Background:Low birthweight is the primary cause of neonatal morbidity and mortality in the United States. The purpose of our study was to identify factors associated with the effectiveness and apparent ineffectiveness of comprehensive, multicomponent, prenatal care programs for preventing low birthweight.Methods:We reviewed obstetric, pediatric, and public health program evaluations, research reports, and commentaries, published in the English language literature, over the last four decades that pertained to the efficacy of prenatal care for preventing low birthweight.Results:The heterogeneous nature of the services delivered and the lack of consistency in the definition of variables made it impossible to use rigorous, quantitative techniques to summarize this evaluation of the literature. Two general limitations of research design that emerged from our reviews were the focus on clusters of commonly associated risk factors, which has blurred the causal pathways linking specific risk factors to low birthweight, and the failure to examine process variables. These two methodologic problems have led investigators to erroneous conclusions that overstate the significance of negative intervention outcomes. The success and failure of low-birthweight prevention programs has rarely been examined in relation to evidence that the intervention actually modified the targeted risk factors.Conclusions:Few rigorous evaluations of well-designed programs have been conducted. Without an improvement in intervention designs and evaluation studies, recommendations to support or curtail the funding of comprehensive, multicomponent prenatal care services are inappropriate. Rigorously obtained evidence of the costs and benefits of approaches to the prevention of low birthweight are sorely needed.