Although gastroesophageal reflux (GER) is a very common phenomenon among preterm infants, its therapeutic management is still an issue of debate among neonatologists. A step-wise approach should be advisable, firstly promoting nonpharmacological interventions and limiting drugs to selected infants unresponsive to the conservative measures or who are suffering from severe GER with clinical complications. Despite of this, a concerning pharmacological overtreatment has been increasingly reported. Most of the antireflux drugs, however, have not been specifically assessed in preterm infants; moreover, serious adverse effects have been noticed in association to their administration. This review mainly aims to draw the state of the art regarding the pharmacological management of GER in preterm infants, analyzing the best piecies of evidence currently available on the most prescribed anti-reflux drugs. Although further trials are required, sodium alginate-based formulations might be considered promising; however, data regarding their safety are still limited. Few piecies of evidence on the efficacy of histamine-2 receptor blockers and proton pump inhibitors in preterm infants with GER are currently available. Nevertheless, a significantly increased risk of necrotizing enterocolitis and infections has been largely reported in association with their use, thereby leading to an unfavorable risk-benefit ratio. The efficacy of metoclopramide in GER’s improvement still needs to be clarified. Other prokinetic agents, such as domperidone and erythromycin, have been reported to be ineffective, whereas cisapride has been withdrawn due to its remarkable cardiac adverse effects. 1. Introduction Gastroesophageal reflux (GER) is very frequent in preterm infants. The incidence in those babies born before 34 weeks of gestation approximately amounts to 22% [1]. In the preterm population GER should not be usually considered a pathological phenomenon, as it might be promoted by a number of physiological factors. Among these, are included the supine posture, which enhances the migration of liquid gastric content through the looser gastroesophageal junction, the immature esophageal motility, which leads to a poor clearance of refluxate, and, eventually, the relatively abundant milk intakes [2]. The linkage between GER, apneas [3] and chronic lung disease is still controversial [4, 5]. In few cases, however, GER may be associated to clinical complications as, for instance, feeding problems, failure to thrive, esophagitis, and lung aspiration [6], thereby lengthening the hospital stay
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