Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation

Abstract

Schistosomes infect ϳ40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial in Schistosoma mansoni did not detect this association. We conducted an observational study among 99 pregnant women living in an area of Schistosoma japonicum endemicity in the Philippines. We enrolled women at 32 weeks gestation and measured S. japonicum and geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-␣] and interleukin 10 [IL-10]), placental (TNF-␣, IL-6, TNF-␣ receptor II [RII], and IL-1␤), and cord (IL-1␤ and TNF-␣ RII) blood, as well as acute subchorionitis and increased TNF-␣ production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1␤, and TNF-␣ production by syncytiotrophoblasts was independently associated with decreased birth weight (both P < 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.Healthy successful pregnancies are characterized by a placental microenvironment that is biased toward a T-helper cell type 2 (Th2) cytokine milieu (16,23). Parasitic diseases, including malaria and leishmaniasis, alter the placental Th2 bias toward a proinflammatory microenvironment and are associated with poor pregnancy outcomes (29,39,48). These data are consistent with animal models of pregnancy that establish that increased systemic and placental gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) levels produce poor pregnancy outcomes (10, 50). They are also consistent with the marked increase in prematurity and IUGR accompanying human pregnancies complicated by systemic proinflammatory diseases, such as systemic lupus erythematosis, rheumatoid arthritis, and falciparum malaria (18,33,55).Human schistosomiasis, caused by three main species of tissue-invasive parasitic trematodes, infects over 200 million individuals, including ϳ40 million women of childbearing age, and remains a significant cause of morbidity and mortality in developing countries (35). Human infection with schistosomes results in the elaboration of proinflammatory cytokines, inc...

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Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses

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Maternal Infection with Schistosoma japonicum Induces a Profibrotic Response in Neonates

“…The collection of all demographic, parasitologic, and birth outcomes data is described in detail in our original publication describing this study population (10). A number of covariates, including gravidity, parity, age, weight, height, smoking status, and socioeconomic status (SES), were determined at the time of enrollment by questionnaire (18).…”

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