The risk of delivering a LBW baby was significantly higher in women infected during the first trimester of pregnancy, even after adjusting for several potential confounding variables such as parity and number of IPTp/SP doses received. Thought the pathogenesis and immunity of malaria in pregnancy has been explored, the contribution of placental immuno-pathology to anaemia and LBW is not fully understood . Plasmodium falciparum-infected erythrocytes sequester in the placenta through adhesion mechanisms, inducing placental inflammatory responses, particularly monocytes infiltrates. Inflammatory cytokines produced by T cell and macrophages, in particular Th1 responses are associated with maternal anaemia, spontaneous abortions and premature deliveries. These cytokines are known to help eliminate the parasites from the placenta but their overproduction can threaten the pregnancy [25, 26]. Acute infection, particularly with high parasites densities have been associated with preterm delivery while chronic infection have been associated with LBW due to intrauterine growth retardation (IUGR) and severe anaemia . Decreased placental growth and/or decreased nutrient transport have been suggested as the possible final common pathways by which malaria leads to IUGR [25, 28]. In this study, malaria infection during the first trimester was strongly associated with LBW. It is unclear whether this is due to a specific consequence of the infection at this particular time, or whether it is related to the higher risk these women have throughout their pregnancy. In any case, the currently recommended IPT/SP does not cover the first trimester of pregnancy as the first SP dose should not be given before quickening, at about 20 weeks of gestation, for fear of possible toxicity for the foetus . There is little information on the use of SP during the first trimester of pregnancy; available reports are limited to small case series from developed countries . Therefore, the only option available for protecting pregnant women during this vulnerable period is the use of long-lasting insecticidal nets (LLIN) whose coverage and use in sub-Saharan Africa, despite major efforts such as campaigns of free mass distribution, is less than optimal [30, 31]. A potentially interesting additional strategy might be the systematic screening and treatment of all pregnant women and this option was recently investigated [32, 33]. However, when considering the difficulty of identifying women at the earliest stage of their pregnancy , such an approach would hardly solve the problem of protecting during the first trimester. Therefore, promoting LLIN through community-based promotional campaigns targeted not only at pregnant women but also at adolescents seems to be the only option available to tackle this specific problem.
The rate of re-infection and the time length to re-infection were suggested as possible indicators to evaluate the preventive efficacy of SP . In this study, the incidence of re-infections was much higher in women having received two as compared to three doses of SP, indicating that the latter is probably more efficacious. Nevertheless, the rate of re-infection was established after treatment with quinine and does not necessarily represent the true preventive efficacy of SP.
The study has some limitations. Information on LLIN ownership and use was not collected and, knowing that this has an impact on the malaria risk during pregnancy , it should probably have been considered as an important confounding factor. However, it is unlikely that this has resulted in biased estimates as LLIN use in the study population was probably very low at the time of the study. In Boromo, a neighbouring district, LLIN use was estimated at about 27% in the high transmission season .
Malaria infection during pregnancy was probably underestimated as it was detected by peripheral blood smears. Placental biopsies were collected during the study but could not be analyzed due to budget constraints.
Despite the network of home visitors implemented and the daily visits carried out for an earlier identification of pregnant women, most of those detected during the first trimester were at ≥ 10 weeks of gestation, a limiting factor for the assessment of infections during the first trimester. For some reasons, mainly socio-cultural factors , women were reluctant to declare their pregnancy earlier and this should be further investigated.
In conclusion, malaria infections occurring in the first trimester of pregnancy seem to have an important effect on LBW, though the mechanisms are not yet understood. Women should be encouraged to use LLIN throughout their pregnancy so that the deleterious effect of malaria infection during the first trimester could be prevented.