Correlation Between Inflammatory Markers in Gingival Crevicular Fluid, Serum and Amniotic Fluids in Periodontal Pregnant Women

Globally, over 4 million babies die within the first 4 weeks of life and a third of these are secondary to pre-term birth. In the United States, pre-term birth is the second leading cause of neonatal mortality. The US pre-term birth (<37 weeks) rate rose to 12.8% in 2006, an increase of 21% since 1990 and the rate of low birthweight (<2500 g) rose to 8.3% in 2006, an increase of 19% since 1990. Neurological disorders, such as cerebral palsy, which is often combined with mental disability, epilepsy, and cognitive impairment, are of special concern for survivors of pre-term birth. Even though pre-term birth occurs in only a small proportion of the infant population, its societal and personal health impact is considerable because of its disproportionately high perinatal morbidity, mortality, and need for costly medical care. However, it is very disappointing that to date, interventions to prevent pre-term birth have proven to be almost universally ineffective.

The main causes of adverse pregnancy outcome(s) are reported to be maternal infection and placental, fetal, or uterine pathosis. Maternal infection and placental pathosis appear to be the most important causal factors, but each can cause pre-term labour, premature pre-term membrane rupture, or result in medically induced pregnancy interruption. Prominent risk factors for pre-term birth include history of previous pre-term birth, demographic characteristics, periodontal disease, and behavioral factors such as tobacco use.

Offenbacher et al. were the first to report a link in humans between poor maternal periodontal health and composite adverse pregnancy outcome of pre-term low birth weight (PLBW). They reported that women with periodontal disease were much more likely than periodontally healthy women to experience pre-term and low birth weight infants (OR=7.5 for all PLBW cases; OR=7.9 for primiparous PLBW cases). Pro-inflammatory mediators generated within the diseased periodontal tissue may affect the maternal-foetal unit. When present in the amniotic fluid, chronic high levels of cytokines and prostaglandins may lead to intra-uterine growth restriction (IUGR), spontaneous pre-term labour, premature rupture of membranes, and pre-term birth. Several studies report associations of adverse pregnancy outcome with higher gingival crevicular fluid levels of PGE2 and IL-1β and elevated amniotic fluid concentrations of PGE2, IL-1β and IL-8 Dörtbudak. It is possible that IL-6 produced in inflamed periodontal tissues can affect the foetal membranes and cause pre-term uterine contractions. There is evidence that the gingival crevicular fluid levels of IL-6 are higher in gingivitis and periodontitis compared with healthy controls.

Bacteria activate cell-mediated immunological responses, leading to the production and release of cytokines, including interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α), prostaglandins, or endotoxins such as lipopolysaccharides, which may precipitate pre-term labour if they reach the foeto-placental unit. Endotoxin or lipopolysaccharide of Gram-negative bacteria may be detected in biological fluids of sterile compartments such as the amniotic cavity. Administration of endotoxin to pregnant animals results in embryo resorption, pre-term labour, and foetal death. A higher risk of spontaneous pre-term delivery has been associated with genetically driven excessive amniotic fluid IL-Iβ or with a disturbance of bioavailability and/or bio-response of this cytokine, which is central to the pro-inflammatory reaction to infectious stimulants. The foetus also has a role in pre-term birth; the foetus recognizes a hostile intrauterine environment and may precipitate labour by premature activation of the foetal-placental parturition pathway.

The causality relationship between periodontal disease and inflammatory mediators' presence in the amnionic fluid was not tested to date. In the present study the investigators aim to investigate the correlation between inflammatory mediators in the serum and their presence in the amniotic fluid. The investigators will further investigate the correlation of the above results with pregnancy outcome (gestation age, foetal weight and health, etc.).

Israel amniocentesis in healthy women is very common. The cellular fraction in the sampled amniotic fluid is used for the amniocentesis test, while the supernatant is discarded. For the present study the investigators aim to use the supernatants of amniocentesis tests done on healthy women (age 21-45) as well as serum. Using ELISA we will quantify the levels of inflammatory markers such as IL-6, TNFα and IL-1β. The investigators will also test the presence of endotoxin and perio-pathogens DNA in the serum and amnionic fluid. Follow-up on data regarding gestational outcome will be also collected.

participants will be followed for the duration of hospital stay, an expected average of 5 weeks