Inflammation is strongly implicated in the pathophysiology of preterm birth. Reduced frequency or function of Regulatory T (Treg) cells in late gestation is associated with spontaneous preterm labour. Whether these Treg cell deficiencies arise in early gestation is unknown.
Using an established Australian biobank, we sought to determine whether changes in Treg cell abundance or phenotype are detectable from early gestation in women that go on to deliver preterm. Peripheral blood mononuclear cells (PBMCs) collected at early (12-16 weeks) and mid (22-26 weeks) gestation as part of the Omega-3 fats to reduce the incidence of prematurity (ORIP) trial (ACTRN12613001142729) were characterised by flow cytometry. Following unblinding to clinical parameters, early and mid-gestation T cell phenotypes from women that went on to deliver at term (39 – 41 weeks, N=92), or preterm (>37 weeks, N=25) were assessed.
Compared to women with uncomplicated term deliveries, women destined to deliver preterm had a 11.0% mean reduction in the frequency of peripheral Treg cells (as a proportion of CD4+ T cells) evident in early gestation (p=0.037). This was associated with elevated conventional T cells (p=0.014) and a corresponding decrease in the ratio of Treg to Tconv cells in women that delivered preterm (p=0.048), indicating a skewed maternal T cell response. Treg cells from preterm women exhibited lower markers of suppressive competence and heightened expression of transcription factors associated with proinflammatory activation. Similar findings were evident when a subset of women meeting strict criteria for spontaneous preterm birth (N=17) were considered.
This data provides compelling evidence of an impaired Treg cell response in early gestation preceding preterm delivery. In ongoing studies, we will expand analysis of PBMC and plasma parameters associated with preterm delivery, with the goal to develop screening tools and interventions to confer protection against early parturition.