BACKGROUND: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances on the molecular basis of virulence and immune evasion have helped identify var2csa as a PAM-specific var gene. METHODOLOGY/PRINCIPAL FINDINGS: The present study presents a genome-wide microarray transcript analysis of 18 P. falciparum parasite isolates freshly collected from the placenta. The proportion of PAM over-expressed genes located in subtelomeric regions as well as that of PAM over-expressed genes predicted to be exported were higher than expected compared to the whole genome. The identification of novel parasite molecules with specificity to PAM and which are likely involved in host-pathogen interactions and placental tropism is described. One of these proteins, PFI1785w, was further characterized as the product of a two-exon PHIST gene, and was more often recognized by serum samples from P. falciparum-exposed women than from men. CONCLUSIONS/SIGNIFICANCE: These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM. These data may be very valuable for future vaccine development.