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Gastroesophageal reflux (GER) is frequently a benign condition in infancy with spontaneous resolution. In the neonatal intensive care unit (NICU), however, it can add to neonatal morbidity if not adequately diagnosed and treated. The objective of the current study was to analyze factors associated with GER in infants in the NICU and correlate them with the severity of the disease.All infants in the NICU (n = 150; born November 1994 through April 1999) who were evaluated by a five-channel pH study to rule out GER were included in the study. Infants were grouped as normal, with a reflux index (RI) of less than 6 (n = 66); mild, with RI of 6 to 14 (n = 42); and severe, with RI of more than 14 (n = 42). Maternal and neonatal data were obtained. Clinical GER was defined as the presence of feeding problems (significant gastric residue or emesis) and medical improvement with antireflux measures and medications.There was no difference in birth weight, gestational age; incidence of patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, or chronic lung disease; and treatment with aminophylline or caffeine among the groups. Infants with mild and severe GER (RI 6–14 and >14) had significantly more clinical GER than the normal group (P = 0.0001). Additionally, infants with RI more than 14 had significantly more respiratory distress syndrome, lower hematocrits at the time of study and longer length of stay than those with no or mild GER (P = 0.02).Infants with severe GER had lower hematocrits despite receiving more blood transfusions and iron therapy. Infants with severe GER also had prolonged hospital stays. Early diagnosis and aggressive management of GER may decrease neonatal morbidity and result in earlier discharge from the NICU.