The broad objective of this study is to contribute to our understanding of the role of schistosomiasis infection in mediating adverse birth outcomes. Data generated from this study will inform the health care priorities of developing nations in which schistosomiasis is endemic. The specific objective of this proposal is to investigate the relationship between S. japonicum infection and adverse birth outcomes. Further, this project will examine both extra-placental and placental mechanisms mediating adverse pregnancy outcomes in the context of S. japonicum infection. Data from this study should have broader implications for our understanding of the pathogenesis of intra-uterine growth retardation for a host of infectious and non-infectious diseases that promote a pro-inflammatory immune response. The proposed study is a randomized controlled trial of Praziquantel for women infected with S. japonicum in endemic villages in Leyte, The Philippines. Women will be treated at approximately 12 weeks gestation, and the impact of therapy on birth weight, intra-uterine growth, maternal hemoglobin, and newborn hemoglobin and iron stores will be assessed. This project will address the hypothesis that pro-inflammatory cytokines that are made in response to S. japonicum infection mediate adverse birth outcomes. Specifically, this proposal hypothesizes that these cytokines will exert detrimental effects both systemically and at the placenta, causing intra-uterine growth retardation and lower birth weight. Systemic effects of these cytokines include anemia of inflammation, with a concomitant decrease in maternal bio-available iron, which will be assessed at 32 weeks by serum transferrin receptor levels. Decreased maternal iron bio-availability will result in decreased transfer of iron to the developing fetus, contributing to intra-uterine growth retardation and lower birth weight. Cord blood ferritin will be used to assess newborn iron stores. Elevated serum pro-inflammatory cytokines have also been associated with elevated levels in the placenta. This proposal will examine placental cytokines at the time of delivery to assess the effect of Praziquantel on placental inflammation and birth weight. A trophoblast apoptosis assay will also be used to assess the effect of maternal serum from 32 weeks gestation on trophoblast apoptosis.
|Park, Sangshin; Bellinger, David C; Adamo, Meredith et al. (2016) Mechanistic Pathways From Early Gestation Through Infancy and Neurodevelopment. Pediatrics 138:|
|Olveda, Remigio M; Acosta, Luz P; Tallo, Veronica et al. (2016) Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 16:199-208|
|McDonald, Emily A; Cheng, Ling; Jarilla, Blanca et al. (2014) Maternal infection with Schistosoma japonicum induces a profibrotic response in neonates. Infect Immun 82:350-5|
|McDonald, Emily A; Pond-Tor, Sunthorn; Jarilla, Blanca et al. (2014) Schistosomiasis japonica during pregnancy is associated with elevated endotoxin levels in maternal and placental compartments. J Infect Dis 209:468-72|
|McDonald, Emily A; Kurtis, Jonathan D; Acosta, Luz et al. (2013) Schistosome egg antigens elicit a proinflammatory response by trophoblast cells of the human placenta. Infect Immun 81:704-12|
|Kalkunte, Satyan; Boij, Roland; Norris, Wendy et al. (2010) Sera from preeclampsia patients elicit symptoms of human disease in mice and provide a basis for an in vitro predictive assay. Am J Pathol 177:2387-98|