Background and Rationale In sub-Saharan Africa, preventive drug strategies against malaria in pregnancy are recommended from the 2nd trimester of pregnancy onwards. Consequently, pregnant women remain insufficiently or not protected during the first trimester of pregnancy. However, this period may be at particular high risk for the fetus since pregnancy-associated parasites that accumulate into the developing placenta may alter fetal development and growth. The consequences of malaria in early pregnancy have been poorly explored so far. Although studies have indicated that malaria before 4 months of pregnancy was associated with poor maternal and child outcomes, they were not specifically designed to address this issue and both selection and confounding biases cannot be ruled out. Our project will provide considerable value-added findings compared with existing studies for four main reasons: (i) pre-conception recruitment of women (allowing the detection of the earliest malarial infections during pregnancy), (ii) intrauterine growth retardation as primary endpoint, (iii) assessment of both women’s nutritional status before and during pregnancy and gestational hypertension as potential confounders, and (iv) detection of submicroscopic malarial infections. Project objectives, design, analysis plan, and expected outcomes Our goal is to assess the consequences of malaria in early pregnancy in both the mother and her fetus by answering the following questions : (1) What is the effect of malaria in the first 3 months of pregnancy on intrauterine growth restriction (IUGR), duration of pregnancy, birth weight and maternal anemia? (2) What are the burden and the consequences of submicroscopic malarial infections in the first trimester of pregnancy for the mother and the fetus? (3) Does women’s nutritional status modify the relation between malaria in early pregnancy and child outcomes? The project will last 42 months. Three tasks will be dedicated to the recruitment and follow-up of 500 pregnant women. For this purpose, 2,000 women of childbearing age living in the area of Abomey-Calavi (South Benin) will be followed-up monthly until they become pregnant. The first 500 to be pregnant will be then followed-up monthly at the facility-level for, specifically, malaria (microscopy and RT-qPCR), gestational hypertension and nutrition (anthropometrics and feeding practices). Five doppler ultrasound scans will be scheduled during pregnancy with the first one between 8 and 14 weeks of gestation to date the pregnancy accurately. The 4th task will use data collected before and during pregnancy to assess the effect of malaria in the first trimester on maternal and child outcomes, using both hierarchical mixed models and path analysis. The main outcome will be IUGR defined as small-fetal/birth weight-for-gestational-age or reduction in growth according to the new WHO charts. The 5th task will be dedicated to project management. In terms of outcomes, our findings will help to introduce new interventions or to revise existing ones, for the prevention of malaria in pregnancy. New strategies are urgently needed, as the short-term efficacy of present guidelines is now questioned. Organizational capacity Valérie Briand (UMR216 IRD/UPD), the coordinator, has a 8-year expertise in the field of epidemiology and prevention of malaria in pregnancy and a great experience in conducting field-studies. She has been the principal investigator of a large clinical trial for the prevention of malaria in Benin. The project’s team involves scientists specialized in epidemiology, biostatistics, anthropology and biology belonging to UMR216, as well as two French collaborators (UMR204-IRD and US953-Inserm) specialized in nutrition and perinatal health and two Beninese collaborators from the Université d’Abomey-Calavi.