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Endotoxin at the Maternal–Fetal Interface in a Resource-Constrained Setting: Risk Factors and Associated Birth Outcomes

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  • 1 Center for International Health Research, Rhode Island Hospital, Providence, Rhode Island;
  • | 2 Department of Pediatrics, Alpert Medical School of Brown University, Providence, Rhode Island;
  • | 3 Department of Immunology, Research Institute for Tropical Medicine, Manila, Philippines;
  • | 4 Division of Transfusion Medicine, University of Massachusetts Medical School, Worcester, Massachusetts;
  • | 5 Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts;
  • | 6 Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Providence, Rhode Island
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Low- and middle-income countries (LMICs) carry a high burden of infectious diseases associated with impaired gut integrity, leading to microbial translocation. Pregnancies in this setting are at high risk of fetal growth restriction (FGR). We examined the association among specific risk factors for impaired gut integrity (schistosomiasis, hookworm infection, and alcohol consumption), blood endotoxin levels, and FGR. Endotoxins, lipopolysaccharide-binding proteins (LBPs), and cytokines were measured in blood from women at 32 weeks gestation, the maternal–fetal interface (MFI) at delivery, and cord blood at delivery. Resolution of schistosomiasis had no impact on endotoxin levels; however, maternal hookworm infection and alcohol consumption were associated with modest increases in endotoxin at the MFI. Cytokines responses within the maternal peripheral blood and blood from the MFI were positively associated with endotoxins, but many cord blood cytokines were negatively associated with endotoxins. Newborns with FGR also had higher levels of endotoxins at the MFI. Risk factors for microbial translocation may lead to increased levels of endotoxins at the MFI, which may contribute to poor growth in utero.

Author Notes

Address correspondence to Emily A. McDonald, Center for International Health Research, Rhode Island Hospital, 55 Claverick St., Providence, RI 02903. E-mail: emily_mcdonald@brown.edu

Financial support: This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (K24 AI112964 to J. F. F. and K01 AI113068 to E. A. M.).

Authors’ addresses: Emily A. McDonald, Ayush Joshi, Hannah W. Wu, and Jennifer F. Friedman, Center for International Health Research, Rhode Island Hospital, Providence, RI, E-mails: emily_mcdonald@brown.edu, ayush_joshi@brown.edu, haiwai_wu@brown.edu, and jennifer_friedman@brown.edu. Ronald Stuart and Jonathan D. Kurtis, Center for International Health Research, Brown University, Providence, RI, E-mails: ronald_stuart@brown.edu and jonathan_kurtis@brown.edu. Remigio M. Olveda, Luz P. Acosta, Veronica Tallo, and Palmera I. Baltazar, Department of Immunology, Research Institute for Tropical Medicine, Manila, Philippines, E-mails: rolvedamd_ritm_doh@yahoo.com, ipacosta@yahoo.com, veronica.tallo2015@gmail.com, and palmerabaltazar@yahoo.com. Jeffrey A. Bailey, Division of Transfusion Medicine, University of Massachusetts Medical School, Worcester, MA, E-mail: jeffrey.bailey@umassmed.edu.

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