Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women
Andrea M. Weckman,
Robyn E. Elphinstone,
John M. Ssenkusu,
Vanessa Tran,
Kathleen Zhong,
Mwayiwawo Madanitsa,
Carole Khairallah,
Linda Kalilani-Phiri,
Victor Mwapasa,
Andrea L. Conroy,
Feiko O. Ter Kuile,
Chloe R. McDonald,
Kevin C. Kain
Affiliations
Andrea M. Weckman
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada
Robyn E. Elphinstone
SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada
John M. Ssenkusu
Department of Epidemiology and Biostatistics, School of Public Health, Makerere University, Kampala, Uganda
Vanessa Tran
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada
Kathleen Zhong
SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada
Mwayiwawo Madanitsa
College of Medicine, University of Malawi, Blantyre, Malawi
Carole Khairallah
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
Linda Kalilani-Phiri
College of Medicine, University of Malawi, Blantyre, Malawi
Victor Mwapasa
College of Medicine, University of Malawi, Blantyre, Malawi
Andrea L. Conroy
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
Feiko O. Ter Kuile
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
Chloe R. McDonald
SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada
Kevin C. Kain
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; SAR Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Toronto, ON, Canada; Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Research Institute, University Health Network-Toronto General Hospital, Toronto, ON, Canada; Corresponding author
Summary: Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labor and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28–33 weeks gestation had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.
