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Maternal serum was collected in the second and third trimesters, and a composite inflammatory score was created using five measured biomarkers (CRP, IL\u20106, IL\u20101ra, IL\u201010, and TNF\u2010\u03b1). Placentas were collected at delivery for histological analysis and four major patterns of placental injury were characterized. Fresh small chorionic villous biopsies were collected for placental genome\u2010wide mRNA profiling. Transcripts showing &gt;2\u2010fold differential expression over the 4\u2010SD range of circulating inflammatory biomarkers were reported, adjusting for potential confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The primary analysis included 601 participants. A one standard deviation increase in the third\u2010trimester inflammatory composite was associated with increased odds of chronic inflammation in the placenta (OR: 1.23, 95% CI 1.01, 1.51;). This was driven primarily by elevations in IL\u201010 (OR: 1.37; 99% CI: 1.06, 1.77). Higher maternal IL\u201010 in circulation was associated with bioinformatic indications of reduced pro\u2010inflammatory gene regulation pathways in the placenta (AP1 decreased 25%, <jats:italic>p<\/jats:italic> = 0.003; NF\u2010kB decreased 53%, <jats:italic>p<\/jats:italic> = 0.003) and indications of increased STAT family signaling pathways which mediate signaling through the IL\u201010 receptor (increased 73%, <jats:italic>p<\/jats:italic> = 0.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that elevated maternal circulating IL\u201010 during pregnancy is associated with chronic inflammatory lesions in the placenta at delivery. Additionally, higher levels of circulating IL\u201010 are associated with upregulated STAT signaling pathways in placental tissues.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70062","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:22:47Z","timestamp":1743769367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Associations of Serum Inflammatory Biomarkers During Pregnancy With Placental Pathology and Placental Gene Expression at Delivery"],"prefix":"10.1111","volume":"93","author":[{"given":"Linda M.","family":"Ernst","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Endeavor Health  Evanston Illinois USA"},{"name":"Department of Pathology University of Chicago Pritzker School of Medicine  Chicago Illinois 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