Assessing placental maturity through histological and transcriptomic analyses in idiopathic spontaneous preterm birth

Abstract Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the underlying mechanistic causes are not well understood. Previous studies have suggested a role for advanced villous maturity in both spontaneous and iatrogenic preterm birth. To better understand pathological and molecular basis of idiopathic spontaneous preterm birth (isPTB), we compared placental morphology and transcriptomic analysis in carefully phenotyped cohorts of PTB due to intraamniotic infection, isPTB, and healthy term placentae. Characteristic features of precocious placental villous maturation were uniquely demonstrated in isPTB placentae. Transcriptomic analyses revealed isPTB candidate genes. These include an upregulation of three IGF binding proteins (IGFBP1, IGFBP2, and IGFBP6), supporting a role for IGF signaling in isPTB. Additional Gene Ontology analyses identified alterations in biological processes such as immunological activation and programmed cell death. Our data suggest that premature placental aging may contribute to the pathogenesis of isPTB and provide a molecular basis of this subset of cases of preterm birth.