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Malaria during pregnancy is a major cause of maternal morbidity as well as fetal and neonatal mortality. Previous studies, including our own, suggested that placental and peripheral cytokine and chemokine levels measured at delivery can be used as biomarkers for pregnancy outcomes. However, the timing of malaria infection during pregnancy matters, and these studies do not address the effect of different cytokines in peripheral blood plasma samples taken at early and midpregnancy and at delivery. Here, we aimed to investigate whether peripheral plasma cytokine levels were associated with pregnancy outcomes in a cohort of 400 Beninese pregnant women. Using a high-sensitivity cytometry-based method, we quantified the levels of interleukin-4 (IL-4), IL-5, IL-10, IL-12p70, and gamma interferon (IFN-γ) in peripheral plasma samples taken at two time points during pregnancy and at delivery in various groups of pregnant women identified with Plasmodium falciparum infection, with anemia, with preterm births, or giving birth to babies who are small for their gestational age. We found that, consistently at all time points, elevated levels of IL-10 were strongly and significantly associated with P. falciparum infection, while the levels of IFN-γ at inclusion and delivery were weakly but also significantly associated. Low levels of IL-5 at delivery were associated with a greater risk of both preterm births and small-for-gestational-age babies. The immunosuppressive effects of IL-10 likely affect the overall cytokine equilibrium during pregnancy in women harboring P. falciparum infections. Our findings highlight the peripheral signature of pregnancy outcomes and strengthen the idea of using cytokines as diagnostic or prognostic markers., (Copyright © 2020 American Society for Microbiology.)

Background: In sub-Saharan Africa, malaria in the first half of pregnancy is harmful for both the mother and her fetus. However, malaria in the first trimester of pregnancy, when women are usually not protected against malaria, has been little investigated. For the first time, we assessed the effects of malaria in the first trimester on maternal and birth outcomes using a preconceptional study design., Methods: From June 2014 to March 2017, 1214 women of reproductive age were recruited and followed monthly until 411 became pregnant. The pregnant women were then followed from 5-6 weeks of gestation until delivery. Path analysis was used to assess the direct effect (ie, not mediated by malaria in the second or third trimester) of malaria in the first trimester on maternal anemia and poor birth outcomes. The cumulative effect of infections during pregnancy on the same outcomes was also evaluated., Results: The prevalence of malaria infections in the first trimester was 21.8%. Malaria in the first trimester was significantly associated with maternal anemia in the third trimester (adjusted odds ratio 2.25, 95% confidence interval 1.11-4.55). While we did not find evidence of any direct effect of first trimester malaria infections on birth outcomes, their association with infections later in pregnancy tended to increase the risk of low birth weights., Conclusions: Malaria infections in the first trimester were highly prevalent and have deleterious effects on maternal anemia. They highlight the need for additional preventive measures, starting in early pregnancy or even before conception., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)