Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic path-ways during pregnancy increase the risk of placental insufficiency and sponta-neous preterm labor and delivery. We conducted a secondary analysis of inflam-matory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the in-flammatory 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 dysre-gulation 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.

Automated summary

Preterm birth is a leading cause of death in children under five. Sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and preterm labor. Study findings suggest a potential causal link between early inflammation, subsequent angiogenic dysregulation, and preterm birth, highlighting the importance of interventions before 24 weeks gestation.