title: Cervical leukocytes and spontaneous preterm birth.
abstract: The objective was to characterise cervical leukocyte populations and inflammatory mediators associated with term and recurrent spontaneous preterm birth (SPTB) in pregnant women with a history of SPTB. A prospective observational study was undertaken on 120 women with a history of SPTB. A cytobrush was used to sample cells from the cervix at 12-25 weeks' gestation. Cells were enumerated and characterised by flow cytometry. Cytokines and chemokines were also measured. Participants were then grouped according to delivery at term (>36+6 weeks), late SPTB (34-36+6 weeks) or early SPTB (<34 weeks). Differences in leukocyte sub-populations, cytokine and chemokine levels were compared with outcome. Cervical leukocytes comprised up to 60% of the host-derived cells. Most of these (90-100%) were polymorphonuclear cells (PMN). Most of the remaining cells were mucosal macrophages expressing CD68 and CD103 in addition to markers shared with blood-borne monocytes. Failure to detect cervical macrophages in at least 250,000 cervical epithelial cells was a feature of women who experienced early SPTB (6 out of 6 cases, 95% CI 61-100%) compared with 34% (30 out of 88 cases, 95% CI 25-43%, P<0.001) of women delivering after 34 weeks. CCL2 (MCP-1) was also low in SPTB before 34 weeks and levels above 75 ng/g and/or the presence of macrophages increased the specificity for birth after 34 weeks from 66% to 82% (55 out of 67 cases, 95% CI 73-91%). Absence of cervical macrophages and low CCL2 may be features of pregnancies at risk of early SPTB.
authors.affiliation: UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. Electronic address: patricia.hunter@ucl.ac.uk.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Hunter
authors.affiliation: UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; University of Oxford Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
authors.forename: Sairah
authors.initials: S
authors.lastname: Sheikh
authors.affiliation: UCL Institute for Women's Health, 86-96 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: David
authors.affiliation: UCL Institute for Women's Health, 86-96 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Peebles
authors.affiliation: UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002584:Cervix Uteri / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000276:immunology / Q000378:metabolism; D011262:Pregnancy Trimester, Second / Q000276:immunology / Q000378:metabolism; D047928:Premature Birth / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2
keywords: Flow cytometry; Leukocyte; Macrophage; Polymorphonuclear cell; Spontaneous preterm birth