Previously, researchers considered proton pump inhibitors (PPIs) to be given to infants with gastroesophageal reflux (GER) to relieve them of uncomfortable symptoms such as crying. However, a systematic review published in the journal Pediatrics by Professor Dorota Gieruszczak-Bialek (Department of Pediatrics, Warsaw Medical University, Poland) and colleagues showed that PPIs do not reduce crying or irritability. Medical Pulse compiled the relevant content as follows: In July 2014, Professor 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) A pooled analysis was performed to review the effectiveness of PPIs. The systematic review identified 176 trials, most of which had some investigator financial conflicts, including being supported by PPI drug companies, authors being employed by PPI manufacturers, or authors holding shares in the relevant manufacturers, Prof. Gieruszczak-Bialek and coauthors note in the paper. The researchers included five placebo-controlled trials in their analysis, each of which involved infants <1 year old with signs and symptoms of GERD in their review. Crying or irritability was the main prognosis in two trials: a randomized clinical trial/crossover study conducted in Australia containing 30 infants aged 3 to 12 months; and another multicenter study conducted in comprehensive pediatric outpatient clinics in the United States and Poland, including 162 infants aged 1 to 11 months. Both trials once again found that serious adverse events (lower respiratory tract infections) occurred more frequently in infants taking lansoprazole at 0.2 to 1.5 mg/kg per day for 4 weeks. "Although there is a broad CI [confidence interval] around the cautionary effect requirement, based on other observations documented, this finding suggests that PPIs administration is not without risk," Prof. Gieruszczak-Bialek and colleagues noted. All five trials examined the efficacy of different doses of esomeprazole, lansoprazole, omeprazole, or pantoprazole, using "reliable methods" such as video surveillance, validated cry diaries, or questionnaires to record crying and irritability. "Some trials showed a reduction in crying/irritability from baseline to the end of the intervention; similar effects were found in the control group. However, the researchers observed no significant differences between study groups. These data do not support the use of PPIs to reduce infant crying and irritability," the researchers wrote. According to the National Institutes of Health, GER is common in infants; about half of infants <3 months of age experience multiple daily spit-ups. By 14 months of age, many healthy infants no longer spit up. The authors note that the evidence base remains limited, but conclude that "even if further studies confirm that PPIs may provide some benefit, there are risks associated with these drugs, particularly an increased risk of gastrointestinal and/or respiratory tract infections, which is likely to outweigh the benefits."