We obtained umbilical cord blood from 5,183 consecutive deliveries of at least 20 weeks' gestation and analyzed them for lead concentration. Those demographic and socioeconomic variables, including lead, which were shown on univariate analysis to be associated with increased risk for congenital anomalies were evaluated and controlled by entering them into a stepwise logistic-regression model with malformation as the outcome. Coffee, alcohol, tobacco, and marijuana use, which were associated with lead level, but not risk of malformation, were also controlled. The model was reduced in steps by eliminating the variables with the highest P value, until the most parsimonious model was created. The relative risk for anomalies associated with lead was then calculated while holding other covariates constant. Lead was found to be associated, in a dose-related fashion, with an increased risk for minor anomalies.
Needleman HL, Rabinowitz M, Leviton A, Linn S, Schoenbaum S. The Relationship Between Prenatal Exposure to Lead and Congenital Anomalies. JAMA. 1984;251(22):2956-2959. doi:10.1001/jama.1984.03340460034021