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Antacid therapy for gastroesophageal reflux in preterm infants: a systematic review. Background: Gastro-oesophageal reflux is prevalent in preterm infants. Despite widespread use in clinical practice, there is still much controversy over the efficacy and safety of drug interventions, particularly antacid therapy. Objective: To systematically review the effects of antacid therapy on preterm infants with symptoms of gastro-oesophageal reflux, and to assess the safety of these interventions. Methods: We carried out an electronic search of the Cochrane central register of controlled trials (CENTRAL, The Cochrane Library), MEDLINE (1966-present), EMBASE (1980-present) and CINAHL (1982-present) as well as other online sources. Participants were preterm infants (<37 weeks gestation) with gastro-oesophageal reflux disease who were receiving care on a neonatal unit. We assessed the effects of histamine-2 receptor antagonists, proton pump inhibitors and alginates against placebo, primarily to see if they reduced the symptoms of reflux. Results: Six studies were included in this review. Meta-analysis could not be carried out due to a lack of studies assessing the same intervention with the same outcomes. Omeprazole therapy significantly reduced the oesophageal acid exposure percentage time with pH<4 (p<0.01) and sodium alginate significantly decreased gastro-oesophageal reflux episodes (p=0.024). Metoclopramide and ranitidine showed a significant increase in gastro-oesophageal reflux disease symptoms versus placebo (p<0.04). No significant results were found for the use of esomeprazole or lansoprazole versus placebo. Conclusions: There is insufficient evidence available to conclude whether antacid therapy is effective or safe when treating gastro-oesophageal reflux disease in preterm infants. Further research is needed into this topic and caution should be taken when administering antacids to preterm infants. Trial registration number: CRD42017078778.