectiveness of PPIs. The systematic review identified 176 trials. Most were characterized by some researcher financial conflict, including support by PPI manufacturers, authors employed by PPI manufacturers, or authors with stock in companies that produce PPIs, Dr Gieruszczak-Bialek and coauthors note.

The authors included five placebo-controlled trials, each involving infants younger than 1 year with signs and symptoms of GERD, in their review. Crying or irritability was the primary outcome in two of the trials: a randomized clinical trial/crossover study of 30 infants aged 3 to 12 months conducted in Australia and a multicenter study of 162 infants aged 1 to 11 months at general pediatric clinics in the United States and Poland. The second of these two trials found that serious adverse events (lower respiratory tract infections) occurred more frequently in infants taking lansoprazole, 0.2 to 1.5 mg/kg per day, for 4 weeks. "Although a wide CI [confidence interval] around the effect calls for caution, the finding is important in light of other observations documenting that the administration of PPIs is not without risk," Dr Gieruszczak-Bialek and colleagues write.

All five trials examined the effectiveness of varying doses of esomeprazole, lansoprazole, omeprazole, or pantoprazole and used "reliable methods," such as video monitoring, a validated cry diary, or questionnaires to document crying and fussiness.

"Some trials showed a decrease in crying/irritability from baseline to the end of the intervention; a similar effect was observed in the control group. However, no significant differences between the study groups were observed. The data do not support the use of PPIs to decrease infant crying and irritability," the researchers write.

According to the National Institutes of Health, GER is common among infants; about half of infants younger than 3 months spit up multiple times per day. By age 14 months, many healthy infants no longer spit up.

The authors note that the evidence base remains limited, yet conclude that "[e]ven if further studies confirm that PPIs offer some benefit, the risks of these drugs, specifically increased risk of gastrointestinal and/or respiratory tract infections, may outweigh the benefits."