The beneficial effects of maternal antenatal glucocorticoid treatment(AGT), including enhanced fetal pulmonary maturity and surfactant production, led to speculation that the treatment also might reduce chronic lung disease(CLD) risk among surviving preterm infants. However, as noted by Crowley,1 clinical trials of AGT have failed to demonstrate a significant benefit in reducing CLD among premature infants. The current study explores the hypothesis among the population of infants born between 9/91 and 8/93 at or below 1500 grams birth weight who were enrolled in a case-cohort study of neonatal intracranial white matter disorders at 4 newborn intensive care units (NICUs) in Massachusetts, New York, and New Jersey. Case-cohort analysis of 590 infants at the two centers with the most extreme rates of CLD, defined by oxygen requirement at 28 postnatal days(Center A=17%, Center B=45%; P<.001), revealed divergent rates of AGT among subjects at the two centers (Center A=49%, Center B=67%; P<.001), however the rates of AGT exposure were in a direction opposite to that expected by CLD risk. Furthermore, AGT exposures were similar for both CLD cases and the group of infants without CLD (nondiseased cohort) at 28 postnatal days (case=64%, cohort=62%) or 36 weeks post-menstrual age (PMA) (case=63%, cohort=64%). In logistic regression models of CLD risk, determined by the need for supplemental oxygen at 28 postnatal days or 36 weeks PMA, 16 demographic, prenatal, and perinatal factors were evaluated. These multivariate analyses revealed that AGT did not contribute significantly to a reduced rate of CLD at 28 postnatal days or 36 weeks PMA. In the context of current perinatal care, AGT might play a less prominent role in modifying CLD risk than do other factors such as immaturity, infection, or NICU care practices.