• A prospective study of maternal drug use during pregnancy and newborn outcomes provided us with an opportunity to assess the relationship between prenatal cocaine use and respiratory distress syndrome among premature infants. Women were consecutively recruited from the prenatal clinics at Boston (Mass) City Hospital between 1984 and 1988 and were interviewed during the prenatal and postpartum period by trained bilingual interviewers. Urine specimens were collected at the time of each interview and were analyzed for marijuana and cocaine metabolites. Following delivery, one of five pediatricians who were "blinded" to the mothers' prenatal and drug history performed a physical examination and abstracted medical information, including the diagnosis of respiratory distress syndrome from the medical record. The study sample consisted of 33 infants born at 34 weeks' or less gestation who were appropriate for gestational age and not exposed to heroin or methadone prenatally. Eight of the mothers of these 33 infants used cocaine prenatally. One (12%) of eight cocaine-exposed infants was diagnosed as having respiratory distress syndrome compared with 13 infants (56%) not exposed to cocaine prenatally. Infants not exposed had an odds ratio of 8.9 (95% confidence interval: 0.9, 83.5) for respiratory distress syndrome compared with infants exposed to cocaine prenatally. When the analysis was controlled for prolonged rupture of membranes, black race, infant gender, or gestational age, the adjusted odds ratio was essentially unchanged. This preliminary observation of a decreased incidence of respiratory distress syndrome among premature infants prenatally exposed to cocaine appears to be biologically plausible and needs to be confirmed in future studies with larger numbers of subjects to control for potentially confounding variables.