title: Maternal Schistosomiasis japonica is associated with maternal, placental, and fetal inflammation.
abstract: Schistosomes infect ∼40 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-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1β), and cord (IL-1β and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (all P < 0.05). After adjusting for confounders, placental IL-1β, and TNF-α 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.
authors.affiliation: Center for International Health Research, Rhode Island Hospital, Brown University Medical School, Providence, RI 02903, USA. Jonathan_Kurtis@Brown.edu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
authors.forename: Ashley
authors.initials: A
authors.lastname: Higashi
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Wu
authors.forename: Fusun
authors.initials: F
authors.lastname: Gundogan
authors.forename: Emily A
authors.initials: EA
authors.lastname: McDonald
authors.forename: Surrendra
authors.initials: S
authors.lastname: Sharma
authors.forename: Sunthorn
authors.initials: S
authors.lastname: PondTor
authors.forename: Blanca
authors.initials: B
authors.lastname: Jarilla
authors.forename: Marriane Joy
authors.initials: MJ
authors.lastname: Sagliba
authors.forename: Analisa
authors.initials: A
authors.lastname: Gonzal
authors.forename: Remigio
authors.initials: R
authors.lastname: Olveda
authors.forename: Luz
authors.initials: L
authors.lastname: Acosta
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000818:Animals; D001724:Birth Weight; D005260:Female; D005315:Fetal Diseases / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D005333:Fetus; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology*; D010679:Philippines; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000276:immunology / Q000473:pathology*; D012549:Schistosoma japonicum / Q000502:physiology*; D012554:Schistosomiasis japonica / Q000097:blood / Q000276:immunology / Q000473:pathology*