Inflammatory Cytokines in GCF and Placental Tissues in Chronic Periodontitis Patients With Preterm Delivery
Condition: Preterm Labor; Periodontitis
MeSH terms: Periodontitis; Chronic Periodontitis; Premature Birth; Obstetric Labor, Premature
Study type: Observational

Summary: 
      Investigators have shown the presence of elevated proinflammatory cytokines in amniotic fluid
      in patients in preterm labor.However, there is limited and mostly negative evidence that the
      elevation of these mediators in gingival crevicular fluid (GCF), and amniotic fluid are
      associated with pregnancy complications in periodontitis patients. Thus this case control
      study will be conducted to

        1. To determine the level of proinflammatory cytokines in gingival crevicular fluid in
           women with spontaneous preterm delivery with chronic periodontitis.

        2. To investigate the expression of macrophage inflammatory protein-1α in placental
           tissues.

        3. To assess the possible correlation between chronic periodontitis and preterm delivery.
    

Detailed description: 
      Periodontal disease is a commonGram-negative chronic anaerobic infection of the periodontium,
      with an estimatedworld prevalence of 10% to 15% (Genco RJ, et al. 1992, Petersen PE & Ogawa
      H. 2005). It Involves both direct tissue damage resulting from plaque bacterial products, and
      indirect damage via host inﬂammatory and immune responsesmediated by interactions between
      numerous cell populations and inflammatory mediators (Yucel-Lindberg T&Båge T.2013).

      Periodontal infections have been associated with different systemic diseases; cardiovascular
      disease, cerebrovascular disease, diabetes mellitus, respiratory infections and others
      including osteoporosis, cancer, rheumatoid arthritis, erectile dysfunction, Alzheimer's
      disease, gastrointestinal disease, prostatitis and renal diseases(Gulati M, et al. 2013).
      Moreover, many investigators have reported an association between periodontal disease and
      adverse pregnancy outcomes, including preterm birth, low birth weight, foetal growth
      restriction, preeclampsia and perinatal mortality (Ide M&Papapanou PN.2013).

      Preterm birth, defined as a live birth before 37 weeks of gestation, is the leading cause of
      infant mortality in both developed and developing countries (Saigal S & Doyle LW. 2008),
      whether following spontaneous preterm labour, premature rupture of membranes, or caesarean
      section due to foetal distress or maternal medical conditions (Goldenberg RL, et al.
      2008).The World Health Organization has recently estimated that annually 12.9 million or 9.6%
      of all children are born preterm worldwide, despite extensive research and public health
      efforts(Beck S, et al. 2010).

      Major causes for preterm birth are intra-amniotic infections which subsequently cause
      inflammation, as well as sterile inflammation (Madan I, et al 2010). Moreover, smoking,
      alcohol consumption, black race, low socio-economic status, low or high maternal body mass
      index, stress, previous preterm birth, advanced maternal age and short cervix are other
      associated risk factors (DjelantikA, et al. 2012).

      Offenbacher et al in 1996 first hypothesized that gram-negative anaerobic pathogens from
      periodontium and associated endotoxins and maternal inflammatory mediators could have a
      possible adverse effect on the developing fetus (Offenbacher S, et al. 1996), whether through
      translocation of periodontal pathogens to the feto-placental unit or the action of the
      periodontal reservoir of inﬂammatory mediators, which elaborated at the remote site of
      infection and trigger prostaglandins synthesis, resulting in cervical dilation, entry of more
      microbes into the uterus, and continuation of the "viscous cycle" resulting in premature
      birth (Gibbas RS, 2001).

      Investigators have shown the presence of elevated proinflammatory cytokines in amniotic
      fluid, such as interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6),
      interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in patients in preterm
      labor(Hillier SL, et al. 1993, Hitti J, et al. 2001, Figueroa R, et al. 2005).However, there
      is limited and mostly negative evidence that the elevation of these mediators in gingival
      crevicular fluid (GCF), and amniotic fluid are associated with pregnancy complications in
      periodontitis patients(Madianos PN, et al. 2013).

      Macrophage inflammatory proteins 1 alpha (MIP-1α/CCL3) is a member of the cysteine-cysteine
      chemokine family which is secreted by macrophages, neutrophils, basophils, dendritic cells,
      lymphocytes and epithelial cells and mediates granulocyte migration and adhesion. It
      stimulates monocytes and/or osteoclast progenitor cells to become active osteoclasts(Menten
      P, et al. 2002), as well as regulating hematopoiesis and stimulating production of other
      inflammatory mediators such as IL-1, TNF alpha(Maurer M & von Stebut E. 2004).

      The Level of MIP-1 in GCF found to discriminate between diseased and healthy periodontal
      sites(Tymkiw KD, et al. 2011). Moreover, its presence whether in cord blood or amniotic fluid
      was elevated in cases of preterm labor (Matoba N, et al 2009, Weissenbacher T, et al. 2013).

      Deliveries prior to 35 weeks of gestation was typically associated with subclinical
      chorioamnionitis, which is considered the most common manifestation and is defined
      histologically by inflammation of the chorion, amnion, and placenta, and found to be
      associated with chronic infections of low virulence organisms (Hagberg H, et al. 2002).
      However, variability in the assessment criteria for the diagnosis of histological
      chorioamnionitis exists within the literature (Holzman C, et al. 2007).

      Since 1996, a number of studies have investigated the potential relationship between
      periodontitis and preterm and low birth weight. However, results have been controversial,
      suggesting the need for more research to confirm or discard this association(Sanz M, et al
      2013). Thus this case control study will be conducted to investigate the association between
      chronic periodontitis and preterm labor through possible correlation between Macrophage
      Inflammatory Protein-1 alpha (MIP-1α), Tumor necrosis factor alpha (TNF-α) and pentrixin 3 in
      placental tissues and its level in GCF.
    

Intervention name(s): incisional biopsy from placenta and GCF sample
Intervention type(s): Procedure
Intervention description(s): A small piece of villous placental tissue (approximately 1 cm3) will be dissected free of maternal decidua from the placental bed after delivery of fetus processed to prepare tissue homogenate according to the standardized technique (Keelan JA, et al. 1999) GCF will be obtained from each patient by filter paper inserted in gingival crevice for few seconds after isolation by cotton.
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Fourty Mothers participating in this study recruited from Maternal-Fetal medicine clinic,
        Faculty of Medicine, Ain Shams University that must undergo delivery without induction,
        i.e. delivery following labour pains not pre-scheduled caesarian sections
      
Biospecimen description: 
      Placental tissue Gingival clevicular fluid from deepest pocket