BackgroundMalaria in Mali remains a primary cause of morbidity and mortality, with women at high risk during pregnancy for placental malaria (PM). We evaluated risk for PM and its association with birth outcomes in a rural to urban longitudinal cohort on the Bandiagara Escarpment and the District of Bamako. MethodsWe collected placental samples (N = 317) from 249 mothers who were participants in our longitudinal cohort study. A placental pathologist and research assistant evaluated the samples by histology in blinded fashion to assess PM infection stage and parasite density. We used generalized estimating equations (GEE) to model the odds of PM infection.ResultsPregnancies in Bamako, beyond secondary education, births in the rainy season (instead of the hot dry season), births in later years of the study, and births to women who had > 3 doses of sulfadoxine-pyrimethamine (SP) instead of no doses of SP were associated with reduced odds of experiencing PM (active and past infections combined). We found improved birth outcomes (+ 285 g birth weight, + 2 cm birth length, + 75 g placental weight) for women who had > 3 doses of SP compared to no doses, but did not detect a difference in birth weight or length for women who had 2 instead of > 3 SP doses. However, at 2 instead of > 3 doses placentas were 36 g lighter and the odds of low birth weight (< 2500 g) were 14% higher. Severe parasite densities were significantly associated with decreases in birth weight, birth length, and placental weight, as were chronic PM infections. The women who received no SP during pregnancy (7% of the study total) were younger and lacked primary school education. The women who received ≥ 3 doses of SP came from more affluent families.ConclusionsWomen who received no doses of SP during pregnancy experienced the most disadvantageous birth outcomes in both Bamako and on the Bandiagara Escarpment. Such women tended to be younger and to have had no primary school education. Targeting such women for antenatal care, which is the setting at which SP is most commonly administered in Mali, will have a more positive impact on public health than focusing on the increment from two to three doses of SP.