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Risk of malaria in infants can be influenced by prenatal factors. In this study, the potential for placental parasitemia at delivery in predicting susceptibility of infants to Plasmodium falciparum (Pf) infections was evaluated. Seventy-two newborns of mothers who were placental malaria negative (PM−) and of mothers who were PM+ with below (PM+ Lo) and above (PM + Hi) median placental parasitemia, were actively monitored during their first year of life.

Median time to first PCR-detected Pf infection was shorter in PM + Lo infants (2.8 months) than in both PM− infants (4.0 months, p = 0.002) and PM + Hi infants (4.1 months, p = 0.01). Total number of new infections was also highest in the PM + Lo group. Only 24% of infants experienced clinical malaria episodes but these episodes occurred earlier in PM + Lo infants than in PM + Hi infants (p = 0.05). The adjusted hazard ratio (95% CI) of having Pf infection was 3.9 (1.8–8.4) and 1.5 (0.7–3.4) for infants in the PM + Lo and PM + Hi groups, respectively. Collectively, low placental parasitemia was associated with increased susceptibility to malaria during infancy. Therefore, malaria in pregnancy preventive regimens, such as sulfadoxine-pyremethamine, that reduce but do not eliminate placental Pf in areas of drug resistance may increase the risk of malaria in infants. When pregnant women become infected with the mosquito-borne parasite Plasmodium falciparum (Pf), parasitized erythrocytes adhere to placental villi and accumulate in the intervillous spaces (IVS), causing a condition referred to as placental malaria (PM).

In addition to eliciting adverse pregnancy outcomes, PM has been identified as a risk factor for early childhood morbidity and mortality. In general, infants born to PM-positive (PM+) mothers have a shorter time to first Pf infection, and first clinical episode of malaria,, a higher incidence of Pf infections early in life, lower hemoglobin levels, and higher risk of dying compared to infants of PM-negative (PM−) mothers. However, the risk of malaria is not homogeneous among infants of PM+ mothers, since some PM+ infants have similar risk outcomes as PM− infants,. There is therefore a need to identify specific prenatal factors associated with increased susceptibility to malaria in infants whose mothers had PM. Factors thought to be important in modifying the susceptibility of infants to malaria include maternal gravidity and the timing of occurrence of malaria during pregnancy.

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For example, infants born to multigravid Tanzanian women had their first microscopically detected infection 12 weeks earlier than infants of primigravid women. Likewise, Gabonese infants born to multigravidae were approximately twice as likely to experience clinical episodes of malaria during the first 30 months of life than infants born to primigravidae. Concerning the timing of infection during pregnancy, when maternal Pf infections occurred within 3 months prior to delivery, Ugandan infants were at a higher risk of infection than when mothers were infected earlier in pregnancy.

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It is possible that prenatal exposure to low levels of malarial antigens, rather than higher levels influences early childhood susceptibility since multigravidae tend to have lower parasite loads than primigravidae,, and women who are infected only late in pregnancy would be infected for a short time. No study has directly investigated the influence of placental parasitemia (parasite load in the placenta) on the risk of malaria in infants. Therefore, the primary objective of this study was to determine if the susceptibility of Cameroonian infants to Pf was modified by maternal placental parasitemia at delivery. Susceptibility was measured by the median time to first post-natal infection or clinical malaria episode, hazard ratios and total number of times infants were infected during the first year of life. We hypothesized that infants born to mothers with low placental parasitemia (PM + Lo) would have shorter times to first Pf infection and experience more infections during the first year of life than infants whose mothers had higher parasitemias (PM + Hi) or whose mothers were negative for Pf (PM−). Secondarily, to determine if PM + Hi mothers experienced more infections and had higher peripheral parasitemia during the course of pregnancy, thereby potentially exposing their fetuses to higher levels of Pf antigens, maternal peripheral blood samples collected during the course pregnancy were also examined for Pf and umbilical cord blood samples at delivery were tested for Pf parasites and parasite products. Study population Seventy-two infants (out of 80 initially enrolled at birth) that permanently resided in a high malaria-transmission village in Cameroon were followed longitudinally during their first year of life (Fig. ).