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Pregnancy-associated malaria is one of the leading causes of low birth weight in malaria endemic areas. In this study, 145 parturient women residing in areas endemic for Plasmodium falciparum in Lambaréné, Gabon, were recruited into the study after delivery, and the association of maternal P. falciparum infection, inflammatory response, and birth weight was studied. At delivery, 10% (15) of the mothers (12 were positive in both peripheral and placental blood smears, 1 was positive in peripheral blood only, and 2 were positive in placenta blood only) were positive for P. falciparum by microscopy and 23% (30) by real-time polymerase chain reaction (PCR). The level of C-reactive protein (CRP) was significantly elevated in microscopically P. falciparum–positive pregnant women (34 mg/L; 95% CI: 3–458) but not in those with sub-microscopic infections (6 mg/L; 95% CI: 1–40) compared with those free of P. falciparum infection (7 mg/L; 95% CI: 1–43). In a multivariate analysis, the presence of microscopic (adjusted OR = 28.6, 95% CI = 4.8–169.0) or sub-microscopic (adjusted OR = 13.2, 95% CI = 2.4–73.0) P. falciparum infection in pregnant women and age of mothers < 21 years (adjusted OR = 9.7 CI = 1.0–89.7), but not CRP levels, were independent predictors for low birth weight. This finding may have important operational implications and emphasizes the need for appropriate diagnostic methods in studies evaluating the outcome of pregnancy-associated malaria.