15: Markers of placental dysfunction and spontaneous preterm birth

Abstract

Placental dysfunction is an understudied potential cause of spontaneous preterm birth (SPTB). Levels of pregnancy-associated plasma protein-A1 (PAPP-A1, a growth-promoting enzyme that cleaves insulin-like growth factor binding protein-1 and -4 [IGFBP1 and IGFBP4]) are decreased, and levels of PAPP-A2 (which downregulates trophoblast differentiation) are increased in maternal serum samples from other pregnancy complications associated with placental dysfunction, including preeclampsia and fetal growth restriction. We sought to compare maternal plasma and placental levels of PAPP-A1, PAPP-A2, IGFBP1, and IGFBP4 across birth outcomes. We performed a case-control study comparing levels of PAPP-A1, PAPP-A2, IGFBP1, and IGFBP4 in maternal plasma and placenta biopsy samples obtained from 20 early SPTB cases (< 32 weeks), 20 term deliveries (38-40 weeks), and 20 medically-indicated preterm births (MPTB, < 32 weeks). Protein levels were measured by enzyme-linked immunosorbent assay. Protein levels were stratified by neonatal sex. Demographics of the study groups are presented in Table 1. Maternal plasma and placental levels of PAPP-A1, PAPP-A2, IGFBP1, and IGFBP4 are presented in Table 2. Among the 60 women in the cohort, placental levels of PAPP-A1 and PAPP-A2 differed by birth outcome (P< .001). Maternal plasma levels of PAPP-A1 and PAPP-A2 were lower in SPTB compared to MPTB and term deliveries (P=0.003 and < 0.001). Placental levels of IGFBP4 were significantly greater in MPTB compared to SPTB and term deliveries (P< 0.001). Mothers of male fetuses had significantly lower plasma levels of IGFBP1 and IGFBP4 compared to females. Plasma levels of PAPP-A1 and PAPP-A2 did not differ by sex. This study demonstrates differential expression of placental proteins that influence trophoblast invasion and differentiation in SPTB cases. Additional studies investigating functional pathways that involve these proteins, such as the sonic hedgehog pathway and insulin-like growth factor axis, in relation to SPTB are warranted.View Large Image Figure ViewerDownload Hi-res image Download (PPT)