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Immunophenotyping and activation status of maternal peripheral blood leukocytes during pregnancy and labour, both term and preterm.

ABSTRACT: The onset of labour in rodents and in humans is associated with physiological inflammation which is manifested by infiltration of activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation and labour, both term and preterm. Peripheral blood was collected from non-pregnant women and pregnant women in the 1st, 2nd and 3rd trimesters. Samples were also collected from women in active labour at term (TL) or preterm (PTL) and compared with women term not-in-labour (TNIL) and preterm not-in-labour (PTNIL). Different leukocyte populations were identified by surface markers such as CD45, CD14, CD15, CD3, CD4, CD8, CD19 and CD56. Their activation status was measured by the expression levels of CD11b, CD44, CD55, CD181 and CD192 proteins. Of all circulating CD45+ leukocytes, we detected significant increases in CD15+ granulocytes (i) in pregnant women versus non-pregnant; (ii) in TL women versus TNIL and versus pregnant women in the 1st/2nd/3rd trimester; (iii) in PTL women versus PTNIL. TL was characterized by (iv) increased expressions of CD11b, CD55 and CD192 on granulocytes; (v) increased mean fluorescent intensity (MFI) of CD55 and CD192 on monocytes; (vi) increased CD44 MFI on CD3+ lymphocytes as compared to late gestation. In summary, we have identified sub-populations of mPLs that are specifically activated in association with gestation (granulocytes) or with the onset of labour (granulocytes, monocytes and lymphocytes). Additionally, beta regression analysis created a set of reference values to rank this association between immune markers of pregnancy and to identify activation status with potential prognostic and diagnostic capability.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5618694 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Immunophenotyping and activation status of maternal peripheral blood leukocytes during pregnancy and labour, both term and preterm.

Zhang Jianhong J Shynlova Oksana O Sabra Sally S Bang Annie A Briollais Laurent L Lye Stephen J SJ

Journal of cellular and molecular medicine 20170421 10

The onset of labour in rodents and in humans is associated with physiological inflammation which is manifested by infiltration of activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation and labour, both term and preterm. Peripheral blood was collected from non-pregnant women and pregnant women in the 1st, 2nd and 3rd trimesters. Samples were also collected from women in active labour at term (TL) or preterm ( ...[more]

PMID: 28429508

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Project description:Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.

Project description:BackgroundPreterm labour and birth (PTL/PTB) is characterised by major health and developmental risks for children, life-changing consequences for their families, and substantial healthcare and economic challenges for wider society. While it is known that PTL/PTB impacts infant healthcare costs in the short and long term in Germany, maternal costs have not been described in detail. The aim of this study was to comprehensively describe costs and resource use among PTL/PTB mothers during pregnancy, at hospitalisation for delivery, and up to three years after delivery-overall and according to gestational age (GA) at delivery.MethodsThis study used data from the Statutory Health Insurance (SHI) sample of the AOK Hessen database in Germany. Mothers aged 12-44 years with deliveries between 2009 and 2013 and > 9 months of medical history prior to delivery were included. PTL/PTB mothers were defined by an International Classification of Diseases, 10th Revision (ICD-10) code for PTL during pregnancy, a diagnosis-related group (DRG) code indicating birthweight < 2500 g, or delivery of an infant < 37 weeks GA. Inpatient and outpatient resource use and total direct medical costs were examined during pregnancy, at delivery hospitalisation, and up to three years post-delivery.ResultsOf all mothers, 2147 (20%) experienced PTL/PTB. During pregnancy, median costs for PTL/PTB mothers were €2130. During delivery hospitalisation, the mean length of stay for all PTL/PTB mothers was 6.0 days, and median costs were €2037. Length of stay and costs declined with increasing GA. Long term, PTL/PTB mothers' total median costs were €607 in Year 1, €332 in Year 2, and €388 in Year 3 post-delivery. In each year after delivery, median costs appeared to be greater for mothers who delivered at lower GAs.ConclusionIn this description of costs and resource use among PTL/PTB mothers in Germany throughout the pregnancy and up to three years after delivery, the greatest costs were noted prior to delivery. Costs appeared to decrease with increasing GA, particularly during the delivery hospitalisation and the first year after delivery.

Project description:Preterm delivery is an important cause of perinatal morbidity and mortality, often precipitated by maternal infection or inflammation. Probiotic-containing foods, such as yogurt, may reduce systemic inflammatory responses. We sought to evaluate whether yogurt consumption during pregnancy is associated with decreased preterm delivery. We studied 965 women enrolled at midpregnancy into a clinical trial of prenatal docosahexaenoic acid supplementation in Mexico. Yogurt consumption during the previous 3 months was categorized as ≥5, 2-4, or <2 cups per week. Preterm delivery was defined as delivery of a live infant before 37 weeks gestation. We used logistic regression to evaluate the association between prenatal yogurt consumption and preterm delivery and examined interaction with maternal overweight status. In this population, 25.4%, 34.2%, and 40.4% of women reported consuming ≥5, 2-4, and <2 cups of yogurt per week, respectively. The prevalence of preterm delivery was 8.9%. Differences in preterm delivery were non-significant across maternal yogurt consumption groups; compared with women reporting <2 cups of yogurt per week, those reporting 2-4 cups of yogurt per week had adjusted odds ratio (aOR) for preterm delivery of 0.81 (95% confidence interval, CI [.46, 1.41]), and those reporting ≥5 cups of yogurt per week had aOR of 0.94 (95% CI [.51, 1.72]). The association between maternal yogurt consumption and preterm delivery differed significantly for nonoverweight women compared with overweight women (p for interaction = .01). Compared with nonoverweight women who consumed <2 cups of yogurt per week, nonoverweight women who consumed ≥5 cups of yogurt per week had aOR for preterm delivery of 0.24 (95% CI [.07, .89]). Among overweight women, there was no significant association. In this population, there was no overall association between prenatal yogurt consumption and preterm delivery. However, there was significant interaction with maternal overweight status; among nonoverweight women, higher prenatal yogurt consumption was associated with reduced preterm delivery.

Dataset Information

Immunophenotyping and activation status of maternal peripheral blood leukocytes during pregnancy and labour, both term and preterm.

Publications

Immunophenotyping and activation status of maternal peripheral blood leukocytes during pregnancy and labour, both term and preterm.

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