High Rates of Placental Inflammation in Samples Collected by the MOMI Consortium

OBJECTIVES: The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. We analyzed full thickness placental samples (e.g., basal plate, placenta/chorionic villi and the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. STUDY DESIGN. The teams collected biopsies from 294 preterm (gestation <37 weeks) and 291 term (gestation ≥37 weeks) births. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were collected in RNAlater, which enabled bulk transcriptomics. RESULTS. The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and the chorionic plate. The rate in chorionic villus samples ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorion plate correlated with preterm birth. The transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, (Gene Ontology) GO analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION. Together these data suggested geographic- and/or population-based differences in placental inflammation and the triggers of preterm birth.