Background: Little is known about the effect of GERD on the outcome of VLBW infants. GERD might affect feeding behavior and, therefore, weight gain. Infants with GERD often have been treated with medications which have central nervous system side effects. Further, a study by deRegneir et al(J Perinatology 1997) has shown that VLBW infants with CLD [who also may have GERD] are at increased risk for delayed growth and development.Objective: To estimate the strength of association between GERD and outcome during infancy in VLBW infants, with and without CLD.Methods: The study sample included 375 VLBW infants (birth weight< 1501 gm) with CLD (use of supplemental oxygen at 36 weeks post-menstrual age) and 345 VLBW infants without CLD. Consecutive infants with CLD were identified and then an infant without CLD was selected who was born closest in time to, and with gestational age within one week of, the CLD infant. All infants were born 1/1/84 to 5/31/95, were cared for in either of the two neonatal intensive care units (NICU) which serve a 17-county region, survived, and were followed through one year of age, adjusted for prematurity. Records were reviewed to ascertain each infant's status with respect to GERD (treated with anti-reflux medications) and the following outcomes at one year adjusted age: presence of cerebral palsy, Bayley Scales Mental Developmental Index(MDI) and Psychomotor Developmental Index (PDI), weight, length, and head circumference percentiles from reference curves, and the number of re-hospitalizations after discharge from the NICU. Results: Among infants with CLD, GERD was not associated with cerebral palsy [odds ratio 1.0(0.5-1.9)], MDI < 68 [1.6 (0.9-3.0)], PDI < 68 [1.1 (0.6-1.9)], head circumference < 10th percentile [1.0 (0.6-1.7)], weight < 10th percentile [0.8 (0.5-1.4)], or length < 10th percentile [1.1 (0.7-1.8)]. However, infants with GERD were hospitalized more frequently (p = 0.004, chi square test for trend). Similarly, among infants without CLD, GERD was associated with an increased frequency of re-hospitalization (p = 0.01) but not with delayed growth or development. Conclusions: Among VLBW infants, GERD is associated with a greater likelihood of re-hospitalization during infancy, but not with delayed growth or development.