PD was defined as the distance in millimeters from the gingival margin to the apical part of the pocket. (the standard therapy), supragingival prophylaxis, and oral hygiene education. The control group will only receive supragingival prophylaxis and oral hygiene education. IGFBP3 Women will be followed throughout their pregnancy and then to childbirth. The main outcomes include periodontal disease status in late pregnancy and birth outcomes measured such as mean birth weight (grams), and mean gestational age (weeks). Periodontal disease will be diagnosed through a Lapaquistat dental examination by measuring probing depth, clinical attachment loss and percentage of bleeding on probing (BOP) between gestational age of 32 and 36 weeks. Local and systemic inflammatory mediators are also included as main outcomes. == Discussion == This will be the first RCT to test whether treating periodontal disease among pre-conception women reduces periodontal disease during pregnancy and prevents adverse birth outcomes. If the effect of pre-pregnancy periodontal treatment is confirmed, this intervention could be recommended for application in low- or middle-income countries to improve both oral health and maternal and child health. == Trial registration == This trial is registered with Chinese Clinical Trial Registry (ChiCTR):ChiCTR-TRC-12001913. Keywords:Pre-conception, Periodontal disease, Birth outcomes, Inflammatory mediators == Background == Periodontal disease is defined as an inflammatory condition of the soft tissues surrounding the teeth (i.e., gingivitis) and the destruction of the supporting structures of the teeth [1-3]. As a persistent bacterial infection, periodontal disease leads to a chronic and systemic challenge with bacterial substances and host-derived inflammatory mediators that are capable of initiating and promoting systemic diseases. There is increasing evidence suggesting that Lapaquistat periodontal disease is associated with systemic diseases such as cardiovascular diseases, diabetes mellitus, as well as adverse pregnancy and birth outcomes [4-8]. == The relationship between periodontal disease and adverse birth outcomes == Since Offenbacher et al. first reported an association between periodontal disease and preterm birth in 1996 [9], substantial evidence has accumulated suggesting periodontal disease may be associated with an increased risk of various adverse pregnancy and birth outcomes such as preterm birth, low birth weight, early pregnancy loss, gestational diabetes and preeclampsia [10]. Inflammatory mediators induced by periodontal disease have downstream effects on biological pathways and tissues. Studies have shown increased levels of interleukin-1 beta (IL-1), IL-6, tumor necrosis factor alpha (TNF-, beta-glucuronidase (glucuronidase), prostaglandin E2 (PGE2), aspartate aminotransferase (AST), metalloproteinase-8 (MMPT-8) and decreased level of osteoprotegerin (OPG) not only in the gingival tissues, gingival cervicular fluid (GCF), saliva, but also in the serum/ plasma of patients affected by periodontal disease [2,11-19]. These inflammatory mediators appear in the systemic circulation and eventually cross the chorioamniotic barrier to finally appear in the amniotic fluid. Additionally, maternal periodontal disease results in placental and fetal exposure to microbes through hematogenous dissemination. Blood-borne bacterial products, especially lipopolysaccharide (LPS), target the chorioamniotic plexus to trigger local PGE and TNF-synthesis. These Lapaquistat host-derived inflammatory mediators urge preterm membrane rupture and labor, resulting in preterm delivery. This poor uteral environment could lead to fetal growth restriction (FGR) and neonatal morbidity. == The optimal time for treating periodontal disease to improve pregnancy outcomes == Attempts at treating periodontal disease during pregnancy to achieve improved outcomes have had inconsistent conclusions. Recently, several large clinical randomized controlled trials failed to conclude that standard periodontal therapy during pregnancy reduced the incidence of adverse pregnancy outcomes (e.g., preterm birth and low birth weight) [20-22] The question of when to treat periodontal disease was put forward. Pregnancy may not be an appropriate period for periodontal disease treatment as discussed by Xiong et al. [23]: 1) Treating periodontal disease during pregnancy may be too late to reduce the local and systemic inflammation activated by oral bacterial pathogens. 2) Dental scaling and root planning during treatment itself may cause bacteremia triggering systemic inflammation, leading to adverse pregnancy and birth outcomes, 3) Because of.