ARRA: An Intervention Trial for Effects of Oral Health Improvement of Adverse Maternal-Fetal Outcomes of Gestational Diabetes

This administrative supplement request addresses the "Advance Translational (T1 & T2} Research" solicitation of the NCRR within the ARRA program. The project proposed for support under an administrative supplement for the CBBO/SD will implement an intervention trial to effectively improve oral health in the GDM women with "at-risk" pregnancies and lower the risk of adverse pregnancy outcomes. The hypothesis to be tested, generated by the outcomes during the initial funding period of the COBRE parent grant, is: "Improvement of the oral health, particularly related to oral infections, of expectant women with GDM will significantly decrease the incidence of adverse pregnancy outcomes". RESEARCH PROJECT PLAN: An Intervention Trial for Effects of Oral Health Improvement on Adverse Maternal-Fetal Outcomes of Gestational Diabetes Two Specific Aims, creating innovative translational research activities in the development of a new collaboration between IDeA partners (Kentucky, Puerto Rico), are defined in this supplement Gestational diabetes mellitus (GDM) is a type of diabetes that develops during pregnancy and disappears following parturition. Of the diabetes seen in pregnancy, only 10% is pre-gestational with the remaining 90% being gestational (1). GDM affects -135,000 pregnant women (3-5 %) annually in the United States, making it the most common metabolic disorder and medical complication of pregnancy (2)· Gestational diabetes begins during pregnancy and disappears following delivery, since the placental hormones are removed following birth. GDM can have a negative impact on both the mother and the fetus. Although GDM develops or is discovered during pregnancy, and usually disappears when the pregnancy is over, 30-50% of women who have had GDM develop documented type 2 diabetes 3-5 years postpartum. Several studies support a relationship between markers of inflammation and abnormalities in glucose metabolism. Further support that diabetes has an inflammatory response component is supported by data examining C-reactive protein (CRP) levels. Inflammatory mediators also play an important role in pregnancy and childbirth (3,4) and are positively correlated with preterm birth/intra-ute'rine fetal growth retardation (PTBIIUGR). Periodontal infections are the result of an interaction between a tooth-associated microbial biofilm and the host defenses (5-8). There is substantial evidence to support a link between periodontal disease and diabetes. Both type 1 diabetes and type 2 diabetes are major risk factors for the development of periodontal disease in certain populations (9-11). Novak et al. (12). Infections are generally known to disturb the metabolic control of diabetes. Therefore, in addition to the negative effects of diabetes on periodontal disease, it is plausible that periodontitis can impact the medical management of diabetes. The association between periodontal inflammation and pregnancy has been well documented and occurs in approximately 30- 100% of pregnant women (13,14) related to plaque bacteria and hormonal alterations. The data from the initial studies provided documentation that GDM serves as a risk factor for periodontal disease, and the combination significantly impacted adverse birth outcomes. Table 1 provides the primary data testing our hypothesis that GDM+PD+ women are at significantly increased risk for adverse maternal outcomes of pregnancy. We demonstrate a 3-fold greater risk of adverse pregnancy outcomes when the women had both GDM and periodontitis. The clinical findings were accompanied by significant differences in systemic inflammatory and immune responses related to both GDM and periodontitis in these women. As noted in Fig. 2 CRP was significantly elevated in GDM patients and was increased in women with periodontitis, whether they were GDM or not. Additionally, fibrinogen was elevated with periodontitis, irrespective of GDM status, albeit this did not reach statistical significant (p