INTRODUCTION: The objective of this study was to evaluate the association between maternal serum analytes and placenta previa. METHODS: Chart review of deliveries from 2004 to 2012 with two comparison groups: placenta previa without accreta and a control group. Patients in the control group were randomly selected from deliveries without placenta previa. Patients with previa were confirmed by third-trimester ultrasonography. Exclusion criteria were placenta previa with pathology-confirmed accreta, multiple gestations, fetal anomalies, or growth restriction. Primary outcomes were maternal serum analytes in the first trimester: pregnancy-associated plasma protein A and free β-human chorionic gonadotropin (β-hCG), and second trimester: α-fetoprotein), free β-hCG, unconjugated estriol, and inhibin. RESULTS: Twenty-six women with previa met inclusion criteria and 43 women in the control group. The groups did not differ with respect to maternal age, gravidity, or parity. Alpha-fetoprotein multiples of the median was significantly higher in women with previa cases than women in the control group (P<.005). Pregnancy-associated plasma protein A multiples of the median was higher (but was not statistically significant) in women with previa than in the women in the control group (P<.064). There were no differences between groups with respect to first-trimester free β-hCG, second-trimester free β-hCG, unconjugated estriol, or inhibin (Table 1). The following analytes were not available on all specimens: second-trimester free β-hCG, unconjugated estriol, and inhibin.CONCLUSIONS: In our women with placenta previa, maternal serum α-fetoprotein was significantly higher than in women in the control group. We also observed higher levels of pregnancy-associated plasma protein A in women with previa but this did not reach statistical significance. Prospective studies are needed to confirm these findings and determine the relationship with pregnancy outcome.